RNAi constructs and methods for inhibiting LPA expression
AssigneeAmgen Inc.
InventorsBin Wu, Michael Ollmann, Oliver Homann, Yuan Cheng
Life of this patent
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Abstract
The present invention relates to RNAi constructs for reducing expression of the LPA gene, which encodes apolipoprotein(a), a component of lipoprotein(a) (Lp(a)) particles. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease, peripheral artery disease, stroke, and myocardial infarction, and to reduce serum Lp(a) levels are also described.
Claims36
An RNAi construct comprising a sense strand and an antisense strand, wherein the antisense strand comprises a region having a sequence that is complementary to a lipoprotein (a) (LPA) mRNA sequence, wherein
- the sense strand comprises or consists of the sequence of SEQ ID NO:
- 79 or SEQ ID NO:
- 80 and the antisense strand comprises or consists of the sequence of SEQ ID NO:
- 194, and wherein all of the nucleotides in the sense and antisense strands are a combination of 2′-O-methyl modified nucleotides and 2′-fluoro modified nucleotides.
An RNAi construct comprising a sense strand and an antisense strand, wherein the antisense strand comprises a region having a sequence that is complementary to an LPA mRNA sequence, wherein the sense strand comprises or consists of the sequence of modified nucleotides according to SEQ ID NO:
- 350 and the antisense strand comprises or consists of the sequence of modified nucleotides according to SEQ ID NO:
- 525.
An RNAi construct comprising a sense strand and an antisense strand, wherein the antisense strand comprises a region having a sequence that is complementary to an LPA mRNA sequence, wherein the sense strand comprises or consists of the sequence of modified nucleotides according to SEQ ID NO:
- 350 and the antisense strand comprises or consists of the sequence of modified nucleotides according to SEQ ID NO:
- 527.
An RNAi construct comprising a sense strand and an antisense strand, wherein the antisense strand comprises a region having a sequence that is complementary to an LPA mRNA sequence, wherein the sense strand comprises or consists of the sequence of modified nucleotides according to SEQ ID NO:
- 354 and the antisense strand comprises or consists of the sequence of modified nucleotides according to SEQ ID NO:
- 525.
Dependencies are inferred from the claim text.