Anti-GM-CSFRα Antibodies for Selective GM-CSF Neutralization
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Solution Overview
Problem
Existing treatments for autoimmune and inflammatory diseases mediated by GM-CSF receptor alpha (GM-CSFRα) are limited in efficacy and specificity, particularly in neutralizing GM-CSF binding to its receptor.
Innovation Solution
Development of anti-GM-CSFRα antibodies that specifically bind to a unique epitope comprising amino acid residues Val50, Glu59, Lys194, Lys195, Arg283, and Ile284, with optimized heavy and light chain complementarity determining regions (CDRs) for enhanced affinity and potency, including full-length IgG antibodies and antigen-binding fragments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments for autoimmune and inflammatory diseases are used, then treatment is provided, but efficacy and specificity in neutralizing GM-CSF binding to its receptor are limited
Solution Approach 1:
The antibody is designed to bind to a specific local epitope on the GM-CSFRα receptor (comprising amino acid residues Val50, Glu59, Lys194, Lys195, Arg283, and Ile284). This localized binding approach provides high specificity for the target receptor while maintaining high efficacy in neutralizing GM-CSF binding, resolving the contradiction between general treatment efficacy and specific target neutralization.
2Reliability
If antibodies with high affinity binding are developed, then binding affinity and inhibitory effects are improved, but manufacturing complexity increases
Solution Approach 1:
The antibody structure incorporates optimized complementarity determining regions (CDRs) with specific amino acid sequences that achieve high binding affinity (Kd from about 0.1 pM to about 1 nM) to GM-CSFRα. By carefully selecting and optimizing the CDR parameters (amino acid compositions and sequences), the antibody achieves superior binding affinity while maintaining a standard IgG structure that is compatible with conventional manufacturing processes, thus balancing high affinity with manageable manufacturing complexity.
Data Source
AI summary
The present application provides antibodies including antigen-binding fragment thereof that specifically recognizing Granulocyte-Macrophage Colony Stimulating Factor Receptor (GM-CSFRα). Also provided are methods of making and using these antibodies.