Transthyretin (TTR) iRNA compositions and methods of use thereof for treating or preventing TTR-associated diseases
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsTracy Zimmermann, Amy Chan, Vasant Jadhav, Martin Maier, Kallanthottathil G. Rajeev
Life of this patent
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Abstract
The present invention provides iRNA agents, e.g., double stranded iRNA agents, that target the transthyretin (TTR) gene and methods of using such iRNA agents for treating or preventing TTR-associated diseases.
Claims75
A double stranded ribonucleic acid (RNAi) agent that inhibits expression of transthyretin (TTR) in a cell, comprising a sense strand differing by no more than 4 modified nucleotides from the nucleotide sequence of 5′-usgsggauUfuCfAfUfguaaccaaga-3′ (SEQ ID NO:
- 10) and an antisense strand differing by no more than 4 modified nucleotides from the nucleotide sequence 5′-usCfsuugGfuuAfcaugAfaAfucccasusc-3′ (SEQ ID NO:
- 7),
- wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U;
- Af, Cf, Gf, and Uf are 2′-fluoro A, C, G, and U;
- and s is a phosphorothioate linkage.
A double stranded ribonucleic acid (RNAi) agent, comprising a sense strand and an antisense strand, wherein the sense strand comprises the nucleotide sequence 5′-usgsggauUfuCfAfUfguaaccaagaL96-3′ (SEQ ID NO:
- 10) and the antisense strand comprises the nucleotide sequence 5′-usCfsuugGfuuAfcaugAfaAfucccasusc-3′ (SEQ ID NO:
- 7),
- wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U;
- Af, Cf, Gf, and Uf are 2′-fluoro A, C, G, and U;
- s is a phosphorothioate linkage;
- and L96 is N-[tris(GalNAc-alkyl)-amidodecanoyl)]-4-hydroxyprolinol.
A double stranded ribonucleic acid (RNAi) agent comprising a sense strand and an antisense strand, wherein the sense strand consists of the nucleotide sequence 5′-usgsggauUfuCfAfUfguaaccaagaL96-3′ (SEQ ID NO:
- 10) and the antisense strand consists of the nucleotide sequence 5′-usCfsuugGfuuAfcaugAfaAfucccasusc-3′ (SEQ ID NO:
- 7),
- wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U;
- Af, Cf, Gf, and Uf are 2′-fluoro A, C, G, and U;
- s is a phosphorothioate linkage;
- and L96 is N-[tris(GalNAc-alkyl)-amidodecanoyl)]-4-hydroxyprolinol.
A method of treating a subject suffering from a TTR-associated disease, comprising administering to the subject a therapeutically effective amount of a double stranded ribonucleic acid (RNAi),
- wherein the double stranded RNAi agent comprises a sense strand differing by no more than 4 modified nucleotides from the nucleotide sequence of 5′-usgsggauUfuCfAfUfguaaccaaga-3′ (SEQ ID NO:
- 10) and an antisense strand differing by no more than 4 modified nucleotides from the nucleotide sequence 5′-usCfsuugGfuuAfcaugAfaAfucccasusc-3′ (SEQ ID NO:
- 7),
- wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U;
- Af, Cf, Gf, and Uf are 2′-fluoro A, C, G, and U;
- and s is a phosphorothioate linkage,
- thereby treating the subject.
A method of treating a subject suffering from a TTR-associated disease, comprising administering to the subject a therapeutically effective amount of a double stranded ribonucleic acid (RNAi) agent,
- wherein the double stranded RNAi agent comprises a sense strand and an antisense strand, wherein the sense strand comprises the nucleotide sequence 5′-usgsggauUfuCfAfUfguaaccaagaL96-3′ (SEQ ID NO:
- 10) and the antisense strand comprises the nucleotide sequence 5′-usCfsuugGfuuAfcaugAfaAfucccasusc-3′ (SEQ ID NO:
- 7)
- wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U;
- Af, Cf, Gf, and Uf are 2′-fluoro A, C, G, and U;
- s is a phosphorothioate linkage;
- and L96 is N-[tris(GalNAc-alkyl)-amidodecanoyl)]-4-hydroxyprolinol, thereby treating the subject.
Dependencies are inferred from the claim text.