Amyloid-beta Binding Proteins Targeting Globulomers
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Solution Overview
Problem
Current antibodies targeting amyloid-beta (Aβ) peptides, particularly Aβ(1-42), have shown therapeutic ineffectiveness due to severe side effects such as increased microhemorrhages in animal models, highlighting the need for antibodies that can selectively bind to Aβ globulomers without inducing adverse effects.
Innovation Solution
Development of antibodies with specific amino acid sequences that bind to Aβ(20-42) globulomers, offering higher affinity and specificity, thereby inhibiting the detrimental effects of Aβ globulomeric forms associated with Alzheimer's disease while minimizing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies target Aβ(1-42) peptides, then therapeutic effect is achieved, but severe side effects such as increased microhemorrhages occur
Solution Approach 1:
The patent applies local quality by designing antibodies with specific amino acid sequences that confer selective binding affinity for Aβ globulomers rather than all Aβ forms. This localized specificity ensures the antibody acts only on the pathological globulomer form while sparing other Aβ species, thereby achieving therapeutic effect without inducing microhemorrhages
Solution Approach 2:
The patent employs parameter changes by modifying the antibody's binding characteristics through specific amino acid sequence design. The antibodies are engineered to recognize unique epitopes on Aβ globulomers with high affinity, changing the binding parameter from non-specific to highly specific, which resolves the contradiction between therapeutic effectiveness and safety
2Reliability
If antibodies bind to Aβ globulomers with high affinity, then therapeutic effectiveness increases, but specificity requirements become more stringent
Solution Approach 1:
The patent applies segmentation by dividing the antibody structure into specific variable regions with defined amino acid sequences that recognize distinct epitopes on Aβ globulomers. This segmented approach to antibody design enables high affinity binding while maintaining specificity through carefully engineered complementarity determining regions
Solution Approach 2:
The patent uses intermediary principles by designing antibodies that act as selective mediators between the immune system and Aβ globulomers. The specific amino acid sequences serve as intermediaries that translate the need for high affinity into precise molecular recognition patterns, achieving both effectiveness and specificity
Data Source
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AI summary
The present invention relates to amyloid-beta (As) binding proteins. Antibodies of the invention have high affinity to As(20-42) globulomer or any A form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided.