Monolithic Anion Exchanger for PCC Purification

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Solution Overview

Problem

Current methods for purifying Prothrombin Complex Concentrate (PCC) and Factor IX from plasma require multiple dilution steps, leading to loss of activity of physiologically active proteins and are inefficient.

Innovation Solution

The process employs sample displacement chromatography with a monolithic anion exchanger as the initial purification step, followed by additional chromatography steps using anion and cation exchangers, allowing for the purification of PCC and FIX from undiluted cryo-poor plasma, which maintains protein activity and reduces the need for multiple dilutions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If multiple dilution steps are used in current purification methods, then the purification process can be completed, but loss of activity of physiologically active proteins occurs

Engineering Contradiction:
Improvepurification effectivenessVSAvoidprotein activity
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The invention changes the concentration parameter by using undiluted or minimally diluted plasma as feedstock, reversing the conventional approach of multiple dilutions. This parameter change maintains protein activity while achieving purification through the chromatographic process designed for concentrated samples

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention extracts and removes impurities directly from undiluted plasma through chromatography, rather than relying on dilution to reduce impurity concentration. The chromatographic system is designed to selectively bind and separate target proteins from the complex plasma matrix at high concentration

Inventive Principle:
Principle #2Taking out (Extraction)

2Manufacturing precision

If multiple dilution steps are performed, then purification can proceed, but the process becomes inefficient

Engineering Contradiction:
Improvepurification effectivenessVSAvoidprocess efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The invention performs preliminary concentration and pre-purification steps before the main chromatographic separation, allowing the subsequent steps to work with optimized sample characteristics. This preliminary action eliminates the need for multiple dilution cycles and accelerates the overall process

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention implements a continuous chromatographic process where undiluted plasma flows through the system without interruption for dilution and re-concentration cycles. The useful action of purification continues uninterrupted, maintaining high productivity while achieving the required purification level

Inventive Principle:
Principle #20Continuity of useful action

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 effectively purifies PCC and FIX with higher specific activity and balances vitamin K-dependent clotting factors and inhibitors, reducing the loss of active proteins and improving the efficiency of the purification process.

Implementation Method 1

chromatography using a monolithic stationary phase, the method comprising a) performing of an initial sample displacement chromatography step of complete plasma or cryo-poor plasma on an anion exchanger to obtain a first fraction enriched in PCC

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 2

the chromatography step is performed with an anion exchanger to obtain a second fraction enriched in PCC

Methodology Applied
Scientific EffectElectrostatic interaction: Ion Repulsion/Attraction

Data Source

PatentUS20230356110A1A process for the purification of prothrombin complex concentrate (PCC) and fix from complete plasma or cryo-poor plasma
Publication Date: 2023.11.09 SARTORIUS BIA SEPARATIONS D O O

AI summary

A process for the purification of Prothrombin Complex Concentrate (PCC) from complete plasma or cryo-poor plasma, in particular undiluted cryo-poor plasma, by means of chromatography using a monolithic stationary phase, the method comprising performing an initial sample displacement chromatography step of complete plasma or cryo-poor plasma on an anion exchanger to obtain a first fraction enriched in PCC.