JP2000502336A - 形態形成タンパク質および刺激因子を使用する組成物および治療方法 - Google Patents
形態形成タンパク質および刺激因子を使用する組成物および治療方法Info
- Publication number
- JP2000502336A JP2000502336A JP9522228A JP52222897A JP2000502336A JP 2000502336 A JP2000502336 A JP 2000502336A JP 9522228 A JP9522228 A JP 9522228A JP 52222897 A JP52222897 A JP 52222897A JP 2000502336 A JP2000502336 A JP 2000502336A
- Authority
- JP
- Japan
- Prior art keywords
- bmp
- protein
- bone
- morphogenic protein
- morphogenic
- 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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- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.哺乳動物における組織形成を誘導するための組成物であって、以下を含み: a)該哺乳動物において始原細胞に接近し得る場合に組織形成を誘導し得る、 形態形成タンパク質; b)該始原細胞からの組織形成を誘導する該形態形成タンパク質の能力を刺す 激し得る、形態形成タンパク質刺激因子;および c)薬学的に受容可能なキャリア; ここで、該形態形成タンパク質刺激因子は、ホルモン、サイトカイン、ペプチ ド、および増殖因子からなる群から選択され、そして以下の仮定; 該始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成 タンパク質がBMPホモダイマー、TGF-β、またはアクチビンである場合、該MPSF はエストロゲンまたはカルシトニンでなくてもよく; 該始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成 タンパク質がBMPホモダイマーまたはTGF-βである場合、該MPSFはFGF、IGF-IIPD GF、またはビタミンDでなくてもよく;そして 該始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成 タンパク質がBMP-2またはBMP-3のホモダイマーである場合、該MPSFは副甲状腺ホ ルモンでなくてもよい; が成立する、組成物。 2.前記形態形成タンパク質が、ダイマー種を産生するためにジスルフィド結合 した1対のサブユニットを含み、かつ少なくとも該サブユニットの1つが、BMP タンパク質ファミリーに属するポリペプチドを含む、請求項1に記載の組成物。 3.前記形態形成タンパク質が骨形成タンパク質である、請求項1に記載の組成 物。 4.前記骨形成タンパク質が、軟骨性骨または膜内骨を形成するように始原細胞 を誘導し得る、請求項3に記載の組成物。 5.前記形態形成タンパク質が、軟骨、腱/靭帯様組織または神経様組織を形成 するように始原細胞を誘導し得る、請求項1〜3のいずれかに記載の組成物。 6.前記形態形成タンパク質が、BMP-2、BMP-4、BMP-5、BMP-6、BMP-7(OP-1)、B MP-8、BMP-9、BMP-10.BMP-11,BMP-12、およびBMP-13、COP-5、COP-7からなる 群から選択されるポリペプチドを含む、請求項1〜3のいずれかに記載の組成物 。 7.前記形態形成タンパク質が、OP-1、BMP-2、BMP-4、およびBMP-6からなる群か ら選択されるポリペプチドを含む、請求項1〜3のいずれかに記載の組成物。 8.前記形態形成タンパク質が、OP-1、BMP-5、およびBMP-6からなる群から選択 されるポリペプチドを含む、請求項1〜3のいずれかに記載の組成物。 9.前記形態形成タンパク質がOP-1を含む、請求項1〜3のいずれかに記載の組 成物。 10.前記ダイマーが、少なくとも1つのBMP-2またはOP-1(BMP-7)サブユニッ トを含むホモダイマーまたはヘテロダイマーである、請求項2に記載の組成物。 11.前記形態形成タンパク質が、宿主細胞中の組換えDNA分子の発現により産 生される、請求項1〜3のいずれかに記載の組成物。 12.前記形態形成タンパク質刺激因子が、インスリン様増殖因子I(IGF-I)、 エストラジオール、線維芽細胞増殖因子(FGF)、成長ホルモン(GH)、成長お よび分化因子(GDF)、ヒドロコルチゾン(HC)、インスリン、プロゲステロン 、副甲状腺ホルモン(PTH)、ビタミンD、レチノイン酸、およびIL-6からなる群 から選択される少なくとも1つの化合物を含む、請求項1〜3のいずれかに記載 の 組成物。 13.前記形態形成タンパク質刺激因子が、哺乳動物においてIGF-I生物活性を 増加させる因子を含む、請求項1〜3のいずれかに記載の組成物。 14.前記哺乳動物においてIGF-I生物活性を増加させる因子が、IGF-Iの改変さ れた形態である、請求項13に記載の組成物。 15.前記IGF-Iの改変された形態が、通常のIGF-Iに比べて哺乳動物においてIG FBPに対する減少した親和性を有する短縮型IGF-I分子である、請求項14に記載 の組成物。 16.前記IGF-Iの改変された形態がdes(1-3)IGF-Iである、請求項15に記載 の組成物。 17.前記形態形成タンパク質刺激因子が、哺乳動物において組織形成を誘導す る前記形態形成タンパク質の能力を相乗的に刺激し得る量で存在する、請求項1 〜3のいずれかに記載の組成物。 18.前記形態形成タンパク質が、少なくとも約1ng/mlの濃度で存在し、かつ 前記形態形成タンパク質刺激因予が、少なくとも約0.01ng/mlの濃度で存在する 、請求項1〜3のいずれかに記載の組成物。 19.前記形態形成タンパク質が、OP-1を約1ng/ml〜約500ng/mlの濃度で含み 、かつ前記形態形成タンパク質刺激因子が、IGF-Iまたはdes(1-3)IGF-Iを約0. 1ng/ml〜約50ng/mlの濃度で含む、請求項1〜3のいずれかに記載の組成物。 20.前記形態形成タンパク質が、OP-1を約1ng/ml〜約500ng/mlの濃度で含み 、かつ前記形態形成タンパク質刺激因子が、エストラジオールを約0.05nM〜約10 00 nMの濃度で含む、請求項1〜3のいずれかに記載の組成物。 21.前記形態形成タンパク質が、OP-1を約1ng/ml〜約500ng/mlの濃度で含み 、かつ前記形態形成タンパク質刺激因子が、成長ホルモンを約5ng/ml〜約1000n g/mlの濃度で含む、請求項1〜3のいずれかに記載の組成物。 22.前記形態形成タンパク質が、OP-1を約1ng/ml〜約500ng/mlの濃度で含み 、かつ前記形態形成タンパク質刺激因子が、ヒドロコルチゾンを約0.05nM〜約5. 0nMの濃度で含む、請求項1〜3のいずれかに記載の組成物。 23.前記形態形成タンパク質が、OP-1を約1ng/ml〜約500ng/mlの濃度で含み 、かつ前記形態形成タンパク質刺激因子が、インスリンを約0.01nM〜約1000nMの 濃度で含む、請求項1〜3のいずれかに記載の組成物。 24.前記形態形成タンパク質が、OP-1を約1ng/ml〜約500ng/mlの濃度で含み 、かつ前記形態形成タンパク質刺激因子が、副甲状腺ホルモンを約10nM〜約1000 nMの濃度で含む、請求項1〜3のいずれかに記載の組成物。 25.前記形態形成タンパク質が、OP-1を約1ng/ml〜約500ng/mlの濃度で含み 、かつ前記形態形成タンパク質刺激因子が、プロゲステロンを約0.05nM〜約1000 nMの濃度で含む、請求項1〜3のいずれかに記載の組成物。 26.組織形成を誘導するのに有用な薬剤の製造のための、請求項1〜25のい ずれかに記載の組成物の、使用。 27.哺乳動物における組織変性状態を処置するための、請求項1〜25のいず れかに記載の組成物の、使用。 28.哺乳動物における移植のための形態形成デバイスであって、該デバイスが 以下を含み: a)移植可能な生体適合性キャリア; b)該キャリア中に配置された形態形成タンパク質、該形態形成タンパク質は 始原細胞に接近し得る場合に組織形成を誘導し得る;および c)該キャリア中に配置された形態形成タンパク質刺激因子、該刺激因子は該 始原細胞から組織形成を誘導する該形態形成タンパク質の能力を刺激し得る; ここで該形態形成タンパク質刺激因子は、ホルモン、サイトカイン、ペプチド 、および増殖因子からなる群から選択され、そして以下の仮定; 該始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成 タンパク質がBMPホモダイマー、TGB-β、またはアクチビンである場合、該MPSF はエストロゲンまたはカルシトニンでなくてもよく; 該始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成 タンパク質がBMPホモダイマーまたはTGB-βである場合、該MPSFはFGF、IGF-II、 PDGF、またはビタミンDでなくてもよく;そして 該始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成 タンパク質がBMP-2またはBMP-3のホモダイマーである場合、該MPSFは副甲状腺ホ ルモンでなくてもよい; が成立する、形態形成デバイス。 29.前記形態形成タンパク質が、ダイマー種を産生するためにジスルフィド結 合した1対のサブユニットを含み、かつ少なくとも該サブユニットの1つが、BM Pタンパク質ファミリーに属するポリペプチドを含む、請求項28に記載の形態 形成デバイス。 30.前記形態形成タンパク質が骨形成タンパク質である、請求項29に記載の 形態形成デバイス。 31.前記キャリアが生体適合性マトリックスをさらに含む、請求項28〜30 のいずれかに記載のデバイス。 32.前記マトリックスが、脱塩され、タンパク質抽出された粒子状の同種骨を 含む、請求項31に記載のデバイス。 33.前記マトリックスが、非コラーゲン性タンパク質中で実質的に枯渇した、 脱塩され、脱脂されたI型不溶性骨コラーゲン粒子を含む、請求項31に記載の デバイス。 34.前記骨形成タンパク質が、軟骨性骨または膜内骨を形成するように始原細 胞を誘導し得る、請求項30に記載のデバイス。 35.前記形態形成タンパク質が、軟骨、腱/靭帯様組織または神経様組織を形 成するように始原細胞を誘導し得る、請求項28〜30のいずれかに記載のデバ イス。 36.前記形態形成タンパク質が、BMP-2、BMP-4、BMP-5、BMP-6、BMP-7(OP-1 )、BMP-8、BMP-9、BMP-10、BMP-11、BMP-12、およびBMP-13、COP-5、およびCOP -7からなる群から選択されるポリペプチドを含む、請求項28〜30のいずれか に記載のデバイス。 37.前記形態形成タンパク質が、OP-1、BMP-2、BMP-4、およびBMP-6からなる 群から選択されるポリペプチドを含む、請求項28〜30のいずれかに記載のデ バイス。 38.前記形態形成タンパク質が、OP-1、BMP-5、およびBMP-6からなる群から選 択されるポリペプチドを含む、請求項28〜30のいずれかに記載のデバイス。 39.前記形態形成タンパク質がOP-1を含む、請求項28〜30のいずれかに記 載のデバイス。 40.前記ダイマーが、少なくとも1つのBMP-2またはOP-1サブユニットを含む ホモダイマーまたはヘテロダイマーである、請求項29に記載のデバイス。 41.前記形態形成タンパク質が、宿主細胞中の組換えDNA分子の発現により産 生される、請求項28〜30のいずれかに記載のデバイス。 42.前記形態形成タンパク質が、COP-5またはCOP-7のアミノ配列に十分重複す るアミノ酸配列を含んでいる少なくとも1つのサブユニットを含み、それによっ て前記種が、キャリア中に配置されかつ哺乳動物中に移植された場合に該哺乳動 物における組織形成を誘導し得る、請求項41に記載のデバイス。 43.前記形態形成タンパク質刺激因子が、インスリン様増殖因子I(IGF-I)、 エストラジオール、線維芽細胞増殖因子(FGF)、成長ホルモン(GH)、成長お よび分化因子(GDF)、ヒドロコルチゾン(HC)、インスリン、プロゲステロン 、副甲状腺ホルモン(PTH)、ビタミンD、レチノイン酸、およびIL-6からなる群 から選択される少なくとも1つの化合物を含む、請求項28〜30のいずれかに 記載のデバイス。 44.前記形態形成タンパク質が、少なくとも約1ng/mlの濃度で存在し、かつ 前記形態形成タンパク質刺激因子が、少なくとも約0.01ng/mlの濃度で存在する 、請求項28〜30のいずれかに記載のデバイス。 45.請求項13〜17または19〜25のいずれかに記載の組成物を含む、請 求項28〜30のいずれかに記載のデバイス。 46.選択された位置において組織形成を誘導するための、請求項28〜45の いずれかに記載の形態形成デバイスの、使用。 47.前記位置が下顎骨である、請求項46に記載の使用。 48.前記位置が、骨折、偽関節骨折、融合、および骨の空隙からなる群から選 択される骨欠損である、請求項46に記載の使用。 49.前記位置が、軟骨および軟組織の修復における使用のための関節である、 請求項46に記載の使用。 50.前記位置が、神経の再生および修復における使用のための神経系付随組織 である、請求項46に記載の使用。 51.哺乳動物における同種移植片の修復および取り込みを加速するための、請 求項31〜33のいずれかに記載のマトリックス含有デバイスの、使用。 52.前記デバイスのマトリックスが同種の骨を含む、請求項31または33に 記載のマトリックス含有デバイスの、使用。 53.哺乳動物における整形外科的欠損、損傷、または奇形(anamoly)の修復の ための移植可能な補綴デバイスであって、以下を含み: a)該哺乳動物における標的組織に隣接して移植可能な表面領域を有する、補 綴インプラント;および b)該表面への増大した組織増殖を促進するのに十分な量で、該表面領域上に 配置された形態形成タンパク質および形態形成タンパク質刺激因子を含む、組成 物; ここで該形態形成タンパク質刺激因子は、ホルモン、サイトカイン、ペプチド 、および増殖因子からなる群から選択され、そして以下の仮定; 始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成タ ンパク質がBMPホモダイマー、TGB-β、またはアクチビンである場合、該MPSFは エストロゲンまたはカルシトニンでなくてもよく; 該始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成 タンパク質がBMPホモダイマーまたはTGB-βである場合、該MPSFはFGF、IGF-II、 PDGF、またはビタミンDでなくてもよく;そして 該始原細胞が骨を形成するように刺激された骨芽細胞であり、かつ該形態形成 タンパク質がBMP-2またはBMP-3のホモダイマーである場合、該MPSFは副甲状腺ホ ルモンでなくてもよい; が成立する、補綴デバイス。 54.前記骨形成タンパク質が、軟骨性骨、膜内骨、軟骨、腱/靭帯様組織、お よび神経組織からなる群から選択される組織を形成するように始原細胞を誘導し 得る、請求項53に記載の補綴デバイス。 55.前記骨形成タンパク質が、BMP-2、BMP-4、BMP-5、BMP-6、OP-1(OP-1)、 BMP-8、BMP-9、BMP-10、BMP-11,BMP-12、およびBMP-13、COP-5、およびCOP-7か らなる群から選択されるポリペプチドを含む、請求項53に記載の補綴デバイス 。 56.前記骨形成タンパク質が、OP-1,BMP-2、BMP-4、およびBMP-6からなる群 から選択されるポリペプチドを含む、ジスルフィド結合したダイマー種を含む、 請求項53に記載の補綴デバイス。 57.前記骨形成タンパク質が、OP-1,BMP-5、およびBMP-6からなる群から選択 されるポリペプチドを含む、ジスルフィド結合したダイマー種を含む、請求項5 3に記載の補綴デバイス。 58.前記骨形成タンパク質がOP-1を含む、請求項53に記載の補綴デバイス。 59.前記骨形成タンパク質が、宿主細胞中の組換えDNA分子の発現により産生 される、請求項53に記載の補綴デバイス。 60.前記形態形成タンパク質刺激因子が、インスリン様増殖因子I(IGF-I)、 エストラジオール、線維芽細胞増殖因子(FGF)、成長ホルモン(GH)、成長お よび分化因子(GDF)、ヒドロコルチゾン(HC)、インスリン、プロゲステロン 、副甲状腺ホルモン(PTH)、ビタミンD、レチノイン酸、およびIL-6からなる群 から選択される少なくとも1つの化合物を含む、請求項53に記載の補綴デバイ ス。 61.前記形態形成タンパク質刺激因子が、哺乳動物においてIGF-I生物活性を 増加させる因子を含む、請求項53に記載の補綴デバイス。 62.前記形態形成タンパク質刺激因子が、哺乳動物において組織形成を誘導す る前記形態形成タンパク質の能力を相乗的に刺激し得る量で存在する、請求項5 3に記載の補綴デバイス。 63.組織修復のための、請求項53〜62のいずれかに記載の移植可能な補綴 デバイスの、使用。
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WO (1) | WO1997021447A1 (ja) |
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CA2238277A1 (en) | 1997-06-19 |
EP0871471B1 (en) | 2004-06-23 |
WO1997021447A1 (en) | 1997-06-19 |
ATE269713T1 (de) | 2004-07-15 |
JP4121558B2 (ja) | 2008-07-23 |
US5916870A (en) | 1999-06-29 |
AU719120B2 (en) | 2000-05-04 |
AU1333297A (en) | 1997-07-03 |
DE69632790T2 (de) | 2005-07-14 |
EP0871471A1 (en) | 1998-10-21 |
US6048964A (en) | 2000-04-11 |
CA2238277C (en) | 2006-10-10 |
DE69632790D1 (de) | 2004-07-29 |
US5948428A (en) | 1999-09-07 |
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