Chugai Seiyaku Kabushiki Kaisha

Junichi Nezu

Tomoyuki Igawa

Naoka Hironiwa

Takahiro Ishiguro

Yumiko Kawai

Atsushi Narita

Atsuhiko Maeda

Hirotake Shiraiwa

Yuichi Hirata

Takeshi Baba

Mika Sakurai

Taichi Kuramochi

Yoshinao Ruike

Shinya Ishii

Shun Shimizu

Takehisa Kitazawa

Shigero Tamba

Miho Funaki

Akihisa Sakamoto

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.

Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly

The present inventors newly discovered that even if an antigen-binding molecule inhibits in vitro some of the physiological activities of an antigen having two or more physiological activities without inhibiting the remaining physiological activities, the molecule can promote elimination of the antigen from blood (from serum or plasma) and as a result reduce the physiological activities in vivo, when the antigen-binding molecule is conferred with the properties: (i) of binding to human FcRn under an acidic pH range condition; (ii) of binding under a neutral pH range condition to human Fc receptor stronger than native human IgG, and (iii) that its antigen-binding activity alters according to the ion concentration.

Methods for producing antibodies promoting disappearance of antigens having plurality of biological activities

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

The invention relates to VEGF-like nucleic acid sequences, their use, and vectors and transformants containing such sequences.

Nucleic acid sequences encoding VEGF-like factors and uses thereof

A novel human gene having a significant homology with a VEGF-C gene, a member of the VEGF family, has been isolated by the PCR method using primers designed based on the sequence of EST that is assumed to be homologous with the C-terminal region of the VEGF-C gene. Mouse and rat genes have been isolated based on the human gene isolated as above. A protein encoded by the above human gene has been isolated by introducing the gene into and expressing it. The isolated protein and genes can be applied to, for example, gene therapy for the VEGF-D deficiency, wound healing, and promotion of collateral vessel formation. Furthermore, VEGF-D protein inhibitors can be used as a novel anticancer drug, etc.

Growing community of inventors

Shizuoka, Japan

Junichi Nezu