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    Antibodies With Modified Affinity To FcRn That Promote Antigen Clearance
    42.
    发明申请
    Antibodies With Modified Affinity To FcRn That Promote Antigen Clearance 审中-公开
    具有改善亲和力的抗体促进抗原清除的FcRn的抗体

    公开(公告)号：US20170002080A1

    公开(公告)日：2017-01-05

    申请号：US15210360

    申请日：2016-07-14

    申请人： Chugai Seiyaku Kabushiki Kaisha

    发明人： Tomoyuki IGAWA ,  Shinya Ishii ,  Atsuhiko Maeda ,  Takashi Nakai

    IPC分类号： C07K16/28 ,  C07K14/735 ,  C07K16/18

    CPC分类号： C07K16/283 ,  A61K2039/505 ,  A61K2039/545 ,  C07K14/70535 ,  C07K16/18 ,  C07K16/248 ,  C07K16/28 ,  C07K16/2866 ,  C07K16/4241 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/52 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/30

    摘要： An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above.The present inventors discovered that antigen uptake into cells is facilitated by an antibody having human FcRn-binding activity at the plasma pH and a lower antigen-binding activity at the early endosomal pH than at the plasma pH; such antibodies can increase the number of antigens to which a single antibody molecule can bind; the reduction of antigen in plasma can be facilitated by administering such an antibody; and antibody pharmacokinetics can be improved by using such antibodies.

    摘要翻译： 本发明人发现，通过在血浆pH下具有人FcRn结合活性的抗体和在早期内体体内的pH低于等离子体pH下抗原结合活性较低的抗体促进了对细胞的吸收; 这样的抗体可以增加单个抗体分子可以结合的抗原的数量; 可以通过施用这样的抗体来促进血浆中抗原的降低; 可以通过使用这样的抗体来改善抗体药代动力学。

    ANTIGEN-BINDING MOLECULE FOR PROMOTING ELIMINATION OF ANTIGENS
    48.
    发明申请
    ANTIGEN-BINDING MOLECULE FOR PROMOTING ELIMINATION OF ANTIGENS 有权

    公开(公告)号：US20220389118A1

    公开(公告)日：2022-12-08

    申请号：US17561207

    申请日：2021-12-23

    申请人： Chugai Seiyaku Kabushiki Kaisha

    发明人： Tomoyuki Igawa ,  Atsuhiko Maeda ,  Kenta Haraya ,  Yuki Iwayanagi ,  Tatsuhiko Tachibana

    IPC分类号： C07K16/46 ,  C07K16/28

    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.

    ANTIBODY MOLECULES
    49.
    发明申请
    ANTIBODY MOLECULES 有权

    公开(公告)号：US20220306755A1

    公开(公告)日：2022-09-29

    申请号：US17829641

    申请日：2022-06-01

    申请人： Chugai Seiyaku Kabushiki Kaisha

    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： C07K16/28 ,  C07K16/46

    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.