DK2726613T3 - Sammensætninger og fremgangsmåder til inhibering af genekspression af hepatitis-b-virus - Google Patents

Sammensætninger og fremgangsmåder til inhibering af genekspression af hepatitis-b-virus Download PDF

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DK2726613T3
DK2726613T3 DK12804876.6T DK12804876T DK2726613T3 DK 2726613 T3 DK2726613 T3 DK 2726613T3 DK 12804876 T DK12804876 T DK 12804876T DK 2726613 T3 DK2726613 T3 DK 2726613T3
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base
artificial sequence
modified
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dsrna
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Daniel Chin
Jochen Deckert
Matthias John
Markus Hossbach
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Arrowhead Pharmaceuticals Inc
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Claims (14)

1. Dobbeltstrenget ribonucleinsyremolekyle der er i stand til at hæmme ekspressionen af et hepatitis-B-virusgen in vitro med mindst 80 %, hvor det dobbeltstrengede ribonucleinsyremolekyle omfatter en sensstreng, der omfatter i rækkefølge nucleotider 1-19 i SEQ ID Nr.: 2,3 eller 6 og en antisensstreng, der mindst delvist er komplementær til sensstrengen; hvor komplementarregionen er mindre end 30 nucleotider i længden; og hvor det dobbeltstrengede ribonucleinsyremolekyle omfatter mindst et modificeret nucleotid.
2. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 1, hvor antisensstrengen omfatter i rækkefølge nucleotider 1-19 i SEQ ID Nr.: 158, 159, 160 eller 163.
3. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 2, hvor det dobbeltstrengede ribonucleinsyremolekyle omfatter sekvenspar, som er valgt blandt gruppen, der består af SEQ ID Nr.: 2/158, 3/159, 3/160 eller 6/163.
4. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 1, hvor antisensstrengen yderligere omfatter et 3'-overhæng på 1 -5 nucleotider i længden.
5. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 4, hvor antisense-stren-gens overhæng omfatter uracil eller nucleotider, som er komplementære til et pregenomisk RNA og/eller et mRNA, som koder for proteinet, der er nødvendigt for replikation eller patogenese af hepatitis-B-virus.
6. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 1, hvor sensstrengen yderligere omfatter et 3'-overhæng på 1-5 nucleotider i længden.
7. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 6, hvori overhænget af sensstrengen omfatter uracil eller nucleotider, som er identiske med et pregenomisk RNA og/eller et mRNA, der koder for proteinet, der er nødvendigt for replikation eller patogenese af hepatitis-B-virus.
8. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 1, hvor det dobbeltstrengede ribonucleinsyremolekyle omfatter mindst ét modificeret nucleotid der er udvalgt fra gruppen, som består af: 2'-0-methyl-modificeret nucleotid, nucleotid, der omfatter en 5'-phosphorthioatgruppe, terminalt nucleotid bundet til et cholesteryl-derivat, terminal nucleotid der er bundet til en dodecansyre-bisdecylamidgruppe, 2'-deoxy-2'-fluormodificeret nucleotid, 2'-deoxymodificeret nucleotid, låst nucleotid, abasisk nucleotid, deoxythymidin, inverteret deoxythymidin, 2'-amino-mo-dificeret nucleotid, 2'-alkyl-modificeret nucleotid, morpholino-nucleotid, phospho-ramidat og ikke-naturlig base, der omfatter nucleotid.
9. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 8, hvor det dobbeltstrengede ribonucleinsyremolekyle indeholder et modificeret nucleotid, et nucleotid af en 5'-phosphorthioatgruppe og en deoxythymidin.
10. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 9, hvor sensstrengen eller antisensstrengen omfatter et overhæng af 1 -2 deoxythymidiner.
11. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 1, hvor det dobbeltstrengede ribonucleinsyremolekyle omfatter sekvensparrene, som er valgt fra gruppen, der består af SEQ ID Nr.: 322/486, 323/487, 324/488 og 327/491.
12. Dobbeltstrenget ribonucleinsyremolekyle ifølge krav 1, hvor det dobbeltstrengede ribonucleinsyremolekyle omfatter en nucleinsyresekvens der koder for den nævnte sensstreng eller antisensstreng.
13. Farmaceutisk sammensætning der omfatter: a) mindst et dobbeltstrenget ribonucleinsyremolekyle som defineret i et hvilket som helst af kravene 1 til 12; eller b) mindst en nucleinsyresekvens der koder for en sensstreng eller en antisensstreng, der omfatter det dobbeltstrengede ribonucleinsyremolekyle som defineret i et hvilket som helst af kravene 1 til 12.
14. Farmaceutisk sammensætning ifølge krav 13, der yderligere omfatter en farmaceutisk acceptabel bærer, stabilisator og/eller fortyndingsmiddel.
DK12804876.6T 2011-06-30 2012-06-28 Sammensætninger og fremgangsmåder til inhibering af genekspression af hepatitis-b-virus DK2726613T3 (da)

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EP11172235 2011-06-30
PCT/US2012/044505 WO2013003520A1 (en) 2011-06-30 2012-06-28 Compositions and methods for inhibiting gene expression of hepatitis b virus
US13/535,454 US8809293B2 (en) 2011-06-30 2012-06-28 Compositions and methods for inhibiting gene expression of hepatitis B virus

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AU (5) AU2012275355B2 (da)
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TWI695066B (zh) 2020-06-01
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JP2014527401A (ja) 2014-10-16
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US8809293B2 (en) 2014-08-19
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EP3418386A2 (en) 2018-12-26
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MX2013013556A (es) 2014-02-27
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JP2023179497A (ja) 2023-12-19
AU2022206748A1 (en) 2022-08-18
JP2017169568A (ja) 2017-09-28
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EP3418386B1 (en) 2021-04-07
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IL230226B (en) 2019-12-31
CA3064103C (en) 2023-03-07
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ES2690538T3 (es) 2018-11-21
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EA201391394A1 (ru) 2014-05-30
EA201690497A2 (ru) 2016-08-31

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