Antigen Binding Proteins Neutralize PCSK9 to Preserve LDLR

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Solution Overview

Problem

Current technologies lack effective solutions to neutralize the LDL-lowering effect of PCSK9 on LDLR, which contributes to elevated serum cholesterol levels, as existing methods fail to adequately inhibit PCSK9's interaction with LDLR.

Innovation Solution

Development of antigen binding proteins that specifically bind to PCSK9, reducing its interaction with LDLR by targeting specific epitopes, thereby increasing LDLR availability and decreasing serum cholesterol levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PCSK9 is present to regulate LDLR levels, then plasma cholesterol control is maintained, but LDLR levels decrease and serum cholesterol increases

Engineering Contradiction:
Improveplasma cholesterol controlVSAvoidLDLR levels
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent introduces an antibody as an intermediary substance that binds to PCSK9, preventing PCSK9 from interacting with LDLR. This mediator blocks the harmful interaction while allowing PCSK9 to continue its natural regulation function, thereby preserving LDLR levels and reducing serum cholesterol.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If PCSK9 interacts with LDLR to lower LDLR levels, then PCSK9's natural function is fulfilled, but therapeutic effect for hypercholesterolemia is reduced

Engineering Contradiction:
ImprovePCSK9 functionVSAvoidhypercholesterolemia
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts or removes PCSK9 from its harmful interaction with LDLR by introducing an antibody that specifically binds to PCSK9. This sequesters PCSK9 in an antibody-PCSK9 complex, preventing it from interacting with LDLR and thereby eliminating the harmful effect while preserving PCSK9's natural function.

Inventive Principle:
Principle #2Taking out (Extraction)

3Quantity of substance

If existing methods are used to inhibit PCSK9, then some inhibition is achieved, but adequate neutralization of PCSK9's LDLR-lowering effect is not achieved

Engineering Contradiction:
ImprovePCSK9 inhibitionVSAvoidneutralization effectiveness
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent employs parameter changes by optimizing the antibody's binding affinity and specificity for PCSK9. By carefully selecting and engineering antibodies with appropriate binding characteristics, the patent achieves adequate neutralization of PCSK9's LDLR-lowering effect, transforming insufficient inhibition into effective therapy.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2215124B9Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9)
Publication Date: 2023.12.27 AMGEN INC
  • EP2215124B9 patent drawingFigure 1A
  • EP2215124B9 patent drawingFigure 1B1
  • EP2215124B9 patent drawingFigure 1B2

AI summary

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.