CEACAM6 Biomarker Detection for PTPN2 Mutation IBD Diagnosis

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Solution Overview

Problem

Inflammatory bowel diseases (IBD) such as Crohn's Disease and Ulcerative Colitis are difficult to diagnose and treat effectively, with existing methods failing to address the increased susceptibility and pathogenesis associated with alterations in the intestinal microbiome and loss-of-function mutations in the PTPN2 gene.

Innovation Solution

Detecting increased expression of CEACAM proteins in biological samples using specific binding agents and administering pharmaceutical compositions that inhibit the binding of adherent-invasive Escherichia coli (AIEC) to CEACAM proteins, particularly CEACAM6, to treat or prevent IBD, celiac disease, and colorectal cancer in patients with PTPN2 gene mutations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional diagnostic methods are used for IBD, then general inflammatory markers can be detected, but they fail to identify specific susceptibility to AIEC colonization associated with PTPN2 mutations

Engineering Contradiction:

Improvediagnostic precisionVSAvoiddetection method complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces CEACAM6 as an intermediary biomarker that mediates between the genetic susceptibility (PTPN2 mutation) and the pathogenic effect (AIEC colonization). By detecting CEACAM6 expression levels, the method indirectly identifies patients with PTPN2 mutations who are susceptible to AIEC, without requiring direct genetic testing or complex microbiome analysis.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces complex genetic analysis systems with a simpler protein expression detection system. Instead of directly analyzing PTPN2 gene mutations or performing complex microbiome sequencing, the invention uses immunohistochemistry or ELISA to detect CEACAM6 protein levels, which serve as a functional readout of the genetic susceptibility.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If existing therapeutic approaches are used for IBD, then general anti-inflammatory effects are achieved, but they do not specifically block AIEC invasion in patients with PTPN2 mutations

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtreatment specificity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by targeting the specific CEACAM6-AIEC interaction pathway in patients with PTPN2 mutations, rather than applying general anti-inflammatory treatments to all IBD patients. The therapeutic agent specifically blocks the adhesion molecule CEACAM6, which is upregulated in PTPN2-mutant patients, thereby providing localized and targeted intervention for this specific pathogenic mechanism.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

Instead of trying to enhance the host's immune response to fight AIEC, the patent inverts the approach by blocking the bacterial adhesion mechanism itself. Rather than stimulating CEACAM6 expression to improve immune recognition, the invention suppresses CEACAM6 function to prevent AIEC attachment, thereby inverting the conventional immunostimulatory approach into an immunoblocking strategy.

Inventive Principle:

Principle #13The other way round (Inversion)

3Object-affected harmful factors

If broad-spectrum anti-inflammatory treatments are administered, then general inflammation is reduced, but the underlying mechanism of AIEC-driven inflammation in PTPN2-mutant patients is not addressed

Engineering Contradiction:

Improveinflammation reductionVSAvoidmechanism-specific information

Core Design Contradiction:

Object-affected harmful factorsVSLoss of information

Solution Approach 1:

The patent employs preliminary action by first identifying patients with PTPN2 mutations through CEACAM6 expression analysis, and then administering targeted anti-CEACAM6 therapy. This preliminary identification and stratification ensures that the specific therapeutic mechanism is applied only to patients who will benefit from it, preserving the mechanism-specific information rather than treating all patients uniformly.

Inventive Principle:

Principle #10Preliminary action

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 method effectively identifies susceptibility to AIEC colonization and blocks AIEC invasion, providing a therapeutic approach to prevent or treat IBD, celiac disease, and colorectal cancer by targeting CEACAM6 in patients with PTPN2 gene mutations, thereby addressing the underlying mechanisms of chronic intestinal inflammation.

Implementation Method 1

contacting the biological sample with a binding agent that specifically binds the CEACAM protein

Methodology Applied

Scientific EffectSpecific binding:

Implementation Method 2

an inhibitory agent capable of inhibiting binding of a CEACAM protein to an adherent-invasive Escherichia coli (AIEC)

Methodology Applied

Scientific EffectBinding inhibition:

Data Source

PatentUS11150237B2Patient-specific biomarkers of <i>Escherichia coli </i>invasion in inflammatory bowel disease

Publication Date: 2021.10.19 RGT UNIV OF CALIFORNIA

AI summary

The present invention provides methods of detecting increased carcinoembryonic antigen-related cell adhesion molecule (CEACAM) protein expression in a biological sample from a patient with a loss of function mutation in a protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene. The invention also provides methods of treating or preventing inflammatory bowel disease (IBD) in a patient with a loss of function mutation in a protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene.