ZEBRA Protein Complex for EBV Diagnosis

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Solution Overview

Problem

Current methods for diagnosing and prognosing lymphoproliferative episodes associated with Epstein-Barr virus (EBV) reactivation in immunocompromised and immunocompetent patients are invasive, costly, and lack standardized, effective biomarkers for early detection and monitoring.

Innovation Solution

A stable protein complex comprising the ZEBRA protein, capable of binding monoclonal antibodies AZ125 and AZ130, is isolated and measured directly in blood or serum, allowing for non-invasive and cost-effective detection of EBV reactivation, which can be used in conjunction with other biomarkers for prognosis and diagnosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current diagnostic methods are used for detecting EBV reactivation, then diagnosis can be performed, but the methods are invasive and costly

Engineering Contradiction:
Improvediagnosis accuracyVSAvoidinvasiveness
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent extracts and measures the ZEBRA protein directly from serum samples, eliminating the need for invasive procedures such as biopsies. This extraction approach allows diagnosis through simple blood sampling while maintaining diagnostic accuracy for EBV reactivation and lymphoproliferative episode detection

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The ZEBRA protein serves as an intermediary biomarker that reflects EBV reactivation status. By measuring this intermediate marker in serum rather than directly assessing viral presence or tissue pathology, the method provides a non-invasive diagnostic approach that maintains reliability

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If current diagnostic methods are used for monitoring lymphoproliferative episodes, then prognosis can be assessed, but the methods lack standardized effective biomarkers

Engineering Contradiction:
Improveprognosis accuracyVSAvoidmethod standardization
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The ZEBRA protein measurement serves multiple functions: it detects EBV reactivation, monitors lymphoproliferative episodes, and provides prognostic information. This single biomarker approach simplifies the diagnostic workflow and enables standardization across different clinical settings while maintaining comprehensive monitoring capability

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent establishes specific concentration thresholds for ZEBRA protein that correlate with different clinical states (EBV reactivation, lymphoproliferative episodes). By defining these parameter ranges, the method achieves standardization and enables reliable prognosis assessment across different patients and laboratories

Inventive Principle:
Principle #35Parameter changes

3Loss of time

If early detection of EBV reactivation is achieved, then timely intervention is possible, but existing methods lack sensitivity and specificity

Engineering Contradiction:
Improvedetection timingVSAvoidsensitivity and specificity
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The ZEBRA protein appears in serum early during EBV reactivation, before full-blown lymphoproliferative episodes develop. By measuring this early marker, the method enables preliminary detection and timely intervention while maintaining high sensitivity and specificity through standardized measurement protocols

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 ZEBRA protein complex provides a reliable, early marker for EBV reactivation, enabling timely detection and monitoring of lymphoproliferative episodes, even in immunocompromised patients, with improved sensitivity and specificity compared to existing methods.

Implementation Method 1

A stable protein complex comprising the ZEBRA protein, capable of binding monoclonal antibodies AZ125 and AZ130

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentEP2788375B1Use of at least one biomarker for the in vitro prognosis or diagnosis of lymphoproliferative episodes associated with the epstein-barr virus (EBV)
Publication Date: 2017.07.12 UNIVERSITE GRENOBLE ALPES
  • EP2788375B1 patent drawingFigure 1
  • EP2788375B1 patent drawing
  • EP2788375B1 patent drawing

AI summary

The present invention relates to a protein complex isolated from its natural environment and comprising the ZEBRA protein of sequence SEQ ID NO: 1, said isolated protein complex having the following properties: - it is more stable than the ZEBRA protein, in particular it is more resistant to the action of proteases than the ZEBRA protein, - it is capable of specifically binding the AZ125 and AZ130 monoclonal antibodies, - it is soluble in a biological fluid, and in particular in a biological fluid chosen from the group consisting of blood and serum, and to the method for demonstrating said complex and the uses of this method for the prognosis or diagnosis of lymphoproliferative episodes associated with EBV.