Affinity Chromatography-Native MS for Fast Antibody Impurity Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods are inadequate for rapidly and sensitively analyzing therapeutic peptides or proteins to detect post-translational modifications, impurities, and drug-to-antibody ratios in biopharmaceutical products, which affect safety, efficacy, and shelf-life.
Innovation Solution
Affinity-based chromatography-coupled native mass spectrometry methods and systems for high-throughput analysis, utilizing affinity-binding molecules like protein A or FcγRIIIa, to characterize peptides or proteins under native conditions, enabling rapid identification and quantification of modifications and impurities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional analytical methods are used for characterizing therapeutic peptides or proteins, then the analysis can be conducted with standard equipment, but the analysis time is long and the sensitivity is insufficient to detect post-translational modifications and impurities
Solution Approach 1:
The patent combines affinity-based chromatography with native mass spectrometry into a coupled system, where the chromatography column is directly connected to the mass spectrometer. This integration allows simultaneous separation and high-sensitivity detection, achieving both rapid analysis and high detection sensitivity for post-translational modifications and impurities without requiring separate analysis steps.
Solution Approach 2:
The patent employs native mass spectrometry conditions that maintain physiological pH and temperature, enabling detection of intact proteins and their modifications with high sensitivity. The mass spectrometer operates in native mode to preserve protein structure while achieving rapid analysis, resolving the contradiction between detection sensitivity and analysis time.
2Reliability
If extensive characterization is performed to ensure product quality, then safety and efficacy are preserved, but the characterization process is time-consuming and reduces productivity
Solution Approach 1:
The coupled chromatography-mass spectrometry system enables continuous analysis without intermediate steps. The chromatography separation flows directly into the mass spectrometer for detection, creating a continuous workflow that maintains product quality through extensive characterization while significantly reducing analysis time and increasing manufacturing throughput.
Solution Approach 2:
The patent replaces traditional mechanical separation and detection methods with a coupled system where mass spectrometry provides rapid, sensitive detection. This substitution enables comprehensive quality characterization to be performed much faster, resolving the contradiction between ensuring product quality and maintaining manufacturing productivity.
3Productivity
If high-throughput analytical methods are developed to improve manufacturing process monitoring, then productivity increases, but the device complexity and method sophistication increase
Solution Approach 1:
The coupled chromatography-mass spectrometry system serves multiple functions simultaneously: separation, detection, and characterization of therapeutic proteins and their modifications. This multi-functional integration achieves high-throughput analysis while consolidating what would otherwise require multiple separate instruments and methods, managing system complexity through functional integration.
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
Provides rapid, sensitive, and high-throughput analysis of peptides or proteins, allowing for effective monitoring and control of biopharmaceutical production and purification processes, including characterization of drug-to-antibody ratios and post-translational modifications.
Implementation Method 1
contacting the sample to a solid surface, wherein the solid surface comprises an affinity-binding molecule of the at least one peptide or protein
Implementation Method 2
characterizing the at least one peptide or protein in the at least one eluent under native conditions using a mass spectrometer
Implementation Method 3
washing the solid surface using a mobile phase to produce at least one eluent, wherein the eluent comprises the at least one peptide or protein
Data Source
AI summary
The present invention provides rapid, sensitive high-throughput methods and systems for characterizing peptides or proteins using affinity-based chromatography-coupled native mass spectrometry to improve manufacturing process of biopharmaceutical products, such as identifying impurities during antibody purification, monitoring post-translational modification variants during production, or characterizing drug-to-antibody ratio of antibody-drug conjugates. The separation profiles of the peptides or proteins are generated and compared to identify or qualify the peptides or proteins, wherein the separation profile is based on differential affinity binding.