Anti-C5a Antibodies Targeting a Novel Epitope for Lower Dosing
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Solution Overview
Problem
Existing antibodies targeting C5a do not effectively inhibit C5a-mediated inflammatory responses due to high binding affinity to C5, requiring high doses and frequent administration, and fail to block C5a's pathogenic effects in conditions like sepsis and asthma.
Innovation Solution
Development of anti-C5a antibodies that bind to a novel epitope on C5a, specifically residues 31-40, with reduced affinity to C5, allowing lower doses and less frequent administration while effectively inhibiting C5a-mediated inflammatory responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-C5a antibodies are used to inhibit C5a-mediated inflammatory responses, then C5a binding is blocked, but high doses and frequent administration are required due to high binding affinity to C5
Solution Approach 1:
The patent modifies the binding parameters of anti-C5a antibodies by targeting a specific epitope (residues 31-40) on C5a, changing the binding characteristics to achieve potent inhibition with lower doses. The antibody design focuses on specific amino acid residues (D31, E32, R40) to optimize binding affinity and selectivity, reducing the quantity of substance needed for effective treatment
2Reliability
If existing anti-C5a antibodies bind with high affinity to C5, then C5a binding is blocked, but the antibodies fail to effectively inhibit C5a-mediated inflammatory responses in conditions like sepsis and asthma
Solution Approach 1:
The patent applies local quality by targeting a specific local region (epitope residues 31-40) on the C5a molecule rather than binding globally to C5. This localized binding approach focuses the therapeutic effect on the pathogenic C5a fragment while avoiding interference with C5 function, thereby effectively inhibiting C5a-mediated inflammatory responses in conditions like sepsis and asthma
3Reliability
If anti-C5a antibodies bind to the C5a molecule, then C5a activity is inhibited, but the antibodies also bind to C5 requiring high doses
Solution Approach 1:
The patent extracts the specific epitope (residues 31-40) from the full C5a molecule as the target for antibody binding. By focusing on this extracted specific region rather than the entire C5/C5a complex, the antibodies achieve high specificity to C5a with reduced cross-reactivity to C5, thereby lowering the administration dose required for effective treatment
Data Source
AI summary
The present application provides antibodies including antigen-binding fragments thereof that specifically recognizing Complement component 5a (C5a). Also provided are methods of making and using these antibodies.