Replaceable Chromatography Columns for Antibody Purification

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Solution Overview

Problem

Current biopharmaceutical production methods face challenges in efficiently and cost-effectively separating antibodies from large volumes of culture solutions using affinity chromatography, leading to variations in purification quality and increased processing time due to the need for repeated use and potential degradation of expensive Protein A columns.

Innovation Solution

A separation method employing a system of replaceable, multi-column chromatography devices with a control system that allows continuous processing and efficient resource use, where the stationary phase is replaced after each batch, ensuring consistent accuracy and reducing costs by optimizing column usage and minimizing downtime.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If a large volume stationary phase is used to process the entire volume of mobile phase in one batch, then separation accuracy is maintained constant, but the device size and cost increase

Engineering Contradiction:
Improveseparation accuracyVSAvoidstationary phase volume
Core Design Contradiction:
Manufacturing precisionVSVolume of stationary object

Solution Approach 1:

The patent divides the large-volume stationary phase into multiple smaller columns (first column and second column). Each column contains a portion of the total stationary phase volume, allowing the system to process large mobile phase volumes while keeping individual column sizes manageable and reducing overall device footprint.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent switches between different columns (dimensions) to maintain separation accuracy. By alternating between the first and second columns for different batches, the system achieves consistent separation performance without requiring a single excessively large column, thus managing the volume constraint.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Manufacturing precision

If the separation column is replaced after each batch, then separation accuracy remains constant, but processing time and device complexity increase

Engineering Contradiction:
Improveseparation accuracyVSAvoidprocessing time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent prepares multiple columns (first and second columns) in advance, each with fresh stationary phase. When one column is being used for separation, another is ready to take over, allowing for seamless batch transitions without lengthy replacement procedures, thus reducing processing time while maintaining accuracy.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system maintains continuous operational capability by having multiple columns available. While one column undergoes replacement or regeneration, another column continues processing, ensuring that the separation process does not experience interruptions that would increase overall processing time.

Inventive Principle:
Principle #20Continuity of useful action

3Volume of stationary object

If multiple columns are used to reduce stationary phase volume per column, then device space is reduced, but system complexity and control requirements increase

Engineering Contradiction:
Improvestationary phase volumeVSAvoidsystem complexity
Core Design Contradiction:
Volume of stationary objectVSDevice complexity

Solution Approach 1:

The first and second columns are designed with identical structures and functions, each capable of performing the complete separation process. This universality simplifies the control system, as the same operating procedures apply to both columns, reducing the complexity that would arise from managing dissimilar components.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent implements a periodic switching pattern between the first and second columns. Columns are alternated in a regular sequence (first column for batch 1, second column for batch 2, and so on), which simplifies control logic compared to irregular or complex switching patterns, thereby managing system complexity while achieving volume reduction.

Inventive Principle:
Principle #19Periodic action

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 constant accuracy and efficient resource utilization in antibody separation, reducing processing time and variation in purification quality by replacing the separation column after each batch, thereby addressing the limitations of existing methods.

Implementation Method 1

a separation method for separating a material to be separated from a mobile phase by passing the mobile phase containing the material to be separated through a stationary phase

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

in the capture step, affinity chromatography is usually used. When the antibody of interest is IgG, very high specific affinity chromatography using Protein A or Protein G as a ligand is used

Methodology Applied
Scientific EffectAffinity chromatography: Adsorption

Data Source

PatentEP3018475B1Separation method
Publication Date: 2022.06.22 HITACHI PLANT SERVICES
  • EP3018475B1 patent drawingFigure 1
  • EP3018475B1 patent drawingFigure 2
  • EP3018475B1 patent drawingFigure 3

AI summary

An object of the present invention is to separate a material to be separated at a low cost and constant accuracy when the material to be separated is separated from a mobile phase containing the material to be separated through the passing of the mobile phase through a stationary phase, even if the mobile phase has a large volume. A separation device characterized in that a separation column provided with a stationary phase having a volume capable of processing the entire volume of a mobile phase containing a material to be separated is provided, the separation column is replaceable, and the usage count of the stationary phase reaches a lifetime count through the processing of one batch.