Jeremy Lee BARYZA,Marcel BLOMMERS,Cesar FERNANDEZ,Erin GENO,Alvar GOSSERT,Paulette GREENIDGE,Dieter HUESKEN,Juerg HUNZIKER,Francois, Jean-Charles NATT,Anup PATNAIK,Andrew PATTERSON,Jean-Michel, Rene R
申请号：
HK16110154.3
公开号：
HK1221912A
申请日:
2016.08.25
申请国别(地区):
HK
年份:
2017
代理人:
摘要：
The disclosure relates to compositions comprising a HBV RNAi agent. In some embodiments, the HBV RNAi agent comprises a sense and an anti-sense strand, each strand being an 18-mer and the strands together forming a blunt-ended duplex, wherein the 3′ end of at least one strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5′ to 3′ order: a spacer； a second phosphate or modified internucleoside linker； and a 3′ end cap. In some embodiments, the 3′ end of both the sense and anti-sense strand further comprise, in 5′ to 3′ order: a spacer； a second phosphate or modified internucleoside linker； and a 3′ end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3′ end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the RNAi agent can be modified on one or both 5′ end. Optionally, the sense strand can comprise a 5′ end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference. The disclosure also pertains to methods of treating, ameliorating and preventing HBV in a patient involving the step of administering to the patient a therapeutic amount of a HBV RNAi agent.
