HRP20211365T1 - Pripravci i postupci za modulaciju ekspresije proteinske kinaze miotonične distrofije (dmpk) - Google Patents

Pripravci i postupci za modulaciju ekspresije proteinske kinaze miotonične distrofije (dmpk) Download PDF

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HRP20211365T1
HRP20211365T1 HRP20211365TT HRP20211365T HRP20211365T1 HR P20211365 T1 HRP20211365 T1 HR P20211365T1 HR P20211365T T HRP20211365T T HR P20211365TT HR P20211365 T HRP20211365 T HR P20211365T HR P20211365 T1 HRP20211365 T1 HR P20211365T1
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segment
modified
linked nucleosides
compound according
modified oligonucleotide
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HRP20211365TT
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Sanjay K. Pandey
Robert A. Macleod
Eric E. Swayze
C. Frank Bennett
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Ionis Pharmaceuticals, Inc.
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    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
    • C12Y207/11—Protein-serine/threonine kinases (2.7.11)
    • C12Y207/11001—Non-specific serine/threonine protein kinase (2.7.11.1), i.e. casein kinase or checkpoint kinase
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    • C12N2310/11—Antisense
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/315—Phosphorothioates
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
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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
    • C12N2310/32—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
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • 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
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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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    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications

Claims (15)

1. Spoj, naznačen time, što sadrži modificirani oligonukleotid koji se sastoji od 10-30 povezanih nukleozida i koji ima nukleobazni slijed koji sadrži odsječak od najmanje osam susjednih nukleobaza 100% komplementarnih s odsječkom jednake duljine nukleobaza 1343-1368 od SEQ ID NO: 1, i/ili nukleobaza 8603-8619 od SEQ ID NO: 2, pri čemu je nukleobazni slijed modificiranog oligonukleotida najmanje 90% komplementaran sa SEQ ID NO: 1 i/ili SEQ ID NO: 2, kada se mjeri duž cjelokupnog modificiranog oligonukleotida i pritom je spoj sposoban za inhibiciju ekpresije DMPK.
2. Spoj, naznačen time, što sadrži modificirani oligonukleotid koji se sastoji od 10-30 povezanih nukleozida gdje modificirani oligonukleotid ima nukleobazni slijed koji sadrži odsječak od najmanje osam susjednih nukleobaza bilo kojeg od SEQ ID NO: 30, 25, 26, 123, 124, 125, 126, 127, 128, 378, 379, 380, 381, 382, 383 i 384, pri čemu je nukleobazni slijed modificiranog oligonukleotida najmanje 90% komplementaran sa SEQ ID NO: 1 i/ili SEQ ID NO: 2, kada se mjeri duž cjelokupnog modificiranog oligonukleotida i pritom je spoj sposoban za inhibiciju ekpresije DMPK.
3. Spoj prema patentnom zahtjevu 1, naznačen time, što modificirani oligonukleotid jest jednolančani oligonukleotid.
4. Spoj prema bilo kojem od patentnih zahtjeva 1-3, naznačen time, što najmanje jedan nukleozid sadrži modificiranu nukleobazu, pri čemu opcionalno modificirana nukleobaza jest 5-metilcitozin.
5. Spoj prema bilo kojem od patentnih zahtjeva 1-4, naznačen time, što najmanje jedan međunukleozidni veznik jest modificirani međunukleozidni veznik, pri čemu opcionalno svaki međunukleozidni veznik jest fosforotioatni međunukleozidni veznik.
6. Spoj prema bilo kojem od patentnih zahtjeva 1-5, naznačen time, što najmanje jedan nukleozid sadrži modificirani šećer.
7. Spoj prema patentnom zahtjevu 6, naznačen time, što najmanje dva nukleozida sadrže modificirani šećer, pri čemu opcionalno svaki od modificiranih šećera ima istu modifikaciju, ili najmanje jedan od modificiranih šećera ima različitu modifikaciju.
8. Spoj prema patentnom zahtjevu 6 ili zahtjevu 7, naznačen time, što modificirani šećer jest biciklički šećer, pri čemu se opcionalno biciklički šećer bira između cEt, LNA, α-L-LNA, ENA i 2'-tio LNA.
9. Spoj prema patentnom zahtjevu 6, naznačen time, što najmanje jedan nukleozid koji sadrži modificirani šećer jest 2'-supstituirani nukleozid, pri čemu se opcionalno 2'-supstituirani nukleozid bira između: 2'-OCH3, 2'-F i 2'-O-metoksietila.
10. Spoj prema bilo kojem od patentnih zahtjeva 1-9, naznačen time, što (a) modificirani oligonukleotid sadrži: i. prazan segment koji se sastoji od vezanih deoksinukleozida; ii. 5' krilni segment koji se sastoji od povezanih nukleozida; iii. 3' krilni segment koji se sastoji od povezanih nukleozida; iv. gdje je prazan segment smješten između 5' krilnog segmenta i 3' krilnog segmenta i pri čemu svaki nukleozid od svakog krilnog segmenta sadrži modificirani šećer; i/ili (b) modificirani oligonukleotid koji se sastoji od 16, 17, 18, 19 ili 20 povezanih nukleozida.
11. Modificirani oligonukleotid, naznačen time, što ima nukleobazni slijed prikazan sa SEQ ID NO: 30, pri čemu se modificirani oligonukleotid sastoji od 16 vezanih nukleozida i sadrži: a. prazan segment koji se sastoji od osam povezanih deoksinukleozida; b. 5' krilni segment koji se sastoji od četiri povezana nukleozida i ima E-E-K-K 5'-krilni motiv; c. 3' krilni segment koji se sastoji od četiri povezana nukleozida i ima K-K-E-E 3'-krilni motiv; d. gdje je prazni segment smješten između 5' krilnog segmenta i 3' krilnog segmenta; e. pri čemu svaki E predstavlja 2'-O-metoksietil šećer i svaki K predstavlja cEt šećer; f. gdje svaki međunukleozidni veznik jest fosforotioatni međunukleozidni veznik; i g. gdje svaki citozinski ostatak jest 5-metilcitozin.
12. Spoj prema patentnom zahtjevu 2, naznačen time, što (a) spoj ima nukleobazni slijed prikazan u SEQ ID NO: 25, pri čemu se modificirani oligonukleotid sastoji od 20 povezanih nukleozida i sadrži: v. prazan segment koji se sastoji od deset povezanih deoksinukleozida; vi. 5' krilni segment koji se sastoji od pet povezanih nukleozida; vii. 3' krilni segment koji se sastoji od pet povezanih nukleozida; viii. gdje je prazan segment smješten između 5' krilnog segmenta i 3' krilnog segmenta; ix. gdje svaki nukleozid svakog krilnog segmenta sadrži 2'-O-metoksietil šećer; x. gdje svaki međunukleozidni veznik jest fosforotioatni međunukleozidni veznik; i xi. gdje svaki citozinski ostatak jest 5-metilcitozin; ili (b) spoj ima nukleobazni slijed prikazan u SEQ ID NO: 26, pri čemu se modificirani oligonukleotid sastoji od 16 povezanih nukleozida i sadrži: i. prazan segment koji se sastoji od osam povezanih deoksinukleozida; ii. 5' krilni segment koji se sastoji od četiri povezana nukleozida i ima E-E-K-K 5'-krilni motiv; iii. 3' krilni segment koji se sastoji od četiri povezana nukleozida i ima K-K-E-E 3'-krilni motiv; iv. gdje je segment praznine smješten između 5' krilnog segmenta i 3' krilnog segmenta; v. gdje svaki E predstavlja 2'-O-metoksietil šećer i svaki K predstavlja cEt šećer; vi. gdje svaki međunukleozidni veznik jest fosforotioatni međunukleozidni veznik; i vii. gdje svaki citozin jest 5-metilcitozin.
13. Spoj prema bilo kojem od patentnih zahtjeva 1-12, naznačen time, što je spoj konjugirani spoj.
14. Pripravak, naznačen time, što sadrži spoj prema bilo kojem od patentnih zahtjeva 1-12, ili njegovu sol i farmaceutski prihvatljiv nosač ili razrjeđivač.
15. Spoj prema bilo kojem od patentnih zahtjeva 1-13 ili pripravak prema zahtjevu 14, naznačen time, što je za uporabu u postupku liječenja miotonične distrofije tipa 1 kod životinje.
HRP20211365TT 2013-08-09 2021-08-26 Pripravci i postupci za modulaciju ekspresije proteinske kinaze miotonične distrofije (dmpk) HRP20211365T1 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201361864439P 2013-08-09 2013-08-09
US201361889337P 2013-10-10 2013-10-10
PCT/US2014/050481 WO2015021457A2 (en) 2013-08-09 2014-08-11 Compounds and methods for modulation of dystrophia myotonica-protein kinase (dmpk) expression
EP14834532.5A EP3030658B1 (en) 2013-08-09 2014-08-11 Compounds and methods for modulation of dystrophia myotonica-protein kinase (dmpk) expression

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US (3) US20160304877A1 (hr)
EP (2) EP3995580A3 (hr)
JP (3) JP2016530882A (hr)
KR (1) KR102589140B1 (hr)
CN (1) CN105452464A (hr)
AU (2) AU2014306284B2 (hr)
BR (1) BR112016002399A2 (hr)
CA (1) CA2920776A1 (hr)
CL (1) CL2016000301A1 (hr)
CY (1) CY1124522T1 (hr)
DK (1) DK3030658T3 (hr)
ES (1) ES2895099T3 (hr)
HR (1) HRP20211365T1 (hr)
HU (1) HUE055867T2 (hr)
IL (3) IL243917B (hr)
LT (1) LT3030658T (hr)
MX (2) MX2016001789A (hr)
PH (1) PH12016500263A1 (hr)
PL (1) PL3030658T3 (hr)
PT (1) PT3030658T (hr)
RS (1) RS62403B1 (hr)
RU (1) RU2690333C2 (hr)
SG (1) SG11201600941YA (hr)
SI (1) SI3030658T1 (hr)
TW (1) TW201536329A (hr)
WO (1) WO2015021457A2 (hr)

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