Astellas Pharma Gmbh

National Cancer Center

Arialys Therapeutics, Inc.

Daisuke Yamajuku

Satoshi Kubo

Takashi Honda

Hiroki Sasaki

Masayuki Komatsu

Takeshi Tsutsumi

Akifumi Morinaka

Yoshiyuki Tenda

Hiromu Sato

Shinji Soga

Fumiko Chiwaki

Masatoshi Yuri

Kazunori Arai

Mako Ogino

Mutsumi Seki

Yuko Kusuzaki

Atsuo Kanno

Takuya Kito

Masashi Maeda

Takuma Mihara

The present invention addresses the problem of providing a novel therapeutic agent for treating patients with anti NMDAR encephalitis. Patients with an anti NMDAR encephalitis have a pathogenic anti-human NR1 antibody that induces internalization of NMDAR on cell surface. As a result, NMDAR function is weakened in the patients' brain. The present inventors found that the one-armed anti-human NR1 antibody according to the present invention binds to NR1 competitively with the pathogenic anti-human NR1 antibody and inhibits the internalization of NMDAR by the pathogenic anti-human NR1 antibody to thereby exhibit therapeutic effect on anti NMDAR encephalitis. Accordingly, the present invention provides a one-armed anti-human NR1 antibody, a polynucleotide encoding the antibody, an expression vector containing the polynucleotide, a host cell transformed by the expression vector, a method for producing the antibody, a pharmaceutical composition comprising the antibody, a use of the antibody in the manufacture of the pharmaceutical composition, and a method for treating anti NMDAR encephalitis using the antibody.

Anti-human NR1 antibody derivative

An objective of the present invention is to provide an anti-TSPAN8/anti-CD3 bispecific antibody and an anti-TSPAN8 antibody usable in treatment or prevention in human. A human monoclonal antibody producing mouse was immunized with a peritoneal disseminated cancer cell isolated from a patient, to obtain an antibody 16B11 and an antibody 16B12 that selectively bind to a peritoneal disseminated cancer cell. These antibodies were anti-TSPAN8 antibodies that bind to the region from amino acid positions 126 to 155 of TSPAN8 and exhibited strong binding activity to TSPAN8 expressed in the peritoneal disseminated cancer cell. Further, an anti-TSPAN8(16B11)-anti-CD3 bispecific antibody produced based on the sequence of 16B11 exhibited a cytotoxic activity against the TSPAN8-expressing cancer cell in vitro, exerted an anti-tumor action on TSPAN8-expressing cancer cell-bearing mice in vivo, and extended the lifetime of peritoneal dissemination model mice.

Anti-TSPAN8/anti-CD3 bispecific antibody and anti-TSPAN8 antibody

Described herein are novel anti-human Ig&#x3b2; antibodies, as well as methods for making the antibodies and using the antibodies to treat or prevent autoimmune disease.

Anti-human Ig&#x3b2; antibody

[Problem] Provided is an anti-human Ig&#x3b2; antibody which crosslinks BCR and Fc&#x3b3;RIIb and has an immunosuppressive function more enhanced than that of an antibody in the prior art. [Means for Solution] An anti-human Ig&#x3b2; antibody comprising a heavy chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 31 to 35 of SEQ ID NO: 2, CDR2 consisting of the amino acid sequence of amino acid numbers 50 to 65 of SEQ ID NO: 2, and CDR3 consisting of the amino acid sequence of amino acid numbers 98 to 108 of SEQ ID NO: 2, a light chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 24 to 38 of SEQ ID NO: 4, CDR2 consisting of the amino acid sequence of amino acid numbers 54 to 60 of SEQ ID NO: 4, and CDR3 consisting of the amino acid sequence of amino acid numbers 93 to 101 of SEQ ID NO: 4, and a heavy chain constant region which is a human Ig&#x3b3;1 constant region having amino acid mutations of S239D, H268D, and L328W.

An anti-human TSLP receptor antibody that specifically binds to human TSLP receptor and inhibits an action of human TSLP through human TSLP receptor. A method for preventing or treating asthma by administering the anti-human TSLP receptor antibody or an antigen-binding fragment thereof. An anti-human TSLP receptor antibody had been studied by the present inventors, and an anti-human TSLP receptor antibody including a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3 was provided. It was revealed that the anti-human TSLP receptor antibody inhibits expression of TARC mRNA induced by TSLP and production of MDC proteins, and suppressed an allergic reaction in a monkeyantigen sensitization model.

Anti-human TSLP receptor antibody

[Problem] To provide an anti-human TSLP receptor antibody that specifically binds to human TSLP receptor and inhibits an action of human TSLP through human TSLP receptor. [Means for Solution] An anti-human TSLP receptor antibody had been studied by the present inventors, and an anti-human TSLP receptor antibody comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3 was provided. It was revealed that the anti-human TSLP receptor antibody inhibits expression of TARC mRNA induced by TSLP and production of MDC proteins, and suppressed an allergic reaction in a monkeyantigen sensitization model, and then the present invention was completed.

Growing community of inventors

Tokyo, Japan

Daisuke Yamajuku