Continuous Biological Molecule Purification Without Pool Tanks

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Solution Overview

Problem

Conventional purification processes for biological molecules, such as therapeutic proteins, are labor-intensive, time-consuming, and require large holding tanks, leading to high costs and limited manufacturing flexibility.

Innovation Solution

A continuous or semi-continuous process that integrates multiple purification steps, including bind and elute chromatography and flow-through purification, eliminating the need for large pool tanks and reducing the number of steps, with the use of stimulus-responsive polymers and in-line static mixers for virus inactivation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional batch purification processes are used with multiple separate steps and holding tanks, then product purity can be maintained, but purification time and manufacturing costs increase significantly

Engineering Contradiction:
Improveproduct purityVSAvoidpurification time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent combines multiple separate batch purification steps into a single continuous process where clarification, chromatography, and polishing steps are integrated and performed simultaneously in a unified system, eliminating the need for sequential processing and intermediate holding tanks

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent implements continuous flow through the purification system where feedstock continuously enters the clarification step, flows through chromatography columns, and proceeds to polishing steps without batch interruptions, maintaining constant productive action throughout the process

Inventive Principle:
Principle #20Continuity of useful action

2Ease of operation

If large pool tanks are used to store intermediate products between process steps, then solution conditions can be adjusted, but physical footprint and manufacturing flexibility are reduced

Engineering Contradiction:
Improvesolution condition adjustmentVSAvoidphysical footprint
Core Design Contradiction:
Ease of operationVSArea of stationary object

Solution Approach 1:

The patent extracts and eliminates the large pool tanks from the process system, replacing them with in-line adjustment mechanisms that modify solution conditions directly within the continuous flow path, removing the need for intermediate storage vessels

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent transitions from spatial storage (pool tanks occupying physical space) to temporal control (in-line adjustment within the flow stream), changing the dimension in which solution condition management occurs from spatial to temporal

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

3Manufacturing precision

If multiple separate batch process steps are performed, then thorough purification can be achieved, but labor intensity and operational complexity increase

Engineering Contradiction:
Improvepurification effectivenessVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple discrete unit operations into an integrated continuous system where clarification, chromatography, and polishing functions are combined in a unified process train, reducing the number of separate equipment items and operational interfaces

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The continuous purification system performs multiple purification functions (clarification, chromatographic separation, polishing) within a single integrated process flow, making the system multi-functional and reducing overall process complexity

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

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 process significantly reduces purification time and costs while maintaining product yield, eliminating the need for large pool tanks and reducing the physical footprint, and achieving efficient impurity removal without sacrificing product purity.

Implementation Method 1

a purification step which employs an affinity ligand called Protein A, isolated from Staphylococcus aureus, and which binds the Fc-region of antibodies

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Implementation Method 2

one or more downstream chromatography steps to separate the protein of interest from various impurities in the clarified cell culture feed

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 3

a cell harvest step, which typically involves use of centrifugation to remove cell and cell debris from a cell culture broth

Methodology Applied
Scientific EffectCentrifugation: Centrifugal Separation

Implementation Method 4

followed by depth filtration

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentEP2867256B1Purification of biological molecules
Publication Date: 2025.09.10 EMD MILLIPORE CORP
  • EP2867256B1 patent drawingFigure 1
  • EP2867256B1 patent drawingFigure 2
  • EP2867256B1 patent drawingFigure 3

AI summary

The present invention relates to improved processes and systems for purification of biological molecules, where the processes can be performed in a continuous manner.