MODULATION OF HEPATITIS B VIRUS (HBV) EXPRESSION
Disclosed herein are antisense compounds and methods for decreasing HBV mRNA, DNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate HBV-related diseases, disorders or conditions.
1 - 72 . (canceled)
73 . A single stranded modified oligonucleotide consisting of 10 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of SEQ ID NO: 789, 802, or 1335, wherein the modified oligonucleotide comprises a modified sugar and is at least 95% complementary to SEQ ID NO: 1.
74 . The single stranded modified oligonucleotide of claim 73 , further comprising a conjugate group.
75 . The single stranded modified oligonucleotide of claim 74 , wherein the conjugate group comprises a carbohydrate.
76 . The single stranded modified oligonucleotide of claim 73 , wherein said modified oligonucleotide is 100% complementary to SEQ ID NO: 1.
77 . The single stranded modified oligonucleotide of claim 73 , wherein at least one internucleoside linkage is a modified internucleoside linkage.
78 . The single stranded modified oligonucleotide of claim 77 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
79 . The single stranded modified oligonucleotide of claim 73 , wherein the modified sugar is a bicyclic sugar.
80 . The single stranded modified oligonucleotide of claim 79 , wherein the modified sugar comprises a 4′-CH 2 —O-2′ group.
81 . The single stranded modified oligonucleotide of claim 73 , wherein at least one nucleoside comprises a modified nucleobase.
82 . The single stranded modified oligonucleotide of claim 81 , wherein the modified nucleobase is a 5-methylcytosine.
83 . The single stranded modified oligonucleotide of claim 73 , wherein the modified oligonucleotide comprises:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides; and
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises the modified sugar.
84 . The single stranded modified oligonucleotide of claim 83 , wherein the gap segment consists of 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 linked nucleosides.
85 . The single stranded modified oligonucleotide of claim 73 , wherein the modified oligonucleotide has a nucleobase sequence comprising at least 13 contiguous nucleobases of SEQ ID NO: 789, 802, or 1335.
86 . The single stranded modified oligonucleotide of claim 85 , further comprising a conjugate group.
87 . The single stranded modified oligonucleotide of claim 86 , wherein the conjugate group comprises a carbohydrate.
88 . The single stranded modified oligonucleotide of claim 85 , wherein said modified oligonucleotide is 100% complementary to SEQ ID NO: 1.
89 . The single stranded modified oligonucleotide of claim 85 , wherein at least one internucleoside linkage is a modified internucleoside linkage.
90 . The single stranded modified oligonucleotide of claim 89 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
91 . The single stranded modified oligonucleotide of claim 85 , wherein the modified sugar is a bicyclic sugar.
92 . The single stranded modified oligonucleotide of claim 91 , wherein the modified sugar comprises a 4′-CH 2 —O-2′ group.
93 . The single stranded modified oligonucleotide of claim 85 , wherein at least one nucleoside comprises a modified nucleobase.
94 . The single stranded modified oligonucleotide of claim 93 , wherein the modified nucleobase is a 5-methylcytosine.
95 . The single stranded modified oligonucleotide of claim 85 , wherein the modified oligonucleotide comprises:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides; and
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises the modified sugar.
96 . The single stranded modified oligonucleotide of claim 95 , wherein the gap segment consists of 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 linked nucleosides.
97 . The single stranded modified oligonucleotide of claim 73 , wherein the modified oligonucleotide has a nucleobase sequence comprising at least 15 contiguous nucleobases of SEQ ID NO: 802, or 1335.
98 . The single stranded modified oligonucleotide of claim 97 , further comprising a conjugate group.
99 . The single stranded modified oligonucleotide of claim 98 , wherein the conjugate group comprises a carbohydrate.
100 . The single stranded modified oligonucleotide of claim 97 , wherein said modified oligonucleotide is 100% complementary to SEQ ID NO: 1.
101 . The single stranded modified oligonucleotide of claim 97 , wherein at least one internucleoside linkage is a modified internucleoside linkage.
102 . The single stranded modified oligonucleotide of claim 101 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
103 . The single stranded modified oligonucleotide of claim 97 , wherein the modified sugar is a bicyclic sugar.
104 . The single stranded modified oligonucleotide of claim 103 , wherein the modified sugar comprises a 4′-CH 2 —O-2′ group.
105 . The single stranded modified oligonucleotide of claim 97 , wherein at least one nucleoside comprises a modified nucleobase.
106 . The single stranded modified oligonucleotide of claim 105 , wherein the modified nucleobase is a 5-methylcytosine.
107 . The single stranded modified oligonucleotide of claim 97 , wherein the modified oligonucleotide comprises:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides; and
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises the modified sugar.
108 . The single stranded modified oligonucleotide of claim 107 , wherein the gap segment consists of 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 linked nucleosides.
109 . A composition comprising the single stranded modified oligonucleotide of claim 73 or salt thereof and at least one of a pharmaceutically acceptable carrier or diluent.
110 . A composition comprising the single stranded modified oligonucleotide of claim 85 or salt thereof and at least one of a pharmaceutically acceptable carrier or diluent.
111 . A composition comprising the single stranded modified oligonucleotide of claim 97 or salt thereof and at least one of a pharmaceutically acceptable carrier or diluent.
112 . A method of preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in an animal comprising administering the single stranded modified oligonucleotide of claim 73 to the animal, thereby preventing, treating, ameliorating, or slowing progression the HBV-related disease, disorder or condition.
113 . A method of preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in an animal comprising administering the single stranded modified oligonucleotide of claim 85 to the animal, thereby preventing, treating, ameliorating, or slowing progression the HBV-related disease, disorder or condition.
114 . A method of preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in an animal comprising administering the single stranded modified oligonucleotide of claim 97 to the animal, thereby preventing, treating, ameliorating, or slowing progression the HBV-related disease, disorder or condition.
115 . The method of claim 112 , wherein administering the single stranded modified oligonucleotide of claim 73 to the animal reduces HBsAG antigen levels in the animal.
116 . The method of claim 113 , wherein administering the single stranded modified oligonucleotide of claim 83 to the animal reduces HBsAG antigen levels in the animal.
117 . The method of claim 114 , wherein administering the single stranded modified oligonucleotide of claim 93 to the animal reduces HBsAG antigen levels in the animal.