Methods and compositions for treating a serpinc1-associated disorder
AssigneeGenzyme Corporation
InventorsAkin Akinc, Benny Sorensen, Pushkal Garg, Gabriel Robbie
Life of this patent
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Abstract
The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the Serpinc1 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of Serpinc1 and to treat subjects having a Serpinc1-associated disease, e.g., a bleeding disorder, such as a hemophilia.
Claims17
A method of preventing at least one symptom in a subject having a disorder that would benefit from reduction in SERPINC1 expression, comprising administering to the subject a dose of about 25 mg to about 100 mg of a double stranded ribonucleic acid (dsRNA) molecule,
- wherein the dsRNA molecule comprises a sense strand and an antisense strand, the antisense strand comprising at least 15 contiguous nucleotides differing by no more than three nucleotides from the nucleotide sequence 5′-UUGAAGUAAAUGGUGUUAACCAG-3′ (SEQ ID NO:
- 15), wherein substantially all of the nucleotides of the sense strand and substantially all of the nucleotides of the antisense strand are modified nucleotides, and wherein the sense strand is conjugated to a ligand attached at the 3′ end.
2-41. (canceled)
A kit comprising
- a) a dose of about 25 mg to about 100 mg of a double stranded ribonucleic acid (dsRNA) molecule comprising a sense strand and an antisense strand,
- wherein the sense strand comprises the sequence 5′-GfsgsUfuAfaCfaCfCfAfuUfuAfcUfuCfaAf-3′ (SEQ ID NO:13) and the antisense strand comprises the sequence 5′-usUfsgAfaGfuAfaAfuggUfgUfuAfaCfcsasg-3′ (SEQ ID NO:14), wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively:
- Af, Cf, Gf and Uf are 2′-fluoro A, C, G, and U, respectively;
- and s is a phosphorothioate linkage;
- and
- wherein a ligand is conjugated to the 3′ end of the sense strand as shown in the following schematic;
- wherein X is O,
- b) instructions for use, and
- c) optionally, means for administering the dsRNA molecule to a subject.
Dependencies are inferred from the claim text.