公开(公告)号：US12122840B2

公开(公告)日：2024-10-22

申请号：US18425859

申请日：2024-01-29

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： Tomoyuki Igawa ,  Hiroyuki Tsunoda ,  Tatsuhiko Tachibana ,  Taichi Kuramochi

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.

公开(公告)号：US20240293402A1

公开(公告)日：2024-09-05

申请号：US18567435

申请日：2022-06-08

申请人： CHUGAI SEIYAKU KABUSHIKI KAISHA

发明人： Kenichi SAKAI ,  Hiromasa UCHIYAMA ,  Tomoyuki MINODA ,  Mayumi YOSHIKAWA ,  Shigemori NATSUMOTO ,  Ryusuke TAKANO

IPC分类号： A61K31/506 ,  A61K9/48

CPC分类号： A61K31/506 ,  A61K9/4858 ,  A61K9/4866

摘要： The present invention provides a pharmaceutical composition having excellent dissolution property and content uniformity and a production method thereof by mixing a p-toluenesulfonate of 7-[[2,3-difluoro-4-[2-[2-methoxyethyl(methyl)amino]ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4,5]deca-9-ene-9-carboxamide with specific additives, and formulating the mixture.

公开(公告)号：US20240270853A1

公开(公告)日：2024-08-15

申请号：US18289627

申请日：2022-06-02

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： Noriyuki Takahashi ,  Masakazu Kanamori ,  Bo Yang

IPC分类号： C07K16/28 ,  A61K39/00 ,  A61P11/00

CPC分类号： C07K16/2851 ,  A61P11/00 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/56

摘要： The invention provides anti-DDR2 antibodies that binds to DDR2, and methods of using the same. The invention further provides isolated nucleic acids encoding the anti-DDR2 antibodies, host cells comprising the same, and methods of producing the anti-DDR2 antibodies. The invention further provides use of the anti-DDR2 antibodies in the manufacture of a medicament.

公开(公告)号：US12060654B2

公开(公告)日：2024-08-13

申请号：US16463218

申请日：2017-11-28

申请人： CHUGAI SEIYAKU KABUSHIKI KAISHA

发明人： Tomoyuki Igawa ,  Hiroyuki Ishikawa

IPC分类号： C40B40/10 ,  C07K16/24 ,  C07K16/28 ,  A61K39/00

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.

公开(公告)号：US20240246922A1

公开(公告)日：2024-07-25

申请号：US18608369

申请日：2024-03-18

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： Yoshiaki Isshiki ,  Fumio Watanabe ,  Masaki Tomizawa ,  Kihito Hada ,  Kazuo Hattori ,  Kenichi Kawasaki ,  Ikumi Hyodo ,  Toshihiro Aoki

IPC分类号： C07D265/02 ,  C07C39/26 ,  C07C69/76 ,  C07C211/55 ,  C07C307/02 ,  C07C317/50 ,  C07C333/20 ,  C07D213/73 ,  C07D213/74 ,  C07D213/80 ,  C07D305/06 ,  C07D307/14 ,  C07D307/93 ,  C07D309/08 ,  C07D309/14 ,  C07D333/72 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D471/04 ,  C07F5/02 ,  C07F7/08

CPC分类号： C07D265/02 ,  C07C39/26 ,  C07C69/76 ,  C07C211/55 ,  C07C307/02 ,  C07C317/50 ,  C07C333/20 ,  C07D213/73 ,  C07D213/74 ,  C07D213/80 ,  C07D305/06 ,  C07D307/14 ,  C07D307/93 ,  C07D309/08 ,  C07D309/14 ,  C07D333/72 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D471/04 ,  C07F5/027 ,  C07F7/0812

摘要： The present disclosure provides, for example, a method of stabilizing the RAF/MEK complex in a subject, the method comprising administering to the subject an effective amount of a compound represented by the general formula below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:




wherein X1, X2, X3 and X4 are each independently —CR2═ or —N═, R2 is, for example, a halogen atom, R1 is, for example, —S(═O)2—NH—R8, R8 is, for example, a C1-6 alkyl group, R3 is, for example, a hydrogen atom, R5 is, for example, a halogen atom, R6 is, for example, a hydrogen atom, and R4 is, for example, a cyclopropyl group.

公开(公告)号：US20240239906A1

公开(公告)日：2024-07-18

申请号：US18432567

申请日：2024-02-05

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： Tomoyuki Igawa ,  Hiroyuki Tsunoda ,  Tatsuhiko Tachibana ,  Taichi ` Kuramochi

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.

公开(公告)号：US20240190960A1

公开(公告)日：2024-06-13

申请号：US18394091

申请日：2023-12-22

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： Tomoyuki IGAWA ,  Naoka HIRONIWA ,  Shogo KAMIKAWAJI ,  Tatsuya KIBAYASHI ,  Nasa SAVORY ,  Futa MIMOTO

IPC分类号： C07K16/28 ,  C12N5/078

CPC分类号： C07K16/2809 ,  C12N5/0634 ,  C07K2317/31

摘要： The present invention relates to a first antigen-binding molecule, a second antigen-binding molecule, and a combination thereof. The second antigen-binding molecule binds to an antigen/antigen-binding molecule complex containing a first antigen and the first antigen-binding molecule, and enhances the binding activity of the first antigen-binding molecule to the first antigen.

公开(公告)号：US20240158785A1

公开(公告)日：2024-05-16

申请号：US18411929

申请日：2024-01-12

申请人： Chugai Seiyaku Kabushiki Kaisha

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.

公开(公告)号：US11964950B2

公开(公告)日：2024-04-23

申请号：US17869226

申请日：2022-07-20

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： Yoshiaki Isshiki ,  Fumio Watanabe ,  Masaki Tomizawa ,  Kihito Hada ,  Kazuo Hattori ,  Kenichi Kawasaki ,  Ikumi Hyodo ,  Toshihiro Aoki

IPC分类号： C07D265/02 ,  C07C39/26 ,  C07C69/76 ,  C07C211/55 ,  C07C307/02 ,  C07C317/50 ,  C07C333/20 ,  C07D213/73 ,  C07D213/74 ,  C07D213/80 ,  C07D305/06 ,  C07D307/14 ,  C07D307/93 ,  C07D309/08 ,  C07D309/14 ,  C07D333/72 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D471/04 ,  C07F5/02 ,  C07F7/08

CPC分类号： C07D265/02 ,  C07C39/26 ,  C07C69/76 ,  C07C211/55 ,  C07C307/02 ,  C07C317/50 ,  C07C333/20 ,  C07D213/73 ,  C07D213/74 ,  C07D213/80 ,  C07D305/06 ,  C07D307/14 ,  C07D307/93 ,  C07D309/08 ,  C07D309/14 ,  C07D333/72 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D471/04 ,  C07F5/027 ,  C07F7/0812

摘要： The present disclosure provides, for example, a compound represented by the general formula below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:




wherein X1, X2, X3 and X4 are each independently —CR2═ or N═, R2 is, for example, a halogen atom, R1 is, for example, —S(═O)2—NH—R8, R8 is, for example, a C1-6 alkyl group, R3 is, for example, a hydrogen atom, R5 is, for example, a halogen atom, R6 is, for example, a hydrogen atom, and R4 is, for example, a cyclopropyl group. The compounds, salts or solvates provided by the present disclosure exhibit high RAF/MEK complex-stabilizing activity and can be used for the treatment or prevention of cell proliferative disorders, particularly cancers.

公开(公告)号：US20240124614A1

公开(公告)日：2024-04-18

申请号：US18269099

申请日：2021-12-22

申请人： Chugai Seiyaku Kabushiki Kaisha

发明人： Yuri IKAWA ,  Nasa SAVORY

IPC分类号： C07K16/46

CPC分类号： C07K16/468 ,  C07K2317/31 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/77

摘要： The present invention provides an antigen-binding molecule (e.g. antibody) with improved cytosol-penetrating ability, the molecule comprising an amino acid substitutions on at least one selected from the group consisting of CDRL1, CDRL2 and CDRL3 in a light-chain variable region, or an antigen-binding fragment (antibody fragment) thereof; and pharmaceutical compositions comprising the antigen-binding molecule; methods for delivering the antigen-binding molecule specifically into the cytosol of a target cell; methods of removing, suppressing, or activating a cytosolic antigen in a target cell-specific manner by using the antigen-binding molecule; and pharmaceutical compositions for diagnosing, preventing, or treating a disease in a subject comprising the antigen-binding molecule.