CA2375825A1 - Complement-resistant non-mammalian dna viruses and uses thereof - Google Patents

Complement-resistant non-mammalian dna viruses and uses thereof Download PDF

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Publication number
CA2375825A1
CA2375825A1 CA002375825A CA2375825A CA2375825A1 CA 2375825 A1 CA2375825 A1 CA 2375825A1 CA 002375825 A CA002375825 A CA 002375825A CA 2375825 A CA2375825 A CA 2375825A CA 2375825 A1 CA2375825 A1 CA 2375825A1
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Prior art keywords
virus
mammalian
cell
cells
genome
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Abandoned
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CA002375825A
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English (en)
French (fr)
Inventor
Frederick M. Boyce
James G. Barsoum
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.)
General Hospital Corp
Biogen Inc
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Individual
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=23285067&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2375825(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Publication of CA2375825A1 publication Critical patent/CA2375825A1/en
Abandoned legal-status Critical Current

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/76—Viruses; Subviral particles; Bacteriophages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
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    • 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
    • C12N2710/14121—Viruses as such, e.g. new isolates, mutants or their genomic sequences
    • 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
    • C12N2710/14122—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
    • C12N2710/14011—Baculoviridae
    • C12N2710/14111—Nucleopolyhedrovirus, e.g. autographa californica nucleopolyhedrovirus
    • C12N2710/14132—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
    • 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
    • C12N2710/14011—Baculoviridae
    • C12N2710/14111—Nucleopolyhedrovirus, e.g. autographa californica nucleopolyhedrovirus
    • C12N2710/14151—Methods of production or purification of viral material
    • 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
    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/60—Vectors comprising as targeting moiety peptide derived from defined protein from viruses
    • C12N2810/6072—Vectors comprising as targeting moiety peptide derived from defined protein from viruses negative strand RNA viruses
    • C12N2810/6081—Vectors comprising as targeting moiety peptide derived from defined protein from viruses negative strand RNA viruses rhabdoviridae, e.g. VSV

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Genetics & Genomics (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Virology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Endocrinology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Obesity (AREA)
  • Plant Pathology (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Mycology (AREA)
  • Psychiatry (AREA)
  • Nutrition Science (AREA)
  • Hospice & Palliative Care (AREA)
CA002375825A 1999-06-10 2000-06-08 Complement-resistant non-mammalian dna viruses and uses thereof Abandoned CA2375825A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/329,368 1999-06-10
US09/329,368 US6183993B1 (en) 1996-09-11 1999-06-10 Complement-resistant non-mammalian DNA viruses and uses thereof
PCT/US2000/015670 WO2000077233A2 (en) 1999-06-10 2000-06-08 Complement-resistant non-mammalian dna viruses and uses thereof

Publications (1)

Publication Number Publication Date
CA2375825A1 true CA2375825A1 (en) 2000-12-21

Family

ID=23285067

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002375825A Abandoned CA2375825A1 (en) 1999-06-10 2000-06-08 Complement-resistant non-mammalian dna viruses and uses thereof

Country Status (6)

Country Link
US (1) US6183993B1 (https=)
EP (1) EP1192266A2 (https=)
JP (1) JP2003502051A (https=)
AU (1) AU5470100A (https=)
CA (1) CA2375825A1 (https=)
WO (1) WO2000077233A2 (https=)

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US6995006B2 (en) * 1997-09-05 2006-02-07 Targeted Genetics Corporation Methods for generating high titer helper-free preparations of released recombinant AAV vectors
US6346415B1 (en) 1997-10-21 2002-02-12 Targeted Genetics Corporation Transcriptionally-activated AAV inverted terminal repeats (ITRS) for use with recombinant AAV vectors
US7074983B2 (en) 1999-11-19 2006-07-11 Kirin Beer Kabushiki Kaisha Transgenic bovine comprising human immunoglobulin loci and producing human immunoglobulin
US7414170B2 (en) * 1999-11-19 2008-08-19 Kirin Beer Kabushiki Kaisha Transgenic bovines capable of human antibody production
WO2001035735A1 (en) * 1999-11-19 2001-05-25 Hematech, Llc Production of ungulates, preferably bovines that produce human immunoglobulins
US7820878B2 (en) * 1999-11-19 2010-10-26 Kyowa Hakko Kirin Co., Ltd. Production of ungulates, preferably bovines that produce human immunoglobulins
US20040146918A1 (en) * 2000-02-18 2004-07-29 Weiner Michael L. Hybrid nucleic acid assembly
WO2002042468A2 (en) * 2000-11-27 2002-05-30 Geron Corporation Glycosyltransferase vectors for treating cancer
CA2440342A1 (en) 2001-03-12 2002-09-19 Ark Therapeutics Ltd. Avidin-pseudotyped viral vectors and their use
GB0128620D0 (en) * 2001-11-29 2002-01-23 Ark Therapeutics Ltd Gene delivery of a viral vector
GB0119852D0 (en) * 2001-08-15 2001-10-10 Univ York Baculovirus
WO2003020322A1 (de) * 2001-09-04 2003-03-13 DeveloGen Aktiengesellschaft für entwicklungsbiologische Forschung Vektor zur induktion einer immunantwort
ES2627445T3 (es) 2002-05-01 2017-07-28 Miltenyi Biotec Technology, Inc. Partículas de vector de lentivirus resistentes a la inactivación por el complemento
US7416890B2 (en) 2002-09-25 2008-08-26 Osaka Industrial Promotion Organization Baculovirus vector, method of producing thereof and method of gene transfer
JP4431039B2 (ja) * 2002-09-25 2010-03-10 財団法人大阪産業振興機構 バキュロウイルスベクター、バキュロウイルスベクター製造方法及び遺伝子導入方法
WO2004044156A2 (en) * 2002-11-08 2004-05-27 Hematech, Llc Transgenic ungulates having reduced prion protein activity and uses thereof
US7527967B2 (en) * 2003-11-25 2009-05-05 Academia Sinica Recombinant baculovirus and virus-like particle
WO2005072364A2 (en) * 2004-01-27 2005-08-11 University Of Florida A modified baculovirus expression system for production of pseudotyped raav vector
US20050196864A1 (en) * 2004-02-10 2005-09-08 Goldman Steven A. Induction and high-yield preparative purification of mesencephalic dopaminergic neuronal progenitor cells and dopaminergic neurons from human embryonic stem cells
NZ550106A (en) * 2004-04-22 2009-06-26 Kyowa Hakko Kirin Co Ltd Transgenic animals and uses thereof
GB0425739D0 (en) * 2004-11-23 2004-12-22 Procure Therapeutics Ltd Humanised baculovirus 2
JP5006312B2 (ja) * 2005-05-27 2012-08-22 エイジェンシー フォー サイエンス， テクノロジー アンド リサーチ バキュロウイルスベクターを使用して核酸分子を胚性幹細胞に送達する方法
US9333249B2 (en) 2006-02-09 2016-05-10 Educational Foundation Jichi Medical University Recombinant baculovirus vaccine
TWI477602B (zh) 2006-02-09 2015-03-21 Educational Foundation Jichi Medical Univ Novel viral vector
DE102006021406B4 (de) * 2006-05-08 2008-08-07 B.R.A.H.M.S Aktiengesellschaft In vitro Verfahren zur Früherkennung von arznei- und suchtmittelinduzierten Leberschäden und zur Erkennung der bereits erreichten Stufe der Leberschädigung

Family Cites Families (17)

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US4745051A (en) 1983-05-27 1988-05-17 The Texas A&M University System Method for producing a recombinant baculovirus expression vector
US4879236A (en) 1984-05-16 1989-11-07 The Texas A&M University System Method for producing a recombinant baculovirus expression vector
FR2579224B1 (fr) 1985-03-25 1987-05-22 Genetica Procede de preparation microbiologique de la serum-albumine humaine
US5004687A (en) 1985-05-21 1991-04-02 University Of Georgia Research Foundation, Inc. Insect virus vector with broadened host range
US5106741A (en) 1985-12-20 1992-04-21 The Upjohn Company Tissue plasminogen activator (TPA) analogs
DE69131908T3 (de) 1991-02-19 2008-04-03 Oxford Biomedica (Uk) Ltd. Viruspartikel mit veraendertem wirtspektrum
US5476781A (en) 1991-02-19 1995-12-19 University Of Florida Research Foundation, Inc. Entomopoxvirus spheroidin gene sequences
AUPM405794A0 (en) * 1994-02-23 1994-03-17 University Of Queensland, The A process for producing viruses or viral proteins
DE4407859C1 (de) 1994-03-04 1995-03-02 Max Planck Gesellschaft Vektor für die leberspezifische Gentherapie
FR2718150B1 (fr) 1994-03-29 1996-04-26 Rhone Poulenc Rorer Sa Virus recombinants, préparation et utilisation en thérapie génique.
CA2200835A1 (en) 1994-09-23 1996-03-28 Frederick M. Boyce Use of a non-mammalian dna virus to express an exogenous gene in a mammalian cell
CA2264953C (en) * 1996-08-16 2008-09-30 The Texas A & M University System Modifying insect cell gylcosylation pathways with baculovirus expression vectors
US6281009B1 (en) * 1996-09-11 2001-08-28 The General Hospital Corporation Use of a non-mammalian DNA virus to express an exogenous gene in a mammalian cell
BR9712978A (pt) * 1996-09-11 2000-04-18 Gen Hospital Corp Vìrus de dna de não-mamìferos possuindo uma proteìna de revestimento alterada
GB9708698D0 (en) * 1997-04-29 1997-06-18 Imperial College Materials for therapy
US6106825A (en) * 1997-05-07 2000-08-22 University Of Florida Entomopoxvirus-vertebrate gene delivery vector and method
DE19735593C2 (de) * 1997-08-15 1999-08-26 Hepavec Ag Fuer Gentherapie Hüllprotein-modifizierter Baculovirus-Vektor für die Gentherapie

Also Published As

Publication number Publication date
US6183993B1 (en) 2001-02-06
EP1192266A2 (en) 2002-04-03
WO2000077233A2 (en) 2000-12-21
JP2003502051A (ja) 2003-01-21
WO2000077233A9 (en) 2002-06-20
WO2000077233A3 (en) 2001-12-06
AU5470100A (en) 2001-01-02

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