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US 12,624,358 B2Granted
Compounds and methods for reducing PLN expression
AssigneeIonis Pharmaceuticals, Inc.
InventorsDieter A. Kubli, Brooke A. Anderson, Adam Mullick, Eric E. Swayze
Life of this patent
Estimating the term…
Abstract
Provided are oligomeric compounds, methods, and pharmaceutical compositions for reducing the amount or activity of PLN RNA in a cell or animal, and in certain instances reducing the amount of phospholamban protein in a cell or animal. Such oligomeric compounds, methods, and pharmaceutical compositions are useful to treat cardiomyopathy, heart failure, or arrhythmia.
Claims10
An oligomeric duplex comprising:
- i) a modified oligonucleotide according to the following chemical notation:
- (SEQ ID NO:
- 1255)
- vPTesAfsUyoAyoAyoAyoUyoAyoGyoAyoUyoUyoCyoUfoGyoUfo
- AyoGyoCyoUyoUysAesAe;
- wherein:
- A=an adenine nucleobase,
- C=a cytosine nucleobase,
- G=a guanine nucleobase,
- T=a thymine nucleobase,
- U=a uracil nucleobase,
- e=a 2′-MOE sugar moiety,
- f=a 2′-fluoro sugar moiety,
- y=a 2′-OMe sugar moiety,
- o=a phosphodiester internucleoside linkage,
- s=a phosphorothioate internucleoside linkage, and
- vP=a 5′ vinyl phosphonate group;
- and
- ii) a conjugated modified oligonucleotide according to the following chemical notation:
- (SEQ ID NO:
- 1041)
- [X]1-
- AesAesGyoCyoUyoAyoCyoAyoGyoAfoAfoUyoCyoUyoAyoUyoUyoUyoAysTesAe,
- wherein:
- C=a cytosine nucleobase,
- A=an adenine nucleobase,
- G=a guanine nucleobase,
- U=a uracil nucleobase,
- T=a thymine nucleobase,
- e=a 2′-MOE sugar moiety,
- f=a 2′-fluoro sugar moiety,
- y=a 2′-OMe sugar moiety,
- o=a phosphodiester internucleoside linkage,
- s=a phosphorothioate internucleoside linkage,
- [X]1=a conjugate group having the following structure (SEQ ID NO:
- 1301):
- or a pharmaceutically acceptable salt thereof.
34 more elements
An oligomeric duplex according to the following chemical structure:
- or a pharmaceutically acceptable salt thereof.
An oligomeric duplex according to the following chemical structure:
Dependencies are inferred from the claim text.