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AssigneeIsis Pharmaceuticals, Inc.
InventorsBrett P. Monia, Michael L. McCaleb, Susan M. Freier, Shuling Guo
Estimating the term…
Disclosed herein are methods for decreasing AIAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing AIAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, AIATD associated liver disease, and pulmonary disease, such as, AIATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting AIAT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, AIATD associated liver disease and pulmonary disease, such as, AIATD associated pulmonary disease.
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and comprising a nucleobase sequence comprising a portion of at least 8, at least 10, at least 12, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of nucleobases 1575 to 1594 of SEQ ID NO:
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and comprising a nucleobase sequence comprising a portion of at least 8, at least 10, at least 12, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of nucleobases 1564 to 1583 of SEQ ID NO:
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and comprising a nucleobase sequence comprising a portion of at least 8, at least 10, at least 12, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of nucleobases 1561 to 1597 of SEQ ID NO:
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and comprising a nucleobase sequence comprising a portion of at least 8, at least 10, at least 12, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of nucleobases 1349 to 1597 of SEQ ID NO:
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and comprising a nucleobase sequence comprising a portion of at least 8, at least 10, at least 12, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of nucleobases 459 to 513 of SEQ ID NO:
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 12, at least 14, at least 16, at least 17, at least 18, at least 19, or 20 contiguous nucleobases of the nucleobase sequence of SEQ ID NO:
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 12, at least 14, at least 16, at least 17, at least 18, at least 19, or 20 contiguous nucleobases of the nucleobase sequence of SEQ ID NO:
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 12, at least 14, at least 16, at least 17, at least 18, at least 19, or 20 contiguous nucleobases of the nucleobase sequences of SEQ ID NO:
The compound of any preceding claim, wherein the modified oligonucleotide consists of 15 to 30, 18 to 24, 19 to 22, or 20 linked nucleosides.
The compound of any preceding claim wherein the nucleobase sequence of the modified oligonucleotide is at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% complementary to SEQ ID NO:
The compound of any preceding claim, consisting of a single-stranded modified oligonucleotide.
The compound of any preceding claim, wherein at least one internucleoside linkage is a modified internucleoside linkage.
The compound of any preceding claim, wherein at least one nucleoside comprises a modified nucleobase.
The compound of any preceding claim, wherein the modified oligonucleotide comprises at least one modified sugar.
The compound of any preceding claim, comprising at least one 2′-O-methoxyethyl nucleoside.
The compound of any preceding claim, wherein the modified oligonucleotide comprises:
A compound according to any of claims 1-23 or a composition according to claim 33, for use in therapy.
A method of reducing A1AT in an animal comprising administering to the animal a modified oligonucleotide targeting an A1AT nucleic acid sequence as shown in SEQ ID NO:
A method of treating, ameliorating and/or preventing an A1ATD associated liver disease in an animal at risk for the A1ATD associated liver disease comprising,
A method of treating, ameliorating and/or preventing an A1ATD associated pulmonary disease in an animal at risk for the A1ATD associated pulmonary disease comprising,
A method of halting progression of an A1ATD associated liver disease comprising,
A method of lowering the risk for developing an A1ATD associated liver disease comprising,
A method of reducing fibrosis in an animal comprising
A method of preventing organ damage, decreasing organ damage and/or improving organ function in an animal comprising
Dependencies are inferred from the claim text.