Kirin Beer Kabushiki Kaisha

Kyowa Hakko Kirin Co., Limited

Kirin Brewery Company, Limited

Kazuhiro Motoki

Yasuhiko Koezuka

Hideaki Yoshida

Shiro Kataoka

Koji Kabaya

Tetsuya Hagiwara

Masayuki Kai

Tatsuo Higa

Takenori Natori

Yasunori Yamaguchi

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

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 invention relates to a method for activating human-derived antigen-presenting cells by in vitro cultivation with at least one of the glycoside compounds represented by formula (A) or salts thereof [preferred example: (2S,3S,4R)-1-(&#x3b1;-D-galactopyranosyloxy)-2-hexacosanoylamino-3,4-octadecanediol], and to human antigen-presenting cells activated by the method. The invention also relates to a method for treatment of cancer and infectious diseases including AIDS with the activated human antigen-presenting cells, and to a use of the activated human antigen-presenting cells in the preparation of medicines for treating such diseases. The invention can provide a satisfactory therapeutic effect on cancer and infectious diseases including AIDS without the need to pulse the human antigen-presenting cells with tumor antigens.

Method for activating human antigen-presenting cells, activated human antigen-presenting cells, and use thereof

A composition for enhancing immunogenicity of tumor cells or pathogen-infected cells comprising a compound having an &agr;-glycosylceramide structure or a salt or solvate thereof is provided. Tumor cells of which immunogenicity is enhanced by the compound having an &agr;-glycosylceramide structure are useful for tumor therapy (cancer vaccine therapy).

Composition for enhancing cellular immunogenicity comprising alpha-glycosylceramides

The present invention relates to a method for the treatment of thrombocytopenia wherein an effective amount of a compound represented by the formula (A) is administered to a patient: wherein R.sub.2 represents H or OH, X is an integer of 0-26 or R represents --(CH.sub.2).sub.7 CH.dbd.CH(CH.sub.2).sub.7 CH.sub.3, and R.sub.1 is a substituent defined by the following (a) to (d):

Pharmaceutical compositions and therapeutic methods

The present invention relates to a pharmaceutical composition (a marrow cell proliferation accelerator, a radioprotective agent, a therapeutic agent for thrombocytopenia) comprising a compound represented by the following formula (A), and to a therapeutic or prophylactic method (a method for accelerating marrow cell proliferation, a method for protecting human against radiation damage, a method for the treatment of thrombocytopenia) characterized in that an effective amount of a compound represented by the following formula (A) is administered to human: ##STR1## wherein R represents ##STR2## (wherein R.sub.2 represents H or OH, X is an integer of 0-26) or --(CH.sub.2).sub.7 CH.dbd.CH(CH.sub.2).sub.7 CH.sub.3, and R.sub.1 is one of the substituents defined by the following (a) to (d):

Method for accelerating marrow cell proliferation

Sphingoglycolipid compounds and therapeutic uses thereof

The present invention relates to a pharmaceutical composition (a marrow cell proliferation accelerator, a radioprotective agent, a therapeutic agent for thrombocytopenia) comprising a compound represented by the following formula (A), and to a therapeutic or prophylactic method (a method for accelerating marrow cell proliferation, a method for protecting human against radiation damage, a method for the treatment of thrombocytopenia) characterized in that an effective amount of a compound represented by the following formula (A) is administered to human: ##STR1## wherein R.sub.2 represents ##STR2## 26) or --(CH.sub.2).sub.7 CH=CH(CH.sub.2).sub.7 CH.sub.3, and R.sub.1, is one of the substituents defined by the following (a) to (d): (a) --CH.sub.2 (CH.sub.2).sub.y CH.sub.3, (b) --CH(OH)(CH.sub.2).sub.y (CH.sub.3).sub.2, and (c) --CH(OH)(CH.sub.2).sub.y CH(CH.sub.3).sub.2, and (d) --CH=CH(CH.sub.2).sub.y CH.sub.3 (wherein Y is an integer of 5-17).

Growing community of inventors

Takasaki, Japan

Kazuhiro Motoki