Monoclonal Antibody for pY1235-MET Detection Specificity

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Solution Overview

Problem

Current methods for assessing MET activation and signaling, particularly phosphorylation at Y1235, are hindered by the lack of specific binding reagents that do not cross-react with other phosphorylation sites, making it difficult to detect and quantify effectively.

Innovation Solution

Development of a monoclonal antibody specifically binding to pY1235-MET, with defined complementary determining regions (CDRs) in its variable regions, allowing for precise detection and measurement of pY1235-MET in samples, along with methods for producing and using this antibody for immunological assays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing binding reagents are used to detect MET phosphorylation, then detection capability is provided, but cross-reactivity with other phosphorylation sites occurs reducing measurement precision

Engineering Contradiction:
Improvedetection precision of pY1235-METVSAvoidspecificity of binding reagent
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies local quality by designing the antibody to recognize a specific local epitope (phosphorylated tyrosine at position 1235) rather than the entire MET protein. The CDRs are engineered to target the precise phosphorylation site, allowing the antibody to distinguish pY1235-MET from other phosphorylated forms of MET or similar proteins, thereby achieving high measurement precision through localized recognition.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If existing binding reagents are used, then general detection is possible, but specific detection of pY1235-MET without cross-reactivity cannot be achieved

Engineering Contradiction:
Improvespecificity for pY1235-METVSAvoiddifficulty in detecting pY1235-MET
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies parameter changes by modifying the binding characteristics of the antibody through specific CDR sequences that are tuned to recognize the phosphorylated tyrosine at position 1235. The antibody was raised against a phosphorylated peptide antigen, which changed the binding parameters to specifically recognize the phosphoepitope, enabling specific detection of pY1235-MET without cross-reactivity to other phosphorylation sites.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If non-specific binding reagents are used, then detection of MET can be performed, but accurate quantification of pY1235-MET phosphorylation is hindered

Engineering Contradiction:
Improvequantification accuracy of pY1235-METVSAvoidreliability of MET activation assessment
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies the intermediary principle by using a highly specific antibody as a mediator between the pY1235-MET target and the detection system. The antibody serves as a selective intermediary that binds only to the phosphorylated form at position 1235, allowing accurate quantification and reliable assessment of MET activation without interference from other phosphorylated forms or similar proteins.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Enables accurate detection and quantification of pY1235-MET, facilitating the assessment of MET activation and the evaluation of MET inhibitors, guiding clinical development and treatment decisions.

Implementation Method 1

an antibody that specifically binds to pY1235-MET

Methodology Applied
Scientific EffectImmunological binding:

Data Source

PatentUS11340219B2Anti-pY1235-MET immunological binding reagent
Publication Date: 2022.05.24 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES
  • US11340219B2 patent drawing
  • US11340219B2 patent drawing
  • US11340219B2 patent drawing

AI summary

Methods and compositions are described herein for assaying the presence or absence of pY1235-MET or a fragment thereof.