JP2007526233A5 - - Google Patents

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JP2007526233A5
JP2007526233A5 JP2006517700A JP2006517700A JP2007526233A5 JP 2007526233 A5 JP2007526233 A5 JP 2007526233A5 JP 2006517700 A JP2006517700 A JP 2006517700A JP 2006517700 A JP2006517700 A JP 2006517700A JP 2007526233 A5 JP2007526233 A5 JP 2007526233A5
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antibody
monoclonal antibody
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Figure 2007526233
抗体131の配列を用いてProtein Data Bankを探索することで、相同抗体およびそれらの構造を同定した。相同抗体の配列の131抗体に対する類似性に基づき、数種類の構造が選択された。Protein Data Bank由来の試料のモデリング用に選択した構造は、Protein Data Bankで同定されている1HEZ、2H1P、1AQK、1DQL、1MF2および1FLRを有していた。次いで、これらの鋳型構造を重ねあわせによってアライメントさせ、用いることで複数の鋳型の中で構造に基づく配列アライメントを生成した。次いで、抗体131の可変領域の配列を鋳型配列に対してアライメントさせた。構造および配列のアライメントを用いることで、131抗体の可変領域における分子モデルを生成した。軽鎖CDR1の配列は、RSSQSLVHSDGNTYLS(配列番号101)であった。軽鎖CDR2の配列は、RISRRFS(配列番号103)であった。軽鎖CDR3の配列はMQSTHVPRT(配列番号105)であった。重鎖CDR1の配列はNYGMH(配列番号108)であった。重鎖CDR2の配列はVIWYDGSDKYYADSVRG(配列番号110)であった。重鎖CDR3の配列はDGYDILTGNPRDFDY(配列番号112)であった。

Claims (31)

  1. 重鎖ポリペプチドおよび軽鎖ポリペプチドを含む単離したヒトモノクローナル抗体であって、前記重鎖または軽鎖ポリペプチドの少なくとも1つが、配列番号2、配列番号19、配列番号142、配列番号144およびこれらの組み合わせからなる群から選択されるアミノ酸配列に少なくとも90%同一であるアミノ酸配列を含む、抗体。
  2. 前記重鎖ポリペプチドが、配列番号2のアミノ酸配列を含む、請求項1に記載の単離したヒトモノクローナル抗体。
  3. 前記軽鎖ポリペプチドが、配列番号142のアミノ酸配列を含む、請求項1に記載の単離したヒトモノクローナル抗体。
  4. 配列LEEKKGNYVVTDHC(配列番号56)からなるペプチドに結合する、請求項1に記載の単離したヒトモノクローナル抗体。
  5. 前記重鎖ポリペプチドが、配列番号2のアミノ酸配列に少なくとも約95%同一であるアミノ酸配列を含み、前記軽鎖ポリペプチドが、配列番号19のアミノ酸配列に少なくとも約95%同一であるアミノ酸配列を含む、請求項1に記載の単離したヒトモノクローナル抗体。
  6. 前記重鎖ポリペプチドが、以下のアミノ酸配列：配列番号108、配列番号110および配列番号112の少なくとも1つを含む、請求項1に記載の単離したヒトモノクローナル抗体。
  7. 前記重鎖ポリペプチドが、以下のアミノ酸配列：配列番号108、配列番号110および配列番号112の3つ全てを含む、請求項1に記載の単離したヒトモノクローナル抗体。
  8. 前記軽鎖ポリペプチドが、以下のアミノ酸配列：配列番号101、配列番号103および配列番号105の少なくとも1つを含む、請求項1に記載の単離したヒトモノクローナル抗体。
  9. 前記軽鎖ポリペプチドが、以下のアミノ酸配列：配列番号101、配列番号103および配列番号105の3つ全てを含む、請求項1に記載の単離したヒトモノクローナル抗体。
  10. 前記重鎖ポリペプチドが、配列番号142のアミノ酸配列に少なくとも約95%同一であるアミノ酸配列を含み、前記軽鎖ポリペプチドが、配列番号144のアミノ酸配列に少なくとも約95%同一であるアミノ酸配列を含む、請求項1に記載の単離したヒトモノクローナル抗体。
  11. 前記重鎖ポリペプチドが、以下のアミノ酸配列：配列番号121、配列番号123および配列番号125の少なくとも1つを含む、請求項1に記載の単離したヒトモノクローナル抗体。
  12. 前記重鎖ポリペプチドが、以下のアミノ酸配列：配列番号121、配列番号123および配列番号125の3つ全てを含む、請求項1に記載の単離したヒトモノクローナル抗体。
  13. 前記軽鎖ポリペプチドが、以下のアミノ酸配列：配列番号101、配列番号116および配列番号118の少なくとも1つを含む、請求項1に記載の単離したヒトモノクローナル抗体。
  14. 前記軽鎖ポリペプチドが、以下のアミノ酸配列：配列番号101、配列番号116および配列番号118の3つ全てを含む、請求項1に記載の単離したヒトモノクローナル抗体。
  15. EGFRvIIIに結合する単離したヒトモノクローナル抗体であって、
    以下の相補性決定領域（CDR）：配列番号142のCDR1である重鎖CDR1；配列番号142のCDR2である重鎖CDR2；配列番号142のCDR3である重鎖CDR3を含む重鎖ポリペプチド；および
    以下のCDR：配列番号144のCDR1である軽鎖CDR1；配列番号144のCDR2である軽鎖CDR2；配列番号144のCDR3である軽鎖CDR3を含む軽鎖ポリペプチド；
    を含む抗体。
  16. 前記重鎖ポリペプチドが、以下のアミノ酸配列：配列番号121、配列番号123および配列番号125の3つ全てを含む、請求項15に記載の単離したヒトモノクローナル抗体。
  17. 前記軽鎖ポリペプチドが、以下のアミノ酸配列：配列番号101、配列番号116および配列番号118の3つ全てを含む、請求項15に記載の単離したヒトモノクローナル抗体。
  18. EGFRvIIIに結合する単離したヒトモノクローナル抗体であって、
    以下の相補性決定領域（CDR）：配列番号2のCDR1である重鎖CDR1；配列番号2のCDR2である重鎖CDR2；配列番号2のCDR3である重鎖CDR3を含む重鎖ポリペプチド；および
    以下のCDR：配列番号19のCDR1である軽鎖CDR1；配列番号19のCDR2である軽鎖CDR2；配列番号19のCDR3である軽鎖CDR3を含む軽鎖ポリペプチド；
    を含む抗体。
  19. 前記重鎖ポリペプチドが、以下のアミノ酸配列：配列番号108、配列番号110および配列番号112の3つ全てを含む、請求項18に記載の単離したヒトモノクローナル抗体。
  20. 前記軽鎖ポリペプチドが、以下のアミノ酸配列：配列番号101、配列番号103および配列番号105の3つ全てを含む、請求項18に記載の単離したヒトモノクローナル抗体。
  21. EGFRvIIIタンパク質上のエピトープに結合する単離したヒトモノクローナル抗体であって、アミノ酸配列LEEKKGNYVVTDHC(配列番号56)に結合する抗体であり、配列番号56中の二番目のリジンが、前記エピトープの一部である、抗体。
  22. EGFRvIIIタンパク質に結合する単離したヒトモノクローナル抗体であって、EGFRvIIIへの結合について請求項1に記載の抗体と競合する抗体。
  23. 哺乳動物組織または細胞中のEGFRvIIIを検出するためのアッセイキットであって、請求項1から22のいずれか一項に記載の少なくとも1つの抗体、および存在する場合抗体とEGFRvIIIの結合を示すための手段を含むキット。
  24. 前記抗体がモノクローナル抗体である、請求項23に記載のアッセイキット。
  25. 前記抗体が標識されている、請求項24に記載のアッセイキット。
  26. 前記抗体が非標識の一次抗体であり、反応を示すための前記手段が抗免疫グロブリンである標識した二次抗体を含む、請求項23に記載のアッセイキット。
  27. 前記抗体が、蛍光色素、酵素、放射性核種および放射線不透過性物質からなる群から選択されるマーカーで標識されている、請求項23に記載のアッセイキット。
  28. EGFRvIIIの発現と関連する細胞の増殖をin vitroで阻害する方法であって、
    EGFRvIIIを発現する細胞を請求項1から22のいずれか一項に記載の少なくとも1つの抗体と接触させることを含む、方法。
  29. 上皮成長因子受容体vIII（EGFRvIII）を発現する癌細胞の治療のための医薬の調製における、請求項1から22のいずれか一項に記載の少なくとも1つの抗体の使用。
  30. 前記癌細胞が上皮細胞である、請求項29に記載の使用。
  31. 前記癌細胞が肺、結腸、胃、腎臓、前立腺、胸部、膠芽細胞または卵巣癌細胞からなる群から選択される、請求項29に記載の使用。
JP2006517700A 2003-06-27 2004-06-25 上皮成長因子受容体の欠失型変異体を認識する抗体、およびそれらの使用 Active JP4800210B2 (ja)

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US48314503P 2003-06-27 2003-06-27
US60/483,145 2003-06-27
US52557003P 2003-11-26 2003-11-26
US60/525,570 2003-11-26
US56245304P 2004-04-15 2004-04-15
US60/562,453 2004-04-15
PCT/US2004/020564 WO2005012479A2 (en) 2003-06-27 2004-06-25 Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof

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