IL-33 Binding Antibodies with Optimized CDR Regions
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Solution Overview
Problem
Current treatments for atopic dermatitis lack effective therapies, with existing antibodies showing suboptimal affinity and efficacy for targeting IL-33, a key cytokine involved in inflammatory responses, necessitating the development of alternative antibodies with improved binding properties.
Innovation Solution
Development of antibodies with specific CDR and framework regions that bind human IL-33 with high affinity, including Antibody 43, 54, and 75, which are optimized for binding to human and cynomolgus IL-33, and formulated into pharmaceutical compositions for therapeutic use in treating atopic dermatitis and other allergic diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used to bind IL-33, then therapeutic treatment is provided, but the binding affinity and efficacy are suboptimal
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure specifically in the CDR regions to enhance binding affinity to IL-33. The optimized antibodies (43, 54, 75) have altered amino acid sequences in their CDRs compared to existing antibodies, resulting in improved binding characteristics and reduced dosage requirements for therapeutic effect.
2Reliability
If existing antibodies are used to treat atopic dermatitis, then some therapeutic effect is achieved, but efficacy is insufficient
Solution Approach 1:
The patent applies local quality by making targeted modifications only to the CDR regions of the antibody while maintaining the overall framework structure. This localized optimization approach improves therapeutic efficacy by enhancing IL-33 binding specificity and affinity without requiring complete redesign of the entire antibody molecule, thus managing structural complexity efficiently.
3Quantity of substance
If higher dosage is administered to compensate for suboptimal affinity, then therapeutic coverage is improved, but treatment complexity and cost increase
Solution Approach 1:
The patent resolves this contradiction by changing the binding affinity parameter of the antibody itself, allowing lower dosages to achieve the same therapeutic coverage. The optimized antibodies require reduced dosing compared to existing antibodies, simplifying treatment regimens and reducing administrative complexity while maintaining adequate therapeutic coverage.
Data Source
AI summary
Antibodies which bind and neutralize human IL-33, and methods of using same, are provided, said antibodies are useful as agents for treating conditions associated with allergic disease including treating atopic dermatitis.