JP2008539715A - Hivに対して中和活性を有するがil2には中和活性を有さない抗体又はその断片 - Google Patents
Hivに対して中和活性を有するがil2には中和活性を有さない抗体又はその断片 Download PDFInfo
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- JP2008539715A JP2008539715A JP2008509516A JP2008509516A JP2008539715A JP 2008539715 A JP2008539715 A JP 2008539715A JP 2008509516 A JP2008509516 A JP 2008509516A JP 2008509516 A JP2008509516 A JP 2008509516A JP 2008539715 A JP2008539715 A JP 2008539715A
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- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1036—Retroviridae, e.g. leukemia viruses
- C07K16/1045—Lentiviridae, e.g. HIV, FIV, SIV
- C07K16/1063—Lentiviridae, e.g. HIV, FIV, SIV env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
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Abstract
【選択図】なし
Description
本発明に従う抗体は、完全な免疫グロブリン、又はその断片、及び特にその抗原結合性部分を云う。
本発明の抗体は、HIVのgp41糖タンパク質の野生型アミノ酸配列に由来するgp41改変ループタンパク質を認識しうる。本発明を実施するために召集されうるgp41タンパク質の野生型アミノ酸配列の例として、HIV−1株HxB2に由来する、配列ID NO 11のアミノ酸配列が挙げられ得る。
本発明の抗体は、P1と呼ばれ、かつ配列ID NO 12のペプチド配列を有するペプチド又はその類似体を認識しない。
HIVに対する、本発明の抗体又はその断片の中和活性は、
本発明の抗体は、実施例の部分において記載されているように得られるFab IgAファージディスプレイライブラリーのスクリーニングにより同定される。
一つの実施態様に従い、本発明は、活性な剤として、本発明の抗体、特にはクローン69、若しくはその断片、本発明のH鎖可変領域、本発明の組み換え抗HIV抗体若しくはその断片、本発明に従う核酸、本発明に従う発現ベクター又は本発明に従う宿主細胞、及び適当なキャリアから選ばれる剤の少なくとも1の有効量を含む医薬組成物に関する。
本発明のモノクローナル抗体又はその断片は、サンプル中のHIV株、特にはHIV−1株をインビトロで検出するための方法において診断的な剤としても用いられうる。
a)サンプルを少なくともの1の本発明の抗体又はその断片と、該抗体又はその断片とgp41タンパク質又はその機能的類似体との間で複合体を形成する為に適当な条件下で接触させること、及び
b)該複合体の存在を検出すること
の工程を含む。
図1:高度に曝露された、持続的にIgG血清陰性(HEPS)の個人の抗HIV−1 IgA含有膣頸部分泌物にさらされたgp41由来のHIV−1タンパク質のイムノブロットを表す。陽性対照として、gp41ペプチドのイムノブロットが、HIV血清陽性の個人から得られた血清を用いて行われた。そして、陰性対照として、同じ実験がHIV血清陰性の個人の血清を用いて行われた。
高度に曝露された、持続的にIgG血清陰性(HEPS)の個人の膣頸部分泌物中の抗HIV−1 IgAの同定
IgAのFabを発現するコンビナトリアルファージディスプレイライブラリーの構築
gp41改変ループタンパク質(配列ID NO 13)上でのFab IgAファージライブラリーのスクリーニング
配列決定は、Taq蛍光ジデオキシヌクレオチドターミネーターサイクルシーケンシングキット(Applied Biosystems)を用いて自動化されたDNAシーケンサーを用いて行われた。二本鎖DNAはバクテリアから調製され、そして配列決定はpComb3Xベクターに夫々のFab鎖の上及び下流で特異的にアニールするプライマーのセット(表2参照)を用いて実施された。
ファージディスプレイライブラリーからの可溶IgA Fabクローンにより実施されたELISAアッセイ
トランスサイトーシスの阻害
ドットブロット
Claims (23)
- 配列ID NO 1、配列ID NO 2、配列ID NO 3のアミノ酸配列を夫々有するCDR1、CDR2及びCDR3又はそれらの機能的類似体から選ばれる少なくとも1の相補性決定領域(CDR)を、H鎖可変領域中に含む、モノクローナル抗体又はその断片。
- 配列ID NO 4、配列ID NO 5、配列ID NO 6のアミノ酸配列を夫々有するCDR1、CDR2及びCDR3又はそれらの機能的類似体から選ばれる少なくとも1のCDRを、L鎖可変領域中に含む、請求項1に従うモノクローナル抗体又はその断片。
- 配列ID NO 12のアミノ酸配列のペプチドを認識しない、請求項1又は2に従うモノクローナル抗体。
- 配列ID NO 13のアミノ酸配列を有するgp41改変ループタンパク質を認識しかつ配列ID NO 12のアミノ酸配列のペプチドを認識しない、モノクローナル抗体又はその断片。
- IgAである、請求項1〜4のいずれか1項に従うモノクローナル抗体又はその断片。
- ヒト抗体である、請求項1〜5のいずれか1項に従うモノクローナル抗体又はその断片。
- 重鎖可変領域が配列ID NO 7のアミノ酸配列を有し、かつ軽鎖可変領域が配列ID NO 8のアミノ酸配列を有する、請求項1〜6のいずれか1項に従うモノクローナル抗体又はその断片。
- HIVを中和する能力を有する、請求項1〜7のいずれか1項に従うモノクローナル抗体又はその断片。
- 中和されるHIVがHIV−1株である、請求項8に従うモノクローナル抗体又はその断片。
- 配列ID NO 3、配列ID NO 4、配列ID NO 5のアミノ酸配列を夫々有するCDR1、CDR2及びCDR3又はそれらの機能的類似体から選ばれる少なくとも1のCDRを含む、H鎖可変領域。
- 請求項10に従うH鎖可変領域であって、配列ID NO 12のアミノ酸配列のペプチドを認識しないH鎖可変領域。
- 配列ID NO 13のアミノ酸配列を有するgp41改変ループタンパク質を認識し、かつ配列ID NO 12のアミノ酸配列のペプチドを認識しない、H鎖可変領域。
- 請求項10〜12のいずれか1項に従うH鎖可変領域を含む、組み換え抗HIV抗体又はその断片。
- 請求項1〜13のいずれか1項に従い定義されるモノクローナル抗体又はその断片をコードする核酸配列。
- 重鎖の核酸配列が配列ID NO 9である、請求項14に従う核酸配列。
- 軽鎖の核酸配列が配列ID NO 10である、請求項14に従う核酸配列。
- 請求項14〜16のいずれか1項に従い定義される核酸配列を含む発現ベクター。
- 請求項14〜16のいずれか1項に従い定義される核酸配列により又は請求項17に従い定義される発現ベクターにより形質転換された宿主細胞。
- 請求項1〜13のいずれか1項に従い定義される抗体又はその断片、請求項14〜16に従い定義される核酸配列、請求項17に従い定義される発現ベクター、又は請求項18に従い定義される宿主細胞から選ばれる有効量の剤を、活性な剤として、及び適当なキャリアを含む、医薬組成物。
- 請求項1〜13のいずれか1項に従い定義される抗体又はその断片、請求項14〜16に従い定義される核酸配列、請求項17に従い定義される発現ベクター、又は請求項18に従い定義される宿主細胞を、HIV感染の予防及び/又は治療に用いられるべきことが意図される医薬を製造するために使用する方法。
- 請求項1〜13のいずれか1項に従い定義される、抗体又はその断片を含む診断用組成物。
- サンプル中のHIV株をインビトロで検出する方法において、少なくとも
a)該サンプルと、請求項1〜13に従い定義される少なくとも1の抗体又はその断片とを、該抗体又はその断片とgp41タンパク質又はその機能的類似体との間で複合体を形成する為に適当な条件下で、接触させること、及び
b)該複合体の存在を検出すること
の工程を含む方法。 - HIVに感染しうる個人に受動免疫療法を提供する方法であって、請求項1〜13のいずれか1項に従い定義される少なくとも1の抗体又はその断片の治療的有効量を該個人に投与することを含む方法。
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PCT/IB2005/001182 WO2006117586A1 (en) | 2005-05-02 | 2005-05-02 | Antibody or a fragment thereof, having neutralizing activity against hiv but not against il2 |
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EP (1) | EP1879617A1 (ja) |
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AU2010210073B2 (en) * | 2009-02-06 | 2016-06-09 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Splitting gp41 |
RU2624046C2 (ru) | 2011-11-07 | 2017-06-30 | Дзе Юнайтед Стейтс Оф Америка, Эз Репрезентед Бай Дзе Секретэри, Департмент Оф Хелт Энд Хьюман Сервисиз | Gp41-нейтрализующие антитела и их применение |
WO2014040024A1 (en) * | 2012-09-10 | 2014-03-13 | Revo Biologics, Inc. | The use of antibodies in treating hiv infection and suppressing hiv transmission |
CN108884149B (zh) | 2015-11-03 | 2022-07-01 | 美国政府(由卫生和人类服务部的部长所代表) | Hiv-1 gp41中和抗体及其用途 |
BR112019002734A2 (pt) | 2016-08-13 | 2019-05-14 | Ubi Ip Holdings | tratamento e remissão virológica sustentada de infecção por hiv por anticorpos para cd4 em pacientes estabilizados por haart |
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