IL4Rα Antibody Binding Affinity Optimization
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Solution Overview
Problem
Current therapeutic antibodies targeting IL-4 and IL-13 receptors, such as Dupilumab, have limitations in binding affinity and blocking activity for IL4Rα, which are crucial for treating type 2 inflammation-related allergic disorders and cancers.
Innovation Solution
Development of a monoclonal antibody or antigen-binding portion with specific amino acid sequences in the heavy and light chain variable regions that exhibit high binding affinity and blocking activity on IL4Rα, comparable or superior to existing antibodies like Dupilumab, allowing for effective interaction with IL4 and IL13 signaling pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic antibodies like Dupilumab are used to target IL-4Rα, then treatment for type 2 inflammation-related disorders is provided, but the binding affinity and blocking activity are limited
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences in the variable regions of the antibody (both heavy and light chains) to optimize binding affinity. Specific substitutions in CDR regions and framework regions are made to enhance the antibody's interaction with IL-4Rα, directly addressing the limitation of current antibodies' binding affinity while maintaining therapeutic effectiveness
2Reliability
If existing antibodies are used with moderate binding affinity, then some blocking activity is achieved, but effective inhibition of IL4Rα-IL4/IL13-IL13Rα1 interactions is insufficient
Solution Approach 1:
The patent applies local quality by making specific amino acid substitutions in key regions of the antibody variable domains, particularly in the CDR regions that directly contact the antigen. This localized optimization of binding interface properties enhances blocking activity at the molecular interaction level, leading to more effective inhibition of signal transduction without requiring changes to the entire antibody structure
Data Source
AI summary
An isolated monoclonal antibody that specifically binds human IL4Rα, or an antigen-binding portion thereof. A nucleic acid molecule encoding the antibody or the antigen-binding portion thereof, an expression vector, a host cell and a method for expressing the antibody or the antigen-binding portion thereof are also provided. The present disclosure further provides a bispecific molecule, an oncolytic virus and a pharmaceutical composition comprising the antibody or the antigen-binding portion thereof, as well as a treatment method using an Anti-IL4Rα antibody or the antigen-binding portion thereof of the disclosure.