Bi-Specific Heavy Chain Polypeptides for IL-23 and TNF-Alpha IBD Targeting

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Solution Overview

Problem

Current treatments for inflammatory bowel disease (IBD) using anti-TNF monoclonal antibodies have limitations, with approximately one-third of patients being primary non-responders and subsequent loss of response in primary responders, necessitating new therapeutic strategies targeting IL-23, which is crucial for intestinal inflammation.

Innovation Solution

Development of polypeptides with immunoglobulin chain variable domains that bind specifically to IL-23, offering increased affinity, specificity, and stability against intestinal proteases, allowing for local delivery and potential combination with anti-TNF-alpha polypeptides for enhanced therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-TNF monoclonal antibodies are used to treat IBD, then mucosal healing and remission are achieved in many patients, but approximately one-third of patients are primary non-responders and subsequent loss of response occurs in primary responders

Engineering Contradiction:

Improveresponse rate to anti-TNF therapyVSAvoidtherapeutic effectiveness across different patient subgroups

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the therapeutic approach by targeting a different cytokine pathway (IL-23) rather than continuing with TNF-alpha inhibition. This allows differentiation of treatment strategies based on patient response patterns, addressing the limitation of anti-TNF antibodies affecting only one-third of patients effectively.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces an intermediary therapeutic agent (anti-IL-23 polypeptide) that mediates treatment for patients who have failed or are intolerant to anti-TNF therapy. This intermediary approach enables sequential treatment strategies to address non-response and loss of response issues.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If IL-23 targeting therapy is developed, then effective treatment is provided for IBD patients non-responsive to anti-TNF therapy, but the polypeptide must achieve superior affinity and stability against intestinal proteases

Engineering Contradiction:

Improvetherapeutic efficacy in anti-TNF non-respondersVSAvoidpolypeptide affinity and stability requirements

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by modifying the polypeptide structure to achieve superior affinity constants and enhanced stability against intestinal proteases. These parameter optimizations enable the polypeptide to effectively bind IL-23 and resist degradation in the gastrointestinal tract, meeting the stringent requirements for therapeutic efficacy in anti-TNF non-responders.

Inventive Principle:

Principle #35Parameter changes

3Length of moving object

If local delivery of IL-23 antagonist is implemented, then gastrointestinal tract-restricted antagonism is achieved, but the polypeptide must maintain stability and potency through the gastrointestinal tract

Engineering Contradiction:

Improvegastrointestinal tract penetrationVSAvoidpolypeptide stability in gastrointestinal environment

Core Design Contradiction:

Length of moving objectVSStability of the object's composition

Solution Approach 1:

The patent converts the harmful effect of gastrointestinal proteases into a selective advantage by designing the polypeptide to resist degradation. The polypeptide's structural features enable it to withstand the harsh gastrointestinal environment, allowing local delivery and gastrointestinal tract-restricted antagonism while maintaining stability and potency throughout the tract.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 polypeptides demonstrate superior potency and stability, providing effective treatment for IBD, especially in patients non-responsive to anti-TNF therapy, with potential for prolonged efficacy through gastrointestinal tract-restricted antagonism of IL-23 and TNF-alpha.

Implementation Method 1

polypeptides comprising an immunoglobulin chain variable domain which binds to interleukin-23 (IL-23)

Methodology Applied

Scientific EffectAntigen-antibody binding:

Data Source

PatentUS12559552B2IL-23 and TNF-alpha binding bi-specific heavy chain polypeptides

Publication Date: 2026.02.24 SORRISO PHARMACEUTICALS INC

AI summary

There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain which binds to IL-23, wherein the immunoglobulin chain variable domain comprises three complementarity determining regions (CDR1-CDR3) and four framework regions (FR1-FR4), wherein CDR1 comprises a sequence sharing 60% or greater sequence identity with SEQ ID NO: 1, CDR2 comprises a sequence sharing 50% or greater sequence identity with SEQ ID NO: 2 and CDR3 comprises a sequence sharing 50% or greater sequence identity with SEQ ID NO: 3.