JP2005514005A - 新規のlna組成物およびその使用 - Google Patents
新規のlna組成物およびその使用 Download PDFInfo
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- JP2005514005A JP2005514005A JP2003525009A JP2003525009A JP2005514005A JP 2005514005 A JP2005514005 A JP 2005514005A JP 2003525009 A JP2003525009 A JP 2003525009A JP 2003525009 A JP2003525009 A JP 2003525009A JP 2005514005 A JP2005514005 A JP 2005514005A
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- Prior art keywords
- nucleic acid
- lna
- target
- oligonucleotide
- acid according
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- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
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| PCT/IB2002/003911 WO2003020739A2 (en) | 2001-09-04 | 2002-09-04 | Novel lna compositions and uses thereof |
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| JP2005514005A true JP2005514005A (ja) | 2005-05-19 |
| JP2005514005A5 JP2005514005A5 (https=) | 2006-01-05 |
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| US (1) | US7060809B2 (https=) |
| EP (1) | EP1446412B1 (https=) |
| JP (1) | JP2005514005A (https=) |
| AU (1) | AU2002334307A1 (https=) |
| CA (1) | CA2459347C (https=) |
| WO (1) | WO2003020739A2 (https=) |
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| JP2013078317A (ja) * | 2006-04-03 | 2013-05-02 | Santaris Pharma As | antimiRNAアンチセンスオリゴヌクレオチドを含む医薬組成物 |
| JP2015502365A (ja) * | 2011-12-12 | 2015-01-22 | オンコイミューニン,インコーポレイティド | オリゴヌクレオチドのイン−ビボ送達 |
| JP2016521753A (ja) * | 2013-06-12 | 2016-07-25 | オンコイミューニン,インコーポレイティド | オリゴヌクレオチドの全身性イン−ビボ送達 |
| WO2019182037A1 (ja) * | 2018-03-20 | 2019-09-26 | 国立大学法人東京工業大学 | 毒性が低減されたアンチセンスオリゴヌクレオチド |
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| EP2213737B1 (en) | 2002-02-01 | 2012-11-07 | Life Technologies Corporation | Double-stranded oligonucleotides |
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| AU2003276666A1 (en) * | 2002-06-12 | 2003-12-31 | Ambion, Inc. | Methods and compositions relating to polypeptides with rnase iii domains that mediate rna interference |
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| US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
| AU2007249349B2 (en) | 2006-05-11 | 2012-03-08 | Isis Pharmaceuticals, Inc. | 5'-Modified bicyclic nucleic acid analogs |
| JP5420412B2 (ja) | 2006-09-14 | 2014-02-19 | アイビス バイオサイエンシズ インコーポレイティッド | 病原体の同定のための標的全ゲノム増幅方法 |
| WO2008046911A2 (en) | 2006-10-20 | 2008-04-24 | Exiqon A/S | Novel human micrornas associated with cancer |
| US8188255B2 (en) | 2006-10-20 | 2012-05-29 | Exiqon A/S | Human microRNAs associated with cancer |
| JP2010510807A (ja) * | 2006-11-27 | 2010-04-08 | 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 | 高コレステロール血症を治療するための方法 |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| EP3536788A1 (en) | 2006-12-21 | 2019-09-11 | QIAGEN GmbH | Microrna target site blocking oligos and uses thereof |
| JP5680304B2 (ja) | 2007-02-23 | 2015-03-04 | アイビス バイオサイエンシズ インコーポレイティッド | 迅速な法医学的dna分析法 |
| US20080274458A1 (en) * | 2007-05-01 | 2008-11-06 | Latham Gary J | Nucleic acid quantitation methods |
| EP2170917B1 (en) | 2007-05-30 | 2012-06-27 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
| US9598724B2 (en) | 2007-06-01 | 2017-03-21 | Ibis Biosciences, Inc. | Methods and compositions for multiple displacement amplification of nucleic acids |
| EP2173760B2 (en) | 2007-06-08 | 2015-11-04 | Isis Pharmaceuticals, Inc. | Carbocyclic bicyclic nucleic acid analogs |
| CA2692579C (en) | 2007-07-05 | 2016-05-03 | Isis Pharmaceuticals, Inc. | 6-disubstituted bicyclic nucleic acid analogs |
| DK2548962T3 (en) | 2007-09-19 | 2016-04-11 | Applied Biosystems Llc | Sirna sequence-independent modification formats to reduce off-target phenotype effects in RNAI and stabilized forms thereof |
| KR101110013B1 (ko) * | 2007-10-05 | 2012-02-29 | (주)바이오니아 | 서열 내에 어베이직 부분을 포함하는 pcr 증폭용프라이머 |
| US8546556B2 (en) * | 2007-11-21 | 2013-10-01 | Isis Pharmaceuticals, Inc | Carbocyclic alpha-L-bicyclic nucleic acid analogs |
| EP2229457A4 (en) | 2007-12-14 | 2011-01-26 | Minitube America Inc | SEX-SPECIFIC SEPARATION OF SPERM AND EMBRYOES |
| WO2009100320A2 (en) | 2008-02-07 | 2009-08-13 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexitol nucleic acid analogs |
| DK2285819T3 (da) | 2008-04-04 | 2013-12-02 | Isis Pharmaceuticals Inc | Oligomere forbindelser omfattende neutralt bundne, terminale bicykliske nukleosider |
| US8148163B2 (en) | 2008-09-16 | 2012-04-03 | Ibis Biosciences, Inc. | Sample processing units, systems, and related methods |
| WO2010033599A2 (en) | 2008-09-16 | 2010-03-25 | Ibis Biosciences, Inc. | Mixing cartridges, mixing stations, and related kits, systems, and methods |
| EP2344893B1 (en) | 2008-09-16 | 2014-10-15 | Ibis Biosciences, Inc. | Microplate handling systems and methods |
| WO2010036698A1 (en) | 2008-09-24 | 2010-04-01 | Isis Pharmaceuticals, Inc. | Substituted alpha-l-bicyclic nucleosides |
| WO2010040112A2 (en) * | 2008-10-03 | 2010-04-08 | Curna, Inc. | Treatment of apolipoprotein-a1 related diseases by inhibition of natural antisense transcript to apolipoprotein-a1 |
| ES2600781T3 (es) | 2008-12-04 | 2017-02-10 | Curna, Inc. | Tratamiento para enfermedades relacionadas con el factor de crecimiento del endotelio vascular (vegf) mediante la inhibición de transcritos antisentido naturales de vegf |
| CN102361985B (zh) | 2008-12-04 | 2017-06-20 | 库尔纳公司 | 通过抑制肿瘤抑制基因的天然反义转录物治疗肿瘤抑制基因相关性疾病 |
| RU2620970C2 (ru) | 2008-12-04 | 2017-05-30 | КьюРНА,Инк., | Лечение связанных с эритропоэтином (еро) заболеваний путем ингибирования природного антисмыслового транскрипта к еро |
| WO2010080493A2 (en) * | 2008-12-18 | 2010-07-15 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services, Centers For Disease Control And Prevention | Real time polymerase chain reaction detection of legionella pneumophila and differentiation form other legionella species |
| AU2010207826B2 (en) | 2009-02-02 | 2013-10-03 | Qiagen Gmbh | Method for quantification of small RNA species |
| EP2396803A4 (en) | 2009-02-12 | 2016-10-26 | Ibis Biosciences Inc | IONIZATION PROBE ASSEMBLIES |
| WO2010093904A2 (en) | 2009-02-12 | 2010-08-19 | Curna, Inc. | Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf |
| KR101805199B1 (ko) * | 2009-02-12 | 2017-12-05 | 큐알엔에이, 인크. | 신경교세포 유래된 신경영양성 인자 (gdnf)에 대한 자연 안티센스 전사체의 저해에 의한 신경교세포 유래된 신경영양성 인자 (gdnf) 관련된 질환의 치료 |
| EP2408919B1 (en) | 2009-03-16 | 2017-10-18 | CuRNA, Inc. | Treatment of nuclear factor (erythroid-derived 2)-like 2 (nrf2) related diseases by inhibition of natural antisense transcript to nrf2 |
| CA2755404C (en) | 2009-03-17 | 2020-03-24 | Curna, Inc. | Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1 |
| EP3249053A1 (en) | 2009-03-27 | 2017-11-29 | Life Technologies Corporation | Methods, compositions, and kits for detecting allelic variants |
| CN102459596B (zh) | 2009-05-06 | 2016-09-07 | 库尔纳公司 | 通过针对脂质转运和代谢基因的天然反义转录物的抑制治疗脂质转运和代谢基因相关疾病 |
| KR101722541B1 (ko) | 2009-05-06 | 2017-04-04 | 큐알엔에이, 인크. | Ttp에 대한 천연 안티센스 전사체의 억제에 의한 트리스테트라프롤린 관련된 질환의 치료 |
| ES2618572T3 (es) | 2009-05-08 | 2017-06-21 | Curna, Inc. | Tratamiento de enfermedades relacionadas con la familia de la distrofina mediante inhibición de un transcrito antisentido natural para la familia de dmd |
| WO2010135329A2 (en) | 2009-05-18 | 2010-11-25 | Curna, Inc. | Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor |
| CA2762987A1 (en) | 2009-05-22 | 2010-11-25 | Joseph Collard | Treatment of transcription factor e3 (tfe3) and insulin receptor substrate 2 (irs2) related diseases by inhibition of natural antisense transcript to tfe3 |
| WO2010135692A2 (en) | 2009-05-22 | 2010-11-25 | Asuragen, Inc. | Mirna biomarkers of prostate disease |
| KR101704988B1 (ko) | 2009-05-28 | 2017-02-08 | 큐알엔에이, 인크. | 항바이러스 유전자에 대한 천연 안티센스 전사체의 억제에 의한 항바이러스 유전자 관련된 질환의 치료 |
| ES2804764T3 (es) | 2009-06-01 | 2021-02-09 | Halo Bio Rnai Therapeutics Inc | Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos |
| ES2629339T3 (es) | 2009-06-16 | 2017-08-08 | Curna, Inc. | Tratamiento de enfermedades relacionadas con la paraoxonasa 1 (pon1) por inhibición de transcrito antisentido natural a pon1 |
| CA2765700C (en) | 2009-06-16 | 2021-01-05 | Opko Curna, Llc | Treatment of collagen gene related diseases by inhibition of natural antisense transcript to a collagen gene |
| ES2618894T3 (es) | 2009-06-24 | 2017-06-22 | Curna, Inc. | Tratamiento de enfermedades relacionadas con el receptor del factor de necrosis tumoral 2 (tnfr2) por inhibición del transcrito natural antisentido para tnfr2 |
| CN102482672B (zh) | 2009-06-26 | 2016-11-09 | 库尔纳公司 | 通过抑制唐氏综合征基因的天然反义转录物治疗唐氏综合征基因相关疾病 |
| EP2290102A1 (en) | 2009-07-08 | 2011-03-02 | Administración General De La Communidad Autónoma De Euskadi | Methods for the diagnosis of multiple sclerosis based on its microRNA expression profiling |
| US9194877B2 (en) | 2009-07-17 | 2015-11-24 | Ibis Biosciences, Inc. | Systems for bioagent indentification |
| US8950604B2 (en) | 2009-07-17 | 2015-02-10 | Ibis Biosciences, Inc. | Lift and mount apparatus |
| US20120252869A1 (en) | 2009-07-24 | 2012-10-04 | Opko Curna, Llc | Treatment of sirtuin (sirt) related diseases by inhibition of natural antisense transcript to a sirtuin (sirt) |
| ES2585360T3 (es) | 2009-08-05 | 2016-10-05 | Curna, Inc. | Tratamiento de enfermedades relacionadas con un gen de la insulina (INS) por inhibición de la transcripción antisentido natural en un gen de la insulina (INS) |
| EP2462153B1 (en) | 2009-08-06 | 2015-07-29 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
| ES2599986T3 (es) | 2009-08-11 | 2017-02-06 | Curna, Inc. | Tratamiento de enfermedades relacionadas con adiponectina (ADIPOQ) mediante la inhibición de un transcrito antisentido natural de una adiponectina (ADIPOQ) |
| EP2789693B1 (en) | 2009-08-13 | 2017-10-04 | Life Technologies Corporation | Amelogenin SNP on chromosome X |
| CN102482670B (zh) | 2009-08-21 | 2018-06-15 | 库尔纳公司 | 通过抑制‘hsp70-相互作用蛋白的c末端’(chip)的天然反义转录物而治疗chip相关疾病 |
| EP2470657B1 (en) | 2009-08-25 | 2019-10-23 | CuRNA, Inc. | Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap |
| EP2470897A4 (en) | 2009-08-28 | 2013-05-29 | Asuragen Inc | MICRO-RNA BIOMARKERS OF PULMONARY DISEASE |
| WO2011032034A2 (en) | 2009-09-10 | 2011-03-17 | University Of Idaho | Nucleobase-functionalized conformationally restricted nucleotides and oligonucleotides for targeting nucleic acids |
| DK2480669T3 (en) | 2009-09-25 | 2018-02-12 | Curna Inc | TREATMENT OF FILAGGRIN- (FLG) RELATED DISEASES BY MODULATING FLG EXPRESSION AND ACTIVITY |
| EP2488668B1 (en) | 2009-10-15 | 2023-07-26 | Life Technologies Corporation | Novel human single nucleotide polymorphisms |
| ES2628739T3 (es) | 2009-10-15 | 2017-08-03 | Ibis Biosciences, Inc. | Amplificación por desplazamiento múltiple |
| AU2010319314C1 (en) | 2009-11-13 | 2016-09-01 | Sarepta Therapeutics, Inc. | Antisense antiviral compound and method for treating influenza viral infection |
| CA2782366A1 (en) | 2009-12-16 | 2011-07-14 | Opko Curna, Llc | Treatment of membrane bound transcription factor peptidase, site 1 (mbtps1) related diseases by inhibition of natural antisense transcript to mbtps1 |
| NO2516648T3 (https=) | 2009-12-23 | 2018-04-07 | ||
| RU2619185C2 (ru) | 2009-12-23 | 2017-05-12 | Курна, Инк. | Лечение заболеваний, связанных с разобщающим белком 2 (ucp2), путем ингибирования природного антисмыслового транскрипта к ucp2 |
| US8921334B2 (en) | 2009-12-29 | 2014-12-30 | Curna, Inc. | Treatment of nuclear respiratory factor 1 (NRF1) related diseases by inhibition of natural antisense transcript to NRF1 |
| US8962585B2 (en) | 2009-12-29 | 2015-02-24 | Curna, Inc. | Treatment of tumor protein 63 (p63) related diseases by inhibition of natural antisense transcript to p63 |
| DK2519632T3 (en) | 2009-12-31 | 2018-07-23 | Curna Inc | TREATMENT OF INSULIN RECEPTOR SUBSTRATE 2- (IRS2) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPTION TO IRS2 AND TRANSCRIPTION FACTOR E3 (TFE3) |
| DK2521784T3 (en) | 2010-01-04 | 2018-03-12 | Curna Inc | TREATMENT OF INTERFERON REGULATORY FACTOR 8- (IRF8) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENCE TRANSCRIPT TO IRF8 |
| KR101853509B1 (ko) | 2010-01-06 | 2018-04-30 | 큐알엔에이, 인크. | 췌장 발달 유전자에 대한 천연 안티센스 전사체의 억제에 의한 췌장 발달 유전자와 관련된 질환의 치료 |
| KR101854926B1 (ko) | 2010-01-11 | 2018-05-04 | 큐알엔에이, 인크. | 성 호르몬 결합 글로불린 (shbg)에 대한 자연 안티센스 전사체의 저해에 의한 성 호르몬 결합 글로불린 (shbg) 관련된 질환의 치료 |
| WO2011085102A1 (en) | 2010-01-11 | 2011-07-14 | Isis Pharmaceuticals, Inc. | Base modified bicyclic nucleosides and oligomeric compounds prepared therefrom |
| DK2529015T3 (en) | 2010-01-25 | 2018-02-26 | Curna Inc | TREATMENT OF RNASE H1-RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO RNASE H1 |
| RU2608496C2 (ru) | 2010-02-22 | 2017-01-18 | Курна, Инк. | Лечение заболеваний, связанных с пирролин-5 карбоксилатредуктазой 1(pycr1), путем ингибирования природного антисмыслового транскрипта к pycr1 |
| WO2011105902A2 (en) | 2010-02-23 | 2011-09-01 | Academisch Ziekenhuis Bij De Universiteit Van Amsterdam | Antagonists of complement component 8-beta (c8-beta) and uses thereof |
| WO2011105901A2 (en) | 2010-02-23 | 2011-09-01 | Academisch Ziekenhuis Bij De Universiteit Van Amsterdam | Antagonists of complement component 9 (c9) and uses thereof |
| WO2011105900A2 (en) | 2010-02-23 | 2011-09-01 | Academisch Ziekenhuis Bij De Universiteit Van Amsterdam | Antagonists of complement component 8-alpha (c8-alpha) and uses thereof |
| WO2011112516A1 (en) | 2010-03-08 | 2011-09-15 | Ico Therapeutics Inc. | Treating and preventing hepatitis c virus infection using c-raf kinase antisense oligonucleotides |
| EP2545173A2 (en) | 2010-03-12 | 2013-01-16 | Sarepta Therapeutics, Inc. | Antisense modulation of nuclear hormone receptors |
| EP3210611B1 (en) | 2010-03-12 | 2019-08-21 | The Brigham and Women's Hospital, Inc. | Methods of treating vascular inflammatory disorders |
| WO2011115818A1 (en) | 2010-03-17 | 2011-09-22 | Isis Pharmaceuticals, Inc. | 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom |
| US9506057B2 (en) | 2010-03-26 | 2016-11-29 | Integrated Dna Technologies, Inc. | Modifications for antisense compounds |
| AU2011230496B2 (en) | 2010-03-26 | 2015-09-17 | Integrated Dna Technologies, Inc. | Methods for enhancing nucleic acid hybridization |
| US8980856B2 (en) | 2010-04-02 | 2015-03-17 | Curna, Inc. | Treatment of colony-stimulating factor 3 (CSF3) related diseases by inhibition of natural antisense transcript to CSF3 |
| KR101900962B1 (ko) | 2010-04-09 | 2018-09-20 | 큐알엔에이, 인크. | 섬유아세포 성장 인자 21 (fgf21)에 대한 자연 안티센스 전사체의 저해에 의한 섬유아세포 성장 인자 21 (fgf21) 관련된 질환의 치료 |
| US8980253B2 (en) | 2010-04-26 | 2015-03-17 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-tRNA synthetase |
| CA2797362C (en) | 2010-04-27 | 2020-12-08 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of isoleucyl trna synthetases |
| KR101869570B1 (ko) | 2010-04-28 | 2018-06-20 | 아이오니스 파마수티컬즈, 인코포레이티드 | 변형된 뉴클레오사이드 및 그로부터 제조된 올리고머 화합물 |
| WO2011139853A2 (en) | 2010-04-28 | 2011-11-10 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of alanyl trna synthetases |
| CA2797374C (en) | 2010-04-29 | 2021-02-16 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of asparaginyl trna synthetases |
| CA2797393C (en) | 2010-04-29 | 2020-03-10 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of valyl trna synthetases |
| US9212390B2 (en) | 2010-04-30 | 2015-12-15 | Exiqon A/S | In situ hybridization method and buffer |
| CN103140233B (zh) | 2010-05-03 | 2017-04-05 | Atyr 医药公司 | 与甲硫氨酰‑tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的发现 |
| US8961961B2 (en) | 2010-05-03 | 2015-02-24 | a Tyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related protein fragments of arginyl-tRNA synthetases |
| RU2018110642A (ru) | 2010-05-03 | 2019-02-27 | Курна, Инк. | Лечение заболеваний, связанных с сиртуином (sirt), путем ингибирования природного антисмыслового транскрипта к сиртуину (sirt) |
| CN103096912A (zh) | 2010-05-03 | 2013-05-08 | Atyr医药公司 | 与苯丙氨酰-α-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现 |
| JP6008844B2 (ja) | 2010-05-04 | 2016-10-19 | エータイアー ファーマ, インコーポレイテッド | p38MULTI−tRNA合成酵素複合体のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
| ES2816898T3 (es) | 2010-05-13 | 2021-04-06 | Sarepta Therapeutics Inc | Compuestos que modulan la actividad de señalización de las interleucinas 17 y 23 |
| EP2568996B1 (en) | 2010-05-14 | 2017-10-04 | aTyr Pharma, Inc. | Therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-beta-trna synthetases |
| TWI586356B (zh) | 2010-05-14 | 2017-06-11 | 可娜公司 | 藉由抑制par4天然反股轉錄本治療par4相關疾病 |
| CN103096914B (zh) | 2010-05-17 | 2015-08-12 | Atyr医药公司 | 与亮氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现 |
| CA2799207C (en) | 2010-05-26 | 2019-03-26 | Curna, Inc. | Treatment of atonal homolog 1 (atoh1) related diseases by inhibition of natural antisense transcript to atoh1 |
| JP5917497B2 (ja) | 2010-05-26 | 2016-05-18 | カッパーアールエヌエー,インコーポレイテッド | メチオニンスルホキシドレダクターゼa(msra)に対する天然アンチセンス転写物の阻害によるmsra関連疾患の治療 |
| CA2800375C (en) | 2010-05-27 | 2021-03-09 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-trna synthetases |
| US8957200B2 (en) | 2010-06-07 | 2015-02-17 | Isis Pharmaceuticals, Inc. | Bicyclic nucleosides and oligomeric compounds prepared therefrom |
| WO2011163499A2 (en) | 2010-06-23 | 2011-12-29 | Opko Curna, Llc | Treatment of sodium channel, voltage-gated, alpha subunit (scna) related diseases by inhibition of natural antisense transcript to scna |
| EP2593125B1 (en) | 2010-07-12 | 2017-11-01 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-trna synthetases |
| CN103068982B (zh) | 2010-07-14 | 2017-06-09 | 库尔纳公司 | 通过抑制盘状大同系物(dlg)的天然反义转录物而治疗dlg相关疾病 |
| AU2011293294B2 (en) | 2010-08-25 | 2016-03-24 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Tyrosyl-tRNA synthetases |
| AU2011299233B2 (en) | 2010-09-07 | 2016-09-15 | Integrated Dna Technologies, Inc. | Modifications for antisense compounds |
| WO2012040403A1 (en) | 2010-09-21 | 2012-03-29 | Life Technologies Corporation | Se33 mutations impacting genotype concordance |
| ES2640755T3 (es) | 2010-10-06 | 2017-11-06 | Curna, Inc. | Tratamiento de enfermedades relacionadas con la Sialidasa 4 (neu4) mediante inhibición del transcrito antisentido natural al gen neu4 |
| US20140031250A1 (en) | 2010-10-07 | 2014-01-30 | David Tsai Ting | Biomarkers of Cancer |
| US9222088B2 (en) | 2010-10-22 | 2015-12-29 | Curna, Inc. | Treatment of alpha-L-iduronidase (IDUA) related diseases by inhibition of natural antisense transcript to IDUA |
| EP3260540A1 (en) | 2010-11-12 | 2017-12-27 | The General Hospital Corporation | Polycomb-associated non-coding rnas |
| ES2657590T3 (es) | 2010-11-23 | 2018-03-06 | Curna, Inc. | Tratamiento de enfermedades relacionadas con nanog mediante inhibición del transcrito antisentido natural a nanog |
| EP2663323B1 (en) | 2011-01-14 | 2017-08-16 | The General Hospital Corporation | Methods targeting mir-128 for regulating cholesterol/lipid metabolism |
| EP2718439B1 (en) | 2011-06-09 | 2017-08-09 | CuRNA, Inc. | Treatment of frataxin (fxn) related diseases by inhibition of natural antisense transcript to fxn |
| BR112013033488B8 (pt) | 2011-06-27 | 2022-11-22 | Eisai R&D Man Co Ltd | Métodos para facilitar o diagnóstico do comprometimento cognitivo devido a doença de alzheimer ou comprometimento cognitivo leve (mci)e kit |
| EP2546358A1 (en) | 2011-07-15 | 2013-01-16 | Laboratorios Del. Dr. Esteve, S.A. | Methods and reagents for efficient control of HIV progression |
| EP2732035A2 (en) | 2011-07-15 | 2014-05-21 | Sarepta Therapeutics, Inc. | Methods and compositions for manipulating translation of protein isoforms from alternative initiation start sites |
| KR101991980B1 (ko) | 2011-09-06 | 2019-06-21 | 큐알엔에이, 인크. | 소형 분자로 전압-개폐된 나트륨 채널 (SCNxA)의 알파 아단위에 관련된 질환의 치료 |
| US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
| CA2851280C (en) | 2011-10-11 | 2021-05-18 | The Brigham And Women's Hospital, Inc. | Micrornas in neurodegenerative disorders |
| EP2788487B1 (en) | 2011-12-08 | 2018-04-04 | Sarepta Therapeutics, Inc. | Oligonucleotide analogues targeting human lmna |
| US20150031750A1 (en) | 2012-03-15 | 2015-01-29 | The Scripps Research Institute | Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf |
| WO2013154799A1 (en) | 2012-04-09 | 2013-10-17 | Isis Pharmaceuticals, Inc. | Tricyclic nucleosides and oligomeric compounds prepared therefrom |
| EP2850092B1 (en) | 2012-04-09 | 2017-03-01 | Ionis Pharmaceuticals, Inc. | Tricyclic nucleic acid analogs |
| EP3597741A1 (en) | 2012-04-27 | 2020-01-22 | Duke University | Genetic correction of mutated genes |
| WO2013184209A1 (en) | 2012-06-04 | 2013-12-12 | Ludwig Institute For Cancer Research Ltd. | Mif for use in methods of treating subjects with a neurodegenerative disorder |
| ES2434853B1 (es) | 2012-06-12 | 2014-09-30 | Fundación Centro Nacional De Investigaciones Cardiovasculares Carlos Iii | Marcador molecular de potencia terapéutica de células madre mesenquimales humanas y sus usos |
| US9029335B2 (en) | 2012-10-16 | 2015-05-12 | Isis Pharmaceuticals, Inc. | Substituted 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom |
| US10086093B2 (en) | 2013-02-28 | 2018-10-02 | The General Hospital Corporation | miRNA profiling compositions and methods of use |
| WO2014164874A2 (en) | 2013-03-13 | 2014-10-09 | Becton, Dickinson And Company | Methods and compositions for modulation of amplification efficiency |
| US9273349B2 (en) | 2013-03-14 | 2016-03-01 | Affymetrix, Inc. | Detection of nucleic acids |
| US9828582B2 (en) | 2013-03-19 | 2017-11-28 | Duke University | Compositions and methods for the induction and tuning of gene expression |
| DK2991656T3 (da) | 2013-05-01 | 2020-03-23 | Ionis Pharmaceuticals Inc | Sammensætninger og fremgangsmåder til modulering af apolipoprotein c-iii-ekspression |
| ES2523016B1 (es) | 2013-05-20 | 2015-09-09 | 3P Biopharmaceuticals | Vectores alfavirales y líneas celulares para la producción de proteínas recombinantes |
| DE102013011304A1 (de) * | 2013-07-02 | 2015-01-22 | Technische Universität Dresden | Verfahren und Anordnung zur Erfassung von Bindungsereignissen von Molekülen |
| JP6618910B2 (ja) | 2013-09-05 | 2019-12-11 | サレプタ セラピューティクス,インコーポレイテッド | 酸性α−グルコシダーゼにおけるアンチセンス誘導エクソン2包含 |
| US11162096B2 (en) | 2013-10-14 | 2021-11-02 | Ionis Pharmaceuticals, Inc | Methods for modulating expression of C9ORF72 antisense transcript |
| AU2014375224A1 (en) | 2014-01-05 | 2016-07-28 | Biomirna Holdings Ltd | Lung cancer determinations using miRNA ratios |
| WO2015120382A1 (en) | 2014-02-07 | 2015-08-13 | The Johns Hopkins University | Predicting response to epigenetic drug therapy |
| WO2015126523A1 (en) * | 2014-02-21 | 2015-08-27 | Clontech Laboratories, Inc. | Spin columns comprising poly(acid) membrane separation matrices, and methods of making and using the same |
| RS60707B1 (sr) | 2014-04-01 | 2020-09-30 | Biogen Ma Inc | Kompozicije za modulaciju ekspresije sod-1 |
| DK3137476T3 (da) | 2014-04-28 | 2019-11-18 | Ionis Pharmaceuticals Inc | Linker-modificerede oligomerforbindelser |
| SG11201608502TA (en) | 2014-05-01 | 2016-11-29 | Ionis Pharmaceuticals Inc | Compositions and methods for modulating complement factor b expression |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| US10301624B2 (en) | 2014-06-25 | 2019-05-28 | The General Hospital Corporation | Targeting human satellite II (HSATII) |
| CN107109411B (zh) | 2014-10-03 | 2022-07-01 | 冷泉港实验室 | 核基因输出的定向增加 |
| EP3221445B1 (en) | 2014-11-20 | 2021-07-14 | The Regents of The University of California | Compositions and methods related to hematologic recovery |
| WO2016094330A2 (en) | 2014-12-08 | 2016-06-16 | 20/20 Genesystems, Inc | Methods and machine learning systems for predicting the liklihood or risk of having cancer |
| WO2016092045A1 (en) | 2014-12-11 | 2016-06-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and kits for predicting medically refractory acute severe colitis |
| US9688707B2 (en) | 2014-12-30 | 2017-06-27 | Ionis Pharmaceuticals, Inc. | Bicyclic morpholino compounds and oligomeric compounds prepared therefrom |
| WO2016112132A1 (en) | 2015-01-06 | 2016-07-14 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
| US10676726B2 (en) | 2015-02-09 | 2020-06-09 | Duke University | Compositions and methods for epigenome editing |
| MA41795A (fr) | 2015-03-18 | 2018-01-23 | Sarepta Therapeutics Inc | Exclusion d'un exon induite par des composés antisens dans la myostatine |
| US10961532B2 (en) | 2015-04-07 | 2021-03-30 | The General Hospital Corporation | Methods for reactivating genes on the inactive X chromosome |
| WO2016167780A1 (en) | 2015-04-16 | 2016-10-20 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
| WO2016177774A1 (en) | 2015-05-04 | 2016-11-10 | Academisch Medisch Centrum | Method of quantifying mirnas using normalization |
| US10849917B2 (en) | 2015-06-01 | 2020-12-01 | Sarepta Therapeutics, Inc. | Antisense-induced exon exclusion in type VII collagen |
| CA2990852A1 (en) | 2015-06-26 | 2016-12-29 | Beth Israel Deaconess Medical Center, Inc. | Cancer therapy targeting tetraspanin 33 (tspan33) in myeloid derived suppressor cells |
| JP2018525037A (ja) | 2015-08-24 | 2018-09-06 | ハロー−バイオ・アールエヌエーアイ・セラピューティックス、インコーポレイテッド | 遺伝子発現の調節のためのポリヌクレオチドナノ粒子及びその使用 |
| EP3858993A1 (en) | 2015-10-09 | 2021-08-04 | Sarepta Therapeutics, Inc. | Compositions and methods for treating duchenne muscular dystrophy and related disorders |
| EP3359685B1 (en) | 2015-10-09 | 2026-01-28 | University Of Southampton | Modulation of gene expression for deregulated protein expression |
| EP4089175A1 (en) | 2015-10-13 | 2022-11-16 | Duke University | Genome engineering with type i crispr systems in eukaryotic cells |
| EP4454637A3 (en) | 2015-11-16 | 2025-01-08 | Olix Pharmaceuticals, Inc. | Treatment of age-related macular degeneration using rna complexes that target myd88 or tlr3 |
| EA201891317A3 (ru) | 2015-11-30 | 2019-04-30 | Дьюк Юниверсити | Терапевтические мишени для коррекции гена дистрофина человека с помощью редактирования генов и способы их применения |
| US11058709B1 (en) | 2015-12-04 | 2021-07-13 | Ionis Pharmaceuticals, Inc. | Methods of treating breast cancer |
| EP3933041B1 (en) | 2015-12-14 | 2024-01-31 | Cold Spring Harbor Laboratory | Antisense oligomers for treatment of autosomal dominant retardation |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| KR102825946B1 (ko) | 2016-02-02 | 2025-06-27 | 올릭스 주식회사 | IL4Rα, TRPA1, 또는 F2RL1을 표적화하는 RNA 복합체를 사용한 아토피 피부염 및 천식의 치료 |
| US11234996B2 (en) | 2016-02-25 | 2022-02-01 | The Brigham And Women's Hospital, Inc. | Treatment methods for fibrosis targeting SMOC2 |
| AU2017234678A1 (en) | 2016-03-16 | 2018-08-16 | Ionis Pharmaceuticals, Inc. | Methods of modulating KEAP1 |
| WO2017161168A1 (en) | 2016-03-16 | 2017-09-21 | Ionis Pharmaceuticals, Inc. | Modulation of dyrk1b expression |
| US20190127713A1 (en) | 2016-04-13 | 2019-05-02 | Duke University | Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use |
| CA3021267A1 (en) | 2016-04-18 | 2017-10-26 | Sarepta Therapeutics, Inc. | Antisense oligomers and methods of using the same for treating diseases associated with the acid alpha-glucosidase gene |
| CN109477109B (zh) | 2016-04-29 | 2022-09-23 | 萨勒普塔医疗公司 | 靶向人lmna的寡核苷酸类似物 |
| US11472824B2 (en) | 2016-05-24 | 2022-10-18 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| MA49775A (fr) | 2016-05-24 | 2020-06-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| MA45183A (fr) | 2016-05-24 | 2019-04-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| MA45362A (fr) | 2016-05-24 | 2019-04-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| TWI737736B (zh) | 2016-05-24 | 2021-09-01 | 美商薩羅塔治療公司 | 製備磷醯二胺嗎啉代寡聚物之方法 |
| EP3471781A4 (en) | 2016-06-17 | 2020-05-06 | Ionis Pharmaceuticals, Inc. | MODULATION OF GYS1 EXPRESSION |
| TW201811807A (zh) | 2016-06-30 | 2018-04-01 | 美商薩羅塔治療公司 | 用於肌肉萎縮症之外顯子跳躍寡聚物 |
| WO2018017754A1 (en) | 2016-07-19 | 2018-01-25 | Duke University | Therapeutic applications of cpf1-based genome editing |
| WO2018017814A1 (en) | 2016-07-20 | 2018-01-25 | President And Fellows Of Harvard College | Peptidoglycan glycosyltransferase inhibitors of sed proteins for treating bacterial infections |
| WO2018053142A2 (en) | 2016-09-14 | 2018-03-22 | President And Fellows Of Harvard College | Methods and compositions for modulating erythropoiesis |
| CA3037046A1 (en) | 2016-10-31 | 2018-05-03 | University Of Massachusetts | Targeting microrna-101-3p in cancer therapy |
| WO2018102745A1 (en) | 2016-12-02 | 2018-06-07 | Cold Spring Harbor Laboratory | Modulation of lnc05 expression |
| WO2018112033A1 (en) | 2016-12-13 | 2018-06-21 | President And Fellows Of Harvard College | Methods and compositions for targeting tumor-infiltrating tregs |
| SI3554554T1 (sl) | 2016-12-19 | 2023-02-28 | Sarepta Therapeutics, Inc. | Oligomerni konjugati, ki preskakujejo ekson za mišično distrofijo |
| IL297528A (en) | 2016-12-19 | 2022-12-01 | Sarepta Therapeutics Inc | Exon-skipping oligomer conjugates for muscular dystrophy |
| SMT202200366T1 (it) | 2016-12-19 | 2022-11-18 | Sarepta Therapeutics Inc | Coniugati di oligomeri per salto di esone per distrofia muscolare |
| US11180756B2 (en) | 2017-03-09 | 2021-11-23 | Ionis Pharmaceuticals | Morpholino modified oligomeric compounds |
| EP3609521A4 (en) | 2017-04-14 | 2021-06-16 | University of Massachusetts | TARGETING OF CELL TROPISM RECEPTORS TO INHIBIT INFECTION BY THE CYTOMEGALOVIRUS |
| CN110536694A (zh) | 2017-04-20 | 2019-12-03 | Atyr 医药公司 | 用于治疗肺部炎症的组合物和方法 |
| US11197884B2 (en) | 2017-08-18 | 2021-12-14 | Ionis Pharmaceuticals, Inc. | Modulation of the notch signaling pathway for treatment of respiratory disorders |
| SG11202001590RA (en) | 2017-08-25 | 2020-03-30 | Stoke Therapeutics Inc | Antisense oligomers for treatment of conditions and diseases |
| US10517889B2 (en) | 2017-09-08 | 2019-12-31 | Ionis Pharmaceuticals, Inc. | Modulators of SMAD7 expression |
| EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
| WO2019067975A1 (en) | 2017-09-28 | 2019-04-04 | Sarepta Therapeutics, Inc. | POLYTHERAPIES FOR TREATING MUSCLE DYSTROPHY |
| WO2019067979A1 (en) | 2017-09-28 | 2019-04-04 | Sarepta Therapeutics, Inc. | POLYTHERAPIES FOR TREATING MUSCLE DYSTROPHY |
| JP2020536058A (ja) | 2017-09-28 | 2020-12-10 | サレプタ セラピューティクス, インコーポレイテッド | 筋ジストロフィーを処置するための併用療法 |
| WO2019079637A2 (en) | 2017-10-18 | 2019-04-25 | Sarepta Therapeutics, Inc. | ANTISENSE OLIGOMERIC COMPOUNDS |
| WO2019144061A1 (en) | 2018-01-19 | 2019-07-25 | Duke University | Genome engineering with crispr-cas systems in eukaryotes |
| WO2019178346A1 (en) * | 2018-03-14 | 2019-09-19 | The Trustees Of The University Of Pennsylvania | Enrichment of nucleic acids |
| US12060558B2 (en) | 2018-05-04 | 2024-08-13 | Stoke Therapeutics, Inc. | Methods and compositions for treatment of cholesteryl ester storage disease |
| US12582702B2 (en) | 2018-05-11 | 2026-03-24 | University Of Massachusetts | Methods for improving leptin sensitivity for the treatment of obesity and diabetes |
| US10758629B2 (en) | 2018-05-29 | 2020-09-01 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| EP3806868A4 (en) | 2018-06-13 | 2022-06-22 | Sarepta Therapeutics, Inc. | EXON SKIPPING OLIGOMERS FOR MUSCULAR DYSTROPHY |
| CN110669839B (zh) * | 2018-07-03 | 2022-04-15 | 北京福安华生物科技有限公司 | 一种检测egfr基因t790m突变的人工模拟分子信标与试剂盒 |
| TW202020153A (zh) | 2018-07-27 | 2020-06-01 | 美商薩羅塔治療公司 | 用於肌肉萎縮症之外顯子跳躍寡聚物 |
| EP3833762A4 (en) | 2018-08-09 | 2022-09-28 | Verseau Therapeutics, Inc. | Oligonucleotide compositions for targeting ccr2 and csf1r and uses thereof |
| EP3843845B1 (en) | 2018-08-29 | 2026-03-11 | University Of Massachusetts | Inhibition of protein kinases to treat friedreich ataxia |
| US11273137B2 (en) | 2018-09-04 | 2022-03-15 | Board Of Trustees Of Michigan State University | Methods and compositions to prevent and treat disorders associated with mutations in the ODC1 gene |
| EP3846824B1 (en) | 2018-09-07 | 2025-06-18 | The General Hospital Corporation | Compositions and methods for immune checkpoint inhibition |
| TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
| BR112021008967A2 (pt) | 2018-11-15 | 2021-08-17 | Ionis Pharmaceuticals, Inc. | moduladores da expressão de irf5 |
| MX2021006737A (es) | 2018-12-13 | 2021-09-23 | Sarepta Therapeutics Inc | Conjugados de oligómeros de salto de exones para distrofia muscular. |
| CN112654714B (zh) | 2018-12-17 | 2024-10-11 | 伊卢米纳剑桥有限公司 | 用于测序的引物寡核苷酸 |
| TW202540426A (zh) | 2019-02-27 | 2025-10-16 | 美商Ionis製藥公司 | Malat1表現之調節劑 |
| KR20210134003A (ko) | 2019-02-27 | 2021-11-08 | 스톡 테라퓨틱스, 인크. | 병태 및 질환의 치료를 위한 안티센스 올리고머 |
| CN114040799A (zh) | 2019-03-12 | 2022-02-11 | 哈佛大学校长及研究员协会 | 治疗癌症的方法和组合物 |
| EP3719144A1 (en) | 2019-04-05 | 2020-10-07 | Fundación para la Investigación Biomédica del Hospital Universitario de la Paz (FIBHULP) | Mir-151a-3p as an universal endogenous control for exosome cargo normalization |
| EP3955966A1 (en) | 2019-04-18 | 2022-02-23 | Sarepta Therapeutics, Inc. | Compositions for treating muscular dystrophy |
| WO2020226960A1 (en) | 2019-05-03 | 2020-11-12 | Dicerna Pharmaceuticals, Inc. | Double-stranded nucleic acid inhibitor molecules with shortened sense strands |
| US20220226269A1 (en) | 2019-06-12 | 2022-07-21 | President And Fellows Of Harvard College | Methods and compositions for modulation of an interspecies gut bacterial pathway for levodopa metabolism |
| EP3999664A1 (en) | 2019-07-19 | 2022-05-25 | Fundación para la Investigación Biomédica del Hospital Universitario de la Paz (FIBHULP) | Method for determining the response to treatment of a patient affected by non-small cell lung carcinoma (nsclc) |
| EP3956450B1 (en) | 2019-07-26 | 2025-08-13 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating gfap |
| EP4013767A4 (en) | 2019-08-15 | 2023-10-25 | Ionis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds and uses thereof |
| CN115485385A (zh) | 2020-03-04 | 2022-12-16 | 瑞泽恩制药公司 | 用于使肿瘤细胞对免疫疗法敏感的方法和组合物 |
| BR112022022889A2 (pt) | 2020-05-11 | 2023-04-04 | Stoke Therapeutics Inc | Oligômeros antissentido de opa1 para tratamento de condições e doenças |
| US20230285357A1 (en) | 2020-05-27 | 2023-09-14 | The Regents Of The University Of California | Compositions and methods for transdifferentiating cells |
| WO2022056454A2 (en) | 2020-09-14 | 2022-03-17 | President And Fellows Of Harvard College | Methods and compositions for treating hpv-positive cancers |
| IL301306A (en) | 2020-09-16 | 2023-05-01 | Harvard College | Methods of treating an individual that has failed an anti-pd-1/anti-pd-l1 therapy |
| MX2024003690A (es) | 2021-09-30 | 2024-06-19 | Sarepta Therapeutics Inc | Oligonucleótidos antisentido que tienen una o más unidades abásicas. |
| JP2024539223A (ja) | 2021-10-22 | 2024-10-28 | サレプタ セラピューティクス, インコーポレイテッド | 末梢ミエリンタンパク質22関連疾患の処置のためのモルフォリノオリゴマー |
| EP4433592A1 (en) | 2021-11-18 | 2024-09-25 | Circularis Biotechnologies, Inc. | Compositions and methods for production of circular nucleic acid molecules |
| EP4437106A2 (en) | 2021-11-24 | 2024-10-02 | Prime Medicine, Inc. | Methods and compositions for inhibiting mismatch repair |
| WO2023150181A1 (en) | 2022-02-01 | 2023-08-10 | President And Fellows Of Harvard College | Methods and compositions for treating cancer |
| IL318625A (en) | 2022-07-29 | 2025-03-01 | Regeneron Pharma | Compositions and methods for transferrin receptor (TFR)-mediated delivery to brain and muscle |
| US20260049309A1 (en) | 2022-08-15 | 2026-02-19 | Novo Nordisk A/S | Regulation of activity of rnai molecules |
| TW202424186A (zh) | 2022-08-25 | 2024-06-16 | 美商生命編輯治療學公司 | Rna引導核酸酶中介基因編輯用之具鎖核酸引導 rna之化學修飾 |
| WO2024064237A2 (en) | 2022-09-21 | 2024-03-28 | Sarepta Therapeutics, Inc. | Dmd antisense oligonucleotide-mediated exon skipping efficiency |
| IL320016A (en) | 2022-11-04 | 2025-06-01 | Regeneron Pharma | Calcium voltage-gated channel auxiliary subunit gamma 1 (cacng1) binding proteins and cacng1-mediated delivery to skeletal muscle |
| AU2023379457A1 (en) | 2022-11-14 | 2025-05-15 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for fibroblast growth factor receptor 3-mediated delivery to astrocytes |
| US20250066776A1 (en) | 2023-04-27 | 2025-02-27 | Sarepta Therapeutics, Inc. | Antisense oligomers for treatment of chronic kidney disease |
| WO2024233864A2 (en) | 2023-05-10 | 2024-11-14 | Dicerna Pharmaceuticals, Inc. | Galnac-conjugated rnai oligonucleotides |
| WO2025038750A2 (en) | 2023-08-14 | 2025-02-20 | President And Fellows Of Harvard College | Methods and compositions for treating cancer |
| WO2025054459A1 (en) | 2023-09-08 | 2025-03-13 | Dicerna Pharmaceuticals, Inc. | Rnai oligonucleotide conjugates |
| WO2025085810A2 (en) | 2023-10-18 | 2025-04-24 | Sarepta Therapeutics, Inc. | Antisense oligomers for treatment of centronuclear myopathies |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US4806463A (en) * | 1986-05-23 | 1989-02-21 | Worcester Foundation For Experimental Biology | Inhibition of HTLV-III by exogenous oligonucleotides |
| 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 |
| DK0820483T3 (da) | 1995-04-07 | 2001-01-02 | Mogens Havsteen Jakobsen | Fremgangsmåde til fotokemisk immobilisering af ligander under anvendelse af quinoner |
| AU9063398A (en) | 1997-09-12 | 1999-04-05 | Exiqon A/S | Oligonucleotide analogues |
| JP2002515514A (ja) * | 1998-05-21 | 2002-05-28 | 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 | オリゴヌクレオチドの局所送逹のための組成物及び方法 |
| CN1350542A (zh) | 1999-03-18 | 2002-05-22 | 埃克西库恩公司 | 木-lna类似物 |
| JP4768132B2 (ja) | 1999-03-24 | 2011-09-07 | エクシコン エ/エス | [2.2.1]ビシクロヌクレオシドの改良された製法 |
| EP1178999B1 (en) | 1999-05-04 | 2007-03-14 | Santaris Pharma A/S | L-ribo-lna analogues |
| US6083482A (en) * | 1999-05-11 | 2000-07-04 | Icn Pharmaceuticals, Inc. | Conformationally locked nucleosides and oligonucleotides |
| US7205105B2 (en) * | 1999-12-08 | 2007-04-17 | Epoch Biosciences, Inc. | Real-time linear detection probes: sensitive 5′-minor groove binder-containing probes for PCR analysis |
| US6352858B1 (en) * | 2000-09-11 | 2002-03-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of BTAK expression |
| US6440739B1 (en) * | 2001-07-17 | 2002-08-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of glioma-associated oncogene-2 expression |
| US20040092462A1 (en) * | 2002-11-13 | 2004-05-13 | Isis Pharmaceuticals Inc. | Modulation of endothelial differentiation gene 2 expression |
| US9150605B2 (en) * | 2002-11-05 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2′-modified nucleosides for use in gene modulation |
-
2002
- 2002-09-04 AU AU2002334307A patent/AU2002334307A1/en not_active Abandoned
- 2002-09-04 CA CA2459347A patent/CA2459347C/en not_active Expired - Lifetime
- 2002-09-04 WO PCT/IB2002/003911 patent/WO2003020739A2/en not_active Ceased
- 2002-09-04 EP EP02797693A patent/EP1446412B1/en not_active Expired - Lifetime
- 2002-09-04 JP JP2003525009A patent/JP2005514005A/ja active Pending
- 2002-09-04 US US10/235,683 patent/US7060809B2/en not_active Expired - Lifetime
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013078317A (ja) * | 2006-04-03 | 2013-05-02 | Santaris Pharma As | antimiRNAアンチセンスオリゴヌクレオチドを含む医薬組成物 |
| JP2015502365A (ja) * | 2011-12-12 | 2015-01-22 | オンコイミューニン,インコーポレイティド | オリゴヌクレオチドのイン−ビボ送達 |
| JP2019073548A (ja) * | 2011-12-12 | 2019-05-16 | オンコイミューニン,インコーポレイティド | オリゴヌクレオチドのイン−ビボ送達 |
| JP2016521753A (ja) * | 2013-06-12 | 2016-07-25 | オンコイミューニン,インコーポレイティド | オリゴヌクレオチドの全身性イン−ビボ送達 |
| JP2019135259A (ja) * | 2013-06-12 | 2019-08-15 | オンコイミューニン,インコーポレイティド | オリゴヌクレオチドの全身性イン−ビボ送達 |
| WO2019182037A1 (ja) * | 2018-03-20 | 2019-09-26 | 国立大学法人東京工業大学 | 毒性が低減されたアンチセンスオリゴヌクレオチド |
| JP2024129413A (ja) * | 2023-03-13 | 2024-09-27 | Kmバイオロジクス株式会社 | T細胞受容体遺伝子再構成断片(TREC)、Igκ鎖遺伝子再構成断片(KREC)およびSMN1遺伝子の量を定量PCRにより同時に測定する方法およびそのための新規プライマー |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002334307A1 (en) | 2003-03-18 |
| EP1446412B1 (en) | 2012-03-07 |
| WO2003020739A2 (en) | 2003-03-13 |
| US20030224377A1 (en) | 2003-12-04 |
| WO2003020739A3 (en) | 2004-06-03 |
| CA2459347C (en) | 2012-10-09 |
| EP1446412A2 (en) | 2004-08-18 |
| CA2459347A1 (en) | 2003-03-13 |
| US7060809B2 (en) | 2006-06-13 |
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