WO1997004099A2 - Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen - Google Patents
Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen Download PDFInfo
- Publication number
- WO1997004099A2 WO1997004099A2 PCT/DE1996/001369 DE9601369W WO9704099A2 WO 1997004099 A2 WO1997004099 A2 WO 1997004099A2 DE 9601369 W DE9601369 W DE 9601369W WO 9704099 A2 WO9704099 A2 WO 9704099A2
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- WO
- WIPO (PCT)
- Prior art keywords
- dna
- virus
- protein
- papillomavirus
- genome
- Prior art date
Links
- 241001631646 Papillomaviridae Species 0.000 title claims abstract description 65
- 241000700605 Viruses Species 0.000 title description 20
- 201000010099 disease Diseases 0.000 title description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 3
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 23
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 22
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 19
- 239000002245 particle Substances 0.000 claims abstract description 16
- 108090000565 Capsid Proteins Proteins 0.000 claims abstract description 8
- 102100023321 Ceruloplasmin Human genes 0.000 claims abstract description 8
- 238000003745 diagnosis Methods 0.000 claims abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
- 238000002255 vaccination Methods 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 15
- 150000001413 amino acids Chemical class 0.000 claims description 14
- 239000013598 vector Substances 0.000 claims description 13
- 239000013604 expression vector Substances 0.000 claims description 12
- 238000010367 cloning Methods 0.000 claims description 8
- 238000001574 biopsy Methods 0.000 claims description 5
- 208000034179 Neoplasms, Glandular and Epithelial Diseases 0.000 claims description 4
- 238000012270 DNA recombination Methods 0.000 claims description 3
- 101710157639 Minor capsid protein Proteins 0.000 claims description 3
- 101710136297 Protein VP2 Proteins 0.000 claims description 3
- 208000010932 epithelial neoplasm Diseases 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 238000012258 culturing Methods 0.000 claims 1
- 108020004414 DNA Proteins 0.000 description 86
- 239000013612 plasmid Substances 0.000 description 11
- 238000009396 hybridization Methods 0.000 description 9
- 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
- 206010041823 squamous cell carcinoma Diseases 0.000 description 3
- 206010059313 Anogenital warts Diseases 0.000 description 2
- 241000894006 Bacteria Species 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
- 241000699670 Mus sp. Species 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 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
- 238000001514 detection method 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
- 238000007169 ligase reaction Methods 0.000 description 2
- 210000004072 lung Anatomy 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
- 238000012163 sequencing technique Methods 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
- 208000009608 Papillomavirus Infections Diseases 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
- 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
- 229960003180 glutathione Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 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
- 230000000644 propagated effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 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
- 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
- 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
Definitions
- Papillomaviruses means for their detection and for the therapy of diseases caused by them
- 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, (1993), pages 6929-6936).
- the invention thus relates to a DNA coding for a peptide of a papillomavirus main capsid protein (L1), the peptide comprising the amino acid sequence of FIGS. 1, 2, 3, 4, 5, 6 , 7, 8, 9 or 10, or an amino acid sequence different from one or more amino acids.
- 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, 9 or 10 or one of these base sequences which are different by one or more base pairs.
- FIG. 1 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 VS19-6 at DSM (German Collection of Microorganisms and Cell Cultures) under DSM 10104 on July 11, 1995.
- Fig. 2 shows the base sequence and the amino acid sequence derived therefrom one for a peptide of L1 one DNA encoding papilloma virus. This DNA was deposited as plasmid VS200-1 with the DSM under DSM 10096 on July 11, 1995.
- 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. This DNA was deposited as plasmid VS201-1 with the DSM under DSM 10097 on July 11, 1995.
- FIG. 4 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from L1 of a papillomavirus. This DNA was deposited as plasmid VS202-8 with the DSM under DSM 10098 on July 11, 1995.
- FIG. 5 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 VS203-2 with the DSM under DSM 10099 on July 11, 1995.
- FIG. 6 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from Ll of a papillomavirus. This DNA was deposited as plasmid VS204-4 with the DSM under DSM 10100 on July 11, 1995.
- FIG. 7 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from Ll of a papillomavirus. This DNA was deposited as plasmid VS205-1 with the DSM under DSM 10101 on July 11, 1995.
- FIG. 8 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from Ll of a papilloma virus. This DNA was deposited as plasmid VS206-2 with the DSM under DSM 10109 on July 13, 1995.
- Fig. 9 shows the • base sequence and the deduced amino acid sequence of a gene coding for a peptide of a papillomavirus Ll DNA.
- This DNA was called a plasmid VS207-22 deposited with the DSM under DSM 10102 on July 11, 1995.
- FIG. 10 shows the base sequence and the amino acid sequence derived therefrom of a DNA coding for a peptide from Ll of a papilloma virus. This DNA was deposited as plasmid VS208-1 with the DSM under DSM 10103 on July 11, 1995.
- the above DNA has the following sequence homology 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 pYlOO and Ycpadi
- animal cells e.g. pKCR, pEF-BOS, cDM8 and pCEV4 must be specified.
- 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. be a DNA coding for Ll or a part thereof.
- 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 preferably used in the present case 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 pWE15 and Super Cosl, and phages such as ⁇ phages, e.g. ⁇ ZAP Expressvector, ⁇ ZAPII Vector and ⁇ gtlO 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 VS19-6 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 65, 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 hybridized with the DNA from FIG. 1, if appropriate in combination with a DNA of the HP virus 65 identified.
- the insert of these clones is then subjected to further cloning in a plasmid vector, whereby a clone is obtained which contains the papillomavirus genome VS19-6-G. The genome is confirmed by sequencing.
- Another object of the invention is a protein encoded by the above papillomavirus genome.
- a protein is e.g. a major capsid protein (Ll) or a minor capsid protein (L2).
- L1 or L2 of the papilloma virus genome VS19-6-G is described by way of example.
- the HP virus 65 related to the DNA of FIG. 1 is used.
- 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 VS19-6-G by parallel restriction cleavages of both genomes and subsequent hybridization with different fragments relating to the L1 or L2 coding DNA. They are confirmed by sequencing.
- the DNA coding for L1 is designated VS19-6-G-L1-DNA and the DNA coding for L2 with VS19-6-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-VS19-6-G-L1 or pGEX-2T-VS19-6-G-L2 is obtained.
- These expression vectors express after transformation of E. coli 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 is called for a further expression of the above-mentioned L1 or L2 coding DNA.
- 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" early "(p7.5k) - or” late "(Psynth, pllK) promoter (cf. Hagensee, M., E. et al., Journal of Virology (1993), pages 315-322).
- the bacculovirus system is preferred.
- a particle comprises an Ll protein
- an L2 protein in addition to an Ll protein.
- a virus-like particle of the latter case is also obtained by inserting the above VS19-6-G-L1 and VS19-6-G-L2 DNAs together into the expression vector pSynwtVI " and the resulting pSynwtVI " VS19-6-G -Ll / L2 is used to infect SF-9 insect cells.
- 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 an L1 of VS19-6-G comprising the virus-like particle.
- the Virus-like particles BALB / c mice 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 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 VS19-6-G
- the total DNA is isolated from an immunosuppressed person. 10 ⁇ g of this DNA are cleaved with the restriction enzyme BamHI 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 DNA from FIG. 1 is used in combination with HP virus 65 DNA as a p 32 -labeled sample. Hybridization with the blotted DNA is obtained.
- 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 ⁇ ZAP Express vector, which has been cleaved and dephosphorylated with BamHI, 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 65 DNA. Hybridization with corresponding phage plaques is obtained.
- the BamHI fragments of VS19-6-G are isolated from these and together with a BamHI -cleaved, phosphorylated plasmid vector, pBluescript, used in a further ligase reaction.
- the recombinant DNA molecules obtained are used to transform bacteria, E. coli XII-Blue.
- a bacterial clone containing the papillomavirus genome VS19-6-G is identified by restriction cleavage or hybridization with the above DNA samples.
- the plasmid of this bacterial clone is designated pBlue-VS19-6-G.
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- General Health & Medical Sciences (AREA)
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- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9506174A JPH11512925A (ja) | 1995-07-19 | 1996-07-19 | パピローマウイルス、その検出用製品及びそれにより生ずる疾病の治療用製品 |
EP96928326A EP0839199A1 (de) | 1995-07-19 | 1996-07-19 | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
US09/000,266 US6322795B1 (en) | 1995-07-19 | 1996-07-19 | Papilloma viruses, agents for detecting them and for treating diseases caused by such viruses |
US09/628,099 US6368832B1 (en) | 1995-07-19 | 2000-05-25 | Papilloma viruses, agents for detecting them and for treating diseases caused by such viruses |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19526386.3 | 1995-07-19 | ||
DE19526386A DE19526386C1 (de) | 1995-07-19 | 1995-07-19 | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/000,266 A-371-Of-International US6322795B1 (en) | 1995-07-19 | 1996-07-19 | Papilloma viruses, agents for detecting them and for treating diseases caused by such viruses |
US09/628,099 Division US6368832B1 (en) | 1995-07-19 | 2000-05-25 | Papilloma viruses, agents for detecting them and for treating diseases caused by such viruses |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1997004099A2 true WO1997004099A2 (de) | 1997-02-06 |
WO1997004099A3 WO1997004099A3 (de) | 2001-04-12 |
Family
ID=7767261
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE1996/001369 WO1997004099A2 (de) | 1995-07-19 | 1996-07-19 | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
Country Status (5)
Country | Link |
---|---|
US (4) | US6322795B1 (de) |
EP (1) | EP0839199A1 (de) |
JP (1) | JPH11512925A (de) |
DE (1) | DE19526386C1 (de) |
WO (1) | WO1997004099A2 (de) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
WO1998042847A2 (de) * | 1997-03-25 | 1998-10-01 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Papillomvirus-hauptcapsid-proteins und deren verwendung in diagnose, therapie und vakzinierung |
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 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002323520B2 (en) * | 2001-08-31 | 2008-02-21 | Gen-Probe Incorporated | Assay for detection of human parvovirus B19 nucleic acid |
KR101600225B1 (ko) | 2005-06-08 | 2016-03-04 | 다나-파버 캔서 인스티튜트 인크. | 예정 세포사 1(pd-1) 경로를 억제함으로써 지속 감염 및 암을 치료하기 위한 방법 및 조성물 |
JP5623747B2 (ja) | 2006-12-27 | 2014-11-12 | エモリー ユニバーシティ | 感染症および腫瘍を処置するための組成物および方法 |
CA2744449C (en) | 2008-11-28 | 2019-01-29 | Emory University | Methods for the treatment of infections and tumors |
EP2576840B1 (de) | 2010-05-25 | 2018-10-17 | QIAGEN Gaithersburg, Inc. | Hybrid-capture-assay mit schneller ergebnislieferung und zugehörige strategisch gekürzte sonden |
JP2019512271A (ja) | 2016-03-21 | 2019-05-16 | デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド | T細胞疲弊状態特異的遺伝子発現調節因子およびその使用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0301289A1 (de) * | 1987-07-11 | 1989-02-01 | BEHRINGWERKE Aktiengesellschaft | Humaner Papillomvirus Typ 41 |
EP0370625A1 (de) * | 1988-10-26 | 1990-05-30 | Georgetown University | DNS-Sequenzen des menschlichen Papillomavirus Typ 52 und Verfahren zu ihrer Verwendung |
WO1994005792A1 (en) * | 1992-09-03 | 1994-03-17 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Self-assembling recombinant papillomavirus capsid proteins |
DE4415743A1 (de) * | 1994-05-04 | 1995-11-09 | Deutsches Krebsforsch | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen |
-
1995
- 1995-07-19 DE DE19526386A patent/DE19526386C1/de not_active Expired - Fee Related
-
1996
- 1996-07-19 US US09/000,266 patent/US6322795B1/en not_active Expired - Fee Related
- 1996-07-19 EP EP96928326A patent/EP0839199A1/de not_active Ceased
- 1996-07-19 WO PCT/DE1996/001369 patent/WO1997004099A2/de not_active Application Discontinuation
- 1996-07-19 JP JP9506174A patent/JPH11512925A/ja active Pending
-
2000
- 2000-05-25 US US09/628,099 patent/US6368832B1/en not_active Expired - Fee Related
-
2002
- 2002-01-23 US US10/056,360 patent/US6555345B2/en not_active Expired - Fee Related
- 2002-01-23 US US10/056,359 patent/US6562597B2/en not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0301289A1 (de) * | 1987-07-11 | 1989-02-01 | BEHRINGWERKE Aktiengesellschaft | Humaner Papillomvirus Typ 41 |
EP0370625A1 (de) * | 1988-10-26 | 1990-05-30 | Georgetown University | DNS-Sequenzen des menschlichen Papillomavirus Typ 52 und Verfahren zu ihrer Verwendung |
WO1994005792A1 (en) * | 1992-09-03 | 1994-03-17 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Self-assembling recombinant papillomavirus capsid proteins |
DE4415743A1 (de) * | 1994-05-04 | 1995-11-09 | Deutsches Krebsforsch | Papillomviren, Mittel zu deren Nachweis sowie zur Therapie von durch sie verursachten Erkrankungen |
Non-Patent Citations (5)
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
WO1998023752A3 (de) * | 1996-11-26 | 1998-07-16 | Deutsches Krebsforsch | Papillomviren, mittel zu deren nachweis sowie zur therapie von durch sie verursachten erkrankungen |
US6413522B1 (en) * | 1996-11-26 | 2002-07-02 | Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts | Papilloma viruses, products for the detection thereof as well as for treating diseases caused by them |
WO1998042847A2 (de) * | 1997-03-25 | 1998-10-01 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Papillomvirus-hauptcapsid-proteins und deren verwendung in diagnose, therapie und vakzinierung |
WO1998042847A3 (de) * | 1997-03-25 | 1999-03-11 | Deutsches Krebsforsch | Papillomvirus-hauptcapsid-proteins und deren verwendung in diagnose, therapie und vakzinierung |
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 |
Also Published As
Publication number | Publication date |
---|---|
EP0839199A1 (de) | 1998-05-06 |
US20020110866A1 (en) | 2002-08-15 |
DE19526386C1 (de) | 1997-01-02 |
US6322795B1 (en) | 2001-11-27 |
US6555345B2 (en) | 2003-04-29 |
US6562597B2 (en) | 2003-05-13 |
JPH11512925A (ja) | 1999-11-09 |
US6368832B1 (en) | 2002-04-09 |
WO1997004099A3 (de) | 2001-04-12 |
US20020110865A1 (en) | 2002-08-15 |
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