WO1998042847A2 - Papillomvirus-hauptcapsid-proteins und deren verwendung in diagnose, therapie und vakzinierung - Google Patents
Papillomvirus-hauptcapsid-proteins und deren verwendung in diagnose, therapie und vakzinierung Download PDFInfo
- Publication number
- WO1998042847A2 WO1998042847A2 PCT/DE1998/000876 DE9800876W WO9842847A2 WO 1998042847 A2 WO1998042847 A2 WO 1998042847A2 DE 9800876 W DE9800876 W DE 9800876W WO 9842847 A2 WO9842847 A2 WO 9842847A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dna
- papilloma virus
- protein
- papillomavirus
- virus
- Prior art date
Links
- 241001631646 Papillomaviridae Species 0.000 title claims abstract description 64
- 108090000565 Capsid Proteins Proteins 0.000 title claims abstract description 10
- 102100023321 Ceruloplasmin Human genes 0.000 title claims abstract description 9
- 238000003745 diagnosis Methods 0.000 title claims abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 6
- 238000002255 vaccination Methods 0.000 title claims abstract description 6
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 23
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 23
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims description 15
- 239000013598 vector Substances 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 13
- 239000013604 expression vector Substances 0.000 claims description 12
- 238000009396 hybridization Methods 0.000 claims description 12
- 239000002245 particle Substances 0.000 claims description 12
- 238000010367 cloning Methods 0.000 claims description 9
- 238000001574 biopsy Methods 0.000 claims description 6
- 208000034179 Neoplasms, Glandular and Epithelial Diseases 0.000 claims description 5
- 208000010932 epithelial neoplasm Diseases 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 238000012163 sequencing technique Methods 0.000 claims description 4
- 208000009608 Papillomavirus Infections Diseases 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 238000012258 culturing Methods 0.000 claims 1
- 108020004414 DNA Proteins 0.000 description 85
- 241000700605 Viruses Species 0.000 description 18
- 239000013612 plasmid Substances 0.000 description 10
- 241000588724 Escherichia coli Species 0.000 description 6
- 201000009030 Carcinoma Diseases 0.000 description 5
- 239000011543 agarose gel Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 241000701959 Escherichia virus Lambda Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 241000700618 Vaccinia virus Species 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 201000010153 skin papilloma Diseases 0.000 description 3
- 206010059313 Anogenital warts Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 238000012270 DNA recombination Methods 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101710121996 Hexon protein p72 Proteins 0.000 description 2
- 101710125418 Major capsid protein Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 101710157639 Minor capsid protein Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 101710136297 Protein VP2 Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 208000000260 Warts Diseases 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000234 capsid Anatomy 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 210000004392 genitalia Anatomy 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000007169 ligase reaction Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108091092566 Extrachromosomal DNA Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 101710112324 Glutathione S-transferase L1 Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 201000004196 common wart Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C12N2710/20011—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
- C12N2710/20011—Papillomaviridae
- C12N2710/20023—Virus like particles [VLP]
Definitions
- the invention relates to a DNA which codes for a peptide of a papillomavirus main capsid protein or a papillomavirus genome. Furthermore, the invention relates to proteins encoded by the papilloma virus genome and antibodies directed against them, and to their use in diagnosis, therapy and vaccination.
- HP viruses Human papilloma viruses
- benign e.g. Warts, genital condylomas, and malignancies, e.g. Carcinomas of the skin and uterus, epithelial neoplasms (see Zur Hausen, H., Biochimica et Biophysica Acta (BBA) 1 288, (1 996), pages 55-78).
- HP viruses are also being considered for the development of malignant tumors in the oropharyngeal area (cf. Zur Hausen, H., Curr. Top. Microbiol. Immunol. 78, (1 977), pages 1-30).
- Papilloma viruses have an icosahedral capsid without a shell, in which a circular, double-stranded DNA molecule of approximately 7900 bp is present.
- the capsid comprises a major capsid protein (L1) and a minor capsid protein (L2). Both proteins, coexpressed or L1 expressed alone, lead to the formation of virus-like particles in vitro (cf. Kirnbauer, R. et al., Journal of Virology, (1 993), pages 6929-6936).
- Papilloma viruses cannot be propagated in monolayer cell culture. Their characterization is therefore extremely difficult, and the detection of papilloma viruses already creates considerable problems. This is particularly true for papilloma viruses in skin carcinomas.
- the object of the present invention is therefore to provide an agent with which papilloma viruses, in particular in carcinomas of the skin, can be detected.
- a means should also be provided to treat these papillomaviruses therapeutically.
- the invention thus relates to a DNA coding for a peptide of a papillomavirus main capsid protein (L1), the peptide representing the amino acid sequence of FIGS. 1, 2, 3, 4, 5, 6 , Fig. 7, Fig. 8 or Fig. 9 or one of them by one or more amino acids different amino acid sequence.
- L1 papillomavirus main capsid protein
- Another object of the invention is a DNA coding for a peptide of a papillomavirus main capsid protein, the DNA being the base sequence of FIG. 1, FIG. 2, FIG. 3, FIG. 4, FIG. 5, FIG. 6, FIG 7, 8 or 9, or a base sequence different from one or more base pairs.
- FIG. 2 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid DL250 at the DSM under DSM 1 1 406 on 1 February 3, 1 997.
- FIG. 3 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from L1 of a papilloma virus. That DNA was deposited as plasmid DL253 at DSM under DSM 1 1407 on Feb. 3, 1 997.
- FIG. 4 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from L1 of a papilloma virus. This DNA was deposited as plasmid DL267 with the DSM under DSM 1 1 408 on February 3, 1 997.
- FIG. 5 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was plasmid DL284 at DSM under DSM 1 1409 on the 3rd of February. 1 997 deposited.
- FIG. 6 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid DL285 with the DSM under DSM 1 1 41 0 on 1 February 3, 997.
- FIG. 7 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from L1 of a papilloma virus. This DNA was deposited as plasmid DL287 at DSM under DSM 1 141 1 on February 13, 1 997.
- FIG. 8 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from L1 of a papilloma virus. This DNA was deposited as plasmid DL297 at the DSM under DSM 1 141 2 on 1 February 3, 1 997.
- FIG. 9 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide of L1 of a papilloma virus.
- This DNA was deposited as plasmid DL332 at the DSM under DSM 1 141 3 on February 1, 1 997.
- the above DNA was compared to the DNA of known papilloma viruses. Sequence homology studies were carried out. A homology that is less than 90% shows a DNA according to the invention as a new HP virus.
- the DNAs according to the invention have the following sequence homologies with known papilloma viruses:
- the above DNA can be present in a vector or expression vector.
- examples of such are known to the person skilled in the art.
- these are e.g. pGEMEX, pUC derivatives, pGEM-T and pGEX-2T.
- yeast e.g. to call pYl OO and Ycpad l
- animal cells e.g. pKCR, pEF-BOS, cDM8 and pCEV4 must be specified.
- suitable cells in order to express the above DNA present in an expression vector.
- suitable cells include the E. coli strains HB101, DH1, x1776, JM101, JM 109 and XU-Blue, the yeast strain Saccharomyces cerevisiae and the animal cells L, NH-3T3, FM3A, CHO, COS, Vero, and Hey.
- papilloma virus genome comprising the above DNA.
- the term "papilloma virus genome” also includes an incomplete genome, i.e. Fragments of a papilloma virus genome comprising the above DNA. This can e.g. a DNA coding for L1 or a part thereof.
- a common method can be used to provide the above papillomavirus genome.
- a method comprising the following method steps is favorable:
- epithelial neoplasm encompasses any neoplasms of epithelial tissue in humans and animals. Examples of such neoplasms are warts, condylomas in the genital area and carcinomas of the skin. The latter are lying preferably used to isolate the above papillomavirus genome.
- vector includes any vector suitable for cloning chromosomal or extrachromosomal DNA.
- examples of such vectors are cosmids such as pWE1 5 and Super Cos1, and phages such as ⁇ -phages, e.g. ⁇ ZAP Expressvector, ⁇ ZAPII Vector and ⁇ gt10 Vector.
- ⁇ phages are preferably used.
- the above vectors are known and are available from Stratagene.
- Papillomavirus genomes according to the invention can be integrated in chromosomal DNA or extrachromosomal. Methods are known to the person skilled in the art to clarify this. He also knows how to find the optimal restriction enzymes for cloning the papillomavirus genomes. It will be based on genomes of known papilloma viruses. In particular, the person skilled in the art will observe the aforementioned HP viruses accordingly.
- a papilloma virus genome designated DL231 -G is described by way of example.
- the total DNA is isolated from a biopsy of a squamous cell carcinoma, cleaved with BamHI and electrophoretically separated in an agarose gel.
- the agarose gel is then subjected to a blotting process, whereby the DNA is transferred to a nitrocellulose membrane.
- This is used in a hybridization process in which the DNA from FIG. 1, possibly in combination with a DNA from HP virus 5c, is used as the labeled sample. Hybridization with the papilloma virus DNA present in the total DNA is obtained.
- the above total DNA cleaved with BamHI is cloned in a ⁇ phage.
- the corresponding clones ie the clones containing the papillomavirus DNA, are identified by hybridization with the DNA from FIG. 1, possibly in combination with a DNA from the HP virus 5c.
- the insert of these clones is then subjected to a further cloning in a plasmid vector, whereby a clone is obtained which contains the papillomavirus genome DL231 -G.
- the genome is confirmed by sequencing.
- papillomavirus genomes are provided. They are named according to the DNAs used for their preparation, with: DL250-G, DL253-G, DL267-G, DL284-G, DL285-G, DL287-G, DL297-G or DL332-G.
- Another object of the invention is a protein encoded by the above papillomavirus genome.
- a protein is e.g. a major capsid protein (L1) or a minor capsid protein (L2).
- L1 or L2 of the papilloma virus genome DL231 -G is described as an example.
- the HP virus 5c which is related to the DNA of FIG. 1, is used for this purpose.
- the complete sequence and the position of individual DNA regions coding for proteins are known from this.
- These DNAs are identified on the papillomavirus genome DL231 -G by parallel restriction cleavages of both genomes and subsequent hybridization with different fragments relating to L1 or L2 coding DNA. They are confirmed by sequencing.
- the DNA coding for L1 is called DL231 -G-L1 DNA and the DNA coding for L2 is called DL231 -G-L2 DNA.
- the DNA coding for L1 or L2 is inserted into an expression vector.
- E. coli examples of such for E. coli, yeast and animal cells are mentioned above.
- vector pGEX-2T for expression in E. coli (cf. Kirnbauer, R. et al., Supra).
- pGEX-2T-DL231 -G-L1 or pGEX-2T-DL1 7-G-L2 is obtained.
- these expression vectors express a glutathione S-transferase-L1 or glutathione S-transferase-L2 fusion protein. These proteins are purified in the usual way.
- the Bacculovirus or vaccinia virus system called.
- Expression vectors that can be used for this are, for example, pEV mod. and pSynwtVI " for the bacculovirus system (cf. Kirnbauer, R. et al., supra).
- vectors with the vaccinia virus are in particular" early "(p7. 5 k) - or” late "( Psynth, pl 1 K) promoter (cf. Hagensee, M., E.
- the bacculovirus system is preferred DNA encoding L1 or L2 in pEV mod. PEVmod.-DL231 -G-L1 or pEVmod.-DL231 -G-L2 is obtained.
- a particle comprises an L1 protein
- an L1 protein in the latter case it contains an L1 protein as well as an L1 protein.
- a virus-like particle of the latter case is also obtained by inserting the above DL231 -G-L1 and DL231 -G-L2 DNAs together into the expression vector pSynwtVI " and the obtained pSynwtVI " DL231 -G-L1 / L2 for infection of SF-9 insect cells is used.
- the above virus-like particles are cleaned in the usual way. They also represent an object of the invention.
- Another object of the invention is an antibody directed against an above protein or virus-like particle.
- Such is produced in the usual way. It is described by way of example for the production of an antibody which is directed against a virus-like particle comprising L1 of DL231 -G.
- the virus-like particle BALB / c mice is injected subcutaneously. This injection is repeated every 3 weeks. About 2 weeks after the last injection, the serum containing the antibody is isolated and tested in the usual way.
- the antibody is a monoclonal antibody.
- the mice are produced Spleen cells removed and fused with myeloma cells in the usual way. The further cloning is also carried out according to known methods.
- the present invention makes it possible to detect papilloma viruses, in particular in carcinomas of the skin.
- the DNA according to the invention can be used as such or encompassed by a further DNA.
- the latter can also be a papilloma virus gome or part of it.
- the present invention also enables the provision of previously unknown papilloma viruses. These are found particularly in carcinomas of the skin. Furthermore, the invention provides proteins and virus-like particles which are due to these papillomaviruses. Antibodies are also provided which are directed against these proteins or particles.
- the present invention thus makes it possible to take diagnostic and therapeutic measures for papillomavirus diseases. In addition, it provides the opportunity to build a vaccine against papillomavirus infections.
- the present invention thus represents a breakthrough in the field of papilloma virus research.
- Example 1 Identification of the papilloma virus genome DL231 -G
- the total DNA is isolated from a biopsy of Verruca vulgaris. 10 yg of this DNA are cleaved with the BamHI restriction enzyme and electrophoresed in a 0.5% agarose gel. At the same time, 10 ⁇ g of the above DNA, which has not been cleaved, are also separated.
- the agarose gel is subjected to a blotting process, whereby the DNA from the agarose gel is transferred to a nitrocellulose membrane. This is used in a hybridization process in which the above 1 in combination with HP virus 5c DNA is used as the p 32 -labeled sample. Hybridization with the blotted DNA is obtained.
- Example 2 Cloning of the papilloma virus genome DL231 -G
- the biopsy DNA obtained from Example 1 is cleaved with the restriction enzyme BamHI.
- the fragments obtained are used in a ligase reaction in which the BamHI-cleaved and dephosphorylated vector ⁇ ZAP Express is also present.
- the recombinant DNA molecules obtained in this way are packaged in bacteriophages and used to infect bacteria.
- the ZAP Express Vector Kit offered by Stratagene is used for these process steps.
- the phage plaques obtained are then subjected to a hybridization process in which the p 32 -labeled DNA from FIG. 1 used in Example 1 is used in combination with p 32 -labeled HP virus 5c DNA. Hybridization with corresponding phage plaques is obtained.
- the BamHI fragments of DL231 -G are isolated from these and used together with a BamHI-cleaved, dephosphorylated plasmid vector, pBluescript, in a further ligase reaction.
- the recombinant DNA molecules obtained are used to transform bacteria, E. coli XL1-Blue.
- a bacterial clone containing the papillomavirus genome DL231 -G is identified by restriction cleavage or hybridization with the above DNA samples.
- the plasmid of this bacterial clone is designated pBlue-DL231 -G.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Engineering & Computer Science (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP54469698A JP2001520519A (ja) | 1997-03-25 | 1998-03-24 | パピローマウイルス主要カプシドタンパク質ならびに診断、治療およびワクチン接種におけるその使用 |
EP98928070A EP0972047A2 (de) | 1997-03-25 | 1998-03-24 | Papillomviren-hauptcapsid-proteins und deren verwendung in diagnose, therapie und vakzinierung |
US09/402,016 US6610303B1 (en) | 1997-03-25 | 1998-03-24 | Papilloma viruses, products for the detection thereof as well as for treating diseases caused by them |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19712541A DE19712541C1 (de) | 1997-03-25 | 1997-03-25 | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen |
DE19712541.7 | 1997-03-25 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1998042847A2 true WO1998042847A2 (de) | 1998-10-01 |
WO1998042847A3 WO1998042847A3 (de) | 1999-03-11 |
Family
ID=7824586
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE1998/000876 WO1998042847A2 (de) | 1997-03-25 | 1998-03-24 | Papillomvirus-hauptcapsid-proteins und deren verwendung in diagnose, therapie und vakzinierung |
Country Status (5)
Country | Link |
---|---|
US (1) | US6610303B1 (de) |
EP (1) | EP0972047A2 (de) |
JP (1) | JP2001520519A (de) |
DE (1) | DE19712541C1 (de) |
WO (1) | WO1998042847A2 (de) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999009177A2 (de) * | 1997-08-13 | 1999-02-25 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
US6228368B1 (en) | 1997-10-06 | 2001-05-08 | Loyola University Of Chicago | Papilloma virus capsomere formulations and method of use |
US6251406B1 (en) | 1996-10-09 | 2001-06-26 | Btg International Limited | Attenuated microorganism strains and their uses |
US7094541B2 (en) | 2001-08-31 | 2006-08-22 | Gen-Probe Incorporated | Assay for detection of human parvovirus B19 nucleic acid |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2011258501B2 (en) | 2010-05-25 | 2016-07-07 | Qiagen Gaithersburg, Inc. | Fast results hybrid capture assay and associated strategically-truncated probes |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997004099A2 (de) * | 1995-07-19 | 1997-02-06 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
WO1998023752A2 (de) * | 1996-11-26 | 1998-06-04 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2661921B1 (fr) * | 1990-05-11 | 1992-08-07 | Pasteur Institut | Sonde a papillomavirus (hpv66), notamment pour le diagnostic in vitro d'infections a papillomavirus, pouvant s'accompagner de neoplasies genitales, et produits genetiquement et immunologiquement lies a ce papillomavirus. |
-
1997
- 1997-03-25 DE DE19712541A patent/DE19712541C1/de not_active Expired - Fee Related
-
1998
- 1998-03-24 US US09/402,016 patent/US6610303B1/en not_active Expired - Fee Related
- 1998-03-24 EP EP98928070A patent/EP0972047A2/de not_active Withdrawn
- 1998-03-24 JP JP54469698A patent/JP2001520519A/ja active Pending
- 1998-03-24 WO PCT/DE1998/000876 patent/WO1998042847A2/de not_active Application Discontinuation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997004099A2 (de) * | 1995-07-19 | 1997-02-06 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
WO1998023752A2 (de) * | 1996-11-26 | 1998-06-04 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
Non-Patent Citations (4)
Title |
---|
ASTORI, G. ET AL.: "Human papillomaviruses are commonly found in normal skin of immunocompetent hosts" JOURNAL OF INVESTIGATIVE DERMATOLOGY, Bd. 110, Nr. 5, 1998, Seiten 752-755, XP002083615 * |
BERKHOUT, R.J. ET AL.: "Nested PCR approach for detection and typing of epidermodysplasia verruciformis-associated human papillomavirus types in cutaneous cancers from renal transplant recipients" JOURNAL CLINICAL MICROBIOLOGY, Bd. 33, 1995, Seiten 690-695, XP002083613 in der Anmeldung erw{hnt * |
DE VILLIERS, E.M. ET AL.: "Prevailing Papillomavirus types in nonmelanoma carcinomas of the skin in renal allograft recipients" INTERNATIONAL JOURNAL OF CANCER, Bd. 73, Nr. 3, 4. November 1997, Seiten 356-361, XP002064130 * |
DELIUS, H. & HOFMANN, B.: "Primer-directed sequencing of human papillomavirus types" CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY, Bd. 186, 1994, Seiten 13-31, XP002083614 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6251406B1 (en) | 1996-10-09 | 2001-06-26 | Btg International Limited | Attenuated microorganism strains and their uses |
US6458368B1 (en) | 1996-10-09 | 2002-10-01 | Btg International Limited | Attenuated microorganism strains expressing HPV proteins |
WO1999009177A2 (de) * | 1997-08-13 | 1999-02-25 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
WO1999009177A3 (de) * | 1997-08-13 | 1999-08-12 | Deutsches Krebsforsch | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
US6488935B1 (en) | 1997-08-13 | 2002-12-03 | Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts | Papilloma viruses, products for the detection thereof as well as for treating diseases caused by them |
US6228368B1 (en) | 1997-10-06 | 2001-05-08 | Loyola University Of Chicago | Papilloma virus capsomere formulations and method of use |
US7371391B2 (en) | 1997-10-06 | 2008-05-13 | Loyola University Of Chicago | Papilloma virus capsomere vaccine formulations and methods of use |
US7754430B2 (en) | 1997-10-06 | 2010-07-13 | Loyola University Of Chicago | Papilloma virus capsomere vaccine formulations and methods of use |
US7094541B2 (en) | 2001-08-31 | 2006-08-22 | Gen-Probe Incorporated | Assay for detection of human parvovirus B19 nucleic acid |
Also Published As
Publication number | Publication date |
---|---|
EP0972047A2 (de) | 2000-01-19 |
DE19712541C1 (de) | 1998-11-05 |
WO1998042847A3 (de) | 1999-03-11 |
US6610303B1 (en) | 2003-08-26 |
JP2001520519A (ja) | 2001-10-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0809700B1 (de) | Papillomavirusähnliche partikel, fusionsproteine sowie verfahren zu deren herstellung | |
DE69434383T2 (de) | Herstellung von menschlichem papillomavirus hüllprotein und virus-ähnlichen teilchen | |
DE19543553B4 (de) | VP-Antigene des JC-Virus | |
DE69836753T2 (de) | Papilloma virus capsomere impfstoff-formulierungen und deren verwendungen | |
DE68922336T2 (de) | Sonden für Papilloma-Virus (HPV49, HPV50, HPV54, HPV55), zu diesem Papilloma-Virus genetisch und immunologisch verwandte Produkte und in vitro Methoden zur Diagnose von Papilloma-Virusinfektionen und Herstellung von Antikörpern gegen diese Papilloma-Viren. | |
DE69104380T2 (de) | Vom genom des papillomavirus-hpv-39 abgeleitete dns-sequenzen, deren anwendung in der in vitro-diagnose und zur herstellung einer immunogenenzusammensetzung. | |
DE69531308T2 (de) | Verfahren zur Herstellung von gereinigten papillomavirus Proteinen | |
DE69631586T2 (de) | Für menschliches papillomavirus stamm 18 kodierende dns | |
DE4415743C2 (de) | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen | |
DE19526386C1 (de) | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen | |
DE69933875T2 (de) | Protein-verabreichungssystem, das dem menschlichen papillomavirus ähnliche partikel benützt. | |
DE19648962C1 (de) | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen | |
DE19735118C1 (de) | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen | |
DE19712541C1 (de) | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen | |
DE4447664C2 (de) | Fusionsproteine, Verfahren zu deren Herstellung sowie deren Anwendung | |
DE19840263C1 (de) | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen | |
DE10059631A1 (de) | T-Zellepitope des Papillomavirus L1-und E7-Proteins und ihre Verwendung in Diagnostik und Therapie | |
DE4332596A1 (de) | Monoklonale Antikörper | |
DE19526752C2 (de) | Hocheffiziente Bildung von Papillomavirusähnlichen Partikeln | |
DE19649606C1 (de) | Systeme zur Bestimmung von Wirksubstanzen gegen HPV-assoziierte Karzinome | |
EP1066321A2 (de) | Formulierung mit papillomavirus-spezifischem protein, seine herstellung und verwendung | |
WO2002055542A2 (de) | Hpv-spezifische peptide, die die bindung von hpv an die wirtszelle blockieren | |
DE19520421A1 (de) | Autoantigen, geeignet zur Feststellung einer Thromboseneigung | |
DE29521486U1 (de) | Papillomavirusähnliche Partikel |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): JP US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): JP US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1998928070 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 1998 544696 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09402016 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 1998928070 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1998928070 Country of ref document: EP |