JP4384597B2 - キメラコイルドコイル分子 - Google Patents
キメラコイルドコイル分子 Download PDFInfo
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- JP4384597B2 JP4384597B2 JP2004513331A JP2004513331A JP4384597B2 JP 4384597 B2 JP4384597 B2 JP 4384597B2 JP 2004513331 A JP2004513331 A JP 2004513331A JP 2004513331 A JP2004513331 A JP 2004513331A JP 4384597 B2 JP4384597 B2 JP 4384597B2
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Description
Claims (18)
- Tie2受容体の結合ドメインであるアンジオポエチン−1のフィブリノーゲン様ドメインに連結されたGCN4、軟骨基質タンパク質または軟骨オリゴマー基質タンパク質のコイルドコイルドメインを含むコイルドコイルキメラ分子であって、該キメラ分子は生物学的に活性な多量体を形成し、該キメラ分子はその非多量体形態では生物学的に不活性である、コイルドコイルキメラ分子。
- 前記コイルドコイルドメインが受容体の細胞外ドメインに連結されている、請求項1に記載のコイルドコイルキメラ分子。
- 請求項1に記載のコイルドコイルキメラ分子をコードする単離された核酸。
- 請求項3に記載の核酸を含む発現ベクター。
- 請求項4に記載のベクターを含む宿主細胞。
- 請求項1に記載のコイルドコイルキメラ分子を含む、可溶性の生物学的に活性な多量体。
- ホモマーである、請求項6に記載の多量体。
- ヘテロマーである、請求項6に記載の多量体。
- 二量体、三量体、四量体、五量体、六量体、七量体、八量体、九量体、または十量体である、請求項6に記載の多量体。
- 前記コイルドコイルドメインが平行または逆平行構造を形成する、請求項6に記載の多量体。
- 請求項1に記載のコイルドコイルキメラ分子を、リガンドに特異的な受容体を発現する細胞の集団に接触させることを含む細胞成長を促進する方法であって、該リガンドが該受容体のアゴニストであり、該コイルドコイルキメラ分子の多量体形態が受容体と相互作用し、その結果細胞成長が促進される方法。
- 請求項1に記載のコイルドコイルキメラ分子を、リガンドに特異的な受容体を発現する細胞の集団に接触させることを含む細胞増殖を促進する方法であって、該リガンドが該受容体のアゴニストであり、該コイルドコイルキメラ分子の多量体形態が受容体と相互作用し、その結果細胞増殖が促進される方法。
- 前記細胞が内皮細胞、造血細胞、またはそれぞれの特異的受容体を発現する他の細胞である、請求項11又は請求項12に記載の方法。
- 請求項1に記載のコイルドコイルキメラ分子を、受容体に特異的なリガンドを発現する細胞の集団に接触させることを含む細胞増殖を減少させるまたは阻害する方法であって、該コイルドコイルキメラ分子の多量体形態がリガンドと相互作用し、その結果細胞増殖が減少または阻害される方法。
- 前記細胞が内皮細胞、造血細胞、またはそれぞれの特異的受容体を発現する他の細胞である、請求項14に記載の方法。
- 請求項1に記載のコイルドコイルキメラ分子を、受容体に特異的なリガンドを含む試料に接触させることを含むリガンド活性を低下させるまたは阻害する方法であって、該コイルドコイルキメラ分子の多量体形態がリガンドに結合し、その結果リガンド活性が低下または阻害される方法。
- (A)コイルドコイルドメインをコードする核酸を、リガンドの受容体結合領域または受容体のリガンド結合領域のいずれかをコードする核酸と組み換えにより連結して、キメラ遺伝子構築物を作製する段階;および(B)該遺伝子構築物を宿主細胞中で発現させてキメラ分子を生産させる段階を含む、請求項1に記載のキメラ分子の作成方法。
- Tie2受容体の結合ドメインであるアンジオポエチン−1のフィブリノーゲン様ドメインに連結されたGCN4、軟骨基質タンパク質または軟骨オリゴマー基質タンパク質のコイルドコイルドメインを含むコイルドコイルキメラ分子を含む放射線に曝された哺乳動物の内皮細胞を放射線障害から防護するための治療用組成物。
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US10/273,180 US7081443B2 (en) | 2002-05-21 | 2002-10-18 | Chimeric comp-ang1 molecule |
PCT/IB2003/003814 WO2003106501A1 (en) | 2002-05-21 | 2003-05-21 | Fusion protein comprising angiopoietin receptor-binding and a multimerization domain |
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EP (1) | EP1549679B1 (ja) |
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KR (1) | KR100611620B1 (ja) |
AT (1) | ATE437893T1 (ja) |
AU (1) | AU2003256001A1 (ja) |
CA (1) | CA2486649C (ja) |
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EP1549679A4 (en) | 2006-06-21 |
US7309586B2 (en) | 2007-12-18 |
JP2006504405A (ja) | 2006-02-09 |
KR20050004198A (ko) | 2005-01-12 |
CA2486649A1 (en) | 2003-12-24 |
US7691366B2 (en) | 2010-04-06 |
US20060074230A1 (en) | 2006-04-06 |
US7081443B2 (en) | 2006-07-25 |
US20030220476A1 (en) | 2003-11-27 |
EP1549679A1 (en) | 2005-07-06 |
WO2003106501A1 (en) | 2003-12-24 |
US20080160574A1 (en) | 2008-07-03 |
EP1549679B1 (en) | 2009-07-29 |
DE60328615D1 (de) | 2009-09-10 |
KR100611620B1 (ko) | 2006-09-01 |
CA2486649C (en) | 2014-08-05 |
ATE437893T1 (de) | 2009-08-15 |
DK1549679T3 (da) | 2009-10-26 |
AU2003256001A1 (en) | 2003-12-31 |
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