Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo

Other

Kakuji Torigoe

Masashi Kurimoto

Haruki Okamura

Keizo Kohno

Tadao Tanimoto

Mutsuko Taniguchi

Toshio Kunikata

Shimpei Ushio

Takanori Okura

Shigeharu Fukuda

Madoka Taniai

Takeshi Ario

Toshi Kunikata

Todao Tanimoto

Shinsaku Nakagawa

Tadanori Mayumi

Yasuo Tsutsumi

A protein which induces the IFN-&#x3b3; production by immunocompetent cells and has a molecular weight of 19,000&#xb1;5,000 daltons on SDS-PAGE or gel filtration method and a pI of 4.8&#xb1;1.0 on chromatofocusing. The protein is isolated from mouse liver and can be purified by a monoclonal antibody specific to it. The monoclonal antibody can be also used for assaying the protein.

IFN-&#x3b3; production inducing protein (IGIF, IL-18)

The present invention has objects to provide a mutant interferon-&#x3b1; protein having a higher anti-viral and anti-tumor activity and to provide an agent for susceptive diseases, which contains the mutant interferon-&#x3b1; protein as an effective ingredient; and solves the above objects by providing a mutant protein which has an amino acid sequence of human interferon-&#x3b1; subtype &#x3b1;8 represented by any one of SEQ ID NOs:1 to 3, where the arginine residue at the 145has been replaced with leucine, isoleucine, or valine residue; the alanine residue at the 146has been replaced with asparagine or serine residue; and the methionine residue at the 149has been replaced with tyrosine residue; and an agent for susceptive diseases, containing the mutant protein.

Mutant interferon &#x3b1; protein and use thereof

A human IFN-&#x3b3; inducing polypeptide and its nucleotide sequence was isolated, purified and characterized. Pharmaceutical compositions containing this novel INF-&#x3b3; inducing polypeptide or active fragments thereof are formulated and monoclonal antibodies are raised against this polypeptide or antigenic fragments thereof. The polypeptide can be used in a method for treating diseases susceptive to treatment with INF-&#x3b3;, and methods for enhancing the cytotoxicity of NK cells or for inducing the formation of LAK cells, such as to treat tumors and malignant pathologies.

Interferon-&#x3b3; inducing polypeptide, pharmaceutical composition thereof, monoclonal antibody thereto, and methods of use

Disclosed are a receptor protein which recognize a novel cytokine, i.e., interleukin-18, a monoclonal antibody specific to the protein, and uses thereof. The receptor protein is useful as pharmaceutical to treat and prevent autoimmune and allergic disease because it suppresses and regulates excessive immunoreaction. The monoclonal antibody specifically reacts with interleukin-18, exhibiting efficacy in purification, detection and inhibition of interleukin-18.

Interleukin-18-receptor proteins

A human IFN-&#x3b3; inducing polypeptide and its nucleotide sequence was isolated, purified and characterized. Pharmaceutical compositions containing this novel IFN-&#x3b3; inducing polypeptide or active fragments thereof are formulated and monoclonal antibodies are raised against this polypeptide or antigenic fragments thereof. The polypeptide can be used in a method for treating diseases susceptive to treatment with IFN-&#x3b3;, and methods for enhancing the cytotoxicity of NK cells or for inducing the formation of LAK cells, such as to treat tumors and malignant pathologies.

Disclosed is a genomic DNA encoding a polypeptide capable of inducing the production of interferon-&ggr; by immunocompetent cells. The genomic DNA efficiently expresses the polypeptide with high biological activities of such as inducing the production of interferon-&ggr; by immunocompetent cells, enhancing killer cells' cytotoxicity and inducing killer cells' formation, when introduced into mammalian host cells. The high biological activities of the polypeptide facilitate its uses to treat and/or prevent malignant tumors, viral diseases, bacterial infectious diseases and immune diseases without serious side effects when administered to humans.

Genomic DNA encoding a polypeptide capable of inducing the production of interferon-&ggr;

Disclosed are a receptor protein which recognize a novel cytokine, i.e., interleukin-18, a monoclonal antibody specific to the protein, and uses thereof. The receptor protein is useful as pharmaceutical to treat and prevent autoimmune and allergic disease because it suppresses and regulates excessive immunoreaction. The monoclonal antibody specifically reacts with interleukin-18 receptor, exhibiting efficacy in purification, detection and inhibition of interleukin-18 receptor.

Monoclonal antibody for human IL-18 receptor

Disclosed are a polypeptide (including that in soluble form) as receptor for a novel cytokine, i.e., interleukin-18, a DNA encoding the polypeptide, and the uses of the polypeptide including pharmaceutical and neutralizer to interleukin-18. Pharmaceuticals with the polypeptide is useful to treat and prevent autoimmune and allergic disease because it suppresses and regulates excessive immunoreaction.

Polypeptides that bind interleukin-18 (IL-18)

A protein which induces the IFN-&ggr; production by immunocompetent cells and has a molecular weight of 19,000&plusmn;5,000 daltons on SDS-PAGE or gel filtration method and a pI of 4.8&plusmn;1.0 on chromatofocusing. The protein is isolated from mouse liver and can be purified by a monoclonal antibody specific to it. The monoclonal antibody can be also used for assaying the protein. Fragments of the protein can be used for production of antibodies, and can be produced recombinantly using appropriate medric acids, host cells and vectors. Fragments of nuclear acids may also be used as probes.

DNA molecule encoding interferon-gamma (IFN-&lgr;) inducing factor (IGIF, IL-18) and DNA fragment thereof

Disclosed is a DNA coding for mammalian L-asparaginase. Transformants introduced with the DNA effectively produce desired amounts of mammalian L-asparaginase such as those from humans, guinea pigs, and mice. The DNA is also useful as a probe for screening a DNA coding for desired mammalian L-asparaginase.

DNA coding for mammalian L-asparaginase

A protein which induces the IFN-&ggr; production by immunocompetent cells and has a molecular weight of 19,000&plusmn;5,000 daltons on SDS-PAGE or gel filtration method and a pI of 4.8&plusmn;1.0 on chromatofocusing. The protein is isolated from mouse liver and can be purified by a monoclonal antibody specific to it. The monoclonal antibody can be also used for assaying the protein.

Interferon-gamma (IFN-&ggr;) inducing factor (IGIF, IL-18) and peptide fragment thereof

A polypeptide which has a molecular weight of 18,500&plusmn;3,000 daltons on SDS-PAGE and a pI of 4.9&plusmn;1.0 on chromatofocusing. The polypeptide strongly induces the IFN-&ggr; production by immunocompetent cells with only a small amount, and does not cause serious side effects even when administered to human in a relatively-high dose. It can be used to treat and/or prevent malignant tumors, viral diseases, bacterial infectious diseases, and immune diseases.

Human Interferon-&ggr;inducing factor

An agent for susceptive diseases, which contains a polypeptide that has a molecular weight of 18,500&plusmn;3,000 daltons on SDS-PAGE and a pI of 4.9&plusmn;1.0 on chromatofocusing, strongly induces the IFN-&ggr; production by immunocompetent cells with only a small amount, and does not cause serious side effects even when administered to human at a relatively-high dose. The agent treats and/or prevents malignant tumors, viral diseases, bacterial infectious diseases, and immune diseases including atopies.

Pharmaceutical composition containing IFN-&ggr; inducing polypeptide or factor for treating and/or preventing IFN-&ggr; susceptive diseases

The receptor for interleukin-18 (IL-18) is described. The invention provides recombinant receptor polypeptides, including soluble receptors and fusion proteins, which specifically bind to IL-18 and inhibit its activity. The polypeptides are thus useful as pharmaceutical agents to treat autoimmune and allergic diseases. They are also useful as affinity reagents to purify IL-18, in assays to detect the ligand, and in screening assays to identify IL-18 agonists or antagonists.

Growing community of inventors

Okayama, Japan

Kakuji Torigoe