Anti-CD47 Antibodies Blocking CD47/SIRP-alpha Interaction
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Solution Overview
Problem
Current anti-CD47 antibodies often cause red blood cell agglutination and have limited efficacy in promoting phagocytosis of tumor cells, while also failing to effectively block the interaction between CD47 and its receptor SIRP-α.
Innovation Solution
Development of anti-CD47 antibodies with high binding affinity to human CD47 proteins that specifically block the CD47/SIRP-α interaction, promoting phagocytosis of tumor cells without causing significant red blood cell agglutination, utilizing specific amino acid sequences in the VH and VL CDR regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-CD47 antibodies are used, then they can bind to CD47 protein, but they cause red blood cell agglutination and have limited efficacy in promoting phagocytosis
Solution Approach 1:
The patent applies local quality by modifying specific amino acid residues at particular positions in the antibody variable regions (VH CDR1 position 3, VH CDR2 positions 5 and 9, VH CDR3 positions 10 and 13, VL CDR1 position 30, VL CDR2 position 50, VL CDR3 position 92). These localized modifications at specific positions improve phagocytosis promotion while eliminating RBC agglutination, rather than making global changes to the entire antibody structure.
Solution Approach 2:
The patent employs parameter changes by systematically varying amino acid sequences at specific positions in the CDR regions to optimize antibody performance. By changing the chemical properties, charge, and structure of amino acids at key positions, the patent achieves enhanced binding affinity to CD47, improved phagocytosis promotion, and eliminated RBC agglutination side effects.
2Reliability
If anti-CD47 antibodies are designed to block CD47/SIRP-α interaction, then they can promote phagocytosis, but they may still cause red blood cell agglutination
Solution Approach 1:
The patent applies local quality by making targeted amino acid modifications specifically in the CDR regions that contact CD47, while leaving other regions unchanged. The specific position modifications (VH CDR1 position 3, VH CDR2 positions 5 and 9, VH CDR3 positions 10 and 13, VL CDR1 position 30, VL CDR2 position 50, VL CDR3 position 92) locally optimize the interaction blocking capability without affecting RBC binding.
Solution Approach 2:
The patent segments the antibody structure into distinct functional regions (VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, VL CDR3) and independently optimizes each segment's amino acid sequence. This segmentation allows separate optimization of CD47 binding affinity, interaction blocking, and RBC agglutination avoidance in different regions of the antibody.
Data Source
AI summary
Provided are anti-CD47 antibodies and fragments thereof. The antibodies and fragments thereof specifically bind to the CD47 protein. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer and atherosclerosis are also provided.