CA2670965C - Influenza vaccine formulation - Google Patents
Influenza vaccine formulation Download PDFInfo
- Publication number
- CA2670965C CA2670965C CA2670965A CA2670965A CA2670965C CA 2670965 C CA2670965 C CA 2670965C CA 2670965 A CA2670965 A CA 2670965A CA 2670965 A CA2670965 A CA 2670965A CA 2670965 C CA2670965 C CA 2670965C
- Authority
- CA
- Canada
- Prior art keywords
- seq
- nos
- peptide
- infa
- peptides
- 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.)
- Expired - Fee Related
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 117
- 238000009472 formulation Methods 0.000 title abstract description 74
- 229960003971 influenza vaccine Drugs 0.000 title description 9
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 208
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 76
- 150000001413 amino acids Chemical class 0.000 claims description 27
- 241000712461 unidentified influenza virus Species 0.000 claims description 19
- 125000000539 amino acid group Chemical group 0.000 claims description 13
- 230000002163 immunogen Effects 0.000 claims description 10
- 239000002671 adjuvant Substances 0.000 claims description 9
- 229940037003 alum Drugs 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 4
- 229960005486 vaccine Drugs 0.000 abstract description 46
- 206010022000 influenza Diseases 0.000 abstract description 34
- 208000002979 Influenza in Birds Diseases 0.000 abstract description 20
- 206010064097 avian influenza Diseases 0.000 abstract description 20
- 101710154606 Hemagglutinin Proteins 0.000 description 45
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 45
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 45
- 101710176177 Protein A56 Proteins 0.000 description 45
- 239000000185 hemagglutinin Substances 0.000 description 39
- 108090000623 proteins and genes Proteins 0.000 description 19
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 238000001228 spectrum Methods 0.000 description 18
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 230000000890 antigenic effect Effects 0.000 description 16
- 238000000034 method Methods 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 230000000840 anti-viral effect Effects 0.000 description 12
- 241000700605 Viruses Species 0.000 description 11
- 241000282412 Homo Species 0.000 description 9
- 239000011347 resin Substances 0.000 description 9
- 229920005989 resin Polymers 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 241000271566 Aves Species 0.000 description 7
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- 238000013461 design Methods 0.000 description 4
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
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- 101710180643 Leishmanolysin Proteins 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000012317 TBTU Substances 0.000 description 2
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
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- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
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- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- PFBUKDPBVNJDEW-UHFFFAOYSA-N dichlorocarbene Chemical group Cl[C]Cl PFBUKDPBVNJDEW-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
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- 238000000605 extraction Methods 0.000 description 2
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- 125000003473 lipid group Chemical group 0.000 description 2
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- 239000000463 material Substances 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 101710141347 Major envelope glycoprotein Proteins 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
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- 230000034994 death Effects 0.000 description 1
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- 229940079593 drug Drugs 0.000 description 1
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- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
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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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- 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
- A61K39/12—Viral antigens
- A61K39/145—Orthomyxoviridae, e.g. influenza virus
-
- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16122—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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86800806P | 2006-11-30 | 2006-11-30 | |
| US60/868,008 | 2006-11-30 | ||
| PCT/CA2007/002164 WO2008064488A1 (en) | 2006-11-30 | 2007-11-30 | Influenza vaccine formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2670965A1 CA2670965A1 (en) | 2008-06-05 |
| CA2670965C true CA2670965C (en) | 2015-02-24 |
Family
ID=39467397
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2670965A Expired - Fee Related CA2670965C (en) | 2006-11-30 | 2007-11-30 | Influenza vaccine formulation |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US7807173B2 (en:Method) |
| EP (1) | EP2097103B1 (en:Method) |
| JP (1) | JP5177451B2 (en:Method) |
| CN (1) | CN101622009B (en:Method) |
| CA (1) | CA2670965C (en:Method) |
| WO (1) | WO2008064488A1 (en:Method) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2670965C (en) * | 2006-11-30 | 2015-02-24 | Variation Biotechnologies Inc. | Influenza vaccine formulation |
| CA2735724C (en) | 2008-06-19 | 2018-07-24 | Variation Biotechnologies Inc. | Compositions and methods for treating influenza |
| WO2011138032A2 (en) * | 2010-05-05 | 2011-11-10 | Artemev, Timur | Universal influenza vaccines and methods for their generation |
| WO2013072768A2 (en) | 2011-11-18 | 2013-05-23 | Variation Biotechnologies, Inc. | Synthetic derivatives of mpl and uses thereof |
| CA2995838A1 (en) * | 2015-08-19 | 2017-02-23 | Rutgers, The State University Of New Jersey | Novel methods of generating antibodies |
| DK3516064T3 (da) | 2016-09-20 | 2025-07-14 | Boehringer Ingelheim Vetmedica Gmbh | Nye promotorer |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7118874B2 (en) * | 1998-10-09 | 2006-10-10 | Variation Biotechnologies Inc. | Immunogenic formulation and process for preparation thereof |
| US6896881B1 (en) * | 1999-09-24 | 2005-05-24 | Mayo Foundation For Medical Education And Research | Therapeutic methods and compositions using viruses of the recombinant paramyxoviridae family |
| CN1163271C (zh) * | 2000-08-10 | 2004-08-25 | 清华大学 | 一种合成肽流感疫苗的制备方法 |
| EA008143B1 (ru) * | 2002-02-08 | 2007-04-27 | Вариейшн Байотекнолоджиз, Инк. | Иммуногенные композиции из вариабельных пептидных эпитопов и способ их получения |
| WO2004080403A2 (en) | 2003-03-07 | 2004-09-23 | Merck & Co. Inc. | Influenza virus vaccine |
| WO2006128294A1 (en) * | 2005-06-01 | 2006-12-07 | Variation Biotechnologies Inc. | Peptide-based influenza vaccine formulation |
| WO2007051036A2 (en) * | 2005-10-26 | 2007-05-03 | Protelix, Inc. | Influenza combinatorial antigen vaccine |
| AU2006311752A1 (en) * | 2005-11-07 | 2007-05-18 | Sidney Kimmel Cancer Center | CD40 ligand fusion protein vaccine |
| EP2069393A2 (en) * | 2006-10-10 | 2009-06-17 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | Avian influenza vaccine |
| CA2670965C (en) * | 2006-11-30 | 2015-02-24 | Variation Biotechnologies Inc. | Influenza vaccine formulation |
-
2007
- 2007-11-30 CA CA2670965A patent/CA2670965C/en not_active Expired - Fee Related
- 2007-11-30 US US11/948,505 patent/US7807173B2/en not_active Expired - Fee Related
- 2007-11-30 CN CN2007800489232A patent/CN101622009B/zh not_active Expired - Fee Related
- 2007-11-30 WO PCT/CA2007/002164 patent/WO2008064488A1/en not_active Ceased
- 2007-11-30 EP EP07855446A patent/EP2097103B1/en not_active Not-in-force
- 2007-11-30 JP JP2009538564A patent/JP5177451B2/ja not_active Expired - Fee Related
-
2010
- 2010-09-03 US US12/875,638 patent/US20110020381A1/en not_active Abandoned
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|---|---|
| EP2097103A4 (en) | 2010-02-24 |
| CN101622009B (zh) | 2012-08-22 |
| EP2097103A1 (en) | 2009-09-09 |
| EP2097103B1 (en) | 2012-10-03 |
| US20110020381A1 (en) | 2011-01-27 |
| US7807173B2 (en) | 2010-10-05 |
| JP5177451B2 (ja) | 2013-04-03 |
| CA2670965A1 (en) | 2008-06-05 |
| US20080193472A1 (en) | 2008-08-14 |
| WO2008064488A1 (en) | 2008-06-05 |
| CN101622009A (zh) | 2010-01-06 |
| JP2010510994A (ja) | 2010-04-08 |
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