Anti-c-Met Antibody CDR Optimization for Binding Affinity and Immunogenicity
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Solution Overview
Problem
Current anti-cancer therapies targeting c-Met, a receptor tyrosine kinase involved in cancer development and resistance to other drugs, require additional effective anti-c-Met antibodies and compositions to overcome limitations in antigen binding affinity and immunogenicity.
Innovation Solution
Development of an anti-c-Met antibody or antigen-binding fragment with specific heavy and light chain complementarity determining regions (CDRs) sequences, including CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, which are optimized for humanization to enhance binding affinity and reduce immunogenicity, and a pharmaceutical composition for preventing or treating cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-c-Met antibodies are used, then c-Met binding is achieved, but binding affinity is insufficient and immunogenicity remains high
Solution Approach 1:
The patent applies parameter changes by optimizing the amino acid sequences of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 regions to achieve higher binding affinity while reducing immunogenicity. Specific amino acid substitutions and optimizations in these complementarity determining regions enable the antibody to bind more effectively to c-Met while being more suitable for human therapeutic use.
Solution Approach 2:
The patent creates a composite antibody structure by combining optimized heavy chain variable region (comprising CDR-H1, CDR-H2, CDR-H3) with light chain variable region (comprising CDR-L1, CDR-L2, CDR-L3) to form an antibody with enhanced properties. This composite approach integrates multiple optimized CDR sequences to achieve both high affinity and low immunogenicity simultaneously.
2Reliability
If additional anti-c-Met antibodies are developed, then therapeutic effectiveness improves, but development complexity increases
Solution Approach 1:
The patent segments the antibody structure into distinct complementarity determining regions (CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3) that can be independently optimized. This segmentation allows for systematic development of multiple antibody variants with different CDR combinations, enabling therapeutic effectiveness improvement while managing development complexity through modular design.
Data Source
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AI summary
An anti c-Met antibody or antibody fragment and pharmaceutical composition comprising same, as well as a method for preventing and treating cancer by administering the antibody to a subject.