Huntingtin (HTT) iRNA agent compositions and methods of use thereof
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsMangala Meenakshi Soundarapandian, James D. McIninch, Mark K. Schlegel, Adam Castoreno
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Abstract
The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a Huntingtin (HTT) gene, as well as methods of inhibiting expression of an HTT gene and methods of treating subjects having an HTT-associated disease or disorder, e.g., Huntington's disease, using such dsRNAi agents and compositions.
Claims30
A double stranded ribonucleic acid (dsRNA) agent, or a pharmaceutically acceptable salt thereof, for inhibiting expression of Huntingtin (HTT) in a cell, comprising a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 4 nucleotides from the nucleotide sequence 5′-gscsgac(Chd)CfuGfGfAfaaagcugasusa-3′ of SEQ ID NO:65 (SEQ ID NO:65) and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 4 nucleotides from the nucleotide sequence 5′-VPusAfsucdAg(C2p)uuuudCcAfgdGgucgcscsg-3′ of SEQ ID NO:79,
- wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
- s is a phosphorothioate linkage;
- Af, Cf, and Gf are 2′-fluoro A, C, and G, respectively;
- (Chd) is 2′-O-hexadecyl-cytosine-3′-phosphate;
- C2p is cytidine-2′-phosphate;
- dA, dG, and dC are 2′-deoxy A, G, and C, respectively;
- and VP is 5′-vinyl phosphonate.
A double stranded ribonucleic acid (dsRNA) agent, or a pharmaceutically acceptable salt thereof, for inhibiting expression of Huntingtin (HTT) in a cell, comprising a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand comprises the nucleotide sequence 5′-gscsgac(Chd)CfuGfGfAfaaagcugasusa-3′ of SEQ ID NO:65 and the antisense strand comprises the nucleotide sequence 5′-VPusAfsucdAg(C2p)uuuudCcAfgdGgucgcscsg-3′ of SEQ ID NO:79,
- wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
- s is a phosphorothioate linkage;
- Af, Cf, and Gf are 2′-fluoro A, C, and G, respectively;
- (Chd) is 2′-O-hexadecyl-cytosine-3′-phosphate;
- C2p is cytidine-2′-phosphate;
- dA, dG and dC are 2′-deoxy A, G, and C, respectively;
- and VP is 5′-vinyl phosphonate.
A double stranded ribonucleic acid (dsRNA) agent, or a pharmaceutically acceptable salt thereof, for inhibiting expression of Huntingtin (HTT) in a cell,
- wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand consists of the nucleotide sequence 5′-gscsgac(Chd)CfuGfGfAfaaagcugasusa-3′ of SEQ ID NO:65 and the antisense strand consists of the nucleotide sequence 5′-VPusAfsucdAg(C2p)uuuudCcAfgdGgucgcscsg-3′ of SEQ ID NO:79,
- wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
- s is a phosphorothioate linkage;
- Af, Cf, and Gf are 2′-fluoro A, C, and G, respectively;
- (Chd) is 2′-O-hexadecyl-cytosine-3′-phosphate;
- C2p is cytidine-2′-phosphate;
- dA, dG and dC are 2′-deoxy A, G, and C, respectively;
- and VP is 5′-vinyl phosphonate.
A sodium salt of a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Huntingtin (HTT) in a cell,
- wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand consists of the nucleotide sequence 5′-gscsgac(Chd)CfuGfGfAfaaagcugasusa-3′ of SEQ ID NO:65 and the antisense strand consists of the nucleotide sequence 5′-VPusAfsucdAg(C2p)uuuudCcAfgdGgucgcscsg-3′ of SEQ ID NO:79,
- wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
- s is a phosphorothioate linkage;
- Af, Cf, and Gf are 2′-fluoro A, C, and G, respectively;
- (Chd) is 2′-O-hexadecyl-cytosine-3′-phosphate;
- C2p is cytidine-2′-phosphate;
- dA, dG and dC are 2′-deoxy A, G, and C, respectively;
- and VP is 5′-vinyl phosphonate.
Dependencies are inferred from the claim text.