US20050084845A1 - Human monoclonal antibody fab fragments directed against hcv e2 glycoprotein and endowed with in vitro neutralizing activity - Google Patents
Human monoclonal antibody fab fragments directed against hcv e2 glycoprotein and endowed with in vitro neutralizing activity Download PDFInfo
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- US20050084845A1 US20050084845A1 US10/502,307 US50230704A US2005084845A1 US 20050084845 A1 US20050084845 A1 US 20050084845A1 US 50230704 A US50230704 A US 50230704A US 2005084845 A1 US2005084845 A1 US 2005084845A1
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- G01N33/5767—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis non-A, non-B hepatitis
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- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
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- C07K16/1081—Togaviridae, e.g. flavivirus, rubella virus, hog cholera virus
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Definitions
- the invention concerns human monoclonal antibody Fab fragments directed against HCV E2 glycoprotein and endowed with in vitro neutralizing activity.
- Hepatitis C virus (VCV) infects about 4% of the world population (World Health Organization, 1999). Over 80% of subjects coming into contact with this pathogen develop a chronic infection as the host immune response is unable to eradicate the infection, with the risk of severe liver diseases such as chronic hepatitis, cirrhosis and liver cell carcinoma [1, 2].
- Bugli et al., 2001 [7] generated a map of E2 protein epitopes that can bind in vitro the panel of anti-E2 human Fabs, showing four discrete regions against which immune response is directed ( FIG. 2 ) [7].
- the presence of antibodies directed against one or more of these regions in the serum of chronically infected patients could be associated with complications, reduced effectiveness of treatment and a different prognosis. It is therefore evident that there is a need for a method to determine antibodies in a biological fluid directed against different epitopes of the HCV E2 protein. An embodiment of the present invention provides this method.
- the antibody of the invention is the antibody e301, which is characterized by the following amino acid sequences of the variable part of the heavy and light chains: e 301 Heavy chain (HC) LLEQSGSEVKKPGSSVRVSCTTSGGTLSDYGFNWLRQAPGQGPEWMG GIIPLFRRTTYGQKFQGRLTITADESTGATYMELSSLRSDDTAVYYCARE KVSVLTGGKSLHYFEYWGKGT e 301 Light chain (LC) MAELTQSPATLSVSPGERATLSCRASQSVSSRLAWYQQKRGQAPSLLIY DTSSRATGVPARFSASGSGTQFTLTISSLQSEDFALYYCQQYNDWPSTF GQGT
- FIG. 1 FIT THEORETICAL BASIS.
- Panel A shows the binding of a Fab-FLAG to its epitopes without competitors.
- preincubation of the antigen with the patient's serum permits quantitative analysis of antibodies directed against the epitope recognized by the Fab in the serum.
- panels B and C the bound antibodies. as they compete with Fab, proportionately diminish the amount bound compared with panel A.
- panels D and E the presence of antibodies not directed against the specific epitope does not minimally influence Fab binding.
- Plates were washed 10 times with PBS/0.05% Tween-20 in an automated plate washer (DiaSorin, Saluggia, Italy) before adding 50 ⁇ l of a 10 ⁇ g/ml solution of anti-FLAG mouse monoclonal antibody M2 (Sigma, St. Louis, Mo.; 10 ⁇ g/ml in PBS) in PBS/BSA 1%. After 1 h incubation at 37° C., wells were washed 10 times with PBS/Tween-20 as above and mouse monoclonal antibody binding was revealed with horseradish peroxidase-conjugated goat anti-mouse IgG (Pierce; 1:8,000 in PBS).
- Substrate was added and plates were read for OD 450 in an automated plate reader after 30 min incubation at room temperature in the dark. All assays were performed at least in double. A negative control antigen (BSA) was always included and the OD reading was subtracted as background.
- BSA negative control antigen
- Fab Inhibiting Titer For the determination of the Fab Inhibiting Titer (FIT) of sera, a concentration of purified FLAG-Fabs yielding in standard conditions an OD 450 reading equal to 50% of maximum reading was used for further experiments of Fab inhibition ELISA. For these experiments, plates were coated and blocked as described above. Progressive 1:4 serum dilutions in PBS/BSA 1% were added in the amount of 50 ⁇ l per ELISA well. After 2 h of incubation at 37° C., purified FLAG-Fab was added directly to serum dilutions to reach the desired final concentration. Plates were incubated for additional 30 min and then processed as described above for FLAG-Fab ELISA.
- FIT Fab Inhibiting Titer
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- Veterinary Medicine (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/128,344 US7727529B2 (en) | 2002-01-30 | 2008-05-28 | Human monoclonal antibody Fab fragments directed against HCV E2 glycoprotein and endowed with in vitro neutralizing activity |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2002RM000049A ITRM20020049A1 (it) | 2002-01-30 | 2002-01-30 | Frammenti fab di anticorpi monoclonali umani diretti contro la glicoproteina e2 di hcv e dotati di potere neutralizzante in vitro. |
| ITRM2002A000049 | 2002-01-30 | ||
| PCT/IT2003/000032 WO2003064473A2 (en) | 2002-01-30 | 2003-01-29 | Human monoclonal antibody fab fragments directed against hcv e2 glycoprotein and endowed with in vitro neutralizing activity |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/128,344 Continuation US7727529B2 (en) | 2002-01-30 | 2008-05-28 | Human monoclonal antibody Fab fragments directed against HCV E2 glycoprotein and endowed with in vitro neutralizing activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20050084845A1 true US20050084845A1 (en) | 2005-04-21 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| US10/502,307 Abandoned US20050084845A1 (en) | 2002-01-30 | 2003-01-29 | Human monoclonal antibody fab fragments directed against hcv e2 glycoprotein and endowed with in vitro neutralizing activity |
| US12/128,344 Expired - Fee Related US7727529B2 (en) | 2002-01-30 | 2008-05-28 | Human monoclonal antibody Fab fragments directed against HCV E2 glycoprotein and endowed with in vitro neutralizing activity |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/128,344 Expired - Fee Related US7727529B2 (en) | 2002-01-30 | 2008-05-28 | Human monoclonal antibody Fab fragments directed against HCV E2 glycoprotein and endowed with in vitro neutralizing activity |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US20050084845A1 (enExample) |
| EP (1) | EP1476468B9 (enExample) |
| JP (1) | JP4287280B2 (enExample) |
| KR (1) | KR101002791B1 (enExample) |
| CN (1) | CN1856508A (enExample) |
| AT (1) | ATE407147T1 (enExample) |
| AU (1) | AU2003208000B2 (enExample) |
| CA (1) | CA2474801C (enExample) |
| DE (1) | DE60323333D1 (enExample) |
| DK (1) | DK1476468T3 (enExample) |
| EA (1) | EA009861B1 (enExample) |
| ES (1) | ES2314179T3 (enExample) |
| IT (1) | ITRM20020049A1 (enExample) |
| NZ (1) | NZ534922A (enExample) |
| RU (1) | RU2004126238A (enExample) |
| WO (1) | WO2003064473A2 (enExample) |
| ZA (1) | ZA200406187B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100104555A1 (en) * | 2008-10-24 | 2010-04-29 | The Scripps Research Institute | HCV neutralizing epitopes |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7723306B2 (en) | 2004-05-10 | 2010-05-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Spray-dried powder comprising at least one 1,4 O-linked saccharose-derivative and methods for their preparation |
| US7727962B2 (en) | 2004-05-10 | 2010-06-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Powder comprising new compositions of oligosaccharides and methods for their preparation |
| US7611709B2 (en) * | 2004-05-10 | 2009-11-03 | Boehringer Ingelheim Pharma Gmbh And Co. Kg | 1,4 O-linked saccharose derivatives for stabilization of antibodies or antibody derivatives |
| ITTO20070066A1 (it) | 2007-01-30 | 2008-07-31 | Pomona Biotechnologies Llc | Anticorpi monoclonali anti-idiotipo mimotopi dell'antigene gp 120 di hiv |
| WO2008107187A1 (en) * | 2007-03-06 | 2008-09-12 | Ribovax Biotechnologies S.A. | Antibodies specific for rubella virus |
| CN101809033A (zh) | 2007-07-25 | 2010-08-18 | 日本国立感染症研究所 | 对丙型肝炎病毒(hcv)感染具有抑制活性的抗体和其用途 |
| AU2008341542B2 (en) * | 2007-12-17 | 2014-12-04 | Medical Research Council Technology | Hepatitis C virus antibodies |
| ITTO20080204A1 (it) | 2008-03-17 | 2009-09-18 | Pomona Biotechnologies Llc | Anticorpi monoclonali atti a reagire con una pluralita di sottotipi del virus influenzale a |
| ITTO20080398A1 (it) | 2008-05-27 | 2009-11-28 | Pomona Biotechnologies Llc | Anticorpi monoclonali aventi proprieta' di cross-neutralizzazione omosubtipica per virus influenzali di tipo a sottotipo h1 |
| WO2010035292A1 (en) * | 2008-09-24 | 2010-04-01 | Natimab Therapeutics S.R.L. | The use of a human monoclonal anti-hcv antibody as a medicament for the therapeutic treatment and prevention of hcv infections |
| ITTO20080964A1 (it) * | 2008-12-22 | 2010-06-23 | Natimab Therapeutics S R L | Anticorpo monoclonale anti-hcv come medicamento per il trattamento terapeutico e la prevenzione di infezioni da hcv |
| IT1395961B1 (it) | 2009-06-01 | 2012-11-02 | Pomona Biotechnologies Llc | Anticorpi monoclonali come medicamento per il trattamento terapeutico e/o profilattico delle infezioni da virus influenzale a (h1n1) di origine suina (s-oiv) |
| CN102596996B (zh) | 2009-10-30 | 2014-06-18 | 东丽株式会社 | 对丙型肝炎病毒(hcv)具有感染抑制活性的抗体及其用途 |
| JP6095984B2 (ja) | 2010-03-01 | 2017-03-15 | アニョロ, ヴィンセントAGNELLO, Vincent | Ｈｃｖ感染患者のクリオグロブリン血症性血管炎およびｂ細胞悪性腫瘍のための予後マーカー |
| CN104119436B (zh) * | 2013-04-27 | 2016-12-28 | 中国科学院上海生命科学研究院 | 抗丙型肝炎病毒的中和性全人单克隆抗体 |
| GB201415714D0 (en) * | 2014-09-05 | 2014-10-22 | Medical Res Council | Antibodies and antigen binding fragments thereof |
| CN105254756B (zh) * | 2015-11-27 | 2018-09-07 | 武汉大学 | 一种针对丙型肝炎病毒包膜蛋白e2的单克隆抗体及应用 |
| KR20180001380U (ko) | 2016-10-31 | 2018-05-10 | 대우조선해양 주식회사 | 해양구조물의 발로 작동시키는 캡스탄 |
| CN118440204A (zh) | 2019-12-27 | 2024-08-06 | 凯奥目生物科学株式会社 | 抗cdcp1抗体 |
| US20230312744A1 (en) | 2020-09-02 | 2023-10-05 | The University Of Tokyo | Modulatory Substance of Tumor Immune Microenvironment, and Preventive, Diagnostic and/or Therapeutic Utilization of the Same |
| US20250375498A1 (en) | 2022-07-28 | 2025-12-11 | The University Of Tokyo | Neurotrimin function inhibitor |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6951646B1 (en) * | 1998-07-21 | 2005-10-04 | Genmab A/S | Anti hepatitis C virus antibody and uses thereof |
| US7091324B2 (en) * | 1998-11-05 | 2006-08-15 | Board Of Trustees Of Leland Stanford Junior University | Prevention and treatment of HCV infection employing antibodies directed against conformational epitopes |
| AU2001273363A1 (en) | 2000-07-12 | 2002-01-21 | General Instrument Corporation | Method and apparatus for downloading objects via an inband channel with minimal subscriber impact |
| JP2004524829A (ja) * | 2000-12-01 | 2004-08-19 | アメリカ合衆国 | Ｃ型肝炎ウイルスのｅ２糖タンパク質に特異的なモノクローナル抗体、ならびにｃ型肝炎の診断、治療、および予防におけるそれらの使用 |
-
2002
- 2002-01-30 IT IT2002RM000049A patent/ITRM20020049A1/it unknown
-
2003
- 2003-01-29 NZ NZ534922A patent/NZ534922A/en not_active IP Right Cessation
- 2003-01-29 AU AU2003208000A patent/AU2003208000B2/en not_active Ceased
- 2003-01-29 DK DK03705004T patent/DK1476468T3/da active
- 2003-01-29 EP EP03705004A patent/EP1476468B9/en not_active Expired - Lifetime
- 2003-01-29 WO PCT/IT2003/000032 patent/WO2003064473A2/en not_active Ceased
- 2003-01-29 KR KR1020047011208A patent/KR101002791B1/ko not_active Expired - Fee Related
- 2003-01-29 CA CA2474801A patent/CA2474801C/en not_active Expired - Lifetime
- 2003-01-29 RU RU2004126238/13A patent/RU2004126238A/ru not_active Application Discontinuation
- 2003-01-29 JP JP2003564093A patent/JP4287280B2/ja not_active Expired - Fee Related
- 2003-01-29 ES ES03705004T patent/ES2314179T3/es not_active Expired - Lifetime
- 2003-01-29 US US10/502,307 patent/US20050084845A1/en not_active Abandoned
- 2003-01-29 CN CNA038030926A patent/CN1856508A/zh active Pending
- 2003-01-29 AT AT03705004T patent/ATE407147T1/de not_active IP Right Cessation
- 2003-01-29 EA EA200401081A patent/EA009861B1/ru not_active IP Right Cessation
- 2003-01-29 DE DE60323333T patent/DE60323333D1/de not_active Expired - Lifetime
-
2004
- 2004-08-03 ZA ZA200406187A patent/ZA200406187B/en unknown
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2008
- 2008-05-28 US US12/128,344 patent/US7727529B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100104555A1 (en) * | 2008-10-24 | 2010-04-29 | The Scripps Research Institute | HCV neutralizing epitopes |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20040077745A (ko) | 2004-09-06 |
| EP1476468B1 (en) | 2008-09-03 |
| WO2003064473A2 (en) | 2003-08-07 |
| EA200401081A1 (ru) | 2005-10-27 |
| US7727529B2 (en) | 2010-06-01 |
| JP4287280B2 (ja) | 2009-07-01 |
| JP2005531286A (ja) | 2005-10-20 |
| ITRM20020049A1 (it) | 2003-07-30 |
| CA2474801A1 (en) | 2003-08-07 |
| NZ534922A (en) | 2008-07-31 |
| EA009861B1 (ru) | 2008-04-28 |
| ES2314179T3 (es) | 2009-03-16 |
| CA2474801C (en) | 2012-03-20 |
| WO2003064473A3 (en) | 2003-12-24 |
| US20080241162A1 (en) | 2008-10-02 |
| ZA200406187B (en) | 2006-06-28 |
| DE60323333D1 (de) | 2008-10-16 |
| EP1476468B9 (en) | 2009-04-08 |
| ATE407147T1 (de) | 2008-09-15 |
| AU2003208000B2 (en) | 2010-05-20 |
| CN1856508A (zh) | 2006-11-01 |
| EP1476468A2 (en) | 2004-11-17 |
| RU2004126238A (ru) | 2005-04-20 |
| KR101002791B1 (ko) | 2010-12-21 |
| ITRM20020049A0 (it) | 2002-01-30 |
| DK1476468T3 (da) | 2009-01-19 |
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| STCB | Information on status: application discontinuation |
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