Invention Grant
- Patent Title: Formats for organic compounds for use in RNA interference
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Application No.: US15025826Application Date: 2014-10-06
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Publication No.: US09988627B2Publication Date: 2018-06-05
- Inventor: Jeremy Lee Baryza , Marcel Blommers , William Chutkow , Cesar Fernandez , Erin Geno , Alvar Gossert , Paulette Greenidge , Dieter Huesken , Juerg Hunziker , Francois Jean-Charles Natt , Anup Patnaik , Andrew Patterson , Jean-Michel Rene Rondeau , Jan Weiler , Meicheng Zhu
- Applicant: Jeremy Lee Baryza , Marcel Blommers , William Chutkow , Cesar Fernandez , Erin Geno , Alvar Gossert , Paulette Greenidge , Dieter Huesken , Juerg Hunziker , Francois Jean-Charles Natt , Anup Patnaik , Andrew Patterson , Jean-Michel Rene Rondeau , Jan Weiler , Meicheng Zhu
- Applicant Address: CH Basel
- Assignee: NOVARTIS AG
- Current Assignee: NOVARTIS AG
- Current Assignee Address: CH Basel
- Agency: Brinks Gilson & Lione
- International Application: PCT/US2014/059301 WO 20141006
- International Announcement: WO2015/051366 WO 20150409
- Main IPC: C12N15/113
- IPC: C12N15/113

Abstract:
The disclosure relates to compositions comprising a RNAi agent having a novel format including a spacer subunit. The disclosure relates to compositions comprising a RNAi agent having a novel format: an 18-mer format with at least one internal spacer. These RNAi agents comprise a first and a second 18-mer strand, wherein the first strand is 18 ribonucleotides or 18 total ribonucleotides and spacer subunit(s), and the second strand is 18 total ribonucleotides and spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand; the two strands form a duplex with at least one blunt end; and the 3 end of one or both strands terminates in a phosphate or modified internucleoside linker and further comprises, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker, and a 3 end cap. In various embodiments, the RNAi agents comprise a first and a second strand, wherein each strand is a 30-mer or shorter, the first strand comprises ribonucleotides, and the second strand comprises ribonucleotides and one or more spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand. In some embodiments, the 3 end of both strands further comprise, in 5 to 3 order: a second 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 first two base-pairing nucleotides on the 3 end of the one or both strand are 2-MOE. Optionally, the RNAi agent can be modified on one or both 5 end. Optionally, the first or second strand is the sense strand, and 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.
Public/Granted literature
- US20160244756A1 NOVEL FORMATS FOR ORGANIC COMPOUNDS FOR USE IN RNA INTERFERENCE Public/Granted day:2016-08-25
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