DK2363481T3 - Forbindelser og fremgangsmåder til modulering af genekspression - Google Patents

Forbindelser og fremgangsmåder til modulering af genekspression Download PDF

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Publication number
DK2363481T3
DK2363481T3 DK11160528.3T DK11160528T DK2363481T3 DK 2363481 T3 DK2363481 T3 DK 2363481T3 DK 11160528 T DK11160528 T DK 11160528T DK 2363481 T3 DK2363481 T3 DK 2363481T3
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certain embodiments
short antisense
certain
seq
antisense compound
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DK11160528.3T
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Sanjay Bhanot
Richard S Geary
Robert Mckay
Brett P Monia
Andrew M Siwkowski
Edward Wancewicz
Punit P Seth
Eric E Swayze
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Ionis Pharmaceuticals Inc
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Priority claimed from PCT/US2007/061183 external-priority patent/WO2007090071A2/en
Application filed by Ionis Pharmaceuticals Inc filed Critical Ionis Pharmaceuticals Inc
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Publication of DK2363481T3 publication Critical patent/DK2363481T3/da

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Claims (14)

1. Kort antisense-forbindelse med en længde på 12 til 14 monomerer, omfattende et 2'-deoxyribonukleotid-gapområde flankeret på hver side af en vinge, hvor hver vinge uafhængigt omfatter 1 til 3 høj-affinitets-modificerede nukleotider der er sukker-modificerede nukleotider der omfatter en bro mellem 4'- og 2'-positionen af sukkeret, og hvor den korte antisense-forbindelse endvidere omfatter en kovalent forbundet konjugeret gruppe.
2. Kort antisense-forbindelse ifølge krav 1 hvor antisense-forbindelsen har en længde på 13 monomerer.
3. Kort antisense-forbindelse ifølge krav 1, hvor hver af broerne, uafhængigt, er 4'-CH2-2', 4^(012)2-2^ 4'-CH2-0-2', 4'-(CH2)2-0-2', 4'-CH2-0-N(Ri)-2' eller 4'-CH2-N(Ri)-0-2', hvor hver Ri uafhængigt er, H, en beskyttelsesgruppe eller Ci-Ci2-alkyl.
4. Kort antisense-forbindelse ifølge krav 1, hvor broen er 4'-CH(CH3)-0-2'.
5. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor den konjugerede gruppe er valgt fra listen bestående af: kolesterol, cholsyre, et thiokolesterol, et Ci6-alkyl, et phospholipid, en polyaminkæde, en polyethylenglycolkæde, adamantan-eddikesyre, en palmityl-del, en octadecylamin-del og en hexylamino-carbonyl-oxykolesterol-del.
6. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1-4, hvor den konjugerede gruppe er forbundet direkte med moderforbindelsen.
7. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1-4, hvor den konjugerede gruppe er forbundet med moderforbindelsen via en forbindelsesgruppe.
8. Kort antisense-forbindelse ifølge krav 7 hvor forbindelsesgruppen er en oligomer af gentagelsesenheder, 8-amino-3,6-dioxaoctansyre (ADO), succinimidyl 4-(N-maleimidomethyl) cyclohexan-l-carboxylat (SMCC), 6-aminohexansyre (AHEX eller Al-IA), et substitueret Ci-Cio-alkyl, et substitueret eller ikke-substitueret C2-Cio-alkenyl eller et substitueret eller ikke-substitueret C2-C10-alkynyl.
9. Kort antisense-forbindelse ifølge et hvilket som helst af de foregående krav, hvor nukleobasesekvensen af antisense-forbindelsen er 100% komplementærtil en målnukleinsyre.
10. Kort antisense-forbindelse ifølge et hvilket som helst af de foregående krav, med et motiv valgt fra gruppen bestående af 1-12-1, 2-10-2, 1-10-1, 1-10-2, 3-8-3, 2-8-2, 1-8-1, og 1-9-2 hvor det første tal betegner antallet af monomerer i 5'-vingen, det andet tal betegner antallet af monomerer i gappet, og det tredje tal betegner antallet af monomerer i 3'-vingen.
11. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1-10, med et 1-1-10-2-motiv, hvor det første tal betegner antallet af monomerer i en første 5'-vinge, det andet tal betegner antallet af monomerer i en anden 5'-vinge, det tredje tal betegner antallet af monomerer i gappet, og det fjerde tal betegner antallet af monomerer i 3'-vingen.
12. Kort antisense-forbindelse ifølge et hvilket som helst af de foregående krav hvor mindst en monomer binding er en modificeret monomer binding, såsom en phosphorthioat-binding.
13. Farmaceutisk sammensætning omfattende en effektiv mængde af en kort antisense forbindelse ifølge et hvilket som helst af de foregående krav og en farmaceutisk acceptabel fortynder, bærer eller excipiens.
14. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1-12 eller den farmaceutiske sammensætning ifølge krav 13, til anvendelse til behandling af en tilstand eller lidelse hos et pattedyrs-, fortrinsvis menneskeligt, individ.
DK11160528.3T 2006-05-05 2007-05-07 Forbindelser og fremgangsmåder til modulering af genekspression DK2363481T3 (da)

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US74663106P 2006-05-05 2006-05-05
US74705906P 2006-05-11 2006-05-11
US80566006P 2006-06-23 2006-06-23
US86455406P 2006-11-06 2006-11-06
PCT/US2007/061183 WO2007090071A2 (en) 2006-01-27 2007-01-27 6-modified bicyclic nucleic acid analogs
EP07811872A EP2021472B1 (en) 2006-05-05 2007-05-07 Compounds and methods for modulating gene expression

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DK07811878.3T DK2019692T3 (da) 2006-05-05 2007-05-07 Forbindelser og fremgangsmåder til modulation af ekspression af gccr
DK11189591.8T DK2458006T3 (da) 2006-05-05 2007-05-07 Forbindelser og fremgangsmåder til modulering af ApoB ekspression.
DK11160528.3T DK2363481T3 (da) 2006-05-05 2007-05-07 Forbindelser og fremgangsmåder til modulering af genekspression
DK07811872.6T DK2021472T3 (da) 2006-05-05 2007-05-07 Forbindelser og fremgangsmåder til modulering af genekspression
DK07811873.4T DK2015758T3 (da) 2006-05-05 2007-05-07 Forbindelser og fremgangsmåder til modulering af ekspression af apob

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DK11189591.8T DK2458006T3 (da) 2006-05-05 2007-05-07 Forbindelser og fremgangsmåder til modulering af ApoB ekspression.

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US (14) US9045754B2 (da)
EP (10) EP2505646A1 (da)
JP (7) JP5731115B2 (da)
KR (1) KR101441700B1 (da)
CN (1) CN103554205A (da)
AT (2) ATE514777T1 (da)
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CN103301475B (zh) 2005-12-28 2016-08-03 斯克里普斯研究所 药物组合物和表达载体以及调节基因表达的方法和核酸分子的应用
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