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ENHANCER OF EXPRESSION LEVEL OF IL-8 GENE OR MHC CLASS II-ASSOCIATED GENE CONTAINING A YAP INHIBITOR AS ACTIVE INGREDIENT

Patent code	P200017335
File No.	H30-026
Posted date	Dec 17, 2020
Application number	P2019-067200
Publication number	P2020-164470A
Date of filing	Mar 29, 2019
Date of publication of application	Oct 8, 2020
Inventor	(In Japanese)白井睦訓 (In Japanese)清木誠 (In Japanese)浅岡洋一 (In Japanese)荻野英賢
Applicant	(In Japanese)国立大学法人山口大学
Title	ENHANCER OF EXPRESSION LEVEL OF IL-8 GENE OR MHC CLASS II-ASSOCIATED GENE CONTAINING A YAP INHIBITOR AS ACTIVE INGREDIENT
Abstract	PROBLEM TO BE SOLVED: To provide agents that enhance the expression level of IL-8 gene or MHC class II-associated gene. SOLUTION: An enhancer of the expression level of IL-8 gene or MHC class II-associated gene containing a YAP inhibitor as an active ingredient is prepared. Preferably, the YAP inhibitor is Verteporfin, Y27632, Blebbistatin, Latrunculin B, Cytochalasin D, Simvastatin, Botulinum C3 toxin, Statin, or Dobutamine.
Outline of related art and contending technology	(In Japanese) 転写共役因子YAP(Yes結合タンパク質：Yes associated protein)はHippoシグナル伝達系の標的分子である。本発明者らは、細胞増殖・細胞死の両者を制御するHippoシグナル伝達系に着目し、YAPが三次元臓器形成に必須の重力耐性遺伝子であることや、YAPは細胞に発生する物理的な力を介して、個々の組織の三次元化だけでなく、複数の組織の配置を制御することにより、重力に抗した立体臓器を構築することを報告した(非特許文献1参照)。そのため、YAPは三次元臓器形成に関与する因子として注目を浴びている。一方、近年、YAPの制御と抗腫瘍免疫応答との関係の研究が進められており、例えば、YAP阻害剤と免疫治療剤とを対象に投与する工程を含む、対象におけるがんを処置する方法（特許文献1参照）や、イベルメクチン又はミルベマイシンDを有効成分として含み、Hippo経路に作用し、YAP1/TAZの活性を抑制する、Hippo経路に異常を有する癌の予防又は治療剤（特許文献2参照）が開示されている。また、YAPの制御と炎症性腸炎との関係の研究も進められており、例えば、インターロイキン6（IL-6）の受容体であるGP130がIL-6と結合することでYAP及びNotchの活性化を引き起こし、腸の修復や再生を促進することが開示されている（非特許文献2参照）。
Field of industrial application	(In Japanese) 本発明は、YAP阻害剤を有効成分とするIL-8遺伝子又はMHC classII関連遺伝子の発現量の増強剤に関する。
Scope of claims	(In Japanese) 【請求項1】 YAP阻害剤を有効成分とするIL-8遺伝子又はMHC classII関連遺伝子の発現量の増強剤。【請求項2】 YAP阻害剤が、ベルテポルフィン、Y27632、ブレビスタチン、ラトランクリンB（Latrunculin B）、サイトカラシンD（Cytochalasin D）、ジンバスタチン、ボツリヌス C3毒素、スタチン、又はドブタミンであることを特徴とする請求項1記載の増強剤。【請求項3】 YAP阻害剤が、YAP遺伝子の発現を抑制する核酸分子であることを特徴とする請求項1記載の増強剤。【請求項4】 YAP遺伝子の発現を抑制する核酸分子が、二本鎖siRNA、microRNA、shRNA、アンチセンス核酸、及びリボザイムからなる群から選択される少なくとも1種の核酸分子であることを特徴とする請求項3記載の増強剤。【請求項5】 YAP阻害剤が、YAPタンパク質に結合する抗体であることを特徴とする請求項1記載の増強剤。【請求項6】 MHC classII関連遺伝子が、CIITA遺伝子であることを特徴とする請求項1～5のいずれか記載の増強剤。
IPC(International Patent Classification)	A61K 45/00 Medicinal preparations containing active ingredients not provided for in groups A61K0031000000-A61K0041000000 A61K 31/409 having four such rings, e.g. porphine derivatives, bilirubin, biliverdine A61K 31/366 having six-membered rings, e.g. delta-lactones A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid (GABA), beta-alanine, epsilon-aminocaproic acid, pantothenic acid A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline A61K 31/427 not condensed and containing further heterocyclic rings A61K 31/403 condensed with carbocyclic rings, e.g. carbazole A61K 35/74 Bacteria A61K 31/7088 Compounds having three or more nucleosides or nucleotides A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links A61K 39/395 Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum A61P 43/00 Drugs for specific purposes, not provided for in groups A61P0001000000-A61P0041000000 A61K 31/713 Double-stranded nucleic acids or oligonucleotides A61P 35/00 Antineoplastic agents A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g antirheumatic agents; Non-steroidal antiinflammatory drugs C12N 15/24 Interleukins C12N 15/12 Genes encoding animal proteins C07K 16/18 against material from animals or humans C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
F-term	4C084AA17 One active component 4C084NA14 Revelation of new medicine effects 4C084ZB01 Medicines that specified by acting on the protective systems of organisms 4C084ZB11 Inflammation drugs 4C084ZB26 Medicines for tumors 4C084ZC01 Medicines with characteristic action on organism functions 4C085AA13 Antibodies for specific substances 4C085BB11 Proteins and polypeptides 4C085BB41 Monovalent antigen-binding fragments (FaB) 4C085BB43 Bi-valent antigen-binding fragments (F(ab=)2) 4C085EE01 Single components (i.e., organic components) 4C086AA01 Medical use claims 4C086AA02 Use of experimental data or evidence of pharmaceutical effects 4C086BA17 Lacton 4C086BC10 Condensed with carbocyclic ring 4C086BC17 Pyridine 4C086BC82 Sulfur or nitrogen in the 1 and 3-position 4C086CB04 Porphyrin compound 4C086CB05 Five and six-membered rings that contain nitrogen 4C086EA16 Nucleoside, nucleotide, or nucleic acid 4C086GA16 Optical isomers 4C086MA01 One component mentioned in the claim 4C086MA04 Claims of medically effective components only 4C086NA14 Revelation of new medicine effects 4C086ZB01 Specific agents that work to enhance organ protective systems 4C086ZB11 Inflammation drugs 4C086ZB26 Medicine for tumors 4C086ZC01 Specific medicine that enhance organ functions 4C087AA01 Inventions for medicinal uses and methods for manufacturing medicines mentioned in claims 4C087AA02 Experimental data with medicinal uses or pharmaceutical applications 4C087BC68 Clostridia 4C087CA16 Proteins (i.e., peptides) 4C087NA14 Expression of new medicinal effects 4C087ZB01 Medicines specifically for boosting the body's protective system 4C087ZB11 Medicines to control inflammation 4C087ZB26 Medicines to combat tumors 4C087ZC01 Medicines working specifically on the body's functions 4C206AA01 Invention of drugs (with claims) 4C206AA02 With testing results of medical applications 4C206FA13 Dobutamines 4C206FA47 With oxygen atoms attached to carbon chains 4C206MA01 Compounding ingredients described in the scope of claims being one ingredient 4C206MA04 Compounding ingredients described in the scope of claims being only efficacious ingredients 4C206NA14 Expression of new efficacies of drugs 4C206ZB01 Drugs specified by action on biophylactic mechanisms 4C206ZB11 Inflammation agents 4C206ZB26 Medicines for tumors 4C206ZC01 Drugs specified by action on vital functions 4H045AA11 Antigens and antibodies 4H045AA30 Applications 4H045CA40 Mammals or birds 4H045DA75 Immunoglobulins (e.g., antibodies) 4H045DA76 Monoclonal antibodies 4H045EA20 Medicines
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Contact Information for " ENHANCER OF EXPRESSION LEVEL OF IL-8 GENE OR MHC CLASS II-ASSOCIATED GENE CONTAINING A YAP INHIBITOR AS ACTIVE INGREDIENT"

Yamaguchi Technology Licensing Organization Ltd.
URL: http://www.tlo.sangaku.yamaguchi-u.ac.jp/
E-mail:
Address: Collaborative Research Center, Yamaguchi University,Tokiwadai 2-16-1, Ube, Yamaguchi 755-8611, Japan , 755-8611
Fax: 81-836-22-9771

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Contact Information for " ENHANCER OF EXPRESSION LEVEL OF IL-8 GENE OR MHC CLASS II-ASSOCIATED GENE CONTAINING A YAP INHIBITOR AS ACTIVE INGREDIENT "

Yamaguchi Technology Licensing Organization Ltd.
URL: http://www.tlo.sangaku.yamaguchi-u.ac.jp/
E-mail:
Address: Collaborative Research Center, Yamaguchi University,Tokiwadai 2-16-1, Ube, Yamaguchi 755-8611, Japan , 755-8611
Fax: 81-836-22-9771

Related data

Specification	P2020-164470A
Publication of unexamined applications	P2020-164470A(PDF,132KB)

Category

Applicant	Yamaguchi Technology Licensing Organization, Ltd. (210) < Technology licensing organization (221)
IPC	A61 (1767) C12 (1445) C07 (1122)
F-term	4C084 (413) 4C085 (174) 4C086 (433) 4C087 (134) 4C206 (141) 4H045 (455)