JP2004509970A - 位置的化学変化による免疫刺激オリゴヌクレオチドアナログの免疫刺激活性の調節 - Google Patents
位置的化学変化による免疫刺激オリゴヌクレオチドアナログの免疫刺激活性の調節 Download PDFInfo
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- JP2004509970A JP2004509970A JP2002531140A JP2002531140A JP2004509970A JP 2004509970 A JP2004509970 A JP 2004509970A JP 2002531140 A JP2002531140 A JP 2002531140A JP 2002531140 A JP2002531140 A JP 2002531140A JP 2004509970 A JP2004509970 A JP 2004509970A
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- immunostimulatory
- nucleoside
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- naturally occurring
- oligonucleotide compound
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PCT/US2001/030137 WO2002026757A2 (en) | 2000-09-26 | 2001-09-26 | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
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JP2002531140A Pending JP2004509970A (ja) | 2000-09-26 | 2001-09-26 | 位置的化学変化による免疫刺激オリゴヌクレオチドアナログの免疫刺激活性の調節 |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004537535A (ja) * | 2001-06-21 | 2004-12-16 | ダイナバックス テクノロジーズ コーポレイション | キメラ免疫調節化合物とその使用方法 |
JP2008502688A (ja) * | 2004-06-15 | 2008-01-31 | 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 | 免疫賦活オリゴヌクレオチドマルチマー |
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 |
US7785610B2 (en) | 2001-06-21 | 2010-08-31 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same—III |
Families Citing this family (174)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
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US7354907B2 (en) * | 2003-02-07 | 2008-04-08 | Idera Pharmaceuticals, Inc. | Short immunomodulatory oligonucleotides |
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US20060257852A1 (en) | 2003-04-10 | 2006-11-16 | Chiron Corporation | 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 |
CA2528597C (en) * | 2003-06-11 | 2014-08-05 | Hybridon, Inc. | Stabilized immunomodulatory oligonucleotides |
EP2363141A1 (en) | 2003-07-15 | 2011-09-07 | Idera Pharmaceuticals, Inc. | Compsition comprising two oligonucleotides linked directly at their 3'ends wherein at leat one oligonucleotide has an accessible 5'end and the compound further comprising IL-2 used for synergistically stimulating an immune response in a patient. |
EP1663316A2 (en) | 2003-09-25 | 2006-06-07 | Coley Pharmaceutical Group, Inc. | Nucleic acid lipophilic conjugates |
GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
DK1961426T3 (da) | 2003-10-02 | 2011-08-08 | Novartis Ag | Kombinationsvacciner mod meningitis |
CN101454451A (zh) | 2003-10-30 | 2009-06-10 | 科勒制药有限公司 | 具有增强免疫刺激能力的c类寡核苷酸类似物 |
CA2549173A1 (en) | 2003-12-08 | 2005-07-07 | Hybridon, Inc. | Modulation of immunostimulatory properties by small oligonucleotide-based compounds |
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 |
WO2005081847A2 (en) * | 2004-02-20 | 2005-09-09 | Hybridon, Inc. | Potent mucosal immune response induced by modified immunomodulatory oligonucleotides |
DE202005022108U1 (de) | 2004-03-09 | 2013-11-12 | Novartis Vaccines And Diagnostics, Inc. | Influenza-Virus-Impfstoffe |
GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
GB0409745D0 (en) | 2004-04-30 | 2004-06-09 | Chiron Srl | Compositions including unconjugated carrier proteins |
RU2379052C2 (ru) | 2004-04-30 | 2010-01-20 | Чирон С.Р.Л. | Вакцинация менингококковыми конъюгатами |
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EP2811027A1 (en) | 2004-05-21 | 2014-12-10 | Novartis Vaccines and Diagnostics, Inc. | Alphavirus vectors for RSV and PIV vaccines |
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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 |
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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 |
CN101203529A (zh) | 2005-02-18 | 2008-06-18 | 诺华疫苗和诊断公司 | 来自脑膜炎/脓毒症相关性大肠杆菌的蛋白质和核酸 |
SG160329A1 (en) | 2005-02-18 | 2010-04-29 | Novartis Vaccines & Diagnostic | Proteins and nucleic acids from meningitis/sepsis-associated escherichia coli |
BRPI0610297A2 (pt) | 2005-04-18 | 2010-06-08 | Novartis Vaccines & Diagnostic | expressão de antìgeno de superfìcie de vìrus da hepatite b para a preparação de vacina |
EP2614709A1 (en) | 2005-07-18 | 2013-07-17 | Novartis AG | Small animal model for HCV replication |
JP2009511636A (ja) | 2005-10-18 | 2009-03-19 | 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, インコーポレイテッド | アルファウイルスレプリコン粒子による粘膜免疫および全身免疫 |
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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 |
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AR058707A1 (es) | 2005-12-22 | 2008-02-20 | Glaxosmithkline Biolog Sa | Vacuna, procedimiento para fabricarla y su uso |
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EP2004226A1 (en) | 2006-03-24 | 2008-12-24 | Novartis Vaccines and Diagnostics GmbH & Co. KG | Storage of influenza vaccines without refrigeration |
JP2009531387A (ja) | 2006-03-30 | 2009-09-03 | 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 | 免疫原性組成物 |
US20100285062A1 (en) | 2006-03-31 | 2010-11-11 | Novartis Ag | Combined mucosal and parenteral immunization against hiv |
EP2054431B1 (en) | 2006-06-09 | 2011-08-31 | Novartis AG | Conformers of bacterial adhesins |
GB0614460D0 (en) | 2006-07-20 | 2006-08-30 | Novartis Ag | Vaccines |
EP2064230A2 (en) | 2006-08-16 | 2009-06-03 | Novartis AG | Immunogens from uropathogenic escherichia coli |
KR20090057015A (ko) | 2006-09-11 | 2009-06-03 | 노파르티스 아게 | 난을 사용하지 않는 인플루엔자 바이러스 백신의 제조 |
CN101517082B (zh) | 2006-09-27 | 2014-01-22 | 科勒制药有限责任公司 | 具有增强的免疫刺激活性的含疏水性T类似物的CpG寡聚核苷酸类似物 |
DE102006050655A1 (de) * | 2006-10-24 | 2008-04-30 | Halmon Beheer B.V. | Pharmazeutische Zusammensetzung zur Behandlung allergischer Erkrankungen |
US20110045022A1 (en) | 2006-12-06 | 2011-02-24 | Theodore Tsai | Vaccines including antigen from four strains of influenza virus |
GB0700562D0 (en) | 2007-01-11 | 2007-02-21 | Novartis Vaccines & Diagnostic | Modified Saccharides |
TW200911304A (en) | 2007-05-24 | 2009-03-16 | Glaxosmithkline Biolog Sa | Lyophillised antigen composition |
EA200901578A1 (ru) | 2007-06-26 | 2010-08-30 | Глаксосмитклайн Байолоджикалс С.А. | Вакцина, содержащая конъюгаты капсульных полисахаридов streptococcus pneumoniae |
PL2185191T3 (pl) | 2007-06-27 | 2013-02-28 | Novartis Ag | Szczepionki przeciwko grypie o małej zawartości dodatków |
GB0713880D0 (en) | 2007-07-17 | 2007-08-29 | Novartis Ag | Conjugate purification |
KR20100063048A (ko) * | 2007-07-31 | 2010-06-10 | 더 존스 홉킨스 유니버시티 | 신생물성 또는 감염성 장애의 면역예방 또는 면역치료를 위한 폴리펩티드-핵산 접합체 |
GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
RU2471497C2 (ru) | 2007-09-12 | 2013-01-10 | Новартис Аг | Мутантные антигены gas57 и антитела против gas57 |
GB0810305D0 (en) | 2008-06-05 | 2008-07-09 | Novartis Ag | Influenza vaccination |
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WO2009081274A2 (en) | 2007-12-21 | 2009-07-02 | Novartis Ag | Mutant forms of streptolysin o |
CA2716212A1 (en) | 2008-02-21 | 2009-08-27 | Novartis Ag | Meningococcal fhbp polypeptides |
EA201071086A1 (ru) | 2008-03-18 | 2011-04-29 | Новартис Аг | Усовершенствованный способ получения вакцинных антигенов вируса гриппа |
CA2746508A1 (en) * | 2008-12-17 | 2010-07-15 | Avi Biopharma, Inc. | Antisense compositions and methods for modulating contact hypersensitivity or contact dermatitis |
CA2749367A1 (en) | 2009-01-12 | 2010-07-15 | Novartis Ag | Cna_b domain antigens in vaccines against gram positive bacteria |
US8568732B2 (en) | 2009-03-06 | 2013-10-29 | Novartis Ag | Chlamydia antigens |
EP3263128A3 (en) | 2009-04-14 | 2018-01-24 | GlaxoSmithKline Biologicals S.A. | Compositions for immunising against staphylococcus aureus |
EP2442826B1 (en) | 2009-06-15 | 2015-07-08 | National University of Singapore | Influenza vaccine, composition, and methods of use |
SG177533A1 (en) | 2009-07-07 | 2012-02-28 | Novartis Ag | Conserved escherichia coli immunogens |
WO2011008974A2 (en) | 2009-07-15 | 2011-01-20 | Novartis Ag | Rsv f protein compositions and methods for making same |
MX2012000734A (es) | 2009-07-16 | 2012-01-27 | Novartis Ag | Inmunogenos destoxificados de escherichia 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 |
CA2772104A1 (en) | 2009-08-27 | 2011-03-03 | Novartis Ag | Hybrid polypeptides including meningococcal fhbp sequences |
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WO2011127316A1 (en) | 2010-04-07 | 2011-10-13 | Novartis 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 |
EA023397B1 (ru) | 2010-05-26 | 2016-05-31 | Селекта Байосайенсиз, Инк. | Комбинированные вакцины с синтетическими наноносителями |
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 |
US9994443B2 (en) | 2010-11-05 | 2018-06-12 | Selecta Biosciences, Inc. | Modified nicotinic compounds and related 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 |
EP2655389A2 (en) | 2010-12-24 | 2013-10-30 | Novartis AG | Compounds |
HUE043879T2 (hu) | 2011-01-26 | 2019-09-30 | Glaxosmithkline Biologicals Sa | RSV-immunizálási rend |
TW201302779A (zh) | 2011-04-13 | 2013-01-16 | Glaxosmithkline Biolog Sa | 融合蛋白質及組合疫苗 |
DK3275892T3 (da) | 2011-05-13 | 2020-04-06 | Glaxosmithkline Biologicals Sa | Præfusions-rsv-f-antigener |
FR2975600B1 (fr) | 2011-05-24 | 2013-07-05 | Assist Publ Hopitaux De Paris | Agents pour le traitement de tumeurs |
US11058762B2 (en) | 2011-07-06 | 2021-07-13 | Glaxosmithkline Biologicals Sa | Immunogenic compositions and uses thereof |
CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
CN103764171B (zh) | 2011-07-08 | 2016-08-17 | 诺华股份有限公司 | 酪氨酸连接方法 |
EP2736921B1 (en) | 2011-07-25 | 2018-06-27 | GlaxoSmithKline Biologicals SA | Compositions and methods for assessing functional immunogenicity of parvovirus vaccines |
WO2013019658A2 (en) | 2011-07-29 | 2013-02-07 | Selecta Biosciences, Inc. | Synthetic nanocarriers comprising polymers comprising multiple immunomodulatory agents |
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 |
CA2854934A1 (en) | 2011-11-07 | 2013-05-16 | Novartis Ag | Carrier molecule comprising a spr0096 and a spr2021 antigen |
DK3260140T3 (da) | 2011-12-05 | 2021-04-19 | Factor Bioscience Inc | Fremgangsmåder og produkter til transficering af celler |
WO2013108272A2 (en) | 2012-01-20 | 2013-07-25 | International Centre For Genetic Engineering And Biotechnology | Blood stage malaria vaccine |
MX2014014067A (es) | 2012-05-22 | 2015-02-04 | Novartis Ag | Conjugado de serogrupo x de meningococo. |
WO2014005958A1 (en) | 2012-07-06 | 2014-01-09 | Novartis Ag | Immunogenic compositions and uses thereof |
CN104602702B (zh) | 2012-09-18 | 2021-08-27 | 葛兰素史密丝克莱恩生物有限公司 | 外膜囊泡 |
CN105307684A (zh) | 2012-10-02 | 2016-02-03 | 葛兰素史密丝克莱恩生物有限公司 | 非直链糖缀合物 |
JP6266000B2 (ja) | 2012-10-03 | 2018-01-24 | 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 | 免疫原性組成物 |
RU2711249C2 (ru) | 2012-11-01 | 2020-01-15 | Фэктор Байосайенс Инк. | Способы и продукты для экспрессии белков в клетках |
RS56886B1 (sr) | 2012-11-30 | 2018-04-30 | Glaxosmithkline Biologicals Sa | Antigeni pseudomonasa i kombinacije antigena |
BR112015016420B1 (pt) * | 2013-01-08 | 2022-12-06 | Idera Pharmaceuticals, Inc | Composto de oligonucleotídeo imunorregulatório, composição farmacêutica e uso do composto iro ou da composição farmacêutica |
US11576958B2 (en) | 2013-02-07 | 2023-02-14 | 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 |
KR20220100078A (ko) | 2014-01-31 | 2022-07-14 | 팩터 바이오사이언스 인크. | 핵산 제조 및 송달을 위한 방법 및 산물 |
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 |
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TR201908550T4 (tr) | 2014-06-04 | 2019-07-22 | Exicure Inc | Profilaktik veya terapötik uygulamalar için lipozomal sferik nükleik asitler tarafından immün modülatörlerin çok değerlikli teslimi. |
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US20170281744A1 (en) | 2014-12-10 | 2017-10-05 | Glaxosmithkline Biologicals Sa | Method of treatment |
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WO2016207853A2 (en) | 2015-06-26 | 2016-12-29 | Seqirus UK Limited | Antigenically matched influenza vaccines |
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 |
WO2017172888A1 (en) | 2016-03-30 | 2017-10-05 | 3M Innovative Properties Company | Article featuring a predetermined pattern of randomly distributed microspheres and methods of making the same |
CA3033788A1 (en) | 2016-08-17 | 2018-02-22 | Factor Bioscience Inc. | Nucleic acid products and methods of administration thereof |
WO2018039629A2 (en) | 2016-08-25 | 2018-03-01 | Northwestern University | Micellar spherical nucleic acids from thermoresponsive, traceless templates |
WO2018178265A1 (en) | 2017-03-31 | 2018-10-04 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
US11167022B2 (en) | 2017-03-31 | 2021-11-09 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
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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 |
JP2024510717A (ja) | 2021-02-22 | 2024-03-11 | 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 | 免疫原性組成物、使用及び方法 |
WO2023201109A1 (en) | 2022-04-15 | 2023-10-19 | Yale University | 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 |
CA2058632C (en) * | 1989-06-05 | 2004-08-24 | Brian C. Froehler | Exonuclease-resistant oligonucleotides and methods for preparing the same |
US6365730B1 (en) * | 1990-06-19 | 2002-04-02 | Gene Shears Pty. Limited | DNA-Armed ribozymes and minizymes |
ATE151076T1 (de) * | 1990-07-02 | 1997-04-15 | Hoechst Ag | Oligonucleotid-analoge mit terminalen 3'-3'-bzw. 5'-5'-internucleotidverknüpfungen |
US5599797A (en) * | 1991-10-15 | 1997-02-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
DE69403642T2 (de) * | 1993-03-30 | 1998-01-08 | Sanofi Sa | 7-deazapurin modifizierte oligonukleotide |
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 |
AU775997B2 (en) * | 1998-12-02 | 2004-08-19 | Bristol-Myers Squibb Company | DNA-protein fusions and uses thereof |
EP1218542B1 (en) * | 1999-09-13 | 2004-03-24 | Nugen Technologies, Inc. | Methods and compositions for linear isothermal amplification of polynucleotide sequences |
CA2398432C (en) * | 2000-01-26 | 2012-06-19 | Hybridon, Inc. | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
CA2407942A1 (en) * | 2000-05-01 | 2001-11-08 | Hybridon, Inc. | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
DE60132471T2 (de) * | 2000-09-26 | 2009-01-15 | Idera Pharmaceuticals, Inc., Cambridge | Modulation der immunostimulatorischen aktivität von immunostimulierenden oligonukleotidanaloga durch positionelle chemische veränderungen |
US7105495B2 (en) * | 2001-04-30 | 2006-09-12 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
US7176296B2 (en) * | 2001-04-30 | 2007-02-13 | 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 |
JP4726630B2 (ja) * | 2003-01-16 | 2011-07-20 | 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 | 修飾された免疫賦活性ジヌクレオチドを用いることによるオリゴヌクレオチドに基づく化合物の免疫賦活特性の調節 |
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 |
CA2528597C (en) * | 2003-06-11 | 2014-08-05 | Hybridon, Inc. | Stabilized immunomodulatory oligonucleotides |
EP2363141A1 (en) * | 2003-07-15 | 2011-09-07 | Idera Pharmaceuticals, Inc. | Compsition comprising two oligonucleotides linked directly at their 3'ends wherein at leat one oligonucleotide has an accessible 5'end and the compound further comprising IL-2 used for synergistically stimulating an immune response in a patient. |
NZ552522A (en) * | 2004-06-15 | 2009-04-30 | Idera Pharmaceuticals Inc | Immunostimulatory oligonucleotide multimers |
US7427405B2 (en) * | 2004-06-15 | 2008-09-23 | Idera Pharmaceuticals, Inc. | Immunostimulatory oligonucleotide multimers |
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 |
-
2001
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- 2003-10-27 US US10/694,207 patent/US7790168B2/en not_active Expired - Fee Related
- 2003-10-27 US US10/694,075 patent/US8716253B2/en active Active
- 2003-10-27 US US10/694,586 patent/US7932367B2/en not_active Expired - Fee Related
-
2005
- 2005-11-09 US US11/270,805 patent/US7833538B2/en not_active Expired - Lifetime
-
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- 2006-12-12 US US11/637,184 patent/US8476416B2/en not_active Expired - Lifetime
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