AR116102A1 - Compuestos y métodos para la reducción de la expresión de lrrk2 - Google Patents

Compuestos y métodos para la reducción de la expresión de lrrk2

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Publication number
AR116102A1
AR116102A1 ARP190101869A ARP190101869A AR116102A1 AR 116102 A1 AR116102 A1 AR 116102A1 AR P190101869 A ARP190101869 A AR P190101869A AR P190101869 A ARP190101869 A AR P190101869A AR 116102 A1 AR116102 A1 AR 116102A1
Authority
AR
Argentina
Prior art keywords
lrrk2
compounds
methods
modified oligonucleotide
modified
Prior art date
Application number
ARP190101869A
Other languages
English (en)
Inventor
Tracy A Cole
Holly Kordasiewicz
Huynh Bui
- Freier Susan M Hoa
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 AR116102A1 publication Critical patent/AR116102A1/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
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7115—Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
    • 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
    • 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
    • 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
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
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    • C12N2310/321—2'-O-R Modification
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    • C12N2310/32—Chemical structure of the sugar
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    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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    • C12N2310/3341—5-Methylcytosine
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    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
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    • 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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    • 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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  • Health & Medical Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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Abstract

Se proporcionan compuestos, métodos y composiciones farmacéuticas para reducir la cantidad o la actividad del ARN de LRRK2 en una célula o animal, y en determinados casos para reducir la cantidad de proteína LRRK2 en una célula o animal. Tales compuestos, métodos y composiciones farmacéuticas son útiles para mejorar al menos un síntoma o característica de una enfermedad neurodegenerativa. Dichos síntomas y características incluyen ataxia, neuropatía y formación de agregados. Tales enfermedades neurodegenerativas incluyen enfermedad de Parkinson. Un compuesto oligomérico, que comprende un oligonucleótido modificado que consiste en 12 a 50 nucleósidos enlazados donde la secuencia de nucleobases del oligonucleótido modificado es al menos 90% complementaria a una porción de longitud equivalente de un ácido nucleico de LRRK2 y donde el oligonucleótido modificado comprende al menos una modificación que se selecciona de un azúcar modificado, y un enlace internucleósido modificado.
ARP190101869A 2018-06-27 2019-07-02 Compuestos y métodos para la reducción de la expresión de lrrk2 AR116102A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201862690790P 2018-06-27 2018-06-27

Publications (1)

Publication Number Publication Date
AR116102A1 true AR116102A1 (es) 2021-03-31

Family

ID=68987149

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Application Number Title Priority Date Filing Date
ARP190101869A AR116102A1 (es) 2018-06-27 2019-07-02 Compuestos y métodos para la reducción de la expresión de lrrk2

Country Status (23)

Country Link
US (2) US11332746B1 (es)
EP (1) EP3814503A4 (es)
JP (2) JP7315594B2 (es)
KR (1) KR20210025055A (es)
CN (1) CN112400019B (es)
AR (1) AR116102A1 (es)
AU (1) AU2019294838A1 (es)
BR (1) BR112020024564A2 (es)
CA (1) CA3104676A1 (es)
CL (1) CL2020003309A1 (es)
CO (1) CO2020015256A2 (es)
CR (1) CR20210044A (es)
EA (1) EA202190140A1 (es)
IL (1) IL279632A (es)
JO (1) JOP20200334A1 (es)
MX (1) MX2020013653A (es)
PE (1) PE20210518A1 (es)
PH (1) PH12021500003A1 (es)
SG (1) SG11202011864XA (es)
TW (1) TWI833770B (es)
UY (1) UY38282A (es)
WO (1) WO2020006267A1 (es)
ZA (1) ZA202007444B (es)

Families Citing this family (14)

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Publication number Priority date Publication date Assignee Title
EP3400300A4 (en) 2016-01-05 2019-08-07 Ionis Pharmaceuticals, Inc. METHODS FOR REDUCING LRRK2 EXPRESSION
WO2019140231A1 (en) 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
WO2019169243A1 (en) 2018-03-02 2019-09-06 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of amyloid-beta precursor protein
RS64641B1 (sr) 2018-06-27 2023-10-31 Bristol Myers Squibb Co Supstituisana jedinjenja naftiridinona korisna kao aktivatori t ćelija
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
CN115298312A (zh) * 2020-01-24 2022-11-04 阿尔尼拉姆医药品有限公司 富亮氨酸重复激酶2(LRRK2)iRNA剂组合物及其使用方法
IL297867A (en) 2020-05-06 2023-01-01 Servier Lab Novel macrocyclic lrrk2 kinase inhibitors
US20230055405A1 (en) * 2020-07-28 2023-02-23 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing app expression
BR112023017834A2 (pt) 2021-03-18 2023-10-03 Servier Lab Inibidores de lrrk2 cinase macrocíclicos
WO2022206816A1 (zh) * 2021-03-30 2022-10-06 南京大学 一种用于治疗帕金森的rna质粒递送系统
TW202305136A (zh) 2021-04-19 2023-02-01 美商戴瑟納製藥股份有限公司 用於抑制核受體次家族1組別h成員3（nr1h3）表現之組成物與方法
CA3217261A1 (en) * 2021-04-20 2022-10-27 Institute For Cancer Research D/B/A The Research Institute Of Fox Chase Cancer Center Malignant mesothelioma susceptibility as a result of germline leucine-rich repeat kinase 2 (lrrk2) alterations
AU2022303358A1 (en) * 2021-06-29 2024-01-18 Alnylam Pharmaceuticals, Inc. Leucine-rich repeat kinase 2 (lrrk2) irna agent compositions and methods of use thereof
WO2023144263A1 (en) * 2022-01-26 2023-08-03 Syddansk Universitet Allele specific splice switching oligonucleotides targeting pseudoexons

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