BCD-133 Anti-IL-5RAlpha Monoclonal Antibody
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Solution Overview
Problem
Current treatments for diseases associated with IL-5Rα, such as asthma and eosinophilic esophagitis, are limited in efficacy and specificity, as existing antibodies may have immunogenicity issues and require genetic modifications to enhance affinity, which can affect binding properties.
Innovation Solution
Development of a fully human monoclonal antibody, BCD-133, that specifically binds to IL-5Rα with affinity comparable to benralizumab, offering enhanced antibody-dependent cytotoxicity and reduced immunogenicity by being de novo derived, thus inhibiting IL-5Rα-mediated activation effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used for treating diseases associated with IL-5Rα, then treatment efficacy is limited, but immunogenicity issues arise requiring genetic modifications
Solution Approach 1:
The patent applies parameter changes by developing a fully human monoclonal antibody (BCD-133) with optimized amino acid sequences that achieve high binding affinity to IL-5Rα without requiring genetic modifications. The antibody was engineered with specific variable region sequences that provide both high efficacy and low immunogenicity, representing a change in the molecular parameters of the antibody structure to resolve the contradiction between treatment efficacy and immunogenicity
Solution Approach 2:
The patent uses copying by creating a fully human antibody sequence based on human germline genes, rather than relying on murine or chimeric antibodies that require humanization. The BCD-133 antibody sequence is derived from human antibody repertoires, copying natural human antibody structures to ensure compatibility with the human immune system, thereby reducing immunogenicity while maintaining therapeutic efficacy
2Manufacturing precision
If genetic modifications are made to enhance antibody affinity, then binding affinity improves, but binding properties may be affected
Solution Approach 1:
The patent applies parameter changes by optimizing the amino acid sequences in the variable regions of the antibody (specifically CDR3 regions) to achieve high binding affinity to IL-5Rα. The BCD-133 antibody was engineered with specific sequence variations in the heavy and light chain variable regions that enhance affinity through controlled parameter changes in the antigen-binding site, while maintaining overall structural integrity and natural binding properties
3Object-affected harmful factors
If fully human monoclonal antibody is developed de novo, then immunogenicity is reduced, but development complexity increases
Solution Approach 1:
The patent uses copying by utilizing human germline antibody gene sequences as templates for developing the BCD-133 fully human monoclonal antibody. By copying and assembling sequences from human antibody repertoires rather than attempting to humanize non-human antibodies, the development process was simplified while ensuring the final product is fully human and minimally immunogenic. This approach avoided the complexity of extensive genetic engineering while achieving the desired fully human characteristic
Data Source
AI summary
The present disclosure relates to biotechnology and provides antibodies that specifically bind to IL-5Rα. The disclosure also relates to DNA encoding the antibodies, the corresponding expression vectors and methods of production thereof, as well as methods of treatment using the antibodies.