Humanized Antibody Binding Amyloid Beta
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Solution Overview
Problem
Current treatments for amyloidosis, including Alzheimer's Disease and macular degeneration, lack effective methods to prevent or reverse amyloid plaque formation and progression, with existing medications offering only modest improvements and significant side effects.
Innovation Solution
Development of humanized antibodies specifically designed to bind to β-amyloid proteins, capable of inhibiting aggregation and dissolving existing plaques, utilizing a combination of rodent-derived CDRs integrated into human framework sequences to minimize immunogenicity and maintain affinity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rodent antibodies are used to target β-amyloid proteins, then binding affinity and plaque reduction efficacy are improved, but immunogenicity increases causing adverse reactions in human patients
Solution Approach 1:
The patent applies local quality by replacing only the framework regions of the rodent antibody with human sequences while preserving the CDR regions that provide binding affinity. This creates a humanized antibody where different regions have different origins: human framework regions minimize immunogenicity while rodent-derived CDR regions maintain high affinity for β-amyloid proteins.
Solution Approach 2:
The humanized antibody is a composite structure combining human and rodent antibody components. The human framework regions are combined with rodent CDR regions to create a chimeric molecule that exhibits both low immunogenicity (from human portions) and high binding affinity (from rodent portions).
2Reliability
If existing medications are used to treat amyloidosis, then some therapeutic effect is achieved, but side effects are significant and disease progression is not effectively halted
Solution Approach 1:
The humanized antibody acts as a specific intermediary that binds to β-amyloid proteins with high affinity, facilitating their clearance without triggering significant immune responses. This targeted approach replaces non-specific medications with a precisely designed biologic that intermediates between the immune system and amyloid pathology.
3Object-affected harmful factors
If full human antibodies are used, then immunogenicity is minimized, but binding affinity and plaque dissolution capability may be reduced
Solution Approach 1:
The patent maintains local quality by preserving the rodent-derived CDR regions that provide high binding affinity while replacing only the framework regions with human sequences. This selective approach ensures that the regions critical for antigen binding retain their original high-affinity characteristics while the framework regions contribute to reduced immunogenicity.
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 humanized antibodies effectively inhibit amyloid aggregation, reduce plaque burden, and potentially slow disease progression with reduced side effects by targeting β-amyloid proteins specifically, offering a more effective treatment for amyloid-related disorders.
Implementation Method 1
allowing the humanized antibody or fragment thereof to bind to β-amyloid antigen to form an immunological complex
Data Source
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AI summary
The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of j3-amyloid proteins. The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid- like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD).