CD19 Antibody CDR Sequence Optimization for Binding Affinity
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Solution Overview
Problem
Current antibodies targeting CD19 for treating B cell-related leukemia and autoimmune diseases have limitations in affinity and specificity, which hampers their effectiveness.
Innovation Solution
Development of a CD19 antibody or antigen binding fragment with specific sequences in the heavy chain variable region (HCDR1-3) and light chain variable region (LCDR1-3) that demonstrate high binding affinity to human CD19, potentially cross-binding to monkey CD19.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies targeting CD19 are used for treating B cell-related leukemia and autoimmune diseases, then treatment can be initiated, but the binding affinity and specificity are insufficient, hampering effectiveness
Solution Approach 1:
The patent applies parameter changes by optimizing the amino acid sequences in the complementarity determining regions (CDRs) of the antibody. Specifically, the heavy chain CDRs (HCDR1-3) and light chain CDRs (LCDR1-3) are designed with specific sequences that enhance binding affinity to CD19. This involves modifying residue compositions and configurations in these critical regions to achieve superior binding characteristics compared to existing antibodies.
Solution Approach 2:
The patent applies local quality by focusing the optimization on specific local regions of the antibody molecule - namely the CDRs in the variable regions of heavy and light chains. Rather than redesigning the entire antibody structure, the invention concentrates on improving the local binding interface through precise sequence selection in HCDR1-3 and LCDR1-3, which are the regions directly responsible for antigen recognition and binding.
2Reliability
If existing antibodies targeting CD19 are used, then treatment can be initiated, but the specificity for human CD19 is insufficient
Solution Approach 1:
The patent applies parameter changes by carefully selecting and optimizing the amino acid sequences in the CDR regions to enhance specificity for human CD19. The heavy chain CDR sequences (HCDR1-3) and light chain CDR sequences (LCDR1-3) are designed with specific residue compositions that confer high specificity for human CD19 epitopes, reducing cross-reactivity with other antigens while maintaining effective binding.
Solution Approach 2:
The patent applies segmentation by dividing the antibody into functional regions - specifically isolating and optimizing the CDR segments (HCDR1-3 and LCDR1-3) that are responsible for antigen specificity. This segmentation allows independent optimization of the binding interface without affecting the overall antibody structure, thereby enhancing specificity while maintaining therapeutic efficacy.
Data Source
AI summary
A CD19 antibody and an application thereof, an antibody or antigen binding fragment specifically binding to human CD19, a multi-characteristic antigen binding molecule, a chimeric antigen receptor, an immune effector cell, a nucleic acid molecule, a vector, a cell, a preparation method, a pharmaceutical composition, a pharmaceutical use, and a disease treatment method. The present invention has great significance for the development of drugs for treating CD19-related diseases.