Humanized Antibody Binding Amyloid Beta Epitopes
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Solution Overview
Problem
Current treatments for amyloidosis, particularly Alzheimer's Disease and age-related macular degeneration, lack effective methods to prevent or reverse the formation of amyloid plaques and associated complications, with existing medications offering only modest improvements and significant side effects.
Innovation Solution
Development of novel, highly specific humanized antibodies that recognize and bind to specific epitopes of beta-amyloid antigens, including monomeric, dimeric, and polymeric forms, capable of inhibiting aggregation and disaggregating preformed fibrils, thereby reducing amyloid burden and alleviating disease symptoms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing medications are used to treat amyloidosis, then some disease symptoms are alleviated, but the treatment effectiveness is modest and significant side effects occur
Solution Approach 1:
The patent employs parameter changes by developing antibodies with optimized binding affinity and specificity parameters. The humanized antibodies are engineered to have enhanced binding characteristics to amyloid-beta epitopes, allowing for more effective treatment at lower doses and reduced immunogenicity compared to rodent antibodies.
Solution Approach 2:
The patent utilizes composite structures by creating humanized antibodies that combine human antibody frameworks with rodent-derived CDR regions. This composite approach maintains high affinity binding while reducing immunogenicity, achieving a balance between effectiveness and safety.
2Measurement precision
If antibodies are developed to recognize multiple forms of beta-amyloid, then the specificity and effectiveness against amyloid plaques is improved, but the complexity of antibody design and production increases
Solution Approach 1:
The patent applies universality by designing antibodies that can recognize multiple conformations and forms of beta-amyloid (monomeric, oligomeric, and fibrillar forms) through a single antibody molecule. The humanized antibodies are engineered to bind to conserved epitopes that are present across different amyloid-beta structures, enabling one antibody to perform multiple diagnostic and therapeutic functions.
Solution Approach 2:
The patent uses humanized antibody frameworks as intermediaries that bridge the gap between rodent-derived high-affinity binding regions and human immune system compatibility. The CDR regions from rodent antibodies provide the binding specificity, while the human framework provides the structural scaffold and reduces immunogenicity.
3Object-affected harmful factors
If humanized antibodies are used instead of rodent antibodies, then immunogenicity is reduced and treatment safety is improved, but the development time and manufacturing complexity increase
Solution Approach 1:
The patent applies the extraction principle by isolating and transferring only the critical antigen-binding CDR regions from rodent antibodies into human antibody frameworks. This selective extraction maintains the essential binding functionality while removing the immunogenic components, achieving a simplified humanized antibody structure that is easier to manufacture than fully de novo human antibodies.
Data Source
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AI summary
The invention provides an artificial hybrid antibody comprising two different heavy/light chain pairs and two different binding sites, or active fragment thereof, wherein a first heavy/light chain pair binds beta-amyloid. The invention also provides a composition comprising the artificial hybrid antibody or active fragment thereof, and the composition for use in a method of treating or alleviating one or more effects of amyloidosis. The invention further provides a cell comprising two different nucleic acid molecules encoding a humanized antibody or epitope-binding fragment thereof that binds to beta-amyloid and method of producing a humanized antibody or epitope-binding fragment thereof that binds to beta-amyloid.