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HRP20201426T1 - Postupci i pripravci za moduliranje ekspresije apolipoproteina (a) - Google Patents

Postupci i pripravci za moduliranje ekspresije apolipoproteina (a) Download PDF

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Publication number
HRP20201426T1
HRP20201426T1 HRP20201426TT HRP20201426T HRP20201426T1 HR P20201426 T1 HRP20201426 T1 HR P20201426T1 HR P20201426T T HRP20201426T T HR P20201426TT HR P20201426 T HRP20201426 T HR P20201426T HR P20201426 T1 HRP20201426 T1 HR P20201426T1
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Croatia
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wing segment
modified oligonucleotide
compound according
linked nucleosides
modified
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HRP20201426TT
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English (en)
Inventor
Rosanne M. Crooke
Mark J. Graham
Susan M. Freier
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Ionis Pharmaceuticals, Inc.
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Publication of HRP20201426T1 publication Critical patent/HRP20201426T1/hr

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    • 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
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Claims (16)

1. Spoj za smanjenje ekspresije apo(a), naznačen time, što sadrži modificirani oligonukleotid koji se sastoji od 15 do 30 povezanih nukleozida i koji ima nukleobaznu sekvencu koja sadrži dio od najmanje 15 uzastopnih nukleobaza komplementarnih s dijelom jednake duljine nukleobaza od 3900 do 3923 iz SEQ ID NO: 1, te pri čemu je nukleobazna sekvenca modificiranog oligonukleotida najmanje 80% komplementarna sa SEQ ID NO: 1.
2. Spoj prema patentnom zahtjevu 1, naznačen time, što se modificirani oligonukleotid sastoji od 18 do 24, 19 do 22, 15 do 25, 16 ili 20 povezanih nukleozida.
3. Spoj prema patentnom zahtjevu 1, naznačen time, što modificirani oligonukleotid obuhvaća nukleobaznu sekvencu koja sadrži dio od najmanje 16, najmanje 18, najmanje 19, ili najmanje 20 uzastopnih nukleobaza komplementarnih s dijelom jednake duljine iz SEQ ID NO: 1.
4. Spoj prema bilo kojem prethodnom patentnom zahtjevu, naznačen time, što je nukleobazna sekvenca modificiranog oligonukleotida najmanje 85%, najmanje 90%, najmanje 95%, ili 100% komplementarna sa SEQ ID NO: 1.
5. Spoj prema bilo kojem prethodnom patentnom zahtjevu, naznačen time, što nukleobazna sekvenca modificiranog oligonukleotida obuhvaća najmanje 15, najmanje 16, najmanje 17, najmanje 18, najmanje 19, ili 20 uzastopnih nukleobaza nukleobazne sekvence iz SEQ ID NO: 58.
6. Spoj prema bilo kojem prethodnom patentnom zahtjevu, naznačen time, što se modificirani oligonukleotid sastoji od 18 do 24 povezanih nukleozida, i pri čemu nukleobazna sekvenca sadrži najmanje 18 uzastopnih nukleobaza nukleobazne sekvence iz SEQ ID NO: 58.
7. Spoj prema bilo kojem prethodnom patentnom zahtjevu, naznačen time, što: (i) modificirani oligonukleotid je jednostrane strukture, (ii) najmanje jedna međunukleozidna veza je modificirana međunukleozidna veza, po izboru pri čemu je najmanje jedna međunukleozidna veza fosforotioatna međunukleozidna veza, (iii) modificirani oligonukleotid obuhvaća najmanje jedan modificirani šećer, po izboru pri čemu: (a) najmanje jedan modificirani šećer je biciklički šećer, po izboru ograničeni etil ili šećer koji sadrži 4'-(CH2)n-O-2' most, pri čemu n je 1 ili 2, ili (b) najmanje jedan modificirani šećer koji sadrži 2'-O-metoksietil, ili je 3'-fluoro-HNA, i/ili (iv) najmanje jedan nukleozid sadrži modificiranu nukleobazu, po izboru pri čemu je modificirana nukleobaza 5-metilcitozin.
8. Spoj prema bilo kojem prethodnom patentnom zahtjevu, naznačen time, što modificirani oligonukleotid obuhvaća: segment procjepa koji se sastoji od povezanih deoksinukleozida; 5' krilni segment koji se sastoji od povezanih nukleozida; 3' krilni segment koji se sastoji od povezanih nukleozida; pri čemu je segment procjepa smješten između 5' krilnog segmenta i 3' krilnog segmenta i pri čemu svaki nukleozid iz svakog krilnog segmenta sadrži modificirani šećer.
9. Spoj prema patentnom zahtjevu 8, naznačen time, što se modificirani oligonukleotid sastoji od 20 povezanih nukleozida i sadrži: segment procjepa koji se sastoji od deset povezanih deoksinukleozida; 5' krilni segment koji se sastoji od pet povezanih nukleozida; 3' krilni segment koji se sastoji od pet povezanih nukleozida; pri čemu je segment procjepa smješten između 5' krilnog segmenta i 3' krilnog segmenta, pri čemu svaki nukleozid iz svakog krilnog segmenta sadrži 2'-O-metoksietil šećer, pri čemu svaka međunukleozidna veza je fosforotioatna veza i pri čemu svaki citozinski ostatak je 5-metilcitozin.
10. Spoj prema bilo kojem prethodnom patentnom zahtjevu, naznačen time, što se modificirani oligonukleotid sastoji od 20 povezanih nukleozida i ima nukleobaznu sekvencu koja sadrži najmanje 15 uzastopnih nukleobaza nukleobazne sekvence iz SEQ ID NO: 58, pri čemu modificirani oligonukleotid obuhvaća: segment procjepa koji se sastoji od deset povezanih deoksinukleozida; 5' krilni segment koji se sastoji od pet povezanih nukleozida; 3' krilni segment koji se sastoji od pet povezanih nukleozida; pri čemu je segment procjepa smješten između 5' krilnog segmenta i 3' krilnog segmenta, pri čemu svaki nukleozid svakog krilnog segmenta sadrži 2'-O-metoksietil šećer, pri čemu svaka međunukleozidna veza je fosforotioatna veza i pri čemu svaki citozinski ostatak je 5-metilcitozin.
11. Spoj koji sadrži modificirani oligonukleotid koji se sastoji od 20 povezanih nukleozida i koji ima nukleobaznu sekvencu iz SEQ ID NO: 58, naznačen time, što modificirani oligonukleotid obuhvaća: segment procjepa koji se sastoji od deset povezanih deoksinukleozida; 5' krilni segment koji se sastoji od pet povezanih nukleozida; 3' krilni segment koji se sastoji od pet povezanih nukleozida; pri čemu je segment procjepa smješten između 5' krilnog segmenta i 3' krilnog segmenta, pri čemu svaki nukleozid svakog krilnog segmenta sadrži 2'-O-metoksietil šećer, pri čemu svaka međunukleozidna veza je fosforotioatna veza i pri čemu svaki citozinski ostatak je 5-metilcitozin.
12. Spoj prema bilo kojem od patentnih zahtjeva 8-11, naznačen time, što je modificirani oligonukleotid jednostrane strukture.
13. Spoj prema bilo kojem prethodnom patentnom zahtjevu, naznačen time, što je spoj konjugirani antisens-spoj.
14. Pripravak, naznačen time, što sadrži spoj prema bilo kojem prethodnom patentnom zahtjevu, pri čemu po izboru spoj je sol, te 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 upotrebu u terapiji.
16. Spoj ili pripravak za uporabu u skladu s patentnim zahtjevom 15, naznačen time, što terapija je liječenje, sprečavanje ili usporavanje napredovanja bolesti povezane s povišenim apo(a) i/ili povišenim Lp(a), po izboru pri čemu je bolest upalna, kardiovaskularna ili metabolička bolest, takav poremećaj ili takvo stanje.
HRP20201426TT 2012-05-24 2013-05-23 Postupci i pripravci za moduliranje ekspresije apolipoproteina (a) HRP20201426T1 (hr)

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US201261651539P 2012-05-24 2012-05-24
EP13793955.9A EP2855500B1 (en) 2012-05-24 2013-05-23 Methods and compositions for modulating apolipoprotein(a) expression
PCT/US2013/042532 WO2013177468A2 (en) 2012-05-24 2013-05-23 Methods and compositions for modulating apolipoprotein(a) expression

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US (3) US20150152411A1 (hr)
EP (3) EP3822352A3 (hr)
JP (3) JP6082809B2 (hr)
KR (4) KR102657351B1 (hr)
CN (2) CN108359668A (hr)
AU (4) AU2013266196A1 (hr)
CA (2) CA3185392A1 (hr)
CY (1) CY1123367T1 (hr)
DK (1) DK2855500T3 (hr)
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HR (1) HRP20201426T1 (hr)
HU (1) HUE051680T2 (hr)
IL (2) IL235746B (hr)
LT (1) LT2855500T (hr)
MX (2) MX360639B (hr)
NZ (1) NZ631071A (hr)
PL (1) PL2855500T3 (hr)
PT (1) PT2855500T (hr)
RU (2) RU2624028C2 (hr)
SI (1) SI2855500T1 (hr)
WO (1) WO2013177468A2 (hr)

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