JP2002512695A - 酸化およびmda修飾の低密度リポタンパク質を検出するためのアッセイ、抗体および標準物 - Google Patents
酸化およびmda修飾の低密度リポタンパク質を検出するためのアッセイ、抗体および標準物Info
- Publication number
- JP2002512695A JP2002512695A JP50362399A JP50362399A JP2002512695A JP 2002512695 A JP2002512695 A JP 2002512695A JP 50362399 A JP50362399 A JP 50362399A JP 50362399 A JP50362399 A JP 50362399A JP 2002512695 A JP2002512695 A JP 2002512695A
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- Prior art keywords
- antibody
- ldl
- assay
- mda
- oxldl
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.サンプル中のMDA修飾LDLおよびOxLDLの検出および/または定量 するための免疫アッセイであって、 a)MDA修飾LDLおよびOxLDLに高親和性を有する第1抗体とサンプ ルとを接触せしめ、 b)次いで、第1抗体とサンプル中に存在するMDA修飾LDLおよびOxL DLとの結合反応を視覚化および/または定量する、 (なお、第1抗体が高い親和性を有するMDA修飾LDLおよびOxLDLは 、apoB−100部分につき少なくとも60の置換リシン部分を含有する) ことを含むアッセイ。 2.第1抗体が高親和性を有するMDA修飾LDLおよびOxLDLが、apo B−100部分に対して少なくとも約90の置換リシン部分を含有する、請求項 1のアッセイ。 3.第1抗体が高親和性を有するMDA修飾LDLおよびOxLDLが、apo B−100部分に対して少なくとも約120の置換リシン部分を含有する、請求 項1のアッセイ。 4.第1抗体が高親和性を有するMDA修飾LDLおよびOxLDLが、apo B−100部分に対して少なくとも約210の置換リシン部分を含有する、請求 項1のアッセイ。 5.第1抗体が高親和性を有するMDA修飾LDLおよびOxLDLが、apo B−100部分に対して少なくとも約240の置換リシン部分を含有する、請求 項1のアッセイ。 6.競合アッセイである、請求項1から5のいずれかのアッセイ。 7.MDA修飾LDLおよび/またはOxLDLが基質に結合しており、サンプ ルおよび第1抗体と、MDA修飾LDLおよびOxLDLに結合している基質と を接触せしめることを含む、請求項6の競合アッセイ。 8.第1抗体が基質に結合し、第1抗体に結合している基質とサンプルとを接触 せしめることを含むサンドウィッチアッセイである、請求項1から5のいずれか のアッセイ。 9.第2抗体を使用し、第2抗体がヒトMDA修飾LDLおよびヒトOxLDL に高親和性を有する、請求項8のアッセイ。 10.第2抗体が天然LDLに高親和性を有する、請求項9のアッセイ。 11.サンプルが組織サンプルであり、それを第1抗体に接触せしめる免疫組織 化学的アッセイである、請求項1から5のいずれかのアッセイ。 12.MDA修飾LDLおよびOxLDLに対する第1抗体の親和性定数が少な くとも約1×1010M-1である、請求項1から11のいずれかのアッセイ。 13.第1抗体が天然LDLに低親和性を有する、請求項1から12のいずれか のアッセイ。 14.天然LDLに対する第1抗体の親和性定数が約1×106M-1以下である 、請求項13のアッセイ。 15.第1抗体が、1997年4月24日またはその頃にBCCMに寄託番号L MBP1660CBで寄託されたハイブリドーマHyb4E6により生産された モノクローナル抗体mAb−4E6である、請求項1から14のいずれかのアッ セイ。 16.MDA修飾LDLおよびOxLDLに対する第2抗体の親和性定数が少な くとも約1×1010M-1である、請求項8から10のいずれかのアッセイ。 17.天然LDLに対する第2抗体の親和性定数が少なくとも約1×109M-1 である、請求項16のアッセイ。 18.第2抗体が、1997年4月24日またはその頃にBCCMに寄託番号L MBP1661CBで寄託されたハイブリドーマHyb8A2により生産された モノクローナル抗体mAb−8A2である、請求項17のアッセイ。 19.サンプルがヒトの体液または組織に由来する、請求項1から18のいずれ かのアッセイ。 20.サンプル中のMDA修飾LDLの検出および/または定量のための免疫サ ンドウィッチアッセイであって、このアッセイにおいてMDA修飾LDLに高親 和性を有する第1抗体が基質に結合し、 (a)サンプル中のMDA修飾LDLの少なくともいくらかが第1抗体に結合 するような結合条件において、第1抗体に結合している基質とサンプルとを接触 せしめ、 (b)次いで基質から非結合のサンプルを除去し、 (c)次いでMDA修飾LDLに高親和性を有する第2抗体と基質とを接触せ しめ、 (d)次いでサンプル中に存在したMDA修飾LDLを視覚化および/または 定量する、 (なお、第1抗体および第2抗体が高親和性を有するMDA修飾LDLは、a poB−100部分につき少なくとも60の置換リシン部分を含有する) ことを含むアッセイ。 21.第1抗体および第2抗体が高親和性を有するMDA修飾LDLが、apo B−100部分に対して少なくとも約90の置換リシン部分を含有する、請求項 20のアッセイ。 22.第1抗体および第2抗体が高親和性を有するMDA修飾LDLが、apo B−100部分に対して少なくとも約120の置換リシン部分を含有する、請求 項20のアッセイ。 23.第1抗体および第2抗体が高親和性を有するMDA修飾LDLが、apo B−100部分に対して少なくとも約210の置換リシン部分を含有する、請求 項20のアッセイ。 24.第1抗体および第2抗体が高親和性を有するMDA修飾LDLが、apo B−100部分に対して少なくとも約240の置換リシン部分を含有する、請求 項20のアッセイ。 25.第1抗体がOxLDLにも高親和性を有する、請求項20から24のいず れかのアッセイ。 26.第1抗体が天然LDLに低親和性を有する、請求項20から25のいずれ かのアッセイ。 27.第1抗体がOxLDLに低親和性を有する、請求項20から24および2 6のいずれかのアッセイ。 28.第2抗体が天然LDLに高親和性を有する、請求項20から27のいずれ かのアッセイ。 29.MDA修飾LDLに対する第1抗体の親和性定数が少なくとも約1×1010 M-1である、請求項20から28のいずれかのアッセイ。 30.天然LDLに対する第1抗体の親和性定数が約1×106M-1以下である 、請求項20から29のいずれかのアッセイ。 31.天然LDLに対する第2抗体の親和性定数が少なくとも約1×109M-1 である、請求項20から30のアッセイ。 32.第1抗体が、1997年4月24日またはその頃にBCCMに寄託番号L MBP1660CBで寄託されたハイブリドーマHyb4E6により生産された モノクローナル抗体mAb−4E6である、請求項20から26および28から 31のいずれかのアッセイ。 33.第1抗体が、1997年4月24日またはその頃にBCCMに寄託番号L MBP1659CBで寄託されたハイブリドーマHyb1H11により生産され たモノクローナル抗体mAb−1H11である、請求項20から24および26 から31のいずれかのアッセイ。 34.第2抗体が、1997年4月24日またはその頃にBCCMに寄託番号L MBP1661CBで寄託されたハイブリドーマHyb8A2により生産された モノクローナル抗体mAb−8A2である、請求項20から33のいずれかのア ッセイ。 35.1997年4月24日またはその頃にBCCMに寄託番号LMBP166 0CBで寄託されたハイブリドーマHyb4E6により生産されたモノクローナ ル抗体mAb−4E6。 36.1997年4月24日またはその頃にBCCMに寄託番号LMBP166 0CBで寄託されたハイブリドーマHyb4E6。 37.1997年4月24日またはその頃にBCCMに寄託番号LMBP166 1CBで寄託されたハイブリドーマHyb8A2により生産されたモノクローナ ル抗体mAb−8A2。 38.1997年4月24日またはその頃にBCCMに寄託番号LMBP166 1CBで寄託されたハイブリドーマHyb8A2。 39. LDLリシン部分の置換程度が生物的材料について普通の貯蔵中に正常 な期間を通じて基本的に一定に止まるMDA修飾LDLを含有する安定な標準物 であって、この標準物のMDA修飾LDLが、マロンジアルデヒドをLDLに、 LDLのapoB−100部分に対するマロンジアルデヒドのあらかじめ測定し た分子比で、接触(インキュベート)せしめてつくられ、LDLの酸化を触媒す る存在金属イオンの能力を低下せしめる薬剤および/または抗酸化剤を含有する 標準物。 40.LDLの酸化を触媒する存在金属イオンの能力を低下せしめる薬剤と抗酸 化剤の両者が存在する、請求項39の標準物。 41.LDLの酸化を触媒する存在金属イオンの能力を低下せしめる薬剤がキレ ート剤である、請求項39および40のいずれかの標準物。 42.キレート剤がEDTAである請求項41の標準物。 43.抗酸化剤が、BHTおよびビタミンEよりなる群から選ばれる請求項39 から42のいずれかの標準物。 44.生理体液をさらに含む、請求項39および43のいずれかの標準物。 45.生理体液が血漿である、請求項44の標準物。 46.少なくとも1つの抗血小板剤および/または凝固阻害剤をさらに含む、請 求項39および45の標準物。 47.請求項39から46のいずれかの標準物を含むMDA修飾LDLのための アッセイ用の安定な検定剤。 48.請求項39から46のいずれかの標準物を含むMDA修飾LDLのための アッセイ用の安定な対照物。 49.請求項39から46のいずれかの標準物を含むOxLDLのためのアッセ イ用の安定な検定剤。 50.請求項39から46のいずれかの標準物を含むOxLDLのためのアッセ イ用の安定な対照物。 51.サンプル中のOxLDLまたはMDA修飾LDLおよび両者を測定するた めのサンドウィッチアッセイ実施用のキットであって、 (a)OxLDLまたはMDA修飾LDLまたは両方に高親和性を有する第1 抗体が結合する基質(OxLDLおよびMDA修飾LDLはapoB−100部 分当り少なくとも60置換リシン部分を夫々有する)、 (b)アッセイ中に第1抗体に結合するOxLDLに、アッセイ中に第1抗体 に結合するMDA修飾LDLに、またはアッセイ中に第1抗体に結合する両者に 、高親和性を有する標識抗体、 を含むキット。 52.標識抗体との反応のための反応物質をさらに含み、標識抗体の存在を表示 する、請求項51のキット。 53.反応物質が酵素を含む、請求項51のキット。 54.請求項47または49のいずれかの安定な検定物をさらに含む、請求項5 1から53のいずれかのキット。 55.請求項48または50のいずれかの安定な検定物をさらに含む、請求項5 1から54のいずれかのキット。
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PCT/EP1997/003493 WO1998059248A1 (en) | 1997-06-20 | 1997-07-01 | Assays, antibodies, and standards for detection of oxidized and mda-modified low density lipoproteins |
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CA (1) | CA2294355C (ja) |
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Cited By (2)
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JP2003529775A (ja) * | 2000-03-31 | 2003-10-07 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 高密度リポタンパク質の機能アッセイ |
JP2007322187A (ja) * | 2006-05-31 | 2007-12-13 | Dai Ichi Pure Chem Co Ltd | 再狭窄の発症リスクを判定する方法 |
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US6727102B1 (en) | 1997-06-20 | 2004-04-27 | Leuven Research & Development Vzw | Assays, antibodies, and standards for detection of oxidized and MDA-modified low density lipoproteins |
US6309888B1 (en) * | 1998-09-04 | 2001-10-30 | Leuven Research & Development Vzw | Detection and determination of the stages of coronary artery disease |
US6596544B1 (en) | 2000-03-31 | 2003-07-22 | The Regents Of The University Of California | Functional assay of high-density lipoprotein |
US7250304B2 (en) | 2000-03-31 | 2007-07-31 | The Regents Of The University Of California | Functional assay of high-density lipoprotein |
WO2001088547A2 (en) * | 2000-05-12 | 2001-11-22 | The Regents Of The University Of California | Standardized oxidized ldl assay |
GB0017641D0 (en) * | 2000-07-18 | 2000-09-06 | Medigene Oy | Peptides and their use |
JP4881535B2 (ja) | 2000-10-20 | 2012-02-22 | ハンブルガー・シュティフトゥング・ツーア・フェルデルング・フォン・ヴィッセンシャフト・ウント・クルトゥーア | 酸化タンパク質、およびその生物活性、該活性メカニズム、該タンパク質の使用およびその阻害から誘導される治療的かつ診断的方法 |
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WO1994023302A1 (en) * | 1993-04-07 | 1994-10-13 | The Australian National University | Immunological assay of oxidatively modified human low density lipoproteins in plasma |
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Cited By (2)
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JP2003529775A (ja) * | 2000-03-31 | 2003-10-07 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 高密度リポタンパク質の機能アッセイ |
JP2007322187A (ja) * | 2006-05-31 | 2007-12-13 | Dai Ichi Pure Chem Co Ltd | 再狭窄の発症リスクを判定する方法 |
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DE69738503T2 (de) | 2009-02-26 |
DE69738503D1 (de) | 2008-03-20 |
EP1021728B8 (en) | 2008-04-23 |
WO1998059248A1 (en) | 1998-12-30 |
EP1021728A1 (en) | 2000-07-26 |
ES2299186T3 (es) | 2008-05-16 |
AU3442397A (en) | 1999-01-04 |
JP4233120B2 (ja) | 2009-03-04 |
CA2294355C (en) | 2006-11-28 |
NZ502369A (en) | 2001-11-30 |
CA2294355A1 (en) | 1998-12-30 |
EP1021728B1 (en) | 2008-02-06 |
ATE385575T1 (de) | 2008-02-15 |
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