PE20212131A1 - Compuestos y metodos para reducir de la expresion de atxn3 - Google Patents

Compuestos y metodos para reducir de la expresion de atxn3

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Publication number
PE20212131A1
PE20212131A1 PE2020001754A PE2020001754A PE20212131A1 PE 20212131 A1 PE20212131 A1 PE 20212131A1 PE 2020001754 A PE2020001754 A PE 2020001754A PE 2020001754 A PE2020001754 A PE 2020001754A PE 20212131 A1 PE20212131 A1 PE 20212131A1
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PE
Peru
Prior art keywords
modified
atxn3
compounds
oligomeric compounds
oligomeric
Prior art date
Application number
PE2020001754A
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English (en)
Inventor
Susan M Freier
Original Assignee
Ionis Pharmaceuticals Inc
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Publication date
Application filed by Ionis Pharmaceuticals Inc filed Critical Ionis Pharmaceuticals Inc
Publication of PE20212131A1 publication Critical patent/PE20212131A1/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
    • 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
    • C12N15/1137—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 against enzymes
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/11—Antisense
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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
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/311—Phosphotriesters
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
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    • C12N2310/3341—5-Methylcytosine
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    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
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    • C12N2320/00—Applications; Uses
    • C12N2320/10—Applications; Uses in screening processes
    • C12N2320/11—Applications; Uses in screening processes for the determination of target sites, i.e. of active nucleic acids
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    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La presente invencion se refiere a compuestos oligomericos que comprende oligonucleotidos modificados de 12 a 50 nucleosidos enlazados, donde la secuencia de nucleobases del oligonucleotido modificado es al menos 90% complementaria a una parte de igual longitud de un acido ATXN3, y en donde el oligonucleotido modificado comprende al menos una modificacion seleccionada de una nucleobase modificada, un azucar modificado, un sustituto de azucar y un enlace internucleosido modificado. Los compuestos oligomericos comprenden oligonucleotidos modificados de 12 a 50 nucleosidos enlazados donde las secuencias de nucleobases adyacentes se exponen en las SEQ ID NO: 15-2787. Adicionalmente algunos compuestos oligomericos son gapmer, entre los compuestos preferidos se presenta: la SEQ ID NO: 423, 1226 y 1673 o uno sal de los mismos. La invencion tambien se refiere a un duplex oligomerico, un compuesto antisentido, composiciones farmaceuticas y metodos de uso relacionados con los compuestos oligomericos. Dichos compuestos son utiles para reducir la cantidad o actividad del ARN de ATXN3 o reducir la cantidad de proteina ATXN3; por lo que pueden mejorar un sintoma o caracteristica de una enfermedad neurodegenerativa tal como ataxia espinocerebelosa tipo 3 (SCA3) asociada a una mutacion del gen ATXN3.
PE2020001754A 2018-05-09 2019-05-09 Compuestos y metodos para reducir de la expresion de atxn3 PE20212131A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862669238P 2018-05-09 2018-05-09
PCT/US2019/031562 WO2019217708A1 (en) 2018-05-09 2019-05-09 Compounds and methods for reducing atxn3 expression

Publications (1)

Publication Number Publication Date
PE20212131A1 true PE20212131A1 (es) 2021-11-05

Family

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PE2020001754A PE20212131A1 (es) 2018-05-09 2019-05-09 Compuestos y metodos para reducir de la expresion de atxn3

Country Status (21)

Country Link
US (2) US11434488B2 (es)
EP (1) EP3799602A4 (es)
JP (1) JP2021522800A (es)
KR (1) KR20210008497A (es)
CN (1) CN112189053B (es)
AR (1) AR115375A1 (es)
AU (1) AU2019266307A1 (es)
BR (1) BR112020021253A2 (es)
CA (1) CA3098144A1 (es)
CL (1) CL2020002888A1 (es)
CO (1) CO2020013433A2 (es)
CR (1) CR20200604A (es)
EA (1) EA202092500A1 (es)
JO (1) JOP20200283A1 (es)
MX (1) MX2020011911A (es)
PE (1) PE20212131A1 (es)
PH (1) PH12020500668A1 (es)
SG (1) SG11202010215TA (es)
TW (1) TW202003541A (es)
UY (1) UY38225A (es)
WO (1) WO2019217708A1 (es)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JOP20190104A1 (ar) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
CA3088112A1 (en) 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
JP2021522800A (ja) 2018-05-09 2021-09-02 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． Ａｔｘｎ３発現を低減するための化合物及び方法
WO2020172559A1 (en) * 2019-02-22 2020-08-27 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing atxn3 expression
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
US20230056569A1 (en) * 2019-11-22 2023-02-23 Alnylam Pharmaceuticals, Inc. Ataxin3 (atxn3) rnai agent compositions and methods of use thereof
CN115667513A (zh) 2020-05-12 2023-01-31 田边三菱制药株式会社 用于调节Ataxin 3表达的化合物、方法和药物组合物
EP4162047A1 (en) * 2020-06-09 2023-04-12 Roche Innovation Center Copenhagen A/S Guanosine analogues for use in therapeutic polynucleotides
WO2022117745A1 (en) 2020-12-03 2022-06-09 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting atxn3
TW202237843A (zh) 2020-12-03 2022-10-01 瑞士商赫孚孟拉羅股份公司 靶向ａｔｘｎ３之反義寡核苷酸

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