IL190775A - Influenza virus-like particles, vaccines containing them and their uses - Google Patents
Influenza virus-like particles, vaccines containing them and their usesInfo
- Publication number
- IL190775A IL190775A IL190775A IL19077508A IL190775A IL 190775 A IL190775 A IL 190775A IL 190775 A IL190775 A IL 190775A IL 19077508 A IL19077508 A IL 19077508A IL 190775 A IL190775 A IL 190775A
- Authority
- IL
- Israel
- Prior art keywords
- particles
- same
- influenza virus
- vaccines containing
- vaccines
- Prior art date
Links
- 206010022000 influenza Diseases 0.000 title 1
- 239000002245 particle Substances 0.000 title 1
- 229960005486 vaccine Drugs 0.000 title 1
Classifications
-
- 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
- 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
- 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
-
- 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
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K14/08—RNA viruses
- C07K14/11—Orthomyxoviridae, e.g. influenza virus
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
-
- 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
- A61K2039/55555—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
- C12N2760/16123—Virus like particles [VLP]
-
- 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)
- Virology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72751305P | 2005-10-18 | 2005-10-18 | |
| US78084706P | 2006-03-10 | 2006-03-10 | |
| US80000606P | 2006-05-15 | 2006-05-15 | |
| US83119606P | 2006-07-17 | 2006-07-17 | |
| US83211606P | 2006-07-21 | 2006-07-21 | |
| US84549506P | 2006-09-19 | 2006-09-19 | |
| PCT/US2006/040862 WO2007047831A2 (en) | 2005-10-18 | 2006-10-18 | Functional influenza virus like particles (vlps) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL190775A0 IL190775A0 (en) | 2008-11-03 |
| IL190775A true IL190775A (en) | 2016-04-21 |
Family
ID=37963272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL190775A IL190775A (en) | 2005-10-18 | 2008-04-10 | Influenza virus-like particles, vaccines containing them and their uses |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1937301B1 (OSRAM) |
| JP (5) | JP5714799B2 (OSRAM) |
| KR (1) | KR101359723B1 (OSRAM) |
| CN (2) | CN103865892B (OSRAM) |
| AU (1) | AU2006304640B2 (OSRAM) |
| BR (1) | BRPI0617486A2 (OSRAM) |
| CA (1) | CA2625406C (OSRAM) |
| DK (1) | DK1937301T3 (OSRAM) |
| ES (1) | ES2543056T3 (OSRAM) |
| HU (1) | HUE026136T2 (OSRAM) |
| IL (1) | IL190775A (OSRAM) |
| NZ (1) | NZ567164A (OSRAM) |
| PL (1) | PL1937301T3 (OSRAM) |
| PT (1) | PT1937301E (OSRAM) |
| RU (1) | RU2483751C2 (OSRAM) |
| SG (1) | SG2014012868A (OSRAM) |
| SI (1) | SI1937301T1 (OSRAM) |
| TW (1) | TWI488968B (OSRAM) |
| WO (1) | WO2007047831A2 (OSRAM) |
Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0250488A (ja) * | 1988-08-11 | 1990-02-20 | Nec Corp | 超伝導配線 |
| US8551756B2 (en) | 2003-07-11 | 2013-10-08 | Novavax, Inc. | Avian influenza chimeric VLPS |
| US9101578B2 (en) | 2006-05-01 | 2015-08-11 | Technovax, Inc. | Polyvalent influenza virus-like particle (VLP) compositions |
| US8778353B2 (en) | 2006-05-01 | 2014-07-15 | Technovax, Inc. | Influenza virus-like particle (VLP) compositions |
| CA2659275C (en) * | 2006-07-27 | 2017-01-10 | Ligocyte Pharmaceuticals, Inc. | Chimeric influenza virus-like particles |
| US8202967B2 (en) | 2006-10-27 | 2012-06-19 | Boehringer Ingelheim Vetmedica, Inc. | H5 proteins, nucleic acid molecules and vectors encoding for those, and their medicinal use |
| CA2615372A1 (en) | 2007-07-13 | 2009-01-13 | Marc-Andre D'aoust | Influenza virus-like particles (vlps) comprising hemagglutinin |
| CN101801411A (zh) * | 2007-07-19 | 2010-08-11 | 诺瓦瓦克斯股份有限公司 | 嵌合水痘带状疱疹病毒病毒样颗粒 |
| WO2009073330A2 (en) | 2007-11-12 | 2009-06-11 | The Trustees Of The University Of Pennsylvania | Novel vaccines against multiple subtypes of influenza virus |
| ES2554703T3 (es) | 2007-11-27 | 2015-12-22 | Medicago Inc. | Partículas recombinantes semejantes al virus de la influenza (VLP) producidas en plantas transgénicas que expresan hemaglutinina |
| CN105753948A (zh) | 2008-07-08 | 2016-07-13 | 麦迪卡格公司 | 可溶性重组流感抗原 |
| CA2730668C (en) * | 2008-07-18 | 2020-04-28 | Medicago Inc. | New influenza virus immunizing epitope |
| EP3542815A1 (en) * | 2008-11-28 | 2019-09-25 | Boehringer Ingelheim Animal Health USA Inc. | Recombinant avian influenza vaccine and uses thereof |
| JP2012525134A (ja) * | 2009-04-30 | 2012-10-22 | サイトス バイオテクノロジー アーゲー | インフルエンザ赤血球凝集素の組成物とその使用 |
| SG175781A1 (en) * | 2009-05-01 | 2011-12-29 | Redbiotec Ag | Recombinant virus-like particles encoded by multi-gene vector |
| TW201738562A (zh) * | 2009-05-28 | 2017-11-01 | 亞培生物股份有限公司 | 體外病原體檢驗技術 |
| EP2445928B1 (en) | 2009-06-24 | 2018-03-28 | Medicago Inc. | Chimeric influenza virus-like particles comprising hemagglutinin |
| MX2012003372A (es) | 2009-09-22 | 2012-05-29 | Medicago Inc | Metodo para preparar proteina derivada de vegetales. |
| WO2011102900A1 (en) * | 2010-02-18 | 2011-08-25 | Technovax, Inc. | Universal virus-like particle (vlp) influenza vaccines |
| US10130697B2 (en) | 2010-03-23 | 2018-11-20 | Wisconsin Alumni Research Foundation (Warf) | Vaccines comprising mutant attenuated influenza viruses |
| JP2012036154A (ja) * | 2010-08-11 | 2012-02-23 | Goshu Yakuhin Kk | 食品 |
| CN101947317B (zh) * | 2010-09-27 | 2012-05-30 | 武汉大学 | 一种h5n1禽流感病毒样颗粒疫苗的规模化制备方法 |
| WO2012122858A1 (zh) * | 2011-03-17 | 2012-09-20 | 中国科学院上海巴斯德研究所 | 一种利用果蝇细胞生产病毒样颗粒的方法及应用 |
| TWI620816B (zh) | 2011-03-23 | 2018-04-11 | 苜蓿股份有限公司 | 植物衍生蛋白回收方法 |
| EA016866B1 (ru) * | 2011-06-06 | 2012-08-30 | Общество С Ограниченной Ответственностью "Форт" (Ооо "Форт") | Вакцина для специфической профилактики гриппа |
| KR101302245B1 (ko) * | 2011-06-27 | 2013-09-02 | 조지아 스테이트 유니버시티 리서치 파운데이션, 인코포레이티드 | 넓은 범위의 교차 방어능력을 갖는 신규한 보강 인플루엔자 백신 |
| AR088028A1 (es) * | 2011-08-15 | 2014-05-07 | Boehringer Ingelheim Vetmed | Proteinas h5, de h5n1 para un uso medicinal |
| WO2013032942A1 (en) | 2011-08-26 | 2013-03-07 | Yoshihiro Kawaoka | Influenza viruses with mutant pb2 gene segment as live attenuated vaccines |
| JP5884100B2 (ja) * | 2011-08-31 | 2016-03-15 | 公益財団法人東京都医学総合研究所 | 新型インフルエンザウイルス由来ヘマグルチニンタンパク質遺伝子を有するDIs株由来組換えワクシニアウイルス |
| CN103930435A (zh) * | 2011-09-30 | 2014-07-16 | 麦迪卡格公司 | 增加植物中病毒样颗粒的产率 |
| US11390878B2 (en) | 2011-09-30 | 2022-07-19 | Medicago Inc. | Increasing protein yield in plants |
| EP2809345A4 (en) * | 2012-02-03 | 2015-11-25 | Univ Emory | IMMUNOSTIMULATING COMPOSITIONS, PARTICLES THEREFOR, AND USES THEREFOR |
| RU2485973C1 (ru) * | 2012-02-28 | 2013-06-27 | Общество с ограниченной ответственностью "НТфарма" | Рекомбинантная трехвалентная вакцина от гриппа человека |
| MX360137B (es) * | 2013-02-21 | 2018-10-24 | Boehringer Ingelheim Vetmedica Gmbh | Proteínas h5 del virus de la influenza h5n1 para usarse como un medicamento. |
| US9649375B2 (en) * | 2013-03-14 | 2017-05-16 | The Administrators Of The Tulane Educational Fund | Immunogenic peptide conjugate and method for inducing an anti-influenza therapeutic antibody response therewith |
| WO2014153674A1 (en) * | 2013-03-28 | 2014-10-02 | Medicago Inc. | Influenza virus-like particle production in plants |
| US12467058B2 (en) | 2013-03-28 | 2025-11-11 | Aramis Biotechnologies Inc. | Influenza virus-like particle production in plants |
| DK3092309T3 (da) | 2014-01-10 | 2021-04-12 | Medicago Inc | Cpmv-forstærkerelementer |
| CN103740655A (zh) * | 2014-01-20 | 2014-04-23 | 瑞鑫百奥生物科技(深圳)有限公司 | H5n1禽流感病毒样颗粒及其应用和制备方法、疫苗 |
| US10563213B2 (en) | 2014-03-27 | 2020-02-18 | Medicago Inc. | Modified CPMV enhancer elements |
| WO2015195218A1 (en) * | 2014-06-20 | 2015-12-23 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Polyvalent influenza virus-like particles (vlps) and use as vaccines |
| WO2015196150A2 (en) | 2014-06-20 | 2015-12-23 | Wisconsin Alumni Research Foundation (Warf) | Mutations that confer genetic stability to additional genes in influenza viruses |
| JP2018530314A (ja) * | 2015-08-28 | 2018-10-18 | ウィスコンシン アルムニ リサーチ ファンデイション | ウイルス様粒子からの感染性インフルエンザウイルスの生成 |
| RU2639491C2 (ru) * | 2015-08-31 | 2017-12-21 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Московский государственный университет имени М.В. Ломоносова" (МГУ) | Вирионы и вирусоподобные частицы вируса мозаики альтернантеры как усилители иммунного ответа |
| CN114617959A (zh) | 2015-09-03 | 2022-06-14 | 诺瓦瓦克斯股份有限公司 | 具有改进的稳定性和免疫原性的疫苗组合物 |
| EP3417056A1 (en) | 2016-02-19 | 2018-12-26 | Wisconsin Alumni Research Foundation (WARF) | Improved influenza b virus replication for vaccine development |
| US11123421B2 (en) * | 2016-04-18 | 2021-09-21 | Versitech Limited | Cold adapted and virulence factor deleted live attenuated vaccine suitable for mucosal delivery |
| WO2019023811A1 (en) | 2017-08-04 | 2019-02-07 | The Hospital For Sick Children | NANOPARTICLE PLATFORM FOR ANTIBODY AND VACCINE DELIVERY |
| CN107353328A (zh) * | 2017-08-23 | 2017-11-17 | 上海市动物疫病预防控制中心 | 一种重组的h9n2亚型禽流感病毒样颗粒及其制备方法和用途 |
| CN110240634B (zh) * | 2018-03-08 | 2022-09-06 | 普莱柯生物工程股份有限公司 | 一种禽流感病毒样颗粒疫苗、及其制备方法和应用 |
| CN108409842A (zh) * | 2018-03-15 | 2018-08-17 | 山东省农业科学院畜牧兽医研究所 | 一种单克隆抗体及其制备方法 |
| US12343390B2 (en) | 2018-08-07 | 2025-07-01 | Wisconsin Alumni Research Foundation (Warf) | Recombinant biologically contained filovirus vaccine |
| JP7655849B2 (ja) | 2018-08-20 | 2025-04-02 | ウィスコンシン アルムニ リサーチ ファンデイション | ヘマグルチニン(ha)タンパク質内の非ドミナントエピトープに対する免疫応答を誘起するためのベクター |
| EP3921413A1 (en) | 2019-02-08 | 2021-12-15 | Wisconsin Alumni Research Foundation (WARF) | Humanized cell line |
| US11390649B2 (en) | 2019-05-01 | 2022-07-19 | Wisconsin Alumni Research Foundation (Warf) | Influenza virus replication for vaccine development |
| WO2021041624A2 (en) | 2019-08-27 | 2021-03-04 | Yoshihiro Kawaoka | Recombinant influenza viruses with stabilized ha for replication in eggs |
| JP2023511444A (ja) | 2020-01-24 | 2023-03-17 | ウィスコンシン アルムニ リサーチ ファンデイション | 安定化されたnaを有する組換えインフルエンザウイルス |
| KR102151962B1 (ko) * | 2020-03-24 | 2020-09-04 | 안병철 | 어린 포유동물의 전염성 질병을 예방 또는 치료하기 위한 혈청 조성물의 제조방법, 상기 방법에 의해 제조된 혈청 조성물 및 이의 용도 |
| JP7672162B2 (ja) * | 2020-03-24 | 2025-05-07 | チョル アン,ビョン | 幼い哺乳動物の粘膜関連伝染性疾病を予防または治療するための血清組成物の製造方法、前記方法によって製造された血清組成物及びその用途 |
| US12290562B2 (en) | 2020-03-25 | 2025-05-06 | Wisconsin Alumni Research Foundation (Warf) | Recombinant multivalent influenza viruses |
| CN113461786B (zh) * | 2020-03-30 | 2022-09-13 | 普莱柯生物工程股份有限公司 | 一种禽流感病毒样颗粒疫苗、及其制备方法和应用 |
| EP4144365A4 (en) | 2020-05-01 | 2024-06-05 | Sinocelltech Ltd. | METHODS FOR IMPROVING THE IMMUNOGENERICITY OF PROTEIN/PEPTIDE ANTIGEN |
| CN112342149A (zh) * | 2020-11-12 | 2021-02-09 | 新疆畜牧科学院兽医研究所(新疆畜牧科学院动物临床医学研究中心) | 一种禽流感病毒样颗粒组装表达系统及其应用 |
| CN112979796A (zh) * | 2021-04-27 | 2021-06-18 | 军事科学院军事医学研究院军事兽医研究所 | 马抗甲型h5n1虎源流感病毒免疫球蛋白和特异性免疫球蛋白及其精制方法 |
| CN113862284B (zh) * | 2021-09-13 | 2023-05-26 | 华南农业大学 | 一种编码重组禽流感病毒ha蛋白的基因、病毒样颗粒、疫苗及制备与应用 |
| CN114262720B (zh) * | 2021-12-27 | 2023-07-25 | 河南兴华生物技术有限公司 | 杆状病毒表达系统的信号肽及其应用 |
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| CN1196788C (zh) | 2000-06-23 | 2005-04-13 | 惠氏控股有限公司 | 野生型和嵌合流感病毒样颗粒(vlp)的装配 |
| AU2003219760A1 (en) | 2002-02-14 | 2003-09-04 | Novavax, Inc. | Optimization of gene sequences of virus-like particles for expression in insect cells |
| US8592197B2 (en) * | 2003-07-11 | 2013-11-26 | Novavax, Inc. | Functional influenza virus-like particles (VLPs) |
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2006
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