PT2287305E - Inibição mediada por interferência de arn de expressão génica usando ácido nucleico de interferência pequeno (sian) - Google Patents
Inibição mediada por interferência de arn de expressão génica usando ácido nucleico de interferência pequeno (sian) Download PDFInfo
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- PT2287305E PT2287305E PT100089291T PT10008929T PT2287305E PT 2287305 E PT2287305 E PT 2287305E PT 100089291 T PT100089291 T PT 100089291T PT 10008929 T PT10008929 T PT 10008929T PT 2287305 E PT2287305 E PT 2287305E
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- nucleotides
- nucleic acid
- molecule
- sian
- pyrimidine
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Claims (25)
- REIVINDICAÇÕES 1. Uma molécula de ácido nucleico de interferência pequeno (siAN) modificada quimicamente capaz de reqular neqativamente a expressão de um qene alvo em células por interferência de ARN (iARN), em que o siAN compreende: (a) uma cadeia sense e uma cadeia antisense; (b) cada cadeia da molécula de ácido nucleico tem independentemente um comprimento de 18 a 24 nucleótidos e o dúplex de siAN compreende de 17 a 23 pares de bases; (c) 5, 6, 7, 8, 9, 10 ou mais nucleótidos de pirimidina da cadeia sense e/ou 5, 6, 7, 8, 9, 10 ou mais nucleótidos de pirimidina da cadeia antisense são modificdos quimicamente com nucleótidos 2'-desoxi, 2'-O-metilo e/ou 2'-desoxi-2'-fluoro; e (d) estando presentes uma ou mais ligações internucleotídicas de fosforotioato e/ou uma molécula de proteção terminal na extremidade 3', na extremidade 5' ou em ambas as extremidades 3' e 5', na mesma cadeia ou numa cadeia diferente do siAN em que a molécula de siAN compreende dois fragmentos oligonucleotídicos separados, em que um fragmento compreende a região sense e um segundo fragmento compreende a região antisense, e em que o fragmento que compreende a região sense inclui um resíduo de proteção terminal na extremidade 5', na extremidade 3' ou em ambas as extremidades 5' e 3'.
- 2. A molécula de siAN, de acordo com a reivindicação 1, em que os nucleótidos de purina na região sense são nucleótidos de 2'-desoxi purina e em que os nucleótidos de pirimidina na região sense são nucleótidos de 2'-desoxi-2'-fluoro pirimidina.
- 3. A molécula de siAN, de acordo com a reivindicação 1, em que os nucleótidos de pirimidina da região antisense são nucleótidos de 2'-desoxi-2'-fluoro pirimidina e em que os nucleótidos de purina na região antisense são nucleótidos de 2'-0-metil purina.
- 4. A molécula de siAN, de acordo com a reivindicação 1, em que os nucleótidos de purina presentes na região antisense são nucleótidos de 2'-desoxi purina e em que os nucleótidos de pirimidina presentes na dita região antisense são nucleótidos de 2'-desoxi-2'-fluoro pirimidina.
- 5. A molécula de siAN, de acordo com qualquer uma das reivindicações 1, 3 e 4, em que a dita região antisense compreende uma ligação internucleotídica de fosforotioato na extremidade 3' da região antisense.
- 6. A molécula de siAN, de acordo com a reivindicação 1, em que cada um dos dois fragmentos da molécula de siAN compreende 21 nucleótidos.
- 7. A molécula de siAN, de acordo com a reivindicação 1, em que 19 nucleótidos de cada fragmento da molécula de siAN formam pares de bases com os nucleótidos complementares do outro fragmento da molécula de siAN, e em que pelo menos dois nucleótidos 3'-terminais de cada fragmento da molécula de siAN não formam pares de bases com os nucleótidos do outro fragmento da molécula de siAN.
- 8. A molécula de siAN, de acordo com a reivindicação 1, em que 19 nucleótidos da região antisense formam pares de bases com a sequência de nucleótidos do ARN que codifica o gene alvo ou uma parte do mesmo.
- 9. A molécula de siAN, de acordo com a reivindicação 1, em que 21 nucleótidos da região antisense formam pares de bases com a sequência de nucleótidos do ARN que codifica o gene alvo ou uma parte do mesmo.
- 10. A molécula de siAN, de acordo com a reivindicação 1, em que os nucleótidos de purina na região sense são ribonucleótidos de purina e em que os nucleótidos de pirimidina na região sense são nucleótidos de 2'-desoxi-2'-fluoro pirimidina, e em que o fragmento sense inclui um resíduo de proteção terminal nas extremidades 5' e 3' .
- 11. A molécula de siAN, de acordo com a reivindicação 1, em que os nucleótidos de purina na região sense são ribonucleótidos de purina, e em que os nucleótidos de pirimidina na região sense são nucleótidos de 2'-0-metil pirimidina, e em que o fragmento sense inclui um resíduo de proteção terminal nas extremidades 5' e 3'.
- 12. A molécula de ácido nucleico, de acordo com a reivindicação 1, em que 5, 6, 7, 8, 9, 10 ou mais nucleótidos de pirimidina da cadeia sense são nucleótidos de 2'-desoxi pirimidina.
- 13. A molécula de ácido nucleico, de acordo com a reivindicação 1, em que 5, 6, 7, 8, 9, 10 ou mais nucleótidos de pirimidina da cadeia sense são nucleótidos de 2'-0-metil pirimidina.
- 14. A molécula de ácido nucleico, de acordo com a reivindicação 1, em que 5, 6, 7, 8, 9, 10 ou mais nucleótidos de pirimidina da cadeia sense são nucleótidos de 2' -desoxi-2'-fluoro pirimidina.
- 15. A molécula de ácido nucleico, de acordo com a reivindicação 1, em que 5, 6, 7, 8, 9, 10 ou mais nucleótidos de pirimidina da cadeia antisense são nucleótidos de 2'-0-metil pirimidina.
- 16. A molécula de ácido nucleico, de acordo com a reivindicação 1, em que 5, 6, 7, 8, 9, 10 ou mais nucleótidos de pirimidina da cadeia antisense são nucleótidos de 2' -desoxi-2'-fluoro pirimidina.
- 17. A molécula de ácido nucleico, de acordo com qualquer reivindicação anterior, em que o resíduo de proteção terminal é um resíduo apurínico ou apirimidínico desoxi invertido.
- 18. A molécula de ácido nucleico, de acordo com qualquer reivindicação anterior, que compreende 1, 2, 3, 4, 5, 6, 7, 8, 9 ou 10 ligações internucleotídicas de fosforotioato.
- 19. A molécula de ácido nucleico, de acordo com qualquer reivindicação anterior, em que a molécula de ácido nucleico compreende ribonucleótidos.
- 20. A molécula de ácido nucleico, de acordo com qualquer reivindicação anterior, em que o ARN alvo é uma sequência de ARN de mamífero.
- 21. A molécula de ácido nucleico, de acordo com qualquer reivindicação anterior, em que o ARN alvo é uma sequência de ARN humano.
- 22. A molécula de ácido nucleico, de acordo com a reivindicação 21, em que a sequência de ARN humano compreende sequências de VEGFr-1, VEGFr-2, HER1, HER2, HER3, HER4, TERT, ARN de telomerase, NFkappaB, Rel-A, NOGO, NOGOr, RAS, RAF, CD20, METAP2, CLCA1, fosfolambano ou PTP1B humanas.
- 23. A molécula de ácido nucleico, de qualquer uma das reivindicações 1 a 19, em que o ARN alvo é uma sequência de ARN virai.
- 24. A molécula de ácido nucleico, de acordo com a reivindicação 23, em que a sequência de ARN virai compreende a sequência de VHB, VHC, VIH-1, VIH-2, WNV, CMV, VSR, vírus da gripe, rinovírus, papilomavírus, VHS ou HILV.
- 25. Uma composição que compreende a molécula de ácido nucleico de acordo com qualquer reivindicação anterior e um veículo ou diluente farmaceuticamente aceitável.
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PT141956276T PT2902406T (pt) | 2002-02-20 | 2003-02-20 | Inibição mediada por interferência de arn de expressão génica usando ácido nucleico de interferência pequeno (sian) |
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PT141956276T PT2902406T (pt) | 2002-02-20 | 2003-02-20 | Inibição mediada por interferência de arn de expressão génica usando ácido nucleico de interferência pequeno (sian) |
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- 2003-02-20 ES ES10008930T patent/ES2394269T3/es not_active Expired - Lifetime
- 2003-02-20 PT PT100089291T patent/PT2287305E/pt unknown
- 2003-02-20 SI SI200332566T patent/SI2902406T1/en unknown
- 2003-02-20 WO PCT/US2003/004951 patent/WO2003070970A2/en not_active Application Discontinuation
- 2003-02-20 AU AU2003216315A patent/AU2003216315A1/en not_active Abandoned
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- 2003-02-20 WO PCT/US2003/005044 patent/WO2003070911A2/en not_active Application Discontinuation
- 2003-02-20 PT PT141956276T patent/PT2902406T/pt unknown
- 2003-02-20 EP EP03716126A patent/EP1458741B1/en not_active Expired - Lifetime
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- 2003-02-20 AU AU2003221258A patent/AU2003221258B2/en not_active Expired
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- 2003-02-20 DK DK10008929.1T patent/DK2287305T4/en active
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- 2003-02-20 CA CA002459532A patent/CA2459532A1/en not_active Abandoned
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- 2003-02-20 EP EP03742826A patent/EP1470257A4/en not_active Withdrawn
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2004
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2006
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2008
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2010
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2012
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2015
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2018
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