Humanized Anti-GPVI Antibody Conformational Epitope Binding
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Solution Overview
Problem
Current anti-Glycoprotein VI antibodies are either immunogenic in humans, have low affinity, short half-life, or induce undesirable GPVI depletion, limiting their effectiveness in treating cardiovascular diseases.
Innovation Solution
Development of a humanized monoclonal antibody with a novel conformational epitope binding to human GPVI, which has strong affinity and does not decrease platelet count or induce GPVI depletion, allowing for specific inhibition of GPVI interaction with collagen and fibrin without immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-GPVI antibodies are used, then GPVI binding activity is achieved, but immunogenicity in humans occurs
Solution Approach 1:
The patent applies humanization to modify the antibody's amino acid sequence parameters, transforming it from a murine antibody to a humanized antibody with human-like sequences. This reduces immunogenicity while preserving GPVI binding activity through careful selection of framework regions and CDRs that maintain affinity for the human GPVI target.
2Reliability
If existing anti-GPVI antibodies are used, then GPVI inhibition is achieved, but platelet count decreases
Solution Approach 1:
The patent targets a specific conformational epitope on GPVI with high specificity. By designing the antibody to bind precisely to this localized epitope structure, the invention achieves GPVI inhibition while avoiding non-specific effects on platelet function and count that plague broader-acting antibodies.
Solution Approach 2:
The patent replaces the mechanism of existing antibodies that cause platelet depletion with a new mechanism based on conformational epitope recognition. This substitution of binding mechanism prevents the harmful depletion effect while maintaining therapeutic GPVI inhibition.
3Reliability
If existing anti-GPVI antibodies are used, then GPVI binding is achieved, but affinity is low
Solution Approach 1:
The patent optimizes the antibody's binding parameters through humanization and affinity maturation processes. By adjusting amino acid sequences in the CDR regions and framework regions, the invention achieves high-affinity binding to human GPVI while maintaining the antibody's structural integrity and specificity.
4Reliability
If existing anti-GPVI antibodies are used, then GPVI targeting is achieved, but half-life is short
Solution Approach 1:
The patent creates a composite antibody structure combining humanized sequences with optimized constant regions. This composite design enhances the antibody's pharmacokinetic properties, including half-life, while preserving its ability to specifically target and bind human GPVI with high affinity.
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 antibody effectively prevents thrombus formation and treats cardiovascular diseases by specifically targeting GPVI without the risks associated with existing antibodies, offering improved efficacy and safety.
Implementation Method 1
a humanized monoclonal antibody with a novel conformational epitope binding to human GPVI, which has strong affinity and does not decrease platelet count or induce GPVI depletion, allowing for specific inhibition of GPVI interaction with collagen and fibrin
Data Source
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AI summary
The present invention relates to humanized anti-human GPVI antibodies and uses thereof.