LINDHOLM, MARIE,ALBÆK, NANNA,RAVN, JACOB,PETRI, ANDREAS,NIELSEN, NIELS FISKER,HEDTJARN, MAJ
申请号：
PE0026672015
公开号：
PE01582016A1
申请日:
2014.06.27
申请国别(地区):
PE
年份:
2016
代理人:
摘要：
Refers to the same oligomeric compounds and conjugated with Target mRNA in the proproteina\u2013convertasa subtilisin \/ kexina Type 9 (PCSK9) in a cell, leading to a reduced expression of PCSK9.The oligomers are antisense oligonucleotides with a length between 12 and 22 nucleotides, which include: (a) a contiguous sequence of between 10 and 16 nucleotides complementary to a segment of sec id no 33 or 34, 45 or (b) a sequence of 16 contiguous complementary nucleotides A Tranche of sec id no 31.The conjugated oligomers comprising: (a) an antisense oligonucleotide, between 12 and 22 nucleotides in length, which comprises a contiguous sequence of between 10 and 16 nucleotides complementary to a segment of sec id no 30, 31, 32, 33, 34 and 45 and (b) at least one fraction co Not njugada (Poly) The nucleotide covalently linked oligonucleotide.Optionally through a Connecting region. In a Preferred aspect, the conjugate comprising a carbohydrate fraction, and more preferably a n\u2013acetilgalactosamina (galnac) monovalent or multivalent.These compounds are useful for the treatment of hypercholesterolemia and Related Disorders, such as atherosclerosis, hyperlipidemia, dyslipidemia, Coronary Artery Disease and Coronary Heart Disease, includingSE REFIERE A COMPUESTOS OLIGOMERICOS Y CONJUGADOS DE LOS MISMOS CON DIANA EN EL ARNm DE LA PROPROTEINA–CONVERTASA SUBTILISINA/KEXINA TIPO 9 (PCSK9) EN UNA CELULA, QUE CONDUCEN A UNA EXPRESION REDUCIDA DE PCSK9. LOS OLIGOMEROS SON OLIGONUCLEOTIDOS ANTISENTIDO CON UNA LONGITUD DE ENTRE 12 Y 22 NUCLEOTIDOS, QUE COMPRENDEN: (A) UNA SECUENCIA CONTIGUA DE ENTRE 10 Y 16 NUCLEOTIDOS COMPLEMENTARIOS A UN TRAMO CORRESPONDIENTE DE SEC ID NO 33, 34 o 45 O (B) UNA SECUENCIA CONTIGUA DE 16 NUCLEOTIDOS COMPLEMENTARIOS A UN TRAMO CORRESPONDIENTE DE SEC ID NO 31. LOS CONJUGADOS DE OLIGOMEROS COMPRENDEN: (A) UN OLIGONUCLEOTIDO ANTISENTIDO DE ENTRE 12 Y 22 NUCLEOTIDOS DE LONGITUD, QUE COMPRENDE UNA SECUENCIA CONTIGUA DE ENTRE 10 Y 16 NUCLEOTIDOS COMPLEMEN
