Spike-Protein Antibody Combinations for SARS-CoV-2 Variant Neutralization
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Solution Overview
Problem
Existing vaccines and antibody treatments for COVID-19 have reduced efficacy against emerging variants of SARS-CoV-2, necessitating the development of medicaments that can effectively prevent and treat infections caused by these variants.
Innovation Solution
Development of antibodies or antigen-binding fragments that specifically bind to the spike protein of SARS-CoV-2, including combinations of antibodies that competitively inhibit or bind to the same epitope, with sequences provided for VH and VL regions, capable of neutralizing various SARS-CoV-2 variants with high potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing vaccines and antibody treatments are used, then initial COVID-19 prevention and treatment efficacy is achieved, but efficacy against emerging variants deteriorates
Solution Approach 1:
The patent develops antibody combinations that target multiple epitopes on the spike protein, enabling a single treatment to effectively neutralize multiple SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron. This multi-functional approach allows the antibody combination to adapt to different variants while maintaining high neutralization efficacy
Solution Approach 2:
The invention uses composite antibody combinations (e.g., RQ33+RQ43, RQ33+RQ40) where each antibody targets different epitopes on the spike protein. This composite approach creates synergistic neutralization effects that are more effective against variants than single antibodies, as the variants would need to escape multiple distinct epitope bindings simultaneously
2Reliability
If single antibody treatments are used, then simplicity of administration is maintained, but neutralization potency against variants is insufficient
Solution Approach 1:
The patent merges multiple monoclonal antibodies into combination treatments where each antibody targets a distinct epitope on the spike protein. This combining approach enhances neutralization potency against variants by requiring the virus to simultaneously escape multiple epitope bindings, thereby overcoming the limitations of single antibody treatments
3Adaptability or versatility
If antibodies targeting conserved epitopes are developed, then broad variant coverage is achieved, but binding affinity to specific variants may be reduced
Solution Approach 1:
The patent segments the spike protein into multiple distinct epitopes and develops antibodies that target each segment. By dividing the neutralization task across multiple epitope-specific antibodies, the combination achieves both broad variant coverage through conserved epitope recognition and high binding affinity through optimized individual antibody-epitope interactions
Data Source
AI summary
The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to the spike protein of SARS-COV-2 and methods of making and using the same. The antibodies can be used, for example, in prophylaxis, post-exposure prophylaxis, or treatment of SARS-COV-2 infection. The antibodies can also be used to detect SARS-COV-2, e.g., an infection in subject.