CN110951731A - 用于调节c9orf72表达的组合物 - Google Patents
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| Application Number | Priority Date | Filing Date | Title |
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| US201261714132P | 2012-10-15 | 2012-10-15 | |
| US61/714,132 | 2012-10-15 | ||
| CN201380053819.8A CN104968783B (zh) | 2012-10-15 | 2013-10-15 | 用于调节c9orf72表达的组合物 |
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| CN201380053819.8A Division CN104968783B (zh) | 2012-10-15 | 2013-10-15 | 用于调节c9orf72表达的组合物 |
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| CN110951731A true CN110951731A (zh) | 2020-04-03 |
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| CN201380053819.8A Expired - Fee Related CN104968783B (zh) | 2012-10-15 | 2013-10-15 | 用于调节c9orf72表达的组合物 |
| CN201911095323.2A Pending CN110951731A (zh) | 2012-10-15 | 2013-10-15 | 用于调节c9orf72表达的组合物 |
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| CN201380053819.8A Expired - Fee Related CN104968783B (zh) | 2012-10-15 | 2013-10-15 | 用于调节c9orf72表达的组合物 |
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Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG171914A1 (en) | 2008-12-02 | 2011-07-28 | Chiralgen Ltd | Method for the synthesis of phosphorus atom modified nucleic acids |
| IN2012DN00720A (enExample) | 2009-07-06 | 2015-06-19 | Ontorii Inc | |
| WO2012039448A1 (ja) | 2010-09-24 | 2012-03-29 | 株式会社キラルジェン | 不斉補助基 |
| MX347361B (es) | 2011-07-19 | 2017-04-12 | Wave Life Sciences Ltd | Metodos para la sintesis de acidos nucleicos funcionalizados. |
| EP2872485B1 (en) | 2012-07-13 | 2020-12-16 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| AU2013331434B2 (en) * | 2012-10-15 | 2019-08-08 | Ionis Pharmaceuticals, Inc. | Compositions for modulating C90RF72 expression |
| WO2014062686A1 (en) | 2012-10-15 | 2014-04-24 | Isis Pharmaceuticals, Inc. | Methods for modulating c9orf72 expression |
| WO2014062736A1 (en) | 2012-10-15 | 2014-04-24 | Isis Pharmaceuticals, Inc. | Methods for monitoring c9orf72 expression |
| RS59283B1 (sr) * | 2013-01-22 | 2019-10-31 | Deutsches Zentrum Fuer Neurodegenerative Erkrankungen E V | Proteini sa dipeptidnim ponovkom kao terapeutsko ciljno mesto kod neurodegenerativnih bolesti sa ekspanzijom heksanukleotidnog ponovka |
| RU2748426C2 (ru) * | 2013-10-11 | 2021-05-25 | Ионис Фармасьютикалз, Инк. | Композиции для модуляции экспрессии c90rf72 |
| US11162096B2 (en) | 2013-10-14 | 2021-11-02 | Ionis Pharmaceuticals, Inc | Methods for modulating expression of C9ORF72 antisense transcript |
| CN106068325B (zh) | 2014-01-16 | 2021-07-09 | 波涛生命科学有限公司 | 手性设计 |
| EP4410805A3 (en) | 2014-03-18 | 2024-11-27 | University of Massachusetts | Raav-based compositions and methods for treating amyotrophic lateral sclerosis |
| US10006027B2 (en) | 2014-03-19 | 2018-06-26 | Ionis Pharmaceuticals, Inc. | Methods for modulating Ataxin 2 expression |
| PL3119888T3 (pl) | 2014-03-19 | 2021-12-20 | Ionis Pharmaceuticals, Inc. | Kompozycje do modulacji ekspresji ataksyny 2 |
| WO2016024205A1 (en) * | 2014-08-15 | 2016-02-18 | Pfizer Inc. | Oligomers targeting hexanucleotide repeat expansion in human c9orf72 gene |
| WO2016060919A1 (en) * | 2014-10-14 | 2016-04-21 | The Board Of Regents Of The University Of Texas System | Allele selective inhibition of mutant c9orf72 foci expression by duplex rnas targeting the expanded hexanucleotide repeat |
| WO2016112132A1 (en) * | 2015-01-06 | 2016-07-14 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
| EP3722424A1 (en) | 2015-04-16 | 2020-10-14 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
| WO2016167780A1 (en) * | 2015-04-16 | 2016-10-20 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
| BR112017028194B1 (pt) * | 2015-07-10 | 2023-03-14 | Ionis Pharmaceuticals, Inc | Composto oligomérico modulador de diaciglicerol aciltransferase 2 (dgat2), composição, e seus usos |
| EP3359667A1 (en) * | 2015-10-05 | 2018-08-15 | ProQR Therapeutics II B.V. | Use of single-stranded antisense oligonucleotide in prevention or treatment of genetic diseases involving a trinucleotide repeat expansion |
| US11260073B2 (en) | 2015-11-02 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating C90RF72 |
| AU2016381174A1 (en) | 2015-12-31 | 2018-05-31 | Ionis Pharmaceuticals, Inc. | Methods for reducing Ataxin-2 expression |
| CA3017532A1 (en) | 2016-04-13 | 2017-10-19 | Ionis Pharmaceuticals, Inc. | Methods for reducing c9orf72 expression |
| EP3518667B1 (en) * | 2016-09-30 | 2024-10-30 | Regeneron Pharmaceuticals, Inc. | Rodents having a hexanucleotide repeat expansion in a c9orf72 locus |
| CN110177544A (zh) | 2016-11-29 | 2019-08-27 | 普尔泰克健康有限公司 | 用于递送治疗剂的外泌体 |
| EP3622073A4 (en) | 2017-05-09 | 2021-01-06 | University of Massachusetts | Methods of treating amyotrophic lateral sclerosis (als) |
| US11179411B2 (en) * | 2017-05-18 | 2021-11-23 | Kyoto University | Composition for prevention or treatment of spinocerebellar ataxia type 36 |
| WO2019060686A1 (en) | 2017-09-22 | 2019-03-28 | University Of Massachusetts | NEW DUAL EXPRESSION VECTORS OF SOD1 AND USES THEREOF |
| US10905707B2 (en) | 2017-11-10 | 2021-02-02 | University Of Massachusetts | Compositions and methods for the treatment of expanded repeat-associated disorders |
| EP3826645A4 (en) | 2018-07-25 | 2023-05-17 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR REDUCING ATXN2 EXPRESSION |
| EP3850098A1 (en) * | 2018-09-12 | 2021-07-21 | uniQure IP B.V. | Rnai induced c9orf72 suppression for the treatment of als/ftd |
| CA3121749A1 (en) | 2018-12-06 | 2020-06-11 | Biogen Ma Inc. | Neurofilament protein for guiding therapeutic intervention in amyotrophic lateral sclerosis |
| WO2020205605A2 (en) * | 2019-03-29 | 2020-10-08 | University Of Massachusetts | OLIGONUCLEOTIDE-BASED MODULATION OF C9orf72 |
| CN114072501A (zh) | 2019-05-06 | 2022-02-18 | 马萨诸塞大学 | 抗c9orf72寡核苷酸及相关方法 |
| EP4125930A4 (en) * | 2020-03-27 | 2025-06-04 | University Of Massachusetts | Dual-acting siRNA-based modulation of C9ORF72 |
| EP4165185A4 (en) * | 2020-06-11 | 2025-09-10 | Genetic Intelligence Inc New York Ny | FLCN GENE MODULATION COMPOSITIONS AND RELATED METHODS |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102076852A (zh) * | 2007-11-09 | 2011-05-25 | Isis药物公司 | 因子7表达的调节 |
| WO2011133923A1 (en) * | 2010-04-23 | 2011-10-27 | Isis Pharmaceuticals, Inc. | Modulation of lactosylceramide synthase (lcs) expression |
| WO2011135396A1 (en) * | 2010-04-30 | 2011-11-03 | Cellectis | Method for modulating double-strand break-induced homologous recombination |
Family Cites Families (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6582908B2 (en) | 1990-12-06 | 2003-06-24 | Affymetrix, Inc. | Oligonucleotides |
| DK0618925T4 (da) | 1991-12-24 | 2012-07-09 | Isis Pharmaceuticals Inc | Antisense-oligonukleotider |
| US5801154A (en) | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US5681940A (en) | 1994-11-02 | 1997-10-28 | Icn Pharmaceuticals | Sugar modified nucleosides and oligonucleotides |
| 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 |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| WO1999014226A2 (en) | 1997-09-12 | 1999-03-25 | Exiqon A/S | Bi- and tri-cyclic nucleoside, nucleotide and oligonucleotide analogues |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| 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 |
| US5998148A (en) | 1999-04-08 | 1999-12-07 | Isis Pharmaceuticals Inc. | Antisense modulation of microtubule-associated protein 4 expression |
| CN102180924A (zh) | 1999-05-04 | 2011-09-14 | 桑塔里斯制药公司 | L-核糖-lna类似物 |
| US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| USH2191H1 (en) * | 2000-10-24 | 2007-06-05 | Snp Consortium | Identification and mapping of single nucleotide polymorphisms in the human genome |
| US20050019915A1 (en) | 2001-06-21 | 2005-01-27 | Bennett C. Frank | Antisense modulation of superoxide dismutase 1, soluble expression |
| JP2005504020A (ja) | 2001-07-03 | 2005-02-10 | 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 | ヌクレアーゼ耐性キメラオリゴヌクレオチド |
| WO2004044136A2 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2’-modified nucleosides for 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 |
| EP1560931B1 (en) | 2002-11-14 | 2011-07-27 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
| US7250496B2 (en) | 2002-11-14 | 2007-07-31 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
| US7790867B2 (en) | 2002-12-05 | 2010-09-07 | Rosetta Genomics Inc. | Vaccinia virus-related nucleic acids and microRNA |
| WO2004106356A1 (en) | 2003-05-27 | 2004-12-09 | Syddansk Universitet | Functionalized nucleotide derivatives |
| ATE555118T1 (de) | 2003-08-28 | 2012-05-15 | Takeshi Imanishi | Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung |
| 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 |
| US20050261233A1 (en) * | 2004-04-21 | 2005-11-24 | Sanjay Bhanot | Modulation of glucose-6-phosphatase translocase expression |
| EP1752536A4 (en) | 2004-05-11 | 2008-04-16 | Alphagen Co Ltd | POLYNUCLEOTIDE CAUSING RNA INTERFERENCE AND METHOD OF REGULATING GENE EXPRESSION WITH THE USE OF THE SAME |
| AU2004320622B2 (en) * | 2004-06-03 | 2012-06-14 | Isis Pharmaceuticals, Inc. | Chimeric gapped oligomeric compositions |
| US20090291437A1 (en) | 2005-11-02 | 2009-11-26 | O'brien Sean | Methods for targeting quadruplex sequences |
| EP2161038B1 (en) | 2006-01-26 | 2013-12-25 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to Huntingtin |
| JP5342881B2 (ja) | 2006-01-27 | 2013-11-13 | 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 | ６−修飾された二環式核酸類似体 |
| EP2505646A1 (en) | 2006-05-05 | 2012-10-03 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of CRP |
| US7547684B2 (en) | 2006-05-11 | 2009-06-16 | Isis Pharmaceuticals, Inc. | 5′-modified bicyclic nucleic acid analogs |
| CA2666191C (en) | 2006-10-09 | 2017-07-11 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of pcsk9 |
| CN102604951A (zh) * | 2006-12-14 | 2012-07-25 | 诺瓦提斯公司 | 治疗肌肉和心血管病症的组合物和方法 |
| WO2008101157A1 (en) | 2007-02-15 | 2008-08-21 | Isis Pharmaceuticals, Inc. | 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom |
| EP2170917B1 (en) | 2007-05-30 | 2012-06-27 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
| EP2173760B2 (en) | 2007-06-08 | 2015-11-04 | Isis Pharmaceuticals, Inc. | Carbocyclic bicyclic nucleic acid analogs |
| DE602007005629D1 (de) * | 2007-06-18 | 2010-05-12 | Commissariat Energie Atomique | Reversibles siRNA-Silencing eines mutierten und endogenen Huntington-Wildtypgens und dessen Anwendung zur Behandlung von Morbus Huntington |
| CA2692579C (en) | 2007-07-05 | 2016-05-03 | Isis Pharmaceuticals, Inc. | 6-disubstituted bicyclic nucleic acid analogs |
| US20090123928A1 (en) | 2007-10-11 | 2009-05-14 | The Johns Hopkins University | Genomic Landscapes of Human Breast and Colorectal Cancers |
| US20110152346A1 (en) | 2007-11-05 | 2011-06-23 | Baltic Technology Development Ltd. | Use of Oligonucleotides with Modified Bases in Hybridization of Nucleic Acids |
| WO2009067647A1 (en) | 2007-11-21 | 2009-05-28 | Isis Pharmaceuticals, Inc. | Carbocyclic alpha-l-bicyclic nucleic acid analogs |
| EP2265627A2 (en) | 2008-02-07 | 2010-12-29 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexitol nucleic acid analogs |
| WO2010036698A1 (en) | 2008-09-24 | 2010-04-01 | Isis Pharmaceuticals, Inc. | Substituted alpha-l-bicyclic nucleosides |
| WO2010120820A1 (en) | 2009-04-13 | 2010-10-21 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulation of smn2 splicing |
| EP2451476A4 (en) | 2009-07-06 | 2013-07-03 | Alnylam Pharmaceuticals Inc | BIOTRAITEMENT BASED ON CELLS |
| EP2462153B1 (en) | 2009-08-06 | 2015-07-29 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
| WO2012005898A2 (en) | 2010-06-15 | 2012-01-12 | Alnylam Pharmaceuticals, Inc. | Chinese hamster ovary (cho) cell transcriptome, corresponding sirnas and uses thereof |
| AU2011282243B2 (en) | 2010-07-19 | 2016-09-22 | Ionis Pharmaceuticals, Inc. | Modulation of nuclear-retained RNA |
| EP2655621B1 (en) | 2010-12-20 | 2018-05-23 | The General Hospital Corporation | Polycomb-associated non-coding rnas |
| WO2012092367A1 (en) | 2010-12-28 | 2012-07-05 | University Of Rochester | Nucleic acid binding compounds, methods of making, and use thereof |
| PE20142463A1 (es) | 2011-04-01 | 2015-01-22 | Isis Pharmaceuticals Inc | Modulacion de la expresion del transductor de senales y activador de la transcripcion 3 (stat3) |
| ES2856266T3 (es) | 2011-04-21 | 2021-09-27 | Glaxo Group Ltd | Modulación de la expresión del virus de la hepatitis B (VHB) |
| EP2751284B1 (en) | 2011-08-31 | 2017-01-11 | The University Of Manchester | Method for diagnosing a neurodegenerative disease. |
| US20140255936A1 (en) * | 2011-09-09 | 2014-09-11 | Mayo Foundation For Medical Education And Research | Detecting frontotemporal dementia and amyotrophic lateral sclerosis |
| US20130157885A1 (en) | 2011-11-17 | 2013-06-20 | Rheonix, Inc. | System and methods for selective molecular analysis |
| JP6317675B2 (ja) * | 2011-11-30 | 2018-04-25 | サレプタ セラピューティクス， インコーポレイテッド | 延長リピート病を処置するためのオリゴヌクレオチド |
| US9725716B2 (en) | 2011-12-06 | 2017-08-08 | Ohio State Innovation Foundation and Research Institute at Nationwide Children's Hospital | Non-ionic, low osmolar contrast agents for delivery of antisense oligonucleotides and treatment of disease |
| HRP20171254T1 (hr) * | 2012-04-23 | 2018-01-12 | Biomarin Technologies B.V. | Oligonukleotidi koji moduliraju rnk s poboljšanim karakteristikama za liječenje neuromišićnih poremećaja |
| AU2013262709A1 (en) | 2012-05-16 | 2015-01-22 | Rana Therapeutics, Inc. | Compositions and methods for modulating MECP2 expression |
| WO2014062736A1 (en) | 2012-10-15 | 2014-04-24 | Isis Pharmaceuticals, Inc. | Methods for monitoring c9orf72 expression |
| WO2014062686A1 (en) | 2012-10-15 | 2014-04-24 | Isis Pharmaceuticals, Inc. | Methods for modulating c9orf72 expression |
| AU2013331434B2 (en) | 2012-10-15 | 2019-08-08 | Ionis Pharmaceuticals, Inc. | Compositions for modulating C90RF72 expression |
| RS59283B1 (sr) | 2013-01-22 | 2019-10-31 | Deutsches Zentrum Fuer Neurodegenerative Erkrankungen E V | Proteini sa dipeptidnim ponovkom kao terapeutsko ciljno mesto kod neurodegenerativnih bolesti sa ekspanzijom heksanukleotidnog ponovka |
| RU2748426C2 (ru) | 2013-10-11 | 2021-05-25 | Ионис Фармасьютикалз, Инк. | Композиции для модуляции экспрессии c90rf72 |
| DE102014204360A1 (de) | 2014-03-10 | 2015-09-10 | Ford Global Technologies, Llc | Verfahren sowie Vorrichtung zur Abschätzung des Abstandes eines in Bewegung befindlichen Fahrzeuges von einem Objekt |
| WO2016024205A1 (en) | 2014-08-15 | 2016-02-18 | Pfizer Inc. | Oligomers targeting hexanucleotide repeat expansion in human c9orf72 gene |
| WO2016050822A2 (en) | 2014-09-30 | 2016-04-07 | Neurimmune Holding Ag | Human-derived anti-dipeptide repeats (dprs) antibody |
| WO2016060919A1 (en) | 2014-10-14 | 2016-04-21 | The Board Of Regents Of The University Of Texas System | Allele selective inhibition of mutant c9orf72 foci expression by duplex rnas targeting the expanded hexanucleotide repeat |
| EP3722424A1 (en) | 2015-04-16 | 2020-10-14 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
| US11260073B2 (en) | 2015-11-02 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating C90RF72 |
| CA3017532A1 (en) | 2016-04-13 | 2017-10-19 | Ionis Pharmaceuticals, Inc. | Methods for reducing c9orf72 expression |
| EP3518667B1 (en) | 2016-09-30 | 2024-10-30 | Regeneron Pharmaceuticals, Inc. | Rodents having a hexanucleotide repeat expansion in a c9orf72 locus |
| BR112020008937A2 (pt) * | 2017-11-08 | 2020-10-20 | Ionis Pharmaceuticals, Inc. | oligonucleotídeos conjugados a uma porção de ligante do receptor glp-1 e seus usos |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102076852A (zh) * | 2007-11-09 | 2011-05-25 | Isis药物公司 | 因子7表达的调节 |
| WO2011133923A1 (en) * | 2010-04-23 | 2011-10-27 | Isis Pharmaceuticals, Inc. | Modulation of lactosylceramide synthase (lcs) expression |
| WO2011135396A1 (en) * | 2010-04-30 | 2011-11-03 | Cellectis | Method for modulating double-strand break-induced homologous recombination |
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