Humanized Anti-β-Glucan Antibodies With High-Affinity Binding
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Solution Overview
Problem
There is a significant need for monoclonal antibodies that exhibit improved binding to β-glucans in clinical, diagnostic, and therapeutic contexts, particularly for humanized antibodies that reduce immunogenicity and enhance efficacy against fungal infections.
Innovation Solution
Development of antibodies or antigen-binding fragments with specific light and heavy chain variable region CDR sequences, capable of binding to β-glucans, including 1,3-β-glucan and 1,6-β-glucan, with at least 70% sequence identity to provided SEQ IDs, which are humanized to minimize immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are engineered to bind to β-glucans, then binding affinity and therapeutic efficacy are improved, but immunogenicity increases due to non-human sequences
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences of the antibody's variable regions (specifically CDRs and framework regions) to achieve optimal binding affinity to β-glucans while reducing immunogenicity. This involves changing sequence parameters, structural parameters, and binding characteristics through rational design and affinity maturation processes.
Solution Approach 2:
The patent segments the antibody structure into distinct functional regions: the variable regions (VH and VL) that bind to β-glucan antigens, and the constant regions that provide effector functions. By separately optimizing the variable regions for binding and the constant regions for reduced immunogenicity, the patent resolves the contradiction between binding affinity and immunogenicity.
2Object-affected harmful factors
If humanized antibodies are developed to reduce immunogenicity, then safety is improved, but binding affinity to β-glucans may be reduced
Solution Approach 1:
The patent applies local quality by making different parts of the antibody have different properties: the CDR regions are optimized for high-affinity binding to β-glucans, while the framework regions are humanized to reduce immunogenicity. This localized optimization allows the antibody to simultaneously achieve low immunogenicity and high binding affinity.
Solution Approach 2:
The patent uses preliminary action by pre-engineering the humanized framework regions before introducing the non-human CDR sequences. This preliminary humanization of the framework provides a stable, low-immunogenicity scaffold that can then accommodate high-affinity binding CDRs without losing the binding capability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The developed antibodies demonstrate improved binding to β-glucans, leading to enhanced clinical, therapeutic, and diagnostic outcomes, particularly in treating fungal infections such as Aspergillus infections, with increased survival rates and reduced fungal burden in immunosuppressed mice.
Implementation Method 1
An antibody may recognise an antigen via the fragment antigen-binding (Fab) variable region
Data Source
AI summary
The present invention relates to antibodies, or antigen-binding fragments thereof, that have binding specificity to β-glucans. Also described are the production of such monoclonal antibodies, and nucleic acids encoding such antibodies.