DK2674494T3 - Enkelt-strenget RNA-molekyle med et nitrogenholdigt alicyklisk skelet - Google Patents
Enkelt-strenget RNA-molekyle med et nitrogenholdigt alicyklisk skelet Download PDFInfo
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Claims (15)
1. Et enkelt-strenget RNA-molekyie omfattende en ekspressions- inhiberende sekvens, der inbiberer ekspressionen af et målgen, hvor: - molekylet omfatter: en region (Xc), en linker region (Lx) og en region (X); - regionen (X) omfatterden ekspressions-inhiberende sekvens; - regionen (Xc) er komplementær til regionen (X); og - linker-regionen (Lx) er repræsenteret ved den følgende formel (i):
hvor: X1 og X2 hver uafhængigt er H2, O, S eller NH; Y1 og Y2 hver uafhængigt er en enkeltbinding, CH2, NH, O eller S; R3 er et hydrogenatom eller en substituent, der er bundet til C-3, 04, C-5 eller 06 på en ring A; L1 er en aikylenkæde sammensat af N-atomer, og et hydrogenatom på en alkyien-carbonatom kan eller kan ikke være substitueret med OH, 0Ra, NH2i NHRa, NRaRb, SH eller SRa, eller L1 er en polyether kæde opnået ved at substituere mindst et carbonatom i alkylenkæden med et oxygenatom, forudsat, at: når Y1 er NH, O eller S, så er et atom bundet til Y1 i L1 carbon, et atom bundet til OR1 i L1 er carbon, og oxygenatomer støder Ikke op til hinanden; L2 er en alkylenkæde bestående af m-atomer, og et hydrogenatom i en alkylengruppe carbonatom kan eller kan ikke være substitueret med OH, ORc, NH2j NHRc:, NRcRd, SH eller SRC, eller L2 er en polyether kæde opnået ved at substituere mindst et carbonatom i alkylenkæden med et oxygenatom, forudsat, at: når Y2 er NH, O eller S, så er et atom bundet til Y2 i L2 carbon, et atom bundet til OR^ i L2 er carbon, og oxygenatomer støder ikke op til hinanden; Ra, Rb, Rc og Rd er hver uafhængigt en substituent eller en beskyttelsesgruppe; i er 1 eller 2; m er et heltal i området fra 0 til 30; n er et heltal i området fra 0 til 30; regionerne (Xc) og (X) er hver forbundet med linker-regionen (Lx) via -OR1- eller -OR2-; og R1 og R2 kan eller kan ikke kan være til stede, og når de er til stede, så er R1 og R2 hver uafhængigt en nukleotidrest eller strukturen med formlen (I).
2. Dei enkeltstrengede molekyle ifølge krav 1, hvor L1 er polyetherkæden, og polyetherkæden er polyethylenglycol.
3. Det enkeltstrengede molekyle ifølge krav 1 eller 2, hvor summen (m + n) af antallet af atomer (n) i L1 og antallet af atomer (m) i L2 er i området fra 0 til 30.
4. Det enkeltstrengede molekyle ifølge et hvilket som helst af de foregående krav, hvor strukturen af formlen (!) er en hvilken som helst af de følgende formler (i-1) til (i-9), hvor n er et heltal fra 0 til 30, m er et heltal fra 0 til 30, og q er et heltal fra 0 til 10:
5. Det enkeltstrengede molekyle ifølge krav 4, hvor: i formlen (1-1), n = 8; i formlen (I-2), n = 3; I formlen (I-3), n = 4 eller 8; formlen (I-4), n = 7 eller 8; i formlen (I-5), n = 3 og m = 4; i formlen (I-6), n = 8 og m = 4; I formlen (I-7), n = 8 og m = 4; i formlen (I-8), n = 5, og m = 4; og i formlen (I-9), q = 1 og m = 4.
6. Dei enkeltstrengede molekyle ifølge krav 4, hvor formlen (1-4) er den følgende formel (1-43), og formel (1-8) er den følgende formel (i-8a):
7. Det enkeltstrengede molekyle ifølge et hvilket søm helst af de foregående krav, hvor antallet af baser (X) i regionen (X), og antallet af baser (Xc) i regionen (Xc) opfylder betingelsen for udtrykkene (3) eller (5): X > Xc ...(3) X = Xc ...(5)
8. Det enkeltstrengede molekyle ifølge krav 7, hvor antallet af baser (X) i regionen (X), og antallet af baser (Xc) i regionen (Xc) opfylder betingelsen for udtrykket (11): X - Xc = 1, 2, eller 3 ... (11).
9. Det enkeltstrengede molekyle ifølge et hvilket som helst af de foregående krav, hvor antallet af baser (X) i regionen (X) er fra 19 til 30.
10. Det enkeltstrengede molekyle ifølge et hvilket som helst aide foregående krav, hvor - det samlede antal baser i molekylet er 38 eller mere; og / eller - det enkeltstrengede molekyle omfatter mindst en modificeret rest og / eller en mærkningssubstans og / eller en stabil isotop.
11 .Sammensætning til inhibering af ekspression af et målgen, hvor sammensætningen omfatter det enkeltstrengede molekyle ifølge et hvilket som helst af de foregående krav.
12. Farmaceutisk sammensætning omfattende det enkeltstrengede molekyle ifølge et hvilket som helst af kravene 1 til 10.
13. Den farmaceutiske sammensætning ifølge krav 12, til anvendelse i behandling af inflammation.
14. In vitro fremgangsmåde til inhibering af ekspression af et målgen, hvilken fremgangsmåde omfatter anvendelse af det enkeltstrengede molekyle ifølge et hvilket som helst af kravene 1 til 10, hvor eventuelt - fremgangsmåden omfatter indgivelse af det enkeltstrengede molekyle til en celle, et væv eller et organ in vitro; eller - ekspression af målgenet inhiberes ved at inducere RNA-interferens.
15. Et enkeltstrenget molekyle ifølge et hvilket som helst af kravene 1 til 10 til anvendelse i en fremgangsmåde til behandling af en sygdom, hvor molekylet omfatter, som den ekspressions-inhiberende sekvens, en sekvens, der inhiberer ekspressionen af et gen, der forårsager sygdommen.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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JP2010174915 | 2010-08-03 | ||
JP2010230806 | 2010-10-13 | ||
JP2010269823 | 2010-12-02 | ||
JP2011152381 | 2011-07-08 | ||
EP11748250.5A EP2436767B1 (en) | 2010-08-03 | 2011-07-28 | Single-stranded RNA molecule having nitrogen-containing alicyclic skeleton |
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DK2674494T3 true DK2674494T3 (da) | 2015-02-23 |
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DK13184178.5T DK2674494T3 (da) | 2010-08-03 | 2011-07-28 | Enkelt-strenget RNA-molekyle med et nitrogenholdigt alicyklisk skelet |
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EP (4) | EP2639307B1 (da) |
JP (3) | JP4965745B2 (da) |
KR (3) | KR101849801B1 (da) |
CN (3) | CN104059911B (da) |
DK (1) | DK2674494T3 (da) |
ES (4) | ES2527660T3 (da) |
HK (2) | HK1189910A1 (da) |
PT (1) | PT2674494E (da) |
TW (2) | TWI572716B (da) |
WO (1) | WO2012017919A1 (da) |
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