Novartis Ag

Seqirus UK Limited

Juerg Hunziker

Francois Jean-Charles Natt

Eric Billy

Christian Rene Schnell

Jean-Michel Rene Rondeau

Jan Weiler

Jeremy Lee Baryza

Andrew William Patterson

Dieter Huesken

Erin Geno

Cesar Fernandez

Alvar Gossert

Paulette Greenidge

Anup Patnaik

Meicheng Zhu

Marcel Blommers

Peter W Mason

Michael Franti

David Morrissey

Heidi Trusheim

Melissa Sackal

Bjoern Keiner

William Chutkow

Meghan Marie Holdorf

Björn Keiner

François Jean-Charles Natt

Francois Natt

Andrew Patterson

The disclosure relates to novel compounds and compositions comprising a RNAi agent comprising a novel compound as a 3' end cap. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.

3' end caps for RNAi agents for use in RNA interference

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&#x2032; to 3&#x2032; order: a spacer; a second phosphate or modified internucleoside linker; and a 3&#x2032; end cap. In some embodiments, the 3&#x2032; end of both the sense and anti-sense strand further comprise, in 5&#x2032; to 3&#x2032; order: a spacer; a second phosphate or modified internucleoside linker; and a 3&#x2032; end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3&#x2032; 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&#x2032; end. Optionally, the sense strand can comprise a 5&#x2032; 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.

Organic compounds to treat hepatitis B virus

3'end caps for RNAi agents for use in RNA interference

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.

Formats for organic compounds for use in RNA interference

Methods for producing reassortant viruses are provided wherein the transcription and/or translation of the hemagglutinin and/or neuraminidase genes are suppressed.

Influenza virus reassortment method

Short interfering ribonucleic acid (siRNA) for oral administration, said siRNA comprising two separate RNA strands that are complementary to each other over at least 15 nucleotides, wherein each strand is 49 nucleotides or less, and wherein at least one of which strands contains at least one chemical modification.

Short interfering ribonucleic acid (siRNA) for oral administration

Influenza virus reassortment

Short interfering ribonucleic acid (siRNA) with improved pharmacological properties

Growing community of inventors

Basel, Switzerland

Juerg Hunziker