Dual-Target Polypeptide Composition for IBD Non-Responders

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Solution Overview

Problem

Current treatments for inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis, particularly in primary non-responders to anti-TNF-alpha agents, are inadequate, with a need for new therapies that can effectively target both TNF-alpha and IL-7R pathways to address inflammation and immune response.

Innovation Solution

Compositions and constructs comprising a TNF-alpha binding polypeptide and an IL-7R binding polypeptide, which can be administered orally, provide enhanced affinity, stability, and efficacy in targeting both pathways, potentially offering additive or synergistic effects in treating IBD.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-TNF-alpha agents are used to treat IBD, then inflammation is reduced, but treatment fails in primary non-responders

Engineering Contradiction:

Improvetreatment efficacyVSAvoidresponse coverage

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines two distinct therapeutic mechanisms into a single composition: anti-TNF-alpha activity (via polypeptides like ID-38F) and anti-IL-7R activity (via polypeptides like ID-A62U). This merging allows the treatment to simultaneously target both the TNF-alpha inflammatory pathway and the IL-7R immune regulation pathway, thereby addressing both responders and non-responders to conventional anti-TNF-alpha therapy with a single agent.

Inventive Principle:

Principle #5Merging (Combining)

2Ease of operation

If single domain antibodies are used, then oral administration is enabled, but stability in gastrointestinal environment is insufficient

Engineering Contradiction:

Improveadministration routeVSAvoidgastrointestinal stability

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent employs single domain antibodies (sdAbs), which are composite protein structures consisting of variable heavy (VH) and variable light (VL) domains that can function independently. These sdAbs are engineered to possess both oral bioavailability and enhanced stability in the gastrointestinal tract, combining the benefits of small size (for oral penetration) with improved structural stability against proteolytic degradation and pH extremes.

Inventive Principle:

Principle #40Composite materials

3Reliability

If TNF-alpha and IL-7R pathways are targeted separately, then each pathway is addressed, but combined efficacy is not achieved

Engineering Contradiction:

Improvepathway targetingVSAvoidtherapeutic effect

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent merges two separate therapeutic functions into a single composition that simultaneously targets TNF-alpha and IL-7R. The composition includes polypeptides with anti-TNF-alpha activity (e.g., ID-38F) and polypeptides with anti-IL-7R activity (e.g., ID-A62U), enabling dual pathway inhibition that produces synergistic or additive therapeutic effects greater than either pathway targeting alone.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS12570736B2Compositions

Publication Date: 2026.03.10 SORRISO PHARMACEUTICALS INC

AI summary

There is provided inter alia a composition comprising a TNF-alpha binding polypeptide and an IL-7R binding polypeptide.