OA10085A - Recombinant virus vectors encoding human papillomavirus proteins - Google Patents

Recombinant virus vectors encoding human papillomavirus proteins Download PDF

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Publication number
OA10085A
OA10085A OA60411A OA60411A OA10085A OA 10085 A OA10085 A OA 10085A OA 60411 A OA60411 A OA 60411A OA 60411 A OA60411 A OA 60411A OA 10085 A OA10085 A OA 10085A
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virus
proteins
recombinant
recombinant virus
sequence
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OA60411A
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English (en)
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Michael Edward Griffith Boursnell
Stephen Charles Inglis
Alan James Munro
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Cantab Pharmaceuticals Res Ltd
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Publication of OA10085A publication Critical patent/OA10085A/en

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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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • 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
    • A61P31/04—Antibacterial agents
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
    • C12P41/004—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of alcohol- or thiol groups in the enantiomers or the inverse reaction
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • 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
    • C12N2710/20011—Papillomaviridae
    • C12N2710/20022—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
    • C12N2710/24011—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

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

Claims (21)

  1. 01 0085 CLAXMS: 10
    1. A recombinant virus vector for use as aninununotherapeutic or vaccine which comprises at least onepair of nucléotide sequences heterologous to said viruswhich encode part of ail of human papillomavirus (HPV)wild-type proteins or mutant proteins immunologicallycross-reactive with said wild-type proteins and whichhâve sufficient sequence homology that recombinationbetween them might be expected; wherein said pair of nucléotide sequences arearranged in said virus vector such that they are invertedwith respect to each other to reduce the likelihood ofrecombination events leading to loss of part or ail ofsaid sequences and said virus vector is able to infect amammalian host cell and express as polypeptide theheterologous nucléotide sequences in said host cell.
  2. 2. A recombinant virus vector according to claim 1wherein the pair of nucléotide sequences encode part orail of the HPV wild-type proteins HPV16E7 and HPV18E7 ormutant proteins immunologically cross-reactive therewith.
  3. 3. A recombinant virus vector according to claim 1wherein the pair of nucléotide sequences encode part orail of the HPV wild-type proteins HPV16E6 and HPV18E6 ormutant proteins immunologically cross-reactive therewith. A recombinant virus vector according to claim 2 «J 010085 which comprises a further pair of nucléotide sequenceswhich encode part or ail of the HPV wild-type proteinsHPV16E6 and HPV18E6 or mutant proteins immunologically cross-reactive therewith.
  4. 5. A recombinant virus vector according to any oneof the preceding claims wherein two or more nucléotidesequences of different said pairs may be fused togetherto form a single open reading frame. flO
  5. 6. A recombinant virus vector according to claim 5wherein the fusions are via a single codon encoding a small neutral amino acid.
  6. 7. A recombinant virus vector according to claim 6wherein the amino acid is glycine. 15
  7. 8. A recombinant virus vector according to claim 4in which the pairs of nucléotide sequences are arrangedin the virus vector according to any one of the optionsas shown in Figure 26. 20 25
  8. 9. A recombinant virus vector according to claim 8 which comprises a first open reading frame having a fused geneticsequence encoding part or ail of the wild-type proteinsE6 and E7 from HPV16; and a separate second open readfng frame having a fusedgenetic sequence encoding part or ail of the wild-type 010085 10 15 25 proteins E6 and E7 from HPV18; wherein the first and second open reading frames may be inverted with respect to one another whereby either: i) the E6 coding sequences of HPV16 and HPV18 areboth located between the E7 coding sequences of HPV16 andHPV18; or ii) the E7 coding sequences of HPV16 and HPV18 areboth located between the E6 coding sequences of HPV16 andHPV18; and wherein any of said wild-type proteins may bereplaced by a mutant protein immunologically cross- reactive therewith.
  9. 10. A recombinant virus vector according to claim 9wherein each of the first and second open reading frameshas a corresponding promoter and the two open readingframes each with its promoter, are arranged next to each other in the virus.
  10. 11. A recombinant virus vector according to claim 10 wherein either: i) the promoters are located between the first andsecond open reading frames whereby the open readingframes are transcribed outwardly; or ii ) the promoters are located outside the first andsecond open reading frames whereby the open readingframes are transcribed inwardly.
  11. 12. A recombinant virus vector according to any one J 010085 ——- 46 10 of daims 8 to 11 which comprises a first open reading frame having a fused genetic sequence encoding part or ail of the wild-type proteins E6 and E7 from HPV16; and a separate second open reading frame having a fusedgenetic sequence encoding part or ail of the wild-typeproteins E6 and E7 from HPV18; wherein the E6 coding sequences of HPV16 and HPV18are both located between the E7 coding sequences of HPV16 and HPV18; and each open reading frame has a correspondingpromoter, the promoters being located between the firstand second open reading frames whereby the open readingframes are transcribed outwardly; and wherein any of said wild-type proteins may bereplaced by a mutant protein immunologically cross- reactive therewith.
  12. 13. A recombinant virus vector according to any oneof the preceding daims wherein eirher or both of thenucléotide sequences in a said pair of nucléotidesequences are altered to make them less homologous thanan équivalent pair of nucléotide sequences encoding wild-type HPV proteins.
  13. 14. A recombinant virus vector according to claim13 wherein the alteration in nucléotide sequence does notresuit in an alteration of the encoded amino acid sequence. 1 010085
  14. 15. A recombinant virus vector according to claim 2wherein the wild-type proteins HPV16E7 and HPV18E7 arereplaced with mutant proteins which are substantiallyhomologous to said wild-type proteins and in which theresidues cys 24 and glu 25 of wild-type protein HPV16E7and the residues cys 27 and glu 29 of wild-type proteinHPV18E7 are replaced with glycine residues.
    15. A recombinant virus vector according to any oneof the preceding daims wherein said heterologousnucléotide sequences may comprise part or ail of thesequences shown in Figures l(a) and l(b).
  15. 17. A recombinant virus vector according to any oneof the preceding daims which is derivable from vaccinia virus.
  16. 18. A recombinant virus vector according to any oneof the preceding daims wherein the nucléotide sequencesare inserted into the virus vector at one or more neutralsites, the disruption of which by the insertion of thenucléotide sequences does not substantially adverselyaffect viral functions relating to the réplicativeability of the virus in the mammalian cell.
  17. 19. A recombinant virus vector according to claim18'which is derivable from vaccinia -. irps and wherein the neutral sites may be one or more of: 48 010085 ισ A) the gap between SalIF17R and SalIF19R of strainWR comprising at least part of the sequence CTATCTACCAGATTATTATGTGTTATAAGGTACTTTTTCT; B) the gap between SalIF19R and SalIF20.5R ofstrain WR comprising at least part of the sequence TATTGTGCTACTGATTCTTCACAGACTGAAGATTGTTGAA; C) a région in SalIG2R of strain WR comprising atleast part of the sequence TCTCTTAAAATGGTTGAGACCAAGCTTCGTTGTAGAAACA; D) a région in HindB3.5R of strain WR comprisingat least part of the sequence TGAGGCTACCTCGACATACGTGTGCGCTATCAAAGTGGAA; E) a sequence having at least 90% sequence 15 20 25 homology to those sequences A) to D) identified above.
  18. 20. A method for making a recombinant virus vectoraccording to daim 18 or claim 19 which comprisesinserting a said heterologous nucléotide sequence into one or more neutral sites in a virus vector, the disruption of such a site by said insertion will notsubstantially adversely affect the réplicative ability of the virus and wherein the neutral site has been previously identified by: (a) analysing a viral genome toidentify open reading frames which are likely to encodefunctional genes; and (b) selecting sites between openreading frames for functional genes or sites withinsequences for non-functional genes.
  19. 21. A recombinant virus vector obtainable by the 49 010085 method of claim 20.
  20. 22. A method which comprises using a recombinantvirus vector according to any one of claims 1 to 19 or toclaim 21 to manufacture a médicament for use as animmunotherapeutic or vaccine against a condition thoughtto be caused by HPV infection, for example cervical cancer.
  21. 23. A method which comprises using a recombinantvirus vector according to any one of claims 1 to 19 or toclaim 21 to specifically activate cells of the immuneSystem to HPV proteins. I
OA60411A 1991-03-14 1993-09-14 Recombinant virus vectors encoding human papillomavirus proteins OA10085A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB919105383A GB9105383D0 (en) 1991-03-14 1991-03-14 An immunotherapeutic for cervical cancer

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OA10085A true OA10085A (en) 1996-12-18

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US (1) US5719054A (fr)
EP (1) EP0576471B1 (fr)
JP (1) JPH06505626A (fr)
KR (1) KR100240183B1 (fr)
CN (1) CN1090239C (fr)
AT (1) ATE208824T1 (fr)
AU (1) AU665531B2 (fr)
BR (1) BR9205771A (fr)
CA (1) CA2106069A1 (fr)
DE (1) DE69232201T2 (fr)
DK (1) DK0576471T3 (fr)
ES (1) ES2168258T3 (fr)
GB (1) GB9105383D0 (fr)
MX (1) MX9205131A (fr)
NO (1) NO310033B1 (fr)
OA (1) OA10085A (fr)
WO (1) WO1992016636A1 (fr)

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AU1414792A (en) 1992-10-21
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