CA2258878C - Liposomal influenza vaccine composition and method - Google Patents
Liposomal influenza vaccine composition and method Download PDFInfo
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- CA2258878C CA2258878C CA002258878A CA2258878A CA2258878C CA 2258878 C CA2258878 C CA 2258878C CA 002258878 A CA002258878 A CA 002258878A CA 2258878 A CA2258878 A CA 2258878A CA 2258878 C CA2258878 C CA 2258878C
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Classifications
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/145—Orthomyxoviridae, e.g. influenza virus
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
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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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
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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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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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
- A61K2039/55505—Inorganic adjuvants
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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
- A61K2039/55522—Cytokines; Lymphokines; Interferons
-
- 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
- A61K2039/55522—Cytokines; Lymphokines; Interferons
- A61K2039/55527—Interleukins
- A61K2039/55533—IL-2
-
- 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
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/829—Liposomes, e.g. encapsulation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (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 |
|---|---|---|---|
| US2006396P | 1996-06-24 | 1996-06-24 | |
| US60/020,063 | 1996-06-24 | ||
| PCT/IL1997/000210 WO1997049423A2 (en) | 1996-06-24 | 1997-06-24 | Liposomal influenza vaccine composition and method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2258878A1 CA2258878A1 (en) | 1997-12-31 |
| CA2258878C true CA2258878C (en) | 2008-03-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002258878A Expired - Fee Related CA2258878C (en) | 1996-06-24 | 1997-06-24 | Liposomal influenza vaccine composition and method |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5919480A (enExample) |
| EP (1) | EP0954286B1 (enExample) |
| JP (2) | JP4227195B2 (enExample) |
| AT (1) | ATE422352T1 (enExample) |
| AU (1) | AU731705B2 (enExample) |
| CA (1) | CA2258878C (enExample) |
| DE (1) | DE69739253D1 (enExample) |
| WO (1) | WO1997049423A2 (enExample) |
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| US7731972B1 (en) * | 2000-02-04 | 2010-06-08 | Vlaams Interuniversitair Instituut Voor Biotechnologie | Immunoprotective influenza antigen and its use in vaccination |
| JP2001521908A (ja) * | 1997-10-31 | 2001-11-13 | シストロン バイオテクノロジー インク． | ワクチンアジュバントとして有用な封入された免疫調節物質 |
| AT407958B (de) | 1999-02-11 | 2001-07-25 | Immuno Ag | Inaktivierte influenza-virus-vakzine zur nasalen oder oralen applikation |
| WO2002038175A1 (en) * | 2000-11-07 | 2002-05-16 | Immunovaccine Technologies Inc. | Vaccines with enhanced immune response and methods for their preparation |
| US7662619B2 (en) * | 2000-11-15 | 2010-02-16 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Sol-fusin: use of GP64-6His to catalyze membrane fusion |
| TWI228420B (en) * | 2001-05-30 | 2005-03-01 | Smithkline Beecham Pharma Gmbh | Novel vaccine composition |
| IL159334A0 (en) * | 2001-06-25 | 2004-06-01 | Yissum Res Dev Co | A method for preparation of vesicles loaded with biological material and different uses thereof |
| DE60232413D1 (en) * | 2001-07-05 | 2009-07-02 | Ltb4 Sweden Ab | Ltb4 als adjuvans für impfstoffe |
| US20050169979A1 (en) * | 2002-07-03 | 2005-08-04 | Dov Michaeli | Liposomal vaccine |
| US20040247661A1 (en) * | 2002-07-03 | 2004-12-09 | Dov Michaeli | Liposomal vaccine |
| US20040208920A1 (en) * | 2002-07-03 | 2004-10-21 | Dov Michaeli | Liposomal vaccine |
| CA2523413A1 (en) | 2003-04-25 | 2004-11-11 | The Penn State Research Foundation | Method and system for systemic delivery of growth arresting, lipid-derived bioactive compounds |
| WO2004100928A1 (de) * | 2003-05-09 | 2004-11-25 | Novosom Ag | Injizierbare liposomale depots zum wirkstoffdelivery |
| EP1666059A4 (en) * | 2003-08-11 | 2008-08-27 | Univ Osaka Res Found | NEW VACCINE WITH AN ADJUVANS FOR TRIGGERING ABSORBENT IMMUNITY |
| CN102172397B (zh) * | 2003-08-21 | 2013-01-30 | 利普泰克有限公司 | 树突细胞的体内靶向 |
| FR2868951B1 (fr) * | 2004-04-15 | 2006-07-21 | Ethypharm Sa | Compositions contenant ds vesicules lamellaires incorporant un principe actif peu soluble dans l'eau et produits intermediaires utiles pour leur preparation |
| US20050260260A1 (en) * | 2004-05-19 | 2005-11-24 | Edward Kisak | Liposome compositions for the delivery of macromolecules |
| WO2006074303A2 (en) * | 2005-01-05 | 2006-07-13 | Philadelphia Health And Education Corporation | Delivery vehicles, bioactive substances and viral vaccines |
| CA2523032A1 (en) | 2005-10-07 | 2007-04-07 | Immunovaccine Technologies Inc. | Vaccines for cancer therapy |
| CN106310293A (zh) * | 2007-09-27 | 2017-01-11 | 免疫疫苗技术有限公司 | 在包括连续疏水相的载体中的脂质体在体内输送多核苷酸中的应用 |
| US20100209452A1 (en) * | 2007-10-03 | 2010-08-19 | Immunovaccine Technologies, Inc | Compositions comprising an antigen, an amphipathic compound and a hydrophobic carrier, and uses thereof |
| EP2231180B1 (en) * | 2008-01-16 | 2016-08-17 | Ben-gurion University Of The Negev Research And Development Authority | Vaccine for alzheimer's disease |
| JP5715051B2 (ja) | 2008-06-05 | 2015-05-07 | イムノバクシーン・テクノロジーズ・インコーポレイテッドＩｍｍｕｎｏｖａｃｃｉｎｅ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｉｎｃ． | リポソーム、抗原、ポリヌクレオチド及び疎水性物質の連続相を含む担体を含む組成物 |
| AU2009272280B2 (en) * | 2008-07-14 | 2015-08-06 | Polypid Ltd. | Sustained-release drug carrier composition |
| EP2391370B1 (en) | 2009-02-02 | 2015-06-03 | Galmed Research and Development Ltd. | Methods and compositions for treating alzheimer's disease |
| WO2011005772A1 (en) | 2009-07-06 | 2011-01-13 | Variation Biotechnologies, Inc. | Methods for preparing vesicles and formulations produced therefrom |
| ES2573427T3 (es) | 2009-07-06 | 2016-06-07 | Variation Biotechnologies Inc. | Procedimientos para preparar vesículas y formulaciones producidas a partir de las mismas |
| IN2012DN00570A (enExample) | 2009-07-14 | 2015-06-12 | Polypid Ltd | |
| AU2010303568B2 (en) * | 2009-10-09 | 2014-07-31 | New York Blood Center, Inc. | Immunopotentiator-linked oligomeric influenza immunogenic compositions |
| CA2783001C (en) | 2010-01-19 | 2017-12-12 | Polypid Ltd. | Sustained-release nucleic acid matrix compositions |
| CA2840079C (en) * | 2010-07-06 | 2018-07-03 | Variation Biotechnologies Inc. | Compositions and methods for treating influenza |
| CN107296792B (zh) | 2011-01-13 | 2021-07-27 | 变异生物技术公司 | 囊泡及由其产生之制剂的制备方法 |
| WO2012097346A1 (en) | 2011-01-13 | 2012-07-19 | Variation Biotechnologies, Inc. | Compositions and methods for treating viral infections |
| CN103998058B (zh) | 2011-10-06 | 2021-11-05 | 免疫疫苗技术有限公司 | 包括激活或增加tlr2活性的佐剂的脂质体组合物及其应用 |
| EP2780350B1 (en) | 2011-11-18 | 2019-03-06 | Variation Biotechnologies Inc. | Synthetic derivatives of mpl and uses thereof |
| CA2894442C (en) | 2012-01-12 | 2020-01-21 | Variation Biotechnologies Inc. | Compositions and methods for treating viral infections |
| US20150079077A1 (en) | 2012-01-27 | 2015-03-19 | Variation Biotechnologies, Inc. | Methods and compositions for therapeutic agents |
| CN103736090B (zh) * | 2014-01-27 | 2016-03-02 | 中国医学科学院医学生物学研究所 | 甲磺酸去铁胺佐剂及含甲磺酸去铁胺佐剂的疫苗 |
| CN110151702A (zh) * | 2019-06-24 | 2019-08-23 | 昆明医科大学 | 聚乙二醇修饰流感疫苗脂质体及其制备方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4117113A (en) * | 1974-06-25 | 1978-09-26 | National Research Development Corporation | Immunological preparations |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4235877A (en) * | 1979-06-27 | 1980-11-25 | Merck & Co., Inc. | Liposome particle containing viral or bacterial antigenic subunit |
| US4534899A (en) | 1981-07-20 | 1985-08-13 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
| US4426330A (en) | 1981-07-20 | 1984-01-17 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
| JPH0720857B2 (ja) * | 1988-08-11 | 1995-03-08 | テルモ株式会社 | リポソームおよびその製法 |
| AU627226B2 (en) * | 1988-08-25 | 1992-08-20 | Liposome Company, Inc., The | Influenza vaccine and novel adjuvants |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| JP3037994B2 (ja) * | 1989-11-02 | 2000-05-08 | テルモ株式会社 | リポソーム表面への蛋白質吸着抑制剤 |
| JP3220180B2 (ja) * | 1991-05-23 | 2001-10-22 | 三菱化学株式会社 | 薬剤含有タンパク質結合リポソーム |
| JPH07504683A (ja) * | 1992-07-08 | 1995-05-25 | シェリング・コーポレーション | Ｇｍ−ｃｓｆのワクチンアジュバントとしての利用 |
| US6326353B1 (en) * | 1993-03-23 | 2001-12-04 | Sequus Pharmaceuticals, Inc. | Enhanced circulation effector composition and method |
| WO1995004524A1 (en) * | 1993-08-06 | 1995-02-16 | Opperbas Holding B.V. | A method for high loading of vesicles with biopolymeric substances |
| AUPM500494A0 (en) * | 1994-04-12 | 1994-05-05 | Minister For Agriculture & Rural Affairs For The State Of New South Wales, The | Composition for use in increasing mucosal immunity |
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- 1997-06-24 DE DE69739253T patent/DE69739253D1/de not_active Expired - Lifetime
- 1997-06-24 AT AT97927355T patent/ATE422352T1/de not_active IP Right Cessation
- 1997-06-24 AU AU31882/97A patent/AU731705B2/en not_active Ceased
- 1997-06-24 WO PCT/IL1997/000210 patent/WO1997049423A2/en not_active Ceased
- 1997-06-24 CA CA002258878A patent/CA2258878C/en not_active Expired - Fee Related
- 1997-06-24 JP JP50263298A patent/JP4227195B2/ja not_active Expired - Fee Related
- 1997-06-24 EP EP97927355A patent/EP0954286B1/en not_active Expired - Lifetime
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2008
- 2008-06-06 JP JP2008149959A patent/JP2008260779A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0954286B1 (en) | 2009-02-11 |
| JP4227195B2 (ja) | 2009-02-18 |
| WO1997049423A2 (en) | 1997-12-31 |
| US5919480A (en) | 1999-07-06 |
| AU3188297A (en) | 1998-01-14 |
| AU731705B2 (en) | 2001-04-05 |
| WO1997049423A3 (en) | 1998-02-19 |
| DE69739253D1 (de) | 2009-03-26 |
| JP2008260779A (ja) | 2008-10-30 |
| EP0954286A2 (en) | 1999-11-10 |
| CA2258878A1 (en) | 1997-12-31 |
| JP2000513352A (ja) | 2000-10-10 |
| ATE422352T1 (de) | 2009-02-15 |
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