JP2004262947A - 網膜の色素沈着された上皮由来の神経栄養性因子 - Google Patents

網膜の色素沈着された上皮由来の神経栄養性因子 Download PDF

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JP2004262947A
JP2004262947A JP2004171939A JP2004171939A JP2004262947A JP 2004262947 A JP2004262947 A JP 2004262947A JP 2004171939 A JP2004171939 A JP 2004171939A JP 2004171939 A JP2004171939 A JP 2004171939A JP 2004262947 A JP2004262947 A JP 2004262947A
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Lincoln V Johnson
ブイ． ジョンソン リンカーン
Joyce Tombran-Tink
トンブラン−ティンク ジョイス
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Abstract

【課題】 網膜の色素沈着された上皮由来の神経栄養性因子の精製と提供。
【解決手段】 腫瘍を処置するための薬学的組成物であって、以下：配列番号１の第１位のＭｅｔから第４１８位のプロリンによりなる色素沈着上皮由来神経栄養因子（ＰＥＤＮＦ）または１または数個のアミノ酸の置換、付加または欠失を有し、かつ細胞の神経単位分化を誘導する活性を有する、該ＰＥＤＮＦの改変体を含む、薬学的組成物であって、１つの実施形態において、上記ＰＥＤＮＦが、以下：Ａｓｐ２５、Ａｓｎ１１、Ｔｈｒ２８、Ｓｅｒ３８、Ｇｌｕ２６、Ｇｌｎ１５、Ｐｒｏ２９、Ｇｌｙ２３、Ａｌａ２５、Ｖａｌ２５、Ｍｅｔ７、Ｉ１ｅ２２、Ｌｅｕ５７、Ｔｙｒ１０、Ｐｈｅ１８、Ｈｉｓ８、Ｌｙｓ２７、Ｔｒｐ３およびＡｒｇ１８のアミノ酸組成物を含む、薬学的組成物。
【選択図】 なし

Description

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（配列表）
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よって、本願発明によって、以下が提供される。
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本発明の特徴と利点は、本発明の特許請求の範囲と詳細な説明を下記の図面を参照してよめばより一層明らかになるであろう。
図１は、RPEならし培地（RPR−CM）に特有のPEDNFタンパク質ダブレット位置を示すクーマシーブルーで染色したSDSポリアクリルアミドゲルである。 図２は、付着させて８日後、電気溶出されたPEDNF２μｇ／mlを含有する結成なしの培地（パネルA)中または血清なしの対照培地（パネルB）中で、７日間刺激したい細胞培養物を示し微分干渉コントラスト顕微鏡の写真である。 図３は、銀で染色した二次元ゲルである。分子量を左側に示しｐHを上部に示してある。

Claims (30)

  1. 腫瘍を処置するための薬学的組成物であって、以下：
    配列番号１の第１位のＭｅｔから第４１８位のプロリンによりなる
    色素沈着上皮由来神経栄養因子（ＰＥＤＮＦ）または
    １または数個のアミノ酸の置換、付加または欠失を有し、かつ細胞の神経単位分化を誘導する活性を有する、該ＰＥＤＮＦの改変体
    を含む、薬学的組成物。
  2. 請求項１に記載の薬学的組成物であって、前記ＰＥＤＮＦが、以下：
    Ａｓｐ２５、Ａｓｎ１１、Ｔｈｒ２８、Ｓｅｒ３８、Ｇｌｕ２６、Ｇｌｎ１５、Ｐｒｏ２９、Ｇｌｙ２３、Ａｌａ２５、Ｖａｌ２５、Ｍｅｔ７、Ｉ１ｅ２２、Ｌｅｕ５７、Ｔｙｒ１０、Ｐｈｅ１８、Ｈｉｓ８、Ｌｙｓ２７、Ｔｒｐ３およびＡｒｇ１８のアミノ酸組成物を含む、薬学的組成物。
  3. 請求項１に記載の薬学的組成物であって、ここで、前記ＰＥＤＮＦまたはその改変体がさらに、分子量５０，０００〜５５，０００を有する糖タンパク質であるという特性を備える、薬学的組成物。
  4. 請求項１に記載の薬学的組成物であって、前記ＰＥＤＮＦが３．９〜７．２のｐＩを有するという特性をさらに備える、薬学的組成物。
  5. 請求項１に記載の薬学的組成物であって、ここで、該組成物が、腫瘍の退縮を誘導するのに有用である、薬学的組成物。
  6. 請求項１に記載の薬学的組成物であって、ここで、該組成物が、腫瘍増殖の速度を鈍化させるのに有用な、薬学的組成物。
  7. 請求項１に記載の薬学的組成物であって、ここで、該組成物が、腫瘍増殖の停止を誘導するのに有用である、薬学的組成物。
  8. 前記腫瘍が、眼性腫瘍である、請求項１に記載の薬学的組成物。
  9. 前記腫瘍が、神経単位腫瘍である、請求項１に記載の薬学的組成物。
  10. 前記腫瘍が、非神経単位起源である、請求項１に記載の薬学的組成物。
  11. 神経損傷を処置するための薬学的組成物であって、以下：
    配列番号１の第１位のＭｅｔから第４１８位のプロリンによりなる
    色素沈着上皮由来神経栄養因子（ＰＥＤＮＦ）、または
    １または数個のアミノ酸の置換、付加または欠失を有し、かつ細胞の神経単位分化を誘導する活性を有する、該ＰＥＤＮＦの改変体
    を含む、薬学的組成物。
  12. 請求項１１に記載の薬学的組成物であって、前記ＰＥＤＮＦが、以下：
    Ａｓｐ２５、Ａｓｎ１１、Ｔｈｒ２８、Ｓｅｒ３８、Ｇｌｕ２６、Ｇｌｎ１５、Ｐｒｏ２９、Ｇｌｙ２３、Ａｌａ２５、Ｖａｌ２５、Ｍｅｔ７、Ｉ１ｅ２２、Ｌｅｕ５７、Ｔｙｒ１０、Ｐｈｅ１８、Ｈｉｓ８、Ｌｙｓ２７、Ｔｒｐ３およびＡｒｇ１８のアミノ酸組成物を含む、薬学的組成物。
  13. 請求項１１に記載の薬学的組成物であって、ここで、前記ＰＥＤＮＦがさらに、分子量５０，０００〜５５，０００を有する糖タンパク質であるという特性を備える、薬学的組成物。
  14. 請求項１１に記載の薬学的組成物であって、前記ＰＥＤＮＦが３．９〜７．２のｐＩを有するという特性をさらに備える、薬学的組成物。
  15. 請求項１１に記載の薬学的組成物であって、ここで、該組成物が、神経再生を誘導するのに有用である、薬学的組成物。
  16. 請求項１１に記載の薬学的組成物であって、ここで、該組成物が、神経単位分化を誘導するのに有用である、薬学的組成物。
  17. 請求項１６に記載の薬学的組成物であって、ここで、前記神経単位分化が網膜芽腫細胞中にある、薬学的組成物。
  18. 眼科疾患を処置するための薬学的組成物であって、以下：
    配列番号１の第１位のＭｅｔから第４１８位のプロリンによりなる
    色素沈着上皮由来神経栄養因子（ＰＥＤＮＦ）、または
    １または数個のアミノ酸の置換、付加または欠失を有し、かつ細胞の神経単位分化を誘導する活性を有する、該ＰＥＤＮＦの改変体
    を含む、薬学的組成物。
  19. 請求項１８に記載の薬学的組成物であって、前記ＰＥＤＮＦが、以下：
    Ａｓｐ２５、Ａｓｎ１１、Ｔｈｒ２８、Ｓｅｒ３８、Ｇｌｕ２６、Ｇｌｎ１５、Ｐｒｏ２９、Ｇｌｙ２３、Ａｌａ２５、Ｖａｌ２５、Ｍｅｔ７、Ｉ１ｅ２２、Ｌｅｕ５７、Ｔｙｒ１０、Ｐｈｅ１８、Ｈｉｓ８、Ｌｙｓ２７、Ｔｒｐ３およびＡｒｇ１８のアミノ酸組成物を含む、薬学的組成物。
  20. 請求項１８に記載の薬学的組成物であって、ここで、前記ＰＥＤＮＦがさらに、分子量５０，０００〜５５，０００を有する糖タンパク質であるという特性を備える、薬学的組成物。
  21. 請求項１８に記載の薬学的組成物であって、前記ＰＥＤＮＦまたはその改変体がさらに３．９〜７．２のｐＩを有するという特性をさらに備える、薬学的組成物。
  22. 前記眼科疾患が網膜疾患である、請求項１８に記載の薬学的組成物。
  23. 前記網膜疾患が、網膜芽症である、請求項２２に記載の薬学的組成物。
  24. 前記網膜疾患が、筋肉変性である、請求項２２に記載の薬学的組成物。
  25. 前記網膜疾患が糖尿病性網膜症である、請求項２２に記載の薬学的組成物。
  26. 前記網膜疾患が色素性網膜炎である、請求項２２に記載の薬学的組成物。
  27. 細胞に対する神経単位応答を誘導する方法であって、請求項１に記載の組成物を細胞に投与する工程を包含する、方法。
  28. 前記細胞が胎芽細胞又は不死化細胞である、請求項１、１１または１８に記載の薬学的組
    成物。
  29. 前記細胞が神経単位細胞である、請求項１、１１または１８に記載の薬学的組成物。
  30. 前記細胞がＹ７９網膜芽腫細胞である、請求項１、１１または１８に記載の薬学的組成物。
JP2004171939A 1992-06-04 2004-06-09 網膜の色素沈着された上皮由来の神経栄養性因子 Pending JP2004262947A (ja)

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DE69333229D1 (de) 2003-11-06
EP0662087A4 (en) 1997-01-29
AU4406993A (en) 1993-12-30
EP1415994A1 (en) 2004-05-06
JP2005112863A (ja) 2005-04-28
CA2137377A1 (en) 1993-12-09
WO1993024529A1 (en) 1993-12-09
EP0662087A1 (en) 1995-07-12
JPH07508646A (ja) 1995-09-28
CA2137377C (en) 2011-03-08
DE69333229T2 (de) 2004-08-12

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