Compounds and methods for modulating glycogen synthase 1
AssigneeIonis Pharmaceuticals, Inc.
InventorsHuynh-Hoa Bui, Bethany Fitzsimmons, Holly Kordasiewicz, Tamar R. Grossman
Life of this patent
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Abstract
Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of GYSI RNA in a cell or subject, and in certain instances reducing the amount of GYSI protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a glycogen storage disease. Such glycogen storage diseases include Lafora disease, adult polyglucosan body disease (APBD), Andersen's disease, and Pompe disease.
Claims42
A modified oligonucleotide according to the following chemical structure:
- (SEQ ID NO:
- 26) or a pharmaceutically acceptable salt thereof.
A modified oligonucleotide according to the following chemical structure:
A modified oligonucleotide according to the following chemical structure:
- (SEQ ID NO:
- 27), or a pharmaceutically acceptable salt thereof.
A modified oligonucleotide according to the following chemical structure:
A modified oligonucleotide according to the following chemical structure:
- (SEQ ID NO:
- 28) or a pharmaceutically acceptable salt thereof.
A modified oligonucleotide according to the following chemical structure:
A modified oligonucleotide according to the following chemical structure:
- (SEQ ID NO:
- 29) or a pharmaceutically acceptable salt thereof.
A modified oligonucleotide according to the following chemical structure:
An oligomeric compound comprising a modified oligonucleotide according to the following chemical notation:
- mCesmCeoGeoTeomCesTdsAdsmCdsAdsGdsGdsAdsTdsTdsTdsTeomCeoTesAesGe (SEQ ID NO:
- 14), wherein:
- A=an adenine nucleobase,
- mC=a 5-methylcytosine nucleobase,
- G=a guanine nucleobase,
- T=a thymine nucleobase,
- e=a 2′-O(CH2)2OCH3 ribosyl sugar moiety,
- d=a 2′-β-D-deoxyribosyl sugar moiety,
- s=a phosphorothioate internucleoside linkage, and
- o=a phosphodiester internucleoside linkage.
An oligomeric compound comprising a modified oligonucleotide according to the following chemical notation:
- TesTeomCeomCeoGesTdsmCdsTdsAdsmCdsAdsGdsGdsAdsTdsTeoTeoTesmCesTe (SEQ ID NO:
- 15), wherein:
- A=an adenine nucleobase,
- mC=a 5-methylcytosine nucleobase,
- G=a guanine nucleobase,
- T=a thymine nucleobase,
- e=a 2′-O(CH2)2OCH3 ribosyl sugar moiety,
- d=a 2′-β-D-deoxyribosyl sugar moiety,
- s=a phosphorothioate internucleoside linkage, and
- o=a phosphodiester internucleoside linkage.
An oligomeric compound comprising a modified oligonucleotide according to the following chemical notation:
- TesTeomCeomCeoGeoTeomCdsTdsAdsmCdsAdsGdsGdsAdsTdsTdsTeoTesmCesTe (SEQ ID NO:
- 15), wherein:
- A=an adenine nucleobase,
- mC=a 5-methylcytosine nucleobase,
- G=a guanine nucleobase,
- T=a thymine nucleobase,
- e=a 2′-O(CH2)2OCH3 ribosyl sugar moiety,
- d=a 2′-β-D-deoxyribosyl sugar moiety,
- S=a phosphorothioate internucleoside linkage, and
- o=a phosphodiester internucleoside linkage.
An oligomeric compound comprising a modified oligonucleotide according to the following chemical notation:
- GesmCeoAeomCeoAesmCdsAdsAdsGdsmTdsAdsAdsAdsGdsmCdsTeoAeoGesm CesAe (SEQ ID NO:
- 16), wherein:
- A=an adenine nucleobase,
- mC=a 5-methylcytosine nucleobase,
- G=a guanine nucleobase,
- T=a thymine nucleobase,
- e=a 2′-O(CH2)2OCH3 ribosyl sugar moiety,
- d=a 2′-β-D-deoxyribosyl sugar moiety,
- s=a phosphorothioate internucleoside linkage, and
- o=a phosphodiester internucleoside linkage.
Dependencies are inferred from the claim text.