Chugai Seiyaku Kabushiki Kaisha

Xencor, Inc.

Izumi Sugo

Shigeyuki Iijima

Masamichi Sugimoto

Gregory Alan Lazar

Bassil I Dahiyat

Kiyotaka Nakano

Hisafumi Okabe

Takahiro Ishiguro

Megumi Tanaka

Tomoyuki Igawa

Masayuki Tsuchiya

Hiroyuki Tsunoda

Jun-Ichi Nezu

Shigeto Kawai

Yasuko Kinoshita

Yasuo Sekimori

Kiyoshi Habu

Takeshi Yoshino

Hiroko Konishi

Kenju Ueno

Kikuo Tomonou

Hiroyuki Tsundoa

Kiyotaka c/o Chugai Seiyaki KK Nakano

Jun-Ichi c/o Chugai Seiyaki KK Nezu

Hiroyuki c/o Chugai Seiyaki KK Tsunoda

Takeshi c/o Chugai Seiyaki KK Yoshino

An anti-glypican-3 antibody comprising one or more amino acid substitutions introduced in the Fc region is disclosed. Preferably, in the anti-glypican-3 antibody, one or more of the amino acid residues at the positions 239, 298, 326, 330 and 332 in the Fc region are substituted with other amino acid residues. Since the Fc-modified anti-glypican-3 antibody of the invention exhibit enhanced ADCC activity, it is useful in treating cancers, such as hepatic cancer. Also disclosed are an anticancer agent comprising the anti-glypican-3 antibody of the invention and a pharmaceutically acceptable carrier, as well as a method of treating a patient with cancer comprising administering to the patient the anticancer agent of the invention.

Anti-glypican-3 antibody

The present inventors revealed that deamidation of an antibody can be suppressed without influencing its activity by substituting a glycine that is located adjacent to an asparagine with another amino acid.

Methods for stabilizing proteins

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

The present invention provides a gene encoding a fucose transporter, a fucose transporter polypeptide, a method for screening for a compound that binds to a fucose transporter or a compound that inhibits fucose transport activity, a cell having inhibited fucose transporter functions, and a cell wherein the expression of the fucose transporter is inhibited. The present invention further relates to a method for producing recombinant protein, and specifically, to a method for producing protein by which fucose existing within the Golgi apparatus of a host cell is decreased, a method for inhibiting the addition of fucose to protein by which fucose existing within the Golgi apparatus of a host cell is decreased upon production of recombinant protein using the host cell, a method for increasing the cytotoxic activity of an antibody by which an antibody is produced using a cell wherein fucose existing within the Golgi apparatus is decreased, and a cell having a Golgi apparatus wherein fucose existing within the Golgi apparatus is decreased.

Fucose transporter

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Shizuoka, Japan

Izumi Sugo