Recombinant VWF Formulation Stability and Pathogen Safety

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current plasma-derived VWF formulations face challenges with quantity and purity issues, as well as risks of blood-borne pathogens such as viruses and Variant Creutzfeldt-Jakob disease, necessitating the development of a stable pharmaceutical formulation using recombinant VWF.

Innovation Solution

A stable liquid pharmaceutical formulation of recombinant von Willebrand Factor (rVWF) is developed, comprising rVWF, a buffering agent, salts, and optionally stabilizing and surfactant agents, with specific concentrations and pH ranges to ensure stability and safety, using a formulation that includes a polypeptide sequence, buffering agents like citrate, and surfactants like TWEEN-80.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If plasma-derived VWF formulations are used, then VWF can be obtained for therapeutic use, but quantity and purity issues arise and there is risk of blood-borne pathogens

Engineering Contradiction:

Improvesafety of VWF formulationVSAvoidquantity and purity of VWF

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent extracts the VWF protein from plasma through a multi-step purification process, separating the desired product from contaminants and pathogens. The purification steps include affinity chromatography, ion exchange chromatography, and filtration, which remove blood-borne pathogens and impurities while recovering VWF, thus resolving the contradiction between obtaining sufficient quantity and ensuring purity/safety

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent creates a safe copy of the VWF protein through recombinant DNA technology. Instead of using plasma-derived VWF that carries pathogen risk, the invention uses genetically engineered cells to produce identical or highly similar VWF molecules, eliminating the risk of blood-borne pathogens while maintaining therapeutic efficacy and allowing for scalable production

Inventive Principle:

Principle #26Copying

2Reliability

If plasma-derived VWF formulations are used, then VWF is available for treatment, but stability and storage issues occur

Engineering Contradiction:

Improveavailability of VWF formulationVSAvoidstability of VWF formulation

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent optimizes formulation parameters including pH (adjusted to specific ranges), ionic strength, presence of stabilizing agents, and temperature conditions to enhance VWF stability. The recombinant production system also allows for controlled post-translational modifications that improve structural stability, enabling the formulation to maintain activity during storage and transport

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If recombinant VWF is produced, then purity and safety are improved, but manufacturing complexity increases

Engineering Contradiction:

Improvepurity of VWFVSAvoidmanufacturing process complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent divides the manufacturing process into distinct modular stages: cell culture setup, protein expression, harvest, multi-step purification (affinity chromatography, ion exchange, filtration), and formulation. Each module can be independently optimized and controlled, making the complex overall process more manageable while ensuring high purity and safety standards are met

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS11191837B2Recombinant VWF formulations

Publication Date: 2021.12.07 TAKEDA PHARMA CO LTD

AI summary

The present invention provides long-term stable pharmaceutical formulations of recombinant von-Willebrand Factor (rVWF) and methods for making and administering said formulations.