Compositions for modulating expression of c9orf72 antisense transcript
AssigneeIonis Pharmaceuticals, Inc.
InventorFrank Rigo
Life of this patent
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Abstract
Disclosed herein are compositions and methods for reducing expression of C9ORF72 antisense transcript in an animal with C9ORF72 antisense transcript specific inhibitors. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Such C9ORF72 antisense transcript specific inhibitors include antisense compounds.
Claims145
A compound comprising a C9ORF72 antisense transcript specific inhibitor.
A pharmaceutical composition comprising a C9ORF72 antisense transcript specific inhibitor and a C9ORF sense transcript specific inhibitor.
Use of the compound of any preceding claim for the manufacture of a medicament for treating a neurodegenerative disease.
A method comprising contacting a cell with an antisense oligonucleotide having the nucleobases sequence of any of SEQ ID NOs:
- 30-84.
A method comprising contacting a cell with a C9ORF72 antisense transcript specific inhibitor.
A method comprising contacting a cell with a C9ORF72 antisense transcript specific inhibitor and a C9ORF72 sense transcript specific inhibitor.
A method comprising contacting a cell with a C9ORF72 antisense transcript specific inhibitor;
- and thereby reducing the level or expression of C9ORF72 antisense transcript in the cell.
A method comprising contacting a cell with a C9ORF72 antisense transcript specific inhibitor and a C9ORF72 sense transcript specific inhibitor;
- and thereby reducing the level or expression of both C9ORF72 antisense transcript and C9ORF72 sense transcript in the cell.
A method, comprising administering to an animal in need thereof a therapeutically effective amount of a C9ORF72 antisense transcript specific inhibitor.
A method, comprising co-administering to an animal in need thereof a therapeutically effective amount of a C9ORF72 antisense transcript inhibitor and a therapeutically effective amount of a C9ORF72 sense transcript inhibitor.
A method, comprising:
- identifying an animal having a C9ORF72 associated disease;
- and
- administering to the animal a therapeutically effective amount of a C9ORF72 antisense transcript specific inhibitor.
A method, comprising:
- identifying an animal having a C9ORF72 associated disease;
- and
- coadministering to the animal a therapeutically effective amount of a C9ORF72 antisense transcript specific inhibitor and a therapeutically effective amount of a C9ORF72 sense transcript inhibitor.
The method of any preceding claim, wherein the C9ORF72 antisense transcript specific antisense compound is at least 80%, at least 85%, at least 90%, 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 a C9ORF72 antisense transcript.
The method of any preceding claim, wherein the C9ORF72 sense transcript specific antisense compound is at least 80%, at least 85%, at least 90%, 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 a C9ORF72 sense transcript.
The method of any preceding claim, wherein the C9ORF72 antisense transcript is SEQ ID NO:
- 13.
The method of any preceding claim, wherein the C9ORF72 sense transcript is any of SEQ ID NO:
- 1-10.
The method of any preceding claim, wherein the contacting or administering reduces C9ORF72 antisense transcript associated RAN translation products.
The method of any preceding claim, wherein the C9ORF72 antisense transcript specific antisense compound is an antisense oligonucleotide.
The method of any preceding claim, wherein the C9ORF72 sense transcript specific antisense compound is an antisense oligonucleotide.
The method of any preceding claim, wherein the antisense oligonucleotide is a gapmer.
A compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides and having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases of any of the nucleobases sequences of SEQ ID NOs:
- 30-99.
A pharmaceutical composition comprising the compound of any preceding claim or salt thereof and at least one of a pharmaceutically acceptable carrier or diluent.
Use of the compound or composition of any preceding claim for the manufacture of a medicament for treating a neurodegenerative disease.
A method comprising administering to an animal the compound or composition of any preceding claim.
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases complementary to an equal length portion of nucleobases 196-280 of SEQ ID NO:
- 13.
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases complementary to an equal length portion of nucleobases 286-315 of SEQ ID NO:
- 13.
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases complementary to an equal length portion of nucleobases 321-415 of SEQ ID NO:
- 13.
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases complementary to an equal length portion of nucleobases 451-516 of SEQ ID NO:
- 13.
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases complementary to an equal length portion of nucleobases 527-588 of SEQ ID NO:
- 13.
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases complementary to an equal length portion of nucleobases 608-636 of SEQ ID NO:
- 13.
A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases complementary to an equal length portion of nucleobases 704-726 of SEQ ID NO:
- 13.
Dependencies are inferred from the claim text.