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PEPTIDE, POLYNUCLEOTIDE, VECTOR, TRANSFORMANT, NFκB INHIBITOR, AND THERAPEUTIC AGENT FOR DISEASES ASSOCIATED WITH ACCELERATED NFκB ACTIVITY meetings

Foreign code F160008892
File No. (S2015-0250-N0)
Posted date Oct 25, 2016
Country WIPO
International application number 2015JP085286
International publication number WO 2016098838
Date of international filing Dec 16, 2015
Date of international publication Jun 23, 2016
Priority data
  • P2014-257827 (Dec 19, 2014) JP
Title PEPTIDE, POLYNUCLEOTIDE, VECTOR, TRANSFORMANT, NFκB INHIBITOR, AND THERAPEUTIC AGENT FOR DISEASES ASSOCIATED WITH ACCELERATED NFκB ACTIVITY meetings
Abstract This peptide has an NFκB inhibitory effect and is any one of the following peptides: (a) a peptide comprising any amino acid sequence from SEQ ID NOs: 1-5; (b) a peptide having an NFκB inhibitory effect and comprising any amino acid sequence from SEQ ID NOs: 1-5, wherein one or a plurality of amino acid residues having been replaced, deleted and/or added; (c) a peptide having an NFκB inhibitory effect and comprising an amino acid sequence that is at least 80% homologous with any amino acid sequence from SEQ ID NOs: 1-5; (d) a peptide in which a cell-penetrating peptide is fused with any peptide selected from (a)-(c); and (e) a peptide in which a Met residue, a MetAla residue or an Ala residue is added to the N terminal of any peptide selected from (a)-(d).
Outline of related art and contending technology BACKGROUND ART
A variety of cytokines in the inflammatory response and responsible for expression of the cell adhesion molecules are known. The inflammatory cytokines bind to a receptor corresponding to each of the various molecules in cells by phosphorylation occurs. This phosphorylation cascade may finally, nuclear transcription factor NFκB is activated, transcription of various inflammatory substances are believed to be promoted. In this way, activation of the inflammatory response is finally collected in the NFκB and, to effectively inhibit the activity of this NFκB as the drug, steroid drug is widely used.
Steroid drug is very potent effect on the other hand, can also cause serious side effects are known. For this reason, an alternative to steroid drug NFκB inhibitor has been desired.
Under such a background, the present inventors, facilitate transcription of the steroid drug in the same manner as NFκB directly inhibit activity can be on the other hand, corticosteroid hormones such as do not affect as novel peptides, found that the MTI-II(for example, see Patent Publication 4874798). Is MTI-II, 102 amino acid residues and a small peptide, having an inhibitory effect on NFκB portion in which, in the first to 75 from the first 32 amino acid sequence corresponding to the region thought to be an acidic amino acid. The present inventors, in the first to 75 from the first 36 amino acid peptide having the sequence from an arginine residue at C-terminus to a membrane-bound 8 peptide consisting of the peptides also referred to as (MPAID(MTI peptide anti-inflammatory drug) ) chemically synthesizing, was added to the cells HeLa, inhibited NFκB transcription promoting activity was confirmed (for example, 'Japan vitamin The Institute of 66 times of a meeting, vitamin, first 88 winding the first 4 signal, the first 260 page' and 'the first 87 times Japan raw Chemical Society convention, biochemical, first 86 winding Chemistry signal, the first 101 page' 4T13a - 04 ', the first page 136' 3P-006" reference). In addition, the peptide was applied to atopic dermatitis model animal administration of, an anti-inflammatory effect in vivo was confirmed in (for example, 'the first 87 times Japan raw Chemical Society convention, biochemical, first 86 winding Chemistry signal, the first 101 page' 4T13a - 04 ', the first page 136' 3P-006" reference).
Scope of claims (In Japanese)[請求項1]
NFκB阻害作用を有する、下記(a)~(e)から選ばれるいずれか1種のペプチド:
(a)配列番号1~5のいずれか1つのアミノ酸配列からなるペプチド、
(b)配列番号1~5のいずれか1つにおいて1個若しくは数個のアミノ酸残基が置換、欠失、及び/又は付加されたアミノ酸配列からなり、かつ、NFκB阻害作用を有するペプチド、
(c)配列番号1~5のいずれか1つのアミノ酸配列に対して80%以上の相同性を有するアミノ酸配列からなり、かつ、NFκB阻害作用を有するペプチド、
(d)前記(a)~(c)から選ばれるいずれか1種のペプチドに膜透過ペプチドが融合されたペプチド、
(e)前記(a)~(d)から選ばれるいずれか1種のペプチドのN末端にMet残基、MetAla残基、又はAla残基が付加されたペプチド。
[請求項2]
前記(b)のペプチドが、配列番号1又は2において1個~4個のアミノ酸残基が置換、欠失、及び/又は付加されたアミノ酸配列からなり、かつ、NFκB阻害作用を有するペプチドである、請求項1に記載のペプチド。
[請求項3]
前記(b)のペプチドが、配列番号3~5のいずれか1つにおいて1個又は2個のアミノ酸残基が置換、欠失、及び/又は付加されたアミノ酸配列からなり、かつ、NFκB阻害作用を有するペプチドである、請求項1に記載のペプチド。
[請求項4]
前記(d)のペプチドが、前記(a)~(c)から選ばれるいずれか1種のペプチドのC末端に膜透過ペプチドが融合されたペプチドである、請求項1~請求項3のいずれか1項に記載のペプチド。
[請求項5]
請求項1~請求項4のいずれか1項に記載のペプチドを有効成分として含むNFκB阻害剤。
[請求項6]
請求項1~請求項4のいずれか1項に記載のペプチドを有効成分として含むNFκB亢進性疾患の治療剤。
[請求項7]
前記NFκB亢進性疾患が炎症性疾患である、請求項6に記載のNFκB亢進性疾患の治療剤。
[請求項8]
請求項1~請求項4のいずれか1項に記載のペプチドをコードするポリヌクレオチド。
[請求項9]
請求項8に記載のポリヌクレオチドを含むベクター。
[請求項10]
請求項9に記載のベクターが導入された形質転換体。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • ST. MARIANNA UNIVERSITY SCHOOL OF MEDICINE
  • Inventor
  • OKAMOTO, Kazuki
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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