CD131-Binding Proteins Neutralize IL-3, IL-5, and GM-CSF Signaling
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Solution Overview
Problem
Current therapeutic antibodies targeting individual cytokines like IL-3, IL-5, and GM-CSF have limited broader application due to redundant and overlapping functions, and variable inflammatory cell infiltrates in conditions such as asthma, with existing treatments like mepolizumab showing no effect on airway obstruction or hyperresponsiveness.
Innovation Solution
Development of CD131-binding proteins with antigen binding domains that neutralize signaling by IL-3, IL-5, and GM-CSF, specifically binding to Site 2 of the CD131 receptor, offering greater efficacy in reducing inflammatory cell survival and eosinophilia compared to standard treatments like prednisolone.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic antibodies targeting individual cytokines (IL-3, IL-5, GM-CSF) are used, then specific cytokine signaling is blocked, but broader application is limited due to redundant and overlapping functions of these cytokines
Solution Approach 1:
The patent applies universality by designing antibodies that target the common beta chain (CD131) shared by multiple cytokine receptors (IL-3R, IL-5R, GM-CSFR). This single antibody can block signaling from multiple different cytokines simultaneously, providing multi-functional activity that addresses the redundant and overlapping functions of individual cytokines in inflammatory airway diseases
2Reliability
If antibodies targeting individual cytokines are used, then specific signaling pathways are inhibited, but treatment effectiveness is reduced due to variable inflammatory cell infiltrates in different patients
Solution Approach 1:
The antibodies designed in this patent target the common beta chain (CD131) that is shared across multiple cytokine receptors. This allows a single therapeutic agent to effectively address variable inflammatory cell infiltrates by simultaneously blocking multiple cytokine signaling pathways (IL-3, IL-5, GM-CSF) that different patient subsets may rely on, thereby improving adaptability to diverse disease presentations
3Reliability
If standard treatments like mepolizumab (anti-IL-5 antibody) are used, then IL-5 signaling is blocked, but no effect is observed on airway obstruction or airway hyperresponsiveness
Solution Approach 1:
The patent overcomes the limitation of single-cytokine targeting by designing antibodies against the common beta chain (CD131) that mediates signaling for IL-3, IL-5, and GM-CSF. This multi-functional approach simultaneously blocks multiple cytokine pathways, providing comprehensive coverage that addresses airway obstruction and hyperresponsiveness more effectively than IL-5-specific antibodies alone
4Reliability
If multiple separate antibodies targeting each cytokine are used, then comprehensive cytokine signaling is blocked, but treatment complexity increases
Solution Approach 1:
The patent merges the functionality of multiple separate antibodies into a single therapeutic agent by targeting the common beta chain (CD131) shared by IL-3R, IL-5R, and GM-CSFR. This consolidation achieves comprehensive cytokine signaling blockade while reducing treatment complexity from multiple agents to one, improving ease of administration and reducing potential drug-drug interactions
Data Source
AI summary
The present disclosure provides a CD131-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain binds to or specifically binds to CD131 and neutralizes signaling by interleukin (IL) 3, IL-5 and granulocyte-macrophage colony stimulating factor (GM-CSF), and uses thereof.