Takeda Chemical Industries, Inc.

Haruo Onda

Masaki Hosoya

Shuji Hinuma

Shoichi Ohkubo

Chieko Kitada

Kazuhiro Ogi

Tetsuya Ohtaki

Yugo Habata

Chiharu Kimura

Yasunori Miyamoto

Akira Arimura

Yasushi Masuda

Yoshihiro Ishibashi

Norio Shimamoto

Ryo Fujii

Shoji Fukusumi

Hidekazu Sawada

Kazuhiro Ohgi

Takuo Kosaka

Kyozo Tsukamoto

The invention provides an ependymin-like protein derived from a mammal, or its partial peptide or its precursor protein, or a salt thereof; a signal peptide; a DNA coding for the protein, etc. a recombinant vector; a transformant; a method of producing the protein; a pharmaceutical composition comprising the protein, etc. or DNA, an antibody against the protein, etc.; and a method for screening and a screening kit for compounds promoting the function of the protein. The protein, its partial peptide or a salt thereof has physiological activities such as a nerve-extending or nerve-regenerating activity, a gliacyte stimulating activity, and so on. The protein, etc. or the DNA is useful as a therapeutic or prophylactic agent for Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), dementia or cerebellar degeneration. The antibody against the protein, etc. can be used in the assay of the protein, etc. in a test sample. Furthermore, the protein, etc. is useful as a screening reagent for compounds or their salts capable of promoting the function of the protein.

Human ependymin-like protein

Galanin receptor proteins, production and use thereof including screening of galanin receptor agonists and antagonists are provided. Galanin receptor proteins, etc. or salts thereof, partial peptides thereof, DNAs coding for the above galanin receptor protein, processes for producing the above receptor protein, methods of screening for a galanin receptor agonist and/or antagonist or screening kits therefor, agonist and/or antagonist compounds or salts thereof obtained by the above screening method or the screening kit, pharmaceutical compositions containing the above compound or its salt, and antibodies against the above receptor protein are provided. It is allowable to efficiently screen a galanin receptor agonist or antagonist by using the galanin receptor protein, the partial peptide thereof, the galanin receptor protein-encoding DNA, the receptor protein-containing cell or its membrane fraction. The pharmaceuticals thus screened or characterized permits various applications including prophylactic and/or therapeutic treatments against a variety of diseases, e.g., stomach ulcer, diabetes, Alzheimer's disease, dementia, etc. and a sedative.

DNA encoding a galanin receptor

This invention discloses a PACAP receptor protein or a salt thereof, a DNA comprising a DNA fragment coding for the protein, a method for preparing the protein, antibody against the protein, and use of the protein, DNA, and antibodies. A PACAP receptor protein was purified from the bovine cerebrum. DNAs coding for PACAP receptor proteins were isolated from bovine, rat and human cDNA libraries, and their nucleotide sequences were determined. Further, amino acid sequences deduced from the nucleotide sequences were determined. The PACAP receptor proteins and the DNAs coding for the proteins of the present invention can be used for (1) acquisition of antibodies and antisera, (2) construction of expression systems of recombinant receptor proteins, (3) development of receptor binding assay systems using said expression systems and screening of potential compounds for drugs, (4) execution of drug design based on the comparison of ligands and receptors which are structurally similar to each other, (5) preparation of probes and PCR primers in gene diagnosis, and the like.

PACAP receptor protein, method for preparing said protein, and use thereof

Disclosed are (1) a DNA containing a cDNA segment coding for human endothelin-2 (SEQ ID NO:1), (2) a precursor of human endothelin-2 (SEQ ID NO:2), (3) a transformant carrying a DNA containing a cDNA segment coding for human endothelin-2, and (4) a method for preparing mature human endothelin-2 which comprises culturing the transformant described in (3), accumulating a protein in a culture medium, and collecting the same, whereby human endothelin-2 and the precursors thereof can be produced in large amounts.

DNA coding for a human vasoconstrictive peptide and use thereof

Disclosed are CHO cells which are capable of continued production of human LH-RH receptor proteins, or cell membrane fractions thereof; recombinant human LH-RH receptor proteins or partial peptides thereof; methods for screening compounds which have affinity for an LH-RH receptor by contacting the compound with the CHO cells or the cell membrane fractions thereof, or the recombinant human LH-RH receptor proteins or the partial peptides thereof; kits for screening them; the compounds which have affinity for the LH-RH receptor obtained by methods for the screening or kits for the screening; and pharmaceutical compositions containing the compound, thereby being able to early provide prophylactic or therapeutic compositions, for example, for prostate cancer, uterine cancer, breast cancer, a pituitary tumor, endometriosis, hysteromyoma or precocious puberty. They are also useful as a pregnancy controlling composition such as contraceptive or a menstrual cycle controlling composition.

Human LH-RH receptor expression cells and use thereof

This invention discloses a PACAP receptor protein or a salt thereof, a DNA comprising a DNA fragment coding for the protein, a method for preparing the protein, antibody against the protein and use of the protein, DNA and antibodies.

PACAP receptor protein, method for preparing said protein, and use

A human receptor protein capable of binding TRH, a DNA coding for said protein, use of the proetein and DNA, a method for preparing said protein, and antibodies to the protein are described. The human TRH receptor protein and the DNA coding for the protein of the present invention are useful as (1) a diagnostic composition for neuropathy (particularly, dementia), (2) a pharmaceutical composition for neuropathy and (3) a material used for screening a TRH receptor agonist or antagonist.

Method of screening for inhibitors of human thyrotropin releasing

This invention discloses a PACAP receptor protein or a salt thereof, a DNA comprising a DNA fragment coding for the protein, a method for preparing the protein, antibody against the protein and use of the protein, DNA and antibodies. A PACAP receptor protein was purified from the bovine cerebrum. DNAs coding for PACAP receptor proteins were isolated from bovine, rat and human cDNA libraries, and their nucleotide sequences were determined. The PACAP receptor proteins and the DNAs coding for the proteins of the present invention can be used for (1) acquisition of antibodies and antisera, (2) construction of expression systems of recombinant receptor proteins, (3) development of receptor binding assay systems using said expression systems and screening of potential compounds for drugs, (4) execution of drug design based on the comparison of ligands and receptors which are structurally similar to each other, (5) preparation of probes and PCR primers in gene diagnosis, and the like.

DNA encoding PACAP receptor protein and method for preparing said protein

DNA primers each having a nucleotide sequence substantially complementary to a nucleotide sequence which codes for Gly-Lys-Arg, Gly-Lys-Lys or Gly-Arg-Arg; methods for amplifying a polynucleotide which codes for a peptide or a precursor protein thereof using said DNA primer; screening methods for a polynucleotide which codes for a peptide comprising an amino acid sequence of Gly-Lys-Arg, Gly-Lys-Lys or Gly-Arg-Arg or a precursor protein thereof from a DNA library, etc. using said DNA; the polynucleotide obtained by said screening method; and the peptide or its precursor protein encoded by said polynucleotide, or a salt thereof. When the DNA primer of the present invention is used, the DNA which codes for a peptide having a useful physiological activity or a precursor protein thereof can be efficiently cloned.

DNA primer and a method for screening DNAS

CHO cells that express human LH-RH receptor

Disclosed are (1) a genomic DNA of human PACAP38; (2) a DNA containing a DNA segment coding for human PACAP38; (3) a DNA of human PACAP 38 promotor; (4) a transformant carrying a vector which contains a DNA of (3) or further contains a DNA coding for a protein downstream from the promotor; and (5) a method for preparing a protein comprising cultivating the transformant described in the above (4), accumulating the protein in a culture product, and collecting the resulting protein such as mature PACAP 38. The DNA gives human PACAP 38 effectively and makes it possible to screen the chemical substance necessary for production of PACAP and is applied to experimental animals to understand their brain functions, which serves to elucidate human brain functions. Human PACAP38 can also be utilized as therapeutic agents about growth and maintenance of human brain nerves.

Genomic DNA exons having exons encoding human pituitary adenylate

Disclosed are (1) a DNA containing a DNA segment coding for PACAP38; (2) a precursor protein of PACAP38; (3) a transformant containing a DNA having a DNA segment coding for PACAP38; (4) a method for preparing mature PACAP38 comprising cultivating the transformant described in the above (3), producing and accumulating a protein in a culture, and collecting the resulting protein; and (5) a method for preparing the above polypeptide comprising condensing a partial amino acid or a peptide which can constitute the mature PACAP38, with a residual portion, and removing a protective group if a product has the protective group. The DNA is applied to experimental animals to understand their brain functions, which serves to elucidate human brain functions. PACAP38 provides information about growth and maintenance of rat and human brain nerves, and can also be utilized as therapeutic agents for various neuropathy.

Pituitary adenylate cyclase activating protein precursor

Disclosed are (1) a DNA containing a DNA segment coding for PACAP38; (2) a precursor protein of PACAP38; (3) a transformant containing a DNA having a DNA segment coding for PACAP38; (4) a method of preparing mature PACAP38 comprising cultivating the transformant described in the above (3), producing and accumulating a protein in a culture, and collecting the resulting protein; and (5) a method for preparing the above polypeptide comprising condensing a partial amino acid or a peptide which can constitute the mature PACAP38, with a residual portion, and removing a protective group if a product has the protective group. The DNA is applied to experimental animals to understand their brain functions, which serves to elucidate human brain functions. PACAP38 provides information about growth and maintenance of rat and human brain nerves, and can also be utilized as therapeutic agents for various neuropathy.

DNA encoding a pitvitary adenylate cyclase activating protein and use

The present invention provides human Interleukin 2-encording messenger RNA which is free of human cells, a method of producing the same from the cells which are capable of producing human Interleukin 2 and a method of producing human Interleukin 2 using the same in an in vitro protein synthesis system.

Growing community of inventors

Tsuchiura, Japan

Haruo Onda