IgG Concentrate Purification via Immunoaffinity Chromatography
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Solution Overview
Problem
Current methods for producing IgG concentrates for intravenous use often result in products with high levels of anti-A and anti-B antibodies, leading to hemolysis and other adverse reactions, and are characterized by polyreactivity generated during the manufacturing process, which can cause side effects such as fever and nausea due to the high dosages required for treatment.
Innovation Solution
A process involving ethanolic fractionation and immunoaffinity chromatography using supports grafted with N-acetylgalactosamine, Galactose, and Fucose groups corresponding to blood group epitopes, followed by filtration to eliminate viruses and particles, significantly reduces anti-A and anti-B antibodies and polyreactive IgG content, resulting in IgG concentrates with undetectable anti-A and anti-B antibodies and low polyreactivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional ethanol precipitation and chromatographic separation are used to produce IgG concentrates, then IgG concentration is achieved, but high levels of anti-A and anti-B antibodies remain causing hemolysis and adverse reactions
Solution Approach 1:
The patent applies extraction by passing the IgG concentrate through immunoaffinity chromatography columns containing supports grafted with N-acetylgalactosamine-Galactose-Fucose groups. These supports specifically bind and remove anti-A and anti-B antibodies from the concentrate, extracting the harmful components while preserving the therapeutic IgG.
Solution Approach 2:
The patent uses immunoaffinity chromatography supports grafted with blood group epitopes as intermediary substances. These supports act as mediators that selectively capture anti-A and anti-B antibodies through specific antigen-antibody interactions, enabling removal of harmful antibodies without directly affecting the IgG concentrate.
2Manufacturing precision
If standard purification processes are used, then IgG is obtained, but polyreactivity is generated during manufacturing causing side effects such as fever and nausea
Solution Approach 1:
The patent converts the harmful polyreactivity generated during manufacturing into a benefit by using the same immunoaffinity chromatography process to remove not only anti-A and anti-B antibodies but also other polyreactive IgG subclasses. The manufacturing process that creates polyreactivity is followed by a purification step that eliminates these harmful byproducts.
Solution Approach 2:
The patent changes the purification parameters by employing immunoaffinity chromatography with specifically grafted supports at controlled pH and temperature conditions. This alters the selectivity of the purification process to specifically target and remove polyreactive IgG while preserving monoreactive therapeutic IgG.
3Reliability
If high dosages are administered to achieve therapeutic effectiveness, then treatment efficacy is improved, but side effects such as fever and nausea increase
Solution Approach 1:
By extracting and removing polyreactive IgG subclasses that cause side effects, the patent enables administration of lower dosages to achieve the same therapeutic effectiveness. The harmful components are taken out, allowing reduced dosing without compromising treatment efficacy.
Solution Approach 2:
The patent changes the quality parameter of the IgG concentrate by reducing polyreactivity through immunoaffinity purification. This parameter change allows for lower therapeutic dosages to be effective, thereby reducing the incidence of side effects associated with high-dose administration.
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 produces IgG concentrates with anti-A and anti-B antibody levels below European Pharmacopoeia thresholds, reducing hemolytic risks and side effects, while maintaining therapeutic effectiveness, and can be implemented on an industrial scale with specific stabilizers for long-term storage and preservation.
Implementation Method 1
immunoaffinity chromatography by percolation of said IgG concentrate on a mixture of supports whose matrices are grafted with N-acetylgalactosamine (GalNAc) - Galactose (Gal) - Fucose (Fuc) and Galactose-Galactose-Fucose groups corresponding to the epitopes of blood groups A and B
Implementation Method 2
specific binding of anti-A and anti-B antibodies to the grafted epitopes on the chromatography supports
Implementation Method 3
filtration for the elimination of viruses and/or particles of size greater than 20 nm
Implementation Method 4
preparation of an IgG concentrate by ethanolic fractionation
Data Source
AI summary
The present invention relates to an immunoglobulin G concentrate for therapeutic use, in which the respective contents of anti-A and anti-B antibodies are in accordance with a negative result in the in vitro indirect Coombs test. This IgG concentrate also has a polyreactive IgG content of between 0.01% and 0.1%, in particular between 0.07% and 0.1%, relative to the total content of IgG.