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ANTI-HIV MONOCLONAL ANTIBODY

Foreign code F110002691
File No. S2007-1203-C0
Posted date Apr 7, 2011
Country WIPO
International application number 2008JP071035
International publication number WO 2009066702
Date of international filing Nov 19, 2008
Date of international publication May 28, 2009
Priority data
  • P2007-299083 (Nov 19, 2007) JP
Title ANTI-HIV MONOCLONAL ANTIBODY
Abstract Disclosed is a monoclonal antibody capable of recognizing V3 loop in an envelope glycoprotein gp120 of an AIDS virus, which is selected from the following antibodies (a) and (b): (a) an antibody which has the amino acid sequence depicted in SEQ ID NO:1 as the amino acid sequence for the H-chain variable region (VH) and the amino acid sequence depicted in SEQ ID NO:2 as the amino acid sequence for the L-chain variable region (VL); and (b) an antibody which has the amino acid sequence depicted in SEQ ID NO:3 as the amino acid sequence for the H-chain variable region (VH) and the amino acid sequence depicted in SEQ ID NO:4 as the amino acid sequence for the L-chain variable region (VL).
Outline of related art and contending technology BACKGROUND ART
Acquired immune deficiency syndrome (Acquired Immunodeficiency Syndrome; AIDS) is, human immunodeficiency virus (Human Immunodeficiency virus; HIV) chronically infected with lentiviruses that caused by a disease state. In recent years, an anti-viral agent for inhibiting the growth of HIV have been developed, and it becomes possible to inhibit the occurrence AIDS. However, a potent anti-viral agent may be used by the displacing HIV and it will be difficult, may still be are incapable of anti-viral treatments. On the other hand, long-term use of antiviral drugs by drug resistance problems such as toxicity or chronic virus is also apparent, the current antiviral therapy is still insufficient state. In addition, anti-viral drugs are expensive, long-term use in developing countries is substantially impossible. Due to these circumstances, the development of vaccines and infestation prevention includes the world is high and, in addition to the development of therapeutics and new side effects are also demanded.
HIV monoclonal antibody neutralized the infection of various kinds have been reported (Burton, DR. et al., Nat.Immunol. 5, p233-236, 2004; Zolla-Pazner, S. et al., Nat.Rev.Immunol. 4, p199-210, 2004; Eda, Y. et al., J.Virol. 80: 5552-5562, 2006). The external coating is roughly divided into their target molecule V1/V2 of the gp120 protein, such as variable region antibodies against V3, antibodies to the CD4 binding site (CD4bs), CD4i (CD4-gp120 binding that occur after the epitope) antibodies and the like. On the other hand, transmembrane protein, gp41 of the neutralizing activity of antibodies reactive to MPR(membrane proximal region) also has been introduced. Among these, have been shown and cross-reaction of the antibody and the V3 KD-247 447-52D, b12 CD4bs antibody, 4E10 antibody and gp41-MPR 2F5, and 2G12 anti-carbohydrate antibodies. V3 Antibody cross-reactivity is to be appreciated that the reaction is limited to the viral strain can be a problem. On the other hand, a number of clinical isolates were gp41-MPR antibody is cross-reaction is observed, the last few years have been noted, they are recently, lymphocytes of the host cell lipids have been shown to cross-reactivity, of autoantibodies to actually HIV cross-react with gp41 was found to be those. In addition, as long as CD3 is also b12 amino acid 18, cross-reactivity to self-antigens suggested (Haynes, BF et al., Science 308, p1906-1908, 2005).
Burton, DR. et al., Nat.Immunol. 5, p233-236, 2004
Zolla-Pazner, S. et al., Nat.Rev.Immunol. 4, p199-210, 2004
Eda, Y. et al., J.Virol. 80:5552-5562, 2006
Haynes, BF et al., Science 308, p1906-1908, 2005
Scope of claims (In Japanese)請求の範囲 [1]
以下の何れかの抗体から選択される、エイズウイルスのエンベロープ糖タンパク質gp120のV3ループを認識するモノクローナル抗体。
(a) H鎖の可変領域(VH)のアミノ酸配列として配列番号1に記載のアミノ酸配列を有し、L鎖の可変領域(VL)のアミノ酸配列として配列番号2に記載のアミノ酸配列を有する抗体;
(b) H鎖の可変領域(VH)のアミノ酸配列として配列番号3に記載のアミノ酸配列を有し、L鎖の可変領域(VL)のアミノ酸配列として配列番号4に記載のアミノ酸配列を有する抗体:

[2]
以下の何れかの抗体から選択される、エイズウイルスのエンベロープ糖タンパク質gp120のCD4結合部位を認識するモノクローナル抗体。
(a) H鎖の可変領域(VH)のアミノ酸配列として配列番号5に記載のアミノ酸配列を有し、L鎖の可変領域(VL)のアミノ酸配列として配列番号6に記載のアミノ酸配列を有する抗体;
(b) H鎖の可変領域(VH)のアミノ酸配列として配列番号7に記載のアミノ酸配列を有し、L鎖の可変領域(VL)のアミノ酸配列として配列番号8に記載のアミノ酸配列を有する抗体;
(c) H鎖の可変領域(VH)のアミノ酸配列として配列番号9に記載のアミノ酸配列を有し、L鎖の可変領域(VL)のアミノ酸配列として配列番号10に記載のアミノ酸配列を有する抗体:

[3]
受託番号FERM BP-11021、又は受託番号FERM BP-11060を有する細胞が産生する、エイズウイルスのエンベロープ糖タンパク質gp120のV3ループを認識するモノクローナル抗体またはその断片。

[4]
受託番号FERM BP-11020、受託番号FERM BP-11022、又は受託番号FERM BP-11023を有する細胞が産生する、エイズウイルスのエンベロープ糖タンパク質gp120のCD4結合部位を認識するモノクローナル抗体。

[5]
長期非進行症例のHIV感染患者のB細胞をgp120に対する結合性についてスクリーニングし、gp120結合抗体を産生するB細胞を選択することによって得られる細胞によって製造される、請求項1から4の何れかに記載の抗体。

[6]
長期非進行症例のHIV感染患者のB細胞をgp120に対する結合性についてスクリーニングし、gp120結合抗体を産生するB細胞を選択し、選択されたB細胞が産生する抗体を採取することを含む、請求項1から5の何れかに記載の抗体の製造方法。

[7]
受託番号FERM BP-11021、又は受託番号FERM BP-11060を有する、請求項1に記載の抗体を産生する細胞。

[8]
受託番号FERM BP-11020、受託番号FERM BP-11022、又は受託番号FERM BP-11023を有する、請求項2に記載の抗体を産生する細胞。

[9]
請求項1から5に記載の少なくとも1種類以上のモノクローナル抗体を含む、HIV感染症の予防及び/又は治療薬。

[10]
請求項1又は3に記載のモノクローナル抗体と、請求項2又は4に記載のモノクローナル抗体とを組み合わせて含む、HIV感染症の予防及び/又は治療薬。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • KUMAMOTO UNIVERSITY
  • Inventor
  • MATSUSHITA, Shuzo
  • YOSHIMURA, Kazuhisa
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MT NL NO PL PT RO SE SI SK TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
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