The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Jun. 05, 2018
Filed:
Oct. 06, 2014
Jeremy Lee Baryza, Cambridge, MA (US);
Marcel Blommers, Basel, CH;
William Chutkow, Cambridge, MA (US);
Cesar Fernandez, Basel, CH;
Erin Geno, Cambridge, MA (US);
Alvar Gossert, Basel, CH;
Paulette Greenidge, Basel, CH;
Dieter Huesken, Basel, CH;
Juerg Hunziker, Basel, CH;
Francois Jean-charles Natt, Basel, CH;
Anup Patnaik, Cambridge, MA (US);
Andrew Patterson, Cambridge, MA (US);
Jean-michel Rene Rondeau, Basel, CH;
Jan Weiler, Cambridge, MA (US);
Meicheng Zhu, Cambridge, MA (US);
Jeremy Lee Baryza, Cambridge, MA (US);
Marcel Blommers, Basel, CH;
William Chutkow, Cambridge, MA (US);
Cesar Fernandez, Basel, CH;
Erin Geno, Cambridge, MA (US);
Alvar Gossert, Basel, CH;
Paulette Greenidge, Basel, CH;
Dieter Huesken, Basel, CH;
Juerg Hunziker, Basel, CH;
Francois Jean-Charles Natt, Basel, CH;
Anup Patnaik, Cambridge, MA (US);
Andrew Patterson, Cambridge, MA (US);
Jean-Michel Rene Rondeau, Basel, CH;
Jan Weiler, Cambridge, MA (US);
Meicheng Zhu, Cambridge, MA (US);
NOVARTIS AG, Basel, CH;
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.