Anti-PD1 Antibody CDR Engineering for Specificity and Affinity
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Solution Overview
Problem
Existing anti-PD1 antibodies for cancer treatment have suboptimal specificity and affinity due to limitations in their development.
Innovation Solution
Development of anti-PD1 antibodies utilizing natural affinity maturation processes to enhance specificity and binding affinity, incorporating specific heavy and light chain complementarity determining regions (CDRs) with defined amino acid sequences or conservative substitutions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-PD1 antibodies are used for cancer treatment, then therapeutic function is provided, but specificity and binding affinity are suboptimal
Solution Approach 1:
The patent applies parameter changes by systematically modifying the amino acid sequences of complementarity-determining regions (CDRs) in the antibody variable domains. Through affinity maturation processes, specific residues in the heavy and light chain CDRs are mutated to optimize binding parameters, achieving both high specificity for PD1 and enhanced binding affinity while resolving the technical contradiction between these two parameters.
2Ease of manufacture
If existing anti-PD1 antibodies are used, then cancer treatment is enabled, but cross-reactivity with related proteins occurs
Solution Approach 1:
The patent applies local quality by making targeted amino acid substitutions specifically in the CDR regions that contact the PD1 antigen. These localized changes in the binding interface enhance specificity for PD1 while maintaining the overall antibody structure and therapeutic function, thereby reducing cross-reactivity with related proteins without sacrificing therapeutic efficacy.
Data Source
AI summary
Described herein are novel anti-PD1 antibody reagents (e.g., antibodies, antigen-binding fragments thereof, and/or chimeric antigen receptors). Also decribed herein antibody-drug conjugates or kits comprising the disclosed antibody reagents, as well as methods of treating cancer by administereing the disclosed antibody reagents.


