Patent ID: 8614309
Filing Date: 2013-12-24
Classification: A61P,C07H,C12N

Abstract:
1. A double-stranded RNA compound having the following structure: wherein each of N and N′ is a modified or an unmodified ribonucleotide or is an unconventional moiety selected from the group consisting of a locked nucleic acid (LNA), a modified deoxyribonucleotide, an unmodified deoxyribonucleotide, a mirror nucleotide and a nucleotide joined to an adjacent nucleotide by a 2′-5′ internucleotide phosphate bond; wherein each of (N)x and (N′)y is an oligonucleotide in which each consecutive N or N′ is joined to the next N or N′ by a covalent bond; wherein Z and Z′ may be present or absent, but if present is independently 1-5 consecutive nucleotides covalently attached at the 3′ terminus of the strand in which it is present; wherein z″ may be present or absent, but if present is a capping moiety covalently attached at the 5′ terminus of (N′)y; wherein x=y=19; wherein (N)x comprises at least five alternating 2′-O-methyl sugar modified ribonucleotides beginning at the 3′ terminus and at least nine 2′-O-methyl sugar modified ribonucleotides in total, and each remaining N is an unmodified ribonucleotide or an unconventional moiety; wherein in (N′)y an unconventional moiety is present at one or more of positions 15, 16, 17 or 18; an unconventional moiety may be present at one or more of positions 1, 2, 3 or 19; and an unmodified ribonucleotide is present at each remaining position; wherein the sequence of (N)x is 5′ AGGAGUUCCACAUUCUGGC 3′(SEQ ID NO:140); and wherein the sequence of (N′)y is 5′ GCCAGAAUGUGGAACUCCU 3′ (SEQ ID NO:139); or a pharmaceutical acceptable salt of such compound.