Hydrophilic Polymer-Coated Sorbents for Native ADC DAR Separation
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Solution Overview
Problem
Current chromatography columns do not provide sufficient resolution of Antibody-Drug Conjugate (ADC) component species, which is crucial for improving product quality, efficacy, and safety in ADCs.
Innovation Solution
A chromatographic stationary phase with a polymer coating comprising a copolymer of hydrophilic monomers, such as 2-Hydroxyethyl methacrylate and Methyl methacrylate, covalently attached to a solid support, allowing for improved separation and resolution of ADCs under mass spectrometry-compatible conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current chromatography columns are used for ADC analysis, then the analysis can be performed, but the resolution of ADC component species is insufficient
Solution Approach 1:
The patent changes the chemical composition parameters of the stationary phase by incorporating specific hydrophilic monomers (2-hydroxyethyl methacrylate, N-acryloyl morpholine) in defined ratios with crosslinking agents. This parameter optimization enables baseline resolution of ADC species with DAR values of 0-8, directly improving measurement precision for product quality assessment
Solution Approach 2:
The stationary phase uses a composite polymer coating formed by copolymerization of multiple monomers including hydrophilic monomers, crosslinking agents, and functional monomers. This composite material structure provides both the necessary resolution for ADC separation and the stability required for reliable product quality assessment
2Measurement precision
If denaturing conditions are used for ADC separation, then separation can be achieved, but the antibody structure is altered and direct MS coupling is prevented
Solution Approach 1:
The patent creates a non-denaturing inert environment in the stationary phase through the use of hydrophilic monomers and controlled crosslinking that maintains antibody native structure. This allows ADCs to be separated based on DAR values while remaining intact for direct coupling to mass spectrometry, preserving both separation resolution and MS compatibility
Solution Approach 2:
The stationary phase parameters are optimized to maintain physiological conditions (pH, ionic strength) that preserve antibody native conformation. The copolymer composition and crosslinking density are specifically tuned to provide separation without denaturation, enabling direct MS coupling for enhanced data quality
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
The solution enables retention of native antibody and baseline resolution of ADCs with varying Drug-to-Antibody Ratios (DARs) without denaturation, facilitating direct coupling to MS for online operations and enhancing data quality.
Implementation Method 1
chromatography compositions and methods for separation of biomolecules, in particular, stationary phases and chromatography columns for improved separation and resolution of ADCs
Data Source
AI summary
The present disclosure provides chromatography compositions and methods for separation of biomolecules, in particular, stationary phases and chromatography columns for improved separation and resolution of DAR species in antibody drug conjugates (ADCs). In one example, a method comprises: (a) exposing the sample to a chromatographic stationary phase of a reverse phase chromatography column, and (b) applying an eluent to the chromatography column to elute the DAR species of antibody-drug conjugate in their native state, wherein the chromatographic stationary phase comprises: a solid support; and a polymer coating on a surface of the solid support; wherein the polymer coating comprises a copolymer comprising a first hydrophilic monomer and a second hydrophilic monomer, wherein the first hydrophilic monomer and second hydrophilic monomer have different hydrophilicity, wherein the copolymer has a tuned hydrophilicity determined by a molar ratio of the first hydrophilic monomer to the second hydrophilic monomer.