CN111868068A - 用于在tau蛋白病变治疗中使用的经修饰的寡核苷酸 - Google Patents

用于在tau蛋白病变治疗中使用的经修饰的寡核苷酸 Download PDF

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Publication number
CN111868068A
CN111868068A CN201980018910.3A CN201980018910A CN111868068A CN 111868068 A CN111868068 A CN 111868068A CN 201980018910 A CN201980018910 A CN 201980018910A CN 111868068 A CN111868068 A CN 111868068A
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oligonucleotide
nucleotides
modified
formula
nucleobase
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Chinese (zh)
Inventor
A·埃布内特
C·范奥特利福迪德瓦勒
S·格里亚兹诺夫
S·马丁内兹蒙特罗
V·K·拉万什
L·拜格尔曼
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Janssen Pharmaceutica NV
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Janssen Pharmaceutica NV
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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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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CN201980018910.3A 2018-03-13 2019-03-13 用于在tau蛋白病变治疗中使用的经修饰的寡核苷酸 Pending CN111868068A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862642499P 2018-03-13 2018-03-13
US62/642499 2018-03-13
PCT/EP2019/056312 WO2019175260A2 (en) 2018-03-13 2019-03-13 Modified oligonucleotides and methods of use in tauopathies

Publications (1)

Publication Number Publication Date
CN111868068A true CN111868068A (zh) 2020-10-30

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Country Status (15)

Country Link
US (2) US11453881B2 (https=)
EP (2) EP3922637A1 (https=)
JP (1) JP2021515784A (https=)
KR (1) KR20200131263A (https=)
CN (1) CN111868068A (https=)
AU (1) AU2019233612A1 (https=)
BR (1) BR112020018365A2 (https=)
CA (1) CA3091979A1 (https=)
EA (1) EA202092156A1 (https=)
ES (1) ES3063421T3 (https=)
IL (1) IL277238A (https=)
MA (1) MA52149A (https=)
MX (1) MX2020009532A (https=)
SG (1) SG11202008895WA (https=)
WO (1) WO2019175260A2 (https=)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2831232A4 (en) 2012-03-30 2015-11-04 Univ Washington METHOD FOR MODULATING TAU EXPRESSION TO REDUCE PROBLEMS AND MODIFY A NEURODEGENERATIVE SYNDROME
TW202246503A (zh) 2013-07-19 2022-12-01 美商百健Ｍａ公司 用於調節τ蛋白表現之組合物
WO2021198958A1 (en) * 2020-04-01 2021-10-07 Janssen Biopharma, Inc. Nucleic acid polymers
TW202310854A (zh) * 2021-07-23 2023-03-16 美商百健Ｍａ公司 用於減少ｔａｕ表現之方法
CN121729493A (zh) * 2023-06-22 2026-03-24 戴纳立制药公司 用于调节τ蛋白表达的组合物和方法
US12551569B2 (en) 2024-03-31 2026-02-17 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of microtubule associated protein tau (MAPT), compositions thereof, and methods of use
WO2026025082A1 (en) * 2024-07-25 2026-01-29 Biogen Ma Inc. Methods for treating alzheimer's disease

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1373768A (zh) * 1999-09-10 2002-10-09 杰龙公司 寡核苷酸n3′→p5′硫代氨基磷酸酯,其合成及应用
US20140121261A1 (en) * 2012-10-26 2014-05-01 Geron Corporation C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders
US20160145617A1 (en) * 2013-07-19 2016-05-26 Ionis Pharmaceuticals, Inc. Compositions for modulating tau expression
US20160237427A1 (en) * 2015-02-04 2016-08-18 Bristol-Myers Squibb Company Tau Antisense Oligomers and Uses Thereof
WO2017109679A1 (en) * 2015-12-21 2017-06-29 Novartis Ag Compositions and methods for decreasing tau expression

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
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
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
ES2234563T5 (es) 1999-02-12 2018-01-17 Daiichi Sankyo Company, Limited Nuevos análogos de nucleósidos y oligonucleótidos
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
US7053207B2 (en) 1999-05-04 2006-05-30 Exiqon A/S L-ribo-LNA analogues
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
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
US7569575B2 (en) 2002-05-08 2009-08-04 Santaris Pharma A/S Synthesis of locked nucleic acid derivatives
WO2004041889A2 (en) 2002-11-05 2004-05-21 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP1794313B1 (en) * 2004-06-21 2013-05-15 Proteome Sciences Plc Screening methods using c-abl, fyn and syk in combination with tau protein
GB0605337D0 (en) * 2006-03-17 2006-04-26 Genomica Sau Treatment of CNS conditions
WO2013180038A1 (ja) * 2012-05-26 2013-12-05 株式会社ボナック デリバリー機能を有する遺伝子発現制御用の一本鎖核酸分子
CN105264091B (zh) * 2013-03-14 2020-02-28 Ionis制药公司 用于调节tau表达的组合物和方法
BR112017014090A2 (pt) * 2014-12-29 2018-03-06 Bonac Corporation composição, e, métodos para produção de uma composição e estabilização de uma molécula de ácido nucleico.

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1373768A (zh) * 1999-09-10 2002-10-09 杰龙公司 寡核苷酸n3′→p5′硫代氨基磷酸酯,其合成及应用
US20140121261A1 (en) * 2012-10-26 2014-05-01 Geron Corporation C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders
US20160145617A1 (en) * 2013-07-19 2016-05-26 Ionis Pharmaceuticals, Inc. Compositions for modulating tau expression
US20160237427A1 (en) * 2015-02-04 2016-08-18 Bristol-Myers Squibb Company Tau Antisense Oligomers and Uses Thereof
WO2017109679A1 (en) * 2015-12-21 2017-06-29 Novartis Ag Compositions and methods for decreasing tau expression

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SG11202008895WA (en) 2020-10-29
AU2019233612A1 (en) 2020-09-10
KR20200131263A (ko) 2020-11-23
ES3063421T3 (en) 2026-04-16
EP3765476A2 (en) 2021-01-20
WO2019175260A3 (en) 2019-11-14
WO2019175260A2 (en) 2019-09-19
CA3091979A1 (en) 2019-09-19
MA52149A (fr) 2021-01-20
JP2021515784A (ja) 2021-06-24
US11453881B2 (en) 2022-09-27
EP3765476B1 (en) 2025-11-26
US20240011029A1 (en) 2024-01-11
MX2020009532A (es) 2020-10-05
EP3765476C0 (en) 2025-11-26
BR112020018365A2 (pt) 2020-12-29
IL277238A (en) 2020-10-29
EA202092156A1 (ru) 2021-04-01
US20210095284A1 (en) 2021-04-01
EP3922637A1 (en) 2021-12-15

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