Chugai Seiyaku Kabushiki Kaisha

Osaka University

Tomoyuki Igawa

Atsuhiko Maeda

Taichi Kuramochi

Hiroyuki Tsunoda

Tatsuhiko Tachibana

Naoka Hironiwa

Hirotake Shiraiwa

Hitoshi Katada

Shojiro Kadono

Futa Mimoto

Shinya Ishii

Yuji Hori

Shun Shimizu

Mika Sakurai

Takahiro Ishiguro

Hiroki Kawauchi

Kenta Haraya

Hiroyuki Ishikawa

Yoshinao Ruike

Takashi Nakai

Junichi Nezu

Kanako Tatsumi

Shigero Tamba

Tetsuo Kojima

Takehisa Kitazawa

Yuki Iwayanagi

Yasuo Sekimori

Masaki Kamimura

Meiri Kawazoe

Hiroyasu Muramatsu

Atsunori Ueyama

Takeshi Baba

Atsushi Muto

Tsukasa Suzuki

Tetsuhiro Soeda

Yumiko Kawai

Keiko Esaki

Miho Funaki

Atsushi Narita

Shu Wen Samantha Ho

Genki Nakamura

Masaru Muraoka

Masayuki Tsuchiya

Takashi Emura

Yutaka Matsuda

Atsushi Matsuo

Zenjiro Sampei

Yasuko Kinoshita

Masayuki Matsushita

Yoshinobu Higuchi

Taro Miyazaki

Keiko Kasutani

Shimon Sakaguchi

Shu Feng

Akira Hayasaka

Hiroki Hayashi

Yuri Teranishi

Kazutaka Yoshihashi

Tatsuya Kawa

Sotaro Naoi

Yukiko Nishida

Chifumi Imai

Chifumi Moriyama

Souhei Ohyama

Reiko Irie

Yasunori Komori

Kazuhiro Ohara

Hiroaki Susumu

Yoshinori Watanabe

Masami Suzuki

Jun-Ichi Nezu

Shigeto Kawai

Daisuke Kameoka

Atsuhiko Kato

Kiyotaka Nakano

Hajime Miyamoto

Izumi Sugo

Noriyuki Takahashi

Yasufumi Kikuchi

Kenji Taniguchi

Akihisa Sakamoto

Masakazu Fukuda

Hiroko Konishi

Megumi Tanaka

Takeaki Kawai

Hiroyoshi Nishikawa

Shigero Tanba

Kiyoaki Sakata

Mika Endoh

Etsuko Takeiri

Eri Hashimoto

Akiko Koga

Takeshi Yoshino

Eriko Murata

Machiko Fujino

Kazuki Kato

The present disclosure provides anti-CTLA-4 antibodies and methods of producing and using the antibodies. The present disclosure also provides nucleic acids encoding the anti-CTLA-4 antibodies and host cells containing the nucleic acids. Furthermore, the present disclosure provides polypeptides containing a variant Fc region containing amino acid alterations in a parent Pc region and methods of producing and using the polypeptides.

Anti-CTLA-4 antibody and use thereof

An objective of the invention is to provide an antibody, a composition for use in detecting or capturing a polypeptide in a sample, and a method for detecting or capturing a polypeptide in sample. The disclosure provides an antibody, a composition for use in detecting or capturing a polypeptide in a sample, and a method for detecting or capturing a polypeptide in sample.

Antibodies, compositions for use in detecting or capturing a polypeptide in a sample, and methods for detecting or capturing a polypeptide in a sample

The present disclosure provides anti-CTLA-4 antibodies and methods of producing and using the antibodies. The present disclosure also provides nucleic acids encoding the anti-CTLA-4 antibodies and host cells containing the nucleic acids. Furthermore, the present disclosure provides polypeptides containing a variant Fc region containing amino acid alterations in a parent Fc region and methods of producing and using the polypeptides.

A multiple antigen-binding molecule fusion molecule containing a multiple antigen-binding molecule (α) having an immune cell antigen-binding region and a cancer antigen-binding region, a cancer tissue-specific protease-cleavable linker (β), and a masking molecule (γ) containing a polypeptide having the amino acid sequence QDGNE (SEQ ID NO: 15), in which the multiple antigen-binding molecule (α) and the masking molecule (γ) are linked via the cancer tissue-specific protease-cleavable linker (β).

Multiple antigen binding molecular fusion, pharmaceutical composition, method for identifying linear epitope, and method for preparing multiple antigen binding molecular fusion

The present inventors have discovered that in living organisms that have received an antigen-binding molecule containing an antigen-binding domain whose binding activity to an antigen changes depending on ion concentration conditions and containing an FcRn-binding domain having FcRn-binding activity in a neutral pH range, immune responses to the antigen are induced. Furthermore, the present inventors have discovered that in living organisms that have received an antigen-binding molecule containing an antigen-binding domain whose binding activity to an antigen changes depending on ion concentration conditions and containing an FcRn-binding domain having FcRn-binding activity in a neutral pH range, immune responses to the antigen are induced, and also the antigen-binding molecule has cytotoxicity or antiproliferative action against cancer cells, foreign biological species, or such that express the antigen to which the antigen-binding molecule binds.

Antigen-binding molecule inducing immune response to target antigen

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.

Heterodimerized polypeptide

It is intended to provide a method for efficiently and stably producing a heteromultimer by incubating homo variants of plural types of heavy chain constant region-containing polypeptides differing in antigen-binding activity under a reducing condition that reorganize the inter-polypeptide disulfide bond between cysteine residues outside of core hinge regions. A feature of the production method of the present invention is that amino acid residues in the core hinge regions do not form any disulfide bond.

Method for producing polypeptide hetero-oligomer

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.

Modified Fc region of antibody

The present inventors have successfully prepared a library consisting essentially of a plurality of antigen-binding molecules differing in sequence from each other, the antigen-binding molecules each comprising an antibody variable region that has binding activity against a first antigen and a second antigen different from the first antigen, but does not bind to the first antigen and the second antigen at the same time. Use of the library of the present invention allows the obtainment of a variable region having enhanced ability to bind to the first antigen and the production of a bispecific antibody against the first antigen and a cancer antigen. Moreover, the present inventors have also successfully prepared an antigen-binding molecule comprising an antibody variable region that has binding activity against three different antigens, but does not bind to these antigens at the same time.

Library of antigen-binding molecules including modified antibody variable region

The present invention relates to a ligand-binding molecule the ligand-binding activity of which is attenuated by the cleavage of a cleavage site, a method for producing the ligand-binding molecule, 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.

Ligand-binding molecule having adjustable ligand-binding activity

The disclosure provides anti-myostatin antibodies and methods of making and using the same. Nucleic acids encoding the anti-myostatin antibodies and host cells comprising the nucleic acids are also provided. The anti-myostatin antibodies have uses that include treating a muscle wasting disease, reducing body fat accumulation, and increasing mass and strength of muscle tissue. The disclosure also provides polypeptides containing a variant Fc region and methods of making and using the same. Nucleic acids encoding the polypeptides and host cells comprising the nucleic acids are also provided. The polypeptides have uses that include suppressing the activation of immune cells; treating an immunological inflammatory disease, autoimmune disease, or viral infection; and increasing muscle mass and strength or reducing body fat accumulation.

Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use

As a result of producing ACE910 variants in which various sites of the constant regions were modified, the inventors discovered bispecific antibodies having FVIII mimetic activity higher than that of ACE910. The inventors also identified mutation positions that elevate the FVIII mimetic activity and discovered methods for elevating the FVIII mimetic activity by using the mutations.

Bispecific antibodies which bind blood coagulation factor VIII and have enhanced activity, and methods of use thereof for treating bleeding and associated conditions

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.

Method of modifying isoelectric point of antibody via amino acid substitution in CDR

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.

Ligand-binding molecule having adjustable ligand binding activity

Growing community of inventors

Shizuoka, Japan

Tomoyuki Igawa