CA2463798C - Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends - Google Patents
Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends Download PDFInfo
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- CA2463798C CA2463798C CA2463798A CA2463798A CA2463798C CA 2463798 C CA2463798 C CA 2463798C CA 2463798 A CA2463798 A CA 2463798A CA 2463798 A CA2463798 A CA 2463798A CA 2463798 C CA2463798 C CA 2463798C
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- 230000003308 immunostimulating effect Effects 0.000 title claims abstract description 131
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- C12N2310/3183—Diol linkers, e.g. glycols or propanediols
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US34476701P | 2001-10-24 | 2001-10-24 | |
| US60/344,767 | 2001-10-24 | ||
| PCT/US2002/034247 WO2003057822A2 (en) | 2001-10-24 | 2002-10-24 | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends |
Publications (2)
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| CA2463798A1 CA2463798A1 (en) | 2003-07-17 |
| CA2463798C true CA2463798C (en) | 2015-02-03 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2463798A Expired - Lifetime CA2463798C (en) | 2001-10-24 | 2002-10-24 | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends |
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| AU (1) | AU2002365141C1 (enExample) |
| CA (1) | CA2463798C (enExample) |
| WO (2) | WO2003035836A2 (enExample) |
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| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| AU2002345847B2 (en) | 2001-06-21 | 2008-05-29 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same |
| US7276489B2 (en) * | 2002-10-24 | 2007-10-02 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends |
| EP1393745A1 (en) * | 2002-07-29 | 2004-03-03 | Hybridon, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5'ends |
| AR040996A1 (es) | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
| DE60335477D1 (de) | 2002-10-11 | 2011-02-03 | Novartis Vaccines & Diagnostic | Polypeptidimpstoffe zum breiten schutz gegen hypervirulente meningokokken-linien |
| MXPA05004588A (es) | 2002-10-29 | 2005-12-14 | Coley Pharmaceutical Group Ltd | Metodos y productos relacionados con el tratamiento y prevencion de infeccion de virus de hepatitis c. |
| WO2004053104A2 (en) | 2002-12-11 | 2004-06-24 | Coley Pharmaceutical Group, Inc. | 5’ cpg nucleic acids and methods of use |
| JP2006516099A (ja) * | 2002-12-23 | 2006-06-22 | ダイナバックス テクノロジーズ コーポレイション | 分枝状の免疫調節化合物及び該化合物の使用方法 |
| PT2172213E (pt) | 2003-01-30 | 2013-06-03 | Novartis Ag | Vacinas injetáveis contra múltiplos serogrupos meningocócicos |
| US7354907B2 (en) * | 2003-02-07 | 2008-04-08 | Idera Pharmaceuticals, Inc. | Short immunomodulatory oligonucleotides |
| NZ543467A (en) | 2003-04-10 | 2008-07-31 | Novartis Vaccines & Diagnostic | The severe acute respiratory syndrome coronavirus |
| JP2006528697A (ja) | 2003-05-16 | 2006-12-21 | イデラ ファーマシューティカルズ インコーポレイテッド | イムノマーを化学療法剤と組み合わせて用いる、癌の相乗的処置 |
| KR101126030B1 (ko) * | 2003-07-15 | 2012-03-19 | 이데라 파마슈티칼즈, 인코포레이티드 | 사이토킨 및/또는 화학치료제 또는 방사선 치료와 연계하여면역자극 올리고누클레오티드 및/또는 이뮤노머 화합물을이용하여 면역계를 공동 상승 자극시키는 방법 |
| AU2004275876B2 (en) | 2003-09-25 | 2011-03-31 | Coley Pharmaceutical Gmbh | Nucleic acid-lipophilic conjugates |
| ATE506963T1 (de) | 2003-10-02 | 2011-05-15 | Novartis Vaccines & Diagnostic | Kombinationsimpfstoffe gegen meningitis |
| GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
| BRPI0416079A (pt) | 2003-10-30 | 2007-01-02 | Coley Pharm Gmbh | análogos de oligonucleotìdeos de classe c com uma potência imunoestimuladora aumentada |
| EP1699814A4 (en) | 2003-12-08 | 2009-01-14 | Hybridon Inc | MODULATION OF IMMUNOSTIMULATORY PROPERTIES OF COMPOUNDS FORMED FROM SMALL OLIGONUCLEOTIDES |
| JP4817599B2 (ja) * | 2003-12-25 | 2011-11-16 | 独立行政法人科学技術振興機構 | 免疫活性増強剤とこれを用いた免疫活性の増強方法 |
| US20050222072A1 (en) * | 2004-02-20 | 2005-10-06 | Hybridon, Inc. | Potent mucosal immune response induced by modified immunomodulatory oligonucleotides |
| US20080254065A1 (en) | 2004-03-09 | 2008-10-16 | Chiron Corporation | Influenza Virus Vaccines |
| JP5718545B2 (ja) | 2004-04-30 | 2015-05-13 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス エスアールエル | 髄膜炎菌結合体ワクチン接種 |
| GB0409745D0 (en) | 2004-04-30 | 2004-06-09 | Chiron Srl | Compositions including unconjugated carrier proteins |
| GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
| GB0410866D0 (en) | 2004-05-14 | 2004-06-16 | Chiron Srl | Haemophilius influenzae |
| EP2848692B1 (en) | 2004-05-21 | 2017-08-16 | Novartis Vaccines and Diagnostics, Inc. | Alphavirus vectors for influenza virus vaccines |
| JP2008501807A (ja) * | 2004-06-08 | 2008-01-24 | コーリー ファーマシューティカル ゲーエムベーハー | 抗原ならびに免疫活性化アゴニストおよび免疫活性化アンタゴニストのための担体基本骨格としての無塩基オリゴヌクレオチド |
| HUE036894T2 (hu) | 2004-06-15 | 2018-08-28 | Idera Pharmaceuticals Inc | Immunstimuláló oligonukleotid multimerek |
| EP1784211A4 (en) | 2004-07-29 | 2010-06-30 | Novartis Vaccines & Diagnostic | IMMUNOGENIC COMPOSITIONS FOR GRAMPOSITIVE BACTERIA SUCH AS STREPTOCOCCUS AGALACTIAE |
| MY159370A (en) * | 2004-10-20 | 2016-12-30 | Coley Pharm Group Inc | Semi-soft-class immunostimulatory oligonucleotides |
| GB0424092D0 (en) | 2004-10-29 | 2004-12-01 | Chiron Srl | Immunogenic bacterial vesicles with outer membrane proteins |
| GB0502095D0 (en) | 2005-02-01 | 2005-03-09 | Chiron Srl | Conjugation of streptococcal capsular saccharides |
| ES2595363T3 (es) | 2005-02-18 | 2016-12-29 | J. Craig Venter Institute, Inc. | Sepsis asociada a las proteínas y los ácidos nucleicos de meningitis / Escherichia coli |
| US8062644B2 (en) | 2005-02-18 | 2011-11-22 | Novartis Vaccines & Diagnostics Srl. | Immunogens from uropathogenic Escherichia coli |
| CA2605179A1 (en) | 2005-04-18 | 2006-10-26 | Novartis Vaccines And Diagnostics, Inc. | Expressing hepatitis b virus surface antigen for vaccine preparation |
| WO2007011777A2 (en) | 2005-07-18 | 2007-01-25 | Novartis Ag | Small animal model for hcv replication |
| CN101355960A (zh) | 2005-10-18 | 2009-01-28 | 诺华疫苗和诊断公司 | 使用α病毒复制子颗粒进行粘膜和全身免疫 |
| WO2007052058A1 (en) | 2005-11-04 | 2007-05-10 | Novartis Vaccines And Diagnostics Srl | Influenza vaccines including combinations of particulate adjuvants and immunopotentiators |
| NZ592713A (en) | 2005-11-04 | 2012-12-21 | Novartis Vaccines & Diagnostic | Adjuvanted influenza vaccines including a cytokine-inducing agents other than an agonist of Toll-Like Receptor 9 |
| HUE051122T2 (hu) | 2005-11-04 | 2021-03-01 | Seqirus Uk Ltd | Sejttenyészetben növesztett influenzavírusból elõállított nemvirion anti-géneket tartalmazó adjuvált vakcinák |
| AU2006310163B2 (en) | 2005-11-04 | 2011-09-15 | Seqirus UK Limited | Influenza vaccine with reduced amount of oil-in-water emulsion as adjuvant |
| JP2009514525A (ja) * | 2005-11-07 | 2009-04-09 | イデラ ファーマシューティカルズ インコーポレイテッド | 修飾された免疫刺激性ジヌクレオチドを含む、オリゴヌクレオチドに基づく化合物の免疫刺激特性 |
| EP1942945B1 (en) * | 2005-11-07 | 2011-10-19 | Idera Pharmaceuticals | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| WO2007081447A2 (en) | 2005-11-22 | 2007-07-19 | Novartis Vaccines And Diagnostics, Inc. | Norovirus and sapovirus antigens |
| GB0524066D0 (en) | 2005-11-25 | 2006-01-04 | Chiron Srl | 741 ii |
| PL3017827T3 (pl) | 2005-12-22 | 2019-04-30 | Glaxosmithkline Biologicals Sa | Szczepionka z koniugatem polisacharydu pneumokokowego |
| HUE049580T2 (hu) | 2006-01-27 | 2020-09-28 | Seqirus Uk Ltd | Hemagglutinint és mátrixfehérjéket tartalmazó, influenza elleni oltóanyagok |
| CA2646539A1 (en) | 2006-03-23 | 2007-09-27 | Novartis Ag | Imidazoquinoxaline compounds as immunomodulators |
| CN101448523A (zh) | 2006-03-24 | 2009-06-03 | 诺华疫苗和诊断有限两合公司 | 无需冷藏储存流感疫苗 |
| KR101541383B1 (ko) | 2006-03-30 | 2015-08-03 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 면역원성 조성물 |
| US20100285062A1 (en) | 2006-03-31 | 2010-11-11 | Novartis Ag | Combined mucosal and parenteral immunization against hiv |
| WO2008020335A2 (en) | 2006-06-09 | 2008-02-21 | Novartis Ag | Immunogenic compositions for streptococcus agalactiae |
| GB0614460D0 (en) | 2006-07-20 | 2006-08-30 | Novartis Ag | Vaccines |
| JP2010507361A (ja) | 2006-07-31 | 2010-03-11 | キュアバック ゲーエムベーハー | 具体的には免疫刺激剤／アジュバントとしての、一般式（Ｉ）：ＧｌＸｍＧｎ、または一般式（ＩＩ）：ＣｌＸｍＣｎで表される核酸 |
| WO2008020330A2 (en) | 2006-08-16 | 2008-02-21 | Novartis Ag | Immunogens from uropathogenic escherichia coli |
| EP4585610A3 (en) | 2006-09-11 | 2025-09-24 | Seqirus UK Limited | Making influenza virus vaccines without using eggs |
| US8110407B2 (en) | 2006-09-14 | 2012-02-07 | Konica Minolta Medical & Graphic, Inc. | Fluorescent semiconductor microparticle assembly, fluorescent labeling agent assembly for biological substance, and bioimaging method and biological substance analysis method using the assemblies |
| MX2009003398A (es) | 2006-09-27 | 2009-08-12 | Coley Pharm Gmbh | Analogos de oligonucleotidos cpg que contienen analogos t hidrofobos con actividad inmunoestimuladora mejorada. |
| PL2121011T3 (pl) | 2006-12-06 | 2014-10-31 | Novartis Ag | Szczepionki zawierające antygeny czterech szczepów wirusa grypy |
| GB0700562D0 (en) | 2007-01-11 | 2007-02-21 | Novartis Vaccines & Diagnostic | Modified Saccharides |
| US20090035360A1 (en) | 2007-05-24 | 2009-02-05 | Dominique Ingrid Lemoine | Lyophilised antigen composition |
| US9610339B2 (en) | 2007-06-26 | 2017-04-04 | Glaxosmithkline Biologicals, S.A. | Vaccine comprising Streptococcus pneumoniae capsular polysaccharide conjugates |
| CN101784283A (zh) | 2007-06-27 | 2010-07-21 | 诺华有限公司 | 低添加流感疫苗 |
| GB0713880D0 (en) | 2007-07-17 | 2007-08-29 | Novartis Ag | Conjugate purification |
| GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
| WO2009030254A1 (en) | 2007-09-04 | 2009-03-12 | Curevac Gmbh | Complexes of rna and cationic peptides for transfection and for immunostimulation |
| AU2008299376B2 (en) | 2007-09-12 | 2013-02-28 | Glaxosmithkline Biologicals S.A. | GAS57 mutant antigens and GAS57 antibodies |
| GB0810305D0 (en) | 2008-06-05 | 2008-07-09 | Novartis Ag | Influenza vaccination |
| GB0818453D0 (en) | 2008-10-08 | 2008-11-12 | Novartis Ag | Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom |
| NZ586430A (en) | 2007-12-21 | 2012-09-28 | Novartis Ag | Mutant forms of streptolysin o (slo) |
| MX2010008468A (es) | 2008-01-31 | 2010-08-30 | Curevac Gmbh | Acidos nucleicos de la formula (i) (nug1xmgnnv)a y derivados de los mismos como un agente/adyuvante inmunoestimulante. |
| US9579372B2 (en) | 2008-02-21 | 2017-02-28 | Glaxosmithkline Biologicals Sa | Meningococcal fHBP polypeptides |
| EA201071086A1 (ru) | 2008-03-18 | 2011-04-29 | Новартис Аг | Усовершенствованный способ получения вакцинных антигенов вируса гриппа |
| WO2010037408A1 (en) | 2008-09-30 | 2010-04-08 | Curevac Gmbh | Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof |
| KR20110071108A (ko) * | 2008-10-06 | 2011-06-28 | 이데라 파마슈티칼즈, 인코포레이티드 | 고콜레스테롤혈증 및 고지혈증 및 이에 관련된 질병의 예방 및 치료에서 톨-유사 수용체의 저해제의 용도 |
| US8465751B2 (en) | 2009-01-12 | 2013-06-18 | Novartis Ag | Cna—B domain antigens in vaccines against gram positive bacteria |
| US8568732B2 (en) | 2009-03-06 | 2013-10-29 | Novartis Ag | Chlamydia antigens |
| CA2758490C (en) | 2009-04-14 | 2023-05-02 | Novartis Ag | Compositions for immunising against staphylococcus aureus |
| JP5551774B2 (ja) | 2009-06-15 | 2014-07-16 | ナショナル ユニヴァーシティー オブ シンガポール | インフルエンザワクチン、組成物、および使用方法 |
| WO2011004263A2 (en) | 2009-07-07 | 2011-01-13 | Novartis Ag | Conserved escherichia coli immunogens |
| SI3178490T1 (sl) | 2009-07-15 | 2022-08-31 | Glaxosmithkline Biologicals S.A. | Sestavki proteina F RSV-ja in postopki za pripravo le-teh |
| HRP20141270T1 (xx) | 2009-07-16 | 2015-03-13 | Novartis Ag | Detoksificirani imunogeni escherichie coli |
| GB0913681D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| GB0913680D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| BR112012004275A2 (pt) | 2009-08-27 | 2016-11-16 | Novartis Ag | polipeptídios híbridos incluindo sequências meningocócicas de fhbp |
| HRP20150566T1 (hr) * | 2009-08-27 | 2015-07-17 | Idera Pharmaceuticals, Inc. | Kompozicija za inhibiciju ekspresije gena i njegova upotreba |
| US20110053829A1 (en) | 2009-09-03 | 2011-03-03 | Curevac Gmbh | Disulfide-linked polyethyleneglycol/peptide conjugates for the transfection of nucleic acids |
| US20120237536A1 (en) | 2009-09-10 | 2012-09-20 | Novartis | Combination vaccines against respiratory tract diseases |
| GB0917002D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Improved shigella blebs |
| GB0917003D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Purification of bacterial vesicles |
| MX373250B (es) | 2009-09-30 | 2020-05-04 | Glaxosmithkline Biologicals S A Star | Conjugación de polisacáridos capsulares de tipo 5 y de tipo 8 de staphylococcus aureus. |
| WO2011039631A2 (en) | 2009-09-30 | 2011-04-07 | Novartis Ag | Expression of meningococcal fhbp polypeptides |
| GB0918392D0 (en) | 2009-10-20 | 2009-12-02 | Novartis Ag | Diagnostic and therapeutic methods |
| EP2493499A1 (en) | 2009-10-27 | 2012-09-05 | Novartis AG | Modified meningococcal fhbp polypeptides |
| GB0919690D0 (en) | 2009-11-10 | 2009-12-23 | Guy S And St Thomas S Nhs Foun | compositions for immunising against staphylococcus aureus |
| WO2011080595A2 (en) | 2009-12-30 | 2011-07-07 | Novartis Ag | Polysaccharide immunogens conjugated to e. coli carrier proteins |
| GB201003333D0 (en) | 2010-02-26 | 2010-04-14 | Novartis Ag | Immunogenic proteins and compositions |
| GB201003924D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| GB201005625D0 (en) | 2010-04-01 | 2010-05-19 | Novartis Ag | Immunogenic proteins and compositions |
| US9744228B2 (en) | 2010-04-07 | 2017-08-29 | Norvartis Ag | Method for generating a parvovirus B19 virus-like particle |
| WO2011130379A1 (en) | 2010-04-13 | 2011-10-20 | Novartis Ag | Benzonapthyridine compositions and uses thereof |
| CN102933267B (zh) | 2010-05-28 | 2015-05-27 | 泰特里斯在线公司 | 交互式混合异步计算机游戏基础结构 |
| GB201009861D0 (en) | 2010-06-11 | 2010-07-21 | Novartis Ag | OMV vaccines |
| EP3153578A1 (en) | 2010-07-06 | 2017-04-12 | Novartis Ag | Norovirus derived immunogenic compositions and methods |
| US9192661B2 (en) | 2010-07-06 | 2015-11-24 | Novartis Ag | Delivery of self-replicating RNA using biodegradable polymer particles |
| CA2801523C (en) | 2010-07-30 | 2021-08-03 | Curevac Gmbh | Complexation of nucleic acids with disulfide-crosslinked cationic components for transfection and immunostimulation |
| GB201101665D0 (en) | 2011-01-31 | 2011-03-16 | Novartis Ag | Immunogenic compositions |
| GB201017519D0 (en) | 2010-10-15 | 2010-12-01 | Novartis Vaccines Inst For Global Health S R L | Vaccines |
| WO2012072769A1 (en) | 2010-12-01 | 2012-06-07 | Novartis Ag | Pneumococcal rrgb epitopes and clade combinations |
| GB201021867D0 (en) | 2010-12-23 | 2011-02-02 | Mologen Ag | Non-coding immunomodulatory DNA construct |
| CA2860331A1 (en) | 2010-12-24 | 2012-06-28 | Novartis Ag | Compounds |
| HRP20190791T1 (hr) | 2011-01-26 | 2019-06-28 | Glaxosmithkline Biologicals Sa | Režim imuniziranja protiv rsv |
| TW201302779A (zh) | 2011-04-13 | 2013-01-16 | Glaxosmithkline Biolog Sa | 融合蛋白質及組合疫苗 |
| SI3275892T1 (sl) | 2011-05-13 | 2020-06-30 | Glaxosmithkline Biologicals S.A. | Prefuzijski RSV F antigeni |
| EP2729168A2 (en) | 2011-07-06 | 2014-05-14 | Novartis AG | Immunogenic compositions and uses thereof |
| CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
| ES2687129T3 (es) | 2011-07-25 | 2018-10-23 | Glaxosmithkline Biologicals Sa | Composiciones y métodos para evaluar la inmunogenicidad funcional de vacunas contra parvovirus |
| CN103917245B (zh) | 2011-09-14 | 2017-06-06 | 葛兰素史密丝克莱恩生物有限公司 | 用于制备糖‑蛋白质糖缀合物的方法 |
| JP6170932B2 (ja) | 2011-11-07 | 2017-07-26 | ノバルティス アーゲー | ｓｐｒ００９６抗原およびｓｐｒ２０２１抗原を含むキャリア分子 |
| WO2013108272A2 (en) | 2012-01-20 | 2013-07-25 | International Centre For Genetic Engineering And Biotechnology | Blood stage malaria vaccine |
| WO2013113326A1 (en) | 2012-01-31 | 2013-08-08 | Curevac Gmbh | Pharmaceutical composition comprising a polymeric carrier cargo complex and at least one protein or peptide antigen |
| AU2013265336A1 (en) | 2012-05-22 | 2014-12-04 | Novartis Ag | Meningococcus serogroup X conjugate |
| JP2015522580A (ja) | 2012-07-06 | 2015-08-06 | ノバルティス アーゲー | 免疫学的組成物およびその使用 |
| RU2662970C2 (ru) | 2012-09-18 | 2018-07-31 | Новартис Аг | Везикулы наружной мембраны |
| WO2014053521A2 (en) | 2012-10-02 | 2014-04-10 | Novartis Ag | Nonlinear saccharide conjugates |
| SG11201500978TA (en) | 2012-10-03 | 2015-07-30 | Glaxosmithkline Biolog Sa | Immunogenic compositions |
| WO2014110081A1 (en) * | 2013-01-08 | 2014-07-17 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| ES2747762T3 (es) | 2013-08-21 | 2020-03-11 | Curevac Ag | Vacuna contra el virus respiratorio sincitial (RSV) |
| EP2870974A1 (en) | 2013-11-08 | 2015-05-13 | Novartis AG | Salmonella conjugate vaccines |
| TW201620927A (zh) | 2014-02-24 | 2016-06-16 | 葛蘭素史密斯克藍生物品公司 | Ｕｓｐａ２蛋白質構築體及其用途 |
| EP3122378B1 (en) | 2014-03-26 | 2019-12-11 | GlaxoSmithKline Biologicals S.A. | Mutant staphylococcal antigens |
| WO2015149944A2 (en) | 2014-04-01 | 2015-10-08 | Curevac Gmbh | Polymeric carrier cargo complex for use as an immunostimulating agent or as an adjuvant |
| US20170281744A1 (en) | 2014-12-10 | 2017-10-05 | Glaxosmithkline Biologicals Sa | Method of treatment |
| TW201639583A (zh) * | 2015-03-20 | 2016-11-16 | 國立研究開發法人醫藥基盤 健康 營養研究所 | 具有免疫賦活活性之含有ＣｐＧ－間隔基－寡核苷酸複合體及其用途 |
| BR112017028011A2 (pt) | 2015-06-26 | 2018-08-28 | Seqirus Uk Ltd | vacinas de gripe correspondentes antigenicamente |
| LU92821B1 (en) | 2015-09-09 | 2017-03-20 | Mologen Ag | Combination comprising immunostimulatory oligonucleotides |
| GB2542425A (en) | 2015-09-21 | 2017-03-22 | Mologen Ag | Means for the treatment of HIV |
| WO2018178265A1 (en) | 2017-03-31 | 2018-10-04 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
| CN110662557A (zh) | 2017-03-31 | 2020-01-07 | 葛兰素史克知识产权开发有限公司 | 免疫原性组合物、用途和治疗方法 |
| JP2020530478A (ja) | 2017-08-14 | 2020-10-22 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 免疫応答を強化する方法 |
| WO2020097923A1 (en) | 2018-11-16 | 2020-05-22 | The University Of Hong Kong | Live attenuated influenza b virus compositions methods of making and using thereof |
| WO2020212461A1 (en) | 2019-04-18 | 2020-10-22 | Glaxosmithkline Biologicals Sa | Antigen binding proteins and assays |
| EP4114848A4 (en) | 2020-02-26 | 2024-04-03 | Versitech Limited | PD-1-BASED VACCINES AGAINST CORONAVIRUS INFECTION |
| AU2023254171A1 (en) | 2022-04-15 | 2024-10-24 | Stradefy Biosciences, Inc. | Exatecan formulation. |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6172208B1 (en) * | 1992-07-06 | 2001-01-09 | Genzyme Corporation | Oligonucleotides modified with conjugate groups |
| JP2000506384A (ja) * | 1996-02-15 | 2000-05-30 | ナショナル インスティチューツ オブ ヘルス | ＲＮａｓｅ Ｌ アクチベーター及びＲＳＶ感染の治療に有効なアンチセンスオリゴヌクレオチド |
| US5856462A (en) * | 1996-09-10 | 1999-01-05 | Hybridon Incorporated | Oligonucleotides having modified CpG dinucleosides |
| ES2284247T3 (es) * | 1998-04-03 | 2007-11-01 | University Of Iowa Research Foundation | Metodos y productos para estimular el sistema inmunitario usando oligonucleotidos y citoquinas inmunoterapeuticos. |
| AU9475001A (en) * | 2000-09-26 | 2002-04-08 | Hybridon Inc | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
| AU2002345847B2 (en) * | 2001-06-21 | 2008-05-29 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same |
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- 2002-10-24 CA CA2463798A patent/CA2463798C/en not_active Expired - Lifetime
- 2002-10-24 JP JP2003558124A patent/JP5005878B2/ja not_active Expired - Lifetime
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| JP2005518402A (ja) | 2005-06-23 |
| WO2003057822A2 (en) | 2003-07-17 |
| KR100945104B1 (ko) | 2010-03-02 |
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| WO2003035836A2 (en) | 2003-05-01 |
| CA2463798A1 (en) | 2003-07-17 |
| AU2002365141B2 (en) | 2007-06-14 |
| KR20040047969A (ko) | 2004-06-05 |
| AU2002365141C1 (en) | 2008-07-24 |
| JP5005878B2 (ja) | 2012-08-22 |
| WO2003057822A9 (en) | 2004-07-01 |
| WO2003057822A3 (en) | 2004-02-26 |
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