JP2017520554A - 炎症性腸疾患の処置のための方法及び医薬組成物 - Google Patents
炎症性腸疾患の処置のための方法及び医薬組成物 Download PDFInfo
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Abstract
Description
1 mepsatpgaq mgvppgsrep spvppdyede flrylwrdyl ypkqyewvli aayvavfvva
61 lvgntlvcla vwrnhhmrtv tnyfivnlsl advlvtaicl pasllvdite swlfghalck
121 vipylqavsv svavltlsfi aldrwyaich pllfkstarr argsilgiwa vslaimvpqa
181 avmecssvlp elanrtrlfs vcderwaddl ypkiyhscff ivtylaplgl mamayfqifr
241 klwgrqipgt tsalvrnwkr psdqlgdleq glsgepqprg raflaevkqm rarrktakml
301 mvvllvfalc ylpisvlnvl krvfgmfrqa sdreavyacf tfshwlvyan saanpiiynf
361 lsgkfreqfk aafscclpgl gpcgslkaps prssashksl slqsrcsisk isehvvltsv
421 ttvlp
本発明者らは、クローン病及びUCを含むヒト炎症性腸疾患(IBD)においてOX1Rが発現されたことを立証している。事実、約40の炎症性結腸試料の免疫組織化学(IHC)実験における、OX1Rに対して惹起された特異抗体の使用で、上皮細胞及び免疫細胞の双方においてOX1Rの異所的存在が明らかになった(図1)。対照的に、正常な結腸粘膜では、OX1Rは発現されていなかった(図1)。
OXAは、DSSで誘発された大腸炎のマウスのDAI(体重及び大腸炎スコア)を改善する。図5に示すように、DSSで誘発された大腸炎のマウスがOxAで処置されると、DAIスコアが改善された(約1.5)。
本願の全般を通して、種々の引用文献により本発明の属する技術分野の状態が説明されている。これらの引用文献の本開示は、参照により本明細書の開示に組み入れられる。
Claims (7)
- 炎症性腸疾患を、それが必要な対象者において処置する方法であって、該対象者に少なくとも一つのOX1Rアゴニストの治療的有効量を投与することを含む方法。
- 前記炎症性腸疾患が、潰瘍性大腸炎、クローン病、とりわけ、回腸炎、微視的大腸炎、細菌若しくはウイルスにより引き起こされる感染性大腸炎、放射線性大腸炎、虚血性大腸炎、小児大腸炎、原因不明の大腸炎、及び明白な解剖学的異常のない機能性腸障害を伴って又は伴わずに、結腸を特異的に冒す状態にあるクローン病である請求項1記載の方法。
- 前記OX1Rアゴニストが、小有機分子、抗体、アプタマー及びポリペプチドからなる群より選択される請求項1記載の方法。
- 前記OX1Rアゴニストが、配列番号2、配列番号3又は配列番号4と少なくとも70%の同一性を有するポリペプチドである請求項1記載の方法。
- 前記OX1Rアゴニストが、配列番号2、配列番号3及び配列番号4からなる群より選択されるポリペプチドである請求項1記載の方法。
- 前記OX1Rアゴニストが、Fcドメインに融合された、配列番号2、配列番号3又は配列番号4により特徴付けられるポリペプチドを含むイムノアドヘシンである請求項1記載の方法。
- 前記OX1Rアゴニストが、コルチコステロイド;免疫抑制性薬物;メサラジン、スルファサラジン、バルサラジド、オルサラジンなどのアミノサリチル酸スルファサラジン;アザチオプリン、6−メルカプトプリン、メトトレキセート、ラパマイシン、シクロスポリン、タクロリムスなどの免疫抑制剤、又はインフリキシマブ、ビジリズマブ、アダリムマブ、ベドリズマブ、ゴリムマブ、トファシチニブなどの生物学的処置からなる群より選択される標準処置と組み合わせて対象者に投与される請求項1記載の方法。
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PCT/EP2015/064028 WO2015197572A1 (en) | 2014-06-24 | 2015-06-23 | Pharmaceutical compositions comprising agonists of orexin-1 receptor ox1r for the treatment of inflammatory bowel diseases |
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