Variant Antibodies Attenuating Staphylococcus aureus IgBP Binding
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Solution Overview
Problem
Current antibody-based therapies for Staphylococcus aureus infections, such as those targeting immunoglobulin binding proteins (IgBPs), have shown limited clinical efficacy due to microbial immune evasion strategies, including non-immune binding to host immunoglobulins, which hinder effective immune responses.
Innovation Solution
Development of anti-microbial variant antibodies with attenuated non-immune binding to microbial IgBPs, specifically designed with amino acid sequences targeting SpA IgBP domains, enhancing antigen-specific immune binding and antimicrobial activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibodies are used to target S. aureus infections, then antibody-based therapy is provided, but the antibodies exhibit non-immune binding to microbial IgBPs which reduces clinical efficacy
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the antibody heavy chain constant region (specifically residues in the Fc domain) to alter the binding properties. This enables the antibody to maintain or enhance immune binding while reducing non-immune binding to microbial IgBPs, thereby improving clinical efficacy without sacrificing therapeutic function.
2Measurement precision
If antibodies with high affinity to microbial antigens are developed, then antigen-specific immune binding is enhanced, but non-immune binding to Fc region of immunoglobulins may increase
Solution Approach 1:
The patent applies local quality by making specific localized modifications to the Fc region of the antibody heavy chain constant region. These targeted amino acid changes in specific residues allow the antibody to differentiate between immune-relevant binding and non-immune binding to IgBPs, enabling high antigen specificity while minimizing harmful Fc region interactions.
3Adaptability or versatility
If standard immunoglobulin structure is used, then general immune function is maintained, but susceptibility to microbial immune evasion strategies persists
Solution Approach 1:
The patent applies parameter changes by modifying specific parameters of the immunoglobulin structure, namely the amino acid sequence of the heavy chain constant region. These changes confer resistance to microbial immune evasion strategies while preserving the antibody's ability to mediate immune responses, thereby improving both reliability and adaptability.
Data Source
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AI summary
Anti-microbial monoclonal antibodies and variant antibodies having a heavy chain constant regions with at least one amino acid substitution are provided. Such antibodies may be used to prevent or treat microbial infections. In one embodiment, an anti-microbial variant antibody is provided that includes an immunoglobulin heavy chain (e.g., an IgG heavy chain) that differs from that of its unmodified parent anti-microbial antibody by at least one amino acid substitution, wherein the variant immunoglobulin heavy chain has attenuated non-immune binding to one or more microbial virulence factors as compared to that of the unmodified parent antibody. In one aspect, the variant anti-microbial IgG antibody includes a variant heavy chain, in which at least one amino acid from the IgG heavy chain constant region is substituted with another amino acid which is different from that present in the parent antibody.