IL-1β Binding Proteins with Optimized CDR Sequences
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Solution Overview
Problem
There is a need for improved antibodies that can effectively bind and neutralize IL-1β to treat IL-1β-associated diseases and detect IL-1β in samples and tissues, as existing antibodies are inadequate in addressing the inflammatory disorders caused by IL-1β.
Innovation Solution
Development of a novel family of binding proteins, including monoclonal antibodies, CDR-grafted antibodies, humanized antibodies, and their fragments, which bind human IL-1β with high affinity and neutralize its activity, utilizing specific amino acid sequences to target IL-1β and modulate its biological functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used to bind IL-1β, then some binding activity is achieved, but the binding affinity and neutralization effectiveness are inadequate for treating inflammatory disorders
Solution Approach 1:
The patent applies parameter changes by modifying amino acid sequences in the antibody variable regions, particularly in the CDR3-H and CDR3-L regions, to optimize binding affinity to IL-1β. The antibodies were engineered with specific mutations in the heavy and light chain variable regions to enhance neutralization effectiveness while maintaining manufacturability through systematic sequence optimization
Solution Approach 2:
The patent creates composite antibody structures by combining optimized heavy chain variable regions with optimized light chain variable regions. The chimeric and humanized antibody constructs integrate different sequence elements from various sources to achieve superior binding properties while maintaining structural integrity for production
2Measurement precision
If existing antibodies are used to detect IL-1β in samples and tissues, then detection is possible, but the detection accuracy and sensitivity are insufficient for effective diagnosis and monitoring
Solution Approach 1:
The patent improves detection precision by engineering antibodies with enhanced binding parameters through amino acid sequence optimization. The modified CDR regions increase affinity and specificity for IL-1β, enabling more accurate and sensitive detection in complex biological samples while maintaining assay feasibility
Data Source
AI summary
The present invention describes IL-1β binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind IL-1β. Binding proteins of the invention have high affinity for IL-1β and neutralize IL-1β activity. A binding protein of the invention can be a full-length antibody or an IL-1β-binding portion thereof. Methods of making and methods of using the binding proteins of the invention are also described. The IL-1β binding proteins of the invention are useful for detecting IL-1β and for inhibiting IL-1β activity, including in a human subject suffering from a disease or disorder in which IL-1β activity is detrimental.