NZ530632A - HCV E1E2 vaccine compositions comprising E1E2 antigens, submicron oil-in-water emulsions and/or CpG oligonucleotides - Google Patents
HCV E1E2 vaccine compositions comprising E1E2 antigens, submicron oil-in-water emulsions and/or CpG oligonucleotidesInfo
- Publication number
- NZ530632A NZ530632A NZ530632A NZ53063202A NZ530632A NZ 530632 A NZ530632 A NZ 530632A NZ 530632 A NZ530632 A NZ 530632A NZ 53063202 A NZ53063202 A NZ 53063202A NZ 530632 A NZ530632 A NZ 530632A
- Authority
- NZ
- New Zealand
- Prior art keywords
- composition
- sequence
- hcv
- oil
- antigen
- Prior art date
Links
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Classifications
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- 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
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- 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
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- 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
- A61K39/29—Hepatitis virus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
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- 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
- A61K2039/5555—Muramyl dipeptides
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- 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
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
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- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
- C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
- C12N2770/24222—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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
- C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
- C12N2770/24234—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)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30222701P | 2001-06-29 | 2001-06-29 | |
| PCT/US2002/020676 WO2003002065A2 (en) | 2001-06-29 | 2002-06-28 | Hcv e1e2 vaccine compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ530632A true NZ530632A (en) | 2007-04-27 |
Family
ID=23166848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ530632A NZ530632A (en) | 2001-06-29 | 2002-06-28 | HCV E1E2 vaccine compositions comprising E1E2 antigens, submicron oil-in-water emulsions and/or CpG oligonucleotides |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20030138458A1 (https=) |
| EP (1) | EP1572124A4 (https=) |
| JP (2) | JP4370161B2 (https=) |
| CN (2) | CN1931365A (https=) |
| AU (1) | AU2002322358B2 (https=) |
| CA (1) | CA2451739A1 (https=) |
| CZ (1) | CZ20033515A3 (https=) |
| HU (1) | HUP0400346A2 (https=) |
| NZ (1) | NZ530632A (https=) |
| RU (1) | RU2316347C2 (https=) |
| SK (1) | SK15762003A3 (https=) |
| WO (1) | WO2003002065A2 (https=) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| CZ20033515A3 (cs) * | 2001-06-29 | 2005-01-12 | Chiron Corporation | Kompozice vakcíny HCV E1E2 |
| CA2388049A1 (en) | 2002-05-30 | 2003-11-30 | Immunotech S.A. | Immunostimulatory oligonucleotides and uses thereof |
| PT2241325E (pt) * | 2002-10-29 | 2012-04-12 | Coley Pharm Gmbh | Utilização de oligonucleótidos cpg no tratamento de infecção com vírus da hepatite c |
| EP1578954A4 (en) | 2002-12-11 | 2010-08-11 | Coley Pharm Group Inc | 5'-CPG NUCLEIC ACIDS AND USE METHOD |
| US20050191358A1 (en) * | 2003-01-14 | 2005-09-01 | Derek O' Hagan | Microparticles with adsorbed polynucleotide-containing species |
| CA2523266A1 (en) * | 2003-04-25 | 2004-11-11 | Chiron Corporation | Compositions comprising cationic microparticles and hcv e1e2 dna and methods of use thereof |
| EP1631264B8 (en) * | 2003-06-02 | 2017-05-24 | GlaxoSmithKline Biologicals SA | Immunogenic compositions based on microparticles comprising adsorbed toxoid and a polysaccharide-containing antigen |
| NZ551319A (en) * | 2004-05-17 | 2010-07-30 | Novartis Vaccines & Diagnostic | Truncated Hepatitis C virus NS5 domain and fusion proteins comprising same |
| FR2878746B1 (fr) | 2004-12-02 | 2007-02-23 | Vetoquinol Sa Sa | Nouvelle composition pharmaceutique utilisable dans le domaine des vaccins |
| CA2646539A1 (en) | 2006-03-23 | 2007-09-27 | Novartis Ag | Imidazoquinoxaline compounds as immunomodulators |
| AU2015234338C1 (en) * | 2006-07-28 | 2017-07-20 | The Trustees Of The University Of Pennsylvania | Improved vaccines and methods for using the same |
| US8324369B2 (en) * | 2007-11-30 | 2012-12-04 | Baylor College Of Medicine | Dendritic cell vaccine compositions and uses of same |
| RU2572826C2 (ru) | 2008-12-02 | 2016-01-20 | Чиралджен, Лтд. | Способ синтеза модифицированных по атому фосфора нуклеиновых кислот |
| CA2767253A1 (en) | 2009-07-06 | 2011-01-13 | Ontorii, Inc. | Novel nucleic acid prodrugs and methods of use thereof |
| WO2011040535A1 (ja) | 2009-09-30 | 2011-04-07 | 東レ株式会社 | Ｃ型肝炎ウイルスワクチン組成物 |
| JP5868324B2 (ja) | 2010-09-24 | 2016-02-24 | 株式会社Wave Life Sciences Japan | 不斉補助基 |
| AU2012284265B2 (en) | 2011-07-19 | 2017-08-17 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| JP6453212B2 (ja) | 2012-07-13 | 2019-01-16 | ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． | キラル制御 |
| CN104684923B (zh) | 2012-07-13 | 2018-09-28 | 株式会社新日本科学 | 手性核酸佐剂 |
| SG11201500239VA (en) | 2012-07-13 | 2015-03-30 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| JP2016520077A (ja) * | 2013-05-15 | 2016-07-11 | ザ ガバナーズ オブ ザ ユニバーシティ オブ アルバータ | Ｅ１ｅ２ｈｃｖワクチン及び使用方法 |
| JPWO2015108046A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
| WO2015108047A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| WO2015108048A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| ES2917473T3 (es) | 2014-01-16 | 2022-07-08 | Wave Life Sciences Ltd | Diseño quiral |
| AU2017341735B2 (en) | 2016-10-11 | 2022-01-13 | Helmholtz Center for Infection Research | Hepatitis C virus immunogenic compositions comprising as an adjuvant a cyclic dinucleotide or an archaeosome and methods of use thereof |
Family Cites Families (24)
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| HU212924B (en) * | 1989-05-25 | 1996-12-30 | Chiron Corp | Adjuvant formulation comprising a submicron oil droplet emulsion |
| US6274148B1 (en) * | 1990-11-08 | 2001-08-14 | Chiron Corporation | Hepatitis C virus asialoglycoproteins |
| WO1993006126A1 (en) * | 1991-09-13 | 1993-04-01 | Chiron Corporation | Immunoreactive hepatitis c virus polypeptide compositions |
| ATE509102T1 (de) * | 1994-07-15 | 2011-05-15 | Univ Iowa Res Found | Immunomodulatorische oligonukleotide |
| US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| AU3241095A (en) * | 1994-07-29 | 1996-03-04 | Chiron Corporation | Novel hepatitis c e1 and e2 truncated polypeptides and methods of obtaining the same |
| BR9506059A (pt) * | 1994-07-29 | 1997-10-28 | Innogenetics Nv | Proteinas envelopes purificadas de virus c para uso de diagnóstico e terapêutico |
| GB9703406D0 (en) * | 1997-02-19 | 1997-04-09 | Chiron Spa | Expression of heterologous proteins |
| WO1998037919A1 (en) * | 1997-02-28 | 1998-09-03 | University Of Iowa Research Foundation | USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE IN THE TREATMENT OF LPS-ASSOCIATED DISORDERS |
| US6406705B1 (en) * | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| GB9712347D0 (en) | 1997-06-14 | 1997-08-13 | Smithkline Beecham Biolog | Vaccine |
| ES2298316T3 (es) | 1997-09-05 | 2008-05-16 | Glaxosmithkline Biologicals S.A. | Emulsiones de aceite en agua que contienen saponinas. |
| ES2175668T3 (es) * | 1997-12-16 | 2002-11-16 | Chiron Corp | Uso de microparticulas combinadas con emulsiones de aceite en agua submicronicas. |
| ATE356630T1 (de) * | 1998-04-03 | 2007-04-15 | Univ Iowa Res Found | Verfahren und produkte zur stimulierung des immunsystems mittels immunotherapeutischer oligonukleotide und zytokine |
| IL138000A0 (en) | 1998-04-09 | 2001-10-31 | Smithkline Beecham Biolog | Adjuvant compositions |
| DE69935606T9 (de) | 1998-10-16 | 2021-03-11 | Glaxosmithkline Biologicals S.A. | Adjuvanzsysteme und impfstoffe |
| DE60014076T2 (de) | 1999-04-19 | 2005-10-13 | Glaxosmithkline Biologicals S.A. | Adjuvans-zusammensetzung, enthaltend saponin und ein immunstimulatorisches oligonukleotid |
| SK287400B6 (sk) * | 1999-09-25 | 2010-08-09 | University Of Iowa Research Foundation | Prostriedok s obsahom imunostimulačnej nukleovej kyseliny a jeho použitie na stimuláciu imunitnej reakcie |
| DE60043708D1 (de) * | 1999-10-13 | 2010-03-04 | Novartis Vaccines & Diagnostic | Verfahren zur erhaltung zellimmuneantworten gegen proteinen |
| EP1239876B1 (en) * | 1999-11-19 | 2008-07-30 | Csl Limited | Hcv vaccine compositions |
| JP2004500366A (ja) * | 1999-12-01 | 2004-01-08 | カイロン コーポレイション | Ｃ型肝炎ウイルス（ｈｃｖ）について特異的な抗体を誘発すること |
| ATE350015T1 (de) * | 2000-09-28 | 2007-01-15 | Novartis Vaccines & Diagnostic | Mikropartikelzusammensetzungen und verfahren zu ihrer herstellung |
| CZ20033515A3 (cs) * | 2001-06-29 | 2005-01-12 | Chiron Corporation | Kompozice vakcíny HCV E1E2 |
| AU2003299994A1 (en) * | 2002-12-27 | 2004-07-29 | Chiron Corporation | Immunogenic compositions containing phospholpid |
-
2002
- 2002-06-28 CZ CZ20033515A patent/CZ20033515A3/cs unknown
- 2002-06-28 HU HU0400346A patent/HUP0400346A2/hu unknown
- 2002-06-28 CN CNA2006101395992A patent/CN1931365A/zh active Pending
- 2002-06-28 NZ NZ530632A patent/NZ530632A/en not_active IP Right Cessation
- 2002-06-28 SK SK1576-2003A patent/SK15762003A3/sk unknown
- 2002-06-28 JP JP2003508307A patent/JP4370161B2/ja not_active Expired - Fee Related
- 2002-06-28 AU AU2002322358A patent/AU2002322358B2/en not_active Ceased
- 2002-06-28 CN CNA028128192A patent/CN1636015A/zh active Pending
- 2002-06-28 CA CA002451739A patent/CA2451739A1/en not_active Abandoned
- 2002-06-28 RU RU2004102520/13A patent/RU2316347C2/ru not_active IP Right Cessation
- 2002-06-28 WO PCT/US2002/020676 patent/WO2003002065A2/en not_active Ceased
- 2002-06-28 EP EP02756345A patent/EP1572124A4/en not_active Withdrawn
- 2002-06-28 US US10/187,257 patent/US20030138458A1/en not_active Abandoned
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2005
- 2005-06-16 US US11/154,324 patent/US20050255124A1/en not_active Abandoned
- 2005-06-28 JP JP2005188972A patent/JP2005298523A/ja active Pending
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2009
- 2009-05-12 US US12/454,074 patent/US20090258033A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1572124A4 (en) | 2007-11-28 |
| CA2451739A1 (en) | 2003-01-09 |
| JP4370161B2 (ja) | 2009-11-25 |
| CZ20033515A3 (cs) | 2005-01-12 |
| WO2003002065A2 (en) | 2003-01-09 |
| CN1636015A (zh) | 2005-07-06 |
| RU2004102520A (ru) | 2005-06-10 |
| RU2316347C2 (ru) | 2008-02-10 |
| US20050255124A1 (en) | 2005-11-17 |
| PL367526A1 (en) | 2005-02-21 |
| SK15762003A3 (sk) | 2005-01-03 |
| US20090258033A1 (en) | 2009-10-15 |
| WO2003002065A3 (en) | 2007-04-19 |
| US20030138458A1 (en) | 2003-07-24 |
| EP1572124A2 (en) | 2005-09-14 |
| JP2005502611A (ja) | 2005-01-27 |
| HUP0400346A2 (en) | 2007-08-28 |
| CN1931365A (zh) | 2007-03-21 |
| JP2005298523A (ja) | 2005-10-27 |
| AU2002322358B2 (en) | 2009-06-18 |
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| RENW | Renewal (renewal fees accepted) | ||
| LAPS | Patent lapsed |