Humanized IL-13 Antibody CDR Optimization
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Solution Overview
Problem
There is a need for improved antibodies that can bind and neutralize human IL-13 with high affinity, as existing antibodies are not sufficient in effectively inhibiting IL-13 activity in human IL-13 associated diseases.
Innovation Solution
Development of a novel family of CDR-grafted, humanized antibodies and fragments that specifically bind to human IL-13, utilizing specific complementarity determining regions (CDRs) and framework regions from human immunoglobulin molecules, with optimized sequences for high affinity and neutralization capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used to bind IL-13, then some binding capability is achieved, but the binding affinity and neutralization effectiveness are insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing the CDR sequences and framework regions of the antibody to achieve higher binding affinity. Specifically, the patent describes optimizing CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 sequences with specific amino acid compositions and lengths to enhance binding to human IL-13, thereby resolving the insufficiency of existing antibodies in terms of binding affinity and neutralization effectiveness.
2Reliability
If antibodies with high binding affinity are developed, then neutralization capability is improved, but the complexity of antibody design and development increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into distinct functional modules: framework regions (FR1-FR4 for heavy chain, FR1'-FR4' for light chain) and complementarity determining regions (CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3). This modular structure allows independent optimization of each CDR region for binding affinity while maintaining the overall antibody architecture, thereby managing design complexity through systematic segmentation of the antibody structure.
Solution Approach 2:
The patent applies universality by designing framework regions with conserved sequences that maintain structural integrity and proper folding across different antibody variants. The framework regions provide universal structural support while the CDR regions provide variable binding specificity, allowing the same framework to support multiple different CDR combinations for different IL-13 epitopes, thus reducing overall design complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antibodies effectively inhibit IL-13 biological activity, providing a therapeutic option for IL-13 related diseases by binding with high affinity and neutralizing IL-13, as demonstrated by their ability to block IL-13 receptor interaction and neutralization potency across various IL-13 preparations.
Implementation Method 1
The antibodies effectively inhibit IL-13 biological activity, providing a therapeutic option for IL-13 related diseases by binding with high affinity and neutralizing IL-13
Data Source
AI summary
The invention relates to antibody molecules having specificity for antigenic determinants of human IL-13, therapeutic uses of the antibody molecules and methods for producing the antibody molecules.