DK2581448T3 - Tricyclo-phosphorothioat-DNA - Google Patents

Tricyclo-phosphorothioat-DNA Download PDF

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DK2581448T3
DK2581448T3 DK11185129T DK11185129T DK2581448T3 DK 2581448 T3 DK2581448 T3 DK 2581448T3 DK 11185129 T DK11185129 T DK 11185129T DK 11185129 T DK11185129 T DK 11185129T DK 2581448 T3 DK2581448 T3 DK 2581448T3
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dna
nucleic acid
acid molecule
mrna
exon
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DK11185129T
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English (en)
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Thomas Voit
Christian Leumann
Luis Garcia
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Ass Inst De Myologie
Universität Bern
Université Pierre Et Marie Curie Paris 6
Inst Nat Santé Et De La Rech Médicale Inserm
Centre Nat Rech Scient
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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
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    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • 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
    • C12N2310/10—Type of nucleic acid
    • 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
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
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    • C12N2310/30—Chemical structure
    • 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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    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/33—Alteration of splicing

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  • Heart & Thoracic Surgery (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
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Claims (13)

1. Nukleinsyremolekyle omfattende tricyclo-nukleosider forbundet af internukleosid phosphorothioat forbindelser (3'-0PS-0-5' forbindelser).
2. Nukleinsyremolekyle ifølge krav 1, omfattende mellem 3 og 50 nukleotider.
3. Nukleinsyremolekyle ifølge krav 1 eller 2, hvilket er komplementært til en målsekvens.
4. Nukleinsyremolekyle ifølge krav 3, hvor nukleinsyremolekylet er et antisense oligonukleotid komplementært til en del af et RNA som kodet for af et gen.
5. Nukleinsyremolekyle ifølge krav 1, omfattende eller bestående af sekvensen 5'-AACCTCGGCTTACCT-3' (SEQ ID NR.:1).
6. Fremgangsmåde til syntetisering af et tricyclo-phosphorothioat-DNA-molekyle, fremgangsmåden omfattende: a) at tilvejebringe et første tricyclo-nukleosid bundet til en faststoffasestøtte, hvilket første nukleotid har en beskyttet 5'-OH-gruppe; b) at afbeskytte 5'-gruppen for at danne en fri 5'-OH-gruppe; c) at omsætte den frie 5'-OH-gruppe med en 5'-beskyttet tricyclonukleosid-S'-O-cyanoethyl-^N-diisopropylaminophosphoramidit monomer for at danne en internukleosid phosphoramidit forbindelse mellem det første og et andet tricyclo-nukleosid; og d) at svovlbehandle internukleosid-phosphoramidit-gruppen for at danne en phosphorothioat internukleosid-forbindelse mellem det første og andet tricyclo-nukleosid.
7. Farmaceutisk sammensætning omfattende et nukleinsyremolekyle ifølge et hvilket som helst af kravene 1 til 4, i en farmaceutisk acceptabel bærer.
8. Nukleinsyremolekyle ifølge et hvilket som helst af kravene 1 til 5, til anvendelse som et lægemiddel.
9. Nukleinsyremolekyle ifølge et hvilket som helst af kravene 1 til 4, til anvendelse i behandlingen af en hjertesygdom.
10. Nukleinsyremolekyle ifølge et hvilket som helst af kravene 1 til 5, til anvendelse i behandlingen afen neuromuskulær eller muskuloskeletal sygdom.
11. Nukleinsyremolekyle ifølge et hvilket som helst af kravene 1 til 5, til anvendelse i behandlingen af en centralnervesystem-sygdom.
12. Nukleinsyremolekyle til anvendelse ifølge et hvilket som helst af kravene 9 til 11, hvor hjerte-, CNS-, neuromuskulær eller muskuloskeletal sygdom resulterer fra en ændring af et gen, hvor ændringen er en i-ramme mutation af et exon, en mutation som forstyrrer den translatoriske læseramme af genet, og tc-DNA'et gør det lettere at springe et exon over for at gendanne læserammen; en skadelig mutation som kan kompenseres ved inklusionen af et atypisk exon i mRNA'et som koder for genet, og tc-DNA'et er komplementært til en ISS eller TSL til stede i et præ-mRNA som er kodet for af genet og gør inklusion lettere af et atypisk exon, eller en mutation som resulterer i tilstedeværelsen af skadelig 3’ CUG amplifikation(er) i et mRNA som kodet for af genet.
13. Nukleinsyremolekyle til anvendelse ifølge krav 10, til behandlingen af Duchenne muskeldystrofi, spinal muskelatrofi, eller Steinerts myotonisk dystrofi.
DK11185129T 2011-10-13 2011-10-13 Tricyclo-phosphorothioat-DNA DK2581448T3 (da)

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EP11185129.1A EP2581448B1 (en) 2011-10-13 2011-10-13 Tricyclo-phosphorothioate DNA

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US (1) US9738891B2 (da)
EP (2) EP2581448B1 (da)
JP (1) JP6181653B2 (da)
CN (1) CN104245935B (da)
AU (1) AU2012322903B2 (da)
BR (1) BR112014009066B8 (da)
CA (2) CA2776651C (da)
DK (1) DK2581448T3 (da)
ES (2) ES2535654T3 (da)
HK (1) HK1186205A1 (da)
IL (1) IL231983B (da)
IN (1) IN2014DN03463A (da)
PL (1) PL2581448T3 (da)
PT (1) PT2581448E (da)
WO (1) WO2013053928A1 (da)

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EP2581448B1 (en) 2015-01-28
JP6181653B2 (ja) 2017-08-16
CN104245935B (zh) 2018-05-08
PL2581448T3 (pl) 2015-08-31
CN104245935A (zh) 2014-12-24
BR112014009066B1 (pt) 2020-08-25
US20140296323A1 (en) 2014-10-02
IN2014DN03463A (da) 2015-06-05
JP2015501144A (ja) 2015-01-15
IL231983A0 (en) 2014-05-28
US9738891B2 (en) 2017-08-22
WO2013053928A1 (en) 2013-04-18
BR112014009066B8 (pt) 2021-02-23
HK1186205A1 (en) 2014-03-07
PT2581448E (pt) 2015-05-21
BR112014009066A2 (pt) 2017-04-18
EP2766479B1 (en) 2017-09-13
CA2851970A1 (en) 2013-04-18
CA2776651C (en) 2021-06-08
EP2581448A1 (en) 2013-04-17
ES2651216T3 (es) 2018-01-25
IL231983B (en) 2018-04-30
AU2012322903B2 (en) 2017-09-14
EP2766479A1 (en) 2014-08-20
AU2012322903A1 (en) 2014-05-29
BR112014009066A8 (pt) 2018-01-09
CA2776651A1 (en) 2013-04-13
ES2535654T3 (es) 2015-05-13

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