Single Domain Antibodies Targeting IL23R for Inflammatory Disease
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Solution Overview
Problem
Current monoclonal antibodies are large and often ineffective in targeting specific epitopes, and existing therapies for conditions like Crohn's disease and tumor metastases have widespread effects due to non-specific inhibition of the IL12/IL23 pathway, necessitating a more targeted approach.
Innovation Solution
Development of single domain antibodies (sdAbs) that specifically bind to the extracellular domain of the IL23R, utilizing CDRs with high sequence identity to achieve selective targeting and modulation of IL23R activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are used to target IL23R, then binding affinity is achieved, but molecular size is too large (150 kDa) limiting access to certain epitopes
Solution Approach 1:
The patent extracts only the essential binding domain (single domain antibody) from the complete monoclonal antibody structure, removing unnecessary portions while retaining the ability to bind IL23R with high affinity. This reduces molecular size from 150 kDa to a much smaller fragment that can access epitopes inaccessible to full-sized antibodies.
Solution Approach 2:
The antibody is segmented into smaller functional units, specifically single domain antibodies that contain only the critical binding region. This segmentation allows the therapeutic agent to maintain binding functionality while achieving a compact size suitable for penetrating dense tissue and reaching hidden epitopes.
2Reliability
If p40 pathway is inhibited to treat inflammatory diseases, then anti-inflammatory effect is achieved, but organ-specific targeting is reduced due to widespread effects
Solution Approach 1:
The patent applies local quality by designing molecules that specifically target IL23R rather than the broader p40 pathway. This localized targeting approach concentrates the therapeutic effect on specific organs or tissues expressing IL23R, reducing systemic side effects while maintaining anti-inflammatory efficacy in the intended target organs.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The IL23R binding sdAbs provide targeted therapy with reduced side effects by selectively inhibiting IL23R, potentially offering improved treatment options for inflammatory diseases and tumor metastases while minimizing impact on the IL12/IL23 pathway.
Implementation Method 1
a IL23R binding molecule that specifically bind to the extracellular domain of IL23R
Data Source
AI summary
The present disclosure relates to biologically active molecules comprising a single domain antibody (sdAb) that specifically binds to the extracellular domain of human IL23R, compositions comprising such antibodies, and methods of use thereof. Further disclosed are sequences of complementarity determining regions (CDR1, CDR2 and CDR3) and polypeptide sequences of human and mouse sdAbs.