CA2756797C - Codon-optimized polynucleotide-based vaccines against human cytomegalovirus infection - Google Patents
Codon-optimized polynucleotide-based vaccines against human cytomegalovirus infection Download PDFInfo
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- CA2756797C CA2756797C CA2756797A CA2756797A CA2756797C CA 2756797 C CA2756797 C CA 2756797C CA 2756797 A CA2756797 A CA 2756797A CA 2756797 A CA2756797 A CA 2756797A CA 2756797 C CA2756797 C CA 2756797C
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| US43554902P | 2002-12-23 | 2002-12-23 | |
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| CA2508228A CA2508228C (en) | 2002-12-23 | 2003-12-19 | Codon-optimized polynucleotide-based vaccines against human cytomegalovirus infection |
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| CA2508228A Division CA2508228C (en) | 2002-12-23 | 2003-12-19 | Codon-optimized polynucleotide-based vaccines against human cytomegalovirus infection |
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Families Citing this family (99)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7105574B1 (en) * | 1999-03-26 | 2006-09-12 | Vical Incorporated | Adjuvant compositions and methods for enhancing immune responses to polynucleotide-based vaccines |
| DE60039198D1 (de) * | 1999-03-26 | 2008-07-24 | Vical Inc | Adjuvanszusammensetzungen zur Erhöhung der Immunantwort bezüglich Polynukleotid-basierenden Impfstoffen |
| WO2004024067A2 (en) * | 2002-09-10 | 2004-03-25 | Vical Incorporated | Codon-optimized polynucleotide-based vaccines against bacillus anthracis infection |
| DE60333035D1 (de) * | 2002-12-23 | 2010-07-29 | Vical Inc | Impfstoffe gegen infektionen mit dem humanen zytomegalivirus auf grundlage von codonoptimierten polynukleotiden |
| CA2508279A1 (en) | 2002-12-23 | 2004-07-22 | Vical Incorporated | Method for freeze-drying nucleic acid/block copolymer/cationic surfactant complexes |
| US7381422B2 (en) * | 2002-12-23 | 2008-06-03 | Vical Incorporated | Method for producing sterile polynucleotide based medicaments |
| EP1607485A1 (en) * | 2004-06-14 | 2005-12-21 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Method for quantifying VEGF121 isoform in a biological sample |
| WO2006060723A2 (en) * | 2004-12-03 | 2006-06-08 | Vical Incorporated | Methods for producing block copolymer/amphiphilic particles |
| CN1307423C (zh) * | 2005-01-08 | 2007-03-28 | 王明丽 | 重组抗原pp65包被酶标反应板的制法及ELISA检测试剂盒 |
| JP2006223194A (ja) * | 2005-02-17 | 2006-08-31 | Tosoh Corp | スタニオカルシン1(STC1)mRNAの測定方法 |
| EP1851238A4 (en) * | 2005-02-24 | 2008-12-31 | Univ Massachusetts | FLUID NUCLEIC ACIDS, POLYPEPTIDES AND USES THEREOF |
| US9303080B2 (en) | 2006-01-13 | 2016-04-05 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, National Institutes Of Health | Codon optimized IL-15 and IL-15R-alpha genes for expression in mammalian cells |
| WO2008051285A2 (en) | 2006-04-01 | 2008-05-02 | Medical Service Consultation International, Llc | Methods and compositions for detecting fungi and mycotoxins |
| MX2009010549A (es) * | 2007-03-30 | 2010-03-15 | Univ New York State Res Found | Virus atenuados utiles para vacunas. |
| WO2009005917A2 (en) * | 2007-05-29 | 2009-01-08 | Vical Incorporated | Methods of treating measles infectious disease in mammals |
| EP2185195A2 (en) | 2007-08-16 | 2010-05-19 | Tripep Ab | Immunogen platform |
| EP3156069B8 (en) | 2008-06-20 | 2020-10-21 | Duke University | Compositions, methods, and kits for eliciting an immune response |
| EP2313503A4 (en) * | 2008-08-01 | 2014-01-08 | Merck Sharp & Dohme | Variant HCMV-PP65, IE1 and IE2 polynucleotides, and uses thereof |
| US20100068718A1 (en) | 2008-08-22 | 2010-03-18 | Hooper Dennis G | Methods and Compositions for Identifying Yeast |
| US20110300205A1 (en) | 2009-07-06 | 2011-12-08 | Novartis Ag | Self replicating rna molecules and uses thereof |
| EP4218799A1 (en) | 2009-07-15 | 2023-08-02 | GlaxoSmithKline Biologicals S.A. | Rsv f protein compositions and methods for making same |
| JP5833443B2 (ja) * | 2009-08-29 | 2015-12-16 | 株式会社バイオメッドコア | 抗原特異的t細胞誘導能測定法 |
| US8962251B2 (en) | 2009-10-08 | 2015-02-24 | Medical Service Consultation International, Llc | Methods and compositions for identifying sulfur and iron modifying bacteria |
| EP2493911B1 (en) * | 2009-10-30 | 2017-10-18 | The Administrators of The Tulane Educational Fund | Peptide compositions and methods for inhibiting herpesvirus infection |
| EP2534164A4 (en) * | 2010-02-11 | 2013-09-11 | Intelligent Med Devices Inc | OLIGONUCLEOTIDES RELATING TO DIFFICULT CLOSTRIDIUM GENES ENCODING TOXIN B. TOXIN A OR TOXIN BINARY |
| US9192661B2 (en) | 2010-07-06 | 2015-11-24 | Novartis Ag | Delivery of self-replicating RNA using biodegradable polymer particles |
| ES2646669T3 (es) | 2010-07-06 | 2017-12-14 | Glaxosmithkline Biologicals Sa | Procedimientos de aumento de una respuesta inmunitaria mediante el suministro de ARN |
| RU2625546C2 (ru) | 2010-07-06 | 2017-07-14 | Новартис Аг | Катионные эмульсии "масло-в-воде" |
| US9770463B2 (en) | 2010-07-06 | 2017-09-26 | Glaxosmithkline Biologicals Sa | Delivery of RNA to different cell types |
| ES2586580T3 (es) | 2010-07-06 | 2016-10-17 | Glaxosmithkline Biologicals Sa | Inmunización de mamíferos grandes con dosis bajas de ARN |
| HUE026646T2 (en) | 2010-07-06 | 2016-07-28 | Glaxosmithkline Biologicals Sa | Preferred liposomes containing lipids of PKA value for delivery of RNA |
| HRP20161352T1 (hr) | 2010-07-06 | 2016-12-02 | Glaxosmithkline Biologicals Sa | Čestice nalik na virione za unos samoreplicirajućih molekula rna |
| DK4226941T3 (da) | 2010-08-31 | 2024-12-02 | Glaxosmithkline Biologicals Sa | Pegylerede liposomer til levering af immunogen-kodende rna |
| US9127321B2 (en) * | 2010-10-06 | 2015-09-08 | The Translational Genomics Research Institute | Method of detecting Coccidioides species |
| KR102266691B1 (ko) | 2010-10-11 | 2021-06-23 | 노파르티스 아게 | 항원 전달 플랫폼 |
| PT2667892T (pt) | 2011-01-26 | 2019-06-07 | Glaxosmithkline Biologicals Sa | Regime de imunização contra o vsr |
| WO2012158613A1 (en) | 2011-05-13 | 2012-11-22 | Novartis Ag | Pre-fusion rsv f antigens |
| JP6184945B2 (ja) | 2011-06-08 | 2017-08-23 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | mRNA送達のための脂質ナノ粒子組成物および方法 |
| EP2729168A2 (en) | 2011-07-06 | 2014-05-14 | Novartis AG | Immunogenic compositions and uses thereof |
| AU2012280901B2 (en) | 2011-07-06 | 2016-11-10 | Glaxosmithkline Biologicals S.A. | Oil-in-water emulsions that contain nucleic acids |
| US11896636B2 (en) | 2011-07-06 | 2024-02-13 | Glaxosmithkline Biologicals Sa | Immunogenic combination compositions and uses thereof |
| TWI570240B (zh) | 2011-09-09 | 2017-02-11 | 默沙東公司 | 作為細胞巨大病毒疫苗之條件式複製cmv |
| CA2872033A1 (en) | 2011-10-11 | 2013-04-18 | Novartis Ag | Recombinant self-replicating polycistronic rna molecules |
| CN111995664B (zh) | 2011-11-11 | 2024-08-02 | 变异生物技术公司 | 用于治疗巨细胞病毒的组合物和方法 |
| BR112014023913B1 (pt) | 2012-03-27 | 2022-08-09 | Variation Biotechnologies Inc | Métodos para detecção de anticorpos neutralizantes de anticitomegalovírus |
| CN104853770A (zh) | 2012-07-06 | 2015-08-19 | 诺华股份有限公司 | 免疫原性组合物及其应用 |
| JP6199965B2 (ja) | 2012-07-11 | 2017-09-20 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | Rpgrx連鎖性網膜変性のaav媒介型遺伝子治療 |
| EP2904119B1 (en) | 2012-10-02 | 2020-06-17 | The General Hospital Corporation d/b/a Massachusetts General Hospital | Methods relating to dna-sensing pathway related conditions |
| HK1214962A1 (zh) | 2013-01-10 | 2016-08-12 | Seqirus UK Limited | 流感病毒免疫原性组合物及其应用 |
| EP2765137A1 (en) | 2013-02-07 | 2014-08-13 | Sanofi Pasteur | Induction of cross-reactive cellular response against rhinovirus antigens |
| BR112015023737A2 (pt) | 2013-03-15 | 2017-10-24 | Applied Food Biotech Inc | polipeptídeo do receptor felino tas2r isolado (ftas2r), composição, polinucleotídeo isolado, par de iniciadores, vetor de expressão, célula hospedeira, cultura celular, oligonucleotídeo, anticorpo isolado ou um fragmento desse, método para identificar um composto que interage com um polipeptídeo do receptor felino tas2r, método para identificar um composto que modula um polipeptídeo do receptor felino tas2r, método para preparar uma composição comestível, método para formular uma composição comestível com palatabilidade intensificada, método para administrar um composto amargo a um animal que necessita desse, método para preparar uma composição comestível para controlar a palatabilidade da composição comestível para um animal, método para produzir uma composição de sabor para revestimento ou incorporação em uma composição comestível a ser administrada para um animal, e composição de sabor para revestimento ou incorporação em uma composição comestível a ser administrada para um animal |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| WO2015130584A2 (en) | 2014-02-25 | 2015-09-03 | Merck Sharp & Dohme Corp. | Lipid nanoparticle vaccine adjuvants and antigen delivery systems |
| WO2017011773A2 (en) * | 2015-07-15 | 2017-01-19 | Modernatx, Inc. | Codon-optimized nucleic acids encoding antibodies |
| MA42502A (fr) | 2015-07-21 | 2018-05-30 | Modernatx Inc | Vaccins contre une maladie infectieuse |
| US11364292B2 (en) | 2015-07-21 | 2022-06-21 | Modernatx, Inc. | CHIKV RNA vaccines |
| EA201891001A1 (ru) | 2015-10-22 | 2018-11-30 | МОДЕРНАТиЭкс, ИНК. | Вакцины на основе нуклеиновых кислот против вируса ветряной оспы (vzv) |
| WO2017070613A1 (en) | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Human cytomegalovirus vaccine |
| EP3364982A4 (en) | 2015-10-22 | 2019-04-17 | ModernaTX, Inc. | VACCINES AGAINST SEXUALLY TRANSMITTED DISEASES |
| EP3364950A4 (en) | 2015-10-22 | 2019-10-23 | ModernaTX, Inc. | VACCINES AGAINST TROPICAL DISEASES |
| US10611800B2 (en) | 2016-03-11 | 2020-04-07 | Pfizer Inc. | Human cytomegalovirus gB polypeptide |
| CN110191954B (zh) | 2016-07-08 | 2024-05-14 | 宾夕法尼亚州大学信托人 | 用于治疗涉及rdh12的病症和疾病的方法和组合物 |
| EP3528827A4 (en) | 2016-10-21 | 2020-11-04 | Merck Sharp & Dohme Corp. | Influenza hemagglutinin protein vaccines |
| MA46584A (fr) | 2016-10-21 | 2019-08-28 | Modernatx Inc | Vaccin contre le cytomégalovirus humain |
| EP3538146A4 (en) | 2016-11-11 | 2020-07-15 | ModernaTX, Inc. | INFLUENZA VACCINE |
| MA50335A (fr) | 2016-12-08 | 2020-08-19 | Modernatx Inc | Vaccins à acide nucléique contre des virus respiratoires |
| EP3582790A4 (en) | 2017-02-16 | 2020-11-25 | ModernaTX, Inc. | VERY POWERFUL IMMUNOGENIC COMPOSITIONS |
| WO2018170270A1 (en) | 2017-03-15 | 2018-09-20 | Modernatx, Inc. | Varicella zoster virus (vzv) vaccine |
| EP3595713A4 (en) | 2017-03-15 | 2021-01-13 | ModernaTX, Inc. | Respiratory syncytial virus vaccine |
| US11576961B2 (en) | 2017-03-15 | 2023-02-14 | Modernatx, Inc. | Broad spectrum influenza virus vaccine |
| US11752206B2 (en) | 2017-03-15 | 2023-09-12 | Modernatx, Inc. | Herpes simplex virus vaccine |
| JP7235676B2 (ja) | 2017-05-17 | 2023-03-08 | ザ ジェネラル ホスピタル コーポレイション | 結節性硬化症の遺伝子治療 |
| AU2018285694B2 (en) | 2017-06-15 | 2025-04-10 | Access To Advanced Health Institute | Nanostructured lipid carriers and stable emulsions and uses thereof |
| EP3681514A4 (en) | 2017-09-14 | 2021-07-14 | ModernaTX, Inc. | RNA VACZINE AGAINST ZIKA VIRUS |
| AU2019212237B2 (en) | 2018-01-29 | 2024-12-12 | Merck Sharp & Dohme Llc | Stabilized RSV F proteins and uses thereof |
| MA54676A (fr) | 2018-01-29 | 2021-11-17 | Modernatx Inc | Vaccins à base d'arn contre le vrs |
| CN109082413B (zh) * | 2018-09-18 | 2023-01-10 | 四川安可瑞新材料技术有限公司 | 抗人IgG单克隆抗体、其杂交瘤细胞株及应用 |
| US11629172B2 (en) | 2018-12-21 | 2023-04-18 | Pfizer Inc. | Human cytomegalovirus gB polypeptide |
| US11351242B1 (en) | 2019-02-12 | 2022-06-07 | Modernatx, Inc. | HMPV/hPIV3 mRNA vaccine composition |
| US12070495B2 (en) | 2019-03-15 | 2024-08-27 | Modernatx, Inc. | HIV RNA vaccines |
| KR20220140901A (ko) | 2020-02-14 | 2022-10-18 | 머크 샤프 앤드 돔 엘엘씨 | Hpv 백신 |
| CN116096430A (zh) | 2020-04-27 | 2023-05-09 | 衣阿华大学研究基金会 | 用于治疗囊性纤维化的组合物和方法 |
| EP4146797A1 (en) | 2020-05-06 | 2023-03-15 | Orchard Therapeutics (Europe) Limited | Treatment for neurodegenerative diseases |
| TWI810589B (zh) | 2020-06-21 | 2023-08-01 | 美商輝瑞股份有限公司 | 人巨細胞病毒糖蛋白B(gB)多肽 |
| US11406703B2 (en) | 2020-08-25 | 2022-08-09 | Modernatx, Inc. | Human cytomegalovirus vaccine |
| WO2022051022A1 (en) | 2020-09-04 | 2022-03-10 | Infectious Disease Research Institute | Co-lyophilized rna and nanostructured lipid carrier |
| CA3173951A1 (en) | 2020-09-04 | 2022-03-10 | Emily VOIGT | Genetically-adjuvanted rna vaccines |
| US20230338501A1 (en) | 2020-09-04 | 2023-10-26 | Access To Advanced Health Institute | Live-attenuated rna hybrid vaccine technology |
| TW202245835A (zh) | 2021-02-04 | 2022-12-01 | 美商默沙東有限責任公司 | 用於肺炎球菌結合物疫苗之奈米乳化液佐劑組合物 |
| EP4323525A2 (en) | 2021-04-16 | 2024-02-21 | Genentech, Inc. | Optimized tlr7 ligands and uses thereof |
| CN117715928A (zh) | 2021-06-14 | 2024-03-15 | 桥生物基因疗法研究有限责任公司 | 用于结节性硬化的基因疗法 |
| AU2022327583A1 (en) | 2021-08-11 | 2024-02-22 | King's College London | Compositions and methods for improved treatment of disorders affecting the central nervous system |
| AR126813A1 (es) | 2021-08-19 | 2023-11-15 | Merck Sharp & Dohme Llc | Nueva nanopartícula lipídica termostable y métodos de uso de la misma |
| WO2023228116A1 (en) | 2022-05-24 | 2023-11-30 | Access To Advanced Health Institute | Intranasal administration of thermostable rna vaccines |
| AU2023336224A1 (en) | 2022-09-09 | 2025-03-27 | Access To Advanced Health Institute | Immunogenic vaccine composition incorporating a saponin |
| EP4594505A1 (en) | 2022-09-30 | 2025-08-06 | Centre National de la Recherche Scientifique | Therapy by trans-splicing of opa1 pre-messenger rnas for the treatment of diseases associated with opa1 gene mutations |
| WO2024147114A1 (en) | 2023-01-06 | 2024-07-11 | Bloomsbury Genetic Therapies Limited | Compositions and methods for treating parkinson's disease |
| WO2024233425A2 (en) | 2023-05-08 | 2024-11-14 | Merck Sharp & Dohme Llc | Polynucleotides encoding norovirus vp1 antigens and uses thereof |
| WO2024254226A1 (en) | 2023-06-09 | 2024-12-12 | Merck Sharp & Dohme Llc | Nanoemulsion adjuvant compositions for human papillomavirus vaccines |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US6100064A (en) | 1984-04-06 | 2000-08-08 | Chiron Corporation | Secreted viral proteins useful for vaccines and diagnostics |
| US6133433A (en) * | 1984-07-27 | 2000-10-17 | City Of Hope | Method for detection and prevention of human cytomegalovirus infection |
| US6242567B1 (en) * | 1984-07-27 | 2001-06-05 | City Of Hope | Method for detection and prevention of human cytomegalovirus infection |
| JPS6147500A (ja) | 1984-08-15 | 1986-03-07 | Res Dev Corp Of Japan | キメラモノクロ−ナル抗体及びその製造法 |
| EP0173494A3 (en) | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Chimeric receptors by dna splicing and expression |
| GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| JPS63501765A (ja) | 1985-11-01 | 1988-07-21 | インタ−ナショナル、ジェネティック、エンジニアリング インコ−ポレ−テッド | 抗体遺伝子のモジュ−ル組立体、それにより産生された抗体及び用途 |
| US6162620A (en) | 1986-03-07 | 2000-12-19 | Cogent Limited | Processes for the production of HCMV glycoproteins, antibodies thereto and HCMV vaccines, and recombinant vectors therefor |
| US5124440A (en) * | 1986-11-24 | 1992-06-23 | The Childrens Hospital, Inc. | Antibody and T cell recognition sites on glycoproteins comprising the GCI complex of human cytomegalovirus |
| US5547834A (en) * | 1988-01-29 | 1996-08-20 | Chiron Corporation | Recombinant CMV neutralizing proteins |
| EP0436537A4 (en) | 1988-01-29 | 1992-04-08 | Chiron Corporation | Recombinant cmv neutralizing proteins |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
| US6174666B1 (en) * | 1992-03-27 | 2001-01-16 | The United States Of America As Represented By The Department Of Health And Human Services | Method of eliminating inhibitory/instability regions from mRNA |
| US5925517A (en) | 1993-11-12 | 1999-07-20 | The Public Health Research Institute Of The City Of New York, Inc. | Detectably labeled dual conformation oligonucleotide probes, assays and kits |
| US5795737A (en) * | 1994-09-19 | 1998-08-18 | The General Hospital Corporation | High level expression of proteins |
| US5656611A (en) | 1994-11-18 | 1997-08-12 | Supratek Pharma Inc. | Polynucleotide compositions |
| US5885971A (en) | 1995-03-24 | 1999-03-23 | The Regents Of The University Of California | Gene therapy by secretory gland expression |
| US5837693A (en) | 1995-03-24 | 1998-11-17 | The Regents Of The University Of California | Intravenous hormone polypeptide delivery by salivary gland expression |
| US5721354A (en) * | 1995-03-31 | 1998-02-24 | Aviron | Human cytomegalovirus DNA sequences |
| US5800981A (en) * | 1996-02-22 | 1998-09-01 | University Of Limburg | Human cytomegalovirus antigen and its use |
| US6020481A (en) | 1996-04-01 | 2000-02-01 | The Perkin-Elmer Corporation | Asymmetric benzoxanthene dyes |
| AU2809897A (en) * | 1996-04-23 | 1997-11-12 | Wistar Institute Of Anatomy And Biology, The | Novel human cytomegalovirus dna constructs and uses therefor |
| FR2753512B1 (fr) * | 1996-09-19 | 1998-12-31 | Sachs Ind Sa | Chaine de transmission notamment pour cycle |
| US6074645A (en) * | 1996-11-12 | 2000-06-13 | City Of Hope | Immuno-reactive peptide CTL epitopes of human cytomegalovirus |
| US6156317A (en) * | 1996-11-12 | 2000-12-05 | City Of Hope | Immuno-reactive peptide CTL epitopes of human cytomegalovirus |
| WO1999002694A1 (en) | 1997-07-09 | 1999-01-21 | The University Of Queensland | Nucleic acid sequence and method for selectively expressing a protein in a target cell or tissue |
| KR100239879B1 (ko) * | 1997-11-05 | 2000-02-01 | 김상조 | 간암 예방 및 치료용 생약제 |
| JP3253590B2 (ja) * | 1998-08-31 | 2002-02-04 | シャープ株式会社 | ハーフトーンマスクの製造方法 |
| DE60039198D1 (de) * | 1999-03-26 | 2008-07-24 | Vical Inc | Adjuvanszusammensetzungen zur Erhöhung der Immunantwort bezüglich Polynukleotid-basierenden Impfstoffen |
| FR2804028B1 (fr) * | 2000-01-21 | 2004-06-04 | Merial Sas | Vaccins adn ameliores pour animaux de rente |
| US6835383B2 (en) * | 2000-03-23 | 2004-12-28 | City Of Hope | Protein kinase deficient, immunologically active CMVpp65 mutants |
| EP1278551A2 (en) | 2000-04-21 | 2003-01-29 | Vical Incorporated | Compositions and methods for (in vivo) delivery of polynucleotide-based therapeutics |
| DE60026199T2 (de) | 2000-05-18 | 2006-11-23 | Geneart Ag | Synthetische Gene für gagpol und deren Verwendungen |
| AU2001270147A1 (en) | 2000-06-23 | 2002-01-08 | Merck & Co., Inc. | Polynucleotide vaccine adjuvants and formulations containing cationic surfactants, and methods of use |
| US20020110567A1 (en) * | 2000-08-10 | 2002-08-15 | Volker Gerdts | In utero oral nucleic acid immunization |
| DE60333035D1 (de) * | 2002-12-23 | 2010-07-29 | Vical Inc | Impfstoffe gegen infektionen mit dem humanen zytomegalivirus auf grundlage von codonoptimierten polynukleotiden |
| US20050283146A1 (en) | 2004-06-17 | 2005-12-22 | Lentz David J | Thermally extended spiral cryotip for a cryoablation catheter |
-
2003
- 2003-12-19 DE DE60333035T patent/DE60333035D1/de not_active Expired - Lifetime
- 2003-12-19 EP EP03814236A patent/EP1587816B1/en not_active Expired - Lifetime
- 2003-12-19 SI SI200332305T patent/SI2311848T1/sl unknown
- 2003-12-19 AT AT03814236T patent/ATE471335T1/de not_active IP Right Cessation
- 2003-12-19 AU AU2003301148A patent/AU2003301148A1/en not_active Abandoned
- 2003-12-19 ES ES10006227T patent/ES2429338T3/es not_active Expired - Lifetime
- 2003-12-19 EP EP10006227.2A patent/EP2311848B1/en not_active Expired - Lifetime
- 2003-12-19 WO PCT/US2003/040685 patent/WO2004058166A2/en not_active Ceased
- 2003-12-19 CA CA2756797A patent/CA2756797C/en not_active Expired - Fee Related
- 2003-12-19 CA CA2508228A patent/CA2508228C/en not_active Expired - Fee Related
- 2003-12-19 JP JP2004563851A patent/JP2006511221A/ja active Pending
- 2003-12-19 PT PT100062272T patent/PT2311848E/pt unknown
- 2003-12-19 US US10/738,986 patent/US7410795B2/en not_active Expired - Fee Related
- 2003-12-19 DK DK10006227.2T patent/DK2311848T3/da active
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2007
- 2007-08-17 US US11/892,020 patent/US7888112B2/en not_active Expired - Fee Related
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2010
- 2010-04-27 JP JP2010101904A patent/JP5129292B2/ja not_active Expired - Fee Related
-
2011
- 2011-01-25 US US13/013,752 patent/US8278093B2/en not_active Expired - Fee Related
-
2012
- 2012-06-18 US US13/525,814 patent/US8673317B2/en not_active Expired - Fee Related
-
2014
- 2014-02-10 US US14/176,813 patent/US9180162B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE471335T1 (de) | 2010-07-15 |
| EP1587816B1 (en) | 2010-06-16 |
| EP1587816A4 (en) | 2006-06-07 |
| ES2429338T3 (es) | 2013-11-14 |
| JP2006511221A (ja) | 2006-04-06 |
| HK1152945A1 (en) | 2012-03-16 |
| JP5129292B2 (ja) | 2013-01-30 |
| AU2003301148A1 (en) | 2004-07-22 |
| PT2311848E (pt) | 2013-10-03 |
| SI2311848T1 (sl) | 2013-11-29 |
| CA2508228A1 (en) | 2004-07-15 |
| US20110177124A1 (en) | 2011-07-21 |
| EP2311848B1 (en) | 2013-07-03 |
| US8673317B2 (en) | 2014-03-18 |
| WO2004058166A2 (en) | 2004-07-15 |
| US20040209241A1 (en) | 2004-10-21 |
| US9180162B2 (en) | 2015-11-10 |
| US20080085870A1 (en) | 2008-04-10 |
| US8278093B2 (en) | 2012-10-02 |
| US7888112B2 (en) | 2011-02-15 |
| EP2311848A1 (en) | 2011-04-20 |
| DE60333035D1 (de) | 2010-07-29 |
| US7410795B2 (en) | 2008-08-12 |
| AU2003301148A8 (en) | 2004-07-22 |
| CA2508228C (en) | 2013-12-17 |
| US20140186382A1 (en) | 2014-07-03 |
| US20130017217A1 (en) | 2013-01-17 |
| DK2311848T3 (da) | 2013-10-14 |
| EP1587816A2 (en) | 2005-10-26 |
| JP2010227101A (ja) | 2010-10-14 |
| CA2756797A1 (en) | 2004-07-15 |
| WO2004058166A3 (en) | 2005-06-16 |
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