Sankyo Company, Limited

Daiichi Sankyo Company, Limited

Daiichi Pharmaceutical Co., Ltd.

Snow Brand Milk Products Co., Ltd.

Fumie Kobayashi

Kanji Higashio

Masaaki Goto

Eisuke Tsuda

Kazuki Yano

Tomonori Morinaga

Hisataka Yasuda

Nobuaki Nakagawa

Nobuyuki Shima

Masatsugu Ueda

Kyoji Yamaguchi

Masahiko Kinosaki

Naohiro Washida

Shin'ichi Mochizuki

Akihiro Tomoyasu

Ken Takahashi

Yoshiji Yamada

Hiroaki Masunaga

Akihiko Murakami

Yasushi Yamashita

Hiromi Ogawa

Shin′ichi Mochizuki

Kaoji Higashio

Tadashi Nakakarumai

Shin-ichi Mochizuki

Toshiko Satake

Nobuaki Nishiura Heights 2-4 Nakagawa

Tomonori 11-12 Saiwaicho 3-Chome Morinaga

Akihiro Sk-Mansion Tomoyasu

Ken Nishiura Heights 1-4 Takahashi

Eisuke Diapalace Jichiidai 5-Bankan 407 Tsuda

Kazuki Nishiura Heights 3-1 Yano

Novel proteins and polypeptides binding to osteoclastogenesis inhibitory factor (OCIF) (OCIF-binding molecules, OBMs) and nucleic acids encoding these proteins and polypeptides are provided. Processes for producing these proteins, polypeptides, and nucleic acid molecules by genetic engineering are provided. Medicinal compounds are provided which comprise proteins and nucleic acids according to the invention, as well as proteins which bind to OBM, including anti-OBM antibodies. These compounds may be used for the treatment of bone disease.

Methods of reducing bone absorption comprising administering an antibody that binds OBM

A protein which inhibits osteoclast differentiation and/or maturation and a method for producing the protein. The protein is produced by human embryonic lung fibroblasts and has a molecular weight of about 60 kD and about 120 kD under non-reducing conditions and about 60 kD under reducing conditions on SDS-polyacrylamide gel electrophoresis. The protein can be isolated and purified from the culture medium of fibroblasts. Furthermore, the protein can be produced by gene engineering. The present invention includes cDNA for producing the protein by gene engineering, antibodies having specific affinity for the protein or a method for determining protein concentration using these antibodies.

Nucleic acid molecules encoding osteoclastogenesis inhibitory factor proteins

The present invention relates to a novel protein which binds to Osteoclastogenesis Inhibitory Factor (OCIF-binding molecule; OBM), a process for preparing the same, DNA encoding said protein, a protein having an amino acid sequence encoded by this DNA, a method for producing said protein by genetic engineering technique, and a pharmaceutical composition containing said protein. In addition, screening methods for a substance for controlling expression of said protein using said protein and the DNA, a substance which inhibits or modulates the biological activity of said protein, or a receptor which transmits the action of said protein through binding to said protein, the substance obtained by the screening methods, and a pharmaceutical composition which contains this substance are disclosed. An antibody for said protein, a process for preparing the same, a measuring method of said protein using the antibody, and a medicine comprising the antibody are also disclosed.

Antibodies to OCIF-binding molecules

A protein which inhibits osteoclast differentiation and/or maturation and a method of production of the protein. The protein is produced by human embryonic lung fibroblasts and has molecular weight of about 60 kD and about 120 kD under non-reducing conditions and about 60 kD under reducing conditions on SDS-polyacrylamide gel electrophoresis, respectively. The protein can be isolated and purified from culture medium of the said fibroblasts. Furthermore, the protein can be produced by gene engineering. The present invention includes cDNA for producing the protein by gene engineering, antibodies having specific affinity to the protein or a method for determination of the protein concentration using the antibodies.

Methods for using the osteoclastogenesis inhibitory factor (OCIF) protein

A novel protein and a process of producing the protein is provided. The protein is a glycoprotein having activity of suppressing the differentiation and/or maturation of adipocyte, having a molecular weight of about 45 kD under non-reducing conditions and about 28 kD and/or 23 kD under reducing conditions, and exhibiting affinity to heparin. A process of producing the protein comprising culturing human fibroblasts and purifying the culture broth by chromatography using an ion exchange column, affinity column, and reverse phase column. A cDNA encoding the protein and a process of producing the protein using the cDNA are also provided. The protein of the present invention is useful as a pharmaceutical composition for preventing or treating obesity or as an antigen for establishing immunological diagnosis, etc.

Protein and processes for producing the same

Proteins and methods for producing the proteins

The present invention relates to a novel protein which binds to Osteoclastogenesis Inhibitory Factor (OCIF-binding molecule; OBM), a process for preparing the same, DNA encoding said protein, a protein having an amino acid sequence encoded by this DNA, a method for producing said protein by genetic engineering technique, and a pharmaceutical composition containing said protein. In addition, screening methods for a substance for controlling expression of said protein using said protein and the DNA, a substance which inhibits or protein through binding to said protein, the substance obtained by the screening methods, and a pharmaceutical composition which contains this substance are disclosed. An antibody for said protein, a process for preparing the same, a measuring method of said protein using the antibody, and a medicine comprising the antibody are also disclosed.

Methods for identifying a substance which specifically binds to an osteoclastogenesis inhibitory factor-binding molecule and modulates the biological activity thereof

A method of diagnosing metabolic bone diseases, especially osteoporosis and arthrosis characterized by determining the concentration of osteoclastgenesis inhibitory factor (OCIF) in humor. Monoclonal antibodies recognizing equally both of monomer type and dimer type of OCIF. Monoclonal antibodies recognizing selectively dimer type of OCIF. And to provide an assay kit for determination of OCIF concentration comprising the aforementioned two antibodies recognizing different epitope of OCIF and having high affinity showing dissociation constant of less than 2&#xd7;10M with antigen. It is useful for a method of diagnosing metabolic bone diseases, especially osteoporosis and arthrosis or for an assay reagent for research thereof.

Method of diagnosing metabolic bone diseases

A protein which inhibits osteoclast diffraction and/or maturation and a method for producing the protein. The protein is produced by human embryonic lung fibroblasts and has a molecular weight of about 60 kD and about 120 kD under non-reducing conditions and about 60 kD under reducing conditions an SDS-polyacrylamide gel electrophoresis. The protein can be isolated and purified from the culture medium of fibroblasts. Furthermore, the protein can be produced by gene engineering. The present invention includes cDNA for producing the protein by gene engineering, antibodies having specific affinity for the protein or a method for determining protein concentration using these antibodies.

Monoclonal antibodies that bind OCIF

A protein which inhibits osteoclast differentiation and/or maturation and a method for producing the protein. The protein is produced by human embryonic lung fibroblasts and has a molecular weight of about 60 kD and about 120 kD under non-reducing conditions and about 60 kD under reducing conditions on SDS-polyacrylamide gel electrophoresis[[, respectively]]. The protein can be isolated and purified from the culture medium of fibroblasts. Furthermore, the protein can be produced by gene engineering. The present invention includes cDNA for producing the protein by gene engineering, antibodies having specific affinity for the protein or a method for determining protein concentration using these antibodies.

Method for diagnosing bone dysbolism

The present invention relates to a TCF mutant having a novel amino acid sequence which is obtained by mutagenesis of one or more amino acid between N-terminus and the first kringle of the amino acid sequence of native TCF and has lowered affinity to heparin and/or elevated biological activity. The present TCF mutant is prepared by gene manipulation of TCF. The TCF mutants of the present invention have proliferative activity and/or growth stimulative activity in hepatocyte and beneficial as a therapeutic agent for various hepatic diseases and an antitumor agent.

TCF mutant

A preventative and/or therapeutic agent to treat and/or prevent organ failure due to mercury exposure, contains as the active ingredient a mutant tumor cytotoxic factor protein (TCF-II). The therapeutic agent comprises a mutant TCF-II protein according to SEQ ID NO. 2 in which amino acid residues Arg-Lys-Arg-Arg have been replaced by Ala-Ala-Ala-Ala, or in which amino acids Lys-Ile-Lys-Thr-Lys-Lys have been replaced by Ala-Ile-Ala-Thr-Ala-Ala (SEQ ID NO. 3).

Method for preventing and/or treating renal disease

Basic osteoblast growth factor II (bOGF-II)

Growing community of inventors

Tochigi, Japan

Fumie Kobayashi