PCSK9 Inhibitor Antibody Reduces Atherosclerotic Plaque Formation
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Solution Overview
Problem
Current therapeutic methods fail to effectively inhibit the progression of atherosclerotic plaque formation in subjects, despite the use of PCSK9 inhibitors, which are known to reduce serum cholesterol levels.
Innovation Solution
A pharmaceutical composition comprising an antibody or antigen-binding protein with specific amino acid sequences is administered subcutaneously to reduce atherosclerotic plaque formation by at least 2% in human subjects with atherosclerosis, using a PCSK9 inhibitor that targets PCSK9 to inhibit its biological function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If PCSK9 inhibitors are administered to reduce serum cholesterol levels, then plasma LDL cholesterol is reduced, but atherosclerotic plaque formation is not effectively inhibited
Solution Approach 1:
The patent introduces a novel PCSK9 inhibitor (a specific antibody or antigen-binding protein with defined amino acid sequences) as an intermediary agent that directly binds to PCSK9, preventing its interaction with LDL receptors. This mediator approach transforms the indirect cholesterol reduction into direct plaque formation inhibition by blocking the pathological process at its source
Solution Approach 2:
The patent changes the therapeutic parameter from general cholesterol reduction to specific inhibition of PCSK9 biological function. By targeting the specific molecular mechanism (PCSK9-LDL receptor interaction) rather than just lowering cholesterol levels, the treatment achieves reliable inhibition of atherosclerotic plaque formation
2Quantity of substance
If existing lipid-modifying therapies are used, then plasma cholesterol levels are reduced, but plaque stability is not sufficiently improved
Solution Approach 1:
The PCSK9 inhibitor acts preliminarily by blocking PCSK9-mediated LDL receptor degradation before atherosclerotic plaques can form or progress. This preventive action stabilizes plaques by maintaining healthy LDL receptor levels on hepatic cells, thereby preventing the accumulation of lipids and inflammatory cells that would otherwise destabilize plaques
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution achieves a significant reduction in atherosclerotic plaque formation by up to 90% and enhances the effects of existing lipid-modifying therapies, such as atorvastatin, by dose-dependently decreasing plasma cholesterol and triglycerides, and improving plaque stability.
Implementation Method 1
administering an inhibitor of PCSK9... an antibody or antigen-binding protein comprising an HCVR having the amino acid sequence of SEQ ID NO:1 and an LCVR having the amino acid sequence of SEQ ID NO:6 (PCSK9 inhibitor)
Implementation Method 2
PCSK9 inhibitors have been reported to reduce serum total cholesterol, LDL cholesterol and serum triglycerides
Implementation Method 3
the PCSK9 inhibitor reduces atherosclerotic plaque formation in the subject by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90%
Data Source
Figure 1A~1D
Figure 2A~2B
Figure 3A~3F
AI summary
The present invention provides methods and compositions for inhibiting atherosclerotic plaque formation in a subject. In certain embodiments, the methods of the present invention comprise selecting a subject who has, or is at risk of developing, atherosclerosis, and administering to the subject a pharmaceutical composition comprising a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody, or antigen binding protein.