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1.发明公开公开(公告)号：US20240117059A1
公开(公告)日：2024-04-11
申请号：US18533360
申请日：2023-12-08
发明人： Tomoyuki Igawa , Atsuhiko Maeda , Futa Mimoto , Taichi Kuramochi
IPC分类号： C07K16/28
CPC分类号： C07K16/2866 , C07K16/2812 , A61K2039/505 , C07K2317/34 , C07K2317/524 , C07K2317/526 , C07K2317/94
摘要： The present invention provides: a modified FcRn-binding domain having an enhanced affinity for the Fc Receptor neonatal (FcRn) at neutral pH; an antigen-binding molecule comprising said FcRn-binding domain, which has low immunogenicity, high stability and form only a few aggregates; a modified antigen-binding molecule having an increased FcRn-binding activity at neutral or acidic pH without an increased binding activity at neutral pH for a pre-existing anti-drug antibody; use of the antigen-binding molecules for improving antigen-binding molecule-mediated antigen uptake into cells; use of the antigen-binding molecules for reducing the plasma concentration of a specific antigen; use of the modified FcRn-binding domain for increasing the total number of antigens to which a single antigen-binding molecule can bind before its degradation; use of the modified FcRn-binding domain for improving pharmacokinetics of an antigen-binding molecule; methods for decreasing the binding activity for a pre-existing anti-drug antibody; and methods for producing said antigen-binding molecules.
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公开(公告)号：US11891434B2
公开(公告)日：2024-02-06
申请号：US15988348
申请日：2018-05-24
发明人： Tomoyuki Igawa , Shinya Ishii , Miho Funaki , Naoka Hironiwa , Atsuhiko Maeda , Junichi Nezu , Yoshinao Ruike , Takeshi Baba , Shun Shimizu
CPC分类号： C07K16/18 , C07K16/248 , C07K16/2866 , C07K16/4291 , G01N33/53 , C07K2317/565
摘要： An objective of the present invention is to provide methods for promoting antigen uptake into cells by antigen-binding molecules, methods for increasing the number of times of antigen binding by one antigen-binding molecule, methods for promoting reduction of the antigen concentration in plasma by administering antigen-binding molecules, and methods for improving the plasma retention of an antigen-binding molecule, as well as antigen-binding molecules that allow enhanced antigen uptake into cells, antigen-binding molecules having an increased number of times of antigen binding, antigen-binding molecules that can promote reduction of the antigen concentration in plasma when administered, antigen-binding molecules with improved plasma retention, pharmaceutical compositions comprising the above antigen-binding molecules, and methods for producing them. The present inventors revealed that the above objective can be achieved by using antigen-binding molecules that show calcium-dependent antigen-antibody reaction.
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公开(公告)号：US11359194B2
公开(公告)日：2022-06-14
申请号：US17020497
申请日：2020-09-14
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
IPC分类号： C12N15/10 , C07K16/00 , C07K16/24 , A61K39/12 , A61K39/145 , C07K16/28 , G01N33/68 , A61K39/00
摘要： The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.
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公开(公告)号：US20200172610A1
公开(公告)日：2020-06-04
申请号：US16697310
申请日：2019-11-27
发明人： Tomoyuki IGAWA , Atsuhiko Maeda , Kenta Haraya , Tatsuhiko Tachibana , Yuki Iwayanagi , Yuji Hori , Genki Nakamura , Masaru Muraoka
摘要： One nonexclusive aspect provides molecules further improved from antibodies that can bind to antigens in an ion concentration-dependent manner. An alternative nonexclusive aspect provides safe and more advantageous Fc region variants that have decreased binding to pre-existing ADA. An alternative nonexclusive aspect provides novel IL-8 antibodies that are superior as pharmaceuticals.
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公开(公告)号：US20190211081A1
公开(公告)日：2019-07-11
申请号：US16298032
申请日：2019-03-11
CPC分类号： C07K16/00 , C07K16/2866 , C07K16/2875 , C07K2317/515 , C07K2317/52 , C07K2317/522 , C07K2317/524 , C07K2317/526 , C07K2317/528 , C07K2317/53 , C07K2317/71 , C07K2317/72 , C07K2317/76 , C07K2317/92 , C07K2317/94
摘要： By altering amino acid sequences, the present inventors successfully produced constant regions that can confer antibodies with particularly favorable properties for pharmaceutical agents. When used to produce antibodies, the altered constant regions produced according to the present invention significantly reduce heterogeneity. Specifically, the antibody homogeneity can be achieved by using antibody heavy chain and light chain constant regions introduced with alterations provided by the present invention. More specifically, the alterations can prevent the loss of homogeneity of antibody molecules due to disulfide bond differences in the heavy chain. Furthermore, in a preferred embodiment, the present invention can improve antibody pharmacokinetics as well as prevent the loss of homogeneity due to C-terminal deletion in antibody constant region.
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公开(公告)号：US20190112393A1
公开(公告)日：2019-04-18
申请号：US15977757
申请日：2018-05-11
摘要： The present inventors created antigen-binding molecules containing an antigen-binding domain and an Fcγ-receptor-binding domain, wherein the molecules have human-FcRn-binding activity in an acidic pH range condition, the antigen-binding domain changes the antigen-binding activity of the antigen-binding molecules depending on the ion-concentration condition, and the Fcγ receptor-binding domain has higher binding activity to the Fcγ receptor in a neutral pH range condition than an Fc region of a native human IgG in which the sugar chain bound at position 297 (EU numbering) is a fucose-containing sugar chain.
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公开(公告)号：US20180282719A1
公开(公告)日：2018-10-04
申请号：US15952951
申请日：2018-04-13
发明人： Tomoyuki IGAWA , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
摘要： The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.
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公开(公告)号：US09969800B2
公开(公告)日：2018-05-15
申请号：US15015287
申请日：2016-02-04
发明人： Tomoyuki Igawa , Atsuhiko Maeda , Genki Nakamura , Masaru Muraoka
CPC分类号： C07K16/244 , A61K2039/505 , C07K16/18 , C07K16/2866 , C07K16/36 , C07K16/40 , C07K16/4291 , C07K2317/14 , C07K2317/24 , C07K2317/31 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/76 , C07K2317/77 , C07K2317/90 , C07K2317/92 , C07K2317/94 , G01N33/6854 , G01N2500/04
摘要： One nonexclusive aspect provides molecules further improved from antibodies that can bind to antigens in an ion concentration-dependent manner. An alternative nonexclusive aspect provides safe and more advantageous Fc region variants that have decreased binding to pre-existing ADA. An alternative nonexclusive aspect provides novel IL-8 antibodies that are superior as pharmaceuticals.
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公开(公告)号：US09890377B2
公开(公告)日：2018-02-13
申请号：US13889512
申请日：2013-05-08
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
CPC分类号： C12N15/1037 , A61K39/12 , A61K39/145 , A61K2039/505 , A61K2039/544 , A61K2039/545 , A61K2039/552 , C07K16/244 , C07K16/248 , C07K16/2866 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C12N2760/16111 , C12N2760/16134 , C12N2770/20071 , G01N33/6854 , G01N2500/00
摘要： The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.
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公开(公告)号：US20170121412A1
公开(公告)日：2017-05-04
申请号：US15263617
申请日：2016-09-13
发明人： Tomoyuki Igawa , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Atsuhiko Maeda
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.
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