SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION FACTOR 6 (STAT6) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsAimee M. Deaton, Jeffrey Zuber
Life of this patent
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Abstract
The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the signal transducer and activator of transcription factor 6 (STAT6) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a STAT6 gene and to methods of preventing and treating a STAT6-associated disorder, e.g., a respiratory disease, e.g., asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, eosinophilic cough, bronchitis, sarcoidosis, pulmonary fibrosis, rhinitis, and sinusitis.
Claims35
A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of signal transducer and activator of transcription factor 6 (STAT6) in a cell,
- wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region,
- a) wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequence of SEQ ID NO:1, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequence of SEQ ID NO:2, and
- wherein the sense strand or the antisense strand is conjugated to one or more lipophilic moieties;
- or
- b) wherein the antisense strand comprises a region of complementarity to an mRNA encoding STAT6, and wherein the region of complementarity comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense nucleotide sequences in any one of Tables 2-3, and
- wherein the sense strand or the antisense strand is conjugated to one or more lipophilic moieties.
-10. (canceled)
The dsRNA agent of claim 9, wherein at least one of the nucleotide modifications is selected from the group a deoxy-nucleotide modification, a 3′-terminal deoxythimidine (dT) nucleotide modification, a 2′-O-methyl nucleotide modification, a 2′-fluoro nucleotide modification, a 2′-deoxy nucleotide modification, a locked nucleotide modification, an unlocked nucleotide modification, a conformationally restricted nucleotide modification, a constrained ethyl nucleotide modification, an abasic nucleotide modification, a 2′-amino nucleotide modification, a 2′-O-allyl nucleotide modification, 2′-C-alkyl nucleotide modification, a 2′-methoxyethyl nucleotide modification, a 2′-O-alkyl-nucleotide modification, a morpholino nucleotide modification, a phosphoramidate modification, a non-natural base comprising nucleotide modification, a tetrahydropyran nucleotide modification, a 1,5-anhydrohexitol nucleotide modification, a cyclohexenyl nucleotide modification, a nucleotide comprising a 5′-phosphorothioate group modification, a nucleotide comprising a 5′-methylphosphonate group modification, a nucleotide comprising a 5′ phosphate or 5′ phosphate mimic modification, a nucleotide comprising vinyl phosphonate modification, a nucleotide comprising adenosine-glycol nucleic acid (GNA) modification, a nucleotide comprising thymidine-glycol nucleic acid (GNA) S-Isomer modification, a nucleotide comprising 2-hydroxymethyl-tetrahydrofurane-5-phosphate modification, a nucleotide comprising 2′-deoxythymidine-3′phosphate modification, a nucleotide comprising 2′-deoxyguanosine-3′-phosphate modification, a 2′-O hexadecyl nucleotide modification, a nucleotide comprising a 2′-phosphate modification, a cytidine-2′-phosphate nucleotide modification, a guanosine-2′-phosphate nucleotide modification, a 2′-O-hexadecyl-cytidine-3′-phosphate nucleotide modification, a 2′-O-hexadecyl-adenosine-3′-phosphate nucleotide modification, a 2′-O-hexadecyl-guanosine-3′-phosphate nucleotide modification, a 2′-O-hexadecyl-uridine-3′-phosphate nucleotide modification, a 5′-vinyl phosphonate (VP) modification, a 2′-deoxyadenosine-3′-phosphate nucleotide modification, a 2′-deoxycytidine-3′-phosphate nucleotide modification, a 2′-deoxyguanosine-3′-phosphate nucleotide modification, a 2′-deoxythymidine-3′-phosphate nucleotide modification, a 2′-deoxyuridine nucleotide modification, and a terminal nucleotide linked to a cholesteryl derivative and a dodecanoic acid bisdecylamide group modification;
- and combinations thereof.
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Dependencies are inferred from the claim text.