IL-33R Antibodies with Engineered CDRs for Inflammatory Disease
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Solution Overview
Problem
Current treatments for conditions like rheumatoid arthritis, asthma, and ulcerative colitis do not adequately target IL-33R, leading to incomplete suppression of Th2-type immune responses and associated inflammation.
Innovation Solution
Development of antibodies specifically binding to IL-33R with high affinity, characterized by specific CDR regions and modifications in the hinge region, which inhibit IL-33 binding and signaling, thereby reducing inflammatory responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for rheumatoid arthritis, asthma, and ulcerative colitis, then general immune suppression is achieved, but IL-33R specific signaling is not adequately blocked leading to incomplete suppression of Th2-type responses
Solution Approach 1:
The patent modifies antibody parameters by engineering specific CDR regions (SEQ ID NO: 1-6) and hinge region mutations (L234A, L235A) to create antibodies with optimized binding affinity and specificity for IL-33R, achieving reliable suppression of Th2-type responses through precise molecular parameter optimization
Solution Approach 2:
The patent creates chimeric and humanized antibody variants that copy the binding properties of the parent antibody while improving pharmacokinetic properties and reducing immunogenicity, allowing for effective IL-33R blockade with optimized therapeutic profiles
2Measurement precision
If antibodies with high affinity for IL-33R are developed, then specific inhibition of IL-33 binding is achieved, but manufacturing complexity increases due to specific CDR region requirements
Solution Approach 1:
The patent segments the antibody structure into distinct functional regions: variable domains with specific CDR regions (SEQ ID NO: 1-6) for high-affinity binding, and constant domains with hinge region mutations (L234A, L235A) for optimized effector functions, allowing independent optimization of each segment
Solution Approach 2:
The patent applies local quality by introducing specific mutations only in the hinge region (L234A, L235A) while maintaining the overall antibody structure, and by designing specific CDR regions (SEQ ID NO: 1-6) that provide high binding affinity without requiring complete restructuring of the antibody molecule
3Duration of action of moving object
If hinge region modifications are introduced to improve antibody properties, then pharmacokinetic profile is enhanced, but manufacturing precision requirements increase
Solution Approach 1:
The patent changes specific parameters in the hinge region (L234A, L235A mutations) to optimize pharmacokinetic properties such as half-life and Fc receptor binding, while using standardized mutation protocols that maintain manufacturing feasibility
Data Source
AI summary
An antibody binding to IL33R characterized in that the heavy chain variable domain comprises a CDR3 region of SEQ ID NO:1, a CDR2 region of SEQ ID NO:2 and a CDR1 region of SEQ ID NO:3 and in that the light chain variable domain comprises a CDR3 region of SEQ ID NO:4, a CDR2 region of SEQ ID NO:5 and a CDR1 region of SEQ ID NO:6 or a a chimeric, humanized or T cell epitope depleted antibody variant thereof has advantageous properties for the treatment of inflammatory diseases.