Velocity Factor Antibody Classification via SPR Kinetics

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Solution Overview

Problem

Current methods for thermodynamic analysis of protein-protein interactions, such as calorimetric assays, require high sample amounts, pure samples, and are limited to equilibrium thermodynamics, while Surface Plasmon Resonance (SPR) instruments can determine kinetic profiles but not entropic or enthalpic binding properties efficiently.

Innovation Solution

A method using the velocity factor, calculated as the ratio of antigen-antibody association rate constants at 37° C. and 13° C., to classify antibodies as entropic or enthalpic binders, allowing for high-throughput selection of antibodies with specific binding properties using surface plasmon resonance and thermodynamic equilibrium data.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If calorimetric assays are used for thermodynamic analysis, then detailed thermodynamic parameters can be determined, but high sample amounts and high sample purity are required

Engineering Contradiction:

Improvethermodynamic parameter determinationVSAvoidsample amount

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent replaces calorimetric measurement (thermal energy measurement) with Surface Plasmon Resonance (optical phenomenon measurement). SPR detects changes in refractive index near the sensor surface when molecules bind, substituting thermal measurement with optical measurement, thereby eliminating the need for high sample amounts and purity requirements associated with calorimetry

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the measurement parameter from thermal energy (calorimetry) to optical properties (SPR resonance). By measuring association rate constants at different temperatures using SPR and calculating the velocity factor, the method achieves thermodynamic analysis with much lower sample requirements while maintaining measurement precision

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If calorimetric assays are used for thermodynamic analysis, then detailed thermodynamic parameters can be determined, but the method is solely able to resolve equilibrium thermodynamics

Engineering Contradiction:

Improvethermodynamic parameter determinationVSAvoidthermodynamic analysis scope

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent makes the SPR instrument perform multiple functions: it can determine both kinetic parameters (association and dissociation rate constants) and thermodynamic parameters (enthalpy, entropy, Gibbs free energy) through temperature-dependent measurements. This multi-functionality allows comprehensive analysis of both equilibrium and non-equilibrium thermodynamics, overcoming the limitation of calorimetry which is restricted to equilibrium measurements

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Productivity

If Surface Plasmon Resonance is used for kinetic profile determination, then high-throughput kinetic data can be obtained, but entropic or enthalpic binding properties cannot be determined efficiently

Engineering Contradiction:

Improvekinetic profile determination throughputVSAvoidentropic or enthalpic binding properties

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary temperature-dependent kinetic measurements to obtain association rate constants at multiple temperatures. These preliminary kinetic data are then used to calculate the velocity factor, which serves as a proxy for detailed thermodynamic analysis. This preliminary action enables high-throughput screening while still providing access to entropic and enthalpic binding properties through the velocity factor classification

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent introduces the velocity factor as an intermediary parameter that bridges kinetic measurements and thermodynamic properties. Instead of directly measuring enthalpy and entropy through complex calorimetric experiments, the velocity factor (ratio of association rate constants at different temperatures) serves as a mediator that provides thermodynamic classification with much higher throughput

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 the selection of high-affinity antibodies with temperature-dependent kinetic profiles, reducing the need for detailed thermodynamic calculations and allowing for the use of crude samples, thereby improving the efficiency and throughput of antibody development.

Implementation Method 1

Surface Plasmon Resonance (SPR) instrumentation allows the rapid determination of temperature-dependent kinetic profiles

Methodology Applied

Scientific EffectSurface plasmon resonance:

Data Source

PatentUS10877030B2Velocity factor

Publication Date: 2020.12.29 F HOFFMANN LA ROCHE INC

AI summary

The current invention is directed to the velocity factor. Based on the velocity factor antibodies can be classified, i.e. antibodies can be characterized on their binding properties as e.g. entropic or enthalpic antigen binder. A velocity factor based classification does not require detailed thermodynamic determinations and/or calculations. The velocity factor is the ratio of the antigen-antibody complex association rate constants ka determined at 37° C. and 13° C. As only two experimental determinations are required to calculate the velocity factor this is a fast and high-throughput suited method.