pH-Responsive Polymers for Biomolecule Purification

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Solution Overview

Problem

Current purification methods for biomolecules, such as therapeutic proteins, are complex, expensive, and face challenges with residual polymer contamination and inefficient flocculation, particularly when using polyelectrolytes, which can foul chromatography media and complicate downstream processes.

Innovation Solution

Development of stimulus-responsive polymers with a polyelectrolyte backbone modified with hydrophobic groups, capable of binding and precipitating biomolecules under specific conditions, allowing for scalable and efficient purification of therapeutic proteins by forming complexes that can be easily separated from impurities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If polyelectrolytes are used for flocculation to purify proteins, then purification can be achieved via selective flocculation, but residual polymer contamination occurs and can foul chromatography media

Engineering Contradiction:
Improvepurification efficiencyVSAvoidresidual polymer contamination
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent employs pH-responsive polymers that change their conformation and binding properties in response to pH changes. During purification, the pH is adjusted to induce polymer precipitation, thereby removing residual polymer contamination while maintaining purification efficiency. This parameter change allows the system to achieve both high productivity and low contamination.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces a pH-responsive polymer as an intermediary agent that facilitates selective flocculation of impurities. The polymer acts as a mediator between the target protein and the purification process, enabling efficient separation while its subsequent pH-induced precipitation removes it from the final product, thus preventing contamination and media fouling.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If stimulus-responsive polymers are used to bind and precipitate biomolecules, then purification efficiency is improved, but process complexity increases

Engineering Contradiction:
Improvepurification efficiencyVSAvoidprocess complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent utilizes pH-responsive polymers that undergo conformational changes and precipitation in response to pH adjustments. This simple parameter change (pH adjustment) triggers the purification process and subsequent polymer removal, achieving high purification efficiency without requiring complex equipment or multi-step procedures. The entire process can be controlled by adjusting a single parameter - pH.

Inventive Principle:
Principle #35Parameter changes

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 stimulus-responsive polymers effectively increase the purity of target biomolecules by selectively binding and precipitating either the target molecule or impurities, reducing residual polymer contamination and simplifying the purification process, thereby improving the efficiency and cost-effectiveness of biomolecule purification.

Implementation Method 1

the use of polymers containing ion species, such as polyelectrolytes. Generally, polyelectrolytes are added to the protein mixture and purification is achieved via selective flocculation of one or more components of the mixture

Methodology Applied
Scientific EffectFlocculation: Flocculation

Implementation Method 2

stimulus-responsive or 'Smart' polymers have been developed which can bind to both soluble (e.g., host cell proteins, DNA, cell culture additives) as well as insoluble (e.g., cells and cellular debris) components

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Data Source

PatentEP3597671B1Stimulus responsive polymers for the purification of biomolecules
Publication Date: 2022.09.21 EMD MILLIPORE CORP
  • EP3597671B1 patent drawingFigure 1
  • EP3597671B1 patent drawingFigure 2
  • EP3597671B1 patent drawingFigure 3

AI summary

The present invention provides novel and improved stimulus responsive polymers and methods of using the same for the purification of biomolecules.