HRP20190826T1 - Konjugati oligonukleotida - Google Patents

Konjugati oligonukleotida Download PDF

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HRP20190826T1
HRP20190826T1 HRP20190826TT HRP20190826T HRP20190826T1 HR P20190826 T1 HRP20190826 T1 HR P20190826T1 HR P20190826T T HRP20190826T T HR P20190826TT HR P20190826 T HRP20190826 T HR P20190826T HR P20190826 T1 HRP20190826 T1 HR P20190826T1
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region
oligomeric compound
compound according
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phosphodiester
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HRP20190826TT
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Nanna ALBÆK
Henrik Frydenlund Hansen
Susanne KAMMLER
Jacob Ravn
Henrik ØRUM
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Roche Innovation Center Copenhagen A/S
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Claims (19)

1. Oligomerni spoj dug od 8 do 35, naznačen time da obuhvaća tri regije: (i) prvu regiju (regiju A) koja je antisense oligomer od 7 do 26 graničnih nukleotida komplementarnih ciljnoj nukleinskoj kiselini koja je sposobna za moduliranje, pri čemu prva regija obuhvaća najmanje jedan nukleozidni analog te time, da su internukleozidne poveznice prve regije 100% različite od fosfodiestera; (ii) drugu regiju (regiju B) kovalentno vezanu na 5` ili 3` završetak nukleotida prve regije putem fosfodiesterske poveznice, pri čemu se regija B sastoji od barem dvije, poput najmanje tri uzastopne DNK i/ili RNK jedinice koje su vezane fosfodiesterskim poveznicama; i (iii) treću regiju koja obuhvaća skupinu tvari konjugata ili ciljnu skupinu tvari, dok je treća regija kovalentno povezana na drugu regiju.
2. Oligomerni spoj prema patentnom zahtjevu 1, naznačen time, da su poveznice među nukleoizidima osim fosfodiestera, odabrane iz skupine koja se sastoji od fosforotioata, fosforoditioata i boranofosfata.
3. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 ili 2, naznačen time, da je ciljna nukleinska kiselina odabrana iz skupine koja se sastoji od mikroRNK, mRNK, lncRNK (duge nekodirajuće RNK), snRNK, snoRNK te virusne RNK.
4. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time, da prva regija oligomernog spoja obuhvaća gamper, miksmer ili totalmer.
5. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 4, naznačen time, da prva regija oligomernog spoja obuhvaća barem jedan biciklički nukleotidni analog (LNA).
6. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time, da prva i druga regija formiraju graničnu nukleotidnu sekvencu.
7. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 6, naznačen time, da je druga regija završetak 5` prve regije.
8. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 6, naznačen time, da je druga regija završetak 3` prve regije.
9. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 8, naznačen time, da se regija B sastoji od dinukleotida sekvence AA, AT, AC, AG, TA, TT, TC, TG, CA, CT, CC, CG, GA, GT, GC, ili GG.
10. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 8, naznačen time, da se regija B sastoji od trinukleotida sekvence AAA, AAT, AAC, AAG, ATA, ATT, ATC, ATG, ACA, ACT, ACC, ACG, AGA, AGT, AGC, AGG, TAA, TAT, TAC, TAG, TTA, TTT, TTC, TAG, TCA, TCT, TCC, TCG, TGA, TGT, TGC, TGG, CAA, CAT, CAC, CAG, CTA, CTG, CTC, CTT, CCA, CCT, CCC, CCG, CGA, CGT, CGC, CGG, GAA, GAT, GAC, CAG, GTA, GTT, GTC, GTG, GCA, GCT, GCC, GCG, GGA, GGT, GGC, ili GGG.
11. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 10, naznačen time, da je druga regija kovalentno vezana na treću regiju na terminalnom nukleozidu druge regije (tj. 3` ili 5` završetak, ovisno o položaju prve regije).
12. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time, da treća regija obuhvaća ne-nukleotidnu aktivnu tvar poput skupine konjugata kao što je sterol, primjerice kolesterol, ili ugljikohidrat poput klastera GalNac/GalNac.
13. Oligomerni spoj prema patentnom zahtjevu 12, naznačen time, da treća regija obuhvaća aktivnu tvar odabranu iz skupine koja se sastoji od: lipofilne skupine (npr. lipida, masne kiseline, sterola), proteina, peptida, protutijela ili njegova fragmenta, polimera, reporterske skupine, boje, liganda receptora, lijeka male molekule, predlijeka i vitamina.
14. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 13, naznačen time, da treća regija obuhvaća ciljanu skupinu.
15. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 14 naznačen time, da su druga i treća regija kovalentno udružene ne-nukleotidnom skupinom povezivača.
16. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 15, naznačen time, da kovalentna poveznica između druge i treće regije obuhvaća skupinu odabranu od fosfodiestera, fosforotioata te fosforoditioata ili boranofosfatne skupine, poput fosfodiesterske skupine.
17. Farmaceutski pripravak, naznačen time, da obuhvaća oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 16 i farmaceutski prihvatljivo sredstvo za razrjeđivanje, nosač, sol ili adjuvant.
18. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 16, naznačen time, da je za primjenu u inhibiciji ciljne nukleinske kiseline u stanici.
19. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 16, naznačen time, da je za primjenu u medicini.
HRP20190826TT 2012-11-15 2019-05-03 Konjugati oligonukleotida HRP20190826T1 (hr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP12192773 2012-11-15
EP13153296 2013-01-30
EP13157237 2013-02-28
EP13174092 2013-06-27
EP13791808.2A EP2920304B1 (en) 2012-11-15 2013-11-14 Oligonucleotide conjugates
PCT/EP2013/073858 WO2014076195A1 (en) 2012-11-15 2013-11-14 Oligonucleotide conjugates

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HRP20190826T1 true HRP20190826T1 (hr) 2019-06-28

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US (4) US20150291958A1 (hr)
EP (3) EP2920307B1 (hr)
JP (3) JP2016503300A (hr)
KR (2) KR102112892B1 (hr)
CN (3) CN104884618A (hr)
AU (2) AU2013346767B2 (hr)
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