Keratin 7 and 19 Heterotypic Complex Detection

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Solution Overview

Problem

Current tumor markers for malignant neoplastic diseases lack sensitivity and specificity, leading to false positives and inefficiencies in diagnosis and prognosis, particularly due to non-malignant disease interference.

Innovation Solution

A composition comprising antibodies or antigen-binding fragments that specifically bind to a heterotypic complex of keratin 7 and keratin 19, recognizing sequences within specific amino acid ranges, allowing for simultaneous and specific binding to improve diagnostic assays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If currently available tumor markers (such as TPA, TPS, CYFRA 21-1) are used for detecting malignant neoplastic disease, then the detection method is simple and cost effective, but the sensitivity and specificity are insufficient leading to false positive results

Engineering Contradiction:
Improvedetection accuracyVSAvoidmarker complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines multiple keratin markers (K7 and K19) into a single diagnostic composition that detects the heterotypic complex formed by these proteins. This merging approach maintains simplicity of use while improving detection accuracy by targeting a specific protein complex rather than individual markers alone, thereby resolving the contradiction between reliability and device complexity.

Inventive Principle:
Principle #5Merging (Combining)

2Measurement precision

If single keratin markers (TPA, TPS, CYFRA 21-1) are used as tumor markers, then the markers are easy to measure and widely accepted, but they lack organ specificity and show elevated levels in nonmalignant diseases

Engineering Contradiction:
Improvemarker specificityVSAvoidassay simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses the heterotypic complex of K7 and K19 as an intermediary target that provides higher specificity than individual markers. The complex acts as a more precise indicator of malignant transformation, reducing false positives from benign conditions while maintaining assay simplicity through a single composition that detects the complex rather than requiring separate tests for multiple markers.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If multiple antibodies targeting different keratin sequences are used simultaneously, then the binding specificity to heterotypic complex is improved, but the composition complexity increases

Engineering Contradiction:
Improvebinding specificityVSAvoidcomposition complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent creates a universal diagnostic composition containing multiple antibodies (anti-K7 and anti-K19) that work together to detect the heterotypic complex. This multi-functional composition maintains high binding specificity while presenting a unified, ready-to-use product that does not require separate preparation steps, thereby achieving reliability without proportionally increasing operational complexity.

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

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

Enhances the sensitivity and specificity of malignant neoplastic disease detection, reducing false positives and improving diagnostic accuracy for conditions like lung, bladder, and ovarian cancers.

Implementation Method 1

at least one first antibody, antigen-binding fragment, or combination thereof recognizes a sequence located within the 256-412 amino acid sequence, or more preferably within the 300-380 amino acid sequence in the keratin 7 moiety of the heterotypic complex of keratin 7 with keratin 19 and/or fragment(s) thereof, and at least one second antibody, antigen-binding fragment, or combination thereof recognizes a sequence located within the 244-400 amino acid sequence, or more preferably within the 311-375 amino acid sequence in the keratin 19 moiety of the heterotypic complex of keratin 7 with keratin 19

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP3102600B1Composition and method for detecting malignant neoplastic disease
Publication Date: 2019.01.16 FUJIREBIO DIAGNOSTICS AB
  • EP3102600B1 patent drawingFigure 1
  • EP3102600B1 patent drawingFigure 2
  • EP3102600B1 patent drawingFigure 3

AI summary

The present invention provides a composition comprising at least two targeting agents, wherein at least one first targeting agent recognizes a keratin 7 peptide and/or fragment(s) thereof, and at least one second targeting agent recognizes a keratin 19 peptide and/or fragment(s) thereof. Said first and second targeting agents are capable of binding specifically and simultaneously to a heterotypic complex of keratin 7 with keratin 19, and/or fragment(s) thereof. The composition of the invention may be used in methods for diagnosing and/or prognosing, predicting efficacy of treatment, assessing outcome of treatment of assessing recurrence of malignant neoplastic disease, such as e.g. lung cancer, bladder cancer, esophagus cancer, and ovarian cancer in a subject.