Charge-Neutral Filter for Biologic Purification

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Solution Overview

Problem

Current bioprocessing methods for purifying biologic agents, such as plasmid DNA, face challenges in achieving high yield and purity due to contaminants like residual RNA, genomic DNA, endotoxins, and proteins, which bind to chromatography resins and reduce the efficiency of the purification process.

Innovation Solution

The method involves using a charge-neutral organic polymer filter in the presence of a kosmotropic agent to selectively remove contaminants. The filter binds to contaminants that exhibit increased hydrophobicity in the presence of the kosmotropic agent, while the biologic agent does not bind, allowing it to pass through and be purified further in subsequent chromatography steps.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If hydrophobic interaction chromatography is used to remove contaminants, then purity of biologic agent is improved, but binding capacity of chromatography column is reduced due to contaminant competition

Engineering Contradiction:

Improvepurity of biologic agentVSAvoidbinding capacity of chromatography column

Core Design Contradiction:

Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent applies preliminary filtration to remove contaminants before the chromatography step. By filtering the biologic agent solution through a filter in the presence of kosmotropic agents before applying to the chromatography column, contaminants are removed in advance, preventing them from competing for binding sites during chromatography. This preliminary action preserves the binding capacity of the chromatography column while still achieving high purity in the final product.

Inventive Principle:

Principle #10Preliminary action

2Manufacturing precision

If multiple filtration and chromatographic steps are used, then purity of biologic agent is improved, but process complexity increases

Engineering Contradiction:

Improvepurity of biologic agentVSAvoidprocess complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent merges the filtration step with the chromatography preparation by performing filtration in the presence of kosmotropic agents that are also used in the subsequent chromatography step. This integration allows the use of the same buffer system for both filtration and chromatography, reducing the number of separate process steps and simplifying the overall workflow while maintaining high purity.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The kosmotropic agents serve multiple functions: they enhance contaminant binding to the filter during filtration, and they are also the elution agents used in the subsequent hydrophobic interaction chromatography step. This multi-functionality reduces the need for separate buffer preparation and exchange steps, thereby simplifying the overall purification process.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Manufacturing precision

If kosmotropic agents are used in hydrophobic interaction chromatography, then removal of hydrophobic contaminants is improved, but precipitation of biologic molecules occurs leading to column fouling

Engineering Contradiction:

Improveremoval of hydrophobic contaminantsVSAvoidprecipitation and fouling of biologic molecules

Core Design Contradiction:

Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent performs preliminary filtration in the presence of kosmotropic agents to remove hydrophobic contaminants before applying the solution to the chromatography column. By removing contaminants in advance, the subsequent chromatography step operates on a cleaner solution, reducing the risk of precipitate formation and column fouling while maintaining effective contaminant removal capability.

Inventive Principle:

Principle #10Preliminary 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 effectively increases the yield and purity of biologic agents by removing contaminants before chromatography, thereby enhancing the recovery of the target product, reducing the size of chromatography columns required, and preventing column fouling.

Implementation Method 1

The filter binds to contaminants that exhibit increased hydrophobicity in the presence of the kosmotropic agent

Methodology Applied

Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 2

contaminants that bind to the charge-neutral organic polymer filter in the presence of said at least one kosmotropic agent

Methodology Applied

Scientific EffectKosmotropic effect:

Data Source

PatentUS20250179116A1Methods for the selective removal of contaminants during a process of purifying biologic agents

Publication Date: 2025.06.05 SARTORIUS BIA SEPARATIONS D O O

AI summary

The present invention relates to methods for the selective removal of contaminants during a process of purifying a biologic agent, comprising a step of subjecting a solution containing (i) said biologic agent and (ii) potential contaminants to a filtration step using a charge-neutral organic polymer filter in the presence of a kosmotropic agent, wherein said one or more contaminants are contaminants that bind to the charge-neutral organic polymer filter in the presence of said at least one kosmotropic agent, while the biologic agent does not bind to the charge-neutral organic polymer filter in the presence of said at least one kosmotropic agent. These methods combine a dual use of the filter for chemical and mechanical removal of contaminants in a single step. The present invention further relates to respective methods for the purification of a biologic agent, as well as respective uses of a charge-neutral organic polymer filter.