DK2441449T3 - Modulation af apolipoprotein C-III-ekspression - Google Patents

Modulation af apolipoprotein C-III-ekspression Download PDF

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DK2441449T3
DK2441449T3 DK11185507.8T DK11185507T DK2441449T3 DK 2441449 T3 DK2441449 T3 DK 2441449T3 DK 11185507 T DK11185507 T DK 11185507T DK 2441449 T3 DK2441449 T3 DK 2441449T3
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apolipoprotein
dna
lll
antisense
artificial sequence
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Rosanne M Crooke
Mark J Graham
Tarbet Kristina M Lemonidis
Kenneth Dobie
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Isis Pharmaceuticals Inc
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Claims (10)

1. Forbindelse 15 til 30 nukleobaser i længde targeteret til den 3'-ikke-translaterede region (3'UTR) af et nukleinsyremolekyle der koder for humant apolipoprotein C-III, hvor forbindelsen specifikt hybridiserer med nukleinsyre-molekylet der koder for humant apolipoprotein C-III og inhiberer ekspressionen af humant apolipoprotein C-III, hvor forbindelsen er mindst 90% komplementær med nukleinsyremolekylet der koder for humant apolipoprotein C-III, til anvendelse i terapi.
2. Forbindelsen til anvendelse ifølge krav 1, hvor forbindelsen er et antisense-oligonukleotid.
3. Forbindelsen til anvendelse ifølge krav 1 eller krav 2, hvor forbindelsen har en sekvens der er mindst 95% eller er 100% komplementær med nukleinsyremolekylet der koder for apolipoprotein C-III.
4. Forbindelsen til anvendelse ifølge et hvilket som helst af de foregående krav, hvor nukleinsyremolekylet er et nukleinsyremolekyle der koder for humant apolipoprotein C-III med sekvensen af SEQ ID NO:4 eller SEQ ID NO: 18.
5. Forbindelsen til anvendelse ifølge et hvilket som helst af de foregående krav, med mindst én modificeret internukleosidbinding, sukkerenhed eller nukleobase.
6. Forbindelsen til anvendelse ifølge krav 5, har mindst én 2'-0-methoxyethylsukkerenhed, phosphorthioat-internukleosidbinding eller 5-methylcytosin.
7. Forbindelsen til anvendelse ifølge et hvilket som helst af de foregående krav, hvor forbindelsen er et kimært antisenseoligonukleotid.
8. Forbindelsen til anvendelse ifølge krav 7, hvor det kimære oligonukleotid er 20 nukleotider i længde, omfattende ti 2'-deoxynucleotider, flankeret på hver side med fem 2'-methoxyethylnukleotider, hvor internukleosidbindingerne er phosphorthioat, og alle cytosinrester er 5-methylcytosiner.
9. Forbindelse til anvendelse ifølge et hvilket som helst af de foregående krav, til anvendelse i behandling af et dyr med en sygdom eller tilstand forbundet med apolipoprotein C-III i et dyr, hvor: (i) sygdommen eller tilstanden involverer unormal lipidmetabolisme; (ii) sygdommen eller tilstanden involverer unormal cholesterolmetabolisme; (iii) sygdommen eller tilstanden er atherosclerose; (iv) sygdommen eller tilstanden er en unormal metabolisk tilstand; (v) sygdommen eller tilstanden er hyperlipidæmi; (vi) sygdommen eller tilstanden er hypertriglyceridæmi (vii) sygdommen eller tilstanden er diabetes; (viii) sygdommen eller tilstanden er fedme; eller (ix) sygdommen eller tilstanden er kardiovaskulær sygdom.
10. Farmaceutisk sammensætning omfattende en effektiv mængde af en forbindelse ifølge krav 1 og et farmaceutisk acceptabelt fortyndingsmiddel eller bærer, til anvendelse i terapi, hvor forbindelsen har en sekvens bestående af nukleobasesekvensen af SEQ ID NO: 87, og er et kimært oligonukleotid 20 nukleotider i længde, omfattende en gap-region bestående af ti 2'-deoxynukleo-tider, flankeret på hver side med fem 2'-0-methoxyethylnukleotider, hvor internukleosidbindingerne er phosphorthioatbindinger igennem hele oligonukleotidet og alle cytosinrester er 5-methylcytosiner.
DK11185507.8T 2003-04-16 2004-04-15 Modulation af apolipoprotein C-III-ekspression DK2441449T3 (da)

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US10/418,780 US7598227B2 (en) 2003-04-16 2003-04-16 Modulation of apolipoprotein C-III expression
EP04749914A EP1622597B1 (en) 2003-04-16 2004-04-15 Modulation of apolipoprotein c-iii expression

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US (6) US7598227B2 (da)
EP (4) EP2441449B1 (da)
AT (1) ATE529103T1 (da)
AU (2) AU2004231550B2 (da)
CA (2) CA2522560C (da)
CY (1) CY1117030T1 (da)
DK (2) DK1622597T3 (da)
ES (3) ES2666405T3 (da)
HU (1) HUE027411T2 (da)
PL (1) PL2441449T3 (da)
PT (1) PT2441449E (da)
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WO (1) WO2004093783A2 (da)

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