Chromatography Beads with Thin Outer Layer for Virus Removal
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Solution Overview
Problem
Current methods for virus removal during monoclonal antibody purification are inadequate, requiring improved technologies to effectively capture and remove viruses from immunoglobulin-containing samples while maintaining high binding capacity and selectivity.
Innovation Solution
The use of chromatography beads with a thin, inactive outer layer and a core functionalized with affinity ligands, such as Protein A or Protein L, which allows for the selective adsorption of monoclonal antibodies while preventing virus penetration, thereby achieving efficient virus removal and purification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional virus removal filters with defined cut-off are used, then virus removal is achieved, but binding capacity and selectivity for monoclonal antibodies are compromised
Solution Approach 1:
The chromatography bead is segmented into two distinct functional zones: an outer inactive layer with defined pore size for virus exclusion, and an inner core functionalized with affinity ligands (Protein A or Protein L) for selective mAb binding. This segmentation allows simultaneous virus removal and maintained binding capacity without compromise.
2Quantity of substance
If chromatography beads with affinity ligands are used for mAb purification, then binding capacity is improved, but virus penetration and contamination risk increase
Solution Approach 1:
The inactive outer layer acts as an intermediary barrier between the virus-containing feed and the affinity ligands in the core. This layer has defined pore size that physically blocks virus penetration while allowing mAbs to reach the ligands through diffusion, thus protecting against virus contamination while maintaining binding capacity.
3Quantity of substance
If chromatography beads with thin outer layer are used, then binding capacity is maintained, but virus exclusion capability is reduced
Solution Approach 1:
The inactive outer layer is designed as a thin film with controlled thickness (1-10 μm) that balances two opposing requirements: thin enough to allow rapid mAb diffusion and maintain high binding capacity, yet with defined pore size structure that provides reliable physical exclusion of viruses. The film's porosity and thickness are optimized to achieve both goals simultaneously.
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 method provides enhanced virus reduction capabilities compared to prior art methods, simplifying downstream processing and ensuring the production of virus-free therapeutic antibodies, as demonstrated by improved log reduction and yield in experimental trials.
Implementation Method 1
an inner core of defined pore size provided with an affinity ligand; adsorbing the immunoglobulin containing proteins to the ligands
Implementation Method 2
a thin lid with a defined pore size and an inner core of defined pore size provided with an affinity ligand
Data Source
AI summary
The present invention relates to a method for removal of large contaminants, such as virus, in a chromatographic process for purification of a target molecule, preferably monoclonal antibodies, mAbs, by using a specifically designed chromatographic bead having a thin outer layer and a core functionalized with a ligand adsorbing the mAbs or parts thereof.