Cross-Neutralizing Alphavirus Antibodies Using Optimized CDR Binding
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Solution Overview
Problem
There is a challenge in efficiently treating infections caused by alphaviruses, which can lead to severe diseases such as arthritis and encephalitis, with existing treatments being inadequate.
Innovation Solution
Development of antigen binding molecules comprising specific CDR sequences that bind to alphaviruses, including CDR-H1, CDR-H2, CDR-H3, CDR-L1, and CDR-L2, with heavy and light chain variable regions showing at least 80% identity to specified sequences, demonstrating binding to multiple alphaviruses and inhibitory activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used for alphavirus infections, then treatment options are limited, but treatment efficacy is insufficient
Solution Approach 1:
The antigen binding molecules are designed to bind to multiple alphavirus species including Chikungunya virus, Mayaro virus, O'nyong'nyong virus, and Ross River virus. This multi-specificity allows a single treatment approach to address various alphavirus infections, thereby improving both treatment efficacy and the versatility of treatment options simultaneously
2Reliability
If antigen binding molecules with high binding affinity are developed, then inhibitory activity increases, but molecular complexity increases
Solution Approach 1:
The patent focuses on optimizing specific local regions of the antibody - the complementarity determining regions (CDRs) - rather than redesigning the entire molecular structure. By engineering the CDR loops to have high affinity for conserved alphavirus epitopes while maintaining the standard antibody framework, the invention achieves potent inhibitory activity without excessive molecular complexity
Data Source
AI summary
The present disclosure provides neutralising human antibodies that binds to an alphavirus. The antibodies are raised against the chikungunya (CHIKV) virus, and show cross-neutralisation and in vivo protection of other alphaviruses.