JP2000509603A - 糖タンパク質ホルモンスーパーアゴニスト - Google Patents
糖タンパク質ホルモンスーパーアゴニストInfo
- Publication number
- JP2000509603A JP2000509603A JP09539866A JP53986697A JP2000509603A JP 2000509603 A JP2000509603 A JP 2000509603A JP 09539866 A JP09539866 A JP 09539866A JP 53986697 A JP53986697 A JP 53986697A JP 2000509603 A JP2000509603 A JP 2000509603A
- Authority
- JP
- Japan
- Prior art keywords
- hormone
- human
- amino acid
- glycoprotein
- positions
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.位置11、13、14、16、17及び20から成る群から選択される位 置でα−サブユニット中に少なくとも3つの塩基性アミノ酸を含むヒト糖タンパ ク質ホルモン。 2.位置11、13、14、16、17及び20から成る群から選択される位 置に第4の塩基性アミノ酸をさらに含む請求項1のヒト糖タンパク質ホルモン。 3.塩基性アミノ酸が位置11、13、16及び20に存在する請求項2のヒ ト糖タンパク質ホルモン。 4.塩基性アミノ酸が位置11、13、17及び20に存在する請求項2のヒ ト糖タンパク質ホルモン。 5.塩基性アミノ酸が位置13、14、16及び20に存在する請求項2のヒ ト糖タンパク質ホルモン。 6.塩基性アミノ酸が位置13、14、17及び20に存在する請求項2のヒ ト糖タンパク質ホルモン。 7.位置11、13、14、16、17及び20から成る群から選択される位 置に第5の塩基性アミノ酸をさらに含む請求項1のヒト糖タンパク質ホルモン。 8.塩基性アミノ酸が位置13、14、16、17及び20に存在する請求項 7のヒト糖タンパク質ホルモン。 9.塩基性アミノ酸が位置11、13、14、16及び20に存在する請求項 7のヒト糖タンパク質ホルモン。 10.塩基性アミノ酸が位置11、13、14、16、17及び20に存在す る請求項1のヒト糖タンパク質ホルモン。 11.塩基性アミノ酸が位置13、16及び20に存在する請求項1のヒト糖 タンパク質ホルモン。 12.甲状腺刺激ホルモンである請求項1〜11のいずれか一項の糖タンパク 質ホルモン。 13.βサブユニットの位置58、63及び69から成る群から選択される少 なくとも1つの位置に塩基性アミノ酸をさらに含む請求項12のヒト甲状腺刺激 ホルモン。 14.βサブユニットの位置58、63及び69に塩基性アミノ酸を含む請求 項13のヒト甲状腺刺激ホルモン。 15.塩基性アミノ酸が位置58に存在する請求項13のヒト糖タンパク質ホ ルモン。 16.塩基性アミノ酸が位置63に存在する請求項13のヒト糖タンパク質ホ ルモン。 17.塩基性アミノ酸が位置69に存在する請求項13のヒト糖タンパク質ホ ルモン。 18.卵胞刺激ホルモンである請求項1〜11のいずれか一項の糖タンパク質 ホルモン。 19.黄体形成ホルモンである請求項1〜11のいずれか一項の糖タンパク質 ホルモン。 20.絨毛性性腺刺激ホルモンである請求項1〜11のいずれか一項の糖タン パク質ホルモン。 21.塩基性アミノ酸がリジンである請求項1〜20のいずれか一項のヒト糖 タンパク質ホルモン。 22.塩基性アミノ酸がリジン及びアルギニンから成る群から選択される請求 項1〜20のいずれか一項のヒト糖タンパク質ホルモン。 23.対象における糖タンパク質ホルモン活性に関連した症状を治療するため の薬剤の製造方法であって、治療量の前記請求項のいずれか一項の適切な糖タン パク質ホルモンを患者に投与することを含む方法。 24.症状が排卵不全である請求項23の方法。 25.症状が黄体期欠損である請求項23の方法。 26.症状が原因不明不妊である請求項23の方法。 27.症状が雄性因子不妊である請求項23の方法。 28.症状が時限性受胎である請求項23の方法。 29.症状が甲状腺癌である請求項23の方法。 30.請求項1〜22のいずれか一項の糖タンパク質ホルモンを補助量投与す ることを含む、対象の生殖を補助する方法。 31.請求項1〜22のいずれか一項のヒト糖タンパク質をコードする核酸。 32.核酸を発現するのに適したベクター中の請求項31の核酸。 33.核酸を発現するのに適した宿主中の請求項32のベクター。 34.位置11、13、14、16、17及び20以外の位置のα−サブユニ ット中に5つ未満のアミノ酸置換を有する請求項1〜22のいずれか一項の糖タ ンパク質ホルモン。 35.位置11、13、14、16、17及び20以外の位置のα−サブユニ ット中に4つ未満のアミノ酸置換を有する請求項1〜22のいずれか一項の糖タ ンパク質ホルモン。 36.位置11、13、14、16、17及び20以外の位置のα−サブユニ ット中に3つ未満のアミノ酸置換を有する請求項1〜22のいずれか一項の糖タ ンパク質ホルモン。 37.位置11、13、14、16、17及び20以外の位置のα−サブユニ ット中に2つ未満のアミノ酸置換を有する請求項1〜22のいずれか一項の糖タ ンパク質ホルモン。 38.αサブユニットの位置11、13、14、16、17及び20以外の位 置にヒト糖タンパク質ホルモンと相同の完全アミノ酸配列を有する請求項1〜2 2のいずれか一項の糖タンパク質ホルモン。 39.ヒト甲状腺刺激ホルモンのβサブユニットの位置58、63及び69に 対応する、糖タンパク質ホルモンのβサブユニット中の位置から成る群から選択 される少なくとも1つの位置に塩基性アミノ酸を含む請求項18、19及び20 のいずれか一項のヒト糖タンパク質。 40.位置11、13、14、16、17及び20から成る群から選択される 少なくとも1つの位置でαサブユニット中に塩基性アミノ酸を含むヒト糖タンパ ク質ホルモン。 41.塩基性アミノ酸が位置11に存在する請求項40のヒト糖タンパク質ホ ルモン。 42.塩基性アミノ酸が位置13に存在する請求項40のヒト糖タンパク質ホ ルモン。 43.塩基性アミノ酸が位置14に存在する請求項40のヒト糖タンパク質ホ ルモン。 44.塩基性アミノ酸が位置16に存在する請求項40のヒト糖タンパク質ホ ルモン。 45.塩基性アミノ酸が位置17に存在する請求項40のヒト糖タンパク質ホ ルモン。 46.塩基性アミノ酸が位置20に存在する請求項40のヒト糖タンパク質ホ ルモン。 47.塩基性アミノ酸がリジンである請求項41〜46のいずれか一項のヒト 糖タンパク質ホルモン。 48.塩基性アミノ酸がリジン及びアルギニンから成る群から選択される請求 項41〜46のいずれか一項のヒト糖タンパク質ホルモン。 49.位置11、13、14、16、17及び20から成る群から選択される 少なくとも2つの位置に塩基性アミノ酸を含む請求項40のヒト糖タンパク質ホ ルモン。 50.塩基性アミノ酸が位置16及び20に存在する請求項49のヒト糖タン パク質ホルモン。 51.塩基性アミノ酸が位置16及び13に存在する請求項49のヒト糖タン パク質ホルモン。 52.塩基性アミノ酸が位置20及び13に存在する請求項49のヒト糖タン パク質ホルモン。 53.塩基性アミノ酸がリジン及びアルギニンから成る群から選択される請求 項49〜52のいずれか一項のヒト糖タンパク質ホルモン。 54.甲状腺刺激ホルモンである請求項41〜52のいずれか一項の糖タンパ ク質ホルモン。 55.βサブユニットの位置58、63及び69から成る群から選択される少 なくとも1つの位置に塩基性アミノ酸をさらに含む請求項54のヒト甲状腺刺激 ホルモン。 56.βサブユニットの位置58、63及び69の位置に塩基性アミノ酸を含 む請求項55のヒト甲状腺刺激ホルモン。 57.塩基性アミノ酸が位置58に存在する請求項55のヒト糖タンパク質ホ ルモン。 58.塩基性アミノ酸が位置63に存在する請求項55のヒト糖タンパク質ホ ルモン。 59.塩基性アミノ酸が位置69に存在する請求項55のヒト糖タンパク質ホ ルモン。 60.卵胞刺激ホルモンである請求項41〜53のいずれか一項の糖タンパク 質ホルモン。 61.黄体形成ホルモンである請求項41〜53のいずれか一項の糖タンパク 質ホルモン。 62.絨毛性性腺刺激ホルモンである請求項41〜53のいずれか一項の糖タ ンパク質ホルモン。 63.対象における糖タンパク質ホルモン活性に関連した症状を治療するため 方法であって、請求項1〜22、31〜39、40〜62及び71〜84のいず れか一項の適切な糖タンパク質ホルモンを患者に治療量投与することを含む方法 。 64.症状が排卵不全である請求項63の方法。 65.症状が黄体期欠損である請求項63の方法。 66.症状が原因不明不妊である請求項63の方法。 67.症状が雄性因子不妊である請求項63の方法。 68.症状が時限性受胎である請求項63の方法。 69.症状が甲状腺癌である請求項63の方法。 70.請求項40〜62の糖タンパク質ホルモンを補助量投与することを含む 、対象における生殖の補助方法。 71.請求項41〜53のいずれか一項のヒト糖タンパク質をコードする核酸 。 72.核酸を発現するのに適したベクター中の請求項71の核酸。 73.核酸を発現するのに適した宿主中の請求項72のベクター。 74.位置11、13、14、16、17及び20以外の位置のα−サブユニ ツト中に5つ未満のアミノ酸置換を有する請求項40〜62のいずれか一項の糖 タンパク質ホルモン。 75.位置11、13、14、16、17及び20以外の位置のα−サブユニ ット中に4つ未満のアミノ酸置換を有する請求項40〜62のいずれか一項の糖 タンパク質ホルモン。 76.位置11、13、14、16、17及び20以外の位置のα−サブユニ ット中に3つ未満のアミノ酸置換を有する請求項40〜62のいずれか一項の糖 タンパク質ホルモン。 77.位置11、13、14、16、17及び20以外の位置のα−サブユニ ット中に2つ未満のアミノ酸置換を有する請求項40〜62のいずれか一項の糖 タンパク質ホルモン。 78.αサブユニットの位置11、13、14、16、17及び20以外の位 置にヒト糖タンパク質ホルモンと相同の完全アミノ酸配列を有する請求項40〜 62のいずれか一項の糖タンパク質ホルモン。 79.ヒト甲状腺刺激ホルモンのβサブユニットの位置58、63及び69に 対応する、甲状腺刺激ホルモン以外の糖タンパク質ホルモンのβサブユニット中 の位置から成る群から選択される少なくとも1つの位置に塩基性アミノ酸を含む 請求項40〜62のいずれか一項のヒト糖タンパク質。 80.野生型ヒト糖タンパク質ホルモンを上回る活性を有する非ヒト糖タンパ ク質ホルモンの塩基性アミノ酸の位置に対応する位置に置換された同一のアミノ 酸を含む、野生型ヒト糖タンパク質ホルモンを上回る活性を有する修飾ヒト糖タ ンパク質ホルモン。 81.野生型糖タンパク質ホルモンを上回る活性を有する別の種由来の糖タン パク質ホルモンの塩基性アミノ酸の位置に対応する位置に置換された同一のアミ ノ酸を含む、同一種由来の野生型糖タンパク質ホルモンを上回る活性を有する修 飾ヒト糖タンパク質ホルモン。 82.非ヒト糖タンパク質ホルモンがウシ由来である請求項80の糖タンパク 質ホルモン。 83.塩基性アミノ酸がリジンである請求項80の糖タンパク質ホルモン。 84.活性が少なくとも3倍増大されている請求項80の糖タンパク質ホルモ ン。 85.ヒトホルモンの超活性非キメラアナログの構築方法であって、以下の工 程を含む方法。 a)別の種由来のより活性なホモログのアミノ酸配列をヒトホルモンと比較す る。 b)ヒトホルモン中のアミノ酸を別の種由来の対応するアミノ酸で置換する。 c)置換ヒトホルモンの活性を測定する。 d)置換ヒトホルモンから超活性アナログを選択する。 86.ヒトホルモンのアンタゴニスト非キメラアナログの構築方法であって、 以下の工程を含む方法。 a)別の種由来のより低活性のホモログのアミノ酸配列をヒトホルモンと比較 する。 b)ヒトホルモン中のアミノ酸を別の種由来の対応するアミノ酸で置換する。 c)置換ヒトホルモンの活性を測定する。 d)置換ヒトホルモンからアンタゴニストアナログを選択する。 87.ホルモンが糖タンパク質ホルモンである請求項85又は86のいずれか 一項の方法。
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PCT/US1996/006483 WO1997042322A1 (en) | 1996-05-08 | 1996-05-08 | Glycoprotein hormone superagonists |
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JP (1) | JP3981413B2 (ja) |
KR (1) | KR20040039320A (ja) |
AT (1) | ATE381617T1 (ja) |
AU (1) | AU714635B2 (ja) |
CA (1) | CA2253441C (ja) |
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US6361992B1 (en) | 1996-05-08 | 2002-03-26 | The United States Of America As Represented By The Department Of Health And Human Services | Thyroid stimulating hormone superagonists |
AU2005223651B2 (en) * | 2004-03-19 | 2012-07-12 | Trophogen, Inc. | Follicle stimulating hormone superagonists |
EP1738174A2 (en) * | 2004-03-31 | 2007-01-03 | Trophogen, Inc. | Human glycoprotein hormone superagonists and uses thereof |
US10457713B2 (en) | 2012-07-30 | 2019-10-29 | Trophogen, Inc. | Glycoprotein hormone long-acting superagonists |
NZ707016A (en) | 2012-07-30 | 2017-08-25 | Trophogen Inc | Glycoprotein hormone long-acting superagonists |
JP2017502079A (ja) | 2013-11-05 | 2017-01-19 | トロフォジェン インコーポレイテッド | 糖タンパク質ホルモン長時間作用性スーパーアゴニスト |
KR101947340B1 (ko) * | 2017-05-05 | 2019-02-12 | 주식회사 유비프로틴 | FSHα 반감기를 증가시키는 방법 |
KR101947341B1 (ko) * | 2017-05-05 | 2019-02-12 | 주식회사 유비프로틴 | FSHβ 반감기를 증가시키는 방법 |
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EP0404458A3 (en) * | 1989-06-19 | 1992-03-04 | Bunge (Australia) Proprietary Limited | Ovine follicle stimulating hormone |
AU672969B2 (en) | 1992-03-10 | 1996-10-24 | United States of America, as represented by The Secretary, Department of Health & Human Services, The | Exchangeable template reaction |
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1996
- 1996-05-08 CA CA2253441A patent/CA2253441C/en not_active Expired - Lifetime
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CA2253441C (en) | 2013-07-16 |
EP1947117A3 (en) | 2008-10-08 |
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EP0954578B1 (en) | 2007-12-19 |
ATE381617T1 (de) | 2008-01-15 |
CA2253441A1 (en) | 1997-11-13 |
EP0954578A1 (en) | 1999-11-10 |
DE69637375D1 (en) | 2008-01-31 |
AU5854996A (en) | 1997-11-26 |
WO1997042322A1 (en) | 1997-11-13 |
JP3981413B2 (ja) | 2007-09-26 |
DE69637375T2 (de) | 2009-02-12 |
KR20040039320A (ko) | 2004-05-10 |
AU714635B2 (en) | 2000-01-06 |
EP1947117A2 (en) | 2008-07-23 |
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