JP2012505221A - 高コレステロール血症および高脂血症ならびにそれらに関連する疾患の予防および処置におけるトル様受容体の阻害剤の使用 - Google Patents
高コレステロール血症および高脂血症ならびにそれらに関連する疾患の予防および処置におけるトル様受容体の阻害剤の使用 Download PDFInfo
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| CA3002443A1 (en) | 2006-11-20 | 2008-05-29 | President And Fellows Of Harvard College | Methods, compositions, and kits for treating pain and pruritis |
| WO2010054288A2 (en) * | 2008-11-07 | 2010-05-14 | National Jewish Health | Diagnosis and treatment of autoimmune diseases by targeting autoimmune-related b cells ("abcs") |
| WO2011005942A2 (en) * | 2009-07-08 | 2011-01-13 | Idera Pharmaceuticals, Inc. | Oligonucleotide-based compounds as inhibitors of toll-like receptors |
| CN102725401A (zh) | 2009-07-10 | 2012-10-10 | 哈佛大学校长及研究员协会 | 作为抗炎药的永久带电荷的钠和钙通道阻断剂 |
| WO2012068470A2 (en) | 2010-11-19 | 2012-05-24 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| WO2014085154A1 (en) | 2012-11-27 | 2014-06-05 | Beth Israel Deaconess Medical Center, Inc. | Methods for treating renal disease |
| JP6385957B2 (ja) | 2013-01-08 | 2018-09-05 | 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Ｉｄｅｒａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | トール様受容体に基づく免疫応答を調節するための免疫調節オリゴヌクレオチド（ｉｒｏ）化合物 |
| JP6286065B2 (ja) | 2014-12-14 | 2018-02-28 | ヴィア アライアンス セミコンダクター カンパニー リミテッド | アウトオブオーダープロセッサの書き込み結合メモリ領域アクセスに依存するロードリプレイを除外する装置及び方法 |
| KR101745524B1 (ko) | 2015-05-29 | 2017-06-12 | 아주대학교산학협력단 | 신규한 tlr2 길항제 |
| WO2016195194A2 (ko) * | 2015-05-29 | 2016-12-08 | 아주대학교산학협력단 | 신규한 tlr2 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 |
| CN105506119A (zh) * | 2016-01-08 | 2016-04-20 | 张君 | 大鼠网膜脂肪组织炎症通路关键因子表达水平的测定方法 |
| CN105695625B (zh) * | 2016-04-29 | 2021-12-17 | 宁波大学 | 一种用于辅助诊断原发性高血压的检测试剂盒及其应用 |
| AU2017277647B2 (en) | 2016-06-08 | 2023-07-27 | President And Fellows Of Harvard College | Engineered viral vector reduces induction of inflammatory and immune responses |
| KR20200085812A (ko) | 2017-11-08 | 2020-07-15 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 바이러스 벡터-유도된 염증 반응을 억제하기 위한 조성물 및 방법 |
| US12440536B2 (en) | 2018-05-18 | 2025-10-14 | The University Of Hong Kong | Compositions of toll-like receptor 5 (TLR5) agonist and methods of use thereof |
| WO2020011869A2 (en) | 2018-07-11 | 2020-01-16 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting tlr2 |
| CN109251956A (zh) * | 2018-09-18 | 2019-01-22 | 青岛大学 | 糖尿病大鼠胰岛内MyD88 mRNA表达及黄芪的调节作用 |
| KR20210143791A (ko) | 2019-03-11 | 2021-11-29 | 녹시온 테라퓨틱스 인코포레이티드 | 하전된 이온 채널 차단제 및 사용 방법 |
| US10780083B1 (en) | 2019-03-11 | 2020-09-22 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| JP7630439B2 (ja) | 2019-03-11 | 2025-02-17 | ノシオン セラピューティクス，インコーポレイテッド | エステル置換イオンチャンネル遮断薬および使用方法 |
| WO2020185928A1 (en) | 2019-03-11 | 2020-09-17 | 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 |
| US10842798B1 (en) | 2019-11-06 | 2020-11-24 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
| JP7513713B2 (ja) | 2019-11-06 | 2024-07-09 | ノシオン セラピューティクス，インコーポレイテッド | 荷電したイオンチャンネル遮断薬および使用方法 |
| CN119118953A (zh) | 2020-03-11 | 2024-12-13 | 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 |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| ES2233426T3 (es) * | 1999-08-13 | 2005-06-16 | Hybridon, Inc. | Modulacion de la estimulacion inmunitaria medida por cpg de oligonucleotido por modificacion de la posicion de los nucleosidos. |
| 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 |
| AU2001257366B2 (en) | 2000-05-01 | 2006-03-16 | 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 |
| WO2003035836A2 (en) * | 2001-10-24 | 2003-05-01 | Hybridon Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends |
| 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 |
| WO2003084527A1 (en) * | 2002-04-08 | 2003-10-16 | Takeda Chemical Industries, Ltd. | Severe sepsis preventive therapeutic agent |
| US20040009949A1 (en) * | 2002-06-05 | 2004-01-15 | 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 |
| SE0201701D0 (sv) | 2002-06-05 | 2002-06-05 | Gotovax Ab | Treatment of epithelial tumors and infections |
| 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 |
| EA200600069A1 (ru) | 2003-06-20 | 2006-08-25 | Коли Фармасьютикал Гмбх | Низкомолекулярные антагонисты toll-подобных рецепторов (tlr) |
| EP1648913A4 (en) * | 2003-07-15 | 2008-09-10 | Idera Pharmaceuticals Inc | SYNERGISTIC STIMULATION OF THE IMMUNE SYSTEM WITH IMMUNOSTIMULATING OLIGONUCLEOTIDES AND / OR IMMUNOMER COMPOUNDS RELATED TO CYTOKINES AND / OR CHEMOTHERAPEAN MEDICAMENTS OR RADIATION THERAPY |
| EP1697389A4 (en) * | 2003-10-24 | 2008-12-24 | Eisai R&D Man Co Ltd | COMPOUNDS AND METHODS FOR TREATING ILLNESS AND SUFFERING TOLL-LIKE RECEPTOR 2 RELATED DISORDERS |
| 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 |
| JP2007534775A (ja) * | 2004-05-28 | 2007-11-29 | セダーズ−シナイ メディカル センター | 脈管の疾患を処置するための方法 |
| NZ553581A (en) * | 2004-09-01 | 2011-04-29 | Dynavax Tech Corp | Methods and compositions for inhibition of innate immune responses and autoimmunity using immunoregulatory polynucleotides with a TGC sequence |
| WO2006063072A2 (en) | 2004-12-08 | 2006-06-15 | 3M Innovative Properties Company | Immunomodulatory compositions, combinations and methods |
| WO2006066003A2 (en) * | 2004-12-17 | 2006-06-22 | Dynavax Technologies Corporation | Methods and compositions for induction or promotion of immune tolerance |
| US20060257411A1 (en) * | 2005-05-06 | 2006-11-16 | Bruce Beutler | Compositions and methods for modulating cells via CD14 and toll-like receptor 4 signaling pathway |
| EP1928500A2 (en) | 2005-09-27 | 2008-06-11 | Coley Pharmaceutical GmbH | Modulation of tlr-mediated immune responses using adaptor oligonucleotides |
| US8399423B2 (en) * | 2005-10-12 | 2013-03-19 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| US8383598B2 (en) * | 2005-10-12 | 2013-02-26 | 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 |
| WO2007047396A2 (en) * | 2005-10-12 | 2007-04-26 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| US8377898B2 (en) * | 2006-10-12 | 2013-02-19 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| CA2694973A1 (en) * | 2007-08-15 | 2009-02-19 | Idera Pharmaceuticals, Inc. | Toll like receptor modulators |
| AU2008317261B2 (en) * | 2007-10-26 | 2015-04-09 | 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 |
| WO2009154609A1 (en) * | 2008-06-17 | 2009-12-23 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
| US11114308B2 (en) | 2018-09-25 | 2021-09-07 | International Business Machines Corporation | Controlling of height of high-density interconnection structure on substrate |
| US11116008B2 (en) | 2018-11-02 | 2021-09-07 | Samsung Electronics Co., Ltd. | Method and device for radio resource allocation in wireless communication system |
| TWI711225B (zh) | 2019-07-01 | 2020-11-21 | 唐虞企業股份有限公司 | 連接器總成 |
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- 2009-10-06 EP EP09740570A patent/EP2349271A2/en not_active Withdrawn
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016518338A (ja) * | 2013-03-15 | 2016-06-23 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 炎症を伴う疾患の治療のためのデスエチルヒドロキシクロロキン |
| US9931335B2 (en) | 2013-03-15 | 2018-04-03 | The Board Of Trustees Of The Leland Stanford Junior University | Desethylhydroxychloroquine for the treatment of diseases associated with inflammation |
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| CA2738816A1 (en) | 2010-04-15 |
| KR20110071108A (ko) | 2011-06-28 |
| US20100098685A1 (en) | 2010-04-22 |
| WO2010042543A2 (en) | 2010-04-15 |
| EP2349271A2 (en) | 2011-08-03 |
| CN102281880A (zh) | 2011-12-14 |
| EP3087988A3 (en) | 2017-03-01 |
| MX2011003625A (es) | 2011-05-31 |
| EP3087988A2 (en) | 2016-11-02 |
| US8853177B2 (en) | 2014-10-07 |
| AU2009302468A1 (en) | 2010-04-15 |
| WO2010042543A3 (en) | 2011-08-11 |
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