JP2001500845A - 骨粗鬆症の治寮のための副甲状腺ホルモン類似体 - Google Patents
骨粗鬆症の治寮のための副甲状腺ホルモン類似体Info
- Publication number
- JP2001500845A JP2001500845A JP10507413A JP50741398A JP2001500845A JP 2001500845 A JP2001500845 A JP 2001500845A JP 10507413 A JP10507413 A JP 10507413A JP 50741398 A JP50741398 A JP 50741398A JP 2001500845 A JP2001500845 A JP 2001500845A
- Authority
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- Japan
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- hpth
- analog
- seq
- leu
- 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.)
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.位置27がLysであり、又は適切な疎水性残基により置換されており、そし てラクタムを形成するために環化されているヒト副甲状腺ホルモンhPTH-(1-31) 類似体。 2.前記環化が、Glu22とLys26との間、又はLys26とAsp30との間で存在する請 求の範囲第1項記載の類似体。 3.前記疎水性残基がLeuである請求の範囲第1項記載の類似体。 4.前記疎水性残基が、オルニチン、シトルリン、α−アミノ酪酸、又は側鎖 に2〜10個の炭素を有するいづれかの線状又は枝分れ鎖の脂肪族α−アミノ酸か ら成る群から選択される、脂肪族鎖の末端で極性又は荷電された基を有する類似 体である請求の範囲第1項記載の類似体。 5.前記疎水性残基が、Ile、ノルロイシン、Met及びオルニチンから成る群か ら選択される請求の範囲第4項記載の類似体。 6.C−末端アミド末端又はC−末端カルボキシル末端のいづれかを有する請 求の範囲第1項記載の類似体。 7.配列番号3を有する請求の範囲第1項記載の類似体。 8.配列番号4を有する請求の範囲第1項記載の類似体。 9.医薬的に許容できるキャリヤー又は賦形剤と共に、請求の範囲第1項記載 のヒト副甲状腺ホルモン(hPTH)-(1-31)類似体を含んで成る、その必要な温血動 物に投与するための組成物。 10.前記類似体における疎水性残基がLeuである請求の範囲第9項記載の組成 物。 11.前記類似体における疎水性残基がIle、ノルロイシン、Met及びオルニチン から成る群から選択される請求の範囲第9項記載の 組成物。 12.前記類似体が配列番号3を有する請求の範囲第9項記載の組成物。 13.前記類似体が配列番号4を有する請求の範囲第9項記載の組成物。 14.処理の必要な温血動物を処理するための方法であって、請求の範囲第1項 記載のヒト副甲状腺ホルモン(hPTH)-(1-31)類似体の治療的有効量をそのような 温血動物に投与することを含んで成る方法。 15.前記類似体における疎水性残基がLeuである請求の範囲第14項記載の方法 。 16.前記類似体における疎水性残基がIle、ノルロイシン、Met及びオルニチン から成る群から選択される請求の範囲第14項記載の方法。 17.前記類似体が配列番号3を有する請求の範囲第14項記載の方法。 18.前記類似体が配列番号4を有する請求の範囲第15項記載の方法。 19.下記アミノ酸配列: 〔配列中、Rは水素、あるいは、いづれか線状又は枝分れ鎖のアルキル、アシル 又はアリール基であり、 R1はSer,Ala又はAibであり、 R2はMet、又は天然に存在する疎水性アミノ酸であり、 R3はHis、又は水溶性アミノ酸であり、 R4はLeu、又は水溶性アミノ酸であり、 R5はAsn、又は水溶性アミノ酸であり、 R6はSer、又は水溶性アミノ酸であり、 R7はMet、又は天然に存在する疎水性アミノ酸であり、 R8はGlu,Lys又はAspであり、 R9はCys,Glu又はOrnであり、 R10はArg,Lys,Orn,Gln,Glu又はAspであり、 R11は天然に存在する疎水性又は極性アミノ酸であり、 R12はGln,Arg,Glu,Asp,Lys又はOrnであり、 XはOH,NH2であり、そして Yは、X,Val-X,Val-His-X,Val-His-Asn-X,Val-His-Asn-Phe-X,Val-His- Asn-Phe-Val-X,Val-His-Asn-Phe-Val-Ala-X、及びVal-His-Asn-Phe-Val-Ala-Le u-Xであり、R3及びR6がLys,Orn,Glu又はAspである場合、1又は2つのア ミノ酸対22と26との、26と30との、27と30との、及び25と29との間で環化され、 但しシクロ(Lys26-Asp30)〔Leu27〕-hPTH-(1-34)-NH2、シクロ(Lys27-Asp30)- hPTH-(1-34)-NH2及びシクロ(Lys26-Asp30)-〔Leu27〕-hPTH-(1-34)-OHを除く〕 を有するヒト副甲状腺ホルモンhPTH及び医薬的に許容できるその塩。 20.前記環化がラクタムの形で存在する請求の範囲第19項記載の類似体。 21.前記ラクタムがi、i+4ラクタムである請求の範囲第20項記載の類似体 。 22.前記ラクタムがGlu22-Lys26ラクタムである請求の範囲第21項記載の類似 体。 23.前記ラクタムがLys26-Asp30ラクタムである請求の範囲第21項記載の類似 体。 24.RがHであり、そしてXがNH2である請求の範囲第20項記載 の類似体。 25.R11がLys又はLeuである請求の範囲第24項記載の類似体。 26.R2及びR7がMet又はNleである請求の範囲第25項記載の類似体。 27.R1がSerであり、R2がMetであり、R7がMetであり、R8がGluであり 、R9がArgであり、R10がLysであり、そしてR12がGlnである請求の範囲第26 項記載の類似体。 28.R3がHis又はLysであり、R4がLeu,Lys又はArgであり、R5がAsn,Or n,Hci,Asp,Arg,Lys,D-Lys,Ser又はGlyであり、そしてR6がSer,Lys,As p又はArgである請求の範囲第27項記載の類似体。 29.R3−R6がHis-Lys-Lys-Lys,His-Leu-Lys-Lys,Lys-Lys-Lys-Lys又はH is-Leu-Lys-Serである請求の範囲第27項記載の類似体。 30.Y=Xである請求の範囲第27項記載の類似体。 31.Y=Val-Xである請求の範囲第27項記載の類似体。 32.Y=Val-Leu-Asn-Phe-Xである請求の範囲第27項記載の類似体。 33.配列番号6を有する請求の範囲第19項記載の類似体。 34.配列番号7を有する請求の範囲第19項記載の類似体。 35.配列番号8を有する請求の範囲第19項記載の類似体。 36.配列番号9を有する請求の範囲第19項記載の類似体。 37.配列番号10を有する請求の範囲第19項記載の類似体。 38.配列番号11を有する請求の範囲第19項記載の類似体。 39.配列番号12を有する請求の範囲第19項記載の類似体。 40.配列番号13を有する請求の範囲第19項記載の類似体。 41.配列番号14を有する請求の範囲第19項記載の類似体。 42.配列番号15を有する請求の範囲第19項記載の類似体。 43.配列番号16を有する請求の範囲第19項記載の類似体。 44.配列番号17を有する請求の範囲第19項記載の類似体。 45.配列番号18を有する請求の範囲第19項記載の類似体。 46.配列番号19を有する請求の範囲第19項記載の類似体。 47.骨形成のためのペプチド構造体をスクリーニングするための方法であって 、 (a)試験動物に麻酔をし、 (b)医薬的に許容できる溶媒に溶解された、候補体ペプチド又は医薬的に許 容できるその塩の有効用量を、前記試験動物に皮下注射し、 (c)前記動物の動脈圧を測定し、それにより、短時間の後の小さな血圧降下 が前記ペプチドの骨形成の表示である方法。 48.前記溶媒が酸性化された塩溶液である請求の範囲第47項記載の方法。 49.前記溶媒が0.0001NのHClを含む請求の範囲第48項記載の方法。 50.前記試験動物がラットであり、そして前記血圧降下が注射の2〜19分後で 、8.5〜36.2%である請求の範囲第49項記載の方法。 51.前記ペプチドが請求の範囲第19項記載のhPTHフラグメントである請求の範 囲第50項記載の方法。 52.前記hPTHの用量が約0.8nモル/110g体重である請求の範囲第51項記載の 方法。 53.前記hPTHが配列番号3のものである請求の範囲第52項記載の方法。 54.前記hPTHが配列番号4のものである請求の範囲第52項記載の方法。
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US08/691,647 | 1996-08-02 | ||
US08/691,647 US5955425A (en) | 1996-08-02 | 1996-08-02 | Parathyroid hormone analogues for the treatment of osteoporosis |
US4056097P | 1997-03-14 | 1997-03-14 | |
US60/040,560 | 1997-03-14 | ||
PCT/CA1997/000547 WO1998005683A1 (en) | 1996-08-02 | 1997-08-01 | Parathyroid hormone analogues for the treatment of osteoporosis |
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JP2007121289A Expired - Fee Related JP4224111B2 (ja) | 1996-08-02 | 2007-05-01 | 骨粗鬆症の治療のための副甲状腺ホルモン類似体 |
JP2008246839A Pending JP2009057386A (ja) | 1996-08-02 | 2008-09-25 | 骨粗鬆症の治療のための副甲状腺ホルモン類似体 |
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JP2008246839A Pending JP2009057386A (ja) | 1996-08-02 | 2008-09-25 | 骨粗鬆症の治療のための副甲状腺ホルモン類似体 |
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JP2010501476A (ja) * | 2006-07-31 | 2010-01-21 | ゼロス セラピューティクス, インコーポレイテッド | 副甲状腺ホルモン類似体およびその使用方法 |
JP2011032282A (ja) * | 2003-01-21 | 2011-02-17 | Unigene Lab Inc | 改善された経口ペプチド送達 |
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EP1141237B1 (en) | 1998-12-31 | 2005-11-02 | The General Hospital Corporation | Pth receptor and screening assay utilizing the same |
EP1221963A4 (en) * | 1999-07-28 | 2006-03-22 | Univ Pennsylvania | METHODS OF INHIBITING OSTEOCLASTOGENESIS |
US6316410B1 (en) * | 1999-09-22 | 2001-11-13 | National Research Council Of Canada | Parathyroid hormone analogues for the treatment of osteoporosis |
US7572765B2 (en) | 2001-07-23 | 2009-08-11 | The General Hospital Corporation | Conformationally constrained parathyroid hormone (PTH) analogs |
WO2003059291A2 (en) | 2002-01-10 | 2003-07-24 | Osteotrophin Llc | Treatment of bone disorders with skeletal anabolic drugs |
EP1567178A4 (en) * | 2002-11-01 | 2009-07-15 | Amgen Inc | MODULATORS OF RECEPTORS FOR NEUTRAL THERAPY HORMONE AND SIDE-HORSE HORMONE-RELATED PROTEINS |
EA014696B1 (ru) | 2006-10-13 | 2010-12-30 | Эли Лилли Энд Компани | Пэгилированный паратиреоидный гормон в качестве модулятора рецептора паратиреоидного гормона и его применение |
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Cited By (3)
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JP2011032282A (ja) * | 2003-01-21 | 2011-02-17 | Unigene Lab Inc | 改善された経口ペプチド送達 |
JP2009508820A (ja) * | 2005-09-06 | 2009-03-05 | ゼロス セラピューティクス, インコーポレイテッド | 副甲状腺ホルモンアナログおよび使用法 |
JP2010501476A (ja) * | 2006-07-31 | 2010-01-21 | ゼロス セラピューティクス, インコーポレイテッド | 副甲状腺ホルモン類似体およびその使用方法 |
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