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公开(公告)号:US12122840B2
公开(公告)日:2024-10-22
申请号:US18425859
申请日:2024-01-29
IPC分类号: C07K16/28 , A61K39/395 , C07K16/00 , G01N33/68
CPC分类号: C07K16/2866 , A61K39/39591 , C07K16/00 , C07K16/28 , G01N33/6854 , C07K2317/24 , C07K2317/565 , C07K2317/732
摘要: The present inventors provide methods for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The present invention also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies, comprising modifying isoelectric point. The present invention further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.
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公开(公告)号:US12060654B2
公开(公告)日:2024-08-13
申请号:US16463218
申请日:2017-11-28
发明人: Tomoyuki Igawa , Hiroyuki Ishikawa
CPC分类号: C40B40/10 , C07K16/244 , C07K16/2818 , C07K16/2866 , A61K2039/505
摘要: The present invention relates to a ligand binding molecule whose ligand binding activity is attenuated by the cleavage of a cleavage site and a method for producing the same, a complex formed by the ligand binding molecule and a ligand, a fusion protein comprising the ligand binding molecule and a ligand, and a pharmaceutical composition comprising the ligand binding molecule or a fusion protein of the ligand binding molecule and a ligand.
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公开(公告)号:US20240239906A1
公开(公告)日:2024-07-18
申请号:US18432567
申请日:2024-02-05
IPC分类号: C07K16/28 , A61K39/395 , C07K16/00 , G01N33/68
CPC分类号: C07K16/2866 , A61K39/39591 , C07K16/00 , C07K16/28 , G01N33/6854 , C07K2317/24 , C07K2317/565 , C07K2317/732
摘要: The present inventors provide methods for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The present invention also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies, comprising modifying isoelectric point. The present invention further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.
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公开(公告)号:US20240158785A1
公开(公告)日:2024-05-16
申请号:US18411929
申请日:2024-01-12
发明人: Tomoyuki Igawa , Shigero Tamba , Shun Shimizu , Kanako Tatsumi , Shojiro Kadono , Hiroki Kawauchi , Kazuhiro Ohara , Masayuki Matsushita , Takashi Emura , Masaki Kamimura
IPC分类号: C12N15/10 , C07K16/00 , C07K16/24 , C07K16/28 , C07K16/30 , C07K16/42 , C07K16/44 , C40B50/06
CPC分类号: C12N15/1093 , C07K16/00 , C07K16/005 , C07K16/248 , C07K16/2809 , C07K16/2863 , C07K16/2866 , C07K16/30 , C07K16/4283 , C07K16/44 , C40B50/06 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/92
摘要: An objective of the present invention is to provide target tissue-specific antigen-binding molecules, antigen-binding molecules whose antigen-binding activity varies depending on the concentration of an unnatural compound, libraries comprising a plurality of the antigen-binding molecules which are different from one another, pharmaceutical compositions comprising the antigen-binding molecules, methods of screening for the antigen-binding molecules, and methods for producing the antigen-binding molecules. The present inventors created antigen-binding domains whose antigen-binding activity varies depending on the concentration of a small molecule compound or antigen-binding molecules containing an antigen-binding domain, and libraries comprising a plurality of the antigen-binding domains which are different from one another or antigen-binding domains, and demonstrated that the above-noted objective could be achieved by using the libraries. Various diseases originating from target tissues can be treated in a target tissue-specific manner by using the antigen-binding molecules of the present invention.
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5.
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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6.
公开(公告)号:US11952422B2
公开(公告)日:2024-04-09
申请号:US16769299
申请日:2018-12-04
发明人: Shun Shimizu , Shu Wen Samantha Ho , Naoka Hironiwa , Mika Sakurai , Taro Miyazaki , Tomoyuki Igawa
CPC分类号: C07K16/2809 , C07K16/2863 , C07K16/2878 , C07K16/303 , C07K2317/24 , C07K2317/31 , C07K2317/33 , C07K2317/526 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/71 , C07K2317/75 , C07K2317/92 , C40B30/04
摘要: Antigen-binding domains that are capable of binding to CD3 and CD137 but do not bind to CD3 and CD137 at the same time and methods of using the same are provided. Methods to obtain antigen binding domains which bind to two or more different antigen more efficiently are also provided.
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公开(公告)号:US20240083939A1
公开(公告)日:2024-03-14
申请号:US18505180
申请日:2023-11-09
发明人: Tomoyuki Igawa , Zenjiro Sampei , Tetsuya Wakabayashi , Eriko Ito
CPC分类号: C07K1/22 , C07K14/70535 , C07K16/2809 , C07K16/2866 , C07K16/303 , C07K16/36 , C07K16/468 , C07K2317/52 , C07K2317/526 , C07K2317/567 , C07K2317/622 , C07K2317/66 , C07K2317/94 , C07K2319/30
摘要: The present invention provides efficient methods based on alteration of the protein A-binding ability, for producing or purifying multispecific antibodies having the activity of binding to two or more types of antigens to high purity through a protein A-based purification step alone. The methods of the present invention for producing or purifying multispecific antibodies which feature altering amino acid residues of antibody heavy chain constant region and/or variable region. Multispecific antibodies with an altered protein A-binding ability, which exhibit plasma retention comparable or longer than that of human IgG1, can be efficiently prepared in high purity by introducing amino acid alterations of the present invention into antibodies.
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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:US11739149B2
公开(公告)日:2023-08-29
申请号:US16704464
申请日:2019-12-05
发明人: Tomoyuki Igawa , Shojiro Kadono , Naoka Hironiwa , Mika Sakurai
CPC分类号: C07K16/2809 , C07K16/2848 , C07K16/2863 , C07K16/2866 , C07K16/2875 , C07K16/2896 , C07K16/30 , C07K16/4283 , C07K2317/24 , C07K2317/31 , C07K2317/526 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2319/00 , C07K2319/70
摘要: The present inventors have successfully prepared an antigen-binding molecule comprising an antibody variable region that has binding activity against a molecule expressed on the surface of a T cell and a molecule expressed on the surface of any other immunocyte, but does not bind to these molecules at the same time. The present invention allows the preparation of an antigen-binding molecule capable of circumventing adverse reactions that may be caused by the cross-linking of T cells to other immunocytes, and provides an antigen-binding molecule suitable as a drug.
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公开(公告)号:US11718672B2
公开(公告)日:2023-08-08
申请号:US17670917
申请日:2022-02-14
发明人: Sotaro Naoi , Shu Feng , Tomoyuki Igawa , Shu Wen Samantha Ho
CPC分类号: C07K16/2809 , C07K16/28 , C07K16/2878 , A61K2039/505 , C07K2317/31 , C07K2317/35 , C07K2317/52 , C07K2317/522 , C07K2317/55 , C07K2317/565 , C07K2317/73 , C07K2317/92
摘要: The disclosure provides multispecific antigen-binding molecules that comprise a first antigen-binding moiety and a second antigen-binding moiety, each of which is capable of binding to CD3 and CD137, but does not bind to CD3 and CD137 at the same time; and a third antigen-binding moiety that is capable of binding to DLL3, preferably human DLL3, which induce T-cell dependent cytotoxity more efficiently whilst circumventing adverse toxicity concerns or side effects that other multispecific antigen-binding molecules may have. The present invention provides multispecific antigen-binding molecules and pharmaceutical compositions that can treat various cancers, especially those associated with DLL3, by comprising the antigen-binding molecule as an active ingredient.
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