Chugai Seiyaku Kabushiki Kaisha

Osaka University

Kabushiki Kaisha Toshiba

Toshiba Energy Systems & Solutions Corporation

Takahiro Ishiguro

Tomoyuki Igawa

Yasuko Kinoshita

Yumiko Kawai

Hirotake Shiraiwa

Junichi Nezu

Atsushi Narita

Hiroyuki Tsunoda

Taichi Kuramochi

Naoka Hironiwa

Kiyotaka Nakano

Mika Sakurai

Izumi Sugo

Koichi Jishage

Yuji Sano

Tatsuhiko Tachibana

Jun-Ichi Nezu

Shigeto Kawai

Masamichi Sugimoto

Yushi Koyama

Megumi Tanaka

Shigeyuki Iijima

Shimon Sakaguchi

Takeshi Yoshino

Toshiaki Tsunenari

Mika Endo

Hiroyoshi Nishikawa

Hiroko Konishi

Akihisa Sakamoto

Otoya Ueda

Naoko Wada

Hiroshi Hino

Shinnosuke Hamajima

Takeshi c/o Chugai Seiyaki KK Yoshino

Hiroyuki c/o Chugai Seiyaki KK Tsunoda

Jun-Ichi c/o Chugai Seiyaki KK Nezu

Kiyotaka c/o Chugai Seiyaki KK Nakano

Hiroyuki Tsundoa

Genetically modified non-human animals which are deficient in expression of an endogenous GPC3 polypeptide and express a human GPC3 polypeptide at a physiologically adequate level; methods for producing the non-human animals; and methods for evaluating test substances using the non-human animals. Furthermore, methods for evaluating test substances regarding their safety, therapeutic effects on diseases, pharmacokinetics, in vivo distribution, and such, using the non-human animals as models.

Gene-modified mouse expressing human GPC3 polypeptide

The present invention provides genetically modified non-human animals which are deficient in at least one or more types of CD3 genes selected from the group consisting of endogenous CD3&#x3b5;, CD3&#x3b4;, and CD3&#x3b3; in its genome and functionally express at least one or more types of human CD3 genes selected from the group consisting of human CD3&#x3b5;, CD3&#x3b4;, and CD3&#x3b3;. In the genetically modified non-human animals of the present invention, mature T cell differentiation and production can take place, and immunocompetent cells including T cells can exert their functions. The genetically modified non-human animals of the present invention enable efficient evaluation and screening in the development of therapeutic agents and therapeutic methods that use human CD3-mediated targeted drugs.

Non-human animal having human CD3 gene substituted for endogenous CD3 gene

It was discovered that antigen-binding molecules comprising (i) a domain that binds to a molecule expressed on the surface of cells having immune response-suppressing functions, and (ii) a T cell receptor complex-binding domain exhibit more superior antitumor effects than conventional antigen-binding molecules by crosslinking T cells with cells having immune response-suppressing functions, and damaging the cells having immune response-suppressing functions.

T cell-redirected antigen-binding molecule for cells having immunosuppression function

The present invention provides anticancer agents comprising as an active ingredient a bispecific antibody that comprises a domain comprising a glypican 3-binding antibody variable region, a domain comprising a T cell receptor complex-binding antibody variable region, and common L chains that can enhance the affinity for the two antigens, as well as pharmaceutical compositions comprising the bispecific antibody as an active ingredient, the compositions being for use in combination with other anticancer agents. The bispecific antibodies are novel molecules which are produced with high efficiency and have strong anti-tumor activity as well as safety and excellent pharmacodynamics. The bispecific antibodies can be expected to be applied to various cancers.

Cell injury inducing therapeutic drug for use in cancer therapy

By replacing the antigen-binding domain, the present inventors discovered novel polypeptide complexes that retain BiTE's strong anti-tumor activity and excellent safety properties, as well as have long half-life in blood and can damage various different target cells.

Cytotoxicity-inducing therapeutic agent

Multi specific antigen-binding molecules maintaining excellent cellular cytotoxicity and high stability, which comprise a domain that contains an antibody variable region having glypican 3-binding activity and a domain that contains an antibody variable region having T-cell receptor complex-binding activity are provided. Since the provided molecules show a strong cytotoxicity against cells and tissues expressing glypican 3, it is possible to produce pharmaceutical compositions for treating or preventing various cancers.

Novel multispecific antigen-binding molecules maintaining excellent cellular cytotoxicity and high stability, which comprise a domain that contains an antibody variable region having glypican 3-binding activity and a domain that contains an antibody variable region having T-cell receptor complex-binding activity, were discovered. Since the molecules of the present invention show a strong cytotoxicity against cells and tissues expressing glypican 3, it is possible to produce novel pharmaceutical compositions for treating or preventing various cancers.

Cytotoxicity-inducing theraputic agent

A method of modulating the plasma half-life of anti-glypican 3 antibody, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody that has a plasma half-life that has been modulated, a method of preparing the anti-glypican 3 antibody and a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient are provided. Disclosed is a method of modulating the plasma half-life of anti-glypican 3 antibody by modifying an amino acid residue that is exposed on the surface of the anti-glypican 3 antibody; and anti-glypican 3 antibody that has a plasma half-life that has been modulated by amino acid residue modification, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody, and a method of preparing the anti-glypican 3 antibody and producing a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient.

Anti-glypican-3 antibody having improved kinetics in plasma

An antibody capable of binding to a specific region of glypican 3, as well as a humanized antibody created based on that antibody are disclosed. The anti-GPC3 antibody of the invention has a higher ADCC activity and CDC activity compared with those of a conventional antibody. The antibody of the present invention is useful as a cell growth inhibitor, an anticancer agent and an agent for diagnosis of cancers.

Anti-glypican 3 antibody

An anti-glypican 3 antibody with modified sugar chains, more specifically, an anti-glypican 3 antibody lacking fucose is provided. The anti-glypican 3 antibody with modified sugar chains of the present invention may be produced by a process comprising introducing a nucleic acid encoding an anti-glypican 3 antibody into host cells with reduced fucose addition capability, such as YB2/0 cells and cells lacking a fucose transporter. The anti-glypican 3 antibody with modified sugar chains of the present invention has a high level of cytotoxic activity and therefore is useful as a cell growth inhibitor such as an anticancer agent.

Anti-glypican 3 antibody having modified sugar chain

Growing community of inventors

Kanagawa, Japan

Takahiro Ishiguro