Organic compositions to treat APOC3-related diseases
First Claim
1. A double-stranded RNAi agent for inhibiting expression of an APOC3 gene in a cell, the RNAi anent comprising a first strand and a second strand, wherein said first strand is less than about 49 nucleotides in length and comprises at least 19 contiguous nucleotides differing by 0 or 1 nucleotides from the nucleotide sequence (5′
- to 3′
) AGCACUGAGAAUACUGUCC (SEQ ID NO;
132), wherein the second strand is substantially complementary to the first strand, wherein the first strand comprises at least one modified nucleotide or modified internucleoside linkage, wherein the 3′
end of the first strand and/or the second strand comprises a 3′
end cap, and wherein the 3′
end of the first and/or second strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5′
to 3′
order;
a spacer, a second phosphate or modified internucleoside linker, and a 3′
end cap.
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Accused Products
Abstract
The present disclosure relates to compositions and methods for treating APOC3-related diseases such as: hypertriglyceridemia (e.g., Type V Hypertriglyceridemia), abnormal lipid metabolism, abnormal cholesterol metabolism, atherosclerosis, hyperlipidemia, diabetes, including Type 2 diabetes, obesity, cardiovascular disease, and coronary artery disease, among other disorders relating to abnormal metabolism or otherwise, using a therapeutically effective amount of a RNAi agent to APOC3.
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Citations
17 Claims
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1. A double-stranded RNAi agent for inhibiting expression of an APOC3 gene in a cell, the RNAi anent comprising a first strand and a second strand, wherein said first strand is less than about 49 nucleotides in length and comprises at least 19 contiguous nucleotides differing by 0 or 1 nucleotides from the nucleotide sequence (5′
- to 3′
) AGCACUGAGAAUACUGUCC (SEQ ID NO;
132), wherein the second strand is substantially complementary to the first strand, wherein the first strand comprises at least one modified nucleotide or modified internucleoside linkage, wherein the 3′
end of the first strand and/or the second strand comprises a 3′
end cap, and wherein the 3′
end of the first and/or second strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5′
to 3′
order;
a spacer, a second phosphate or modified internucleoside linker, and a 3′
end cap. - View Dependent Claims (2, 3, 4, 5, 7, 8, 9, 10, 11)
- to 3′
-
6. A double-stranded RNAi agent for inhibiting expression of an APOC3 gene in a cell, the RNAi agent comprising a first strand and a second strand, wherein said first strand is less than about 49 nucleotides in length and comprises at least 19 continuous nucleotides differing by 0 or 1 nucleotides from the nucleotide sequence (5′
- to 3′
) AGCACUGAGAAUACUGUCC (SEQ ID NO;
132), and wherein the second strand is substantially complementary to the first strand, wherein the RNAi agent is ligated to an N-Acctylgalactosamine-containing compound that comprises the following structure;
- View Dependent Claims (16)
- to 3′
-
12. A double-stranded RNAi agent for inhibiting expression of an APOC3 gene in a cell, the RNAi agent comprising a first strand and a second strand wherein the first strand and second strand comprise the duplex pair of SEQ ID NOs:
- 484/438, 485/438, 486/438;
487/438;
488/438;
489/438;
491/438;
496/438;
497/438;
498/438;
499/438;
501/438;
502/438;
or 503/439. - View Dependent Claims (13, 14, 15, 17)
- 484/438, 485/438, 486/438;
Specification