HRP20191664T1 - Sastavi i postupci za moduliranje ekspresije komplementa faktora b - Google Patents

Sastavi i postupci za moduliranje ekspresije komplementa faktora b Download PDF

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HRP20191664T1
HRP20191664T1 HRP20191664T HRP20191664T1 HR P20191664 T1 HRP20191664 T1 HR P20191664T1 HR P20191664 T HRP20191664 T HR P20191664T HR P20191664 T1 HRP20191664 T1 HR P20191664T1
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compound according
modified
segment
wing
modified oligonucleotide
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Thazha P Prakash
Punit P Seth
Eric E Swayze
Tamar R Grossman
Michael L Mccaleb
Andrew T Watt
Susan M Freier
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Ionis Pharmaceuticals Inc
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Claims (14)

1. Spoj koji sadrži modificirani oligonukleotid i konjugiranu skupinu, gdje modificirani oligonukleotid se sastoji od 20 do 30 vezanih nukleozida i ima nukleobaznu sekvencu SEQ ID NO: 440, gdje je oligonukleotid bar 80% komplementaran sa SEQ ID NO: 1 ili 2 i gdje konjugirana skupina obuhvaća:
2. Spoj prema zahtjevu 1, gdje modificirani oligonukleotid sadrži barem jednu modificiranu internukleozidnu vezu, barem jedan modificirani šećer, ili barem jednu modificiranu nukleobazu, opcionalno gdje modificirana internukleozidna veza je fosforotioatna internukleozidna veza.
3. Spoj prema zahtjevu 2, gdje modificirani oligonukleotid sadrži: a) barem 1 fosforodiestersku internukleozidnu vezu; b) barem 2 fosforodiesterske internukleozidne veze; c) barem 3 fosforodiesterske internukleozidne veze; d) barem 4 fosforodiesterske internukleozidne veze; e) barem 5 fosforodiesterskih internukleozidnih veza; f) barem 6 fosforodiesterskih internukleozidnih veza; ili g) barem 7 fosforodiesterskih internukleozidnih veza, opcionalno gdje: i) svaka internukleozidna veza modificiranog oligonukleotida je izabrana iz fosforodiesterske internukleozidne veze i fosforotioatne internukleozidne veze; ili ii) svaka internukleozidna veza modificiranog oligonukleotida sadrži fosforotioatnu internukleozidnu vezu.
4. Spoj prema zahtjevu 2 ili 3, gdje: a) modificirani šećer je biciklički šećer, opcionalno gdje je biciklički šećer izabran iz skupine koju čine: 4’-(CH2)-O-2’ (LNA); 4’-(CH2)2-O-2’ (ENA); i 4’-CH(CH3)-O-2’ (cEt); ili b) modificirani šećer je 2’-O-metoksietil; i/ili c) modificirana nukleobaza je 5-metilcitozin.
5. Spoj prema bilo kojem od zahtjeva 1-4, gdje modificirani oligonukleotid sadrži: (a) segment praznine koji se sastoji od povezanih deoksinukleozida; (b) 5’ segment „krila“ koji se sastoji od povezanih nukleozida; i (c) 3’ segment „krila“ koji se sastoji od povezanih nukleozida; gdje segment praznina je smješten odmah pored i između 5’ segmenta „krila“ i 3’ segmenta „krila“ i gdje svaki nukleozid svakog segmenta „krila“ sadrži modificirani šećer.
6. Spoj prema zahtjevu 5, gdje modificirani oligonukleotid se sastoji od 20 povezanih nukleozida koji imaju nukleobaznu sekvencu koja se sastoji od sekvence navedene u SEQ ID NO: 440, gdje modificirani oligonukleotid sadrži segment praznina koji se sastoji od deset povezanih deoksinukleozida; 5’ segment "krila" koji se sastoji od pet povezanih nukleozida; i 3’ segment „krila“ koji se sastoji od pet povezanih nukleozida; gdje segment razmaka je smješten između 5’ segmenta „krila“ i 3’ segmenta „krila“, gdje svaki nukleozid svakog segmenta „krila“ se sastoji od 2’-O-metoksietil šećera; gdje svaka internukleozidna veza je fosforotioatna veza i gdje svaki citozin je 5-metilcitozin.
7. Spoj prema bilo kojem od zahtjeva 1-5, gdje je oligonukleotid bar 85%, 90%, 95% ili 100% komplementaran sa SEQ ID NO: 1 ili 2.
8. Spoj prema bilo kojem od zahtjeva 1-7, gdje: a) spoj je jednolančan; ili b) spoj je dvolančan; i/ili c) spoj sadrži: i) ribonukleotide; ili ii) deoksiribonukleotide.
9. Spoj prema bilo kojem od zahtjeva 1-8, gdje konjugirana skupina je povezana s modificiranim oligonukleotidom: i) na 5’ kraju modificiranog oligonukleotida; ili ii) na 3’ kraju modificiranog oligonukleotida.
10. Spoj prema zahtjevu 1 koji ima formulu: a) gdje ili R1 je -OCH2CH2OCH3 (MOE) i R2 je H; ili R1 i R2 zajedno tvore most, gdje R1 je -O- i R2 je -CH2-, -CH(CH3)-, ili -CH2CH2-, i R1 i R2 su direktno povezani tako da je tako dobiveni most izabran između : -O-CH2-, -O-CH(CH3)-, i -O-CH2CH2-; i za svaki par R3 i R4 na istom prstenu, neovisno od svakog prstena : ili R3 je izabran između H i -OCH2CH2OCH3 i R4 je H; ili R3 i R4 zajedno tvore most, gdje R3 je -O-, i R4 je-CH2-, -CH(CH3)-, ili -CH2CH2- i R3 i R4 su direktno povezani tako da je dobiveni most izabran između : -O-CH2-, -O-CH(CH3)-, i -O-CH2CH2-; i R5 je izabran između H i -CH3; i Z je izabran između S- i O-; b) c) ili d)
11. Spoj prema zahtjevu 1 koji ima formulu:
12. Sastav koji sadrži spoj prema bilo kojem od zahtjeva 1-11 ili njegova sol i barem jedan farmaceutski prihvatljiv nosač ili razrjeđivač.
13. Spoj prema bilo kojem od zahtjeva 1-11 ili sastav prema zahtjevu 12 za upotrebu u liječenju, prevenciji ili ublažavanju bolesti u vezi s deregulacijom alternativnog puta komplementa kod subjekta.
14. Spoj ili sastav za upotrebu prema zahtjevu 13, gdje je bolest: a) makularna degeneracija, starosna makularna degeneracija (AMD), vlažna AMD, suha AMD ili geografska atrofija; b) bolest bubrega, opcionalno gdje je bolest lupus nefritis, sistemski eritemski lupus (SLE), bolest gustih naslaga (DDD), C3 glomerulonefritis (C3GN), CFHR5 nefropatija ili atipični hemolitičko-uremički sindrom (aHUS).
HRP20191664 2014-05-01 2019-09-16 Sastavi i postupci za moduliranje ekspresije komplementa faktora b HRP20191664T1 (hr)

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US201461987471P 2014-05-01 2014-05-01
US201462076273P 2014-11-06 2014-11-06
EP15786214.5A EP3137596B1 (en) 2014-05-01 2015-05-01 Compositions and methods for modulating complement factor b expression
PCT/US2015/028916 WO2015168635A2 (en) 2014-05-01 2015-05-01 Compositions and methods for modulating complement factor b expression

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