Cation Exchange Chromatography Media for Antibody Purification

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Solution Overview

Problem

Current cation exchange chromatography media are inadequate for efficiently separating antibody monomers from aggregates in antibody drug manufacturing processes, leading to impurities and reduced antigen recognition ability, with existing methods facing challenges in high adsorption capacity and high flow rate performance.

Innovation Solution

A cation exchange chromatography media is developed by polymerizing a monomer containing at least one sulfone group, bonded to porous particles, specifically using a copolymer of 2-acrylamide-2-methylpropanesulfonic acid with neutral or weak cation monomers, providing high antibody adsorptivity and efficient separation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional cation exchange chromatography media are used, then antibody aggregates can be eliminated, but the adsorption capacity is low and separation efficiency is insufficient

Engineering Contradiction:
Improveadsorption capacityVSAvoidseparation efficiency
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the chemical parameters of the chromatography media by incorporating specific sulfonic acid groups and controlling the crosslinking degree (5-20%) to optimize both adsorption capacity and separation efficiency for antibody purification

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite chromatography media by combining porous particles with specific polymer matrices containing sulfonic acid groups, achieving enhanced performance for separating antibody monomers from aggregates

Inventive Principle:
Principle #40Composite materials

2Productivity

If high adsorption capacity is achieved, then productivity increases, but the media may not maintain performance at high flow rates

Engineering Contradiction:
Improveadsorption capacityVSAvoidflow rate performance
Core Design Contradiction:
ProductivityVSSpeed

Solution Approach 1:

The patent utilizes porous particles as the base media with optimized pore structures that allow high adsorption capacity while maintaining excellent flow rate performance, enabling efficient antibody purification at high speeds

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent optimizes physical parameters including pore size, crosslinking degree, and particle density to achieve a balance between high adsorption capacity and high flow rate performance

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If protein A chromatography is used for initial purification, then antibody is captured efficiently, but antibody aggregates are not effectively separated

Engineering Contradiction:
Improveantibody capture efficiencyVSAvoidaggregate separation purity
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent employs a segmented purification approach where protein A chromatography performs initial antibody capture, followed by cation exchange chromatography with the specialized media for aggregate separation, dividing the purification process into functional stages

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a specialized cation exchange media as an intermediary step between protein A chromatography and final product formulation, enabling effective aggregate removal while preserving antibody activity

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

The media enables high-purity separation of antibody monomers from aggregates, achieving high dynamic binding capacity and efficient separation performance, suitable for antibody drug manufacturing processes.

Implementation Method 1

separation of an antibody monomer from aggregates thereof using a chromatography media having a mixed mode ligand... a separation method utilizing an electrostatic interaction in ion exchange chromatography

Methodology Applied
Scientific EffectElectrostatic interaction: Ion Repulsion/Attraction

Implementation Method 2

cation exchange chromatography media for purifying of an antibody... structure formed by bonding a base media containing porous particles with a copolymer composed of a strong cation monomer unit... ion exchange capacity

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Data Source

PatentEP2910943B1Cation exchange chromatography carrier for refining of antibodies and its use and method for separation of antibody monomers from aggregates thereof
Publication Date: 2021.11.10 JNC CORP
  • EP2910943B1 patent drawingFigure 1
  • EP2910943B1 patent drawingFigure 2
  • EP2910943B1 patent drawing

AI summary

To provide a cation exchange chromatography media that can be preferably used for purifying of an antibody drug, particularly, a cation exchange chromatography media having satisfactory performance of separation of an antibody monomer from a aggregates thereof to be produced in an antibody drug manufacturing process. The cation exchange chromatography media for purifying of the antibody comprises a base media involving porous particles and a polymer containing, in the range of 30 to 100 mol% based on the total monomer, at least one kind of strong cation exchange monomer unit represented by formula (1) or formula (2), and ion exchange capacity of the cation exchange chromatography media is from 60 to 300 µmol/mL: (wherein, R1, R2 and R3 are each independently a hydrogen atom or methyl, A1 and A2 are -R4-SO3M, here, R4 is alkylene having 2 to 4 carbons, and M is a hydrogen atom, Na or K.)