Wise Binding Agents Target Cystine Knot Domain
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Solution Overview
Problem
Current therapeutic options for excessive fibrosis are limited, and there is a need for effective treatments that can prevent or treat kidney and lung fibrosis, as well as associated damage and organ dysfunction.
Innovation Solution
Development of binding agents, such as antibodies, that specifically target the cystine knot domain of the WISE protein to inhibit its activity, thereby reducing tissue injury and fibrosis in organs like the kidneys, lungs, skin, eye, liver, and heart, and improving organ function or delaying organ dysfunction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If WISE knockout mice are used to study fibrosis, then protection from kidney injury and reduced fibrosis is observed, but it is unpredictable whether acute inhibition of WISE activity using an inhibitor such as an antibody could provide therapeutic benefit
Solution Approach 1:
The patent uses binding agents (antibodies) as intermediaries to acutely inhibit WISE activity in vivo. These antibodies specifically bind to WISE protein, blocking its function without requiring complete knockout of the gene, thus providing a therapeutic approach that bridges the gap between knockout mouse findings and clinical application.
2Measurement precision
If binding agents target the cystine knot domain of WISE, then specific binding and inhibition of WISE activity is achieved, but the complexity of identifying and characterizing specific epitopes increases
Solution Approach 1:
The patent segments the WISE protein into distinct domains, specifically focusing on the cystine knot domain (amino acids 71-170) as a target for binding agents. By identifying and characterizing epitopes within this specific segment, the patent achieves precise binding while simplifying the overall approach to target identification.
Solution Approach 2:
The patent applies local quality by concentrating binding agent development on the specific cystine knot domain of WISE rather than the entire protein. This localized approach allows for high-specificity binding while reducing the complexity of characterizing the entire protein structure.
3Reliability
If WISE deletion is performed to protect from tubular injury, then reduced mortality is observed, but the complexity of genetic modification and breeding increases
Solution Approach 1:
The patent uses binding agents as intermediaries to achieve WISE inhibition without requiring genetic deletion. This approach replicates the protective effects observed in WISE knockout mice while avoiding the complexities of genetic modification and breeding programs.
Data Source
AI summary
The present invention relates to binding agents for WISE, and includes for their manufacture and use.