Mitsubishi Tanabe Pharma Corporation

The University of Tokyo

Yasuhiro Fujino

Hiroshi Ochi

Masayuki Hayashi

Yoshihiro Shimizu

Tsutomu Yoshikawa

Hiroshi Ikegami

Takuya Ueda

Takashi Kanamori

Kouichi Wada

Shinsuke Ooike

Hideo Tomozane

Kotomi Oda

Masahiko Morioka

Makoto Sakiyama

Risako Fujita

Daisuke Abe

An antibody has an antagonistic effect against IL-33. In particular an isolated human anti-IL-33 neutralizing monoclonal antibody has framework regions with amino acid sequences from a germline, including combinations and fragments of such sequences. The epitopes for a plurality of anti-IL-33 monoclonal antibodies were identified, human anti-IL-33 neutralizing monoclonal antibodies were obtained, and the complementarity-determining regions that achieve high binding ability to IL-33 was specified by introducing mutations in the complementarity-determining regions. The identified complementarity-determining regions were used to produce the foregoing human anti-IL-33 neutralizing monoclonal antibodies having framework regions.

Human anti-IL-33 neutralizing monoclonal antibody

An object of the present invention is to provide an antibody having antagonistic effect against IL-33, in particular an isolated human anti-IL-33 neutralizing monoclonal antibody wherein amino acid sequences of framework regions are amino acid sequences that are amino acid sequences from a germline or a combination of amino acid sequences thereof, or a fragment thereof. The epitopes for a plurality of anti-IL-33 monoclonal antibodies were identified, human anti-IL-33 neutralizing monoclonal antibodies were obtained, and the complementarity-determining regions that achieve high binding ability to IL-33 was specified by introducing mutations in the complementarity-determining regions. The identified complementarity-determining regions were used to produce a human anti-IL-33 neutralizing monoclonal antibody having framework regions comprising amino acid sequences that are amino acid sequences of a germline or a combination of amino acid sequences thereof.

The polynucleotide construct of (1) or (2) below is used to perform ribosome display, CIS display and/or mRNA display in order to screen a Fab against an antigen of interest: (1) a polynucleotide construct which monocistronically comprises a ribosome-binding sequence, Fab first chain-coding sequence, linker peptide-coding sequence, Fab second chain-coding sequence and scaffold-coding sequence in this order, and further comprises at its 3'-end a structure necessary for maintaining a complex with the Fab encoded by itself; and (2) a polynucleotide construct which comprises a Fab first chain-expressing cistron and a Fab second chain-expressing cistron each containing a ribosome-binding sequence, a Fab first chain-coding sequence or Fab second chain-coding sequence, and a scaffold-coding sequence in this order, the first Fab-expressing cistron further comprising at its 3&#x2032;-end a ribosome stall sequence, said Fab second chain-expressing cistron further comprising at its 3&#x2032;-end a structure necessary for maintaining a complex with the Fab encoded by itself.

Polynucleotide construct capable of displaying fab in a cell-free translation system, and method for manufacturing and screening fab using same

A therapeutic drug for cancer containing a substance selected from the group consisting of a novel cyanopyridine derivative, a pharmaceutically acceptable salt, a hydrate, a water adduct and a solvate as an active ingredient can be provided.

Cyanopyridine derivative and use thereof as medicine

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Osaka, Japan

Yasuhiro Fujino