Anti-glycan Antibodies Targeting sLeA and sLeC for Colitis
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Solution Overview
Problem
Existing anti-glycan antibodies have limited immunogenicity and low binding affinity to carbohydrate antigens, making them unsuitable for pharmaceutical development, particularly for treating digestive system disorders like inflammatory bowel disease and cancers.
Innovation Solution
Development of antibodies or antigen-binding portions thereof with high specificity and affinity for sialyl Lewis A (sLeA) and sialyl Lewis C (sLeC), with a binding affinity of KD 60 μM or less for sLeA and KD 100 μM or less for sLeC, while not binding to sialyl Lewis X (sLeX).
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-glycan antibodies are used, then they can bind to carbohydrate antigens, but they have low binding affinity and limited immunogenicity
Solution Approach 1:
The patent applies parameter changes by systematically modifying antibody variables (affinity maturation, humanization, isotype selection) to transform conventional low-affinity anti-glycan antibodies into high-affinity therapeutic candidates. Specific parameter optimizations include achieving KD values of 60 μM or less for sLeA and 100 μM or less for sLeC, while maintaining humanized sequences for pharmaceutical development suitability.
2Reliability
If antibodies target sLeA and sLeC, then they show therapeutic efficacy in colitis models, but they must avoid binding to sLeX to ensure specificity
Solution Approach 1:
The patent applies local quality by designing antibodies with highly specific epitope recognition that distinguishes between structurally similar glycans. The antibody variables are engineered to recognize specific local structural features of sLeA and sLeC (such as the sialyl Lewis A disaccharide structure) while excluding sLeX, achieving selective binding through localized structural discrimination.
Solution Approach 2:
The patent utilizes asymmetry in the glycan recognition mechanism by targeting the asymmetric structural differences between sLeA/sLeC and sLeX. The antibody binding sites are designed to accommodate the specific spatial arrangement of epitopes on sLeA and sLeC while rejecting the symmetric or differently arranged sLeX structure, enabling selective therapeutic activity.
3Reliability
If high affinity anti-glycan antibodies are developed, then they become suitable for pharmaceutical use, but carbohydrate antigens generally have limited immunogenicity
Solution Approach 1:
The patent employs intermediary strategies by using humanized antibody sequences as mediators between the carbohydrate antigen and the immune system. The humanized variables maintain high affinity binding to glycan epitopes while the humanized framework regions improve immunogenicity and reduce host immune responses, effectively mediating the interaction between carbohydrate antigens and the host immune system for therapeutic development.
Data Source
AI summary
The present disclosure provides antibodies, or an antigen binding portion thereof, that bind to sLeA and sLeC. as well as polynucleotides, vectors, host cells, pharmaceutical compositions, and methods related thereto.