ES2544877T3 - Compuestos oligonucleótidos inmuno reguladores (IRO) para modular la respuesta inmune basada en receptor semejante a Toll - Google Patents
Compuestos oligonucleótidos inmuno reguladores (IRO) para modular la respuesta inmune basada en receptor semejante a Toll Download PDFInfo
- Publication number
- ES2544877T3 ES2544877T3 ES10013989.8T ES10013989T ES2544877T3 ES 2544877 T3 ES2544877 T3 ES 2544877T3 ES 10013989 T ES10013989 T ES 10013989T ES 2544877 T3 ES2544877 T3 ES 2544877T3
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- nucleotide
- oligonucleotide
- iro
- administration
- seq
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Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72603405P | 2005-10-12 | 2005-10-12 | |
| US726034P | 2005-10-12 | ||
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Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005001055A2 (en) * | 2003-06-11 | 2005-01-06 | Hybridon, Inc. | Stabilized immunomodulatory oligonucleotides |
| CN104278037B (zh) | 2005-10-12 | 2020-09-15 | 艾德拉药物股份有限公司 | 基于变异应答调制Toll样受体的免疫调节寡核苷酸(IRO)化合物 |
| EP2446903B1 (en) | 2006-11-20 | 2019-10-09 | President and Fellows of Harvard College | Compositions for treating itch |
| ES2539353T3 (es) * | 2007-08-01 | 2015-06-30 | Idera Pharmaceuticals, Inc. | Nuevos agonistas sintéticos de TLR9 |
| AU2008286735A1 (en) | 2007-08-15 | 2009-02-19 | Idera Pharmaceuticals, Inc. | Toll like receptor modulators |
| WO2009086352A2 (en) * | 2007-12-26 | 2009-07-09 | Centocor, Inc. | Cynomolgus toll-like receptor 3 |
| WO2009154610A1 (en) * | 2008-06-17 | 2009-12-23 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| CN101643496B (zh) * | 2008-08-07 | 2015-09-09 | 长春华普生物技术有限公司 | 一种具有免疫抑制功能的寡核苷酸 |
| WO2010039615A2 (en) * | 2008-10-03 | 2010-04-08 | Centocor Ortho Biotech Inc. | Papio cynocephalus toll-like receptor 3 |
| MX2011003625A (es) * | 2008-10-06 | 2011-05-31 | Idera Pharmaceuticals Inc | Uso de inhibidores de receptores tipo toll en la prevencion y tratamiento de hipercolesterolemia e hiperlipidemia y enfermedades relacionadas con esto. |
| CN102388139A (zh) * | 2008-11-04 | 2012-03-21 | 艾德拉药物股份有限公司 | 通过反义寡核苷酸来调制Toll样受体5表达 |
| AU2009323766B2 (en) | 2008-12-02 | 2016-10-06 | Wave Life Sciences Ltd. | Method for the synthesis of phosphorus atom modified nucleic acids |
| CA2750499A1 (en) * | 2009-01-30 | 2010-08-05 | Idera Pharmaceuticals, Inc. | Novel synthetic agonists of tlr9 |
| BRPI1009842B8 (pt) | 2009-03-25 | 2021-05-25 | Univ Texas | uso de agonista de tlr9 e agonista de tlr2/6 na preparação de uma composição farmacêutica para tratamento, inibição ou atenuação de uma infecção microbiana, bem como composição farmaceuticamente aceitável compreendendo os referidos agonistas |
| EP2437791B1 (en) * | 2009-06-01 | 2017-03-22 | Idera Pharmaceuticals, Inc. | Potentiation of autoimmune and inflammatory disease treatments by immune regulatory oligonucleotide (iro) antagonists of tlr7 and tlr9 |
| SG177564A1 (en) | 2009-07-06 | 2012-02-28 | Ontorii Inc | Novel nucleic acid prodrugs and methods of use thereof |
| EP2451974A2 (en) * | 2009-07-08 | 2012-05-16 | Idera Pharmaceuticals, Inc. | Oligonucleotide-based compounds as inhibitors of toll-like receptors |
| JP6205133B2 (ja) | 2009-07-10 | 2017-09-27 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 抗炎症剤としての恒久的に荷電したナトリウムおよびカルシウムチャンネルブロッカー |
| DE102009034779A1 (de) | 2009-07-25 | 2011-02-03 | Emc Microcollections Gmbh | Synthetische Analoga bakterieller Lipopeptide und ihre Anwendung zur Therapie und Prophylaxe allergischer Erkrankungen |
| ES2538347T3 (es) * | 2009-08-27 | 2015-06-19 | Idera Pharmaceuticals, Inc. | Composiciones para inhibir expresión genética y usos de las mismas |
| BR112012007137A2 (pt) | 2009-09-30 | 2015-09-15 | Harvard College | metodos para modulacao da autofagia por meio da modulacao de produtos genicos inibidores da autofagia |
| CN103153346A (zh) | 2010-06-16 | 2013-06-12 | 戴纳瓦克斯技术公司 | 使用tlr7和/或tlr9抑制剂的治疗方法 |
| EP2620428B1 (en) | 2010-09-24 | 2019-05-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| EP2640420B1 (en) | 2010-11-19 | 2018-08-15 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| GB201021867D0 (en) | 2010-12-23 | 2011-02-02 | Mologen Ag | Non-coding immunomodulatory DNA construct |
| US9605019B2 (en) | 2011-07-19 | 2017-03-28 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| JP6246121B2 (ja) * | 2012-07-13 | 2017-12-13 | 株式会社新日本科学 | キラル核酸アジュバント |
| JP6268157B2 (ja) | 2012-07-13 | 2018-01-24 | 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ | 不斉補助基 |
| SG10201912895PA (en) | 2012-07-13 | 2020-02-27 | Wave Life Sciences Ltd | Chiral control |
| WO2014085154A1 (en) | 2012-11-27 | 2014-06-05 | Beth Israel Deaconess Medical Center, Inc. | Methods for treating renal disease |
| CA2896537C (en) * | 2013-01-08 | 2021-10-12 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| AR095882A1 (es) | 2013-04-22 | 2015-11-18 | Hoffmann La Roche | Terapia de combinación de anticuerpos contra csf-1r humano con un agonista de tlr9 |
| EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| JPWO2015108047A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| PT3094728T (pt) | 2014-01-16 | 2022-05-19 | Wave Life Sciences Ltd | Desenho quiral |
| US10286065B2 (en) | 2014-09-19 | 2019-05-14 | Board Of Regents, The University Of Texas System | Compositions and methods for treating viral infections through stimulated innate immunity in combination with antiviral compounds |
| US9688993B2 (en) | 2015-02-13 | 2017-06-27 | Idera Pharmaceuticals, Inc. | Toll-like receptor 9 antagonist and methods of use thereof |
| CN104807994B (zh) * | 2015-04-29 | 2016-08-24 | 大连理工大学 | 一种基于脱碱基位点的免标记凝血酶检测方法 |
| KR101745520B1 (ko) * | 2015-05-29 | 2017-06-12 | 아주대학교산학협력단 | 신규한 tlr4 길항제 |
| CN108348774A (zh) | 2015-08-03 | 2018-07-31 | 哈佛大学校长及研究员协会 | 带电离子通道阻断剂及其应用 |
| 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 |
| US20190046638A1 (en) | 2016-04-01 | 2019-02-14 | Checkmate Pharmaceuticals, Inc. | Fc RECEPTOR-MEDIATED DRUG DELIVERY |
| JP7034951B2 (ja) | 2016-06-08 | 2022-03-14 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 操作されたウイルスベクターは炎症および免疫応答の誘導を低減する |
| CA3044484A1 (en) | 2016-11-23 | 2018-05-31 | Berlin Cures GmbH | Aptamers for use in inhibition and/or suppression of tlr9 activation |
| US11806364B2 (en) | 2017-09-28 | 2023-11-07 | Industry-Academic Cooperation Foundation, Yonsei University | Method for producing myeloid-derived suppressor cells, myeloid-derived suppressor cells produced thereby, and methods thereof |
| WO2019094548A1 (en) | 2017-11-08 | 2019-05-16 | President And Fellows Of Harvard College | Compositions and methods for inhibiting viral vector-induced inflammatory responses |
| WO2019160866A2 (en) | 2018-02-13 | 2019-08-22 | Checkmate Pharmaceuticals, Inc. | Compositions and methods for tumor immunotherapy |
| AU2019251421B2 (en) | 2018-04-09 | 2025-05-01 | Checkmate Pharmaceuticals | Packaging oligonucleotides into virus-like particles |
| MX2021010869A (es) | 2019-03-11 | 2022-01-19 | Nocion Therapeutics Inc | Bloqueadores de canales iónicos sustituidos por éster y métodos para su uso. |
| US10780083B1 (en) | 2019-03-11 | 2020-09-22 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| WO2020185881A1 (en) | 2019-03-11 | 2020-09-17 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| US11377422B2 (en) | 2019-03-11 | 2022-07-05 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| US10828287B2 (en) | 2019-03-11 | 2020-11-10 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| CN113874383A (zh) * | 2019-03-13 | 2021-12-31 | 朴东辉 | 具有抗炎活性的寡核苷酸 |
| US10933055B1 (en) | 2019-11-06 | 2021-03-02 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| CN114828845A (zh) | 2019-11-06 | 2022-07-29 | 诺西恩医疗公司 | 带电的离子通道阻滞剂及其使用方法 |
| US12162851B2 (en) | 2020-03-11 | 2024-12-10 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| KR20230022830A (ko) | 2020-03-11 | 2023-02-16 | 녹시온 테라퓨틱스 인코포레이티드 | 하전된 이온 채널 차단제 및 사용 방법 |
| CN114099535B (zh) * | 2020-12-10 | 2023-01-03 | 南京吉迈生物技术有限公司 | Toll样受体9(TLR9)激动剂水凝胶免疫调节组合物 |
| AU2021401085A1 (en) * | 2020-12-16 | 2023-07-06 | Dynavax Technologies Corporation | Method for quantifying cpg-containing oligonucleotides in formulations comprising alum |
| EP4637788A1 (en) | 2022-12-19 | 2025-10-29 | Six Therapeutics Inc. | Compositions and methods of using cpg oligonucleotides |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US239733A (en) * | 1881-04-05 | William w | ||
| US97719A (en) * | 1869-12-07 | E-benez ee sperry | ||
| AUPO203996A0 (en) | 1996-08-30 | 1996-09-26 | Novogen Research Pty Ltd | Therapeutic uses |
| US6426334B1 (en) | 1997-04-30 | 2002-07-30 | Hybridon, Inc. | Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal |
| CA2381993A1 (en) | 1999-08-13 | 2001-02-22 | Hybridon, Inc. | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
| US6899891B2 (en) | 1999-12-16 | 2005-05-31 | Harry J. Siskind | Nutritional composition, methods of producing said composition and methods of using said composition |
| CA2398432C (en) | 2000-01-26 | 2012-06-19 | Hybridon, Inc. | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
| DE60109916T2 (de) * | 2000-05-01 | 2006-01-19 | Hybridon, Inc., Cambridge | MODULATION EINER OLIGONUKLEOTID- CpG-VERMITTELTEN IMMUNSTIMULATION DURCH POSITIONELLE MODIFIKATION VON NUKLEOSIDEN |
| 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 |
| SE0201701D0 (sv) * | 2002-06-05 | 2002-06-05 | Gotovax Ab | Treatment of epithelial tumors and infections |
| AU2003243409A1 (en) * | 2002-06-05 | 2003-12-22 | Coley Pharmaceutical Group, Inc. | Method for treating autoimmune or inflammatory diseases with combinations of inhibitory oligonucleotides and small molecule antagonists of immunostimulatory cpg nucleic acids |
| EP1393745A1 (en) * | 2002-07-29 | 2004-03-03 | Hybridon, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5'ends |
| WO2004094671A2 (en) * | 2003-04-22 | 2004-11-04 | Coley Pharmaceutical Gmbh | Methods and products for identification and assessment of tlr ligands |
| CA2526212C (en) * | 2003-05-16 | 2013-08-27 | Hybridon, Inc. | Synergistic treatment of cancer using immunomers in conjunction with chemotherapeutic agents |
| MXPA05013922A (es) * | 2003-06-20 | 2006-02-24 | Coley Pharm Group Inc | Antagonistas de receptor tipo toll de molecula pequena. |
| CA2532926A1 (en) * | 2003-07-15 | 2005-02-03 | Hybridon, Inc. | Combined use of immunostimulatory oligonucleotides and cytokines or radiation |
| US20050239733A1 (en) | 2003-10-31 | 2005-10-27 | Coley Pharmaceutical Gmbh | Sequence requirements for inhibitory oligonucleotides |
| GB0329146D0 (en) | 2003-12-16 | 2004-01-21 | Glaxosmithkline Biolog Sa | Vaccine |
| EP2305693B1 (en) | 2004-09-01 | 2015-07-15 | Dynavax Technologies Corporation | Methods and compositions for inhibition of innate immune responses and autoimmunity |
| WO2006063072A2 (en) | 2004-12-08 | 2006-06-15 | 3M Innovative Properties Company | Immunomodulatory compositions, combinations and methods |
| JP2008524237A (ja) | 2004-12-17 | 2008-07-10 | ダイナバックス テクノロジーズ コーポレイション | 免疫寛容の誘導又は促進のための方法及び組成物 |
| EA200800943A1 (ru) | 2005-09-27 | 2008-12-30 | Коли Фармасьютикал Гмбх | Модуляция tlr-опосредуемых иммунных ответов с использованием олигонуклеотидов-адаптеров |
| US8383598B2 (en) | 2005-10-12 | 2013-02-26 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| US8399423B2 (en) | 2005-10-12 | 2013-03-19 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| US8426375B2 (en) | 2005-10-12 | 2013-04-23 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| CN104278037B (zh) | 2005-10-12 | 2020-09-15 | 艾德拉药物股份有限公司 | 基于变异应答调制Toll样受体的免疫调节寡核苷酸(IRO)化合物 |
| US8377898B2 (en) | 2006-10-12 | 2013-02-19 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| AU2008286735A1 (en) | 2007-08-15 | 2009-02-19 | Idera Pharmaceuticals, Inc. | Toll like receptor modulators |
| EP2361980B1 (en) | 2007-10-26 | 2016-12-07 | Dynavax Technologies Corporation | Methods and compositions for inhibition of immune responses and autoimmunity |
| US20090131512A1 (en) | 2007-10-31 | 2009-05-21 | Dynavax Technologies Corp. | Inhibition of type I in IFN production |
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| US8357665B2 (en) | 2013-01-22 |
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| AU2006304205B2 (en) | 2011-09-08 |
| EP1934239B1 (en) | 2015-07-15 |
| KR101455081B1 (ko) | 2014-10-27 |
| US20160138022A1 (en) | 2016-05-19 |
| JP6406793B2 (ja) | 2018-10-17 |
| US20170145417A1 (en) | 2017-05-25 |
| US20130267583A1 (en) | 2013-10-10 |
| EP2982679A1 (en) | 2016-02-10 |
| CN104278037A (zh) | 2015-01-14 |
| WO2007047396A3 (en) | 2007-12-21 |
| US9206430B2 (en) | 2015-12-08 |
| JP2009515823A (ja) | 2009-04-16 |
| AU2006304205C1 (en) | 2012-11-15 |
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