HEPATITIS D VIRUS (HDV) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
First Claim
1. A double stranded RNAi agent for inhibiting expression of hepatitis D virus (HDV) in a cell, wherein said double stranded RNAi agent comprises a sense strand and an antisense strand forming a double-stranded region selected from the group consisting of(a) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:
- 29, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
30;
(b) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
31, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
32;
(c) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
33, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
34;
(d) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
35, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
36;
(e) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
37, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
38;
(f) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
39, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
40;
(g) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
41, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
42;
(h) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
43, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
44; and
(i) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
2551, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
2552;
wherein substantially all of the nucleotides of said sense strand and substantially all of the nucleotides of said antisense strand are modified nucleotides,wherein said sense strand is conjugated to a ligand attached at the 3′
-terminus, andwherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker.
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Accused Products
Abstract
The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the hepatitis D virus (HDV) genome, and methods of using such RNAi agents to inhibit expression of one or more HBV genes and methods of treating subjects having an HDV infection and/or HDV-associated disorder.
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Citations
105 Claims
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1. A double stranded RNAi agent for inhibiting expression of hepatitis D virus (HDV) in a cell, wherein said double stranded RNAi agent comprises a sense strand and an antisense strand forming a double-stranded region selected from the group consisting of
(a) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO: - 29, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
30;(b) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
31, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
32;(c) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
33, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
34;(d) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
35, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
36;(e) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
37, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
38;(f) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
39, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
40;(g) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
41, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
42;(h) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
43, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
44; and(i) a sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
2551, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
2552;wherein substantially all of the nucleotides of said sense strand and substantially all of the nucleotides of said antisense strand are modified nucleotides, wherein said sense strand is conjugated to a ligand attached at the 3′
-terminus, andwherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker. - View Dependent Claims (4, 6, 8, 9, 11, 17, 19, 20, 22, 31, 47, 53, 70)
- 29, and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO;
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2. (canceled)
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3. (canceled)
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5. (canceled)
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7. (canceled)
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10. (canceled)
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12-16. -16. (canceled)
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18. (canceled)
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21. (canceled)
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23. A double stranded RNAi agent for inhibiting expression of hepatitis D virus (HDV) in a cell, wherein said double stranded RNAi agent comprises a sense strand and an antisense strand forming a double-stranded region,
wherein said sense strand comprises any one of the sense sequences provided in any one of Table 11, 12, 31, and 32, and said antisense strand comprises any one of the antisense sequences provided in any one of Table 11, 12, 31, and 32, wherein substantially all of the nucleotides of said sense strand and substantially all of the nucleotides of said antisense strand are modified nucleotides, wherein said sense strand is conjugated to a ligand attached at the 3′ - -terminus, and
wherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker.
- -terminus, and
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24-30. -30. (canceled)
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32-38. -38. (canceled)
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39. A composition for inhibiting expression of hepatitis D virus (HDV) in a cell, said composition comprising:
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(a) a first double-stranded RNAi agent comprising a first sense strand and a first antisense strand forming a double-stranded region, wherein substantially all of the nucleotides of said first sense strand and substantially all of the nucleotides of said first antisense strand are modified nucleotides, wherein said first sense strand is conjugated to a ligand attached at the 3′
-terminus, andwherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker; and (b) a second double-stranded RNAi agent comprising a second sense strand and a second antisense strand forming a double-stranded region, wherein substantially all of the nucleotides of said second sense strand and substantially all of the nucleotides of said second antisense strand are modified nucleotides, wherein said second sense strand is conjugated to a ligand attached at the 3′
-terminus, andwherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker; wherein the first and second sense strands each independently comprise a sequence selected from the group consisting of any one of the sense sequences of AD-70260.1, AD-70232.1, AD-70249.1, AD-70244.1, AD-70272.1, AD-70228.1, AD-70255.1, AD-70278.1, AD-70295.1, AD-67200.1, AD-67211.1, AD-67199.1, AD-67202.1, AD-67208.1, AD-67210.1, AD-70259.1, AD-70267.1, AD-70272.1, AD-70271.1, AD-70268.1, AD-70269.1, AD-70232.1, AD-70256.1, AD-70257.1, or AD-70275.1, and wherein the first and second antisense strands each independently comprise a sequence selected from the group consisting of any one of the antisense sequences of AD-70260.1, AD-70232.1, AD-70249.1, AD-70244.1, AD-70272.1, AD-70228.1, AD-70255.1, AD-70278.1, AD-70295.1, AD-67200.1, AD-67211.1, AD-67199.1, AD-67202.1, AD-67208.1, AD-67210.1, AD-70259.1, AD-70267.1, AD-70272.1, AD-70271.1, AD-70268.1, AD-70269.1, AD-70232.1, AD-70256.1, AD-70257.1, or AD-70275.1.
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40-43. -43. (canceled)
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44. A double stranded RNAi agent comprising the sense strand nucleotide sequence and the antisense strand nucleotide sequence of any one of the RNAi agents provided in any one of Table 11, 12, 31, and 32.
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45. (canceled)
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46. (canceled)
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48-52. -52. (canceled)
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54-69. -69. (canceled)
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71-91. -91. (canceled)
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93-97. -97. (canceled)
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99-103. -103. (canceled)
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105-111. -111. (canceled)
Specification