Factor X Purification via Immobilized Metal Ion Affinity Chromatography
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Solution Overview
Problem
Current treatments for factor X deficiency, such as plasma and prothrombin complex concentrates, are inefficient, require large volumes, pose risks of volume overload, thrombotic side effects, and have variable dosing due to high prothrombin contamination, necessitating a more effective method for separating factor X from prothrombin.
Innovation Solution
A method utilizing immobilized metal ion affinity chromatography (IMAC) to separate factor X from prothrombin, followed by anion exchange chromatography for further purification, allowing for efficient virus reduction and pharmaceutical formulation of factor X with reduced prothrombin content.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If plasma or prothrombin complex concentrates are used to treat factor X deficiency, then factor X can be delivered to patients, but large infusion volumes are required which cause volume overload and osmotic imbalance
Solution Approach 1:
The patent extracts and isolates factor X from plasma or prothrombin complex concentrates using chromatography techniques. This extraction removes the harmful volume component while retaining the therapeutic factor X, allowing concentrated delivery without volume overload risks
Solution Approach 2:
The patent changes the concentration parameter of factor X through purification processes. By increasing factor X concentration from approximately 1 unit per mL in plasma to highly concentrated purified forms, the required infusion volume is dramatically reduced while maintaining therapeutic efficacy
2Quantity of substance
If prothrombin complex concentrates are used to deliver factor X, then factor X is available in higher concentration, but prothrombin contamination causes thrombotic side effects
Solution Approach 1:
The patent selectively extracts factor X from prothrombin complex concentrates using specific chromatography methods. This removes the harmful prothrombin component while isolating pure factor X, eliminating the source of thrombotic side effects
Solution Approach 2:
The patent achieves local quality by creating a highly purified factor X product with specific purity characteristics. The chromatography process targets factor X specifically, giving the final product the local quality of high factor X purity without prothrombin contamination that causes thrombosis
3Quantity of substance
If plasma is used for factor X treatment, then factor X can be administered, but refrigerated or frozen storage is required which restricts patient availability
Solution Approach 1:
The patent changes the stability parameter of factor X through purification and formulation. The highly purified factor X product achieves enhanced stability that allows storage at higher temperatures compared to plasma, improving availability to patients without refrigeration infrastructure
4Quantity of substance
If prothrombin complex concentrates are used for factor X delivery, then factor X is available, but variable dosing occurs due to high prothrombin content
Solution Approach 1:
The patent extracts factor X specifically from prothrombin complex concentrates, removing the variable prothrombin component. This results in a standardized factor X product with consistent potency and predictable dosing
Solution Approach 2:
The patent changes the purity and consistency parameters of the factor X product. Through chromatographic purification, the product achieves standardized factor X content without variable prothrombin contamination, enabling precise and reliable dosing
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 enables the production of highly purified factor X with reduced prothrombin contamination, facilitating a stable and effective pharmaceutical product that can be stored at higher temperatures, reducing the risk of thrombotic side effects and improving treatment efficacy for factor X deficiency.
Implementation Method 1
a) adsorbing the starting material onto an immobilised metal ion affinity chromatography substrate
Implementation Method 2
The eluate from step b) is applied to an anion exchange chromatography medium
Data Source
AI summary
Methods for preparing Factor X, activated Factor X, inactivated factor X and inactivated factor Xa, compositions comprising Factor X and Factor Xa, inactivated Factor X and inactivated Factor Xa and methods of medical treatment using Factor X, Factor Xa, activated Factor X and inactivated Factor Xa are disclosed. The preparation methods comprise a chromatography step using an immobilised metal ion affinity chromatography substrate.