JPH11502416A - 診断、予防および治療のための多発性硬化症に関与するウイルス性物質およびヌクレオチドフラグメント - Google Patents
診断、予防および治療のための多発性硬化症に関与するウイルス性物質およびヌクレオチドフラグメントInfo
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- JPH11502416A JPH11502416A JP9508179A JP50817997A JPH11502416A JP H11502416 A JPH11502416 A JP H11502416A JP 9508179 A JP9508179 A JP 9508179A JP 50817997 A JP50817997 A JP 50817997A JP H11502416 A JPH11502416 A JP H11502416A
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. ゲノムが、配列SEQ ID NO:46、SEQ ID NO:51、SE Q ID NO:52、SEQ ID NO:53、SEQ ID NO:56、SE Q ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SE Q ID NO:61、SEQ ID NO:89、これらの配列の相補配列、およ びこれらと等価の配列であって、特に、100個連なるモノマーのどこの配列に 対しても、前記配列SEQ ID NO:46、SEQ ID NO:51、SEQ ID NO:52、SEQ ID NO:53、SEQ ID NO:56、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:89と少なくとも50%、好ましくは少 なくとも70%の相同性を示すヌクレオチド配列、およびこれらの配列の相補配 列を含む群から選択されたヌクレオチド配列を含むことを特徴とする、単離もし くは精製された状態のウイルス性物質。 2. SEQ ID NO:1と同一もしくは等価の配列を備えたサブ領域を除く 、envおよびpol遺伝子およびgag遺伝子の一部を含むそのゲノムの領域 が、少なくとも30個連なるアミノ酸のどこの配列に対しても、SEQ ID N O:46、SEQ ID NO:51、SEQ ID NO:52、SEQ ID N O:53、SEQ ID NO:56、SEQ ID NO:58、SEQ ID N O:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID N O:89およびこれらの相補配列を含む群から選択されたいずれかのヌクレオチ ド配列にコードされたペプチド配列と少なくとも50%、好ましくは少なくとも 70%の相同性を示すあらゆるポリペプチドをコードすることを特徴とする、単 離もしくは精製された状態のウイルス性物質。 3. pol遺伝子が、SEQ ID NO:1を除いて、SEQ ID NO:5 7と部分的もしくは全体的に同一もしくは等価のヌクレオチド配列を含むことを 特徴とする、単離もしくは精製された状態のウイルス性物質。 4. gag遺伝子が、SEQ ID NO:88と全体的もしくは部分的に同一 もしくは等価のヌクレオチド配列を含むことを特徴とする、単離もしくは精製さ れた状態のウイルス性物質。 5. ゲノムが、配列SEQ ID NO:46、SEQ ID NO:51、SE Q ID NO:52、SEQ ID NO:53、SEQ ID NO:56、SE Q ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SE Q ID NO:61、SEQ ID NO:89、これらの配列の相補配列、およ びこれらと等価の配列であって、特に、100個連なるモノマーのどこの配列に 対しても、前記配列SEQ ID NO:46、SEQ ID NO:51、SEQ ID NO:52、SEQ ID NO:53、SEQ ID NO:56、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:89と少なくとも50%、好ましくは少 なくとも70%の相同性を示すヌクレオチド配列、およびこれらの配列の相補配 列を含む群から選択されたヌクレオチド配列を含むことを特徴とする、多発性硬 化症に係る単離もしくは精製された状態のウイルス性物質。 6. SEQ ID NO:1と同一もしくは等価の配列を備えたサブ領域を除く 、envおよびpol遺伝子およびgag遺伝子の一部を含むそのゲノムの領域 が、少なくとも30個連なるアミノ酸のどこの配列に対しても、SEQ ID N O:46、SEQ ID NO:51、SEQ ID NO:52、SEQ ID N O:53、SEQ ID NO:56、SEQ ID NO:58、SEQ ID N O:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID N O:89およびこれらの相補配列を含む群から選択されたいずれかのヌクレオチ ド配列にコードされたペプチド配列と少なくとも50%、好ましくは少なくとも 70%の相同性を示すあらゆるポリペプチドをコードすることを特徴とする、多 発性硬化症に係る単離もしくは精製された状態のウイルス性物質。 7. pol遺伝子が、SEQ ID NO:1を除いて、SEQ ID NO:5 7と部分的もしくは全体的に同一もしくは等価のヌクレオチド配列を含むことを 特徴とする、多発性硬化症に係る単離もしくは精製された状態のウイルス性物質 。 8. gag遺伝子が、SEQ ID NO:88と全体的もしくは部分的に同一 もしくは等価のヌクレオチド配列を含むことを特徴とする、多発性硬化症に係る 単離もしくは精製された状態のウイルス性物質。 9. ゲノムが、配列SEQ ID NO:51、SEQ ID NO:56、SE Q ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SE Q ID NO:89、これらの配列の相補配列、およびこれらと等価の配列であ って、特に、100個連なるモノマーのどこの配列に対しても、前記配列SEQ ID NO:51、SEQ ID NO:56、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:89と少なく とも50%、好ましくは少なくとも70%の相同性を示すヌクレオチド配列、お よびこれらの配列の相補配列を含む群から選択されたヌクレオチド配列を含むこ とを特徴とする、慢性関節リウマチに係る単離もしくは精製された状態のウイル ス性物質。 10. SEQ ID NO:1と同一もしくは等価の配列を備えたサブ領域を除 く、pol遺伝子およびgag遺伝子の一部を含むそのゲノムの領域が、少なく とも30個連なるアミノ酸のどこの配列に対しても、SEQ ID NO:51、 SEQ ID NO:56、SEQ ID NO:59、SEQ ID NO:60、 SEQ ID NO:61、SEQ ID NO:89およびこれらの相補配列を含 む群から選択されたいずれかのヌクレオチド配列にコードされたペプチド配列と 少なくとも50%、好ましくは少なくとも70%の相同性を示すあらゆるポリペ プチドをコードすることを特徴とする、慢性関節リウマチに係る単離もしくは精 製された状態のウイルス性物質。 11. pol遺伝子が、SEQ ID NO:1を除いて、SEQ ID NO: 57と部分的もしくは全体的に同一もしくは等価のヌクレオチド配列を含むこと を特徴とする、慢性関節リウマチに係る単離もしくは精製された状態のウイルス 性物質。 12. gag遺伝子が、SEQ ID NO:88と全体的もしくは部分的に同 一もしくは等価のヌクレオチド配列を含むことを特徴とする、慢性関節リウマチ に係る単離もしくは精製された状態のウイルス性物質。 13. 以下の配列、すなわち (a)SEQ ID NO:1によって定義されたヌクレオチドフラグメントの全 配列を除く、MSRV−1ウイルスの部分的もしくは全体的なpol遺伝子の全 てのゲノム配列; (b)MSRV−1の部分的もしくは全体的なenv遺伝子の全てのゲノム配列 ; (c)MSRV−1のgag遺伝子の全ての部分的なゲノム配列; (d)MSRV−1ウイルスのpol遺伝子とenv遺伝子に重複するゲノム配 列の全て、およびpol遺伝子とgag遺伝子に重複するゲノム配列の全て; (e)SEQ ID NO:1によって定義付けられた配列と同一もしくは該配列 に内在するあらゆるヌクレオチド配列を除く、クローンFBd3(SEQ ID NO:46)、t pol(SEQ ID NO:51)、JLBc1(SEQ I D NO:52)、JLBc2(SEQ ID NO:53)、GM3(SEQ I D NO:56)、FBd13(SEQ ID NO:58)、LB19(SEQ ID NO:59)、LTRGAG12(SEQ ID NO:60)、FP6( SEQ ID NO:61)、G+E+A(SEQ ID NO:89)を含む群か ら選択される部分的および全体的なクローンの全ての配列; (f)前記ゲノム配列に相補的な配列; (g)前記配列(a)〜(e)と等価の配列、特に、100個連なるモノマーの どこの配列に対しても、前記配列(a)〜(e)と少なくとも50%、好ましく は70%の相同性を示すヌクレオチド配列、 を含む群から選択されたヌクレオチド配列を含むヌクレオチドフラグメントであ って、配列ERV−9を含んだり、ERV−9から構成されることのないヌクレ オチドフラグメント。 14. 以下の配列、すなわち (a)SEQ ID NO:1によって定義されたヌクレオチドフラグメントの全 配列を除く、MSRV−1ウイルスの部分的もしくは全体的なpol遺伝子の全 てのゲノム配列; (b)MSRV−1のgag遺伝子の全ての部分的なゲノム配列; (c)MSRV−1ウイルスのpol遺伝子とenv遺伝子に重複するゲノム配 列の全て、およびpol遺伝子とgag遺伝子に重複するゲノム配列の全て; (d)SEQ ID NO:1によって定義付けられた配列と同一もしくはこの配 列に内在するあらゆるヌクレオチド配列を除く、クローンt pol(SEQ I D NO:51)、GM3(SEQ ID NO:56)、LB19(SEQ ID NO:59)、LTRGAG12(SEQ ID NO:60)、FP6(SE Q ID NO:61)、G+E+A(SEQ ID NO:89)を含む群から選 択される部分的および全体的なクローンの全ての配列; (e)前記ゲノム配列に相補的な配列; (f)前記配列(a)〜(e)と等価の配列、特に、100個連なるモノマーの どこの配列に対しても、前記配列(a)〜(e)と少なくとも50%、好ましく は70%の相同性を示すヌクレオチド配列、 を含む群から選択されたヌクレオチド配列を含むヌクレオチドフラグメントであ って、配列ERV−9を含んだり、ERV−9から構成されることのないヌクレ オチドフラグメント。 15. SEQ ID NO:1に定義されたヌクレオチドフラグメントの全体的 な配列を除く、MSRV−1ウイルスのpol遺伝子の部分的もしくは全体的な ゲノム配列、もしくは前記部分的もしくは全体的なゲノム配列に等価なあらゆる 配列、特に該ゲノム配列に相同な配列に同一のヌクレオチド配列を含む、請求項 14記載のフラグメント。 16. 以下の配列、すなわち − 配列SEQ ID NO:40、SEQ ID NO:62もしくはSEQ I D NO:89から選択されたヌクレオチド配列; − SEQ ID NO:40、SEQ ID NO:62もしくはSEQ ID N O:89に相補的な配列; − SEQ ID NO:40、SEQ ID NO:62もしくはSEQ ID N O:89に等価、および特に相同な配列; − SEQ ID NO:39、SEQ ID NO:63もしくはSEQ ID N O:90に定義されたペプチド配列の全てまたは一部をコードする配列; − SEQ ID NO:39、SEQ ID NO:63もしくはSEQ ID N O:90に等価、特に相同なペプチド配列の全てもしくは一部をコードする配列 であって、MSRV−1ウイルスに感染した患者、あるいはMSRV−1ウイル スが再活性化された患者の血清で認識されうる配列 を含む群から選択されたヌクレオチド配列に部分的もしくは全体的に等価のヌク レオチド配列を含む、請求項15記載のヌクレオチドフラグメント。 17. MSRV−1ウイルスのenv遺伝子の部分的もしくは全体的なゲノム 配列に等しいヌクレオチド配列、該ヌクレオチド配列に相補的なあらゆる配列に 等しいヌクレオチド配列、もしくは該ヌクレオチド配列に等価なあらゆる配列に 等しいヌクレオチド配列であって、特に該配列に相同なヌクレオチド配列を含む ことを特徴とする、請求項13記載のフラグメント。 18. SEQ ID NO:1によって定義付けられた配列と同一もしくはこの 配列に内在するあらゆるヌクレオチド配列を除く、クローンFBd3(SEQ ID NO:46)、t pol(SEQ ID NO:51)、JLBc1(SE Q ID NO:52)、JLBc2(SEQ ID NO:53)、GM3(SEQ ID NO:56)、FBd13(SEQ ID NO:58)、LB19(SE Q ID NO:59)、LTRGAG12(SEQ ID NO:60)、FP6 (SEQ ID NO:61)、G+E+A(SEQ ID NO:89)を含む群 から選択されたクローンの部分的または全体的な配列に等しいヌクレオチド配列 を含むことを特徴とする、請求項13記載のフラグメント。 19. SEQ ID NO:1によって定義付けられた配列と同一もしくはこの 配列に内在するあらゆるヌクレオチド配列を除く、クローンt pol(SEQ ID NO:51)、GM3(SEQ ID NO:56)、LB19(SEQ I D NO:59)、LTRGAG12(SEQ ID NO:60)、FP6(S EQ ID NO:61)、G+E+A(SEQ ID NO:89)を含む群から 選択されたクローンの部分的または全体的な配列に等しいヌクレオチド配列を含 むことを特徴とする、請求項14記載のフラグメント。 20. 病原性成分のゲノムに所属または内在し、請求項13ないし19のいず れか一項に記載のあらゆるフラグメントと特異的にハイブリダイズすることがで きることを特徴とする、多発性硬化症にかかる病原性および/または感染性成分 の検出のための核酸プローブ。 21. 病原性成分のゲノムに所属または内在し、請求項14、15、16およ び19のいずれか一項に記載のあらゆるフラグメントと特異的にハイブリダイズ することができることを特徴とする、慢性関節リウマチにかかる病原性および/ または感染性成分の検出のための核酸プローブ。 22. 請求項13ないし19のいずれか一項に記載のフラグメントのヌクレオ チド配列の少なくとも一部に等しいまたは等価なヌクレオチド配列を含み、特に 10個連なるモノマーのどこの配列に対しても、前記フラグメントの少なくとも 前記部位と少なくとも70%の相同性を示すヌクレオチド配列を含むことを特徴 とする、ウイルス性物質のRNAもしくはDNAの重合による増幅用のプライマ ー。 23. ヌクレオチド配列が、SEQ ID NO:47〜SEQ ID NO:5 0、SEQ ID NO:55およびSEQ ID NO:64〜SEQ ID NO :86を含む群から選択されたいずれか一つの配列に等しいことを特徴とする、 請求項22記載のプライマー。 24. 請求項1ないし12のいずれか一項に記載のウイルス性物質のゲノムフ ラグメント、あるいは請求項13ないし19のいずれか一項に記載のフラグメン トを含む、複製ベクター等のRNAもしくはDNA。 25. MSRV−1ウイルスに感染した患者の血清および/またはMSRV− 1ウイルスが再活性化された患者の血清に認識される抗原決定基を形成もしくは 含有するオリゴペプチド等の、請求項13ないし19のいずれか一項に記載のヌ クレオチドフラグメントに属するあらゆる読み枠にコードされたペプチド。 26. 5’−3’の方向に、SEQ ID NO:1のヌクレオチド181から 始まってヌクレオチド330で終わる読み枠にコードされることを特徴とする、 請求項25に記載の抗原性ポリペプチド。 27. MSRV−1ウイルスに感染した患者の血清および/またはMSRV− 1ウイルスが再活性化された患者の血清に認識される抗原性のオリゴポリペプチ ド等の、SEQ ID NO:39、SEQ ID NO:63およびSEQ ID NO:87に定義された配列に、部分的もしくは全体的に同一もしくは等価であ ることを特徴とするポリペプチド。 28. ペプチド配列が、SEQ ID NO:41〜SEQ ID NO:44、 SEQ ID NO:63およびSEQ ID NO:87を含む群から選択された 配列と同一であることを特徴とする、請求項27に記載の抗原性オリゴペプチド 。 29. MSRV−1ウイルスに感染した患者の血清および/またはMSRV− 1ウイルスが再活性化された患者の血清に認識される抗原決定基を形成もしくは 含有するオリゴペプチド等の、請求項14、15、16および19のいずれか一 項に記載のヌクレオチドフラグメントに属するあらゆる読み枠にコードされたペ プチド。 30. 5’−3’の方向に、SEQ ID NO:1のヌクレオチド181から 始まってヌクレオチド330で終わる読み枠にコードされることを特徴とする、 請求項29に記載の抗原性ポリペプチド。 31. MSRV−1ウイルスに感染した患者の血清および/またはMSRV− 1ウイルスが再活性化された患者の血清に認識される抗原性のオリゴポリペプチ ド等の、SEQ ID NO:39またはSEQ ID NO:63に定義された配 列に、部分的もしくは全体的に同一もしくは等価であることを特徴とするポリペ プチド。 32. ペプチド配列が、SEQ ID NO:41〜SEQ ID NO:44お よびSEQ ID NO:63を含む群から選択された配列と同一であることを特 徴とする、請求項31に記載の抗原性オリゴペプチド。 33. 請求項25ないし28のいずれか一項に記載の抗原性ポリペプチドから なる免疫原性成分に対するヒトもしくは動物の体の免疫学的反応によって得られ ることを特徴とする、MSRV−1ウイルスに対して向けられたモノクローナル もしくはポリクローナル抗体。 34. 請求項29ないし32のいずれか一項に記載の抗原性ポリペプチドから なる免疫原性成分に対するヒトもしくは動物の体の免疫学的反応によって得られ ることを特徴とする、MSRV−1ウイルスに対して向けられたモノクローナル もしくはポリクローナル抗体。 35. 反応性物質として、請求項25ないし32のいずれか一項に記載の抗原 性ペプチド等のペプチド、もしくは該ペプチドに対する抗体等の抗リガンドを含 むことを特徴とする、MSRV−1ウイルスの検出、もしくはこのウイルスに対 する暴露の検出のための試薬。 36. 請求項25ないし28のいずれか一項に記載の抗原性ペプチド等のペプ チド、もしくは請求項33記載の前記ペプチドに対する抗体等の抗リガンドを含 む、診断、予防もしくは治療用組成物。 37. 請求項29ないし32のいずれか一項に記載の抗原性ペプチド等のペプ チド、もしくは請求項34記載の前記ペプチドに対する抗体等の抗リガンドを含 む、診断、予防もしくは治療用組成物。 38. 請求項36または37記載のワクチン組成物等の能動免疫治療用組成物 。 39. ヌクレオチド配列SEQ ID NO:1を備えたフラグメントの配列を 除く、前記フラグメントの配列と部分的に同一である、請求項13ないし19の いずれか一項に記載のヌクレオチドフラグメントあるいはオリゴヌクレオチド等 のポリヌクレオチドを含む、多発性硬化症に係る少なくとも一つの病原性および /または感染性成分の発現を阻害するための、診断、予防もしくは治療用組成物 。 40. ヌクレオチド配列SEQ ID NO:1を備えたフラグメントの配列を 除く、前記フラグメントの配列と部分的に同一である、請求項14、15、16 および19のいずれか一項に記載のヌクレオチドフラグメントあるいはオリゴヌ クレオチド等のポリヌクレオチドを含む、慢性関節リウマチに係る少なくとも一 つの病原性および/または感染性成分の発現を阻害するための、診断、予防もし くは治療用組成物。 41. 多発性硬化症に係る病原性および/または感染性成分に所属もしくは由 来すると推定されるRNAおよび/またはDNA、もしくはそれらの相補的RN Aおよび/またはDNAを、請求項13ないし19のいずれか一項に記載のヌク レオチドフラグメントもしくはオリゴヌクレオチド等のポリヌクレオチドであっ て、ヌクレオチド配列SEQ ID NO:1を備えたフラグメントの配列を除く 前記フラグメントの配列と部分的に同一である配列のヌクレオチドを含む組成物 と接触させることを特徴とする、生物学的サンプル中の多発性硬化症に係る病原 性および/または感染性成分を検出する方法。 42. 慢性関節リウマチに係る病原性および/または感染性成分に所属もしく は由来すると推定されるRNAおよび/またはDNA、もしくはそれらの相補的 RNAおよび/またはDNAを、請求項14、15、16および19のいずれか 一項に記載のヌクレオチドフラグメントもしくはオリゴヌクレオチド等のポリヌ クレオチドであって、ヌクレオチド配列SEQ ID NO:1を備えたフラグメ ントの配列を除く前記フラグメントの配列と部分的に同一である配列のヌクレオ チドを含む組成物と接触させることを特徴とする、生物学的サンプル中の慢性関 節リウマチに係る病原性および/または感染性成分を検出する方法。 43. 生物学的サンプルを、請求項25ないし28のいずれか一項に記載の抗 原性ペプチド等のペプチド、もしくは請求項33に記載の前記ペプチドに対する 抗体等の抗リガンドと接触させることを特徴とする、生物学的サンプルにおける 多発性硬化症に係る病原性および/または感染性成分の存在もしくは暴露を検出 する方法。 44. 生物学的サンプルを、請求項29ないし32のいずれか一項に記載の抗 原性ペプチド等のペプチド、もしくは請求項34に記載の前記ペプチドに対する 抗体等の抗リガンドと接触させることを特徴とする、生物学的サンプルにおける 慢性関節リウマチに係る病原性および/または感染性成分の存在もしくは暴露を 検出する方法。 45. 免疫学的に適合する固相支持体に支持された請求項35記載の試薬を含 むMSRV−1ウイルスを検出するための装置であって、免疫学的反応が起こる 条件下で、抗MSRV−1抗体を含みそうな血液もしくは脳脊髄液のサンプル等 の生物学的サンプルを前記試薬と接触させる手段と、前記試薬と共に形成された 免疫複合体を検出する手段とを含むことを特徴とする、MSRV−1ウイルスを 検出するための装置。 46. 血液もしくは脳脊髄液のサンプル等の生物学的サンプル中の抗MSRV −1抗体の検出方法であって、可能な免疫反応が起こる条件下で、前記サンプル と、抗体からなる請求項35記載の試薬とを接触させ、前記試薬と共に形成され た免疫複合体の存在を検出することを特徴とする、抗MSRV−1抗体の検出方 法。
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FR2737500B1 (fr) * | 1995-08-03 | 1997-08-29 | Bio Merieux | Materiel viral et fragments nucleotidiques associes a la sclerose en plaques, a des fins de diagnostic, prophylactiques et therapeutiques |
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