DK2534248T3 - Selektiv reduktion af allelvarianter - Google Patents

Selektiv reduktion af allelvarianter Download PDF

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DK2534248T3
DK2534248T3 DK11740542.3T DK11740542T DK2534248T3 DK 2534248 T3 DK2534248 T3 DK 2534248T3 DK 11740542 T DK11740542 T DK 11740542T DK 2534248 T3 DK2534248 T3 DK 2534248T3
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wing
oligonucleotide
certain embodiments
modified
disease
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C Frank Bennett
Susan M Freier
Sarah Greenlee
Eric E Swayze
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Ionis Pharmaceuticals Inc
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Claims (12)

1. Modificeret antisense-oligonukleotid til anvendelse i behandling, forebyggelse eller lindring af en sygdom, hvor sygdommen er forårsaget af ekspressionen af en mutant-allel indeholdende en enkeltnukleotidpolymorfisme og hvor det modificerede antisense-oligonukleotid selektivt reducerer ekspressionen af mutantallelen, hvor det modificerede antisense-oligonukleotid består af 15 til 20 bundne nukleosider målrettet til et enkeltnukleotidpolymorfisme-sted på mutantallelen der er associeret med sygdommen og i stand til selektivt at reducere ekspressionen af mutantallelen, hvor det modificerede oligonukleotid er 100% komplementært til enkeltnukleotidpolymorfisme-stedet lokaliseret på den mutantallelen, hvor det modificerede oligonukleotid er enkelt-strenget og omfatter et wing-gap-wing-motiv med en 5' wing region positioneret ved 5'-enden af et deoxynukleosid-gap, og en 3' wing region positioneret ved 3'-enden af deoxynukleosid-gapet, hvor hver af nukleosiderne af hver wing-region omfatter et modificeret sukker eller sukkersurrogat, hvor wing-gap-wing-motivet er en hvilket som helst af gruppen bestående af 5-10-5, 2-9-6, 3-9-3, 3-9-4, 3-9-5, 4-7-4, 4-9-3, 4-9-4, 4-9-5, 4-10-5, 4-11-4, 4-11-5, 5-7-5, 5-8-6, 5-9-3, 5-9-5, 5-10-4, 6-7-6, 6-8-5, og 6-9-2, og hvor enkeltnukleosidpolymorfismen annealerer til en nukleobase inde i gap-segmentet, og hvor position 4, 5, eller 6 af det modificerede oligonukleotid, som talt fra 5'-terminus af gap'et, annealerer med enkeltnukleotidpolymorfismen.
2. Oligonukleotidet til anvendelse ifølge krav 1, hvor sygdommen er valgt fra gruppen bestående af Alzheimer's sygdom, Creutzfeldt-Jakob sygdom, fatal familiær søvnløshed, Alexander sygdom, Parkinson's sygdom, amyotrof lateral sclerose, dentato-rubral og pallido-luysian atrofi DRPA, spino-cerebellar ataxi, Torsion dystoni, myokardiopati, kronisk obstruktiv pulmonær sygdom (COPD), leversygdom, hepatocellulær carcinom, systemisk lupus erythematosus, hypercholesterolæmi, brystcancer, astma, Type 1 diabetes, Rheumatoid arthritis, Graves sygdom, SLE, spinal- og bulbær muskulær atrofi, Kennedy's sygdom, progressiv childhood posterior subkapsulært katarakt, cholesterolgaldestensygdom, arthrosclerose, kardiovaskulær sygdom, primær hypercalciuria, alfa-thallasæmi, obsessiv compulsiv sygdom, angst, comorbid depression, kongenitale visuelle defekter, hypertension, metabolisk syndrom, prostatacancer, kongenital myasthenisk syndrom, perifer arteriel sygdom, atrial fibrillation, sporadisk pheochromocytoma, kongenital misdannelser, Machado-Joseph sygdom, Huntington's sygdom, og Autosomal Dominant Retinitis Pigmentosa sygdom.
3. Oligonukleotidet til anvendelse ifølge krav 1, hvor sygdommen er Huntington's sygdom og enkeltnukleotidpolymorfisme-stedet er på en mutant allel der er associeret med Huntington's sygdom.
4. Oligonukleotidet til anvendelse ifølge et hvilket som helst af de foregående krav, hvor enkeltnukleotidpolymorfisme-stedet indeholder en differentierings-polymorfisme.
5. Oligonukleotidet til anvendelse ifølge et hvilket som helst af de foregående krav, hvor det modificerede antisense-oligonukleotid består af 15 til 19 bundne nukleosider.
6. Oligonukleotidet til anvendelse ifølge et hvilket som helst af de foregående krav, hvor wing-gap-wing-motivet er et hvilket som helst fra gruppen bestående af 2-9-6, 4-9-5, og 4-11-4.
7. Oligonukleotidet til anvendelse ifølge et hvilket som helst af de foregående krav, hvor det modificerede sukker eller sukkersurrogat er en 2'-O-methoxyethyl-modificeret sukker.
8. Oligonukleotidet til anvendelse ifølge et hvilket som helst af kravene 1-6, hvor mindst én af wing-regionerne omfatter et 4'- til 2'-bicyklisk nukleosid og mindst ét af de tilbageværende wing-nukleosider er et ikke-bicyklisk 2'-modificeret nukleosid, fx et 2'-O-methoxyethylnucleosid.
9. Oligonukleotidet til anvendelse ifølge krav 8, hvor det 4'- til 2'-bicykliske nukleosid er et 4'-CH(CH3)-O-2'-bicyclisk nukleosid.
10. Oligonukleotidet til anvendelse ifølge et hvilket som helst af de foregående krav, hvor mindst én internukleosidbinding er en modificeret internukleosid-binding, eller hver internukleosidbinding er en phosphorthioat-internukleosid-binding.
11. Oligonukleotidet til anvendelse ifølge et hvilket som helst af de foregående krav, hvor mindst ét nukleosid omfatter en modificeret nukleobase, fx 5'-methylcytosin.
12. Oligonukleotidet til anvendelse ifølge et hvilket som helst af de foregående krav, hvor oligonukleotidet anvendes i en farmaceutisk sammensætning ved at kombinere oligonukleotidet og et farmaceutisk acceptabelt fortyndingsmiddel eller bærer.
DK11740542.3T 2010-02-08 2011-02-08 Selektiv reduktion af allelvarianter DK2534248T3 (da)

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US37163510P 2010-08-06 2010-08-06
PCT/US2011/024103 WO2011097643A1 (en) 2010-02-08 2011-02-08 Selective reduction of allelic variants

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EP (3) EP3321361B1 (da)
JP (4) JP6006120B2 (da)
AU (3) AU2011213562B2 (da)
CA (1) CA2789005A1 (da)
DK (1) DK2534248T3 (da)
ES (1) ES2733708T3 (da)
IL (2) IL221272A (da)
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Publication number Priority date Publication date Assignee Title
US9394333B2 (en) 2008-12-02 2016-07-19 Wave Life Sciences Japan Method for the synthesis of phosphorus atom modified nucleic acids
WO2011005761A1 (en) 2009-07-06 2011-01-13 Ontorii, Inc Novel nucleic acid prodrugs and methods use thereof
WO2012039448A1 (ja) 2010-09-24 2012-03-29 株式会社キラルジェン 不斉補助基
WO2012109395A1 (en) * 2011-02-08 2012-08-16 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
RU2014105311A (ru) 2011-07-19 2015-08-27 Уэйв Лайф Сайенсес Пте. Лтд. Способы синтеза функционализованных нуклеиновых кислот
DK2742136T3 (da) 2011-08-11 2017-11-20 Ionis Pharmaceuticals Inc Gapmerforbindelser omfattende 5'-modificerede deoxyribonukleosider i gap og anvendelser deraf
US20150315595A1 (en) * 2012-03-12 2015-11-05 Santaris Pharma A/S Compositions and Methods for Modulation of ATXN3 Expression
EP2831232A4 (en) 2012-03-30 2015-11-04 Univ Washington METHODS OF MODULATING THE EXPRESSION OF TAU TO REDUCE THE STROKE AND MODIFY A NEURODEGENERATIVE SYMPTOM
EP2839006B1 (en) * 2012-04-20 2018-01-03 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
RU2015104762A (ru) 2012-07-13 2018-08-31 Уэйв Лайф Сайенсес Лтд. Хиральный контроль
MX356830B (es) 2012-07-13 2018-06-15 Shin Nippon Biomedical Laboratories Ltd Adyuvante de acido nucleico quiral.
CN104684893B (zh) 2012-07-13 2016-10-26 日本波涛生命科学公司 不对称辅助基团
EP2906699A4 (en) 2012-10-11 2016-06-08 Ionis Pharmaceuticals Inc OLIGOMER COMPOUNDS WITH BICYCLIC NUCLEOSIDES AND USES THEREOF
EP3459549B1 (en) * 2012-10-12 2022-04-06 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
US9909128B2 (en) * 2012-11-15 2018-03-06 The Regents Of The University Of California Splice modulating oligonucleotides that inhibit cancer
EP2951304B1 (en) 2013-02-04 2020-07-08 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
ES2807379T3 (es) * 2013-03-14 2021-02-22 Ionis Pharmaceuticals Inc Composiciones y métodos para regular la expresión de Tau
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
EP3095459A4 (en) 2014-01-15 2017-08-23 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having antitumor effect and antitumor agent
US10322173B2 (en) 2014-01-15 2019-06-18 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent
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
ES2917473T3 (es) 2014-01-16 2022-07-08 Wave Life Sciences Ltd Diseño quiral
GB201410693D0 (en) 2014-06-16 2014-07-30 Univ Southampton Splicing modulation
SG11201702682PA (en) 2014-10-03 2017-04-27 Cold Spring Harbor Lab Targeted augmentation of nuclear gene output
MA43072A (fr) 2015-07-22 2018-05-30 Wave Life Sciences Ltd Compositions d'oligonucléotides et procédés associés
EP4285912A2 (en) 2015-09-25 2023-12-06 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating ataxin 3 expression
KR102422625B1 (ko) 2015-10-09 2022-07-20 유니버시티 오브 사우스앰톤 유전자 발현의 조절 및 탈조절된 단백질 발현의 스크리닝
EP3377629B1 (en) 2015-11-18 2023-07-05 Rosalind Franklin University of Medicine and Science Antisense compounds targeting leucine-rich repeat kinase 2 (lrrk2) for the treatment of parkinsons disease
US10370667B2 (en) 2015-11-18 2019-08-06 Rosalind Franklin University Of Medicine And Science Antisense compounds targeting leucine-rich repeat kinase 2 (LRRK2) for the treatment of parkinsons disease
PT3386511T (pt) 2015-12-10 2021-07-14 Ptc Therapeutics Inc Métodos para tratamento da doença de huntington
US11096956B2 (en) 2015-12-14 2021-08-24 Stoke Therapeutics, Inc. Antisense oligomers and uses thereof
SG11201804443UA (en) 2015-12-14 2018-06-28 Cold Spring Harbor Laboratory Antisense oligomers for treatment of autosomal dominant mental retardation-5 and dravet syndrome
US10478503B2 (en) 2016-01-31 2019-11-19 University Of Massachusetts Branched oligonucleotides
MA45270A (fr) * 2016-05-04 2017-11-09 Wave Life Sciences Ltd Compositions d'oligonucléotides et procédés associés
JOP20190065A1 (ar) 2016-09-29 2019-03-28 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن tau
JOP20190104A1 (ar) * 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
EP3548005A4 (en) 2016-11-29 2020-06-17 Puretech Health LLC EXOSOMES FOR THE ADMINISTRATION OF THERAPEUTIC AGENTS
WO2018226622A1 (en) 2017-06-05 2018-12-13 Ptc Therapeutics, Inc. Compounds for treating huntington's disease
MX2019015580A (es) 2017-06-28 2020-07-28 Ptc Therapeutics Inc Metodos para tratar la enfermedad de huntington.
CA3067591A1 (en) 2017-06-28 2019-01-03 Ptc Therapeutics, Inc. Methods for treating huntington's disease
JP6827148B2 (ja) 2017-08-25 2021-02-10 ストーク セラピューティクス，インク． 状態および疾患の処置のためのアンチセンスオリゴマー
CA3094703A1 (en) 2018-03-27 2019-10-03 Ptc Therapeutics, Inc. Compounds for treating huntington's disease
UY38225A (es) 2018-05-09 2019-11-29 Ionis Pharmaceuticals Inc Compuestos y métodos para reducir de la expresión de atxn3
SG11202012674PA (en) 2018-06-27 2021-01-28 Ptc Therapeutics Inc Heterocyclic and heteroaryl compounds for treating huntington's disease
EP3833763A4 (en) 2018-08-10 2023-07-19 University of Massachusetts MODIFIED OLIGONUCLEOTIDES TARGETING SNPs
WO2020198509A2 (en) 2019-03-26 2020-10-01 University Of Massachusetts Modified oligonucleotides with increased stability
CN114502730A (zh) * 2019-08-09 2022-05-13 马萨诸塞大学 经化学修饰的靶向snp的寡核苷酸
BR112022007947A2 (pt) 2019-11-01 2022-07-12 Novartis Ag Uso de modulador de splicing para tratamento que retarda a progressão da doença de huntington
WO2021178374A2 (en) * 2020-03-05 2021-09-10 Synerk Inc. Compounds and methods for reducing apoe expression
WO2021231107A1 (en) 2020-05-11 2021-11-18 Stoke Therapeutics, Inc. Opa1 antisense oligomers for treatment of conditions and diseases
CA3212650A1 (en) * 2021-03-08 2022-09-15 Les Laboratoires Servier Antisense oligonucleotides for inhibiting alpha-synuclein expression
TW202304446A (zh) 2021-03-29 2023-02-01 瑞士商諾華公司 剪接調節子用於減慢杭丁頓氏舞蹈症進展的治療之用途

Family Cites Families (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2699808A (en) 1944-10-06 1955-01-18 Mark W Lowe Apparatus for peeling tomatoes
US2699508A (en) 1951-12-21 1955-01-11 Selectronics Inc Method of mounting and construction of mounting for low frequency piezoelectric crystals
US6582908B2 (en) 1990-12-06 2003-06-24 Affymetrix, Inc. Oligonucleotides
WO1994014226A1 (en) 1992-12-14 1994-06-23 Honeywell Inc. Motor system with individually controlled redundant windings
US5801154A (en) 1993-10-18 1998-09-01 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of multidrug resistance-associated protein
US5656408A (en) 1996-04-29 1997-08-12 Xerox Corporation Coated carrier particles
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
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
WO1999014226A2 (en) 1997-09-12 1999-03-25 Exiqon A/S Bi- and tri-cyclic nucleoside, nucleotide and 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
WO2000052210A2 (en) 1999-03-01 2000-09-08 Variagenics, Inc. Methods for targeting rna molecules
US6753422B2 (en) 1999-03-01 2004-06-22 O'brien Thomas G. Odc allelic analysis method for assessing carcinogenic susceptibility
DK1178999T3 (da) 1999-05-04 2007-08-06 Santaris Pharma As L-RIBO-LNA-analoger
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
WO2001079283A1 (en) 2000-04-13 2001-10-25 University Of British Columbia Modulating cell survival by modulating huntingtin function
CA2452458A1 (en) 2001-07-03 2003-01-16 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
WO2003013437A2 (en) 2001-08-07 2003-02-20 University Of Delaware Compositions and methods for the prevention and treatment of huntington's disease
US20050096284A1 (en) * 2002-02-20 2005-05-05 Sirna Therapeutics, Inc. RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA)
CA2504929C (en) 2002-11-05 2014-07-22 Charles Allerson Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
US7696345B2 (en) 2002-11-05 2010-04-13 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP2314691A3 (en) 2002-11-14 2012-01-18 Dharmacon, Inc. Fuctional and hyperfunctional siRNA
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
JP4731324B2 (ja) 2003-08-28 2011-07-20 武 今西 Ｎ−ｏ結合性架橋構造型新規人工核酸
ES2485848T3 (es) * 2003-09-12 2014-08-14 University Of Massachusetts ARN de interferencia para el tratamiento de trastornos relacionados con la ganancia de función
EP1677822B1 (en) 2003-09-18 2014-04-23 Isis Pharmaceuticals, Inc. 4'-thionucleosides and oligomeric compounds
AU2005252663B2 (en) * 2004-06-03 2011-07-07 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
EP2397563A3 (en) 2004-09-17 2012-07-18 Isis Pharmaceuticals, Inc. Enhanced antisense oligonucleotides
EP2316967A1 (en) * 2005-06-28 2011-05-04 Medtronic, Inc. Methods and sequences to preferentially suppress expression of mutated huntingtin gene.
SI2161038T1 (sl) 2006-01-26 2014-05-30 Isis Pharmaceuticals, Inc. Sestavki in njihove uporabe, usmerjeni proti huntingtinu
DE602007009487D1 (de) 2006-01-27 2010-11-11 Isis Pharmaceutical Inc 6-modifizierte bicyclische nukleinsäureanaloga
EP2015758B1 (en) 2006-05-05 2014-04-02 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression apob
CN101490074B (zh) 2006-05-11 2013-06-26 Isis制药公司 5’-修饰的双环核酸类似物
US9273356B2 (en) 2006-05-24 2016-03-01 Medtronic, Inc. Methods and kits for linking polymorphic sequences to expanded repeat mutations
EP2046993A4 (en) * 2006-07-07 2010-11-17 Univ Massachusetts RNA INTERFERENCE COMPOSITIONS AND METHOD FOR TREATING MORBUS HUNTINGTON
ES2526295T5 (es) 2006-10-18 2021-05-04 Ionis Pharmaceuticals Inc Compuestos antisentido
EP2102340A2 (en) * 2006-11-27 2009-09-23 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8093222B2 (en) * 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
EP2125852B1 (en) 2007-02-15 2016-04-06 Ionis Pharmaceuticals, Inc. 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom
WO2008143774A2 (en) 2007-05-01 2008-11-27 University Of Massachusetts Methods and compositions for locating snp heterozygosity for allele specific diagnosis and therapy
CA2688321A1 (en) 2007-05-30 2008-12-11 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
ATE462787T1 (de) 2007-06-18 2010-04-15 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
WO2009135322A1 (en) 2008-05-09 2009-11-12 The Universtity Of British Columbia Methods and compositions for the treatment of huntington's disease
US8987435B2 (en) 2008-10-24 2015-03-24 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
AT507215B1 (de) 2009-01-14 2010-03-15 Boehler Edelstahl Gmbh & Co Kg Verschleissbeständiger werkstoff
AU2011213563B2 (en) * 2010-02-08 2015-12-24 Ionis Pharmaceuticals, Inc. Selective reduction of allelic variants
US9984408B1 (en) 2012-05-30 2018-05-29 Amazon Technologies, Inc. Method, medium, and system for live video cooperative shopping
US9778708B1 (en) 2016-07-18 2017-10-03 Lenovo Enterprise Solutions (Singapore) Pte. Ltd. Dual sided latching retainer for computer modules

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