AU2007257094B2 - Compounds and methods for modulating expression of SGLT2 - Google Patents
Compounds and methods for modulating expression of SGLT2 Download PDFInfo
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- AU2007257094B2 AU2007257094B2 AU2007257094A AU2007257094A AU2007257094B2 AU 2007257094 B2 AU2007257094 B2 AU 2007257094B2 AU 2007257094 A AU2007257094 A AU 2007257094A AU 2007257094 A AU2007257094 A AU 2007257094A AU 2007257094 B2 AU2007257094 B2 AU 2007257094B2
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Families Citing this family (384)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
| US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| US20060009410A1 (en) * | 2002-11-13 | 2006-01-12 | Crooke Rosanne M | Effects of apolipoprotein B inhibition on gene expression profiles in animals |
| JP2005244488A (ja) | 2004-02-25 | 2005-09-08 | Matsushita Electric Ind Co Ltd | 複合機 |
| US20050287558A1 (en) | 2004-05-05 | 2005-12-29 | Crooke Rosanne M | SNPs of apolipoprotein B and modulation of their expression |
| EP2096170B1 (en) * | 2005-09-19 | 2011-08-10 | Isis Pharmaceuticals, Inc. | Modulation of glucagon receptor expression |
| JP5713377B2 (ja) | 2005-12-28 | 2015-05-07 | ザ スクリプス リサーチ インスティテュート | 薬物標的としての天然アンチセンスおよび非コードrna転写物 |
| US7764650B2 (en) | 2006-03-02 | 2010-07-27 | Intel Corporation | Mobile station and method for fast roaming with integrity protection and source authentication using a common protocol |
| ES2569558T3 (es) | 2006-04-03 | 2016-05-11 | Roche Innovation Center Copenhagen A/S | Composición farmacéutica que comprende oligonucleótidos antisentido anti-ARNmi |
| MX2008012219A (es) | 2006-04-03 | 2008-10-02 | Santaris Pharma As | Composicion farmaceutica que comprende oligonucleotidos antisentido anti-miarn. |
| WO2007131237A2 (en) | 2006-05-05 | 2007-11-15 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of ptp1b |
| WO2008011431A2 (en) * | 2006-07-17 | 2008-01-24 | Sirna Therapeutics Inc. | Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina) |
| EP2410053B2 (en) | 2006-10-18 | 2020-07-15 | Ionis Pharmaceuticals, Inc. | Antisense compounds |
| KR20090103894A (ko) | 2006-11-27 | 2009-10-01 | 아이시스 파마수티컬즈 인코포레이티드 | 고콜레스테롤혈증을 치료하는 방법 |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US8470791B2 (en) * | 2007-03-22 | 2013-06-25 | Santaris Pharma A/S | RNA antagonist compounds for the inhibition of Apo-B100 expression |
| KR20150090284A (ko) | 2007-03-24 | 2015-08-05 | 젠자임 코포레이션 | 인간 아포리포프로틴 b에 상보적인 안티센스 올리고뉴클레오타이드 투여 |
| WO2008132234A2 (en) | 2007-05-01 | 2008-11-06 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of beta-catenin |
| AU2008250033A1 (en) | 2007-05-11 | 2008-11-20 | Enzon Pharmaceuticals, Inc. | RNA antagonist compounds for the modulation of HER3 |
| US8278283B2 (en) † | 2007-07-05 | 2012-10-02 | Isis Pharmaceuticals, Inc. | 6-disubstituted or unsaturated bicyclic nucleic acid analogs |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US8318496B2 (en) * | 2007-10-04 | 2012-11-27 | Isis Pharmaceuticals, Inc. | Compounds and methods for improving cellular uptake of oligomeric compounds |
| AU2008306327B2 (en) | 2007-10-04 | 2014-05-15 | Roche Innovation Center Copenhagen A/S | Micromirs |
| EP2225377B1 (en) | 2007-11-26 | 2014-01-08 | Santaris Pharma A/S | Lna antagonists targeting the androgen receptor |
| US8450290B2 (en) | 2007-11-26 | 2013-05-28 | Enzon Pharmaceuticals, Inc. | Methods for treating androgen receptor dependent disorders including cancers |
| US20100323967A1 (en) * | 2007-12-07 | 2010-12-23 | Santaris Pharma A/S | RNA Antagonist Compounds for the Modulation of MCL-1 |
| CN104975020B (zh) | 2008-02-11 | 2020-01-17 | 菲奥医药公司 | 经修饰的RNAi多核苷酸及其用途 |
| US8404659B2 (en) | 2008-03-07 | 2013-03-26 | Santaris Pharma A/S | Pharmaceutical compositions for treatment of MicroRNA related diseases |
| WO2009117589A1 (en) | 2008-03-21 | 2009-09-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising tricyclic nucleosides and methods for their use |
| EP2274423A2 (en) | 2008-04-04 | 2011-01-19 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity |
| US20110224280A1 (en) * | 2008-04-16 | 2011-09-15 | Niels Fisker Nielsen | Pharmaceutical Composition Comprising Anti PCSK9 Oligomers |
| EP2291200A4 (en) | 2008-05-22 | 2012-05-30 | Isis Pharmaceuticals Inc | PROCESS FOR MODULATING THE EXPRESSION OF RBP4 |
| EP2297322A1 (en) | 2008-06-04 | 2011-03-23 | The Board of Regents of The University of Texas System | Modulation of gene expression through endogenous small rna targeting of gene promoters |
| WO2009148605A2 (en) * | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| EP2317847B1 (en) | 2008-07-29 | 2019-04-17 | The Board of Regents of The University of Texas System | Selective inhibition of polyglutamine protein expression |
| ES2541442T3 (es) | 2008-08-01 | 2015-07-20 | Roche Innovation Center Copenhagen A/S | Modulación mediada por microARN de factores estimulantes de colonias |
| MX2011002143A (es) | 2008-08-25 | 2011-07-20 | Excaliard Pharmaceuticals Inc | Oligonucleotidos antisentido dirigidos contra el factor de crecimiento del tejido conectivo y usos de los mismos. |
| EP3375451A1 (en) | 2008-08-25 | 2018-09-19 | Excaliard Pharmaceuticals, Inc. | Method for reducing scarring during wound healing using antisense compounds directed to ctgf |
| US8796443B2 (en) | 2008-09-22 | 2014-08-05 | Rxi Pharmaceuticals Corporation | Reduced size self-delivering RNAi compounds |
| CN102239260B (zh) | 2008-10-03 | 2017-04-12 | 库尔纳公司 | 通过抑制针对载脂蛋白‑a1的天然反义转录物治疗载脂蛋白‑a1相关疾病 |
| KR101773551B1 (ko) * | 2008-10-15 | 2017-08-31 | 아이오니스 파마수티컬즈, 인코포레이티드 | 인자 11 발현의 조정 |
| CN102264374B (zh) * | 2008-10-24 | 2015-01-07 | Isis制药公司 | 5′和2′双取代的核苷和由其制备的低聚化合物 |
| KR101881596B1 (ko) | 2008-12-02 | 2018-07-24 | 웨이브 라이프 사이언시스 재팬 인코포레이티드 | 인 원자 변형된 핵산의 합성 방법 |
| ES2629630T3 (es) | 2008-12-04 | 2017-08-11 | Curna, Inc. | Tratamiento de enfermedades relacionadas con eritropoyetina (EPO) mediante inhibición del transcrito antisentido natural a EPO |
| KR101840618B1 (ko) | 2008-12-04 | 2018-03-20 | 큐알엔에이, 인크. | 종양 억제 유전자에 대한 천연 안티센스 전사체의 억제에 의해 종양 억제 유전자 관련된 질환의 치료 |
| CA2746003C (en) | 2008-12-04 | 2020-03-31 | Opko Curna, Llc | Treatment of vascular endothelial growth factor (vegf) related diseases by inhibition of natural antisense transcript to vegf |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| US20130064834A1 (en) | 2008-12-15 | 2013-03-14 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia using antibodies to pcsk9 |
| WO2010078536A1 (en) * | 2009-01-05 | 2010-07-08 | Rxi Pharmaceuticals Corporation | Inhibition of pcsk9 through rnai |
| MX2011007776A (es) * | 2009-02-03 | 2011-08-12 | Hoffmann La Roche | Compsiciones y metodos para inhibir la expresion de genes ptp1b. |
| WO2010090762A1 (en) | 2009-02-04 | 2010-08-12 | Rxi Pharmaceuticals Corporation | Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| ES2560107T3 (es) | 2009-02-12 | 2016-02-17 | Curna, Inc. | Tratamiento de enfermedades relacionadas con el factor neurotrófico derivado de cerebro (BDNF) por inhibición de transcrito antisentido natural para BDNF |
| CN102439149B (zh) * | 2009-02-12 | 2018-01-02 | 库尔纳公司 | 通过抑制针对胶质细胞衍生神经营养因子(gdnf)的天然反义转录物来治疗gdnf相关的疾病 |
| WO2010107838A1 (en) | 2009-03-16 | 2010-09-23 | Isis Pharmaceuticals, Inc. | Targeting apolipoprotein b for the reduction of apolipoprotein c-iii |
| CN102482677B (zh) | 2009-03-16 | 2017-10-17 | 库尔纳公司 | 通过抑制nrf2的天然反义转录物治疗核因子(红细胞衍生2)‑样2(nrf2)相关疾病 |
| CA2755404C (en) | 2009-03-17 | 2020-03-24 | Joseph Collard | Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1 |
| US8815586B2 (en) | 2009-04-24 | 2014-08-26 | The Board Of Regents Of The University Of Texas System | Modulation of gene expression using oligomers that target gene regions downstream of 3′ untranslated regions |
| WO2010122538A1 (en) | 2009-04-24 | 2010-10-28 | Santaris Pharma A/S | Pharmaceutical compositions for treatment of hcv patients that are non-responders to interferon |
| EP2427553A4 (en) | 2009-05-06 | 2012-11-07 | Opko Curna Llc | TREATMENT OF LIPID TRANSPORT AND METABOLISM-RELATED DISEASES BY INHIBITING THE NATURAL ANTISENSE TRANSCRIPT AGAINST A LIPID TRANSPORT AND METABOLIC TREATMENT |
| ES2609655T3 (es) | 2009-05-06 | 2017-04-21 | Curna, Inc. | Tratamiento de enfermedades relacionadas con tristetraprolina (TTP) mediante inhibición de transcrito antisentido natural para TTP |
| WO2010129861A2 (en) | 2009-05-08 | 2010-11-11 | Curna, Inc. | Treatment of dystrophin family related diseases by inhibition of natural antisense transcript to dmd family |
| BRPI1012769A2 (pt) * | 2009-05-15 | 2018-01-30 | Hoffmann La Roche | composições e métodos para inibir expressão de genes de receptor de glicocorticóide (gcr) |
| US8957037B2 (en) | 2009-05-18 | 2015-02-17 | Curna, Inc. | Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor |
| CN102549158B (zh) | 2009-05-22 | 2017-09-26 | 库尔纳公司 | 通过抑制针对转录因子e3(tfe3)的天然反义转录物来治疗tfe3和胰岛素受体底物蛋白2(irs2)相关的疾病 |
| CA2764683A1 (en) | 2009-05-28 | 2010-12-02 | Joseph Collard | Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene |
| JP6128846B2 (ja) | 2009-06-16 | 2017-05-17 | クルナ・インコーポレーテッド | パラオキソナーゼ(pon1)に対する天然アンチセンス転写物の抑制によるpon1遺伝子関連疾患の治療 |
| CN102695797B (zh) | 2009-06-16 | 2018-05-25 | 库尔纳公司 | 通过抑制针对胶原基因的天然反义转录物来治疗胶原基因相关的疾病 |
| WO2010151671A2 (en) | 2009-06-24 | 2010-12-29 | Curna, Inc. | Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2 |
| ES2583691T3 (es) | 2009-06-26 | 2016-09-21 | Curna, Inc. | Tratamiento de enfermedades relacionadas con un gen del síndrome de Down mediante la inhibición de una transcripción antisentido natural a un gen del síndrome de Down |
| RU2612521C2 (ru) | 2009-07-06 | 2017-03-09 | Онтории, Инк. | Новые пролекарства нуклеиновых кислот и способы их применения |
| EP2456870A1 (en) | 2009-07-21 | 2012-05-30 | Santaris Pharma A/S | Antisense oligomers targeting pcsk9 |
| JP2013500017A (ja) | 2009-07-24 | 2013-01-07 | カッパーアールエヌエー,インコーポレイテッド | サ−チュイン(sirt)への天然アンチセンス転写物の阻止によるサ−チュイン(sirt)関連疾患の治療 |
| EP2462229B1 (en) | 2009-08-05 | 2016-05-11 | CuRNA, Inc. | Treatment of insulin gene (ins) related diseases by inhibition of natural antisense transcript to an insulin gene (ins) |
| CN102625841A (zh) | 2009-08-11 | 2012-08-01 | 欧科库尔纳有限责任公司 | 通过抑制脂连蛋白(adipoq)的天然反义转录物治疗脂连蛋白(adipoq)相关疾病 |
| CA2771228C (en) | 2009-08-21 | 2020-12-29 | Opko Curna, Llc | Treatment of 'c terminus of hsp70-interacting protein' (chip) related diseases by inhibition of natural antisense transcript to chip |
| KR101892760B1 (ko) | 2009-08-25 | 2018-08-28 | 큐알엔에이, 인크. | IQGAP에 대한 천연 안티센스 전사체의 억제에 의한 GTPase 활성화 단백질을 함유하는 IQ 모티프(IQGAP)와 관련된 질환의 치료 |
| JP6175236B2 (ja) | 2009-09-25 | 2017-08-09 | カッパーアールエヌエー,インコーポレイテッド | フィラグリン(flg)の発現および活性の調整によるflg関連疾患の処置 |
| US20120270929A1 (en) * | 2009-09-25 | 2012-10-25 | Isis Pharmaceuticals, Inc. | Modulation of ttc39 expression to increase hdl |
| KR20120093956A (ko) * | 2009-10-12 | 2012-08-23 | 메디뮨 엘엘씨 | 종양 분류를 위한 ir-a 및 ir-b의 정량 |
| WO2011046983A2 (en) | 2009-10-12 | 2011-04-21 | Smith Holdings, Llc | Methods and compositions for modulating gene expression using oligonucleotide based drugs administered in vivo or in vitro |
| US20110110860A1 (en) | 2009-11-02 | 2011-05-12 | The Board Of Regents Of The University Of Texas System | Modulation of ldl receptor gene expression with double-stranded rnas targeting the ldl receptor gene promoter |
| WO2011054811A1 (en) | 2009-11-03 | 2011-05-12 | Santaris Pharma A/S | Rna antagonists targeting hsp27 combination therapy |
| NO2513310T3 (enExample) | 2009-12-16 | 2018-03-31 | ||
| NO2516648T3 (enExample) | 2009-12-23 | 2018-04-07 | ||
| CA2782375C (en) | 2009-12-23 | 2023-10-31 | Opko Curna, Llc | Treatment of uncoupling protein 2 (ucp2) related diseases by inhibition of natural antisense transcript to ucp2 |
| KR101853508B1 (ko) | 2009-12-29 | 2018-06-20 | 큐알엔에이, 인크. | 종양 단백질 63 (p63)에 대한 천연 안티센스 전사체의 억제에 의한 p63에 관련된 질환의 치료 |
| KR101838305B1 (ko) | 2009-12-29 | 2018-03-13 | 큐알엔에이, 인크. | NRF1(Nuclear Respiratory Factor 1)에 대한 천연 안티센스 전사체의 억제에 의한 핵 호흡 인자 1 관련된 질환의 치료 |
| CN102791862B (zh) | 2009-12-31 | 2017-04-05 | 库尔纳公司 | 通过抑制胰岛素受体底物2(irs2)和转录因子e3(tfe3)的天然反义转录物而治疗irs2相关疾病 |
| CN102906264B (zh) | 2010-01-04 | 2017-08-04 | 库尔纳公司 | 通过抑制干扰素调节因子8(irf8)的天然反义转录物而治疗irf8相关疾病 |
| JP5963680B2 (ja) | 2010-01-06 | 2016-08-03 | カッパーアールエヌエー,インコーポレイテッド | 膵臓発生遺伝子に対する天然アンチセンス転写物の阻害による膵臓発生遺伝子疾患の治療 |
| ES2677969T3 (es) * | 2010-01-08 | 2018-08-07 | Ionis Pharmaceuticals, Inc. | Modulación de la expresión tipo angiopoyetina 3 |
| CA2786535C (en) | 2010-01-11 | 2019-03-26 | Curna, Inc. | Treatment of sex hormone binding globulin (shbg) related diseases by inhibition of natural antisense transcript to shbg |
| US20110172296A1 (en) * | 2010-01-12 | 2011-07-14 | Bennett C Frank | Modulation of transforming growth factor-beta 1 expression |
| JP5981850B2 (ja) | 2010-01-25 | 2016-08-31 | カッパーアールエヌエー,インコーポレイテッド | RNaseH1に対する天然アンチセンス転写物の阻害によるRNaseH1関連疾患の治療 |
| US9574191B2 (en) | 2010-02-03 | 2017-02-21 | The Board Of Regents Of The University Of Texas System | Selective inhibition of polyglutamine protein expression |
| EP3321361B1 (en) | 2010-02-08 | 2019-03-27 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| EP3208347B1 (en) * | 2010-02-08 | 2019-08-14 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| CN102844435B (zh) | 2010-02-22 | 2017-05-10 | 库尔纳公司 | 通过抑制吡咯啉‑5‑羧酸还原酶1(pycr1)的天然反义转录物而治疗pycr1相关疾病 |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2545173A2 (en) * | 2010-03-12 | 2013-01-16 | Sarepta Therapeutics, Inc. | Antisense modulation of nuclear hormone receptors |
| KR20180044433A (ko) | 2010-03-24 | 2018-05-02 | 알엑스아이 파마슈티칼스 코포레이션 | 진피 및 섬유증성 적응증에서의 rna 간섭 |
| RU2612884C2 (ru) | 2010-04-02 | 2017-03-13 | Курна, Инк. | Лечение заболеваний, связанных с колониестимулирующим фактором 3 (csf3), путем ингибирования природного антисмыслового транскрипта k csf3 |
| CN102858979B (zh) | 2010-04-09 | 2018-01-26 | 库尔纳公司 | 通过抑制成纤维细胞生长因子21(fgf21)的天然反义转录物而治疗fgf21相关疾病 |
| KR101936011B1 (ko) * | 2010-05-03 | 2019-01-07 | 큐알엔에이, 인크. | 시르투인 (sirt)에 대한 자연 안티센스 전사체의 저해에 의한 시르투인 (sirt) 관련된 질환의 치료 |
| TWI531370B (zh) | 2010-05-14 | 2016-05-01 | 可娜公司 | 藉由抑制par4天然反股轉錄本治療par4相關疾病 |
| US8895528B2 (en) | 2010-05-26 | 2014-11-25 | Curna, Inc. | Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1 |
| US8980858B2 (en) | 2010-05-26 | 2015-03-17 | Curna, Inc. | Treatment of methionine sulfoxide reductase a (MSRA) related diseases by inhibition of natural antisense transcript to MSRA |
| US8716258B2 (en) | 2010-06-04 | 2014-05-06 | The Board Of Regents, The University Of Texas System | Regulation of metabolism by miR-378 |
| WO2011156734A2 (en) | 2010-06-11 | 2011-12-15 | Hitachi Chemical Co., Ltd. | Method of characterizing vascular diseases |
| WO2011156763A1 (en) * | 2010-06-11 | 2011-12-15 | Hitachi Chemical Co., Ltd. | Methods for characterizing kidney function |
| EP2582397A4 (en) * | 2010-06-15 | 2014-10-29 | Isis Pharmaceuticals Inc | COMPOUNDS AND METHOD FOR MODULATING INTERACTION BETWEEN PROTEINS AND TARGET NUCLEIC ACIDS |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| KR101914309B1 (ko) | 2010-06-23 | 2018-11-02 | 큐알엔에이, 인크. | 전압 작동 나트륨 통로, 알파 소단위(scna)에 대한 자연 안티센스 전사체의 저해에 의한 전압 작동 나트륨 통로, 알파 소단위(scna) 관련된 질환의 치료 |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| JP5998131B2 (ja) | 2010-07-14 | 2016-09-28 | カッパーアールエヌエー,インコーポレイテッド | Discslargehomolog(dlg)dlg1への天然アンチセンス転写物の阻害によるdlg関連疾患の治療 |
| WO2012029870A1 (ja) * | 2010-08-31 | 2012-03-08 | 国立大学法人大阪大学 | オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する脂質異常症治療剤 |
| WO2012034942A1 (en) | 2010-09-13 | 2012-03-22 | Santaris Pharma A/S | Compounds for the modulation of aurora kinase b expression |
| JP5868324B2 (ja) | 2010-09-24 | 2016-02-24 | 株式会社Wave Life Sciences Japan | 不斉補助基 |
| KR101886457B1 (ko) | 2010-10-06 | 2018-08-07 | 큐알엔에이, 인크. | 시알리다아제 4 (neu4)에 대한 자연 안티센스 전사체의 저해에 의한 neu4 관련된 질환의 치료 |
| WO2012054723A2 (en) | 2010-10-22 | 2012-04-26 | Opko Curna Llc | Treatment of alpha-l-iduronidase (idua) related diseases by inhibition of natural antisense transcript to idua |
| EP2638163B1 (en) | 2010-11-12 | 2017-05-17 | The General Hospital Corporation | Polycomb-associated non-coding rnas |
| US9920317B2 (en) | 2010-11-12 | 2018-03-20 | The General Hospital Corporation | Polycomb-associated non-coding RNAs |
| US10000752B2 (en) | 2010-11-18 | 2018-06-19 | Curna, Inc. | Antagonat compositions and methods of use |
| WO2012066093A1 (en) | 2010-11-19 | 2012-05-24 | Santaris Pharma A/S | Compounds for the modulation of pdz-binding kinase (pbk) expression |
| WO2012066092A1 (en) | 2010-11-19 | 2012-05-24 | Santaris Pharma A/S | Compounds for the modulation of aurora kinase a expression |
| US8771696B2 (en) | 2010-11-23 | 2014-07-08 | Regeneron Pharmaceuticals, Inc. | Method of reducing the severity of stress hyperglycemia with human antibodies to the glucagon receptor |
| JO3756B1 (ar) | 2010-11-23 | 2021-01-31 | Regeneron Pharma | اجسام مضادة بشرية لمستقبلات الجلوكاجون |
| ES2657590T3 (es) | 2010-11-23 | 2018-03-06 | Curna, Inc. | Tratamiento de enfermedades relacionadas con nanog mediante inhibición del transcrito antisentido natural a nanog |
| MX347602B (es) | 2011-01-28 | 2017-05-03 | Sanofi Biotechnology | Composiciones farmaceuticas que comprenden anticuerpos humanos frente a pcsk9. |
| PT2670411T (pt) | 2011-02-02 | 2019-06-18 | Excaliard Pharmaceuticals Inc | Compostos anti sentido visando um fator de crescimento do tecido conetivo (ctfg) para utilização num método de tratamento de queloides ou cicatrizes hipertróficas |
| WO2012109395A1 (en) * | 2011-02-08 | 2012-08-16 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| WO2012110457A2 (en) | 2011-02-14 | 2012-08-23 | Santaris Pharma A/S | Compounds for the modulation of osteopontin expression |
| CA2832972C (en) * | 2011-04-13 | 2019-04-30 | Isis Pharmaceuticals, Inc. | Antisense modulation of ptp1b expression |
| WO2012143427A1 (en) | 2011-04-19 | 2012-10-26 | Santaris Pharma A/S | Anti polyomavirus compounds |
| CA2871089A1 (en) | 2011-04-20 | 2012-10-26 | Smith Holdings, Llc | Methods and compositions for modulating gene expression using components that self assemble in cells and produce rnai activity |
| TWI678375B (zh) | 2011-06-09 | 2019-12-01 | 可娜公司 | 藉由抑制共濟蛋白(frataxin,fxn)之天然反股轉錄本治療fxn相關疾病 |
| US9719129B2 (en) | 2011-06-10 | 2017-08-01 | Hitachi Chemical Co., Ltd. | Methods for isolating vesicles from biological fluids |
| BR112014001244A2 (pt) | 2011-07-19 | 2017-02-21 | Wave Life Sciences Pte Ltd | métodos para a síntese de ácidos nucléicos funcionalizados |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| EP3205725B1 (en) | 2011-08-11 | 2019-03-27 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| CN103874486A (zh) | 2011-09-06 | 2014-06-18 | 库尔纳公司 | 用小分子治疗与电压门控钠通道的α亚基(SCNxA)相关的疾病 |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2756080B1 (en) | 2011-09-14 | 2019-02-20 | Translate Bio MA, Inc. | Multimeric oligonucleotide compounds |
| PL4252857T3 (pl) | 2011-09-16 | 2025-03-03 | Regeneron Pharmaceuticals, Inc. | Sposoby redukowania poziomów lipoproteiny(a) poprzez podawanie inhibitora proproteinowej konwertazy subtylizyny keksyny-9 (pcsk9) |
| US8865674B2 (en) * | 2011-09-20 | 2014-10-21 | Isis Pharmaceuticals, Inc. | Antisense modulation of GCGR expression |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| KR20140084232A (ko) | 2011-10-25 | 2014-07-04 | 아이시스 파마수티컬즈 인코포레이티드 | Gccr 발현의 안티센스 조절 |
| ES2707232T3 (es) | 2011-12-16 | 2019-04-03 | Univ Nat Corp Tokyo Medical & Dental | Acido nucleico bicatenario quimérico |
| EP2825648B1 (en) | 2012-03-15 | 2018-09-05 | CuRNA, Inc. | Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf |
| AU2013202595B2 (en) * | 2012-03-30 | 2016-04-21 | Biogen Ma Inc. | Methods for modulating Tau expression for reducing seizure and modifying a neurodegenerative syndrome |
| WO2013159108A2 (en) | 2012-04-20 | 2013-10-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
| US10837014B2 (en) | 2012-05-16 | 2020-11-17 | Translate Bio Ma, Inc. | Compositions and methods for modulating SMN gene family expression |
| BR112014028646A2 (pt) * | 2012-05-16 | 2017-08-15 | Rana Therapeutics Inc | Composições e métodos para modulação da expressão de pten |
| KR20160074368A (ko) | 2012-05-16 | 2016-06-28 | 라나 테라퓨틱스, 인크. | Utrn 발현을 조절하기 위한 조성물 및 방법 |
| AU2013262709A1 (en) | 2012-05-16 | 2015-01-22 | Rana Therapeutics, Inc. | Compositions and methods for modulating MECP2 expression |
| WO2013173638A1 (en) | 2012-05-16 | 2013-11-21 | Rana Therapeutics, Inc. | Compositions and methods for modulating smn gene family expression |
| EA201492120A1 (ru) | 2012-05-16 | 2015-10-30 | Рана Терапьютикс, Инк. | Композиции и способы для модулирования экспрессии atp2a2 |
| BR112014028631A2 (pt) | 2012-05-16 | 2017-10-17 | Rana Therapeutics Inc | composições e métodos para modulação da expressão da família de genes da hemoglobina |
| CN104583398A (zh) * | 2012-05-16 | 2015-04-29 | Rana医疗有限公司 | 用于调节基因表达的组合物和方法 |
| US20160002624A1 (en) | 2012-05-17 | 2016-01-07 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide compositions |
| KR102657351B1 (ko) * | 2012-05-24 | 2024-04-16 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포지질단백질 (a) 발현을 조절하는 방법들 및 조성물들 |
| US9663784B2 (en) | 2012-05-26 | 2017-05-30 | Bonac Corporation | Single-stranded nucleic acid molecule for regulating expression of gene having delivering function |
| BR112015000723A2 (pt) | 2012-07-13 | 2017-06-27 | Shin Nippon Biomedical Laboratories Ltd | adjuvante de ácido nucléico quiral |
| CN112007045A (zh) | 2012-07-13 | 2020-12-01 | 波涛生命科学有限公司 | 手性控制 |
| ES2862073T3 (es) | 2012-07-13 | 2021-10-06 | Wave Life Sciences Ltd | Grupo auxiliar asimétrico |
| WO2014043544A1 (en) | 2012-09-14 | 2014-03-20 | Rana Therapeutics, Inc. | Multimeric oligonucleotide compounds |
| WO2014045126A2 (en) | 2012-09-18 | 2014-03-27 | Uti Limited Partnership | Treatment of pain by inhibition of usp5 de-ubiquitinase |
| US9695418B2 (en) | 2012-10-11 | 2017-07-04 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleosides and uses thereof |
| EP2906255B1 (en) | 2012-10-12 | 2023-02-22 | Ionis Pharmaceuticals, Inc. | Antisense compounds and uses thereof |
| EP2906697A4 (en) | 2012-10-15 | 2016-06-22 | Ionis Pharmaceuticals Inc | METHOD FOR MONITORING THE C9ORF72 EXPRESSION |
| RU2730677C2 (ru) | 2012-10-15 | 2020-08-24 | Ионис Фармасьютикалз, Инк. | Соединение для модуляции экспрессии гена c9orf72 и его применение |
| CA2889044A1 (en) * | 2012-11-15 | 2014-05-22 | Roche Innovation Center Copenhagen A/S | Anti apob antisense conjugate compounds |
| WO2014080004A1 (en) | 2012-11-26 | 2014-05-30 | Santaris Pharma A/S | Compositions and methods for modulation of fgfr3 expression |
| MX2015009056A (es) | 2013-01-30 | 2015-10-05 | Hoffmann La Roche | Conjugados de oligonucleotidos de acido nucleico bloqueado y carbohidratos. |
| DK2951191T3 (en) * | 2013-01-31 | 2019-01-14 | Ionis Pharmaceuticals Inc | PROCEDURE FOR MANUFACTURING OLIGOMERIC COMPOUNDS USING MODIFIED CLUTCH PROTOCOLS |
| EP2961853B1 (en) | 2013-02-28 | 2018-09-19 | The Board of Regents of The University of Texas System | Methods for classifying a cancer as susceptible to tmepai-directed therapies and treating such cancers |
| US20160108395A1 (en) | 2013-03-01 | 2016-04-21 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
| KR20150130430A (ko) | 2013-03-14 | 2015-11-23 | 아이시스 파마수티컬즈 인코포레이티드 | 타우 발현을 조절하는 조성물 및 방법 |
| WO2014153209A1 (en) | 2013-03-14 | 2014-09-25 | Andes Biotechnologies S.A. | Antisense oligonucletotides for treatment of cancer stem cells |
| WO2014145356A1 (en) * | 2013-03-15 | 2014-09-18 | MiRagen Therapeutics, Inc. | Bridged bicyclic nucleosides |
| EP2986599A1 (en) | 2013-04-17 | 2016-02-24 | Pfizer Inc. | N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases |
| BR112015027322A8 (pt) * | 2013-05-01 | 2018-01-02 | Isis Pharmaceuticals Inc | Compostos antissenso conjugados e sua utilização |
| US9662649B2 (en) | 2013-05-06 | 2017-05-30 | Hitachi Chemical Company America, Ltd. | Devices and methods for capturing target molecules |
| JP2016520310A (ja) | 2013-05-24 | 2016-07-14 | ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブRoche Innovation Center Copenhagen A/S | B細胞cll/リンパ腫11a(bcl11a)のオリゴヌクレオチドモデュレーター及びその使用 |
| US10111953B2 (en) | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
| CA2913499A1 (en) | 2013-05-30 | 2014-12-04 | National University Corporation Tokyo Medical And Dental University | Double-stranded agents for delivering therapeutic oligonucleotides |
| CA2914721A1 (en) | 2013-06-07 | 2014-12-11 | Regeneron Pharmaceuticals, Inc. | Methods for inhibiting atherosclerosis by administering an inhibitor of pcsk9 |
| CN105324119A (zh) | 2013-06-16 | 2016-02-10 | 国立大学法人东京医科齿科大学 | 具有外显子跳跃效应的双链反义核酸 |
| MX391977B (es) | 2013-06-27 | 2025-03-21 | Roche Innovation Ct Copenhagen As | Oligómeros antisentido y conjugados con diana en la proteína-convertasa subtilisina/kexina tipo 9(pcsk9). |
| TWI772856B (zh) | 2013-07-19 | 2022-08-01 | 美商百健Ma公司 | 用於調節τ蛋白表現之組合物 |
| WO2015023941A1 (en) | 2013-08-16 | 2015-02-19 | Rana Therapeutics, Inc. | Oligonucleotides targeting euchromatin regions of genes |
| BR112016007751A2 (pt) | 2013-10-11 | 2017-09-12 | Ionis Pharmaceuticals Inc | composições para modulação de expressão de c9orf72 |
| JP6616298B2 (ja) | 2013-11-12 | 2019-12-04 | サノフィ・バイオテクノロジー | Pcsk9阻害剤と共に使用するための投薬レジメン |
| WO2015100394A1 (en) | 2013-12-24 | 2015-07-02 | Isis Pharmaceuticals, Inc. | Modulation of angiopoietin-like 3 expression |
| CN105899663B (zh) | 2013-12-26 | 2019-07-26 | 学校法人东京医科大学 | 用于基因表达控制的人工模拟miRNA及其用途 |
| CN106068324B (zh) | 2013-12-27 | 2020-12-29 | 株式会社博纳克 | 控制基因表达的人工匹配型miRNA及其用途 |
| US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| 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 |
| EP3095459A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having antitumor effect and antitumor agent |
| CN113278617A (zh) | 2014-01-16 | 2021-08-20 | 波涛生命科学有限公司 | 手性设计 |
| BR122020024446B8 (pt) | 2014-05-01 | 2022-06-28 | Ionis Pharmaceuticals Inc | Compostos para modulação da expressão do receptor do hormônio de crescimento |
| MX380866B (es) * | 2014-05-01 | 2025-03-12 | Ionis Pharmaceuticals Inc | Composiciones y métodos para modular la expresión del factor b del complemento. |
| EP3845547A1 (en) | 2014-05-01 | 2021-07-07 | Ionis Pharmaceuticals, Inc. | Galnac3 conjugated modified oligonucleotide for modulating angiopoietin-like 3 expression |
| GB201408623D0 (en) | 2014-05-15 | 2014-07-02 | Santaris Pharma As | Oligomers and oligomer conjugates |
| US10570169B2 (en) | 2014-05-22 | 2020-02-25 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| CA2955294A1 (en) | 2014-07-16 | 2016-01-21 | Sanofi Biotechnology | Methods for treating patients with heterozygous familial hypercholesterolemia (hefh) |
| WO2016019270A1 (en) * | 2014-07-31 | 2016-02-04 | Academia Sinica | An antagonistic pd-1 aptamer and its applications in cancer therapy related applications |
| WO2016024205A1 (en) | 2014-08-15 | 2016-02-18 | Pfizer Inc. | Oligomers targeting hexanucleotide repeat expansion in human c9orf72 gene |
| US11198874B2 (en) * | 2014-08-20 | 2021-12-14 | Lifesplice Pharma Llc | SCN8A splice modulating oligonucleotides and methods of use thereof |
| EP3191591A1 (en) | 2014-09-12 | 2017-07-19 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting complement component c5 and methods of use thereof |
| CN107001461A (zh) | 2014-09-16 | 2017-08-01 | 瑞泽恩制药公司 | 抗胰高血糖素抗体及其使用方法 |
| CN107109411B (zh) | 2014-10-03 | 2022-07-01 | 冷泉港实验室 | 核基因输出的定向增加 |
| CN106795200B (zh) | 2014-10-10 | 2020-06-19 | 豪夫迈·罗氏有限公司 | Galnac亚磷酰胺、其核酸缀合物及其用途 |
| EP3207138B1 (en) | 2014-10-17 | 2020-07-15 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof |
| EP3212794B1 (en) | 2014-10-30 | 2021-04-07 | Genzyme Corporation | Polynucleotide agents targeting serpinc1 (at3) and methods of use thereof |
| WO2016070060A1 (en) | 2014-10-30 | 2016-05-06 | The General Hospital Corporation | Methods for modulating atrx-dependent gene repression |
| US10266895B2 (en) | 2014-11-05 | 2019-04-23 | Hitachi Chemical Company Ltd. | Exosomes and microvesicles in intestinal luminal fluids and stool and use of same for the assessment of inflammatory bowel disease |
| WO2016077537A1 (en) | 2014-11-12 | 2016-05-19 | Hitachi Chemical Co., Ltd. | Method and device for diagnosing organ injury |
| WO2016077687A1 (en) | 2014-11-14 | 2016-05-19 | Voyager Therapeutics, Inc. | Compositions and methods of treating amyotrophic lateral sclerosis (als) |
| US10815481B2 (en) | 2014-12-16 | 2020-10-27 | Roche Innovation Center Copenhagen A/S | Chiral library screen |
| WO2016104775A1 (ja) | 2014-12-27 | 2016-06-30 | 株式会社ボナック | 遺伝子発現制御のための天然型miRNAおよびその用途 |
| CN115181778A (zh) | 2015-02-04 | 2022-10-14 | 百时美施贵宝公司 | 选择治疗性分子的方法 |
| TW201641691A (zh) | 2015-02-04 | 2016-12-01 | 必治妥美雅史谷比公司 | Tau反義寡聚物及其用途 |
| WO2016130943A1 (en) | 2015-02-13 | 2016-08-18 | Rana Therapeutics, Inc. | Hybrid oligonucleotides and uses thereof |
| WO2016149455A2 (en) | 2015-03-17 | 2016-09-22 | The General Hospital Corporation | The rna interactome of polycomb repressive complex 1 (prc1) |
| EP3273974A4 (en) | 2015-03-26 | 2018-11-07 | Women and Infants Hospital of Rhode Island Inc. | Therapy for malignant disease |
| JP6602847B2 (ja) | 2015-03-27 | 2019-11-06 | 株式会社ボナック | デリバリー機能と遺伝子発現制御能を有する一本鎖核酸分子 |
| WO2016164746A1 (en) | 2015-04-08 | 2016-10-13 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the lect2 gene |
| MX366128B (es) | 2015-04-16 | 2019-06-28 | Ionis Pharmaceuticals Inc | Composiciones para modular la expresion de c90rf72. |
| EP3310918B1 (en) | 2015-06-18 | 2020-08-05 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof |
| US20180188257A1 (en) | 2015-06-19 | 2018-07-05 | University Of Rochester | Septin proteins as novel biomarkers for detection and treatment of müllerian cancers |
| ES2917181T3 (es) * | 2015-07-10 | 2022-07-07 | Ionis Pharmaceuticals Inc | Moduladores de diacilglicerol aciltransferasa 2 (DGAT2) |
| MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| US10772956B2 (en) | 2015-08-18 | 2020-09-15 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or eliminating the need for lipoprotein apheresis in patients with hyperlipidemia by administering alirocumab |
| JP6624704B2 (ja) | 2015-08-31 | 2019-12-25 | 日立化成株式会社 | 尿路上皮疾患の評価のための分子法 |
| CN108135845B (zh) | 2015-09-18 | 2021-10-29 | Dnarx公司 | 用于体内核酸表达的系统和方法 |
| EP3359685A1 (en) | 2015-10-09 | 2018-08-15 | University Of Southampton | Modulation of gene expression and screening for deregulated protein expression |
| EP3365446A4 (en) | 2015-10-19 | 2019-06-26 | Phio Pharmaceuticals Corp. | SMALL SELF-LEANING NUCLEIC ACID COMPOUNDS TURNED AGAINST LONG NON-CODING RNA |
| US10955407B2 (en) | 2015-10-22 | 2021-03-23 | Roche Innovation Center Copenhagen A/S | In vitro toxicity screening assay |
| US11260073B2 (en) | 2015-11-02 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating C90RF72 |
| CN113952353A (zh) | 2015-11-06 | 2022-01-21 | Ionis制药公司 | 调节载脂蛋白(a)表达 |
| MA67580B1 (fr) | 2015-11-12 | 2024-09-30 | F. Hoffmann-La Roche Ag | Oligonucléotides pour induire l'expression de paternal ube3a |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| US11083745B2 (en) | 2015-12-14 | 2021-08-10 | Cold Spring Harbor Laboratory | Antisense oligomers for treatment of autosomal dominant mental retardation-5 and Dravet Syndrome |
| US11384112B2 (en) | 2016-02-17 | 2022-07-12 | Tokyo Institute Of Technology | Artificial nucleoside and artificial nucleotide, and artificial oligonucleotide |
| WO2017152182A1 (en) | 2016-03-04 | 2017-09-08 | Rhode Island Hospital | Targeting microrna for cancer treatment |
| HRP20210315T1 (hr) | 2016-03-14 | 2021-04-16 | F. Hoffmann - La Roche Ag | Oligonukleotidi za smanjenje ekspresije pd-l1 |
| EP3442983A1 (en) | 2016-04-14 | 2019-02-20 | H. Hoffnabb-La Roche Ag | TRITYL-MONO-Ga1NAc COMPOUNDS AND THEIR USE |
| WO2017188898A1 (en) | 2016-04-29 | 2017-11-02 | Nanyang Technological University | G-quadruplex-containing antisense oligonucleotides |
| WO2017194498A1 (en) * | 2016-05-12 | 2017-11-16 | Roche Innovation Center Copenhagen A/S | Enhanced coupling of stereodefined oxazaphospholidine phosphoramidite monomers to nucleoside or oligonucleotide |
| JP7012033B2 (ja) | 2016-06-17 | 2022-02-10 | エフ.ホフマン-ラ ロシュ アーゲー | インビトロ腎毒性スクリーニングアッセイ |
| MA45496A (fr) | 2016-06-17 | 2019-04-24 | Hoffmann La Roche | Molécules d'acide nucléique pour la réduction de l'arnm de padd5 ou pad7 pour le traitement d'une infection par l'hépatite b |
| WO2017216340A1 (en) | 2016-06-17 | 2017-12-21 | F. Hoffmann-La Roche Ag | In vitro nephrotoxicity screening assay |
| JOP20190065A1 (ar) | 2016-09-29 | 2019-03-28 | Ionis Pharmaceuticals Inc | مركبات وطرق لتقليل التعبير عن tau |
| US11260134B2 (en) | 2016-09-29 | 2022-03-01 | National University Corporation Tokyo Medical And Dental University | Double-stranded nucleic acid complex having overhang |
| CN109661233A (zh) | 2016-10-06 | 2019-04-19 | Ionis 制药公司 | 缀合低聚化合物的方法 |
| US20190248888A1 (en) | 2016-10-20 | 2019-08-15 | Regeneron Pharmaceuticals, Inc. | Methods of lowering blood glucose levels |
| US10787665B2 (en) * | 2016-11-03 | 2020-09-29 | Ohio State Innovation Foundation | Antisense oligomers targeting HOXB-AS3 long non-coding RNA |
| AU2017368050A1 (en) | 2016-11-29 | 2019-06-20 | Puretech Lyt, Inc. | Exosomes for delivery of therapeutic agents |
| EP3568477A1 (en) | 2017-01-13 | 2019-11-20 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating rela expression |
| US20190367920A1 (en) | 2017-01-13 | 2019-12-05 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating nfkb1 expression |
| WO2018130582A1 (en) | 2017-01-13 | 2018-07-19 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating rel expression |
| EP3568481A1 (en) | 2017-01-13 | 2019-11-20 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating relb expression |
| EP3568480A1 (en) | 2017-01-13 | 2019-11-20 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides for modulating nfkb2 expression |
| US11572558B2 (en) | 2017-02-06 | 2023-02-07 | Nissan Chemical Corporation | Single-stranded oligonucleotide |
| WO2018155450A1 (ja) * | 2017-02-21 | 2018-08-30 | 国立大学法人大阪大学 | アンチセンスオリゴ核酸 |
| WO2018165564A1 (en) | 2017-03-09 | 2018-09-13 | Ionis Pharmaceuticals, Inc. | Morpholino modified oligomeric compounds |
| EP3600428A4 (en) | 2017-03-23 | 2020-08-26 | Dnarx | SYSTEMS AND METHODS FOR THE EXPRESSION OF NUCLEIC ACIDS IN VIVO |
| JOP20190215A1 (ar) * | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
| WO2018181428A1 (ja) | 2017-03-29 | 2018-10-04 | 塩野義製薬株式会社 | 核酸医薬及び多分岐脂質の複合体 |
| NO344051B1 (en) * | 2017-05-04 | 2019-08-26 | Patogen As | Novel virus in Fish and Method for detection |
| WO2018204786A1 (en) | 2017-05-05 | 2018-11-08 | Voyager Therapeutics, Inc. | Compositions and methods of treating amyotrophic lateral sclerosis (als) |
| JP6952366B2 (ja) * | 2017-05-26 | 2021-10-20 | 国立研究開発法人国立循環器病研究センター | Pcsk9を標的としたアンチセンス核酸 |
| WO2019004420A1 (ja) | 2017-06-30 | 2019-01-03 | 国立大学法人東京医科歯科大学 | ヘテロ二本鎖型antimiR |
| CN110997918A (zh) | 2017-07-26 | 2020-04-10 | 日产化学株式会社 | 单链寡核苷酸 |
| SMT202400071T1 (it) | 2017-08-25 | 2024-03-13 | Stoke Therapeutics Inc | Oligomeri antisenso per il trattamento di condizioni e malattie |
| PE20200868A1 (es) | 2017-10-16 | 2020-08-31 | Hoffmann La Roche | OLIGONUCLEOTIDOS ANTISENTIDO Y CONJUGADOS QUE LOS COMPRENDEN PARA LA REDUCCION DEL ARNm DE PAPD5 Y PAPD7 |
| WO2019079240A1 (en) | 2017-10-16 | 2019-04-25 | Voyager Therapeutics, Inc. | TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) |
| EP4454654A3 (en) | 2017-10-16 | 2025-02-19 | Voyager Therapeutics, Inc. | Treatment of amyotrophic lateral sclerosis (als) |
| EP3724333A2 (en) | 2017-12-11 | 2020-10-21 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating fndc3b expression |
| JP2021507253A (ja) | 2017-12-21 | 2021-02-22 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | Htra1 rnaアンタゴニストについてのコンパニオン診断 |
| JP2021508327A (ja) | 2017-12-22 | 2021-03-04 | ロシュ イノベーション センター コペンハーゲン エーエス | 新規のチオホスホラミダイト |
| EP4092117A1 (en) | 2017-12-22 | 2022-11-23 | Roche Innovation Center Copenhagen A/S | Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage |
| EP4074724A1 (en) | 2017-12-22 | 2022-10-19 | Roche Innovation Center Copenhagen A/S | Oligonucleotides comprising a phosphorodithioate internucleoside linkage |
| EP3737758A1 (en) | 2018-01-10 | 2020-11-18 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating pias4 expression |
| KR20200109338A (ko) | 2018-01-12 | 2020-09-22 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | 알파-시누클레인 안티센스 올리고뉴클레오티드 및 이의 용도 |
| SG11202006528XA (en) | 2018-01-12 | 2020-08-28 | Bristol Myers Squibb Co | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
| EP3737760A1 (en) | 2018-01-12 | 2020-11-18 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating gsk3b expression |
| CN120310791A (zh) | 2018-01-12 | 2025-07-15 | 百时美施贵宝公司 | 靶向α-突触核蛋白的反义寡核苷酸及其用途 |
| JP2021510525A (ja) | 2018-01-17 | 2021-04-30 | ロシュ イノベーション センター コペンハーゲン エーエス | Erc1発現を調節するためのオリゴヌクレオチド |
| WO2019145386A1 (en) | 2018-01-26 | 2019-08-01 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating csnk1d expression |
| KR20200140805A (ko) | 2018-02-21 | 2020-12-16 | 브리스톨-마이어스 스큅 컴퍼니 | Camk2d 안티센스 올리고뉴클레오티드 및 그의 용도 |
| WO2019167995A1 (ja) | 2018-02-28 | 2019-09-06 | 国立大学法人東京医科歯科大学 | 虚血病変部位特異的な遺伝子治療法 |
| EP3766972B1 (en) | 2018-03-14 | 2025-04-23 | Institute of Science Tokyo | Nucleic acid complex |
| WO2019181946A1 (ja) | 2018-03-19 | 2019-09-26 | 国立大学法人東京医科歯科大学 | 毒性が軽減した核酸 |
| CA3094303A1 (en) * | 2018-03-20 | 2019-09-26 | Tokyo Institute Of Technology | Antisense oligonucleotide reduced in toxicity |
| JP7262816B2 (ja) | 2018-03-22 | 2023-04-24 | 国立大学法人 東京医科歯科大学 | ヘテロ核酸のbbb通過脂質リガンド |
| CN112513297B (zh) | 2018-03-28 | 2024-10-22 | 得克萨斯州大学系统董事会 | 鉴定从外排体分离的dna中的表观遗传改变 |
| PE20211912A1 (es) | 2018-04-05 | 2021-09-28 | Centre Nat Rech Scient | Uso de inhibidores de fubp1 para el tratamiento de infeccion de virus de hepatitis b |
| JP2021523227A (ja) | 2018-05-04 | 2021-09-02 | ストーク セラピューティクス,インク. | コレステリルエステル蓄積症の処置のための方法及び組成物 |
| MY204000A (en) | 2018-05-09 | 2024-07-31 | Ionis Pharmaceuticals Inc | Compounds and methods for reducing fxi expression |
| JP7557378B2 (ja) * | 2018-06-14 | 2024-09-27 | アイオーニス ファーマシューティカルズ, インコーポレーテッド | Stmn2発現を増加させるための化合物及び方法 |
| JP7565218B2 (ja) | 2018-07-02 | 2024-10-10 | ボイジャー セラピューティクス インコーポレイテッド | 筋萎縮性側索硬化症および脊髄に関連する障害の治療 |
| KR102585973B1 (ko) | 2018-07-03 | 2023-10-10 | 에프. 호프만-라 로슈 아게 | 타우 발현을 조절하기 위한 올리고뉴클레오티드 |
| CR20210015A (es) | 2018-07-13 | 2021-03-22 | Hoffmann La Roche | Oligonucleótidos para modular la expresión de rtel 1 |
| EP3831408A4 (en) | 2018-07-27 | 2021-11-17 | Osaka University | COMPOSITION TO INHIBIT AGING, PREVENT, IMPROVE, OR TREAT AGE-RELATED DISEASES, OR EXTEND LIFE |
| CN119912512A (zh) | 2018-07-31 | 2025-05-02 | 罗氏创新中心哥本哈根有限公司 | 包含三硫代磷酸酯核苷间键的寡核苷酸 |
| MX2021001019A (es) | 2018-07-31 | 2021-04-19 | Roche Innovation Ct Copenhagen As | Oligonucleotidos que comprenden enlace internucleosidico de fosforotritioato. |
| US11911484B2 (en) | 2018-08-02 | 2024-02-27 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| US12097263B2 (en) | 2018-08-02 | 2024-09-24 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| US12018087B2 (en) | 2018-08-02 | 2024-06-25 | Dyne Therapeutics, Inc. | Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject |
| US20220193250A1 (en) | 2018-08-02 | 2022-06-23 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| US12370264B1 (en) | 2018-08-02 | 2025-07-29 | Dyne Therapeutics, Inc. | Complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and method of delivering oligonucleotide to a subject |
| WO2020077390A1 (en) * | 2018-10-18 | 2020-04-23 | Murdoch University | Antisense therapy for ptp1b related conditions |
| CA3130431A1 (en) | 2019-02-20 | 2020-08-27 | Roche Innovation Center Copenhagen A/S | Phosphonoacetate gapmer oligonucleotides |
| JP2022521512A (ja) | 2019-02-20 | 2022-04-08 | ロシュ イノベーション センター コペンハーゲン エーエス | 新規ホスホルアミダイト |
| US12492399B2 (en) | 2019-03-14 | 2025-12-09 | Rena Therapeutics Inc. | Nucleic acid complex for regulating IHH expression |
| WO2020209285A1 (ja) | 2019-04-08 | 2020-10-15 | 国立大学法人東京医科歯科大学 | 筋疾患治療用医薬組成物 |
| JP7692829B2 (ja) | 2019-07-30 | 2025-06-16 | 塩野義製薬株式会社 | Murf1を標的とする核酸医薬 |
| KR20220070433A (ko) | 2019-08-14 | 2022-05-31 | 코디악 바이오사이언시즈, 인크. | Stat6을 표적으로 하는 세포외 소포-aso 작제물 |
| US20230132093A1 (en) | 2019-08-14 | 2023-04-27 | Codiak Biosciences, Inc. | Extracellular vesicle-nlrp3 antagonist |
| CN114641570A (zh) | 2019-08-14 | 2022-06-17 | 科迪亚克生物科学公司 | 具有靶向kras的反义寡核苷酸的细胞外囊泡 |
| EP4013878A1 (en) | 2019-08-14 | 2022-06-22 | Codiak BioSciences, Inc. | Extracellular vesicle-aso constructs targeting cebp/beta |
| CA3147366A1 (en) | 2019-08-14 | 2021-02-18 | Adam T. BOUTIN | Extracellular vesicles with stat3-antisense oligonucleotides |
| KR20220062517A (ko) | 2019-08-15 | 2022-05-17 | 아이오니스 파마수티컬즈, 인코포레이티드 | 결합 변형된 올리고머 화합물 및 이의 용도 |
| CN114269924A (zh) * | 2019-08-23 | 2022-04-01 | 国立大学法人东海国立大学机构 | Rna作用抑制剂及其应用 |
| JP7737667B2 (ja) | 2019-09-18 | 2025-09-11 | 国立大学法人東京科学大学 | 核酸複合体 |
| WO2021062058A1 (en) | 2019-09-25 | 2021-04-01 | Codiak Biosciences, Inc. | Sting agonist comprising exosomes for treating neuroimmunological disorders |
| US20240117346A1 (en) | 2019-10-11 | 2024-04-11 | National University Corporation Tokyo Medical And Dental University | Modified hetero nucleic acids |
| EP4081639A1 (en) | 2019-12-24 | 2022-11-02 | F. Hoffmann-La Roche AG | Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv |
| AU2020415322A1 (en) | 2019-12-24 | 2022-06-16 | F. Hoffmann-La Roche Ag | Pharmaceutical combination of antiviral agents targeting HBV and/or an immune modulator for treatment of HBV |
| CA3169474A1 (en) | 2020-01-31 | 2021-08-05 | Sanwa Kagaku Kenkyusho Co., Ltd. | Antisense oligonucleotide of atn1 |
| JPWO2021177418A1 (enExample) | 2020-03-04 | 2021-09-10 | ||
| WO2021184020A1 (en) | 2020-03-13 | 2021-09-16 | Codiak Biosciences, Inc. | Methods of treating neuroinflammation |
| WO2021184021A1 (en) | 2020-03-13 | 2021-09-16 | Codiak Biosciences, Inc. | Extracellular vesicle-aso constructs targeting pmp22 |
| US20230174981A1 (en) | 2020-03-16 | 2023-06-08 | National University Corporation Tokyo Medical And Dental University | Heteronucleic acid containing morpholino nucleic acid |
| WO2021188611A1 (en) | 2020-03-18 | 2021-09-23 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant |
| CA3173647A1 (en) | 2020-05-11 | 2021-11-18 | Isabel AZNAREZ | Opa1 antisense oligomers for treatment of conditions and diseases |
| JP7751302B2 (ja) | 2020-06-15 | 2025-10-08 | リードファーマ株式会社 | 架橋型ヌクレオシドおよびヌクレオチド |
| US20230364127A1 (en) | 2020-10-06 | 2023-11-16 | Codiak Biosciences, Inc. | Extracellular vesicle-aso constructs targeting stat6 |
| US20230263808A1 (en) * | 2020-10-16 | 2023-08-24 | University Of Florida Research Foundation, Incorporated | Therapeutic uses of glucocorticoids with anabolic effects in skeletal muscle |
| US11987795B2 (en) | 2020-11-24 | 2024-05-21 | The Broad Institute, Inc. | Methods of modulating SLC7A11 pre-mRNA transcripts for diseases and conditions associated with expression of SLC7A11 |
| CR20230308A (es) | 2020-12-11 | 2023-09-08 | Civi Biopharma Inc | Entrega oral de conjugados antisentido que tienen por blanco a pcsk9 |
| WO2022136466A1 (en) | 2020-12-23 | 2022-06-30 | Argonaute RNA Limited | Treatment of cardiovascular disease |
| IL304048A (en) | 2020-12-31 | 2023-08-01 | Dyne Therapeutics Inc | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| JP2024512236A (ja) | 2021-02-17 | 2024-03-19 | ロンザ セールス アーゲー | 細胞外ベシクル-nlrp3アンタゴニスト |
| US20240209368A1 (en) | 2021-04-01 | 2024-06-27 | Lonza Sales Ag | Extracellular vesicle compositions |
| US20240240183A1 (en) | 2021-05-25 | 2024-07-18 | National University Corporation Tokyo Medical And Dental University | Heteronucleic acid containing scpBNA or AmNA |
| CN117858946A (zh) | 2021-05-29 | 2024-04-09 | 强新科技国际研究院 | 作为新型基因沉默技术的非对称短双链体dna及其应用 |
| US20240254490A1 (en) | 2021-05-29 | 2024-08-01 | 1Globe Health Institute Llc | Short Duplex DNA as a Novel Gene Silencing Technology and Use Thereof |
| CA3222167A1 (en) | 2021-05-31 | 2022-12-08 | Rena Therapeutics Inc. | Ligand-binding nucleic acid complex |
| US11633498B2 (en) | 2021-07-09 | 2023-04-25 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| US11638761B2 (en) | 2021-07-09 | 2023-05-02 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy |
| US11969475B2 (en) | 2021-07-09 | 2024-04-30 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| EP4373934A1 (en) | 2021-07-19 | 2024-05-29 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating subjects having or at risk of developing a non-primary hyperoxaluria disease or disorder |
| CA3228120A1 (en) | 2021-08-04 | 2023-02-09 | The University Of Tokyo | Hairpin nucleic acid composition |
| JPWO2023022229A1 (enExample) | 2021-08-19 | 2023-02-23 | ||
| US20240390508A1 (en) | 2021-08-21 | 2024-11-28 | Takeda Pharmaceutical Company Limited | Human transferrin receptor binding peptide-drug conjugate |
| JP2024532476A (ja) * | 2021-09-02 | 2024-09-05 | モレキュラー アクシオム エルエルシー | Nlrp3またはnlrp1発現を調節するための組成物及び方法 |
| EP4402263A2 (en) | 2021-09-14 | 2024-07-24 | Argonaute Rna Limited | Treatment of cardiovascular disease |
| EP4403191A1 (en) | 2021-09-15 | 2024-07-24 | National University Corporation Tokyo Medical and Dental University | Heteronucleic acid including 2'-modified nucleoside |
| CN118159654A (zh) | 2021-09-20 | 2024-06-07 | 阿尔尼拉姆医药品有限公司 | 抑制素亚基βE(INHBE)调节剂组合物及其使用方法 |
| WO2023080159A1 (ja) | 2021-11-02 | 2023-05-11 | レナセラピューティクス株式会社 | リガンド結合核酸複合体 |
| WO2023083906A2 (en) | 2021-11-11 | 2023-05-19 | F. Hoffmann-La Roche Ag | Pharmaceutical combinations for treatment of hbv |
| DE102021131135A1 (de) | 2021-11-26 | 2023-06-01 | Zf Cv Systems Global Gmbh | Funkkommunikationsmodul und Verfahren zum Absetzen eines Notrufs per Funkkommunikation |
| WO2023111210A1 (en) | 2021-12-17 | 2023-06-22 | F. Hoffmann-La Roche Ag | Combination of oligonucleotides for modulating rtel1 and fubp1 |
| TW202400787A (zh) | 2022-03-16 | 2024-01-01 | 美商安彼瑞可股份有限公司 | 改良siRNA生物可利用性之GalNAc組合物 |
| KR20240163743A (ko) | 2022-03-28 | 2024-11-19 | 엠피리코 인크. | 변형된 올리고뉴클레오티드 |
| AU2023254846A1 (en) | 2022-04-15 | 2024-10-10 | Dyne Therapeutics, Inc. | Muscle targeting complexes and formulations for treating myotonic dystrophy |
| CN120659627A (zh) | 2022-07-29 | 2025-09-16 | 瑞泽恩制药公司 | 用于转铁蛋白受体(tfr)介导的脑和肌肉递送的组合物和方法 |
| EP4581143A1 (en) | 2022-08-29 | 2025-07-09 | University of Rochester | Antisense oligonucleotide-based anti-fibrotic therapeutics |
| EP4340411A1 (en) | 2022-09-19 | 2024-03-20 | Cellnex Italia S.p.A | System for monitoring the operating state of the emergency call service into tunnels |
| JPWO2024071099A1 (enExample) | 2022-09-29 | 2024-04-04 | ||
| WO2024098061A2 (en) | 2022-11-04 | 2024-05-10 | Genkardia Inc. | Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure |
| US20240182561A1 (en) | 2022-11-04 | 2024-06-06 | Regeneron Pharmaceuticals, Inc. | Calcium voltage-gated channel auxiliary subunit gamma 1 (cacng1) binding proteins and cacng1-mediated delivery to skeletal muscle |
| JP2025538220A (ja) | 2022-11-14 | 2025-11-26 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | アストロサイトへの線維芽細胞増殖因子受容体3媒介送達のための組成物および方法 |
| WO2024175586A2 (en) | 2023-02-21 | 2024-08-29 | Vib Vzw | Inhibitors of synaptogyrin-3 expression |
| WO2024175588A1 (en) | 2023-02-21 | 2024-08-29 | Vib Vzw | Oligonucleotides for modulating synaptogyrin-3 expression |
| WO2024226761A2 (en) | 2023-04-26 | 2024-10-31 | Voyager Therapeutics, Inc. | Compositions and methods for treating amyotrophic lateral sclerosis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005038013A1 (en) * | 2003-10-07 | 2005-04-28 | Isis Pharmaceuticals, Inc. | Artisense oligonucleotides optimized for kidney targeting |
Family Cites Families (260)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US469863A (en) * | 1892-03-01 | John marks | ||
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US4458066A (en) * | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4500707A (en) * | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
| US5132418A (en) * | 1980-02-29 | 1992-07-21 | University Patents, Inc. | Process for preparing polynucleotides |
| US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
| US4668777A (en) * | 1981-03-27 | 1987-05-26 | University Patents, Inc. | Phosphoramidite nucleoside compounds |
| US4415732A (en) | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
| US4973679A (en) | 1981-03-27 | 1990-11-27 | University Patents, Inc. | Process for oligonucleo tide synthesis using phosphormidite intermediates |
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
| DE3329892A1 (de) * | 1983-08-18 | 1985-03-07 | Köster, Hubert, Prof. Dr., 2000 Hamburg | Verfahren zur herstellung von oligonucleotiden |
| USRE34069E (en) | 1983-08-18 | 1992-09-15 | Biosyntech Gmbh | Process for the preparation of oligonucleotides |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
| FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
| US5405938A (en) * | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5034506A (en) * | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5185444A (en) * | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| DE3788914T2 (de) * | 1986-09-08 | 1994-08-25 | Ajinomoto Kk | Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere. |
| US5276019A (en) * | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| JP2828642B2 (ja) | 1987-06-24 | 1998-11-25 | ハワード フローレイ インスティテュト オブ イクスペリメンタル フィジオロジー アンド メディシン | ヌクレオシド誘導体 |
| US5712257A (en) | 1987-08-12 | 1998-01-27 | Hem Research, Inc. | Topically active compositions of mismatched dsRNAs |
| US4924624A (en) * | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
| US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
| US5403711A (en) * | 1987-11-30 | 1995-04-04 | University Of Iowa Research Foundation | Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved |
| ATE151467T1 (de) * | 1987-11-30 | 1997-04-15 | Univ Iowa Res Found | Durch modifikationen an der 3'-terminalen phosphodiesterbindung stabilisierte dna moleküle, ihre verwendung als nukleinsäuresonden sowie als therapeutische mittel zur hemmung der expression spezifischer zielgene |
| IE61148B1 (en) | 1988-03-10 | 1994-10-05 | Ici Plc | Method of detecting nucleotide sequences |
| WO1989009221A1 (en) | 1988-03-25 | 1989-10-05 | University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
| US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US5194599A (en) * | 1988-09-23 | 1993-03-16 | Gilead Sciences, Inc. | Hydrogen phosphonodithioate compositions |
| US5256775A (en) | 1989-06-05 | 1993-10-26 | Gilead Sciences, Inc. | Exonuclease-resistant oligonucleotides |
| US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| US5721218A (en) * | 1989-10-23 | 1998-02-24 | Gilead Sciences, Inc. | Oligonucleotides with inverted polarity |
| US5399676A (en) * | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
| US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
| DE69034150T2 (de) | 1989-10-24 | 2005-08-25 | Isis Pharmaceuticals, Inc., Carlsbad | 2'-Modifizierte Oligonukleotide |
| US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
| US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
| US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
| US5587470A (en) * | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5872232A (en) | 1990-01-11 | 1999-02-16 | Isis Pharmaceuticals Inc. | 2'-O-modified oligonucleotides |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US6005087A (en) * | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5623065A (en) | 1990-08-13 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Gapped 2' modified oligonucleotides |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5149797A (en) | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
| US5220007A (en) * | 1990-02-15 | 1993-06-15 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of RNA and production of encoded polypeptides |
| US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
| US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| DK0455905T3 (da) * | 1990-05-11 | 1998-12-07 | Microprobe Corp | Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider |
| US5223618A (en) * | 1990-08-13 | 1993-06-29 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analog compounds |
| US5541307A (en) * | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5378825A (en) * | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5608046A (en) * | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| JPH0874B2 (ja) * | 1990-07-27 | 1996-01-10 | アイシス・ファーマシューティカルス・インコーポレーテッド | 遺伝子発現を検出および変調するヌクレアーゼ耐性、ピリミジン修飾オリゴヌクレオチド |
| US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
| US5386023A (en) * | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| PT98562B (pt) | 1990-08-03 | 1999-01-29 | Sanofi Sa | Processo para a preparacao de composicoes que compreendem sequencias de nucleo-sidos com cerca de 6 a cerca de 200 bases resistentes a nucleases |
| US6852536B2 (en) | 2001-12-18 | 2005-02-08 | Isis Pharmaceuticals, Inc. | Antisense modulation of CD36L 1 expression |
| US5177196A (en) * | 1990-08-16 | 1993-01-05 | Microprobe Corporation | Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof |
| US5214134A (en) * | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
| US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
| JPH06505704A (ja) * | 1990-09-20 | 1994-06-30 | ギリアド サイエンシズ,インコーポレイテッド | 改変ヌクレオシド間結合 |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| US5220006A (en) | 1990-10-23 | 1993-06-15 | The United States Of America As Represented By The Department Of Health And Human Services | Identification of a suppressor of atherogenic apolipoprotein |
| US6582908B2 (en) * | 1990-12-06 | 2003-06-24 | Affymetrix, Inc. | Oligonucleotides |
| AU665939B2 (en) | 1990-12-21 | 1996-01-25 | Rockefeller University, The | Liver enriched transcription factor |
| US5672697A (en) | 1991-02-08 | 1997-09-30 | Gilead Sciences, Inc. | Nucleoside 5'-methylene phosphonates |
| US5965722A (en) * | 1991-05-21 | 1999-10-12 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ras gene with chimeric and alternating oligonucleotides |
| US5578444A (en) | 1991-06-27 | 1996-11-26 | Genelabs Technologies, Inc. | Sequence-directed DNA-binding molecules compositions and methods |
| WO1993001286A2 (en) | 1991-06-28 | 1993-01-21 | Massachusetts Institute Of Technology | Localized oligonucleotide therapy |
| US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
| US5877009A (en) | 1991-08-16 | 1999-03-02 | Trustees Of Boston University | Isolated ApoA-I gene regulatory sequence elements |
| DE4129653A1 (de) | 1991-09-06 | 1993-03-11 | Boehringer Mannheim Gmbh | Verfahren zum nachweis aehnlicher nukleinsaeuren |
| US5408038A (en) | 1991-10-09 | 1995-04-18 | The Scripps Research Institute | Nonnatural apolipoprotein B-100 peptides and apolipoprotein B-100-apolipoprotein A-I fusion peptides |
| EP0538194B1 (de) * | 1991-10-17 | 1997-06-04 | Novartis AG | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
| US5594121A (en) * | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| US5484908A (en) * | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| TW393513B (en) | 1991-11-26 | 2000-06-11 | Isis Pharmaceuticals Inc | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| DE637965T1 (de) | 1991-11-26 | 1995-12-14 | Gilead Sciences Inc | Gesteigerte bildung von triple- und doppelhelices aus oligomeren mit modifizierten pyrimidinen. |
| US5792608A (en) | 1991-12-12 | 1998-08-11 | Gilead Sciences, Inc. | Nuclease stable and binding competent oligomers and methods for their use |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| EP0726963A4 (en) | 1991-12-23 | 1998-05-13 | Chiron Corp | PROBES FOR -i (CHLAMYDIAE) FOR USE IN SOLUTION PHASE SANDWICH HYBRIDIZATION METHODS |
| US5700922A (en) | 1991-12-24 | 1997-12-23 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| FR2692265B1 (fr) | 1992-05-25 | 1996-11-08 | Centre Nat Rech Scient | Composes biologiquement actifs de type phosphotriesters. |
| US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
| NL9300058A (nl) * | 1992-06-18 | 1994-01-17 | Stichting Rega V Z W | 1,5-anhydrohexitol nucleoside analoga en farmaceutisch gebruik daarvan. |
| EP0577558A2 (de) * | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| US5652355A (en) * | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
| WO1994002499A1 (en) | 1992-07-27 | 1994-02-03 | Hybridon, Inc. | Oligonucleotide alkylphosphonothioates |
| US6180403B1 (en) | 1999-10-28 | 2001-01-30 | Isis Pharmaceuticals Inc. | Antisense inhibition of tumor necrosis factor alpha converting enzyme (TACE) expression |
| JPH08504559A (ja) | 1992-12-14 | 1996-05-14 | ハネウエル・インコーポレーテッド | 個別に制御される冗長巻線を有するモータシステム |
| JPH08508714A (ja) | 1993-01-25 | 1996-09-17 | ハイブライドン インコーポレイテッド | オリゴヌクレオチド・アルキルホスホネートおよびアルキルホスホノチオエート |
| US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
| US5434058A (en) | 1993-02-09 | 1995-07-18 | Arch Development Corporation | Apolipoprotein B MRNA editing protein compositions and methods |
| IL108340A (en) * | 1993-03-04 | 1996-10-16 | Innova Sa | Citric acid extraction |
| GB9304620D0 (en) * | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Compounds |
| GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
| ES2107205T3 (es) | 1993-03-30 | 1997-11-16 | Sanofi Sa | Analogos de nucleosidos aciclicos y secuencias oligonucleotidas que los contienen. |
| CA2159632A1 (en) | 1993-03-31 | 1994-10-13 | Ashis Kumar Saha | Novel 5'-substituted nucleosides and oligomers produced therefrom |
| HU9501974D0 (en) | 1993-03-31 | 1995-09-28 | Sterling Winthrop Inc | Oligonucleotides with amide linkages replacing phosphodiester linkages |
| DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
| FR2705099B1 (fr) | 1993-05-12 | 1995-08-04 | Centre Nat Rech Scient | Oligonucléotides phosphorothioates triesters et procédé de préparation. |
| US5502177A (en) * | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
| US5801154A (en) * | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US6235470B1 (en) | 1993-11-12 | 2001-05-22 | The Johns Hopkins University School Of Medicine | Detection of neoplasia by analysis of saliva |
| US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| US5446137B1 (en) * | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| JP3585238B2 (ja) | 1993-12-09 | 2004-11-04 | トーマス ジェファーソン ユニバーシティー | 真核細胞における部位特異的突然変異誘発のための化合物および方法 |
| US5519134A (en) * | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
| US5646269A (en) | 1994-04-28 | 1997-07-08 | Gilead Sciences, Inc. | Method for oligonucleotide analog synthesis |
| US5525711A (en) * | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| US6103890A (en) | 1994-05-18 | 2000-08-15 | Ribozyme Pharmaceuticals, Inc. | Enzymatic nucleic acids that cleave C-fos |
| US5656612A (en) | 1994-05-31 | 1997-08-12 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
| US5485908A (en) * | 1994-07-12 | 1996-01-23 | Coin Acceptors, Inc. | Pattern recognition using artificial neural network for coin validation |
| US5618065A (en) * | 1994-07-21 | 1997-04-08 | Hitachi Metals, Ltd. | Electric welding pipe joint having a two layer outer member |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5792747A (en) | 1995-01-24 | 1998-08-11 | The Administrators Of The Tulane Educational Fund | Highly potent agonists of growth hormone releasing hormone |
| US5652356A (en) | 1995-08-17 | 1997-07-29 | Hybridon, Inc. | Inverted chimeric and hybrid oligonucleotides |
| KR0185334B1 (ko) | 1995-11-02 | 1999-04-01 | 김은영 | 인간 혈장 아포지단백질 비-100에 결합하는 생쥐 항체를 암호하는 씨디엔에이 |
| CA2249985A1 (en) | 1996-03-26 | 1997-10-02 | Glaxo Group Limited | Tumour necrosis factor alpha convertase |
| DE69719220T2 (de) | 1996-11-18 | 2004-01-22 | Takeshi Imanishi | Neue nucleotidanaloga |
| AU6435698A (en) | 1997-02-20 | 1998-09-09 | Johns Hopkins School Of Medicine, The | Control of (il4) production as a therapeutic regulator of immune function |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| US6133246A (en) | 1997-08-13 | 2000-10-17 | Isis Pharmaceuticals Inc. | Antisense oligonucleotide compositions and methods for the modulation of JNK proteins |
| AU9063398A (en) | 1997-09-12 | 1999-04-05 | Exiqon A/S | Oligonucleotide analogues |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| GB9721240D0 (en) | 1997-10-08 | 1997-12-03 | Zeneca Ltd | Assay |
| US6156315A (en) | 1997-10-10 | 2000-12-05 | The Trustees Of Columbia University In The City Of New York | Method for inhibiting the binding of low density lipoprotein to blood vessel matrix |
| EP0911344B1 (en) | 1997-10-15 | 2004-03-03 | Fujirebio Inc. | Anti-Apo-B-48 monoclonal antibody, hybridoma, and methods of use |
| DK1049767T3 (da) | 1998-01-08 | 2005-09-19 | Aventis Pharma Inc | En transgen kanin, der udtrykker et funktionelt humant lipoprotein(A) |
| US6238921B1 (en) | 1998-03-26 | 2001-05-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of human mdm2 expression |
| US6949367B1 (en) | 1998-04-03 | 2005-09-27 | Epoch Pharmaceuticals, Inc. | Modified oligonucleotides for mismatch discrimination |
| US20030228597A1 (en) * | 1998-04-13 | 2003-12-11 | Cowsert Lex M. | Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation |
| US6300319B1 (en) | 1998-06-16 | 2001-10-09 | Isis Pharmaceuticals, Inc. | Targeted oligonucleotide conjugates |
| US6007995A (en) | 1998-06-26 | 1999-12-28 | Isis Pharmaceuticals Inc. | Antisense inhibition of TNFR1 expression |
| US6043352A (en) | 1998-08-07 | 2000-03-28 | Isis Pharmaceuticals, Inc. | 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides |
| EP0979869A1 (en) | 1998-08-07 | 2000-02-16 | Hoechst Marion Roussel Deutschland GmbH | Short oligonucleotides for the inhibition of VEGF expression |
| US5945290A (en) | 1998-09-18 | 1999-08-31 | Isis Pharmaceuticals, Inc. | Antisense modulation of RhoA expression |
| US6410323B1 (en) | 1999-08-31 | 2002-06-25 | Isis Pharmaceuticals, Inc. | Antisense modulation of human Rho family gene expression |
| US6172216B1 (en) | 1998-10-07 | 2001-01-09 | Isis Pharmaceuticals Inc. | Antisense modulation of BCL-X expression |
| RU2233844C2 (ru) * | 1999-02-12 | 2004-08-10 | Санкио Компани Лимитед | Новые нуклеозидные и олигонуклеотидные аналоги |
| DE60045706D1 (de) | 1999-03-18 | 2011-04-21 | Exiqon As | Detektion von genmutationen mittels lna primer |
| US6436640B1 (en) | 1999-03-18 | 2002-08-20 | Exiqon A/S | Use of LNA in mass spectrometry |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| AU3274600A (en) | 1999-03-18 | 2000-10-09 | Exiqon A/S | One step sample preparation and detection of nucleic acids in complex biologicalsamples |
| US20040171566A1 (en) | 1999-04-06 | 2004-09-02 | Monia Brett P. | Antisense modulation of p38 mitogen activated protein kinase expression |
| US6140124A (en) | 1999-04-06 | 2000-10-31 | Isis Pharmaceuticals Inc. | Antisense modulation of P38 mitogen activated protein kinase expression |
| US5998148A (en) | 1999-04-08 | 1999-12-07 | Isis Pharmaceuticals Inc. | Antisense modulation of microtubule-associated protein 4 expression |
| AU776362B2 (en) | 1999-05-04 | 2004-09-09 | Roche Innovation Center Copenhagen A/S | L-ribo-LNA analogues |
| US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| US6033910A (en) | 1999-07-19 | 2000-03-07 | Isis Pharmaceuticals Inc. | Antisense inhibition of MAP kinase kinase 6 expression |
| JP4151751B2 (ja) | 1999-07-22 | 2008-09-17 | 第一三共株式会社 | 新規ビシクロヌクレオシド類縁体 |
| AU6910100A (en) | 1999-08-18 | 2001-03-13 | Lawrence Chan | Apolipoprotein b mrna-specific ribozyme |
| PL354997A1 (en) | 1999-09-25 | 2004-03-22 | University Of Iowa Research Foundation | Immunostimulatory nucleic acids |
| US20020123617A1 (en) | 1999-12-23 | 2002-09-05 | Starling Gary C. | Novel immunoglobulin superfamily members of APEX-1, APEX-2 and APEX-3 and uses thereof |
| IL149694A0 (en) | 1999-12-23 | 2002-11-10 | Exiqon As | Therapeutic uses of lna-modified oligonucleotides |
| US6261840B1 (en) | 2000-01-18 | 2001-07-17 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
| US7179796B2 (en) | 2000-01-18 | 2007-02-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
| US20020055479A1 (en) | 2000-01-18 | 2002-05-09 | Cowsert Lex M. | Antisense modulation of PTP1B expression |
| US6602857B1 (en) | 2000-01-18 | 2003-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
| WO2001052902A1 (en) | 2000-01-24 | 2001-07-26 | Isis Pharmaceuticals, Inc. | Antisense modulation of inducible nitric oxide synthase expression |
| US20030064950A1 (en) | 2001-02-23 | 2003-04-03 | Ntambi James M. | Methods for reducing body fat and increasing lean body mass by reducing stearoyl-CoA desaturase 1 activity |
| CA2400573A1 (en) | 2000-03-28 | 2001-10-04 | Isis Pharmaceuticals Inc. | Alteration of cellular behavior by antisense modulation of mrna processing |
| WO2001077384A2 (de) | 2000-04-07 | 2001-10-18 | Epigenomics Ag | DETEKTION VON SNPs UND CYTOSIN-METHYLIERUNGEN |
| AU2001251612A1 (en) | 2000-04-14 | 2001-10-30 | Millennium Pharmaceuticals, Inc. | Roles of jak/stat family members in tolerance induction |
| EP1314734A1 (en) | 2000-08-29 | 2003-05-28 | Takeshi Imanishi | Novel nucleoside analogs and oligonucleotide derivatives containing these analogs |
| US20040024144A1 (en) * | 2000-09-14 | 2004-02-05 | Robert Solomon | Aqueous dispersions of comb copolymers and coatings produced therefrom |
| WO2002026768A2 (en) | 2000-09-29 | 2002-04-04 | Genaissance Pharmaceuticals, Inc. | Haplotypes of the por gene |
| US6426220B1 (en) | 2000-10-30 | 2002-07-30 | Isis Pharmaceuticals, Inc. | Antisense modulation of calreticulin expression |
| US20030008373A1 (en) | 2001-04-17 | 2003-01-09 | Myriad Genetics, Incorporated | APOA1-interacting proteins and use thereof |
| JP2002355074A (ja) | 2001-01-24 | 2002-12-10 | Univ Tsukuba | 腸管出血性病原性大腸菌o157:h7に特異的な核酸分子およびポリペプチド並びにこれらの使用方法 |
| EP1239051A3 (en) | 2001-01-30 | 2004-03-17 | Aeomica, Inc. | Human posh-like protein 1 |
| US6878729B2 (en) | 2001-05-04 | 2005-04-12 | The Procter & Gamble Company | Medicinal uses of dihydropyrazoles |
| US6660737B2 (en) | 2001-05-04 | 2003-12-09 | The Procter & Gamble Company | Medicinal uses of hydrazones |
| AU2002317437A1 (en) | 2001-05-18 | 2002-12-03 | Cureon A/S | Therapeutic uses of lna-modified oligonucleotides in infectious diseases |
| US20050019915A1 (en) | 2001-06-21 | 2005-01-27 | Bennett C. Frank | Antisense modulation of superoxide dismutase 1, soluble expression |
| US6964950B2 (en) * | 2001-07-25 | 2005-11-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of C-reactive protein expression |
| US7425545B2 (en) * | 2001-07-25 | 2008-09-16 | Isis Pharmaceuticals, Inc. | Modulation of C-reactive protein expression |
| US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
| US7888324B2 (en) | 2001-08-01 | 2011-02-15 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| AU2002334307A1 (en) | 2001-09-04 | 2003-03-18 | Exiqon A/S | Novel lna compositions and uses thereof |
| US7297485B2 (en) | 2001-10-15 | 2007-11-20 | Qiagen Gmbh | Method for nucleic acid amplification that results in low amplification bias |
| CA2477611A1 (en) | 2002-03-01 | 2003-09-12 | Ravgen, Inc. | Rapid analysis of variations in a genome |
| PT2264172T (pt) * | 2002-04-05 | 2017-12-06 | Roche Innovation Ct Copenhagen As | Compostos oligoméricos para a modulação da expressão do hif-1α. |
| US7569575B2 (en) | 2002-05-08 | 2009-08-04 | Santaris Pharma A/S | Synthesis of locked nucleic acid derivatives |
| WO2003097662A1 (en) | 2002-05-15 | 2003-11-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
| JP2005525829A (ja) * | 2002-05-20 | 2005-09-02 | ファルマシア・コーポレーション | 糖質コルチコイド受容体発現のアンチセンス調節 |
| US7393950B2 (en) | 2002-08-29 | 2008-07-01 | Hong Kong University Of Science & Technology | Antisense oligonucleotides targeted to human CDC45 |
| US20040219565A1 (en) | 2002-10-21 | 2004-11-04 | Sakari Kauppinen | Oligonucleotides useful for detecting and analyzing nucleic acids of interest |
| CA2505090A1 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Conjugated oligomeric compounds and their use in gene modulation |
| EP1560839A4 (en) * | 2002-11-05 | 2008-04-23 | Isis Pharmaceuticals Inc | CHIMERIC OLIGOMER COMPOUNDS AND THEIR USE IN GENE MODULATION |
| AU2003291753B2 (en) | 2002-11-05 | 2010-07-08 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| WO2004044181A2 (en) * | 2002-11-13 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
| US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| US20060009410A1 (en) | 2002-11-13 | 2006-01-12 | Crooke Rosanne M | Effects of apolipoprotein B inhibition on gene expression profiles in animals |
| EP2213738B1 (en) | 2002-11-14 | 2012-10-10 | Dharmacon, Inc. | siRNA molecules targeting Bcl-2 |
| DK2284269T3 (en) | 2002-11-18 | 2017-10-23 | Roche Innovation Ct Copenhagen As | Antisense design |
| CA2512389A1 (en) | 2003-01-03 | 2004-07-29 | Bristol-Myers Squibb Company | Methods of producing c-aryl glucoside sglt2 inhibitors |
| US20040185559A1 (en) | 2003-03-21 | 2004-09-23 | Isis Pharmaceuticals Inc. | Modulation of diacylglycerol acyltransferase 1 expression |
| US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
| CA2522637C (en) | 2003-04-17 | 2014-01-21 | Alnylam Pharmaceuticals, Inc. | Modified irna agents |
| US7750142B2 (en) | 2003-04-28 | 2010-07-06 | Isis Pharmaceuticals, Inc. | Modulation of glucagon receptor expression |
| US7399853B2 (en) | 2003-04-28 | 2008-07-15 | Isis Pharmaceuticals | Modulation of glucagon receptor expression |
| CA2524761A1 (en) | 2003-05-12 | 2005-02-10 | Union Carbide Chemicals & Plastics Technology Corporation | Process for control of polymer fines in a gas-phase polymerization |
| EP1648914A4 (en) | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
| JP2005060664A (ja) | 2003-07-31 | 2005-03-10 | Asahi Glass Co Ltd | 含フッ素化合物、含フッ素ポリマーとその製造方法およびそれを含むレジスト組成物 |
| US7825235B2 (en) | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
| ATE555118T1 (de) | 2003-08-28 | 2012-05-15 | Takeshi Imanishi | Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung |
| US20050074801A1 (en) | 2003-09-09 | 2005-04-07 | Monia Brett P. | Chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry |
| US20050053981A1 (en) * | 2003-09-09 | 2005-03-10 | Swayze Eric E. | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
| JP5379347B2 (ja) | 2003-09-18 | 2013-12-25 | アイシス ファーマシューティカルズ, インコーポレーテッド | 4’−チオヌクレオシドおよびオリゴマー化合物 |
| US20050191653A1 (en) | 2003-11-03 | 2005-09-01 | Freier Susan M. | Modulation of SGLT2 expression |
| DK2708541T3 (en) | 2003-11-13 | 2015-02-23 | Isis Pharmaceuticals Inc | 5,6-dihydroxy-isoindole derivatives as linkers for oligomeric solid phase synthesis |
| WO2005061710A1 (en) * | 2003-12-23 | 2005-07-07 | Santaris Pharma A/S | Oligomeric compounds for the modulation of bcl-2 |
| EP1711606A2 (en) | 2004-01-20 | 2006-10-18 | Isis Pharmaceuticals, Inc. | Modulation of glucocorticoid receptor expression |
| US20050287558A1 (en) | 2004-05-05 | 2005-12-29 | Crooke Rosanne M | SNPs of apolipoprotein B and modulation of their expression |
| CA2569419A1 (en) | 2004-06-03 | 2005-12-22 | Isis Pharmaceuticals, Inc. | Double strand compositions comprising differentially modified strands for use in gene modulation |
| US8394947B2 (en) | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
| WO2006085973A2 (en) * | 2004-07-02 | 2006-08-17 | Avi Biopharma, Inc. | Antisense antibacterial method and compound |
| ES2663810T3 (es) | 2004-08-10 | 2018-04-17 | Kastle Therapeutics, Llc | Métodos para modular los niveles de lipoproteínas y colesterol en humanos |
| EP1799859B1 (en) * | 2004-09-17 | 2014-07-02 | Isis Pharmaceuticals, Inc. | Enhanced antisense oligonucleotides |
| AR051446A1 (es) | 2004-09-23 | 2007-01-17 | Bristol Myers Squibb Co | Glucosidos de c-arilo como inhibidores selectivos de transportadores de glucosa (sglt2) |
| AU2005304110B2 (en) | 2004-11-09 | 2009-06-11 | Enzon Pharmaceuticals, Inc. | LNA oligonucleotides and the treatment of cancer |
| MX2007005558A (es) | 2004-11-09 | 2008-01-31 | Santaris Pharma As | Oligonucleotidos de lna potentes para la inhibicion dela expresion de hif-1a. |
| JP2009507499A (ja) | 2005-09-15 | 2009-02-26 | サンタリス ファーマ アー/エス | Apo−b100発現の抑制のためのrnaアンタゴニスト化合物 |
| EP2096170B1 (en) * | 2005-09-19 | 2011-08-10 | Isis Pharmaceuticals, Inc. | Modulation of glucagon receptor expression |
| WO2007035759A1 (en) | 2005-09-19 | 2007-03-29 | Johnson & Johnson Pharmaceutical Research & Development L.L.C. | Modulation of glucocorticoid receptor expression |
| EP1984381B1 (en) | 2006-01-27 | 2010-09-29 | Isis Pharmaceuticals, Inc. | 6-modified bicyclic nucleic acid analogs |
| MX2008012219A (es) | 2006-04-03 | 2008-10-02 | Santaris Pharma As | Composicion farmaceutica que comprende oligonucleotidos antisentido anti-miarn. |
| US20070238698A1 (en) * | 2006-04-07 | 2007-10-11 | Hsien-Chih Lin | Method for manufacturing drinking water having chitosan |
| WO2007131237A2 (en) | 2006-05-05 | 2007-11-15 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of ptp1b |
| JP2007311707A (ja) * | 2006-05-22 | 2007-11-29 | Ushio Inc | 紫外線発光素子パッケージ |
| CA2666191C (en) | 2006-10-09 | 2017-07-11 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of pcsk9 |
| EP2410053B2 (en) | 2006-10-18 | 2020-07-15 | Ionis Pharmaceuticals, Inc. | Antisense compounds |
| KR20150090284A (ko) | 2007-03-24 | 2015-08-05 | 젠자임 코포레이션 | 인간 아포리포프로틴 b에 상보적인 안티센스 올리고뉴클레오타이드 투여 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005038013A1 (en) * | 2003-10-07 | 2005-04-28 | Isis Pharmaceuticals, Inc. | Artisense oligonucleotides optimized for kidney targeting |
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