Top > Search of International Patents > AMYLOID β-PROTEIN-SPECIFIC PRODUCTION-INHIBITING POLYPEPTIDE

AMYLOID β-PROTEIN-SPECIFIC PRODUCTION-INHIBITING POLYPEPTIDE meetings

Foreign code F130007723
Posted date Nov 29, 2013
Country WIPO
International application number 2013JP050663
International publication number WO 2013108780
Date of international filing Jan 16, 2013
Date of international publication Jul 25, 2013
Priority data
  • P2012-006687 (Jan 17, 2012) JP
  • P2012-208277 (Sep 21, 2012) JP
Title AMYLOID β-PROTEIN-SPECIFIC PRODUCTION-INHIBITING POLYPEPTIDE meetings
Abstract The main purpose of the invention is to develop a compound that specifically inhibits the production of Aβ-protein and serves as an active ingredient of a drug to treat and/or prevent Alzheimer's disease. Provided to achieve this goal are a polypeptide that binds to the N-terminal region of βCTF, the polypeptide having an amino acid sequence shown by any one of SEQ ID NO: 1, 13, 14, and 22; and a γ-secretase activity inhibitor, β-secretase activity inhibitor, Aβ-protein production-inhibiting agent, and an agent for treating and/or preventing Alzheimer's disease, the inhibitors and agents containing this polypeptide.
Outline of related art and contending technology BACKGROUND ART
Amyloid β protein (hereinafter, sometimes referred to herein A β protein.) Is, as one of the etiology of Alzheimer's disease is believed to be the 1 protein. Specifically, this A β protein is accumulated in the brain, of Alzheimer's disease has been recognized as one of the 1. Such A β protein, the brain due to build up the molecular structure of the rigid fibrous form, in the brain and nerve cells can be lethal to, a neurological function is damaged as a result of developing Alzheimer's disease are considered.
A β protein, cell transmembrane protein amyloid precursor protein (hereinafter, sometimes referred to as APP herein.) Is cleaved by β secretase cell transmembrane protein β CTF is, by cutting the γ secretase further free from the cell membrane, and store the brain thought.
A β γ secretase protein is cleaved by β CTF, known AICD and divided into, is cleaved by β secretase APP by, releasing sAPP β is also known (Fig. 1).
If based on mature APP, 653-694 A β protein corresponds to amino acid residue, β CTF is 653-751 corresponding to amino acid residue. In addition, sAPP β corresponds to the amino acid residue is 18-652, 701-751 AICD is corresponding to the amino acid residue.
From the above, inhibitors of γ secretase protein Alzheimer's disease, inhibit the buildup of protein A β effect has been considered as.
However, each transmembrane protein Pen-2, presenilin, secretase, Aph-1 and γ secretase is known as a complex comprising, belong to the aspartic acid protease, as well as the above-described APP APLP1, APLP2, Notch, Jagged 2, Delta 1, E-cadherin, N-cadherin, CD44, ErbB4, Nectin 1, LRP1 such as a transmembrane protein, and the like receptor substrate for protease.
Therefore, the effect of limiting the production of a protein A β in order to obtain, L-685,458, DAPT, γ secretase LY-411,575 such as the use of an inhibitor, a protein other than β CTF for γ-secretase described above as the enzymatic activity of the protease but also restrains the, agent such as it is used as the inhibitor, there is a possibility that side effects such as are feared.
For example, an inhibitor of γ secretase LY-411,575 is one of 1, atrophy of the spleen and thymus to mature B cells to reduce the number of cells have been reported and the like, such an inhibitor when it is a pharmaceutical composition, such as a side effect of immune suggested a possibility to cause a (non-patent document 1). Further, γ secretase enzyme activity itself is lowered, abnormalities in the skin, squamous cell carcinomas, and the like can also cause enlargement of the spleen have been reported (non-patent document 2).
In addition, the production of a protein in the mechanism of functionalities A β, β secretase inhibiting the enzymatic activity of a compound is considered to be effective, β secretase knockout mice, a decrease in the number and report such as birth, is not preferable as an agent for Alzheimer's disease.
Then, non-steroidal anti-inflammatory drugs (hereinafter, sometimes referred to as NSAIDs herein.) The production of a protein A β is effective as an inhibitor such as findings exist, some of the familial Alzheimer's disease (for example, in the case of a mutation in a presenilin.) Is, known to be ineffective (non-patent document 3). Further mild cognitive impairment and Alzheimer's disease γ secretase is isolated from patients that activity is modified, to reduce the effect of the γ secretase model dju aerator A β 42 found to be lower (non-patent document 4).
In addition, the extracellular region of the β CTF FLAG tag to N-terminus when expressed, in the presence of anti-FLAG antibody, not degradation of the γ-secretase (non-patent document 5).
Scope of claims (In Japanese)請求の範囲 [請求項1]
配列番号1、13、14、又は22の何れか1つにて示されるアミノ酸配列を有し、βCTFのN末端領域に結合するポリペプチド。

[請求項2]
配列番号2~14、及び22の何れか1つにて示されるアミノ酸配列を有する、請求項1に記載のポリペプチド。

[請求項3]
配列番号2~8、10~12、14、又は22の何れか1つにて示されるアミノ酸配列を有する、請求項1に記載のポリペプチド。

[請求項4]
(項1-3)配列番号3、4、6、10、11、14、又は22の何れか1つにて示されるアミノ酸配列を有する、請求項1に記載のポリペプチド。

[請求項5]
請求項1~4の何れか1項に記載のポリペプチドを含む、γセクレターゼ活性阻害剤。

[請求項6]
配列番号3にて示されるアミノ酸配列を有するポリペプチドを含む請求項5に記載の、γセクレターゼ活性阻害剤。

[請求項7]
請求項1~4の何れか1項に記載のポリペプチドを含む、βセクレターゼ活性阻害剤。

[請求項8]
配列番号6にて示されるアミノ酸配列を有するポリペプチドを含む請求項7に記載の、βセクレターゼ活性阻害剤。

[請求項9]
請求項1~4の何れか1項に記載のポリペプチドを含む、Aβタンパク質産生抑制剤。

[請求項10]
配列番号6にて示されるアミノ酸配列を有するポリペプチドを含む請求項9に記載の、Aβタンパク質産生抑制剤。

[請求項11]
請求項1~4の何れか1項に記載のポリペプチドを含む、アルツハイマー病治療及び/又は予防剤。

[請求項12]
配列番号6に示されるアミノ酸配列を有するポリペプチドを含む、請求項11に記載のアルツハイマー病治療及び/又は予防剤。

[請求項13]
請求項1~4の何れか1つに記載のポリペプチドを、アルツハイマー病患者に投与する工程を含む、アルツハイマー病を治療及び/又は予防する方法。

[請求項14]
アルツハイマー病の治療及び/又は予防における使用のための、請求項1~4の何れか1つに記載のポリペプチド。

[請求項15]
アルツハイマー病を治療及び/又は予防するための、医薬の製造のための、請求項1~4の何れか1つに記載のポリペプチドの使用。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • THE DOSHISHA
  • Inventor
  • IHARA, Yasuo
  • FUNAMOTO, Satoru
  • SASAKI, Toru
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 IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT 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 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 ML MR NE SN TD TG

PAGE TOP

close
close
close
close
close
close