RNAi reagents for inhibiting pcsk9 expression, pharmaceutical compositions and methods of use thereof
By designing modified nucleotide double-stranded RNAi reagents to specifically inhibit PCSK9 gene expression, the problems of tolerance and poor efficacy of existing inhibitors have been solved, achieving the therapeutic effect of effectively reducing LDL-C levels and reducing the risk of cardiovascular disease.
CN121548641APending Publication Date: 2026-02-17ARROWHEAD PHARMACEUTICALS INC
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Patent Information
- Application Number
- CN202480029446.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2023-03-02
- Filing Date
- 2024-02-29
- Publication Date
- 2026-02-17
AI Technical Summary
Technical Problem
Existing PCSK9 inhibitors have tolerance issues and poor efficacy in treating hypercholesterolemia, necessitating the development of more effective methods to inhibit PCSK9 gene expression.
Method used
A double-stranded RNAi reagent containing modified nucleotides was designed to inhibit the expression of PCSK9 mRNA by specifically binding to it. N-acetyl-galactosamine was used as a targeting ligand to prepare a drug composition that directly targets the PCSK9 gene in hepatocytes.
Benefits of technology
It effectively inhibits PCSK9 gene expression, reduces LDL-C levels in the blood, reduces atherosclerotic plaques and the risk of cardiovascular disease, and provides an option for improving cardiovascular health in patients with hypercholesterolemia.
✦ Generated by Eureka AI based on patent content.
Abstract
The present disclosure relates to RNAi agents, e.g., double-stranded RNAi agents, e.g., small interfering RNA (siRNA) molecules, capable of inhibiting the expression of the proprotein convertase subtilisin kexin 9 (PCSK9) gene. Pharmaceutical compositions comprising the PCSK9 RNAi agent and methods of using the same are also disclosed. In some embodiments, the PCSK9 RNAi agents disclosed herein can be conjugated to targeting ligands, including ligands comprising N-acetyl-galactosamine, to facilitate delivery to hepatocytes. In vivo delivery of the PCSK9 RNAi agent provides inhibition of expression of the PCSK9 gene, and thus reduction of the PCSK9 protein. RNAi agents may be used in methods of treating diseases or conditions mediated at least in part by PCSK9 gene expression, said diseases or conditions include, inter alia, hypercholesterolemia, familial hypercholesterolemia including heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), familial low beta-lipoproteinemia, hyperlipidemia, coronary artery disease, polygene dyslipidemia, heart disease, cardiovascular disease (CVD) comprising clinical atherosclerotic cardiovascular diseases (ASCVD).
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