Humanized Anti-TRBV9 Antibodies With Preserved Binding Affinity
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Solution Overview
Problem
Existing monoclonal antibodies targeting the TRBV9 family of T cell receptors have a relatively low degree of humanization, leading to potential decreases in affinity and solubility, which limits their effectiveness in treating autoimmune and oncological diseases such as ankylosing spondylitis, celiac disease, and T cell lymphomas.
Innovation Solution
Development of humanized monoclonal antibodies with specific binding affinity to the TRBV9 family beta-chain region, featuring increased humanization through amino acid substitutions in the framework regions of the heavy and light chain variable domains, enhancing their therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are humanized to reduce immunogenicity, then therapeutic safety is improved, but binding affinity and solubility may decrease
Solution Approach 1:
The patent applies local quality by making specific amino acid substitutions only in the framework regions (FR1, FR2, FR3, FR4) of the variable domains, while preserving the CDR regions intact. This localized modification approach allows humanization to improve therapeutic safety without compromising the binding affinity determined by the CDR-antigen interface.
Solution Approach 2:
The patent employs parameter changes by systematically substituting amino acid residues at specific positions in the framework regions to increase humanization. These controlled parameter changes (amino acid substitutions) modify the antibody's physical and immunological properties while maintaining or enhancing binding characteristics through rational design.
2Loss of time
If existing monoclonal antibodies with low humanization are used, then development time is reduced, but therapeutic effectiveness decreases
Solution Approach 1:
The patent applies preliminary action by pre-identifying and substituting critical amino acid positions in the framework regions before conducting binding assays. This upfront humanization design, based on predicted immunogenicity at specific positions, accelerates the development process while ensuring therapeutic effectiveness is achieved in later validation stages.
Data Source
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AI summary
The invention relates to a monoclonal humanized antibody or antigen-binding fragment thereof that specifically bind to the TRBV9 family of the human T cell receptor. The invention also relates to a nucleic acid encoding said antibody or antigen-binding fragment thereof, an expression vector, a method for preparing said antibody, and use of said antibody in treatment of diseases or disorders associated with the human T cell receptor family. The invention is directed to generation of antibodies that can be used for treating, in particular AS, celiac disease and malignant blood diseases, the pathogenesis of which involves the TRBV9 family TCRs.