CA2667055C - Antisense compounds - Google Patents
Antisense compounds Download PDFInfo
- Publication number
- CA2667055C CA2667055C CA2667055A CA2667055A CA2667055C CA 2667055 C CA2667055 C CA 2667055C CA 2667055 A CA2667055 A CA 2667055A CA 2667055 A CA2667055 A CA 2667055A CA 2667055 C CA2667055 C CA 2667055C
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- CA
- Canada
- Prior art keywords
- nucleoside
- bicyclic
- wing
- substituted
- modified
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 302
- 230000000692 anti-sense effect Effects 0.000 title description 146
- 241001465754 Metazoa Species 0.000 claims abstract description 19
- 239000002777 nucleoside Substances 0.000 claims description 246
- 125000003835 nucleoside group Chemical group 0.000 claims description 122
- 108091034117 Oligonucleotide Proteins 0.000 claims description 120
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 86
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 86
- -1 bicyclic nucleoside Chemical class 0.000 claims description 85
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 85
- 125000002619 bicyclic group Chemical group 0.000 claims description 46
- 230000014509 gene expression Effects 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 230000000295 complement effect Effects 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
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- 125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 claims description 14
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- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
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- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/315—Phosphorothioates
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12N2310/3341—5-Methylcytosine
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12N2310/341—Gapmers, i.e. of the type ===---===
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2320/00—Applications; Uses
- C12N2320/50—Methods for regulating/modulating their activity
- C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
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- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US85289406P | 2006-10-18 | 2006-10-18 | |
| US60/852,894 | 2006-10-18 | ||
| PCT/US2007/081850 WO2008049085A1 (en) | 2006-10-18 | 2007-10-18 | Antisense compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2667055A1 CA2667055A1 (en) | 2008-04-24 |
| CA2667055C true CA2667055C (en) | 2017-05-09 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2667055A Active CA2667055C (en) | 2006-10-18 | 2007-10-18 | Antisense compounds |
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| DK (3) | DK2092065T4 (OSRAM) |
| ES (3) | ES2377327T5 (OSRAM) |
| WO (1) | WO2008049085A1 (OSRAM) |
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| EP2505646A1 (en) | 2006-05-05 | 2012-10-03 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of CRP |
| JP5665317B2 (ja) * | 2006-10-18 | 2015-02-04 | 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 | アンチセンス化合物 |
| DK2149605T3 (da) * | 2007-03-22 | 2013-09-30 | Santaris Pharma As | Korte RNA antagonist forbindelser til modulering af det ønskede mRNA |
| WO2009046426A2 (en) * | 2007-10-04 | 2009-04-09 | Isis Pharmaceuticals, Inc. | Compounds and methods for improving cellular uptake of oligomeric compounds |
| US8846639B2 (en) | 2008-04-04 | 2014-09-30 | Isis Pharmaceutical, Inc. | Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity |
| AU2009305636A1 (en) | 2008-10-15 | 2010-04-22 | Ionis Pharmaceuticals, Inc. | Modulation of Factor 11 expression |
| SG171914A1 (en) | 2008-12-02 | 2011-07-28 | Chiralgen Ltd | Method for the synthesis of phosphorus atom modified nucleic acids |
| IN2012DN00720A (OSRAM) | 2009-07-06 | 2015-06-19 | Ontorii Inc | |
| DK2534248T3 (en) | 2010-02-08 | 2018-11-19 | Ionis Pharmaceuticals Inc | SELECTIVE REDUCTION OF ALLELVARIANS |
| EP2534262B1 (en) | 2010-02-08 | 2016-12-14 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| AU2011282243B2 (en) | 2010-07-19 | 2016-09-22 | Ionis Pharmaceuticals, Inc. | Modulation of nuclear-retained RNA |
| US8648053B2 (en) | 2010-10-20 | 2014-02-11 | Rosalind Franklin University Of Medicine And Science | Antisense oligonucleotides that target a cryptic splice site in Ush1c as a therapeutic for Usher syndrome |
| US9920317B2 (en) | 2010-11-12 | 2018-03-20 | The General Hospital Corporation | Polycomb-associated non-coding RNAs |
| EP3260540A1 (en) | 2010-11-12 | 2017-12-27 | The General Hospital Corporation | Polycomb-associated non-coding rnas |
| EP3521451A1 (en) | 2010-11-17 | 2019-08-07 | Ionis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| EP3467109A1 (en) | 2011-02-08 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| WO2012161806A1 (en) * | 2011-02-25 | 2012-11-29 | Isis Pharmaceuticals, Inc. | Modulation of stat3 expression |
| ES2856266T3 (es) | 2011-04-21 | 2021-09-27 | Glaxo Group Ltd | Modulación de la expresión del virus de la hepatitis B (VHB) |
| US9353371B2 (en) | 2011-05-02 | 2016-05-31 | Ionis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with usher syndrome |
| MX347361B (es) | 2011-07-19 | 2017-04-12 | Wave Life Sciences Ltd | Metodos para la sintesis de acidos nucleicos funcionalizados. |
| ES2651514T3 (es) * | 2011-08-11 | 2018-01-26 | Ionis Pharmaceuticals, Inc. | Compuestos oligoméricos gapados que comprenden deoxirribonucleósidos modificados en 5 ' -en la brecha y usos de ellos |
| EP3533873A1 (en) | 2011-09-14 | 2019-09-04 | Translate Bio MA, Inc. | Multimeric oligonucleotide compounds |
| US9243291B1 (en) * | 2011-12-01 | 2016-01-26 | Isis Pharmaceuticals, Inc. | Methods of predicting toxicity |
| EP2839008A4 (en) * | 2012-03-12 | 2015-12-02 | Roche Innovation Ct Copenhagen As | COMPOSITIONS AND METHODS FOR MODULATING ATXN3 EXPRESSION |
| EP2839006B1 (en) | 2012-04-20 | 2018-01-03 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| AU2013262709A1 (en) | 2012-05-16 | 2015-01-22 | Rana Therapeutics, Inc. | Compositions and methods for modulating MECP2 expression |
| DK2850186T3 (en) | 2012-05-16 | 2019-04-08 | Translate Bio Ma Inc | COMPOSITIONS AND PROCEDURES FOR MODULATING SMN GENFAMILY EXPRESSION |
| WO2013173605A1 (en) * | 2012-05-16 | 2013-11-21 | Rana Therapeutics, Inc. | Compositions and methods for modulating pten expression |
| US10837014B2 (en) | 2012-05-16 | 2020-11-17 | Translate Bio Ma, Inc. | Compositions and methods for modulating SMN gene family expression |
| KR20160074368A (ko) | 2012-05-16 | 2016-06-28 | 라나 테라퓨틱스, 인크. | Utrn 발현을 조절하기 위한 조성물 및 방법 |
| EP2850182A4 (en) | 2012-05-16 | 2016-01-20 | Rana Therapeutics Inc | COMPOSITIONS AND METHODS FOR MODULATING ATP2A2 GENE EXPRESSION |
| CA2873769A1 (en) | 2012-05-16 | 2013-11-21 | Rana Therapeutics Inc. | Compositions and methods for modulating hemoglobin gene family expression |
| WO2013173789A2 (en) | 2012-05-17 | 2013-11-21 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide compositions |
| US9574193B2 (en) | 2012-05-17 | 2017-02-21 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein (a) expression |
| RU2624028C2 (ru) | 2012-05-24 | 2017-06-30 | Ионис Фармасьютикалз, Инк. | Способы и композиции для модулирования экспрессии аполипопротеина (а) |
| WO2013181665A1 (en) | 2012-06-01 | 2013-12-05 | Isis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with fibronectin |
| US9487780B2 (en) | 2012-06-01 | 2016-11-08 | Ionis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with fibronectin |
| EP2872147B1 (en) | 2012-07-13 | 2022-12-21 | Wave Life Sciences Ltd. | Method for making chiral oligonucleotides |
| AU2013287630B2 (en) | 2012-07-13 | 2017-05-25 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| EP2872485B1 (en) | 2012-07-13 | 2020-12-16 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| US20150247141A1 (en) | 2012-09-14 | 2015-09-03 | Rana Therapeutics, Inc. | Multimeric oligonucleotide compounds |
| WO2014059353A2 (en) | 2012-10-11 | 2014-04-17 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleosides and uses thereof |
| EP4144845B1 (en) * | 2012-10-12 | 2024-04-24 | Ionis Pharmaceuticals, Inc. | Antisense compounds and uses thereof |
| CN104854242B (zh) * | 2012-12-05 | 2018-03-16 | 阿尔尼拉姆医药品有限公司 | PCSK9 iRNA组合物及其使用方法 |
| AU2014222150A1 (en) | 2013-03-01 | 2015-09-10 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
| PL2970974T3 (pl) * | 2013-03-14 | 2018-01-31 | Alnylam Pharmaceuticals Inc | Kompozycje komponentu C5 dopełniacza iRNA i sposoby ich zastosowania |
| PL2992098T3 (pl) | 2013-05-01 | 2019-09-30 | Ionis Pharmaceuticals, Inc. | Kompozycje i sposoby modulowania ekspresji hbv i ttr |
| TW201536329A (zh) | 2013-08-09 | 2015-10-01 | Isis Pharmaceuticals Inc | 用於調節失養性肌強直蛋白質激酶(dmpk)表現之化合物及方法 |
| US11162096B2 (en) | 2013-10-14 | 2021-11-02 | Ionis Pharmaceuticals, Inc | Methods for modulating expression of C9ORF72 antisense transcript |
| DK3077510T3 (da) | 2013-12-02 | 2020-06-08 | Ionis Pharmaceuticals Inc | Antisense-forbindelser og anvendelser deraf |
| 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 |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| 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 |
| CN106068325B (zh) | 2014-01-16 | 2021-07-09 | 波涛生命科学有限公司 | 手性设计 |
| PL3119888T3 (pl) | 2014-03-19 | 2021-12-20 | Ionis Pharmaceuticals, Inc. | Kompozycje do modulacji ekspresji ataksyny 2 |
| US10006027B2 (en) | 2014-03-19 | 2018-06-26 | Ionis Pharmaceuticals, Inc. | Methods for modulating Ataxin 2 expression |
| SG11201608109TA (en) | 2014-04-01 | 2016-10-28 | Ionis Pharmaceuticals Inc | Compositions for modulating sod-1 expression |
| PH12016502062B1 (en) | 2014-05-01 | 2023-01-27 | Ionis Pharmaceuticals Inc | Compositions and methods for modulating complement factor b expression |
| WO2015187989A1 (en) | 2014-06-04 | 2015-12-10 | Isis Pharmaceuticals, Inc. | Antisense compounds targeting apolipoprotein e receptor 2 |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| EP3760208B1 (en) | 2014-06-25 | 2024-05-29 | The General Hospital Corporation | Targeting human satellite ii (hsatii) |
| WO2016040748A1 (en) | 2014-09-12 | 2016-03-17 | Ionis Pharmaceuticals, Inc. | Compositions and methods for detection of smn protein in a subject and treatment of a subject |
| AU2015318782A1 (en) | 2014-09-18 | 2017-04-06 | The University Of British Columbia | Allele-specific therapy for Huntington Disease haplotypes |
| EP3201339A4 (en) | 2014-10-03 | 2018-09-19 | Cold Spring Harbor Laboratory | Targeted augmentation of nuclear gene output |
| CA2966044A1 (en) | 2014-10-30 | 2016-05-06 | The General Hospital Corporation | Methods for modulating atrx-dependent gene repression |
| US20180112217A1 (en) * | 2014-11-19 | 2018-04-26 | Roche Innovation Center Copenhagen A/S | Stereospecific Phosphorothioate LNA |
| JP6689279B2 (ja) * | 2014-12-16 | 2020-05-20 | 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 | キラル毒性のスクリーニング方法 |
| WO2016112132A1 (en) | 2015-01-06 | 2016-07-14 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
| US10538763B2 (en) | 2015-01-16 | 2020-01-21 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulation of DUX4 |
| PE20171766A1 (es) | 2015-02-04 | 2017-12-21 | Hoffmann La Roche | Oligomeros antisentido de tau y usos de estos |
| EP3254104B1 (en) | 2015-02-04 | 2021-08-25 | Bristol-Myers Squibb Company | Methods of selecting therapeutic molecules |
| AU2016219052B2 (en) * | 2015-02-13 | 2022-06-02 | Translate Bio Ma, Inc. | Compositions and methods for modulating RNA |
| US10758558B2 (en) | 2015-02-13 | 2020-09-01 | Translate Bio Ma, Inc. | Hybrid oligonucleotides and uses thereof |
| US11129844B2 (en) | 2015-03-03 | 2021-09-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating MECP2 expression |
| EP3271460A4 (en) | 2015-03-17 | 2019-03-13 | The General Hospital Corporation | RNA INTERACTOM OF POLYCOMB REPRESSIVE COMPLEX 1 (PRC1) |
| WO2016167780A1 (en) | 2015-04-16 | 2016-10-20 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
| MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| EP3353303B1 (en) | 2015-09-25 | 2023-08-02 | 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 |
| WO2017096395A1 (en) | 2015-12-04 | 2017-06-08 | Ionis Pharmaceuticals, Inc. | Methods of treating breast cancer |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| KR102604132B1 (ko) | 2015-12-14 | 2023-11-17 | 콜드스프링하버러보러토리 | 상염색체 우성 정신 지체 5 및 드라베 증후군의 치료를 위한 안티센스 올리고머 |
| AU2016381174A1 (en) | 2015-12-31 | 2018-05-31 | Ionis Pharmaceuticals, Inc. | Methods for reducing Ataxin-2 expression |
| WO2017120365A1 (en) | 2016-01-05 | 2017-07-13 | Ionis Pharmaceuticals, Inc. | Methods for reducing lrrk2 expression |
| JP6853537B2 (ja) | 2016-02-17 | 2021-03-31 | 国立大学法人東京工業大学 | 人工ヌクレオシド及び人工ヌクレオチド並びに人工オリゴヌクレオチド |
| US10577607B2 (en) | 2016-03-16 | 2020-03-03 | Ionis Pharmaceuticals, Inc. | Modulation of DYRK1B expression |
| EP3429690A4 (en) | 2016-03-16 | 2019-10-23 | Ionis Pharmaceuticals, Inc. | METHOD FOR MODULATING KEAP1 |
| MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| US11236339B2 (en) | 2016-06-17 | 2022-02-01 | Ionis Pharmaceuticals, Inc. | Modulation of GYS1 expression |
| 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 |
| US20180028554A1 (en) * | 2016-07-05 | 2018-02-01 | Biomarin Technologies B.V. | Oligomers Having Bicyclic Scaffold Moeities |
| US11118179B2 (en) | 2016-09-23 | 2021-09-14 | Synthena Ag | Mixed tricyclo-DNA, 2′-modified RNA oligonucleotide compositions and uses thereof |
| WO2018055577A1 (en) * | 2016-09-23 | 2018-03-29 | Synthena Ag | Mixed tricyclo-dna, 2'-modified rna oligonucleotide compositions and uses thereof |
| 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 |
| JOP20190104A1 (ar) | 2016-11-10 | 2019-05-07 | Ionis Pharmaceuticals Inc | مركبات وطرق لتقليل التعبير عن atxn3 |
| 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 |
| US11033570B2 (en) | 2016-12-02 | 2021-06-15 | Cold Spring Harbor Laboratory | Modulation of Lnc05 expression |
| EP3584319A4 (en) | 2017-02-06 | 2021-04-14 | Nissan Chemical Corporation | SINGLE-STRAND OLIGONUCLEOTIDE |
| US11261440B2 (en) | 2017-02-21 | 2022-03-01 | Osaka University | Antisense oligonucleic acid |
| JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
| US20200115710A1 (en) | 2017-06-30 | 2020-04-16 | National University Corporation Tokyo Medical And Dental University | HETERO DOUBLE-STRANDED antimiR |
| JP2020534253A (ja) | 2017-08-08 | 2020-11-26 | ウェーブ ライフ サイエンシーズ リミテッド | オリゴヌクレオチド組成物及びその方法 |
| WO2019036613A1 (en) | 2017-08-18 | 2019-02-21 | Ionis Pharmaceuticals, Inc. | MODULATION OF THE NOTCH SIGNALING PATHWAY FOR THE 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 |
| WO2019073018A1 (en) | 2017-10-13 | 2019-04-18 | Roche Innovation Center Copenhagen A/S | METHODS OF IDENTIFYING ANTISENSE OLIGONUCLEOTIDE IMPROVED OLIGONUCLEOTIDE PHOSPHOROTHIOATE STEREODEFINIS VARIANTS USING PARTIALLY STEREODEFINIS OLIGONUCLEOTIDE SUB LIBRARIES |
| EP3645723A1 (en) | 2017-10-16 | 2020-05-06 | H. Hoffnabb-La Roche Ag | NUCLEIC ACID MOLECULE FOR REDUCTION OF PAPD5 AND PAPD7 mRNA FOR TREATING HEPATITIS B INFECTION |
| TWI809004B (zh) | 2017-11-09 | 2023-07-21 | 美商Ionis製藥公司 | 用於降低snca表現之化合物及方法 |
| JP2021505175A (ja) | 2017-12-11 | 2021-02-18 | 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 | Ｆｎｄｃ３ｂの発現を調節するためのオリゴヌクレオチド |
| WO2019115417A2 (en) | 2017-12-12 | 2019-06-20 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating rb1 expression |
| WO2019126641A2 (en) | 2017-12-21 | 2019-06-27 | Ionis Pharmaceuticals, Inc. | Modulation of frataxin expression |
| CN111512160B (zh) | 2017-12-21 | 2024-04-09 | 豪夫迈·罗氏有限公司 | Htra1 rna拮抗剂的伴随诊断 |
| CA3085406A1 (en) | 2017-12-22 | 2019-06-27 | Roche Innovation Center Copenhagen A/S | Oligonucleotides comprising a phosphorodithioate internucleoside linkage |
| MX2020005754A (es) | 2017-12-22 | 2020-08-20 | Roche Innovation Ct Copenhagen As | Oligonucleotidos gapmeros que comprenden un enlace internucleosido fosforoditioato. |
| EP4092118A1 (en) | 2017-12-22 | 2022-11-23 | Roche Innovation Center Copenhagen A/S | Novel thiophosphoramidites |
| CN111699258A (zh) | 2018-01-10 | 2020-09-22 | 哥本哈根罗氏创新中心 | 用于调控pias4表达的寡核苷酸 |
| JP2021510295A (ja) | 2018-01-12 | 2021-04-22 | 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 | Ｇｓｋ３ｂ発現を調節するためのオリゴヌクレオチド |
| CA3088522A1 (en) | 2018-01-15 | 2019-07-18 | Ionis Pharmaceuticals, Inc. | Modulators of dnm2 expression |
| WO2019141656A1 (en) | 2018-01-17 | 2019-07-25 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating erc1 expression |
| EP3740573A1 (en) | 2018-01-18 | 2020-11-25 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting srebp1 |
| WO2019145386A1 (en) | 2018-01-26 | 2019-08-01 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating csnk1d expression |
| RU2020125769A (ru) | 2018-02-09 | 2022-03-10 | Дженентек, Инк. | Олигонуклеотиды для модуляции экспрессии tmem106b |
| US11332733B2 (en) | 2018-02-12 | 2022-05-17 | lonis Pharmaceuticals, Inc. | Modified compounds and uses thereof |
| 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 |
| WO2019169243A1 (en) | 2018-03-02 | 2019-09-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for the modulation of amyloid-beta precursor protein |
| TWI840345B (zh) | 2018-03-02 | 2024-05-01 | 美商Ionis製藥公司 | Irf4表現之調節劑 |
| EP3766972B1 (en) | 2018-03-14 | 2025-04-23 | Institute of Science Tokyo | Nucleic acid complex |
| US11851654B2 (en) | 2018-03-19 | 2023-12-26 | National University Corporation Tokyo Medical And Dental University | Nucleic acid with reduced toxicity |
| MX2020009765A (es) | 2018-03-20 | 2021-01-08 | Tokyo Inst Tech | Oligonucleotido antisentido reducido en toxicidad. |
| US11661601B2 (en) | 2018-03-22 | 2023-05-30 | Ionis Pharmaceuticals, Inc. | Methods for modulating FMR1 expression |
| 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 |
| PE20201349A1 (es) | 2018-04-11 | 2020-11-30 | Ionis Pharmaceuticals Inc | Moduladores de la expresion de ezh2 |
| EP3788169A4 (en) | 2018-05-04 | 2022-08-10 | Stoke Therapeutics, Inc. | Methods and compositions for treatment of cholesteryl ester storage disease |
| WO2019215175A1 (en) | 2018-05-08 | 2019-11-14 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for modulating myh7 expression |
| UY38225A (es) | 2018-05-09 | 2019-11-29 | Ionis Pharmaceuticals Inc | Compuestos y métodos para reducir de la expresión de atxn3 |
| CU20200082A7 (es) | 2018-05-09 | 2021-06-08 | Ionis Pharmaceuticals Inc | Compuestos y métodos para la reducción de la expresión de fxi |
| JP7379387B2 (ja) | 2018-06-05 | 2023-11-14 | エフ． ホフマン－ラ ロシュ アーゲー | Ａｔｘｎ２発現を制御するためのオリゴヌクレオチド |
| WO2019241648A1 (en) * | 2018-06-14 | 2019-12-19 | Ionis Pharmaceuticals, Inc. | Compounds and methods for increasing stmn2 expression |
| TWI833770B (zh) | 2018-06-27 | 2024-03-01 | 美商Ionis製藥公司 | 用於減少 lrrk2 表現之化合物及方法 |
| WO2020007700A1 (en) | 2018-07-02 | 2020-01-09 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting spi1 |
| WO2020007772A1 (en) | 2018-07-02 | 2020-01-09 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting gbp-1 |
| WO2020007702A1 (en) | 2018-07-02 | 2020-01-09 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting bcl2l11 |
| CR20210178A (es) * | 2018-07-03 | 2021-05-11 | Hoffmann La Roche | OLIGONUCLEÓTIDOS PARA MODULAR LA EXPRESIÓN DE TAU (Divisional 2021-0058) |
| WO2020007889A1 (en) | 2018-07-05 | 2020-01-09 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting stat1 |
| WO2020007826A1 (en) | 2018-07-05 | 2020-01-09 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting mbtps1 |
| WO2020011743A1 (en) | 2018-07-09 | 2020-01-16 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting mafb |
| WO2020011653A1 (en) | 2018-07-09 | 2020-01-16 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting kynu |
| WO2020011869A2 (en) | 2018-07-11 | 2020-01-16 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting tlr2 |
| WO2020011745A2 (en) | 2018-07-11 | 2020-01-16 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting cers6 |
| WO2020011744A2 (en) | 2018-07-11 | 2020-01-16 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting cers5 |
| AU2019300324A1 (en) | 2018-07-13 | 2021-01-21 | F. Hoffmann-La Roche Ag | Oligonucleotides for modulating RTEL1 expression |
| US12496311B2 (en) | 2018-07-17 | 2025-12-16 | Aronora, Inc. | Methods for safely reducing thrombopoietin |
| EP3826645A4 (en) | 2018-07-25 | 2023-05-17 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR REDUCING ATXN2 EXPRESSION |
| JP7182308B2 (ja) | 2018-07-27 | 2022-12-02 | 国立大学法人大阪大学 | 老化の抑制、加齢性の疾患もしくは症状の予防、改善、もしくは治療、または寿命の延長のための組成物 |
| WO2020025527A1 (en) | 2018-07-31 | 2020-02-06 | Roche Innovation Center Copenhagen A/S | Oligonucleotides comprising a phosphorotrithioate internucleoside linkage |
| EP4122943B1 (en) | 2018-07-31 | 2024-05-29 | Roche Innovation Center Copenhagen A/S | Oligonucleotides comprising a phosphorotrithioate internucleoside linkage |
| 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 |
| 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 |
| 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 |
| SG11202100928QA (en) | 2018-08-02 | 2021-02-25 | Dyne Therapeutics Inc | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| WO2020038971A1 (en) | 2018-08-23 | 2020-02-27 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting vcan |
| WO2020038976A1 (en) | 2018-08-23 | 2020-02-27 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting usp8 |
| WO2020038973A1 (en) | 2018-08-23 | 2020-02-27 | Roche Innovation Center Copenhagen A/S | Antisense oligonucleotides targeting sptlc1 |
| EP3620519A1 (en) | 2018-09-04 | 2020-03-11 | F. Hoffmann-La Roche AG | Use of isolated milk extracellular vesicles for delivering oligonucleotides orally |
| CN112969709A (zh) | 2018-11-01 | 2021-06-15 | 豪夫迈·罗氏有限公司 | 靶向tia1的反义寡核苷酸 |
| TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
| EP3880821A4 (en) | 2018-11-15 | 2023-01-25 | Ionis Pharmaceuticals, Inc. | IRF5 EXPRESSION MODULATORS |
| TWI841633B (zh) | 2018-11-21 | 2024-05-11 | 美商Ionis製藥公司 | 用於減少朊病毒表現之化合物及方法 |
| US12485136B2 (en) * | 2018-12-03 | 2025-12-02 | Takeda Pharmaceuticals U.S.A., Inc. | Methods for the treatment of trinucleotide repeat expansion disorders associated with MLH3 activity |
| EP3898975A2 (en) | 2018-12-21 | 2021-10-27 | Boehringer Ingelheim International GmbH | Antisense oligonucleotides targeting card9 |
| WO2020152303A1 (en) | 2019-01-25 | 2020-07-30 | F. Hoffmann-La Roche Ag | Lipid vesicle for oral drug delivery |
| EP3917540A1 (en) | 2019-01-31 | 2021-12-08 | Ionis Pharmaceuticals, Inc. | Modulators of yap1 expression |
| BR112021016460A2 (pt) | 2019-02-20 | 2021-10-13 | Roche Innovation Center Copenhagen A/S | Oligonucleotídeo gapmer antissenso de fita simples, sal farmaceuticamente aceitável de um oligonucleotídeo, conjugado, composição farmacêutica e invenção |
| MX2021009949A (es) | 2019-02-20 | 2021-09-21 | Roche Innovation Ct Copenhagen As | Fosforamiditas novedosas. |
| CN113474633A (zh) | 2019-02-26 | 2021-10-01 | 罗氏创新中心哥本哈根有限公司 | 寡核苷酸配制方法 |
| KR20210134686A (ko) | 2019-02-27 | 2021-11-10 | 아이오니스 파마수티컬즈, 인코포레이티드 | Malat1 발현의 조절인자 |
| JP7530106B2 (ja) | 2019-03-14 | 2024-08-07 | レナセラピューティクス株式会社 | Ｉｈｈ発現を調節するための核酸複合体 |
| TWI874376B (zh) | 2019-03-29 | 2025-03-01 | 美商Ionis製藥公司 | 用於調節ube3a-ats 之化合物及方法 |
| US11286485B2 (en) | 2019-04-04 | 2022-03-29 | Hoffmann-La Roche Inc. | Oligonucleotides for modulating ATXN2 expression |
| JP7687682B2 (ja) | 2019-04-08 | 2025-06-03 | 国立大学法人東京科学大学 | 筋疾患治療用医薬組成物 |
| CN113950529A (zh) | 2019-06-06 | 2022-01-18 | 豪夫迈·罗氏有限公司 | 靶向atxn3的反义寡核苷酸 |
| EP3956450B1 (en) | 2019-07-26 | 2025-08-13 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating gfap |
| US20220370491A1 (en) | 2019-09-18 | 2022-11-24 | National University Corporation Tokyo Medical And Dental University | Nucleic acid complex |
| WO2021070959A1 (ja) | 2019-10-11 | 2021-04-15 | 国立大学法人東京医科歯科大学 | 修飾ヘテロ核酸 |
| EP4043473A4 (en) | 2019-10-11 | 2024-03-27 | Sumitomo Chemical Company, Limited | Method for producing nucleic acid oligomers |
| JP7644499B2 (ja) * | 2019-11-27 | 2025-03-12 | 国立大学法人東京科学大学 | アンチセンス核酸の毒性を軽減する方法 |
| WO2021130266A1 (en) | 2019-12-24 | 2021-07-01 | F. Hoffmann-La Roche Ag | Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv |
| EP4081217A1 (en) | 2019-12-24 | 2022-11-02 | F. Hoffmann-La Roche AG | Pharmaceutical combination of antiviral agents targeting hbv and/or an immune modulator for treatment of hbv |
| CA3161513A1 (en) | 2020-01-28 | 2021-08-05 | Irwin DAVIDSON | Antisense oligonucleotide targeting linc00518 for treating melanoma |
| CN115003680B (zh) | 2020-01-29 | 2025-01-28 | 住友化学株式会社 | 制备核酸寡聚物的方法 |
| JP7777452B2 (ja) | 2020-01-29 | 2025-11-28 | 住友化学株式会社 | 核酸オリゴマーの製造方法 |
| JP7753106B2 (ja) | 2020-01-31 | 2025-10-14 | 株式会社三和化学研究所 | Ａｔｎ１のアンチセンスオリゴヌクレオチド |
| BR112022016238A2 (pt) | 2020-02-28 | 2022-10-11 | Ionis Pharmaceuticals Inc | Compostos e métodos para modular smn2 |
| JPWO2021177418A1 (OSRAM) | 2020-03-04 | 2021-09-10 | ||
| WO2021178374A2 (en) * | 2020-03-05 | 2021-09-10 | Synerk Inc. | Compounds and methods for reducing apoe expression |
| JPWO2021187392A1 (OSRAM) | 2020-03-16 | 2021-09-23 | ||
| KR20220160010A (ko) | 2020-03-27 | 2022-12-05 | 스미또모 가가꾸 가부시끼가이샤 | 핵산 올리고머의 제조 방법 |
| JP2023522622A (ja) * | 2020-04-17 | 2023-05-31 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | Ｔｄｐ－４３及びｆｕｓ凝集を抑制するための組成物及び方法 |
| CA3181546A1 (en) | 2020-05-01 | 2021-11-04 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating atxn1 |
| MX2022014151A (es) | 2020-05-11 | 2022-11-30 | Stoke Therapeutics Inc | Oligomeros antisentido de opa1 para tratamiento de afecciones y enfermedades. |
| TW202216996A (zh) | 2020-06-29 | 2022-05-01 | 美商Ionis製藥公司 | 調節ｐｌｐ１之化合物及方法 |
| KR20230034969A (ko) | 2020-07-09 | 2023-03-10 | 스미또모 가가꾸 가부시끼가이샤 | 핵산 올리고머의 제조 방법 |
| UY39344A (es) | 2020-07-28 | 2022-02-25 | Ionis Pharmaceuticals Inc | Compuestos y métodos para reducir la expresión de app |
| CA3186935A1 (en) | 2020-08-07 | 2022-02-10 | Paymaan JAFAR-NEJAD | Compounds and methods for modulating scn2a |
| KR20230074205A (ko) | 2020-09-24 | 2023-05-26 | 스미또모 가가꾸 가부시끼가이샤 | 핵산 올리고머의 제조 방법 |
| WO2022109139A1 (en) | 2020-11-18 | 2022-05-27 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
| AR124227A1 (es) | 2020-12-03 | 2023-03-01 | Hoffmann La Roche | Oligonucleótidos antisentido que actúan sobre atxn3 |
| AR124229A1 (es) | 2020-12-03 | 2023-03-01 | Hoffmann La Roche | Oligonucleótidos antisentido que actúan sobre atxn3 |
| IL303800A (en) | 2020-12-18 | 2023-08-01 | Ionis Pharmaceuticals Inc | Compounds and methods for modulating factor xii |
| EP4271816A4 (en) | 2020-12-31 | 2025-04-02 | Dyne Therapeutics, Inc. | MUSCLE TARGETING COMPLEXES AND RELATED USES FOR THE TREATMENT OF MYOTONIC DYSTROPHY |
| US20240083990A1 (en) | 2021-01-26 | 2024-03-14 | Universite Brest Bretagne Occidentale | Novel stim1 splicing variants and uses thereof |
| IL308353A (en) | 2021-05-10 | 2024-01-01 | Entrada Therapeutics Inc | Compositions and methods for modulating tissue distribution of intracellular therapies |
| WO2022240795A1 (en) * | 2021-05-10 | 2022-11-17 | Q-State Biosciences, Inc. | Compositions targeting sodium channel 1.6 |
| US20240240183A1 (en) | 2021-05-25 | 2024-07-18 | National University Corporation Tokyo Medical And Dental University | Heteronucleic acid containing scpBNA or AmNA |
| CN117412773A (zh) | 2021-05-31 | 2024-01-16 | 瑞纳治疗公司 | 配体结合核酸复合物 |
| AU2022293556A1 (en) | 2021-06-18 | 2024-01-18 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing ifnar1 expression |
| CA3222824A1 (en) | 2021-06-23 | 2022-12-29 | Entrada Therapeutics, Inc. | Antisense compounds and methods for targeting cug repeats |
| 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 |
| US11633498B2 (en) | 2021-07-09 | 2023-04-25 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
| EP4389891A4 (en) | 2021-08-19 | 2025-10-29 | Univ Nat Corp Tokyo Medical & Dental | MODIFIED HETERONUCLEIC ACID CONTAINING MORPHOLINO NUCLEIC ACID |
| WO2023026994A1 (ja) | 2021-08-21 | 2023-03-02 | 武田薬品工業株式会社 | ヒトトランスフェリンレセプター結合ペプチド－薬物コンジュゲート |
| WO2023034870A2 (en) | 2021-09-01 | 2023-03-09 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing dmpk expression |
| WO2023042876A1 (ja) | 2021-09-15 | 2023-03-23 | 国立大学法人東京医科歯科大学 | ２'－修飾ヌクレオシドを含むヘテロ核酸 |
| EP4410770A1 (en) | 2021-09-28 | 2024-08-07 | Sumitomo Chemical Company, Limited | Production method for purified dichloroacetic acid |
| 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 |
| CN118318042A (zh) | 2021-11-03 | 2024-07-09 | 豪夫迈·罗氏有限公司 | 用于调节载脂蛋白e4表达的寡核苷酸 |
| AU2022384619A1 (en) | 2021-11-11 | 2024-04-11 | F. Hoffmann-La Roche Ag | Pharmaceutical combinations for treatment of hbv |
| CN118434860A (zh) | 2021-12-20 | 2024-08-02 | 豪夫迈·罗氏有限公司 | 苏糖核酸反义寡核苷酸及其方法 |
| WO2023141507A1 (en) | 2022-01-20 | 2023-07-27 | Genentech, Inc. | Antisense oligonucleotides for modulating tmem106b expression |
| IL315546A (en) | 2022-03-16 | 2024-11-01 | Empirico Inc | GALNAC compositions to improve siRNA bioavailability |
| JPWO2023182274A1 (OSRAM) | 2022-03-23 | 2023-09-28 | ||
| AU2023245603A1 (en) | 2022-03-28 | 2024-11-07 | Empirico Inc. | Modified oligonucleotides |
| CA3255934A1 (en) | 2022-04-15 | 2023-10-19 | Dyne Therapeutics, Inc. | MUSCLE TARGETTING COMPLEXES AND FORMULATIONS FOR THE TREATMENT OF MYOTONIC DYSTROPHY |
| KR20250042734A (ko) | 2022-07-22 | 2025-03-27 | 스미또모 가가꾸 가부시끼가이샤 | 올리고뉴클레오티드의 제조 방법 |
| CN119585232A (zh) | 2022-07-28 | 2025-03-07 | 住友化学株式会社 | 硫化溶液 |
| WO2024026474A1 (en) | 2022-07-29 | 2024-02-01 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle |
| EP4332221A1 (en) | 2022-08-29 | 2024-03-06 | Roche Innovation Center Copenhagen A/S | Threose nucleic acid antisense oligonucleotides and methods thereof |
| EP4581143A1 (en) | 2022-08-29 | 2025-07-09 | University of Rochester | Antisense oligonucleotide-based anti-fibrotic therapeutics |
| IL319629A (en) | 2022-09-23 | 2025-05-01 | Ionis Pharmaceuticals Inc | Compounds and methods for reducing MECP2 expression |
| CA3266197A1 (en) * | 2022-09-29 | 2024-04-04 | Celanese Eva Performance Polymers Llc | IMPLANTABLE MEDICAL DEVICE FOR THE ADMINISTRATION OF NUCLEIC ACID |
| EP4596694A1 (en) | 2022-09-29 | 2025-08-06 | Institute Of Science Tokyo | Nucleic acid molecule containing 5'-cyclopropylene modification |
| EP4477659A4 (en) | 2022-10-27 | 2025-07-30 | Sumitomo Chemical Co | METHOD FOR PRODUCING AN OLIGONUCLEOTIDE |
| 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 |
| AU2023379457A1 (en) | 2022-11-14 | 2025-05-15 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for fibroblast growth factor receptor 3-mediated delivery to astrocytes |
| KR20250128304A (ko) | 2022-12-26 | 2025-08-27 | 스미또모 가가꾸 가부시끼가이샤 | 올리고뉴클레오티드의 제조 방법 |
| WO2024153586A1 (en) | 2023-01-16 | 2024-07-25 | Institut National De Recherche Pour L'agriculture, L'alimentation Et L'environnement | Antisense molecules and their uses for the treatment of coronavirus infection, in particular the treatment of covid-19 related to sars-cov-2 infection |
| CN121127250A (zh) * | 2023-03-14 | 2025-12-12 | 托马斯杰弗逊大学 | 用于治疗癌症的组合物和方法 |
Family Cites Families (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| 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 |
| US5591722A (en) * | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| ATE190981T1 (de) | 1989-10-24 | 2000-04-15 | Isis Pharmaceuticals Inc | 2'-modifizierte nukleotide |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| 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 |
| DE69032425T2 (de) | 1990-05-11 | 1998-11-26 | Microprobe Corp., Bothell, Wash. | Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden |
| US6582908B2 (en) | 1990-12-06 | 2003-06-24 | Affymetrix, Inc. | Oligonucleotides |
| ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
| US5359044A (en) * | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| US20010044145A1 (en) * | 1991-12-24 | 2001-11-22 | Monia Brett P. | Methods of using mammalian RNase H and compositions thereof |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| FR2692265B1 (fr) | 1992-05-25 | 1996-11-08 | Centre Nat Rech Scient | Composes biologiquement actifs de type phosphotriesters. |
| 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 |
| EP0673559A1 (en) | 1992-12-14 | 1995-09-27 | Honeywell Inc. | Motor system with individually controlled redundant windings |
| MX9306994A (es) | 1992-12-15 | 1994-06-30 | Ericsson Telefon Ab L M | Sistema de control de flujo para interruptores de paquete. |
| US5446786A (en) * | 1993-03-03 | 1995-08-29 | Northern Telecom Limited | Two-wire telecommunications line detection arrangements |
| DE69404289T2 (de) | 1993-03-30 | 1998-02-19 | Sanofi Sa | Acyclische nucleosid analoge und sie enthaltende oligonucleotidsequenzen |
| 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. |
| US5801154A (en) | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5519134A (en) * | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| 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 |
| WO2005121370A2 (en) | 2004-06-03 | 2005-12-22 | Isis Pharmaceuticals, Inc. | Oligomeric compounds that facilitate risc loading |
| 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 |
| US6043352A (en) | 1998-08-07 | 2000-03-28 | Isis Pharmaceuticals, Inc. | 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides |
| ATE287897T2 (de) | 1999-02-12 | 2005-02-15 | Sankyo Co | Analoga von nukleosiden und oligonukleotiden |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| US7098192B2 (en) * | 1999-04-08 | 2006-08-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of STAT3 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 |
| US20040002153A1 (en) | 1999-07-21 | 2004-01-01 | Monia Brett P. | Modulation of PTEN expression via oligomeric compounds |
| 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 |
| AU2002317437A1 (en) * | 2001-05-18 | 2002-12-03 | Cureon A/S | Therapeutic uses of lna-modified oligonucleotides in infectious diseases |
| US7888324B2 (en) * | 2001-08-01 | 2011-02-15 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| US7407943B2 (en) * | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
| US7569575B2 (en) | 2002-05-08 | 2009-08-04 | Santaris Pharma A/S | Synthesis of locked nucleic acid derivatives |
| US20040219565A1 (en) | 2002-10-21 | 2004-11-04 | Sakari Kauppinen | Oligonucleotides useful for detecting and analyzing nucleic acids of interest |
| 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 |
| EP2336318B1 (en) | 2002-11-13 | 2013-04-24 | Genzyme Corporation | Antisense modulation of apolipoprotein b expression |
| CA2506576C (en) | 2002-11-18 | 2018-03-06 | Santaris Pharma A/S | Antisense gapmer oligonucleotides |
| PT1592793E (pt) | 2003-02-10 | 2009-09-30 | Santaris Pharma As | Compostos oligoméricos para a modulação da expressão de survivina |
| WO2004106356A1 (en) | 2003-05-27 | 2004-12-09 | Syddansk Universitet | Functionalized nucleotide derivatives |
| US7457046B2 (en) * | 2003-07-01 | 2008-11-25 | Canon Kabushiki Kaisha | Zoom lens system and image-taking apparatus |
| ATE555118T1 (de) | 2003-08-28 | 2012-05-15 | Takeshi Imanishi | Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung |
| US20050053981A1 (en) * | 2003-09-09 | 2005-03-10 | Swayze Eric E. | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
| US20050074801A1 (en) | 2003-09-09 | 2005-04-07 | Monia Brett P. | Chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry |
| BRPI0413930A (pt) * | 2003-09-18 | 2006-10-24 | Isis Pharmaceuticals Inc | composto oligomérico ou sal farmaceuticamente aceitável deste, composição farmacêutica ou veterinária, métodos para inibir a expressão de eif4e em uma célula, tecido ou órgão, para diminuir a proliferação de uma célula em que eif4e é expressado, e para prevenir ou tratar uma condição ou doença métodos para prevenir ou diminuir a angiogênese, e o crescimento de tumor em um paciente, oligonucleotìdeo de anti-sentido, composição farmacêutica ou veterinária, e, uso de um composto oligomérico ou sal farmaceuticamente aceitável deste |
| EP1706489B9 (en) | 2003-12-23 | 2011-01-05 | Santaris Pharma A/S | Oligomeric compounds for the modulation of bcl-2 |
| GB0407382D0 (en) * | 2004-03-31 | 2004-05-05 | Univ Cambridge Tech | Therapeutic methods and means |
| EP1931780B1 (en) | 2005-08-29 | 2016-01-06 | Regulus Therapeutics Inc. | Antisense compounds having enhanced anti-microrna activity |
| EP2338991B1 (en) * | 2005-08-29 | 2017-01-18 | Regulus Therapeutics Inc. | Methods for use in modulating MIR-122a |
| 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 |
| JP5665317B2 (ja) * | 2006-10-18 | 2015-02-04 | 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 | アンチセンス化合物 |
| WO2008111908A1 (en) | 2007-03-15 | 2008-09-18 | Jyoti Chattopadhyaya | Five- and six-membered conformationally locked 2',4'- carbocyclic ribo-thymidines for the treatment of infections and cancer |
| 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 |
| AU2008286771B2 (en) † | 2007-08-15 | 2013-08-15 | Isis Pharmaceuticals, Inc. | Tetrahydropyran nucleic acid analogs |
| US8389488B2 (en) | 2007-11-05 | 2013-03-05 | Isis Pharmaceuticals, Inc. | Antidotes to antisense compounds |
| 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 |
| US8846639B2 (en) | 2008-04-04 | 2014-09-30 | Isis Pharmaceutical, Inc. | Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity |
| WO2010036698A1 (en) | 2008-09-24 | 2010-04-01 | Isis Pharmaceuticals, Inc. | Substituted alpha-l-bicyclic nucleosides |
| WO2010108035A1 (en) | 2009-03-18 | 2010-09-23 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating toxic and proinflammatory effects |
| EP2462153B1 (en) | 2009-08-06 | 2015-07-29 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
| WO2012027033A1 (en) | 2010-07-19 | 2012-03-01 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating target nuclear and sub-nuclear nucleic acid molecules in cells and animals |
| EP3467109A1 (en) | 2011-02-08 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| ES2856266T3 (es) | 2011-04-21 | 2021-09-27 | Glaxo Group Ltd | Modulación de la expresión del virus de la hepatitis B (VHB) |
| ES2651514T3 (es) | 2011-08-11 | 2018-01-26 | Ionis Pharmaceuticals, Inc. | Compuestos oligoméricos gapados que comprenden deoxirribonucleósidos modificados en 5 ' -en la brecha y usos de ellos |
| EP2839006B1 (en) * | 2012-04-20 | 2018-01-03 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| WO2014059353A2 (en) * | 2012-10-11 | 2014-04-17 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleosides and uses thereof |
| SI3043827T1 (sl) | 2013-09-13 | 2019-08-30 | Ionis Pharmaceuticals, Inc. | Modulatorji komplementnega faktorja B |
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