Humanized Anti-IL-23 Antibodies Resolving Immunogenicity
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Solution Overview
Problem
Current therapeutic antibodies targeting IL-23p19 face challenges due to immunogenicity issues, leading to reduced efficacy and potential anaphylactic responses, and existing humanized antibodies struggle to maintain antigen binding affinity and biological properties.
Innovation Solution
Development of humanized or chimeric recombinant antibodies specifically designed to bind human IL-23p19, utilizing selected CDRs and framework regions to inhibit IL-23 activity, with the ability to block IL-23-mediated immune responses in inflammatory and autoimmune disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rodent-derived monoclonal antibodies are used to target IL-23p19, then therapeutic efficacy is achieved, but immunogenicity increases leading to reduced efficacy and potential anaphylactic responses
Solution Approach 1:
The patent applies parameter changes by modifying the antibody sequence composition from rodent-derived to humanized or fully human sequences. This changes the immunogenic parameters while maintaining the functional parameters (antigen binding affinity and therapeutic efficacy) through careful selection of CDR regions from rodent antibodies combined with human framework regions.
Solution Approach 2:
The patent uses human framework regions as an intermediary between rodent CDR sequences and the final therapeutic antibody. This intermediary structure allows the rodent CDRs to maintain their antigen-binding specificity while the human framework reduces immunogenicity, serving as a bridge between the two requirements.
2Object-affected harmful factors
If humanized antibodies are developed to reduce immunogenicity, then immunogenicity is reduced, but antigen binding affinity and biological properties may be compromised
Solution Approach 1:
The patent segments the antibody structure into distinct functional regions: CDR regions are retained from rodent antibodies to preserve antigen binding affinity, while framework regions are replaced with human sequences to reduce immunogenicity. This segmentation allows independent optimization of each region's properties.
Solution Approach 2:
The patent applies local quality by giving different parts of the antibody different origins: rodent CDR regions provide high-affinity binding properties locally, while human framework regions provide low-immunogenicity properties locally. This localized optimization resolves the global contradiction between affinity and immunogenicity.
Data Source
AI summary
Engineered antibodies to human IL-23p19 are provided, as well as uses thereof, e.g. in treatment of inflammatory, autoimmune, and proliferative disorders.