CD19 Antibody CDR Engineering for High Affinity and Lower Deamidation
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Solution Overview
Problem
Existing anti-human CD19 antibodies suffer from deamidation hotspots in their sequences and have lower affinity for the target CD19, limiting their effectiveness in treating B-cell lineage malignancies and autoimmune diseases.
Innovation Solution
Development of anti-human CD19 antibodies with specific CDR sequences (SEQ ID NO: 43-48) and mutations (L234A, L235A, P329G) that enhance affinity and cross-reactivity with human and cynomolgus CD19, formulated as humanized or chimeric monoclonal IgG1 antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-CD19 antibody sequences are used, then the antibodies can be produced and have basic binding capability, but they have deamidation hotspots and lower affinity for CD19
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences of the antibody variable regions (VH and VL domains). Specific mutations are introduced to eliminate deamidation hotspots (asparagine and glutamine residues prone to deamidation) and to enhance binding affinity to CD19. The optimized sequences maintain immunoglobulin structure while improving stability and affinity through targeted sequence parameter changes.
2Reliability
If antibody sequences are optimized for higher affinity, then binding strength to CD19 increases, but the complexity of antibody design and production increases
Solution Approach 1:
The patent applies local quality by making targeted modifications only in specific regions of the antibody molecule - the variable domains (VH and VL) that directly contact the antigen. The constant domains remain unchanged, preserving standard immunoglobulin properties. This localized optimization approach improves affinity and stability without unnecessarily complicating the entire antibody structure or production process.
Data Source
AI summary
The present invention relates to antibodies against human CD19 (anti-human CD19 antibodies), methods for their production, pharmaceutical compositions containing these antibodies, and methods of using the same.