WO2002086101A3 - Core-glycosylated hcv envelope proteins - Google Patents

Core-glycosylated hcv envelope proteins Download PDF

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Publication number
WO2002086101A3
WO2002086101A3 PCT/BE2002/000064 BE0200064W WO02086101A3 WO 2002086101 A3 WO2002086101 A3 WO 2002086101A3 BE 0200064 W BE0200064 W BE 0200064W WO 02086101 A3 WO02086101 A3 WO 02086101A3
Authority
WO
WIPO (PCT)
Prior art keywords
envelope proteins
hcv envelope
glycosylated
core
oligomannoses
Prior art date
Application number
PCT/BE2002/000064
Other languages
French (fr)
Other versions
WO2002086101A2 (en
Inventor
Erik Depla
Alfons Bosman
Geert Deschamps
Erwin Sablon
Manfred Suckow
Isabelle Samson
Gert Verheyden
Original Assignee
Innogenetics Nv
Erik Depla
Alfons Bosman
Geert Deschamps
Erwin Sablon
Manfred Suckow
Isabelle Samson
Gert Verheyden
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to MXPA03009632A priority Critical patent/MXPA03009632A/en
Priority to CA002443781A priority patent/CA2443781A1/en
Priority to KR1020037013778A priority patent/KR100950104B1/en
Priority to AU2002257392A priority patent/AU2002257392B2/en
Priority to NZ529324A priority patent/NZ529324A/en
Priority to HU0303924A priority patent/HUP0303924A2/en
Priority to BR0209034-1A priority patent/BR0209034A/en
Priority to EP02727059A priority patent/EP1417298A2/en
Application filed by Innogenetics Nv, Erik Depla, Alfons Bosman, Geert Deschamps, Erwin Sablon, Manfred Suckow, Isabelle Samson, Gert Verheyden filed Critical Innogenetics Nv
Priority to IL15842202A priority patent/IL158422A0/en
Priority to JP2002583616A priority patent/JP4173741B2/en
Priority to SK1314-2003A priority patent/SK13142003A3/en
Publication of WO2002086101A2 publication Critical patent/WO2002086101A2/en
Priority to HR20030946A priority patent/HRP20030946A2/en
Publication of WO2002086101A3 publication Critical patent/WO2002086101A3/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C07K14/08RNA viruses
    • C07K14/18Togaviridae; Flaviviridae
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525Virus
    • A61K2039/5258Virus-like particles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/01Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/50Fusion polypeptide containing protease site
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011Details
    • C12N2770/24011Flaviviridae
    • C12N2770/24211Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • C12N2770/24222New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011Details
    • C12N2770/24011Flaviviridae
    • C12N2770/24211Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • C12N2770/24223Virus like particles [VLP]

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Communicable Diseases (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

The current invention relates to HCV envelope proteins or parts thereof which are the product of expression in eukaryotic cells. More particularly said HCV envelope proteins are characterized in that on average up to 80 % of their N-glycosylation sites are core-glycosylated. Of these N-glycosylated sites more than 70 % are glycosylated with an oligomannose containing 8 to 10 mannoses. Furthermore, the ratio of the oligomannoses with structure Man(7)-GlcNAc(2) over the oligomannose with structure Man(8)-GlcNAc(2) is less than or equal to 0.45. Less than 10 % of the oligomannoses is terminated with an α1,3 linked mannose. The HCV envelope proteins of the invention are particularly suited for diagnostic, prophylactic and therapeutic purposes. A suitable eukaryotic cell for production of the HCV envelope proteins of the invention is a Hansenula cell.
PCT/BE2002/000064 2001-04-24 2002-04-24 Core-glycosylated hcv envelope proteins WO2002086101A2 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
BR0209034-1A BR0209034A (en) 2001-04-24 2002-04-24 Glycosylated hcv wrap proteins in the nucleus
KR1020037013778A KR100950104B1 (en) 2001-04-24 2002-04-24 Core-glycosylated HCV envelope proteins
AU2002257392A AU2002257392B2 (en) 2001-04-24 2002-04-24 Core-glycosylated hcv envelope proteins
NZ529324A NZ529324A (en) 2001-04-24 2002-04-24 Core-glycosylated HCV envelope proteins made in yeast cells
HU0303924A HUP0303924A2 (en) 2001-04-24 2002-04-24 Core-glycosylated hcv envelope proteins
MXPA03009632A MXPA03009632A (en) 2001-04-24 2002-04-24 Core-glycosylated hcv envelope proteins.
EP02727059A EP1417298A2 (en) 2001-04-24 2002-04-24 Core-glycosylated hcv envelope proteins
CA002443781A CA2443781A1 (en) 2001-04-24 2002-04-24 Core-glycosylated hcv envelope proteins
IL15842202A IL158422A0 (en) 2001-04-24 2002-04-24 Core-glycosylated hcv envelope proteins
JP2002583616A JP4173741B2 (en) 2001-04-24 2002-04-24 Core glycosylated HCV envelope protein
SK1314-2003A SK13142003A3 (en) 2001-04-24 2002-04-24 Core-glycosylated HCV envelope proteins
HR20030946A HRP20030946A2 (en) 2001-04-24 2003-11-20 Core-glycosylated hcv envelope proteins

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP01870088 2001-04-24
EP01870088.0 2001-04-24
US30560401P 2001-07-17 2001-07-17
US60/305,604 2001-07-17

Publications (2)

Publication Number Publication Date
WO2002086101A2 WO2002086101A2 (en) 2002-10-31
WO2002086101A3 true WO2002086101A3 (en) 2004-02-19

Family

ID=34072546

Family Applications (3)

Application Number Title Priority Date Filing Date
PCT/BE2002/000063 WO2002086100A2 (en) 2001-04-24 2002-04-24 Expression of core-glycosylated hcv envelope proteins in yeast
PCT/BE2002/000062 WO2002085932A2 (en) 2001-04-24 2002-04-24 Constructs and methods for expression of recombinant hcv envelope proteins
PCT/BE2002/000064 WO2002086101A2 (en) 2001-04-24 2002-04-24 Core-glycosylated hcv envelope proteins

Family Applications Before (2)

Application Number Title Priority Date Filing Date
PCT/BE2002/000063 WO2002086100A2 (en) 2001-04-24 2002-04-24 Expression of core-glycosylated hcv envelope proteins in yeast
PCT/BE2002/000062 WO2002085932A2 (en) 2001-04-24 2002-04-24 Constructs and methods for expression of recombinant hcv envelope proteins

Country Status (20)

Country Link
US (3) US7238356B2 (en)
EP (3) EP1414942A2 (en)
JP (2) JP4261195B2 (en)
KR (1) KR100950104B1 (en)
CN (1) CN1636050A (en)
AR (3) AR035869A1 (en)
AU (3) AU2002308449B2 (en)
BR (2) BR0209034A (en)
CA (3) CA2443781A1 (en)
CZ (1) CZ20032853A3 (en)
HU (1) HUP0303924A2 (en)
MX (2) MXPA03009626A (en)
NZ (2) NZ529324A (en)
OA (1) OA13092A (en)
PL (1) PL366621A1 (en)
RU (1) RU2274643C2 (en)
SK (1) SK13142003A3 (en)
WO (3) WO2002086100A2 (en)
YU (1) YU84103A (en)
ZA (3) ZA200308272B (en)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040185061A1 (en) * 1994-07-29 2004-09-23 Innogenetics N.V. Redox reversible HCV proteins with native-like conformation
EP1414942A2 (en) * 2001-04-24 2004-05-06 Innogenetics N.V. Expression of core-glycosylated hcv envelope proteins in yeast
DE10143490C2 (en) * 2001-09-05 2003-12-11 Gsf Forschungszentrum Umwelt Recombinant MVA with the ability to express HCV structural antigens
CA2504711A1 (en) * 2002-11-08 2004-05-21 Innogenetics N.V. Hcv vaccine compositions comprising e1 and ns3 peptides
US7439042B2 (en) * 2002-12-16 2008-10-21 Globeimmune, Inc. Yeast-based therapeutic for chronic hepatitis C infection
JP4371739B2 (en) * 2003-09-02 2009-11-25 株式会社東芝 Electronic device having serial ATA interface and power saving method of serial ATA bus
EP1602664A1 (en) * 2004-03-08 2005-12-07 Innogenetics N.V. HCV E1 comprising specific disulfide bridges
EP1574517A1 (en) 2004-03-09 2005-09-14 Innogenetics N.V. HCV E1 comprising specific disulfide bridges
JP4885476B2 (en) * 2004-05-21 2012-02-29 株式会社日本触媒 Method for introducing protein and / or peptide into cell
SG156652A1 (en) * 2004-10-18 2009-11-26 Globeimmune Inc Yeast-based therapeutic for chronic hepatitis c infection
AU2011254055B2 (en) * 2004-10-18 2012-12-20 Globeimmune, Inc. Yeast-based therapeutic for chronic hepatitis C infection
US20060234360A1 (en) * 2005-04-13 2006-10-19 Paola Branduardi Ascorbic acid production from D-glucose in yeast
US7951384B2 (en) * 2005-08-05 2011-05-31 University Of Massachusetts Virus-like particles as vaccines for paramyxovirus
US9216212B2 (en) 2005-08-05 2015-12-22 University Of Massachusetts Virus-like particles as vaccines for paramyxovirus
PE20070796A1 (en) * 2005-10-24 2007-08-15 Wyeth Corp PROTEIN PRODUCTION METHOD USING ANTI-SENESCENCE COMPOUNDS
WO2007136865A2 (en) * 2006-05-19 2007-11-29 Glycofi, Inc Recombinant vectors
AU2015234338C1 (en) * 2006-07-28 2017-07-20 The Trustees Of The University Of Pennsylvania Improved vaccines and methods for using the same
CN101563362B (en) * 2006-08-25 2015-02-11 麦克法兰布奈特医疗研究与公共健康研究所有限公司 Recombinant HCV E2 glycoprotein
US8728489B2 (en) 2008-09-19 2014-05-20 Globeimmune, Inc. Immunotherapy for chronic hepatitis C virus infection
US8580270B2 (en) 2008-09-30 2013-11-12 University Of Massachusetts Respiratory synctial virus (RSV) sequences for protein expression and vaccines
US20100104555A1 (en) * 2008-10-24 2010-04-29 The Scripps Research Institute HCV neutralizing epitopes
DE102009044224A1 (en) * 2009-10-09 2011-04-28 PomBio Tech GmbH Starterzentrum der Universität des Saarlandes Campus Geb. A1-1 Method for production of HCV virus-like particles
UA118537C2 (en) 2010-12-22 2019-02-11 Байєр Інтеллектуал Проперті Гмбх Enhanced immune response in bovine species
US20140155469A1 (en) 2011-04-19 2014-06-05 The Research Foundation Of State University Of New York Adeno-associated-virus rep sequences, vectors and viruses
WO2012152823A1 (en) 2011-05-09 2012-11-15 Ablynx Nv Method for the production of immunoglobulin single variable domains
US10155950B2 (en) * 2014-02-28 2018-12-18 Bayer Animal Health Gmbh Immunostimulatory plasmids
EP3374500A1 (en) * 2015-11-13 2018-09-19 Mammedov, Tarlan Production of in vivo n-deglycosylated recombinant proteins by co-expression with endo h
DK3184642T3 (en) * 2015-12-22 2019-08-12 Bisy E U yeast
WO2018055535A2 (en) 2016-09-21 2018-03-29 The Governors Of The University Of Alberta Hepatitis c virus immunogenic compositions and methods of use thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996004385A2 (en) * 1994-07-29 1996-02-15 Innogenetics N.V. Purified hepatitis c virus envelope proteins for diagnostic and therapeutic use
WO1999054735A1 (en) * 1998-04-17 1999-10-28 Innogenetics N.V. Improved immunodiagnostic assays using reducing agents
WO1999067285A1 (en) * 1998-06-24 1999-12-29 Innogenetics N.V. Particles of hcv envelope proteins: use for vaccination

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4395395A (en) * 1979-05-21 1983-07-26 The United States Of America As Represented By The Department Of Health And Human Services Detection of non-A, non-B hepatitis associated antigen
EP0288198A3 (en) 1987-04-20 1989-03-29 Takeda Chemical Industries, Ltd. Production of peptide
US5135854A (en) * 1987-10-29 1992-08-04 Zymogenetics, Inc. Methods of regulating protein glycosylation
US5683864A (en) * 1987-11-18 1997-11-04 Chiron Corporation Combinations of hepatitis C virus (HCV) antigens for use in immunoassays for anti-HCV antibodies
US5350671A (en) * 1987-11-18 1994-09-27 Chiron Corporation HCV immunoassays employing C domain antigens
US5698390A (en) * 1987-11-18 1997-12-16 Chiron Corporation Hepatitis C immunoassays
JP2791418B2 (en) * 1987-12-02 1998-08-27 株式会社ミドリ十字 Method for producing heterologous protein, recombinant DNA, transformant
NO177065C (en) * 1988-09-26 1995-07-12 Labofina Sa Process for the preparation of enzymatically active human lysozyme
US5747239A (en) * 1990-02-16 1998-05-05 United Biomedical, Inc. Synthetic peptides specific for the detection of antibodies to HCV, diagnosis of HCV infection and preventions thereof as vaccines
US6312889B1 (en) * 1990-04-04 2001-11-06 Chiron Corporation Combinations of hepatitis c virus (HCV) antigens for use in immunoassays for anti-HCV antibodies
WO1992001800A1 (en) * 1990-07-20 1992-02-06 Chiron Corporation Method for integrative transformation of yeast using dispersed repetitive elements
CA2047792C (en) 1990-07-26 2002-07-02 Chang Y. Wang Synthetic peptides specific for the detection of antibodies to hcv, diagnosis of hcv infection and prevention thereof as vaccines
HU227547B1 (en) 1991-06-24 2011-08-29 Novartis Vaccines & Diagnostic Hepatitis c virus (hcv) polypeptides
AU4659993A (en) 1992-07-07 1994-01-31 Merck & Co., Inc. Vaccine comprising mixed pres1+pres2+s and core particle
EP0979867A3 (en) 1993-11-04 2007-06-13 Innogenetics N.V. Immunodominant human T-cell epitopes of hepatitis C virus
ZA9610456B (en) * 1995-12-20 1997-06-20 Novo Nordisk As N-terminally extended proteins expressed in yeast
US5935824A (en) * 1996-01-31 1999-08-10 Technologene, Inc. Protein expression system
WO1998028429A1 (en) * 1996-12-20 1998-07-02 Novo Nordisk A/S N-terminally extended proteins expressed in yeast
WO1999024466A2 (en) 1997-11-06 1999-05-20 Innogenetics N.V. Multi-mer peptides derived from hepatitis c virus envelope proteins for diagnostic use and vaccination purposes
EP1049790A1 (en) * 1998-01-23 2000-11-08 Novo Nordisk A/S Process for making desired polypeptides in yeast
CZ20021819A3 (en) 1999-10-27 2003-06-18 Innogenetics N. V. Oxidizing-reducing reversible HCV proteins with conformation similar to native proteins
MXPA02008886A (en) 2001-01-11 2003-04-25 Innogenetics Nv Purified hepatitis c virus envelope proteins for diagnostic and therapeutic use.
EP1414942A2 (en) * 2001-04-24 2004-05-06 Innogenetics N.V. Expression of core-glycosylated hcv envelope proteins in yeast
JP2005516939A (en) 2001-12-18 2005-06-09 イノジェネティックス・ナムローゼ・フェンノートシャップ Purified hepatitis C virus coat protein for diagnostic and therapeutic uses
CA2504711A1 (en) * 2002-11-08 2004-05-21 Innogenetics N.V. Hcv vaccine compositions comprising e1 and ns3 peptides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996004385A2 (en) * 1994-07-29 1996-02-15 Innogenetics N.V. Purified hepatitis c virus envelope proteins for diagnostic and therapeutic use
WO1999054735A1 (en) * 1998-04-17 1999-10-28 Innogenetics N.V. Improved immunodiagnostic assays using reducing agents
WO1999067285A1 (en) * 1998-06-24 1999-12-29 Innogenetics N.V. Particles of hcv envelope proteins: use for vaccination

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HELENIUS ARI: "How N-linked oligosaccharides affect glycoprotein folding in the endoplasmic reticulum.", MOLECULAR BIOLOGY OF THE CELL, vol. 5, no. 3, 1994, pages 253 - 265, XP009008191, ISSN: 1059-1524 *
KURODA S ET AL: "HEPATITIS B VIRUS ENVELOPE L PROTEIN PARTICLES SYNTHESIS AND ASSEMBLY IN SACCHAROMYCES CEREVISIAE, PURIFICATION AND CHARACTERIZATION", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 267, no. 3, 25 January 1992 (1992-01-25), pages 1953 - 1961, XP002937464, ISSN: 0021-9258 *
KURODA S ET AL: "SACCHAROMYCES CEREVISIAE CAN RELEASE HEPATITIS B VIRUS SURFACE ANTIGEN (HBSAG) PARTICLES INTO THE MEDIUM BY ITS SECRETORY APPARATUS", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, SPRINGER VERLAG, BERLIN, DE, vol. 40, no. 2/3, 1993, pages 333 - 340, XP009000216, ISSN: 0175-7598 *

Also Published As

Publication number Publication date
ZA200308274B (en) 2005-01-24
WO2002085932A3 (en) 2003-03-13
PL366621A1 (en) 2005-02-07
KR100950104B1 (en) 2010-03-30
AU2002308449B2 (en) 2008-05-29
WO2002086100A2 (en) 2002-10-31
ZA200308277B (en) 2004-07-08
WO2002085932A2 (en) 2002-10-31
JP4261195B2 (en) 2009-04-30
BR0209033A (en) 2005-01-11
AU2002252856A1 (en) 2002-11-05
HUP0303924A2 (en) 2004-03-01
US20030108561A1 (en) 2003-06-12
ZA200308272B (en) 2005-01-24
AU2002257392B2 (en) 2007-05-10
RU2003130955A (en) 2005-04-20
US7238356B2 (en) 2007-07-03
JP4173741B2 (en) 2008-10-29
US20030211597A1 (en) 2003-11-13
AR035869A1 (en) 2004-07-21
CN1636050A (en) 2005-07-06
WO2002086100A3 (en) 2004-02-19
WO2002086101A2 (en) 2002-10-31
EP1381671A2 (en) 2004-01-21
SK13142003A3 (en) 2004-11-03
CA2443781A1 (en) 2002-10-31
YU84103A (en) 2006-05-25
RU2274643C2 (en) 2006-04-20
AR035868A1 (en) 2004-07-21
JP2004536052A (en) 2004-12-02
EP1414942A2 (en) 2004-05-06
CZ20032853A3 (en) 2004-08-18
MXPA03009626A (en) 2004-06-30
JP2004532029A (en) 2004-10-21
NZ529019A (en) 2004-05-28
US7048930B2 (en) 2006-05-23
CA2444006A1 (en) 2002-10-31
EP1417298A2 (en) 2004-05-12
AR035867A1 (en) 2004-07-21
MXPA03009632A (en) 2004-06-30
KR20030094359A (en) 2003-12-11
OA13092A (en) 2006-11-10
US20030152940A1 (en) 2003-08-14
CA2443740A1 (en) 2002-10-31
US7314925B2 (en) 2008-01-01
NZ529324A (en) 2005-08-26
BR0209034A (en) 2005-02-01

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