JP4601252B2 - Hivウイルスに対して活性な自然抗体 - Google Patents
Hivウイルスに対して活性な自然抗体 Download PDFInfo
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- JP4601252B2 JP4601252B2 JP2002571550A JP2002571550A JP4601252B2 JP 4601252 B2 JP4601252 B2 JP 4601252B2 JP 2002571550 A JP2002571550 A JP 2002571550A JP 2002571550 A JP2002571550 A JP 2002571550A JP 4601252 B2 JP4601252 B2 JP 4601252B2
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- hiv
- igg
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
図1
一次HIV-1単離体、SF162WT、92HT593B、および組換えNL-HX-ADAウイルスの抗IgG抗体による中和。各滴定曲線が単一の実験からのデータを表す。種々の実験における抗IgGの濃度は夫々109.7、12.3、80.0μg/mlであり、全IgGについて1000−3333μg/mlであり、HIVIGについて10000mgである。抗IgGおよび全IgG調製物を下記のように得た。HIVIGをHIV-1感染者の血清から調製した。
アフィニティー精製抗体のSDS-PAGE分離。抗IgGおよび全IgGを下記のように調製した。抗IgG抗体の電気泳動分離で予想どおりの量のIgGを得た。加えて、高分子量のタンパク質のバンドが存在したが、弱かった。
抗IgG抗体を2人の正常人血清のプールから、全ヒトIgG(GimmaBind セファロース4Bアフィニティーカラムから精製)が結合したセファロースビーズ(CNBr活性化セファロース4B)を用いるアフィニティークロマトグラフィ−により精製した。原則として、5−7mgのIgG抗体/0.5−0.6gのセファロースビーズを用いた。結合を製造業者の指示書に従い行った。カラムを5xPBSで平衡にし、熱不活化血清(1ml)を充填し、5xPBSで1:1に稀釈した。インキュベーションを1時間室温または一夜4℃で行った。30mlの5xPBSで洗った後、結合している抗体を0.1Mクエン酸塩、pH=2.5で、ベースTRISを含有する試験管中に溶出した。集めた溶出液を濃縮し、透析し(Centricon YM, 30000 MW cut-off)、10%SDS-PAGEで分析すると、IgGバンドが顕著に表れた(図2)。
ウイルス中和を公表のプロトコール(22)に従ってPBMCにおいて調べた。中和アッセイを抗体の異なる4調製物について、5の別個の実験で実施した。
1. Mascola, JR, Snyder, SW, Weislow, OS. Belay, SM, Belshe, RB, Schwartz, DH, Clements, ML, Dolin, R, Graham, BS, Gorse, GJ, Keefer, MC, McElrath, MJ, Walker, MC, Wagner, KF, McNeil, JG, McCutchan, FE, and Burke, DS: エンベロープ・サブユニット・ワクチン産物での免疫は、ヒト免疫不全症ウイルスタイプ1の実験室適用単離体に対する中和抗体を誘発するが、一次単離体に対する中和抗体を誘発しない J Infect Dis 1996; 173:340-348.
2. Montefiori, DC, and Evans, TG: 強力な広い交差反応性中和抗体をつくるToward およびHIVタイプ1ワクチン AIDS Res Hum Retroviruses 1999; 15:689-698;
3. Moore, JP, Coa, Y, Leu, Qin, L, Korber, B, and Ho, DD: ヒト免疫不全症ウイルスタイプ1の分岐間および分岐内の中和: 遺伝子学的分岐が中和セロタイプに相当しないが、gp120 抗原性セロタイプに部分的に相当する J Virol 1996; 70:427-444;
4. Weber, J, Fenyo, EM, Beddows, S, Kaleeby, P, Bjorndal, A, and the WHO Network for HIV Isolation and Characterization: HIV-1単離体の中和セロタイプは遺伝学的サブタイプにより予測されない J Viro1 1996; 70:7827-7832;
5. Burton, DR, Pyati, J, Koduri, R, Sharp, SJ, Thornton, GB, Parren, PWHI, Sawyer, LSW, Hendry, RM, Dunlop, N, Nara, PL, Lamacchia, M, Garratty, E, Stiehm, ER, Bryson, YJ, Cao, Y, Moore, JO, Ho, DD, and Barbas III, CF: 組換えヒト・モノクローナル抗体によるHIV-1一次単離体の効率的な中和 Science 1994; 266:1024-1027;
6. Mascola, JR, Louder, MK, VanCott, TC, Sapan, CV, Lambert, JS, Muenz, LR, Bunow, B, Birx, DL, and Robb, ML: モノクローナル抗体 2F5 および 2G12 と組合された高免疫抗HIV免疫グロブリンによるヒト免疫不全症ウイルス(HIV)タイプ1の一次単離体の強力かつ相乗的中和 J Virol 1997; 71:7198-7206;
7. Trkola, A, Pomales, AB, Yuan, H, Kober, B, Maddon, PJ, Allaway, GP, Katinger, H, Barbas III, CF, Burton, DR, Ho, DD, and Moore, JP: ヒト・モノクローナル抗体および四量体 CD4-IgG によるヒト免疫不全症ウイルスタイプ1の一次単離体の交差分岐中和 J Virol 1995; 69:6609-6617;
8. Moore, JP, and Trkola, A: JIVタイプ1共受容体、中和セロタイプ、ワクチンの開発 AIDS Res Human Retroviruses to 1997; 13:733-736;
9. Coutinho A: クローナル選択およびネットワークを越えて Immunological Reviews 1989; 110:63-67;
10. Avrames, S: 自然自己抗体: "horror autotexicus" から "gnothi seauton"へ Immunol Today 1991; 12:154-159;
11. Moller, G: 抗免疫グロブリン血清のBリンパ球機能に対する作用 Scand J Immunol 1978; 8:469-474;
12. Race, EM, Ramsey, KM, Lucia, HL, and Cloyd, MW: ヒト免疫不全症ウイルスが標準的試験により検出されない抗体を誘発する; 診断の示唆およびウイルス免疫学 Virology 1991; 184:716-722;
13. Nara, PL, and Garrity, R: 見かけ上の刷込み: 複合ワクチンの広い分布の戦略 Vaccine 1998; 16:1780-17787;
14. Zubler, RH, Perrin, LH, Doucet, A, Zhang, X, Huang, YP, and Miescher, PA: 陽性血および陰性血の個体におけるHIV反応性B細胞の頻度 Clin Exp Immunol 1991; 87:31-36;
15. Davis, D, Chaudhri, B, Stephens, DM, Carne, CA, Willers, C, and Lachmann, PJ: ヒト免疫不全症ウイルスタイプ1の膜貫通タンパク質 (gp41)内におけるエピトープの免疫優越は、非関連抗原に対する類似のエピトープへの宿主の前曝露により測定し得る J Gen Virol 1990; 71:1975-1983;
16. Velijovic, V, Metlas, R, Kohler, H, Urnovitz, HB, Prljic, J, Veljkovic, N, Johnson, E, and Mueller, S: 新世紀の始まりにおけるエイズの流行:新エイズワクチンの戦略 Vaccine 2000; 19: 1855-1863;
17. Wang, QL, Wang, HT, Blalock, E, Moller, S, and K"hlerm H: ヒト免疫不全症ウイルス-1感染個体における自己抗体により認識されるイディオタイプ・ペプチドの同定 in AIDS 1995; 96:775-780;
18. Veljkovic, V, and Metlas, R: HIV-1エンベロープ遺伝子における免疫グロブリン組換エレメントの同定 Immunol Lett 1991; 31:11-14;
19. Metlas, R, Veljkovic, V, Paladini, DR, and Pongor, S: ヒト免疫不全症ウイルスタイプ1エンペロープタンパク質 gp120 のV3ループと免疫グロブリン可変領域とのタンパク質およびDNA配列の相同性 Biochem Biophys Res Commun 1991; 179:1056-1062;
20. Metlas, R. Skerl, V, Veljkovic, V, Colombatti, A, and Pongor, S: HIV-1エンペロープ糖タンパク質 gpl20 の免疫グロブリン様ドメインは、いくつかの共通ヒトタンパク質の推測内部イメージをコードする Viral Immunol 1994; 7:215-219;
21. Metlas, R, Trajkovic, D, Srdic, T, Veljkovic, V, and Colombatti, A: 正常人の抗V3および抗IgG抗体が相補的構造を共有する JAIDS 1999; 21:266-270;
22. Pinter, A, Honnen, WJ, Tilley, SA: ヒト免疫不全症ウイルスタイプ1 gp120 のV3およびCD4−結合ドメインに影響する配座変化は env プロセシングおよびこれらの部位へのリガンド結合に関連する J Virol 1993; 67:5692-5697;
23. Holmberg, D, Andersson, A, Carlsson, L, and Forsgren, S: B細胞結合性の確立および機能的影響 Immunological Reviews 1989; 110:89-103;
24. Ochsenbein, AF, and Zinkernagel, RM: 天然抗体および5補体が先天性および獲得性免疫に結合する Immunol Today 2000; 21:624-629;
25. Fearon, DT, and Locksley, RM: 獲得性免疫応答における先天性免疫の構造的役割 Science 1996; 272:50-54.
Claims (2)
- HIV−1感染の予防または処置用の医薬組成物であって、ヒトIgG全フラクションに対するヒト抗体を含み、該ヒト抗体が、ヒトIgG全フラクションに結合した樹脂を用いて、HIV非感染正常人に由来する血清のアフィニティークロマトグラフィーにより得られ、そして、該ヒト抗体がHIV−1一次単離体を中和することができる、医薬組成物。
- HIV−1感染の受動免疫療法のための、請求項1に記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI20010500 ITMI20010500A1 (it) | 2001-03-09 | 2001-03-09 | Auto-anticorpi naturali e il loro uso nella terapia di malattie da virus dell'immunodeficienza umana |
IT2001MI002285A ITMI20012285A1 (it) | 2001-10-31 | 2001-10-31 | Anticorpi naturali attivi contro il virus hiv |
PCT/EP2002/002454 WO2002072637A1 (en) | 2001-03-09 | 2002-03-06 | Natural antibodie active against hiv virus |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2004532198A JP2004532198A (ja) | 2004-10-21 |
JP2004532198A5 JP2004532198A5 (ja) | 2010-07-01 |
JP4601252B2 true JP4601252B2 (ja) | 2010-12-22 |
Family
ID=26332768
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002571550A Expired - Fee Related JP4601252B2 (ja) | 2001-03-09 | 2002-03-06 | Hivウイルスに対して活性な自然抗体 |
Country Status (28)
Country | Link |
---|---|
US (2) | US20040106771A1 (ja) |
EP (1) | EP1366080B1 (ja) |
JP (1) | JP4601252B2 (ja) |
KR (1) | KR100871455B1 (ja) |
CN (1) | CN1494554A (ja) |
AP (1) | AP2003002852A0 (ja) |
AT (1) | ATE346870T1 (ja) |
AU (1) | AU2002257620B2 (ja) |
BR (1) | BR0207931A (ja) |
CA (1) | CA2440131A1 (ja) |
CY (1) | CY1108852T1 (ja) |
CZ (1) | CZ20032418A3 (ja) |
DE (1) | DE60216422T2 (ja) |
DK (1) | DK1366080T3 (ja) |
EE (1) | EE200300377A (ja) |
ES (1) | ES2278022T3 (ja) |
HR (1) | HRP20030701A2 (ja) |
HU (1) | HUP0303423A3 (ja) |
IL (2) | IL157753A0 (ja) |
MX (1) | MXPA03007976A (ja) |
NO (1) | NO20033934L (ja) |
PL (1) | PL366785A1 (ja) |
PT (1) | PT1366080E (ja) |
RS (1) | RS51011B (ja) |
RU (1) | RU2003125554A (ja) |
SI (1) | SI1366080T1 (ja) |
TN (1) | TNSN03066A1 (ja) |
WO (1) | WO2002072637A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100330102A1 (en) | 2009-06-26 | 2010-12-30 | Wezen Biopharmaceuticals Srl A Socio Unico | Immunoglobulin preparation for the treatment of hiv-1 infection |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
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US4639513A (en) * | 1984-02-02 | 1987-01-27 | Cuno Inc. | Intravenously injectable immunoglobulin G (IGG) and method for producing same |
US5788687A (en) * | 1994-02-01 | 1998-08-04 | Caphco, Inc | Compositions and devices for controlled release of active ingredients |
US5982866A (en) * | 1997-04-25 | 1999-11-09 | At&T Corporation | Method and apparatus for forwarding caller identification for a credit card or calling card call to an automatic number identification system of a telephone network |
DE19815430B4 (de) * | 1998-04-07 | 2005-12-15 | T-Mobile Deutschland Gmbh | Verfahren zum Verbindungsaufbau von einem Mobilfunknetz zu einer Zielrufnummer eines privaten Kommunikationsnetzes |
DK2272870T3 (da) * | 1998-06-09 | 2013-08-05 | Csl Behring Ag | Fremgangsmåde til fremstilling af immunoglobuliner med henblik på intravenøs indgivelse og andre immunoglobulin-lignende produkter. |
AU5610900A (en) * | 1999-06-14 | 2001-01-02 | Wilshire Cellular, Inc. | Method and apparatus for communicating via virtual office telephone extensions |
US6818247B1 (en) * | 2000-03-31 | 2004-11-16 | Advanced Cardiovascular Systems, Inc. | Ethylene vinyl alcohol-dimethyl acetamide composition and a method of coating a stent |
US6970719B1 (en) * | 2000-06-15 | 2005-11-29 | Sprint Spectrum L.P. | Private wireless network integrated with public wireless network |
US7336668B2 (en) * | 2001-09-24 | 2008-02-26 | Christopher Lyle Adams | Communication management system with line status notification for key switch emulation |
US8040873B2 (en) * | 2001-11-07 | 2011-10-18 | Alcatel Lucent | Distributed integration of legacy PBX system with SIP networks |
US20030105799A1 (en) * | 2001-12-03 | 2003-06-05 | Avaz Networks, Inc. | Distributed processing architecture with scalable processing layers |
US7546143B2 (en) * | 2001-12-18 | 2009-06-09 | Fuji Xerox Co., Ltd. | Multi-channel quiet calls |
US7146163B2 (en) * | 2002-10-01 | 2006-12-05 | Isp Operator Corporation | Sender-address-based telecommunications operator callback system and method |
US20040086093A1 (en) * | 2002-10-29 | 2004-05-06 | Schranz Paul Steven | VoIP security monitoring & alarm system |
US7904068B2 (en) * | 2003-06-06 | 2011-03-08 | At&T Intellectual Property I, L.P. | System and method for providing integrated voice and data services utilizing wired cordless access with unlicensed spectrum and wired access with licensed spectrum |
US7715413B2 (en) * | 2003-10-23 | 2010-05-11 | Emerj, Inc. | Multi-network exchange system for telephony applications |
CA2553209C (en) * | 2004-01-14 | 2012-05-01 | Research In Motion Limited | System and method for wirelessly provisioning a mobile communication device |
US8254989B2 (en) * | 2004-07-29 | 2012-08-28 | Sprint Spectrum L.P. | Method and system for account balance restriction on application of cellular-PBX integration service |
US20060294245A1 (en) * | 2005-06-22 | 2006-12-28 | Newstep Networks, Inc. | Method and system for a communications session join function to facilitate the provision of enhanced communications services |
US20070091907A1 (en) * | 2005-10-03 | 2007-04-26 | Varad Seshadri | Secured media communication across enterprise gateway |
-
2002
- 2002-03-06 CA CA002440131A patent/CA2440131A1/en not_active Abandoned
- 2002-03-06 AT AT02727364T patent/ATE346870T1/de not_active IP Right Cessation
- 2002-03-06 RU RU2003125554/15A patent/RU2003125554A/ru not_active Application Discontinuation
- 2002-03-06 RS YUP-701/03A patent/RS51011B/sr unknown
- 2002-03-06 ES ES02727364T patent/ES2278022T3/es not_active Expired - Lifetime
- 2002-03-06 PL PL02366785A patent/PL366785A1/xx not_active IP Right Cessation
- 2002-03-06 AU AU2002257620A patent/AU2002257620B2/en not_active Ceased
- 2002-03-06 EE EEP200300377A patent/EE200300377A/xx unknown
- 2002-03-06 CZ CZ20032418A patent/CZ20032418A3/cs unknown
- 2002-03-06 CN CNA028060636A patent/CN1494554A/zh active Pending
- 2002-03-06 IL IL15775302A patent/IL157753A0/xx unknown
- 2002-03-06 BR BR0207931-3A patent/BR0207931A/pt not_active IP Right Cessation
- 2002-03-06 PT PT02727364T patent/PT1366080E/pt unknown
- 2002-03-06 KR KR1020037011648A patent/KR100871455B1/ko not_active IP Right Cessation
- 2002-03-06 SI SI200230478T patent/SI1366080T1/sl unknown
- 2002-03-06 DE DE60216422T patent/DE60216422T2/de not_active Expired - Lifetime
- 2002-03-06 US US10/469,870 patent/US20040106771A1/en not_active Abandoned
- 2002-03-06 EP EP02727364A patent/EP1366080B1/en not_active Expired - Lifetime
- 2002-03-06 HU HU0303423A patent/HUP0303423A3/hu unknown
- 2002-03-06 WO PCT/EP2002/002454 patent/WO2002072637A1/en active IP Right Grant
- 2002-03-06 MX MXPA03007976A patent/MXPA03007976A/es unknown
- 2002-03-06 DK DK02727364T patent/DK1366080T3/da active
- 2002-03-06 JP JP2002571550A patent/JP4601252B2/ja not_active Expired - Fee Related
- 2002-03-06 AP APAP/P/2003/002852A patent/AP2003002852A0/en unknown
-
2003
- 2003-07-08 TN TNPCT/EP2002/002454A patent/TNSN03066A1/en unknown
- 2003-09-02 HR HR20030701A patent/HRP20030701A2/xx not_active Application Discontinuation
- 2003-09-04 IL IL157753A patent/IL157753A/en not_active IP Right Cessation
- 2003-09-05 NO NO20033934A patent/NO20033934L/no not_active Application Discontinuation
-
2006
- 2006-08-22 US US11/507,450 patent/US20070020290A1/en not_active Abandoned
-
2007
- 2007-02-15 CY CY20071100205T patent/CY1108852T1/el unknown
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