Kyowa Hakko Kirin Co., Limited

Kirin Beer Kabushiki Kaisha

Kirin Pharma Kabushiki Kaisha

Genzyme Corporation

Shiro Kataoka

Tetsuya Yoshino

Tomoyuki Tahara

Yoshikatsu Kanai

Kazumasa Hasegawa

Hitoshi Endou

Hideaki Yoshida

Kazuhiro Motoki

Masayuki Kai

Tetsuya Hagiwara

Hamao Umezawa

Shohachi Nakajima

Atsuo Odagawa

Takafumi Tomura

Eiji Mori

Tomonori Tawara

Noriko Otani

Beverly Teicher

Nakayuki; Honma

A human antibody or a functional fragment thereof having specific binding ability to CD98 which is derived from the cell membrane of cancer cells and is in the form of a complex with a protein having an amino acid transporter activity (for example, LAT1) is disclosed. This antibody binds to CD98 in the form of a dimer with LAT1 on the surface of cancer cells, specifically attacks cancer cells expressing CD98 via the immune system by ADCC or CDC, and further inhibits amino acid uptake of the cancer cells via LAT1, to suppress growth of the cancer cells. Accordingly, a preventive and therapeutic agent for cancer comprising this antibody or a fragment thereof, which acts on various cancers, is specific to cancer, and causes no side effect, is provided.

Anti-CD98 antibody processes

This invention provides an agonist antibody to a human thrombopoietin receptor (human c-Mpl), and pharmaceutical compositions comprising the same for use in treatment of thrombocytopenia. The disclosed agonist antibody comprises (1) antibody constant regions comprising heavy and light chain constant regions, each of which may optionally contain domain substitutions, or may contain deletions, substitutions, additions, or insertions of amino acid residues, and (2) antibody variable regions capable of binding to and activating a human thrombopoietin receptor. The-agonist antibody further induces colony formation at a concentration of 10,000 ng/ml or lower, and has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less.

Agonist antibody to human thrombopoietin receptor

Anti-CD98 antibody

This invention provides an agonist antibody to a human thrombopoietin receptor (alias: human c-Mpl). More particularly, this invention provides an agonist antibody to a human thrombopoietin receptor, wherein the agonist antibody comprises: antibody constant regions comprising (1) amino acid sequences in a heavy chain constant region and a light chain constant region of a human antibody, (2) an amino acid sequence of a heavy chain constant region with a domain substituted between human antibody subclasses, and an amino acid sequence of a light chain constant region of a human antibody, or (3) amino acid sequences comprising a deletion(s), substitution(s), addition(s), or insertion(s) of one or several amino acid residues in the amino acid sequences of (1) or (2) above; and antibody variable regions capable of binding to and activating a human thrombopoietin receptor; and wherein the agonist antibody has the properties: (a) that the antibody induces colony formation at a concentration of 10,000 ng/ml or lower as determined by the CFU-MK colony formation assay using human umbilical-cord-blood-derived CD34+ cells; and (b) that the antibody has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less in the cell proliferation assay using UT7/TPO cell. Also provided is a pharmaceutical composition for treating thrombocytopenia comprising said antibody.

The present invention provides: an antibody or a antibody fragment thereof, which can bind to A33, which specifically attacks A33-expressing tumor cells with the use of ADCC and CDC based on the immune system, and for which no HAHA is produced; and a preventive or therapeutic agent for various malignant tumors including solid tumors that are currently treated with difficulty, which contains the antibody or an antibody fragment thereof. Specifically, the antibody or a functional fragment thereof is capable of binding to A33 and is produced by a hybridoma M10 (accession No. FERM BP-10107), M96 (accession No. FERM BP-10108), M165 (accession No. FERM BP-10106), N26 (accession No. FERM BP-10109), Q47 (accession No. FERM BP-10104), Q54 (accession No. FERM BP-10105), or R5 (accession No. FERM BP-10107). The preventive or therapeutic agent for tumors contains the antibody or a functional fragment thereof.

Anti-A33 antibody

This invention provides an anti-HLA-DR monoclonal antibody. This invention relates to an antibody binding to HLA-DR or a functional fragment thereof having (a) life-extending effects in nonhuman animals bearing HLA-DR-expressing cancer cells and (b) activity of suppressing immune responses lower than that of L243, or an antibody binding to HLA-DR or a functional fragment thereof exhibiting immunosuppressive activity equivalent to or higher than that of the mouse anti-HLA-DR monoclonal antibody L243 (ATCC HB-55).

Anti-HLA-DR antibody

Anti-TRAIL-R1 and R2 antibodies or functional fragments thereof, having at least one property selected from the following (a) to (c) of: (a) having activity to induce apoptosis in carcinoma cells expressing TRAIL-R1 and/or TRAIL-R2; (b) not having effect on normal human cells expressing TRAIL-R1 and/or TRAIL-R2; and (c) not inducing human hepatocyte toxicity.

Anti-TRAIL-R antibodies

An anthracycline compound, R20X2, of the following formula (II) is produced by a process which comprises subjecting an anthracycline compound, R20X3, of the following formula (I) or a salt thereof to reaction in the co-presence of (1) acetone and/or dimethylformamide and (2) an aqueous solution containing ammonium ion and/or trialkylamine. ##STR1## The anthracycline compound, R20X2, can be produced not only by the cultivation of actinomycetes but also, in accordance with the process as shown above, by chemical conversion of the anthracycline compound, R20X3, in a high yield.

Process for production of anthracycline compound R20X2

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Tokyo, Japan

Shiro Kataoka