PE20211398A1 - Compuestos y metodos para reducir la expresion de la atxn2 - Google Patents

Compuestos y metodos para reducir la expresion de la atxn2

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Publication number
PE20211398A1
PE20211398A1 PE2021000083A PE2021000083A PE20211398A1 PE 20211398 A1 PE20211398 A1 PE 20211398A1 PE 2021000083 A PE2021000083 A PE 2021000083A PE 2021000083 A PE2021000083 A PE 2021000083A PE 20211398 A1 PE20211398 A1 PE 20211398A1
Authority
PE
Peru
Prior art keywords
reduce
atxn2
compounds
methods
modified
Prior art date
Application number
PE2021000083A
Other languages
English (en)
Inventor
Susan M Freier
Priyam Singh
Frank Rigo
Paymaan Jafar-Nejad
Holly Kordasiewicz
Original Assignee
Ionis Pharmaceuticals Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ionis Pharmaceuticals Inc filed Critical Ionis Pharmaceuticals Inc
Publication of PE20211398A1 publication Critical patent/PE20211398A1/es

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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
    • 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
    • A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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    • C12N2310/11—Antisense
    • 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
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    • C12N2310/14—Type of nucleic acid interfering N.A.
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
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    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
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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
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3525—MOE, methoxyethoxy

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
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  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Botany (AREA)
  • Inorganic Chemistry (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La presente invencion se refiere a un compuesto oligomerico que comprende un oligonucleotido modificado que consiste en 12 a 50 nucleosidos, donde la secuencia de nucleobases del oligonucleotido modificado es al menos 90% complementaria a la secuencia del acido nucleico de ataxina-2 (ATXN2) y comprende al menos una modificacion seleccionada de un resto de azucar modificado y un enlace internucleosido modificado. Se proporcionan compuestos, metodos y composiciones farmaceuticas para reducir la cantidad o actividad del ARN de ATXN2 en una celula o un animal y, en determinados casos, para reducir la cantidad de la proteina Ataxina-2 en una celula o un animal. La invencion es util para mejorar enfermedades neurodegenerativas que incluyen la ataxia espinocerebelosa tipo 2 (SCA2), la esclerosis lateral amiotrofica (ELA) y la enfermedad de Parkinson.
PE2021000083A 2018-07-25 2019-07-25 Compuestos y metodos para reducir la expresion de la atxn2 PE20211398A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862703240P 2018-07-25 2018-07-25
PCT/US2019/043424 WO2020023737A1 (en) 2018-07-25 2019-07-25 Compounds and methods for reducing atxn2 expression

Publications (1)

Publication Number Publication Date
PE20211398A1 true PE20211398A1 (es) 2021-07-27

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PE2021000083A PE20211398A1 (es) 2018-07-25 2019-07-25 Compuestos y metodos para reducir la expresion de la atxn2

Country Status (22)

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US (2) US11078486B2 (es)
EP (1) EP3826645A4 (es)
JP (2) JP7411632B2 (es)
KR (1) KR20210038589A (es)
CN (1) CN112423767B (es)
AR (1) AR115847A1 (es)
AU (1) AU2019310097A1 (es)
BR (1) BR112021000308A2 (es)
CA (1) CA3106986A1 (es)
CL (1) CL2021000159A1 (es)
CO (1) CO2021000196A2 (es)
CR (1) CR20210100A (es)
EA (1) EA202190299A1 (es)
IL (1) IL280123A (es)
JO (1) JOP20210018A1 (es)
MX (1) MX2021000922A (es)
PE (1) PE20211398A1 (es)
PH (1) PH12021500007A1 (es)
SG (1) SG11202100077PA (es)
UY (1) UY38316A (es)
WO (1) WO2020023737A1 (es)
ZA (1) ZA202100108B (es)

Families Citing this family (11)

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RU2019130898A (ru) 2014-03-19 2019-11-11 Ионис Фармасьютикалз, Инк. Композиции для модуляции экспрессии атаксина 2
US10385341B2 (en) * 2014-04-01 2019-08-20 Biogen Ma Inc. Compositions for modulating SOD-1 expression
US20200283800A1 (en) * 2017-10-23 2020-09-10 Prevail Therapeutics, Inc. Gene therapies for neurodegenerative diseases
PE20201501A1 (es) 2018-01-12 2020-12-29 Bristol Myers Squibb Co Oligonucleotidos antisentido que actuan sobre alfa-sinucleina, y usos de estos
AU2019310097A1 (en) 2018-07-25 2021-02-04 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing ATXN2 expression
WO2021159008A2 (en) * 2020-02-07 2021-08-12 Maze Therapeutics, Inc. Compositions and methods for treating neurodegenerative diseases
CN115702243A (zh) * 2020-06-09 2023-02-14 罗氏创新中心哥本哈根有限公司 用于治疗性多核苷酸的鸟苷类似物
WO2023107893A2 (en) * 2021-12-06 2023-06-15 The Board Of Trustees Of The Leland Stanford Junior University Treatment of neuorodegenerative diseases through the inhibition of ataxin-2
WO2023239747A2 (en) * 2022-06-06 2023-12-14 University Of Utah Research Foundation Methods of modulating atxn2 expression
WO2023250368A2 (en) * 2022-06-24 2023-12-28 Eli Lilly And Company Atxn2 rna interference agents
WO2024056902A2 (en) * 2022-09-16 2024-03-21 Christopher Shaw Compositions and methods for treating neurological diseases

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