Anti-B7H3 Antibody Binding Compounds with Optimized CDRs
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-B7H3 antibody compounds have high dissociation rates from their antibody-antigen complexes, limiting their therapeutic efficacy in targeting B7H3-expressing tumors.
Innovation Solution
Development of novel antibody binding compounds with specific amino acid sequences and structures that enhance the affinity for B7H3, characterized by equilibrium binding constants of 100 nM or less, comprising specific complementarity determining regions (CDRs) and framework residues, assembled in IgG or Fab formats with disulfide bonds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-B7H3 antibody compounds are used, then they can bind to B7H3 target molecule, but they have high dissociation rates from antibody-antigen complexes which limits therapeutic efficacy
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences in the complementarity determining regions (CDRs) of the antibody. Specifically, it identifies and modifies key amino acid residues at positions HC2:39, HC2:50, and HC3:100 to optimize the binding affinity and reduce dissociation rates, thereby improving therapeutic efficacy while maintaining stable antibody-antigen complex formation
Solution Approach 2:
The patent applies local quality by making specific localized amino acid substitutions at critical positions within the CDR regions rather than throughout the entire antibody structure. The modifications are concentrated at positions HC2:39, HC2:50, and HC3:100 which are locally responsible for antigen binding, allowing precise optimization of binding stability without affecting other functional regions of the antibody
2Strength
If novel antibody binding compounds with specific amino acid sequences are developed to enhance affinity, then binding strength to B7H3 is improved, but the complexity of the antibody structure increases
Solution Approach 1:
The patent makes targeted amino acid substitutions at specific positions (HC2:39, HC2:50, HC3:100) within the CDR regions to enhance binding affinity. This localized modification approach improves binding strength to B7H3 while minimizing structural complexity by leaving the rest of the antibody framework unchanged
Solution Approach 2:
The patent creates composite antibody structures by combining modified CDR regions with established framework regions. The novel antibody binding compounds comprise specific amino acid sequences at key positions integrated into a proven antibody scaffold, achieving enhanced affinity through the combination of optimized binding sites and stable structural framework
Data Source
AI summary
The invention is directed to novel antibody binding compounds specific for the human B7H3 and uses of such compounds for diagnostic and therapeutic purposes.