ES2130184T3 - Polipeptidos y vacunas recombinantes contra el herpesvirus bovino de tipo 1. - Google Patents

Polipeptidos y vacunas recombinantes contra el herpesvirus bovino de tipo 1.

Info

Publication number
ES2130184T3
ES2130184T3 ES92924523T ES92924523T ES2130184T3 ES 2130184 T3 ES2130184 T3 ES 2130184T3 ES 92924523 T ES92924523 T ES 92924523T ES 92924523 T ES92924523 T ES 92924523T ES 2130184 T3 ES2130184 T3 ES 2130184T3
Authority
ES
Spain
Prior art keywords
herpesvirus type
bovine herpesvirus
against bovine
recombinant polypeptides
vaccines against
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
ES92924523T
Other languages
English (en)
Inventor
Lorne Babiuk
Den Hurk Sylvia Van
Tim Zamb
David Fitzpatrick
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Saskatchewan
Original Assignee
University of Saskatchewan
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
Application filed by University of Saskatchewan filed Critical University of Saskatchewan
Application granted granted Critical
Publication of ES2130184T3 publication Critical patent/ES2130184T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • 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
    • A61K39/12—Viral antigens
    • 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
    • A61K39/12—Viral antigens
    • A61K39/245—Herpetoviridae, e.g. herpes simplex virus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • 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
    • A61K2039/70—Multivalent vaccine
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/14011—Baculoviridae
    • C12N2710/14111—Nucleopolyhedrovirus, e.g. autographa californica nucleopolyhedrovirus
    • C12N2710/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2710/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
    • C12N2710/16622—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
    • C12N2710/16634—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16711—Varicellovirus, e.g. human herpesvirus 3, Varicella Zoster, pseudorabies
    • C12N2710/16722—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16711—Varicellovirus, e.g. human herpesvirus 3, Varicella Zoster, pseudorabies
    • C12N2710/16734—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16711—Varicellovirus, e.g. human herpesvirus 3, Varicella Zoster, pseudorabies
    • C12N2710/16771—Demonstrated in vivo effect
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/24011—Poxviridae
    • C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
    • C12N2710/24141—Use of virus, viral particle or viral elements as a vector
    • C12N2710/24143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/30—Vector systems having a special element relevant for transcription being an enhancer not forming part of the promoter region
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/01—DNA viruses
    • G01N2333/03—Herpetoviridae, e.g. pseudorabies virus

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Wood Science & Technology (AREA)
  • Urology & Nephrology (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Public Health (AREA)
  • Physics & Mathematics (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Mycology (AREA)
  • General Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Plant Pathology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Food Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)

Abstract

SON PROVISTAS SUBUNIDADES DE VACUNAS RECOMBINANTES CONTRA EL HERPESVIRUS DE BOVINO TIPO 1 (BHV-1), COMO TAMBIEN LOS METODOS DE VACUNACION Y LOS METODOS DE PRODUCIR RECOMBINANTEMENTE LAS SUBUNIDADES ANTIGENAS O SECUENCIAS NUCLEOTIDAS EMPLEADAS EN LA VACUNA. PREFERIBLEMENTE, LA SUBUNIDAD ES UN ANTIGENO BVV-1 GIV TRUNCADO.
ES92924523T 1991-12-11 1992-12-11 Polipeptidos y vacunas recombinantes contra el herpesvirus bovino de tipo 1. Expired - Lifetime ES2130184T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US80552491A 1991-12-11 1991-12-11
US07/921,849 US5585264A (en) 1988-07-15 1992-07-29 Nucleotide sequences encoding recombinant bovine herpesvirus type-1 GI, GIII and GIV polypeptides

Publications (1)

Publication Number Publication Date
ES2130184T3 true ES2130184T3 (es) 1999-07-01

Family

ID=27122795

Family Applications (1)

Application Number Title Priority Date Filing Date
ES92924523T Expired - Lifetime ES2130184T3 (es) 1991-12-11 1992-12-11 Polipeptidos y vacunas recombinantes contra el herpesvirus bovino de tipo 1.

Country Status (6)

Country Link
US (3) US5585264A (es)
EP (2) EP0888777A3 (es)
AT (1) ATE178802T1 (es)
DE (1) DE69228944T2 (es)
ES (1) ES2130184T3 (es)
WO (1) WO1993011792A1 (es)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5585264A (en) * 1988-07-15 1996-12-17 University Of Saskatchewan Nucleotide sequences encoding recombinant bovine herpesvirus type-1 GI, GIII and GIV polypeptides
FR2693472B1 (fr) * 1992-06-26 1994-12-23 Rhone Merieux Mutants du virus de la rhinotrachéite infectieuse bovine, délétés dans l'un des gènes des glycoprotéines mineures, vaccins préparés à partir de ces souches, méthodes de production et méthodes d'utilisation.
DK0586076T3 (da) * 1992-08-07 2003-10-20 Wyeth Corp Rekombinant adenovirus-vacciner
ES2088371B1 (es) * 1995-02-01 1997-04-16 Hipra Lab Sa Procedimiento para la produccion en forma recombinante de antigenos de la glicoproteina ge de herpesvirus bovino tipo 1 y su uso en la diferenciacion serologica entre animales infectados y animales vacunados.
KR100564268B1 (ko) * 1996-10-23 2006-03-27 와이어쓰 백신
CN1324139C (zh) * 1996-10-23 2007-07-04 惠氏 疫苗
US6299881B1 (en) * 1997-03-24 2001-10-09 Henry M. Jackson Foundation For The Advancement Of Military Medicine Uronium salts for activating hydroxyls, carboxyls, and polysaccharides, and conjugate vaccines, immunogens, and other useful immunological reagents produced using uronium salts
PT873752E (pt) * 1997-04-23 2004-07-30 Pfizer Encapsulacao com base em solvente aquoso de uma vacina de uma subunidade do virus do herpes bovino de tipo-1
DE69921773D1 (de) * 1998-01-16 2004-12-16 Univ Johns Hopkins Orale verabreichung von nukleinsäure-impstoffen durch partikelkomplexe
DK1035133T3 (da) 1999-02-17 2005-05-02 Pfizer Prod Inc Fusionsproteiner, der omfatter bærere, som kan inducere et dobbelt immunrespons
US6964847B1 (en) 1999-07-14 2005-11-15 Packard Biosciences Company Derivative nucleic acids and uses thereof
GB9929272D0 (en) * 1999-12-10 2000-02-02 Diagnology Limited Assay
US20020090382A1 (en) * 2000-08-01 2002-07-11 University Of Pittsburgh Of The Commonwealth System Of Higher Education Antiviral compounds and methods
ATE324376T1 (de) * 2001-01-16 2006-05-15 Invitrogen Corp Reagenz zur isolierung von rna
JP2009530027A (ja) * 2006-03-20 2009-08-27 メデイカル コンポーネンツ，インコーポレーテツド 静脈アクセスポート組立品、及び、その組立と使用方法
BRPI1101186B1 (pt) * 2011-12-29 2019-06-25 Universidade Federal De Minas Gerais Proteínas recombinantes, polinucleotídeos e vacinas contra herpesvírus bovinos
CN116218909B (zh) * 2023-02-13 2024-08-09 华南农业大学 表达IBRV-gD和BVDV-E2的重组杆状病毒表达系统、构建方法及应用

Family Cites Families (13)

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Publication number Priority date Publication date Assignee Title
GB1340418A (en) * 1971-06-29 1973-12-12 Jackson Bradwell Ltd Balancing machines
GB1390468A (en) * 1973-03-30 1975-04-16 Rit Rech Ind Therapeut Herpes simplex type 2 virus vaccine and method of production and use
JPS5649382A (en) * 1979-09-28 1981-05-02 Dainippon Pharmaceut Co Ltd 6-fluoro-7-cyclic amino-1,8-naphthylidine derivative and its salt
US4335105A (en) * 1979-11-13 1982-06-15 Iowa State University Research Foundation, Inc. Specific antigen vaccine for TGE in swine
US4709011A (en) * 1982-02-18 1987-11-24 University Patents, Inc. Materials and methods for herpes simplex virus vaccination
JPS6051120A (ja) * 1983-08-31 1985-03-22 Chemo Sero Therapeut Res Inst 単純ヘルペスサブユニットワクチン
US4642333A (en) * 1983-09-16 1987-02-10 Stanley Person Immunologically reactive non-glycosylated amino acid chains of glycoprotein B of herpes virus types 1 and 2
NL8303501A (nl) * 1983-10-12 1985-05-01 Centraal Diergeneeskundig Inst Deletiemutant van een herpesvirus en vaccin, dat dit virus bevat.
JPS6153226A (ja) * 1984-08-24 1986-03-17 Chemo Sero Therapeut Res Inst 単純ヘルペスサブユニツトワクチンの精製方法
EP0289550B1 (en) * 1986-10-20 1996-04-10 Chiron Corporation Vaccine for use in the therapeutic treatment of hsv
US5151267A (en) * 1988-07-15 1992-09-29 University Of Saskatchewan Bovine herpesvirus type 1 polypeptides and vaccines
US5585264A (en) * 1988-07-15 1996-12-17 University Of Saskatchewan Nucleotide sequences encoding recombinant bovine herpesvirus type-1 GI, GIII and GIV polypeptides
ES2141076T3 (es) * 1988-09-01 2000-03-16 Bayer Ag Proteina del receptor de rinovirus humano que inhibe la infectividad del virus.

Also Published As

Publication number Publication date
EP0618814A1 (en) 1994-10-12
WO1993011792A1 (en) 1993-06-24
EP0888777A3 (en) 1999-06-02
ATE178802T1 (de) 1999-04-15
US5585264A (en) 1996-12-17
EP0888777A2 (en) 1999-01-07
DE69228944T2 (de) 1999-12-02
EP0618814B1 (en) 1999-04-14
US5858989A (en) 1999-01-12
US5879895A (en) 1999-03-09
DE69228944D1 (de) 1999-05-20

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