CA2909868C - Compounds and methods for enhanced cellular uptake - Google Patents

Compounds and methods for enhanced cellular uptake Download PDF

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Publication number
CA2909868C
CA2909868C CA2909868A CA2909868A CA2909868C CA 2909868 C CA2909868 C CA 2909868C CA 2909868 A CA2909868 A CA 2909868A CA 2909868 A CA2909868 A CA 2909868A CA 2909868 C CA2909868 C CA 2909868C
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certain embodiments
compound
modified oligonucleotide
modified
nucleoside
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French (fr)
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CA2909868A1 (en
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Balkrishen Bhat
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Regulus Therapeutics Inc
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Regulus Therapeutics Inc
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    • C—CHEMISTRY; METALLURGY
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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
    • C12N15/113—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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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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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
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    • C12N5/0602—Vertebrate cells
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/11—Antisense
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • C12N2310/141—MicroRNAs, miRNAs
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/31—Chemical structure of the backbone
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/315—Phosphorothioates
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    • C12N2310/32—Chemical structure of the sugar
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • C—CHEMISTRY; METALLURGY
    • 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
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C—CHEMISTRY; METALLURGY
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/999—Small molecules not provided for elsewhere

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  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
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  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CA2909868A 2013-05-01 2014-04-30 Compounds and methods for enhanced cellular uptake Active CA2909868C (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201361818441P 2013-05-01 2013-05-01
US201361818447P 2013-05-01 2013-05-01
US61/818,447 2013-05-01
US61/818,441 2013-05-01
US201361822115P 2013-05-10 2013-05-10
US61/822,115 2013-05-10
US201361895708P 2013-10-25 2013-10-25
US61/895,708 2013-10-25
PCT/US2014/036136 WO2014179445A1 (en) 2013-05-01 2014-04-30 Compounds and methods for enhanced cellular uptake

Publications (2)

Publication Number Publication Date
CA2909868A1 CA2909868A1 (en) 2014-11-06
CA2909868C true CA2909868C (en) 2021-10-19

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CA2909868A Active CA2909868C (en) 2013-05-01 2014-04-30 Compounds and methods for enhanced cellular uptake

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US (3) US9506030B2 (https=)
EP (1) EP2992096B1 (https=)
JP (1) JP6649248B2 (https=)
CN (1) CN105164261B (https=)
AU (1) AU2014259953B2 (https=)
CA (1) CA2909868C (https=)
IL (1) IL241973B (https=)
NZ (1) NZ630921A (https=)
TW (1) TWI680767B (https=)
WO (1) WO2014179445A1 (https=)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3459549B1 (en) 2012-10-12 2022-04-06 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
US9506030B2 (en) 2013-05-01 2016-11-29 Regulus Therapeutics Inc. Compounds and methods for enhanced cellular uptake
SG10201803157XA (en) 2013-05-01 2018-05-30 Regulus Therapeutics Inc Microrna compounds and methods for modulating mir-122
US9994846B2 (en) 2013-10-25 2018-06-12 Regulus Therapeutics Inc. MicroRNA compounds and methods for modulating miR-21 activity
WO2015179693A1 (en) 2014-05-22 2015-11-26 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
EP3151839A4 (en) * 2014-06-06 2018-02-28 Ionis Pharmaceuticals, Inc. Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds
KR20170033439A (ko) 2014-08-07 2017-03-24 레굴루스 테라퓨틱스 인크 대사 장애에 대한 마이크로rna의 표적화
US10577388B2 (en) 2015-10-02 2020-03-03 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugation process
CN113817735A (zh) 2015-10-08 2021-12-21 Ionis制药公司 用于调节血管紧张素原表达的化合物和方法
US10955407B2 (en) 2015-10-22 2021-03-23 Roche Innovation Center Copenhagen A/S In vitro toxicity screening assay
AU2017286811A1 (en) * 2016-06-17 2018-11-22 Ionis Pharmaceuticals, Inc. Modulation of gys1 expression
JP7012033B2 (ja) 2016-06-17 2022-02-10 エフ．ホフマン－ラ ロシュ アーゲー インビトロ腎毒性スクリーニングアッセイ
CN109328236B (zh) 2016-06-17 2022-10-25 豪夫迈·罗氏有限公司 体外肾毒性筛选测定法
CA3043768A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents
CR20200260A (es) * 2017-12-15 2020-08-01 Bayer Animal Health Gmbh Composiciones inmunoestimulantes
CN111655851A (zh) 2018-01-18 2020-09-11 哥本哈根罗氏创新中心 靶向srebp1的反义寡核苷酸
CN112105745A (zh) 2018-05-07 2020-12-18 罗氏创新中心哥本哈根有限公司 用于寡核苷酸治疗剂的大规模平行发现方法
US12005120B2 (en) 2018-05-08 2024-06-11 Regulus Therapeutics Inc. Galnac conjugated modified oligonucleotides as miR-122 inhibitor having HCV antiviral activity with reduced hyperbilirubinemia side-effect
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
WO2020011744A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
JP2021531278A (ja) * 2018-07-20 2021-11-18 レグルス セラピューティクス インコーポレイテッド オリゴヌクレオチドの経口送達のための方法
CN111377985B (zh) * 2018-12-29 2023-11-10 苏州瑞博生物技术股份有限公司 化合物和缀合物及其制备方法和用途
CN111041025B (zh) 2019-12-17 2021-06-18 深圳市瑞吉生物科技有限公司 基于结合N-乙酰半乳糖胺多肽的mRNA靶向分子及其制备方法
CN111744019B (zh) 2020-07-01 2023-08-04 深圳瑞吉生物科技有限公司 基于甘露糖的mRNA靶向递送系统及其应用
CN116916968A (zh) * 2020-10-30 2023-10-20 托德·斯皮尔 基于寡核苷酸的治疗剂及其用途
LT4136092T (lt) 2020-11-18 2024-09-25 Ionis Pharmaceuticals, Inc. Junginiai ir būdai, skirti angiotenzinogeno raiškos moduliavimui
WO2022186350A1 (ja) * 2021-03-03 2022-09-09 国立大学法人東京大学 非環式スレオニノール核酸
US12042509B2 (en) 2021-10-01 2024-07-23 Adarx Pharmaceuticals, Inc. Prekallikrein-modulating compositions and methods of use thereof
AU2023408479A1 (en) 2022-12-19 2025-05-01 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar)
ES3030929T3 (en) 2022-12-19 2025-07-02 Arnatar Therapeutics Inc Arnatar compounds and methods for enhanced cellular uptake
TW202448484A (zh) 2023-04-20 2024-12-16 美商雅迪克斯製藥公司 Ｍａｐｔ調節組合物及其使用方法
CN121335980A (zh) 2023-05-26 2026-01-13 阿达尔克斯制药有限公司 Sod1调节组合物及其使用方法
EP4562158A1 (en) 2023-06-13 2025-06-04 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar) for angiotensinogen
EP4731763A1 (en) 2023-06-20 2026-04-29 Adarx Pharmaceuticals, Inc. Lrrk2-modulating compositions and methods of use thereof
EP4671372A3 (en) 2024-01-29 2026-03-11 Arnatar Therapeutics, Inc Translation enhancing nucleic acid compounds: aso coupled translation - upregulation 1 (act-up1) and uses thereof
WO2025165891A1 (en) 2024-01-29 2025-08-07 Arnatar Therapeutics, Inc Translation enhancing nucleic acid compounds: aso coupled translation - upregulation 1 (act-up1) and uses thereof
WO2025184391A1 (en) * 2024-02-27 2025-09-04 Arrakis Therapeutics, Inc. Covalent inhibitors and uses thereof

Family Cites Families (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995030746A1 (en) 1994-05-10 1995-11-16 The General Hospital Corporation Antisense inhibition of hepatitis c virus
AU728176B2 (en) * 1995-05-04 2001-01-04 Gilead Sciences, Inc. Nucleic acid ligand complexes
CN1120707C (zh) 1995-11-22 2003-09-10 约翰斯·霍普金斯大学 增强生物分子的细胞摄取的配体
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6656730B1 (en) 1999-06-15 2003-12-02 Isis Pharmaceuticals, Inc. Oligonucleotides conjugated to protein-binding drugs
AU7406700A (en) 1999-10-04 2001-05-10 Exiqon A/S Design of high affinity rnase h recruiting oligonucleotide
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
CN100406065C (zh) 2000-12-01 2008-07-30 细胞工厂治疗公司 糖基化/半乳糖基化肽、双官能接头和核苷酸单体/多聚体的缀合物以及相关的组合物和使用方法
CN1344803A (zh) * 2001-09-27 2002-04-17 吴昌 核酸靶分子选择及扩增方法
WO2004041889A2 (en) 2002-11-05 2004-05-21 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
ES2702942T3 (es) 2003-04-17 2019-03-06 Alnylam Pharmaceuticals Inc Agentes de ARNi modificados
US20050256071A1 (en) * 2003-07-15 2005-11-17 California Institute Of Technology Inhibitor nucleic acids
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
EP1661905B9 (en) 2003-08-28 2012-12-19 IMANISHI, Takeshi Novel artificial nucleic acids of n-o bond crosslinkage type
AU2004275876B2 (en) 2003-09-25 2011-03-31 Coley Pharmaceutical Gmbh Nucleic acid-lipophilic conjugates
WO2005061710A1 (en) 2003-12-23 2005-07-07 Santaris Pharma A/S Oligomeric compounds for the modulation of bcl-2
EP1768998A2 (en) * 2004-04-27 2007-04-04 Alnylam Pharmaceuticals Inc. Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety
AU2005330637B2 (en) 2004-08-04 2012-09-20 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
US20090203132A1 (en) * 2004-09-09 2009-08-13 Swayze Eric E Pyrrolidinyl groups for attaching conjugates to oligomeric compounds
US20060148740A1 (en) 2005-01-05 2006-07-06 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
US20120122801A1 (en) 2005-01-05 2012-05-17 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
US20080206869A1 (en) 2005-01-24 2008-08-28 Avaris Ab Nucleic Acid Complex
AU2006279906B2 (en) 2005-08-10 2012-05-10 Alnylam Pharmaceuticals, Inc. Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
US20070213292A1 (en) 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
AU2007211082B2 (en) 2006-01-27 2012-09-27 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of microRNAs
WO2007090071A2 (en) 2006-01-27 2007-08-09 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
EP2007888A2 (en) 2006-04-03 2008-12-31 Santaris Pharma A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
SG10201406016SA (en) 2006-04-03 2014-11-27 Stella Aps Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
CA2927045A1 (en) 2006-10-03 2008-04-10 Muthiah Manoharan Lipid containing formulations
DK2152879T3 (da) 2007-05-01 2013-02-18 Santaris Pharma As RNA antagonistforbindelser til modulering af beta-catenin
CA2688321A1 (en) 2007-05-30 2008-12-11 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
DK2173760T4 (en) 2007-06-08 2016-02-08 Isis Pharmaceuticals Inc Carbocyclic bicyclic nukleinsyreanaloge
AU2008272918B2 (en) 2007-07-05 2012-09-13 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
EP2623599B1 (en) 2007-10-04 2019-01-02 Roche Innovation Center Copenhagen A/S Micromirs
WO2009068033A2 (en) 2007-11-26 2009-06-04 Santaris Pharma A/S Lna antagonists targeting the androgen receptor
WO2009073809A2 (en) 2007-12-04 2009-06-11 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
CA2717792A1 (en) 2008-03-07 2009-09-11 Santaris Pharma A/S Pharmaceutical compositions for treatment of microrna related diseases
WO2010076248A1 (en) 2008-12-31 2010-07-08 Santaris Pharma A/S Use of lna apob antisense oligomers for the treatment of acute coronary syndromes
ES2599979T3 (es) 2009-04-24 2017-02-06 Roche Innovation Center Copenhagen A/S Composiciones farmacéuticas para el tratamiento de pacientes de VHC que no responden al interferón
BR112012008865A2 (pt) 2009-10-16 2019-09-24 Glaxo Group Ltd inibidores de hbv anti-sentido.
SI2539451T1 (sl) 2010-02-24 2016-04-29 Arrowhead Research Corporation Sestavki za ciljano dostavo sirna
EP2553019A1 (en) 2010-03-26 2013-02-06 Mersana Therapeutics, Inc. Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof
WO2011130458A2 (en) 2010-04-13 2011-10-20 John Rossi Rna aptamers against baff-r as cell-type specific delivery agents and methods for their use
WO2012007477A1 (en) 2010-07-12 2012-01-19 Santaris Pharma A/S Anti hcv oligomers
AU2011343664B2 (en) 2010-12-17 2015-10-08 Arrowhead Pharmaceuticals, Inc. Galactose cluster-pharmacokinetic modulator targeting moiety for siRNA
CA3131967A1 (en) 2010-12-29 2012-07-05 F. Hoffman-La Roche Ag Small molecule conjugates for intracellular delivery of nucleic acids
WO2013033230A1 (en) * 2011-08-29 2013-03-07 Isis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
WO2013068348A1 (en) 2011-11-07 2013-05-16 Santaris Pharma A/S Lna oligomers for improvement in hepatic function
CN104837996A (zh) 2012-11-15 2015-08-12 罗氏创新中心哥本哈根有限公司 抗apob反义缀合物化合物
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
AU2014211406B2 (en) 2013-01-30 2019-07-18 Roche Innovation Center Copenhagen A/S LNA oligonucleotide carbohydrate conjugates
US9506030B2 (en) 2013-05-01 2016-11-29 Regulus Therapeutics Inc. Compounds and methods for enhanced cellular uptake
SG10201803157XA (en) 2013-05-01 2018-05-30 Regulus Therapeutics Inc Microrna compounds and methods for modulating mir-122
DK2992098T3 (da) 2013-05-01 2019-06-17 Ionis Pharmaceuticals Inc Sammensætninger og fremgangsmåder til modulering af hbv- og ttr-ekspression

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