IL-17 Functional Activity Assay via Intermediary Cells
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Solution Overview
Problem
Current methods for treating rheumatoid arthritis are hindered by variability in patient response to IL-17 inhibitors, as circulating IL-17 levels are low and do not accurately reflect the functional contribution of IL-17 in the inflammatory process, lacking a reliable marker for determining the effectiveness of IL-17 inhibitors and predicting patient response.
Innovation Solution
A process to determine the functional IL-17 pro-inflammatory dependent level (IPDL) in biological samples by measuring inflammatory markers produced by IL-17-sensitive cells, both with and without anti-IL-17 antibodies, allowing for the assessment of IL-17's bioavailability and activity in complex samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If circulating IL-17 levels are measured by ELISA in plasma, then the concentration of IL-17 can be quantified, but the measurement does not reflect the functional significance of IL-17 in the inflammatory phenomenon
Solution Approach 1:
The patent introduces an intermediary assay system consisting of IL-17-sensitive target cells (such as synovial cells or endothelial cells) that mediate the detection process. These cells are incubated with the patient's plasma sample, and their response (inflammatory marker production) serves as an indirect measure of functional IL-17 activity, bridging the gap between simple concentration measurement and functional assessment
Solution Approach 2:
The patent replaces the direct biochemical detection mechanism (ELISA) with a cellular response-based mechanism. Instead of directly detecting IL-17 protein concentration through antibody-antigen binding, the system uses living cells to transduce the biological signal, measuring the functional outcome (inflammatory marker secretion) rather than the molecular presence alone
2Productivity
If IL-17 inhibitors are administered to patients, then treatment can be provided, but patient response varies significantly with up to 30% showing no response
Solution Approach 1:
The patent implements preliminary action by performing the functional IL-17 activity assay on patient plasma samples before administering IL-17 inhibitor treatment. This pre-treatment assessment identifies patients with high functional IL-17 activity who are likely to respond to therapy, enabling selective treatment assignment and avoiding ineffective treatments for non-responders
Solution Approach 2:
The patent establishes a feedback mechanism where the functional IL-17 activity level measured in patient plasma provides information that feeds back into treatment decision-making. This feedback loop allows clinicians to adjust treatment strategies based on individual patient functional status, improving overall treatment effectiveness and reducing wasteful prescribing
3Measurement precision
If in vitro assays using synovial tissues are performed to determine functional IL-17, then functional activity can be assessed, but the process does not resemble determination in complex biological samples from patients
Solution Approach 1:
The patent achieves universality by developing an assay system that functions across multiple sample types and clinical contexts. The same basic protocol (incubating IL-17-sensitive target cells with plasma sample and measuring inflammatory marker production) can be applied to various patient populations and sample types, making the method broadly applicable in clinical settings while maintaining functional assessment accuracy
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 approach enables better prediction of patient response to IL-17 inhibitor treatments, evaluation of treatment efficacy, and identification of patients at risk for cardiovascular events and bone destruction, providing a novel marker independent of circulating IL-17 levels.
Implementation Method 1
measuring the level of said inflammatory marker produced by said cells incubated in the presence of this same biological sample, in the presence of antibodies which neutralize the biological activity of IL-17
Implementation Method 2
IL-17A induces the production of numerous cytokines and chemokines, such as IL-6, G-CSF, IL-1β and IL-8
Data Source
AI summary
The invention relates to an in vitro process for determining the functional IL-17 pro-inflammatory dependent level (IPDL) of a biological sample, comprising the following steps:a) measuring the level of an inflammatory marker produced by IL-17-sensitive cells incubated in the presence of a biological sample,b) measuring the level of said inflammatory marker produced by said cells incubated in the presence of a biological sample, in the presence of antibodies which neutralize the biological activity of IL-17, andc) determining the IPDL level, which is the difference between the level of said inflammatory marker measured in step a) and the level of said inflammatory marker measured in step b).