Antibody Engineering for Dengue Virus Neutralization
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Solution Overview
Problem
Current antibody agents, such as 4E11 and 4E5A, are effective against three Dengue Virus serotypes but lack sufficient neutralization capability against the fourth serotype, DV4, due to structural features that hinder binding efficacy.
Innovation Solution
Development of antibody variants with specific structural feature modifications that enhance binding affinity and neutralization potency against DV4, while maintaining or improving neutralization capabilities for the other serotypes, by targeting epitopes like the EDIII domain of the E protein.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If reference antibody 4E11 is used, then binding to all four DV serotypes is achieved, but neutralization capability against DV4 is insufficient
Solution Approach 1:
The patent applies local quality by making specific modifications at particular locations in the antibody structure (CDR regions) to improve binding to DV4 while preserving overall functionality. The antibody 4E11's complementarity determining regions are selectively modified at specific positions to enhance affinity for DV4 epitopes without compromising binding to other serotypes.
Solution Approach 2:
The patent employs parameter changes by modifying amino acid sequences at specific positions in the antibody variable regions. These sequence modifications alter the binding parameters (affinity, specificity) to achieve effective neutralization of DV4 while maintaining cross-reactivity with other serotypes.
2Reliability
If reference antibody 4E5A is used, then binding to all four DV serotypes is achieved, but neutralization capability against DV4 is insufficient
Solution Approach 1:
The patent applies local quality by making specific modifications at particular locations in the antibody structure (CDR regions) to improve binding to DV4 while preserving overall functionality. The antibody 4E5A's complementarity determining regions are selectively modified at specific positions to enhance affinity for DV4 epitopes without compromising binding to other serotypes.
Solution Approach 2:
The patent employs parameter changes by modifying amino acid sequences at specific positions in the antibody variable regions. These sequence modifications alter the binding parameters (affinity, specificity) to achieve effective neutralization of DV4 while maintaining cross-reactivity with other serotypes.
3Reliability
If structural modifications are made to improve DV4 binding, then neutralization of DV4 is enhanced, but binding to other serotypes may be affected
Solution Approach 1:
The patent applies local quality by making specific modifications at particular locations in the antibody structure (CDR regions) to improve binding to DV4 while preserving overall functionality. The modifications are localized to specific complementarity determining regions that interact with DV4 epitopes, leaving other regions intact to maintain binding to other serotypes.
Solution Approach 2:
The patent applies segmentation by separating the antibody into functional regions (CDR regions and framework regions) and making modifications only in specific CDR regions responsible for DV4 binding. This modular approach allows independent optimization of DV4 binding without affecting other serotype binding capabilities.
Data Source
AI summary
The present invention provides, among other things, antibody agents (e.g., antibodies, and/or antigen-binding fragments thereof) that bind to DV epitopes, as well as compositions containing them and methods of designing, providing, formulating, using, identifying and/or characterizing them. In some embodiments, provided antibody agents show significant binding to a plurality of DV serotypes. In some embodiments, provided antibody agents show significant binding to all four DV serotypes. Such antibody agents are useful, for example, in the prophylaxis, treatment, diagnosis, and/or study of DV.