CA2423487C - Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes - Google Patents
Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes Download PDFInfo
- Publication number
- CA2423487C CA2423487C CA2423487A CA2423487A CA2423487C CA 2423487 C CA2423487 C CA 2423487C CA 2423487 A CA2423487 A CA 2423487A CA 2423487 A CA2423487 A CA 2423487A CA 2423487 C CA2423487 C CA 2423487C
- Authority
- CA
- Canada
- Prior art keywords
- immunostimulatory
- nucleoside
- modified
- deoxyguanosine
- deoxycytidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 230000003308 immunostimulating effect Effects 0.000 title claims abstract description 254
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- 238000000034 method Methods 0.000 claims abstract description 55
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- 239000002777 nucleoside Substances 0.000 claims description 79
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 42
- -1 N4-alkylcytidine Chemical compound 0.000 claims description 37
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 claims description 33
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- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 claims description 31
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- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 claims description 30
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims description 24
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Applications Claiming Priority (7)
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| US23545300P | 2000-09-26 | 2000-09-26 | |
| US23545200P | 2000-09-26 | 2000-09-26 | |
| US60/235,452 | 2000-09-26 | ||
| US60/235,453 | 2000-09-26 | ||
| US71289800A | 2000-11-15 | 2000-11-15 | |
| US09/712,898 | 2000-11-15 | ||
| PCT/US2001/030137 WO2002026757A2 (en) | 2000-09-26 | 2001-09-26 | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
Publications (2)
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| CA2423487A1 CA2423487A1 (en) | 2002-04-04 |
| CA2423487C true CA2423487C (en) | 2015-12-15 |
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| CA2423487A Expired - Lifetime CA2423487C (en) | 2000-09-26 | 2001-09-26 | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
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| EP (2) | EP2292632A3 (enExample) |
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| WO (1) | WO2002026757A2 (enExample) |
Families Citing this family (182)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US20030022854A1 (en) | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
| US6977245B2 (en) | 1999-04-12 | 2005-12-20 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
| AU2001227889A1 (en) | 2000-01-14 | 2001-07-24 | The United States of America, represented by The Secretary, Department of Health & Human Services | Oligodeoxynucleotide and its use to induce an immune response |
| AU9475001A (en) * | 2000-09-26 | 2002-04-08 | Hybridon Inc | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
| AU2002231336B2 (en) * | 2000-12-27 | 2007-06-28 | Surefire Medical, Inc. D/B/A Trisalus Life Sciences | Immunomodulatory polynucleotides and methods of using the same |
| GB0114719D0 (en) * | 2001-06-15 | 2001-08-08 | Glaxo Group Ltd | Compound |
| US7785610B2 (en) | 2001-06-21 | 2010-08-31 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same—III |
| AU2002345847B2 (en) | 2001-06-21 | 2008-05-29 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same |
| US7666674B2 (en) | 2001-07-27 | 2010-02-23 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of sterically stabilized cationic liposomes to efficiently deliver CPG oligonucleotides in vivo |
| US7354909B2 (en) | 2001-08-14 | 2008-04-08 | The United States Of America As Represented By Secretary Of The Department Of Health And Human Services | Method for rapid generation of mature dendritic cells |
| 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 |
| WO2003035836A2 (en) * | 2001-10-24 | 2003-05-01 | Hybridon Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends |
| US8466116B2 (en) | 2001-12-20 | 2013-06-18 | The Unites States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of CpG oligodeoxynucleotides to induce epithelial cell growth |
| AU2002366710A1 (en) | 2001-12-20 | 2003-07-09 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of | USE OF CpG OLIGODEOXYNUCLEOTIDES TO INDUCE ANGIOGENESIS |
| CA2388049A1 (en) | 2002-05-30 | 2003-11-30 | Immunotech S.A. | Immunostimulatory oligonucleotides and uses thereof |
| 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 |
| US8263091B2 (en) | 2002-09-18 | 2012-09-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating and preventing infections in immunocompromised subjects with immunostimulatory CpG oligonucleotides |
| DE60335477D1 (de) | 2002-10-11 | 2011-02-03 | Novartis Vaccines & Diagnostic | Polypeptidimpstoffe zum breiten schutz gegen hypervirulente meningokokken-linien |
| WO2004053104A2 (en) | 2002-12-11 | 2004-06-24 | Coley Pharmaceutical Group, Inc. | 5’ cpg nucleic acids and methods of use |
| PT1575977E (pt) | 2002-12-23 | 2009-12-15 | Dynavax Tech Corp | Oligonucleótidos de sequência imunoestimuladora e métodos de utilização dos mesmos |
| US8158768B2 (en) | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
| CA2512484A1 (en) * | 2003-01-16 | 2004-05-08 | Hybridon, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by utilizing modified immunostimulatory dinucleotides |
| 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 |
| ATE491463T1 (de) | 2003-02-20 | 2011-01-15 | Univ Connecticut Health Ct | Verfahren zur herstellung von alpha (2) makroglobulin-antigen-molekül-komplexen |
| KR100681470B1 (ko) | 2003-03-03 | 2007-02-12 | 연세대학교 산학협력단 | 면역반응 증진용 올리고뉴크레오타이드 |
| 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 |
| EP2371834B1 (en) * | 2003-06-11 | 2016-02-17 | Idera Pharmaceuticals, Inc. | Stabilized immunomodulatory oligonucleotides |
| 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 |
| GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
| ATE506963T1 (de) | 2003-10-02 | 2011-05-15 | Novartis Vaccines & Diagnostic | Kombinationsimpfstoffe gegen meningitis |
| 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 |
| GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
| 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 |
| 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 |
| US7427405B2 (en) * | 2004-06-15 | 2008-09-23 | Idera Pharmaceuticals, Inc. | Immunostimulatory oligonucleotide multimers |
| 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 |
| DE102004051804A1 (de) * | 2004-10-21 | 2006-04-27 | Max-Delbrück-Centrum Für Molekulare Medizin (Mdc) | Beta-L-N4-Hydroxycytosin-Desoxynucleoside und ihre Verwendung als pharmazeutische Mittel zur Prophylaxe oder Therapie von viralen Erkrankungen |
| 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 |
| US8062644B2 (en) | 2005-02-18 | 2011-11-22 | Novartis Vaccines & Diagnostics Srl. | Immunogens from uropathogenic Escherichia coli |
| 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 |
| 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 |
| 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 |
| WO2007052058A1 (en) | 2005-11-04 | 2007-05-10 | Novartis Vaccines And Diagnostics Srl | Influenza vaccines including combinations of particulate adjuvants and immunopotentiators |
| US7470674B2 (en) * | 2005-11-07 | 2008-12-30 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| US7776834B2 (en) * | 2005-11-07 | 2010-08-17 | Idera Pharmaceuticals, Inc. | 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 |
| JP2009520502A (ja) * | 2005-12-20 | 2009-05-28 | 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 | Ｃｇジヌクレオチド修飾物を含有するトール様受容体の新規な合成アゴニスト |
| PL3017827T3 (pl) | 2005-12-22 | 2019-04-30 | Glaxosmithkline Biologicals Sa | Szczepionka z koniugatem polisacharydu pneumokokowego |
| GB0607088D0 (en) | 2006-04-07 | 2006-05-17 | Glaxosmithkline Biolog Sa | Vaccine |
| 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 |
| 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 |
| MX2009003398A (es) | 2006-09-27 | 2009-08-12 | Coley Pharm Gmbh | Analogos de oligonucleotidos cpg que contienen analogos t hidrofobos con actividad inmunoestimuladora mejorada. |
| DE102006050655A1 (de) * | 2006-10-24 | 2008-04-30 | Halmon Beheer B.V. | Pharmazeutische Zusammensetzung zur Behandlung allergischer Erkrankungen |
| 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 |
| MX2010001194A (es) * | 2007-07-31 | 2010-07-30 | Univ Louisiana State | Conjugado de polipeptido-acido nucleico para inmunoprofilaxis o inmunoterapia para desordenes neoplasicos o infecciones. |
| GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
| 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) |
| 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 |
| WO2010080554A1 (en) | 2008-12-17 | 2010-07-15 | Avi Biopharma, Inc. | Antisense compositions and methods for modulating contact hypersensitivity or contact dermatitis |
| 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 |
| US20120237536A1 (en) | 2009-09-10 | 2012-09-20 | Novartis | Combination vaccines against respiratory tract diseases |
| GB0917003D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Purification of bacterial vesicles |
| GB0917002D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Improved shigella blebs |
| 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 |
| GB201003920D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Method of treatment |
| 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 |
| US20110293700A1 (en) | 2010-05-26 | 2011-12-01 | Selecta Biosciences, Inc. | Nanocarrier compositions with uncoupled adjuvant |
| 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 |
| 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 |
| EP2640190A4 (en) | 2010-11-05 | 2016-05-11 | Selecta Biosciences Inc | MODIFIED NICOTINIC COMPOUNDS AND ASSOCIATED METHODS |
| 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 |
| FR2975600B1 (fr) | 2011-05-24 | 2013-07-05 | Assist Publ Hopitaux De Paris | Agents pour le traitement de tumeurs |
| CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
| EP2729168A2 (en) | 2011-07-06 | 2014-05-14 | Novartis AG | Immunogenic compositions and uses thereof |
| US9149541B2 (en) | 2011-07-08 | 2015-10-06 | Novartis Ag | Tyrosine ligation process |
| ES2687129T3 (es) | 2011-07-25 | 2018-10-23 | Glaxosmithkline Biologicals Sa | Composiciones y métodos para evaluar la inmunogenicidad funcional de vacunas contra parvovirus |
| CN109172819A (zh) | 2011-07-29 | 2019-01-11 | 西莱克塔生物科技公司 | 产生体液和细胞毒性t淋巴细胞（ctl）免疫应答的合成纳米载体 |
| 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 |
| DK3260140T3 (da) | 2011-12-05 | 2021-04-19 | Factor Bioscience Inc | Fremgangsmåder og produkter til transficering af celler |
| US8497124B2 (en) | 2011-12-05 | 2013-07-30 | Factor Bioscience Inc. | Methods and products for reprogramming cells to a less differentiated state |
| WO2013108272A2 (en) | 2012-01-20 | 2013-07-25 | International Centre For Genetic Engineering And Biotechnology | Blood stage malaria vaccine |
| 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 |
| BR122019025681B1 (pt) | 2012-11-01 | 2023-04-18 | Factor Bioscience Inc | Método para inserir uma sequência de ácido nucleico em uma localização segura de um genoma de uma célula |
| JP6340011B2 (ja) | 2012-11-30 | 2018-06-06 | 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 | シュードモナス抗原および抗原の組み合わせ |
| WO2014110081A1 (en) * | 2013-01-08 | 2014-07-17 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| WO2014124228A1 (en) | 2013-02-07 | 2014-08-14 | Children's Medical Center Corporation | Protein antigens that provide protection against pneumococcal colonization and/or disease |
| GB201310008D0 (en) | 2013-06-05 | 2013-07-17 | Glaxosmithkline Biolog Sa | Immunogenic composition for use in therapy |
| WO2015117021A1 (en) | 2014-01-31 | 2015-08-06 | Factor Bioscience Inc. | Methods and products for nucleic acid production and delivery |
| 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 |
| US10434064B2 (en) | 2014-06-04 | 2019-10-08 | Exicure, Inc. | Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications |
| CA2968531A1 (en) | 2014-11-21 | 2016-05-26 | Northwestern University | The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
| US20170281744A1 (en) | 2014-12-10 | 2017-10-05 | Glaxosmithkline Biologicals Sa | Method of treatment |
| EP3543339A1 (en) | 2015-02-13 | 2019-09-25 | Factor Bioscience Inc. | Nucleic acid products and methods of administration thereof |
| 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 |
| JP6972006B2 (ja) | 2016-03-30 | 2021-11-24 | スリーエム イノベイティブ プロパティズ カンパニー | ランダムに分散された微小球の所定のパターンを主とする物品及びその製造方法 |
| CN109803977B (zh) | 2016-08-17 | 2023-03-17 | 菲克特生物科学股份有限公司 | 核酸产品及其施用方法 |
| WO2018039629A2 (en) | 2016-08-25 | 2018-03-01 | Northwestern University | Micellar spherical nucleic acids from thermoresponsive, traceless templates |
| 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 |
| WO2018178265A1 (en) | 2017-03-31 | 2018-10-04 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
| WO2018209270A1 (en) | 2017-05-11 | 2018-11-15 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (snas) |
| 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 |
| EP3890775A1 (en) | 2018-12-06 | 2021-10-13 | GlaxoSmithKline Biologicals S.A. | Immunogenic compositions |
| WO2020212461A1 (en) | 2019-04-18 | 2020-10-22 | Glaxosmithkline Biologicals Sa | Antigen binding proteins and assays |
| WO2021003462A1 (en) | 2019-07-03 | 2021-01-07 | Factor Bioscience Inc. | Cationic lipids and uses thereof |
| US10501404B1 (en) | 2019-07-30 | 2019-12-10 | Factor Bioscience Inc. | Cationic lipids and transfection methods |
| US20230066762A1 (en) | 2019-08-05 | 2023-03-02 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
| EP3799884A1 (en) | 2019-10-01 | 2021-04-07 | GlaxoSmithKline Biologicals S.A. | Immunogenic compositions |
| EP4114848A4 (en) | 2020-02-26 | 2024-04-03 | Versitech Limited | PD-1-BASED VACCINES AGAINST CORONAVIRUS INFECTION |
| WO2022175423A1 (en) | 2021-02-22 | 2022-08-25 | Glaxosmithkline Biologicals Sa | Immunogenic composition, use and methods |
| AU2023254171A1 (en) | 2022-04-15 | 2024-10-24 | Stradefy Biosciences, Inc. | Exatecan formulation. |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) * | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US5149798A (en) | 1989-04-06 | 1992-09-22 | Worcester Foundation For Experimental Biology | Process for synthesizing oligonucleotides and their analogs adaptable to large scale syntheses |
| JPH05500799A (ja) * | 1989-06-05 | 1993-02-18 | ギリアド サイエンシス，インコーポレイテッド | エキソヌクレアーゼ抵抗性オリゴヌクレオチドおよびその調製方法 |
| US6365730B1 (en) * | 1990-06-19 | 2002-04-02 | Gene Shears Pty. Limited | DNA-Armed ribozymes and minizymes |
| DK0464638T3 (da) * | 1990-07-02 | 1997-10-13 | Hoechst Ag | Oligonukleotidanaloge med terminale 3-3- eller 5-5-internukleotidbindinger. |
| US5599797A (en) * | 1991-10-15 | 1997-02-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| EP0691980B1 (en) * | 1993-03-30 | 1997-06-04 | Sanofi | 7-deazapurine modified oligonucleotides |
| AU1436995A (en) * | 1993-12-30 | 1995-07-17 | Chemgenes Corporation | Synthesis of propargyl modified nucleosides and phosphoramidites and their incorporation into defined sequence oligonucleotides |
| US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US5693773A (en) * | 1995-06-07 | 1997-12-02 | Hybridon Incorporated | Triplex-forming antisense oligonucleotides having abasic linkers targeting nucleic acids comprising mixed sequences of purines and pyrimidines |
| CA2181421C (en) * | 1995-07-18 | 2007-02-13 | Tsutomu Takahashi | Para-oriented aromatic polyamide porous film |
| US5856462A (en) * | 1996-09-10 | 1999-01-05 | Hybridon Incorporated | Oligonucleotides having modified CpG dinucleosides |
| US6444650B1 (en) * | 1996-10-01 | 2002-09-03 | Geron Corporation | Antisense compositions for detecting and inhibiting telomerase reverse transcriptase |
| US6077833A (en) * | 1996-12-31 | 2000-06-20 | Isis Pharmaceuticals, Inc. | Oligonucleotide compositions and methods for the modulation of the expression of B7 protein |
| US6028183A (en) * | 1997-11-07 | 2000-02-22 | Gilead Sciences, Inc. | Pyrimidine derivatives and oligonucleotides containing same |
| FR2771189B1 (fr) * | 1997-11-14 | 2000-01-07 | Eastman Kodak Co | Procede pour minimiser l'oxydation aerienne des revelateurs photographiques |
| JPH11209289A (ja) * | 1998-01-22 | 1999-08-03 | Taisho Pharmaceut Co Ltd | 粘膜免疫誘起剤 |
| US6562798B1 (en) * | 1998-06-05 | 2003-05-13 | Dynavax Technologies Corp. | Immunostimulatory oligonucleotides with modified bases and methods of use thereof |
| WO2000006588A1 (en) * | 1998-07-27 | 2000-02-10 | University Of Iowa Research Foundation | STEREOISOMERS OF CpG OLIGONUCLEOTIDES AND RELATED METHODS |
| US6172216B1 (en) * | 1998-10-07 | 2001-01-09 | Isis Pharmaceuticals Inc. | Antisense modulation of BCL-X expression |
| ES2280131T3 (es) * | 1998-12-02 | 2007-09-01 | Adnexus Therapeutics, Inc. | Fusiones de adn-proteina y utilizaciones de las mismas. |
| IL148091A0 (en) * | 1999-09-13 | 2002-09-12 | Nugen Technologies Inc | Methods and compositions for linear isothermal amplification of polynucleotide sequences |
| US6815429B2 (en) * | 2000-01-26 | 2004-11-09 | Hybridon, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
| PT1278761E (pt) * | 2000-05-01 | 2005-08-31 | Hybridon Inc | Modulacao da estimulacao imunitaria mediada por oligonucleotidos de cpg, por modificacao posicional de nucleosidos |
| AU9475001A (en) * | 2000-09-26 | 2002-04-08 | Hybridon Inc | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
| US7176296B2 (en) * | 2001-04-30 | 2007-02-13 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
| US7105495B2 (en) * | 2001-04-30 | 2006-09-12 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
| 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 |
| CA2512484A1 (en) * | 2003-01-16 | 2004-05-08 | Hybridon, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by utilizing modified immunostimulatory dinucleotides |
| 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 |
| US7323319B2 (en) * | 2003-05-29 | 2008-01-29 | The University Of Southern Mississippi | RNA containing coenzymes, biotin, or fluorophores, and methods for their preparation and use |
| EP2371834B1 (en) * | 2003-06-11 | 2016-02-17 | Idera Pharmaceuticals, Inc. | Stabilized immunomodulatory oligonucleotides |
| 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 |
| US7427405B2 (en) * | 2004-06-15 | 2008-09-23 | Idera Pharmaceuticals, Inc. | Immunostimulatory oligonucleotide multimers |
| HUE036894T2 (hu) * | 2004-06-15 | 2018-08-28 | Idera Pharmaceuticals Inc | Immunstimuláló oligonukleotid multimerek |
| US20070093439A1 (en) * | 2005-10-25 | 2007-04-26 | Idera Pharmaceuticals, Inc. | Short immunomodulatory oligonucleotides |
| US7470674B2 (en) * | 2005-11-07 | 2008-12-30 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
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