AU2003232951B2 - Chimaeric human papillomavirus 16 L1 proteins comprising an L2 peptide, virus-like particles prepared therefrom and a method for preparing the particles. - Google Patents
Chimaeric human papillomavirus 16 L1 proteins comprising an L2 peptide, virus-like particles prepared therefrom and a method for preparing the particles. Download PDFInfo
- Publication number
- AU2003232951B2 AU2003232951B2 AU2003232951A AU2003232951A AU2003232951B2 AU 2003232951 B2 AU2003232951 B2 AU 2003232951B2 AU 2003232951 A AU2003232951 A AU 2003232951A AU 2003232951 A AU2003232951 A AU 2003232951A AU 2003232951 B2 AU2003232951 B2 AU 2003232951B2
- Authority
- AU
- Australia
- Prior art keywords
- hpv
- dna sequence
- peptide
- polypeptide
- chimaeric
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 117
- 238000000034 method Methods 0.000 title claims abstract description 19
- 239000002245 particle Substances 0.000 title claims description 16
- 101000641177 Human papillomavirus type 16 Major capsid protein L1 Proteins 0.000 title 1
- 241000701806 Human papillomavirus Species 0.000 claims abstract description 93
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 64
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 48
- 229920001184 polypeptide Polymers 0.000 claims abstract description 46
- 229960005486 vaccine Drugs 0.000 claims abstract description 12
- 239000013598 vector Substances 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 239000002773 nucleotide Substances 0.000 claims description 27
- 125000003729 nucleotide group Chemical group 0.000 claims description 27
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 17
- 210000004027 cell Anatomy 0.000 claims description 15
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- 238000012986 modification Methods 0.000 claims description 9
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- 230000000890 antigenic effect Effects 0.000 claims description 5
- 230000002163 immunogen Effects 0.000 claims description 5
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 3
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 3
- 208000009608 Papillomavirus Infections Diseases 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 241001631646 Papillomaviridae Species 0.000 description 7
- 238000004448 titration Methods 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 6
- 241000238631 Hexapoda Species 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 210000002845 virion Anatomy 0.000 description 5
- 241000701646 Kappapapillomavirus 2 Species 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 108090000565 Capsid Proteins Proteins 0.000 description 3
- 102100023321 Ceruloplasmin Human genes 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 241000341655 Human papillomavirus type 16 Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
- 201000010881 cervical cancer Diseases 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- 229940021993 prophylactic vaccine Drugs 0.000 description 3
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- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
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- 101710157639 Minor capsid protein Proteins 0.000 description 2
- 101710136297 Protein VP2 Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
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- 150000007523 nucleic acids Chemical group 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 206010059313 Anogenital warts Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 208000000907 Condylomata Acuminata Diseases 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 101710121996 Hexon protein p72 Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000701828 Human papillomavirus type 11 Species 0.000 description 1
- 101150034230 LI gene Proteins 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 208000000260 Warts Diseases 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000025009 anogenital human papillomavirus infection Diseases 0.000 description 1
- 201000004201 anogenital venereal wart Diseases 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
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- 238000012790 confirmation Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
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- 230000007717 exclusion Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
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- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000001262 western blot Methods 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5258—Virus-like particles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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]
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)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- AIDS & HIV (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ZA2002/3957 | 2002-05-17 | ||
| ZA200203957 | 2002-05-17 | ||
| PCT/IB2003/001912 WO2003097673A2 (en) | 2002-05-17 | 2003-05-19 | Chimeric human papillomavirus 16 l1 proteins comprising an l2 peptide,virus-like particles prepared therefrom and a method for preparing the particles. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2003232951A1 AU2003232951A1 (en) | 2003-12-02 |
| AU2003232951B2 true AU2003232951B2 (en) | 2009-07-23 |
Family
ID=29550639
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003232951A Ceased AU2003232951B2 (en) | 2002-05-17 | 2003-05-19 | Chimaeric human papillomavirus 16 L1 proteins comprising an L2 peptide, virus-like particles prepared therefrom and a method for preparing the particles. |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US7407807B2 (enExample) |
| EP (1) | EP1506222B2 (enExample) |
| JP (2) | JP4614765B2 (enExample) |
| AT (1) | ATE424409T1 (enExample) |
| AU (1) | AU2003232951B2 (enExample) |
| CA (1) | CA2486450C (enExample) |
| CY (1) | CY1109257T1 (enExample) |
| DE (1) | DE60326449D1 (enExample) |
| DK (1) | DK1506222T3 (enExample) |
| ES (1) | ES2323634T5 (enExample) |
| PT (1) | PT1506222E (enExample) |
| SI (1) | SI1506222T1 (enExample) |
| WO (1) | WO2003097673A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0228715D0 (en) * | 2002-12-09 | 2003-01-15 | Glaxosmithkline Biolog Sa | Vaccine |
| WO2006119516A2 (en) | 2005-04-29 | 2006-11-09 | University Of Cape Town | Expression of viral proteins in plants |
| ES2310062B1 (es) | 2005-07-15 | 2009-11-13 | Bionostra, S.L. | Particulas pseudovirales vacias quimericas derivadas del virus causante de la enfermedad de la bursitis infecciosa (ibdv), procedimiento de obtencion y aplicaciones. |
| CN1328287C (zh) * | 2005-12-29 | 2007-07-25 | 西安交通大学 | Hpv16 l1蛋白模拟肽及其用于制备hpv16诊断试剂和疫苗的用途 |
| WO2009055491A2 (en) * | 2007-10-22 | 2009-04-30 | University Of Rochester | Respiratory syncytial virus vaccine based on chimeric papillomavirus virus-like particles or capsomeres |
| PE20120563A1 (es) | 2009-06-25 | 2012-05-17 | Glaxosmithkline Biolog Sa | Construcciones novedosas de proteina del virus de papiloma humano (hpv) y su uso en la prevencion de la enfermedad por el hpv |
| WO2011017162A2 (en) * | 2009-08-03 | 2011-02-10 | The Johns Hopkins University | Methods for enhancing antigen-specific immune responses |
| EP2576840B1 (en) | 2010-05-25 | 2018-10-17 | QIAGEN Gaithersburg, Inc. | Fast results hybrid capture assay and associated strategically-truncated probes |
| KR102013801B1 (ko) | 2011-12-01 | 2019-08-23 | 유니버시티 오브 케이프 타운 | Ｈｐｖ 키메라 입자 |
| WO2015009853A1 (en) * | 2013-07-16 | 2015-01-22 | University Of Louisville Research Foundation, Inc. | Compositions for mucusal delivery, useful for treating papillomavirus infections |
| JP7017811B2 (ja) * | 2020-02-13 | 2022-02-09 | 国立研究開発法人農業・食品産業技術総合研究機構 | ウイルス様粒子及びその使用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5618536A (en) * | 1992-09-03 | 1997-04-08 | The United States Of America As Represented By The Department Of Health And Human Services | Chimeric papillomavirus-like particles |
| AU4270196A (en) * | 1994-10-07 | 1996-05-02 | Lutz Gissmann | Papilloma virus-like particles, fusion proteins and process for producing the same |
| GB9621091D0 (en) * | 1996-10-09 | 1996-11-27 | Fondation Pour Le Perfectionem | Attenuated microorganisms strains and their uses |
| US6228368B1 (en) † | 1997-10-06 | 2001-05-08 | Loyola University Of Chicago | Papilloma virus capsomere formulations and method of use |
| DE19812941A1 (de) † | 1998-03-24 | 1999-10-07 | Medigene Ag | Arzneimittel zur Vermeidung oder Behandlung von Papillomavirusspezifischem Tumor |
| US6926897B1 (en) † | 1998-03-24 | 2005-08-09 | Medigene Aktiengesellschaft | Medicament for the avoidance or treatment of papillomavirus-specific tumour |
| ATE344052T1 (de) * | 1998-08-14 | 2006-11-15 | Merck & Co Inc | Protein-verabreichungssystem, das dem menschlichen papillomavirus ähnliche partikel benützt. |
| GB9921146D0 (en) † | 1999-09-07 | 1999-11-10 | Smithkline Beecham Biolog | Novel composition |
| CN102458440A (zh) † | 2009-04-10 | 2012-05-16 | 约翰·霍普金斯大学 | 作为广谱人类乳头状瘤病毒(hpv)疫苗的乳头状瘤病毒样颗粒(vlp) |
-
2003
- 2003-05-19 PT PT03727750T patent/PT1506222E/pt unknown
- 2003-05-19 CA CA2486450A patent/CA2486450C/en not_active Expired - Fee Related
- 2003-05-19 WO PCT/IB2003/001912 patent/WO2003097673A2/en not_active Ceased
- 2003-05-19 US US10/514,878 patent/US7407807B2/en not_active Expired - Fee Related
- 2003-05-19 SI SI200331600T patent/SI1506222T1/sl unknown
- 2003-05-19 JP JP2004506346A patent/JP4614765B2/ja not_active Expired - Fee Related
- 2003-05-19 AU AU2003232951A patent/AU2003232951B2/en not_active Ceased
- 2003-05-19 DE DE60326449T patent/DE60326449D1/de not_active Expired - Lifetime
- 2003-05-19 ES ES03727750T patent/ES2323634T5/es not_active Expired - Lifetime
- 2003-05-19 AT AT03727750T patent/ATE424409T1/de active
- 2003-05-19 EP EP03727750A patent/EP1506222B2/en not_active Expired - Lifetime
- 2003-05-19 DK DK03727750T patent/DK1506222T3/da active
-
2008
- 2008-07-16 US US12/174,104 patent/US8163557B2/en not_active Expired - Lifetime
-
2009
- 2009-06-04 CY CY20091100595T patent/CY1109257T1/el unknown
-
2010
- 2010-06-16 JP JP2010137490A patent/JP2010263899A/ja not_active Withdrawn
Non-Patent Citations (3)
| Title |
|---|
| Jochmus, I. et al. (1999) Archives of Medical Research 30: 269-274 * |
| Muller, M. et al. (1997) Virology 234: 93-111 * |
| Slupetzky, K. et al. (2001) Journal of General Virology 82: 2799-2804 * |
Also Published As
| Publication number | Publication date |
|---|---|
| PT1506222E (pt) | 2009-06-12 |
| JP4614765B2 (ja) | 2011-01-19 |
| CA2486450C (en) | 2013-11-19 |
| WO2003097673A3 (en) | 2004-03-18 |
| ATE424409T1 (de) | 2009-03-15 |
| EP1506222B2 (en) | 2012-05-23 |
| US8163557B2 (en) | 2012-04-24 |
| WO2003097673A2 (en) | 2003-11-27 |
| US20060035319A1 (en) | 2006-02-16 |
| JP2010263899A (ja) | 2010-11-25 |
| EP1506222B1 (en) | 2009-03-04 |
| ES2323634T3 (es) | 2009-07-22 |
| US7407807B2 (en) | 2008-08-05 |
| CA2486450A1 (en) | 2003-11-27 |
| JP2006507797A (ja) | 2006-03-09 |
| DK1506222T3 (da) | 2009-07-06 |
| WO2003097673B1 (en) | 2004-04-22 |
| DE60326449D1 (de) | 2009-04-16 |
| SI1506222T1 (sl) | 2009-10-31 |
| ES2323634T5 (es) | 2012-09-04 |
| EP1506222A2 (en) | 2005-02-16 |
| AU2003232951A1 (en) | 2003-12-02 |
| US20090047302A1 (en) | 2009-02-19 |
| CY1109257T1 (el) | 2014-07-02 |
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