Formyl Group Porous Matrix for Antibody Purification
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Solution Overview
Problem
Current adsorbents for antibody purification, such as sugar chain cleavage-type and spacer-type porous base matrices, face issues with strength, ligand leakage, and efficiency, particularly at high linear speeds and alkaline conditions, leading to complications in antibody drug purification.
Innovation Solution
A formyl group-containing porous base matrix is developed using a spacer with a specific moiety derived from a 5- or 6-membered ring structure, which is introduced through periodate oxidation, providing high strength and minimizing ligand leakage, and is used in conjunction with a cellulose base matrix to enhance adsorption and purification efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If sugar chain cleavage-type porous base matrix is used, then ligand leakage is reduced, but mechanical strength is poor and cannot withstand high linear speeds
Solution Approach 1:
The patent uses a composite structure combining a porous base matrix with a spacer arm that contains a 5- or 6-membered ring. This composite approach allows the base matrix to provide mechanical strength while the spacer arm with formyl group enables stable ligand immobilization, resolving the contradiction between strength and ligand leakage reduction.
Solution Approach 2:
The spacer arm acts as an intermediary between the base matrix and the affinity ligand. It provides a stable formyl group for ligand immobilization while maintaining mechanical integrity, thus mediating between the requirements for low ligand leakage and high mechanical strength.
2Quantity of substance
If spacer-type porous base matrix with formyl group is used, then adsorption capacity is high, but ligand leakage occurs when formyl group introduction is insufficient
Solution Approach 1:
The patent introduces formyl groups locally at specific positions on the spacer arm rather than throughout the entire base matrix. This localized introduction ensures sufficient formyl groups for high adsorption capacity while maintaining stable ligand immobilization and preventing leakage.
Solution Approach 2:
The patent optimizes the parameters of formyl group introduction, including the amount of periodate used and reaction conditions, to achieve the right balance between sufficient formyl group content for high adsorption capacity and stable ligand immobilization to prevent leakage.
3Productivity
If conventional porous base matrices are used for upscaling, then purification capacity increases, but compaction occurs leading to liquid flow problems
Solution Approach 1:
The composite structure of base matrix plus spacer arm with 5- or 6-membered ring provides enhanced mechanical strength that allows the adsorbent to withstand the stresses of large-scale purification operations at high linear speeds without compaction, while maintaining high purification capacity.
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 new adsorbent achieves high adsorption capacity, reduces ligand leakage, and ensures safety and purity during treatment and purification, enabling efficient and rapid antibody purification with improved mechanical strength and stability.
Implementation Method 1
affinity adsorbents are able to efficiently purify a target substance
Implementation Method 2
adsorbents obtained by immobilizing protein A as an affinity ligand on a porous base matrix as medical adsorbents
Implementation Method 3
a polysaccharide gel having vicinal hydroxy groups is oxidized through periodate oxidation so as to generate formyl groups on the sugar chain
Implementation Method 4
it is preferable from an industrial perspective to use the reaction between a formyl group on a porous base matrix and an amino group on an affinity ligand so as to effect immobilization
Data Source
AI summary
The present invention relates to a porous base matrix having formyl group, which base matrix has a structure represented by the formula (2) as a spacer, which structure is obtained by cleaving a group represented by the formula (1):wherein, R1 represents a group forming a five-membered ring or a six-membered ring with —CH(OH)—CH(OH)—; a method for producing the porous base matrix; and an adsorbent obtained by binding a ligand on the porous base matrix. By the present invention, a high-intensity base matrix for an adsorbent and an adsorbent are provided. The amount of a ligand leaked from the adsorbend is small.