NRG1 Fusion Junction Detection for Faster Cancer Diagnosis

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Solution Overview

Problem

There is a need for quicker and more robust diagnosis of NRG1 fusions and identification of heretofore unknown NRG1 fusion partners and break points in various tumor types.

Innovation Solution

The disclosure provides novel NRG1 fusions with novel fusion partners such as VAPB, PVALB, DAAM1, ASPH, ZFAT, and DSCAML1, and previously undisclosed fusion junctions with CADM1, CD44, SLC3A2, VTCN1, CDH1, CXADR, GTF2E2, CSMD1, PTN, ST14, THBS1, AGRN, APP, WRN, NOTCH2, CD74, SDC4, and SLC4A4, along with methods for detecting these fusions using nucleic acid probes and antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional diagnostic methods are used for NRG1 fusions, then the diagnosis can be performed with existing tools, but the diagnosis is not quick or robust enough and unknown fusion partners cannot be identified

Engineering Contradiction:
Improvediagnosis accuracyVSAvoiddiagnosis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the diagnostic approach by creating specific detection methods for different NRG1 fusion types (e.g., NRG1::ASPH, NRG1::DAAM1, NRG1::VAPB). Each fusion type has dedicated detection protocols, allowing parallel processing of multiple fusion possibilities simultaneously, thus reducing overall diagnostic time while maintaining high accuracy for each specific fusion type.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary identification of fusion break points and fusion partners before comprehensive diagnostic analysis. By pre-characterizing the fusion types and preparing specific detection reagents (antibodies, probes) in advance, the actual diagnostic process can proceed quickly without needing to develop detection methods during the diagnostic procedure.

Inventive Principle:
Principle #10Preliminary action

2Adaptability or versatility

If comprehensive screening for all NRG1 fusion partners is performed, then all possible fusions can be identified, but the complexity of detection methods increases

Engineering Contradiction:
Improvefusion partner coverageVSAvoiddetection method complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent develops universal detection approaches that can identify multiple fusion partners using the same basic methodology. The detection system uses common technical platforms (e.g., immunohistochemistry with specific antibodies, molecular probing) that can be applied across different fusion types, reducing the need for entirely separate complex methods for each fusion partner while maintaining comprehensive coverage.

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

Solution Approach 2:

The patent simplifies detection complexity by changing detectable parameters - using specific antibodies that recognize fusion-specific epitopes, or molecular probes targeting fusion junction regions. By focusing detection on specific molecular signatures (break points, fusion-specific sequences) rather than attempting to detect all possible fusion characteristics, the method achieves comprehensive partner identification with manageable detection complexity.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20250305053A1New NRG1 fusions, fusion junctions and methods for detecting them
Publication Date: 2025.10.02 MERUS NV

AI summary

The disclosure relates to the field of neuregulin-1 (NRG1) fusions, methods for detecting such, identifying or diagnosing patients with such fusions and methods of treatment of a cancer, a tumor or an aberrant cell comprising an NRG1 fusion. Also, it relates to the field of therapeutic (human) compounds for the treatment of subjects with an ErbB-2/ErbB-3 positive cancer that comprise a NRG1 fusion.