JP2014195454A5 - - Google Patents

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JP2014195454A5
JP2014195454A5 JP2014087047A JP2014087047A JP2014195454A5 JP 2014195454 A5 JP2014195454 A5 JP 2014195454A5 JP 2014087047 A JP2014087047 A JP 2014087047A JP 2014087047 A JP2014087047 A JP 2014087047A JP 2014195454 A5 JP2014195454 A5 JP 2014195454A5
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peptide
receptor
polypeptide
protease
hormone
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JP2014087047A
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JP2014195454A (ja
JP5891258B2 (ja
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Priority claimed from GB0810785A external-priority patent/GB0810785D0/en
Priority claimed from GBGB0810782.3A external-priority patent/GB0810782D0/en
Priority claimed from GB0820884A external-priority patent/GB0820884D0/en
Priority claimed from GB0820965A external-priority patent/GB0820965D0/en
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Publication of JP2014195454A publication Critical patent/JP2014195454A/ja
Publication of JP2014195454A5 publication Critical patent/JP2014195454A5/ja
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Claims (14)

  1. 先端巨大症の治療に使用するためのポリペプチドであって、
    a.下垂体腫瘍細胞におけるエキソサイトーシス融合装置のタンパク質を切断することができる非細胞傷害性プロテアーゼ、
    b.エンドサイトーシスを受けて、下垂体腫瘍細胞内のエンドソームに組み込まれ得る、前記下垂体腫瘍細胞上の結合部位に結合するペプチドターゲティング部分(TM)、及び
    c.エンドソームの内部からエンドソーム膜を通過して前記下垂体腫瘍細胞の細胞質ゾル中に前記プロテアーゼを移行させる細菌又はウイルスの移行ドメイン
    を含み、
    クロストリジウムの神経毒の天然H CC 結合ドメインを欠如する
    ポリペプチド。
  2. 下垂体腫瘍細胞が、ソマトトロピノーマに由来する、又はそれの原因となる、請求項1に記載のポリペプチド。
  3. TMが、成長ホルモン放出ホルモン(GHRH)受容体;ソマトスタチン(SST)受容体、コルチスタチン(CST)受容体;グレリン受容体;ボンベシン受容体;ウロテンシン受容体;メラニン凝集ホルモン受容体1;KiSS−1受容体;ゴナドトロピン放出ホルモン(GnRH)受容体;及び/又は、プロラクチン放出ペプチド受容体を含む群から選択される受容体に結合する、請求項1又は2に記載のポリペプチド。
  4. TMが、成長ホルモン放出ホルモン(GHRH)ペプチド、ソマトスタチンペプチド、コルチスタチンペプチド、グレリンペプチド、ボンベシンペプチド、ウロテンシンペプチド、メラニン凝集ホルモンペプチド、KISS−1ペプチド、ゴナドトロピン放出ホルモン(GnRH)ペプチド、又はプロラクチン放出ペプチドを含む、請求項1〜3のいずれかに記載のポリペプチド。
  5. 非細胞傷害性プロテアーゼが、クロストリジウムの神経毒L鎖又はIgAプロテアーゼを含む、請求項1〜4のいずれかに記載のポリペプチド。
  6. 移行ドメインが、クロストリジウムの神経毒移行ドメインを含む、請求項1〜5のいずれかに記載のポリペプチド。
  7. a.下垂体腫瘍細胞におけるエキソサイトーシス融合装置のタンパク質を切断することができる非細胞傷害性プロテアーゼ、
    b.エンドサイトーシスを受けて、下垂体腫瘍細胞内のエンドソームに組み込まれ得る、前記下垂体腫瘍細胞上の結合部位に結合するペプチドターゲティング部分(TM)、及び
    c.エンドソームの内部からエンドソーム膜を通過して前記下垂体腫瘍細胞の細胞質ゾル中に前記プロテアーゼを移行させる細菌又はウイルスの移行ドメイン
    を含み、
    クロストリジウムの神経毒の天然H CC 結合ドメインを欠如し、
    配列番号7、8、9、10、11、12、13、14、15、16、18、19、20、21、22、23、24、26、27、28、29、30、31、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、又は94のいずれか1つに対して、少なくとも90〜92%、又は少なくとも95〜97%、又は少なくとも98〜99%の配列同一性を有するアミノ酸配列を含む
    ポリペプチド。
  8. TMが、成長ホルモン放出ホルモン(GHRH)受容体;ソマトスタチン(SST)受容体、コルチスタチン(CST)受容体;グレリン受容体;ボンベシン受容体(例えばBRS−1、BRS−2、若しくはBRS−3);ウロテンシン受容体(例えばウロテンシンII受容体);メラニン凝集ホルモン受容体1;KiSS−1受容体;ゴナドトロピン放出ホルモン(GnRH)受容体;及び/又はプロラクチン放出ペプチド受容体を含む群から選択される受容体に結合する、請求項7に記載のポリペプチド。
  9. TMが、成長ホルモン放出ホルモン(GHRH)ペプチド、ソマトスタチンペプチド、コルチスタチンペプチド、グレリンペプチド、ボンベシンペプチド、ウロテンシンペプチド、メラニン凝集ホルモンペプチド、KISS−1ペプチド、ゴナドトロピン放出ホルモン(GnRH)ペプチド、又はプロラクチン放出ペプチドを含む、請求項7又は8に記載のポリペプチド。
  10. 移行ドメインが、クロストリジウムの神経毒移行ドメインを含み、及び/又は非細胞傷害性プロテアーゼが、クロストリジウムの神経毒プロテアーゼ若しくはIgAプロテアーゼを含む、請求項7〜9のいずれかに記載のポリペプチド。
  11. 請求項7〜10のいずれかに記載のポリペプチドをコードする核酸。
  12. 配列番号17又は25のいずれか1つに対して、少なくとも90〜94%、又は少なくとも95〜97%又は少なくとも98〜99%の配列同一性を有する核酸配列を含む、請求項11に記載のポリペプチドをコードする核酸。
  13. 非細胞傷害性プロテアーゼ成分と移行成分の間に位置する認識部位(切断部位)でポリペプチドを切断するプロテアーゼと、ポリペプチドとを接触させること、及び前記ポリペプチドを二重鎖ポリペプチドに変換することを含み、前記非細胞傷害性プロテアーゼ成分及び前記移行成分が、ジスルフィド結合によってともに結合される、請求項5に記載のポリペプチドを活性化させる方法。
  14. 請求項13の方法によって得ることができる二重鎖ポリペプチド。
JP2014087047A 2008-06-12 2014-04-21 神経内分泌疾患の抑制 Expired - Fee Related JP5891258B2 (ja)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
GB0810785A GB0810785D0 (en) 2008-06-12 2008-06-12 Suppression of neuroendocrine diseases
GBGB0810782.3A GB0810782D0 (en) 2008-06-12 2008-06-12 Suppression of cancers
GB0810785.6 2008-06-12
GB0810782.3 2008-06-12
GB0820884.5 2008-11-14
GB0820884A GB0820884D0 (en) 2008-11-14 2008-11-14 Suppression of neuroendocrine diseases
GB0820965.2 2008-11-17
GB0820965A GB0820965D0 (en) 2008-11-17 2008-11-17 Suppression of cancers

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JP2014195454A5 true JP2014195454A5 (ja) 2014-11-27
JP5891258B2 JP5891258B2 (ja) 2016-03-22

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US (1) US20110171191A1 (ja)
EP (3) EP2719392B1 (ja)
JP (2) JP5728380B2 (ja)
KR (1) KR101642363B1 (ja)
CN (2) CN104328100B (ja)
AU (1) AU2009259033B2 (ja)
BR (1) BRPI0915888E2 (ja)
CA (1) CA2727082C (ja)
ES (2) ES2614990T3 (ja)
IL (1) IL209855A (ja)
WO (1) WO2009150469A2 (ja)
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