Secretory IgA and IgM Manufacturing with Affinity Purification
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Solution Overview
Problem
Existing technologies have failed to provide a scalable and high-purity manufacturing process for orally administered human polyclonal semisynthetic secretory IgA and IgM therapeutics to treat necrotizing enterocolitis, which is resistant to gastrointestinal tract degradation and suitable for infants.
Innovation Solution
A process involving the formation of affinity-tagged secretory IgA and IgM using recombinant human secretory component, purified through a solid phase support resin, to create dimeric and polymeric forms resistant to gastrointestinal degradation, enabling oral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If human plasma derived IgA is combined with recombinant secretory component to produce secretory IgA, then biological activity and resistance to gastrointestinal degradation are improved, but manufacturing complexity and purification requirements increase
Solution Approach 1:
The patent uses an affinity tag as an intermediary element that facilitates the binding between recombinant secretory component and plasma-derived IgA, enabling selective purification through affinity chromatography. This intermediary mechanism resolves the complexity by providing a controlled interaction point for combining components and separating the final secretory IgA product from other plasma proteins.
Solution Approach 2:
The patent modifies the secretory component by introducing an affinity tag at specific locations (N-terminus or C-terminus), which changes the biochemical parameters of the protein to enable selective binding to affinity columns. This parameter change allows for efficient purification and scaling of the manufacturing process while maintaining the biological activity of the secretory IgA.
2Manufacturing precision
If affinity tagging and solid phase purification are implemented, then manufacturing precision and product purity are improved, but process time and production costs increase
Solution Approach 1:
The affinity tag is introduced during the expression of the secretory component in recombinant cells, performing the purification function in advance before the final product formation. This preliminary action allows for selective binding and purification to occur in a single chromatography step rather than requiring multiple sequential purification steps, thereby reducing overall process time while maintaining high product purity.
Solution Approach 2:
The patent extracts unwanted plasma proteins and impurities from the mixture through affinity chromatography, selectively removing them while retaining the secretory IgA complex. This extraction approach concentrates the desired product and eliminates contaminants in a single efficient operation, achieving high purity without requiring extensive multi-step purification processes.
3Productivity
If semisynthetic secretory IgA is produced using plasma derived IgA and recombinant secretory component, then scalability and commercial quantity production are improved, but manufacturing complexity increases
Solution Approach 1:
The patent segments the manufacturing process into distinct modular steps: (1) production of recombinant secretory component with affinity tag in cell culture, (2) purification of secretory component, (3) combination with plasma-derived IgA, and (4) final purification of secretory IgA. This segmentation allows each step to be optimized independently and scaled separately, facilitating commercial production while maintaining process control and product quality.
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 process allows for the production of secretory IgA and IgM therapeutics that effectively inhibit necrotizing enterocolitis symptoms by mimicking naturally secreted intestinal secretory IgA, providing resistance to degradation and reducing treatment costs.
Implementation Method 1
The secretory component being modified to contain an affinity tag or an epitope tag to form secretory IgA and/or secretory IgM containing said affinity tag or epitope tag that is useful for capture by a solid phase support resin
Data Source
AI summary
A process for synthesizing and separating secretory IgA from a mixture of IgA monomer and IgA dimer is provided The process includes covalently binding affinity tagged or epitope tagged recombinant secretory component to the IgA dimer in the mixture and then binding the affinity tagged or an epitope tagged secretory IgA to immobilized moieties on the solid phase support resin to which the affinity tag or epitope tag binds and then eluting the affinity tagged or an epitope tagged secretory IgA with release buffer. A process for synthesizing and separating secretory IgM from a mixture of IgM and other plasma proteins is provided. A process is provided for inhibiting or preventing symptoms of necrotizing enterocolitis in a subject that includes the oral administration to the subject of a human polyclonal secretory IgA formed by the conjugation of human recombinant secretory component and pooled human plasma derived dimeric and polymeric.