Blood-Based Mass Spectrometry Classifier for Immune Checkpoint Inhibitor Response Prediction

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Solution Overview

Problem

Current methods for predicting the effectiveness of immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA4 agents, in cancer patients are limited by the lack of standardized biomarkers and the invasive nature of tissue biopsies.

Innovation Solution

A method using mass spectrometry on blood-based samples to generate class labels predicting patient benefit from immune checkpoint inhibitors, by comparing integrated intensity values with a reference set of class-labeled mass spectral data.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If tissue biopsy methods are used to predict response to immune checkpoint inhibitors, then measurement precision of biomarkers is improved, but ease of operation deteriorates due to invasive procedures

Engineering Contradiction:

Improvebiomarker detection accuracyVSAvoidsample collection invasiveness

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses mass spectrometry as an intermediary technique to analyze blood-based samples instead of requiring direct tissue biopsy. The mass spectrometry system detects biomarkers in circulating blood components, serving as a mediator between the need for accurate biomarker measurement and the desire for non-invasive sampling.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical tissue biopsy procedure with a mass spectrometry-based analytical system. Instead of physically extracting and examining tissue samples through surgical means, the system uses mass spectrometry to detect biomarkers in blood samples, substituting a mechanical invasive procedure with an analytical chemical method.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If standardized biomarkers are implemented for predicting immune checkpoint inhibitor response, then reliability of prediction is improved, but device complexity increases due to required infrastructure

Engineering Contradiction:

Improveprediction consistencyVSAvoidmass spectrometry system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent develops a mass spectrometry-based platform that can analyze multiple different biomarkers and predict responses to various types of cancer treatments. The same analytical system serves multiple diagnostic functions, making the complex device applicable to broader clinical scenarios and justifying its complexity through multi-purpose utility.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Productivity

If expensive immune checkpoint inhibitor therapies are administered without prediction testing, then productivity of treatment delivery is improved, but loss of substance increases due to ineffective treatments

Engineering Contradiction:

Improvetreatment delivery efficiencyVSAvoidwaste of expensive medication

Core Design Contradiction:

ProductivityVSLoss of substance

Solution Approach 1:

The patent performs prediction testing before administering expensive immune checkpoint inhibitor therapies. By conducting mass spectrometry analysis of blood samples in advance, the system identifies which patients are likely to respond to treatment, allowing clinicians to pre-select appropriate candidates and avoid administering expensive medications to patients who would not benefit, thereby preventing waste.

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

This method allows for the non-invasive prediction of patient response to immune checkpoint inhibitors, guiding treatment decisions and potentially reducing healthcare costs by identifying likely beneficiaries of expensive therapies.

Implementation Method 1

conducting mass spectrometry on a blood-based sample of the patient

Methodology Applied

Scientific EffectMass spectrometry:

Data Source

PatentUS12230398B2Predictive test for patient benefit from antibody drug blocking ligand activation of the T-cell programmed cell death 1 (PD-1) checkpoint protein and classifier development methods

Publication Date: 2025.02.18 BIODESIX INC

AI summary

A method is disclosed of predicting cancer patient response to immune checkpoint inhibitors, e.g., an antibody drug blocking ligand activation of programmed cell death 1 (PD-1) or CTLA4. The method includes obtaining mass spectrometry data from a blood-based sample of the patient, obtaining integrated intensity values in the mass spectrometry data of a multitude of pre-determined mass-spectral features; and operating on the mass spectral data with a programmed computer implementing a classifier. The classifier compares the integrated intensity values with feature values of a training set of class-labeled mass spectral data obtained from a multitude of melanoma patients with a classification algorithm and generates a class label for the sample. A class label “early” or the equivalent predicts the patient is likely to obtain relatively less benefit from the antibody drug and the class label “late” or the equivalent indicates the patient is likely to obtain relatively greater benefit from the antibody drug.