Antibody Separation Matrix with High Ligand Density
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Solution Overview
Problem
Current separation matrices for monoclonal antibodies in affinity chromatography processes are limited in productivity, as they are designed for conventional batch chromatography, preventing the full potential of continuous chromatography processes like PCC/SMB from being reached.
Innovation Solution
A separation matrix with high-density, spherical particles covalently immobilized with antibody-binding protein ligands, such as Protein A variants, on a crosslinked polysaccharide substrate, providing high binding capacity and rapid mass transport, along with a multicolumn chromatography system for continuous separation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional separation matrices designed for batch chromatography are used in continuous chromatography processes, then the process setup is simple, but the productivity is limited and cannot reach full potential
Solution Approach 1:
The patent applies parameter changes by modifying the physical and chemical parameters of the separation matrix. Specifically, it uses particles with optimized size distribution (volume-weighted median diameter 30-55 μm), high ligand density (>10 mg/ml), and controlled porosity to enable rapid mass transport and high binding capacity suitable for continuous chromatography processes
Solution Approach 2:
The patent employs composite materials by combining crosslinked polysaccharide particles with covalently immobilized antibody-binding protein ligands (such as Protein A or variants). This composite structure provides both the mechanical stability needed for continuous processing and the high binding capacity required for productivity enhancement
2Productivity
If residence time is reduced to increase productivity in continuous chromatography, then the throughput increases, but the binding capacity may be compromised
Solution Approach 1:
The patent utilizes porous materials with optimized porosity and pore size distribution to enable rapid mass transport of antibodies into and out of the particle interior. This allows high binding capacity to be achieved even at very short residence times, as the porous structure facilitates quick equilibration between mobile and stationary phases
Solution Approach 2:
The patent applies preliminary action by pre-optimizing the matrix properties (particle size, porosity, ligand density) before the actual separation process. This pre-preparation ensures that when the continuous chromatography process runs at high throughput with short residence times, the matrix is already configured to maximize binding capacity under these rapid flow conditions
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
Enables high productivity with very short residence times and high binding capacity, allowing for efficient continuous separation of monoclonal antibodies.
Implementation Method 1
affinity chromatography on matrices comprising coupled Staphylococcus Protein A (SpA) or variants of SpA
Implementation Method 2
porous, suitably spherical, particles to which antibody-binding protein ligands have been covalently immobilized
Data Source
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AI summary
The invention discloses a separation matrix comprised of porous spherical particles to which antibody-binding protein ligands have been covalently immobilized, wherein the density of said ligands is in the range of 10.5 - 15 mg/ml and the volume-weighted median diameter of said particles is in the range of 30 - 55 µm. The invention further discloses a method of separation of antibodies by affinity chromatography which employs the said separation matrix within a chromatography column.