Poxvirus Purification Process Retaining Extracellular Enveloped Viruses

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current poxvirus purification processes primarily focus on intracellular mature virus (IMV) particles, discarding extracellular enveloped virus (EEV) particles, despite EEVs potentially offering greater therapeutic and prophylactic efficacy due to their additional surface proteins, which could provide targeted infection specificity and enhanced therapeutic effects.

Innovation Solution

A process for producing and purifying recombinant poxviruses, specifically extracellular enveloped viruses (EEVs) with no targeted infection specificity, using a combination of depth filtration, microfiltration, and diafiltration to obtain high-titer EEV compositions free from animal-derived products, thereby overcoming the limitations of existing methods that rely on animal-derived compounds and fail to retain EEVs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If current poxvirus purification processes focus on IMV particles, then IMV purification efficiency is improved, but EEV particles are discarded despite their potential therapeutic efficacy

Engineering Contradiction:
ImproveIMV purification efficiencyVSAvoidEEV particles
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The purification process is segmented into multiple sequential filtration steps (depth filtration, microfiltration, diafiltration) that separately address different purification needs, allowing selective retention of EEV particles while removing contaminants

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The process changes physical parameters (filtration pore sizes, pressure gradients, buffer compositions) across different stages to optimize for EEV retention rather than IMV purification, transforming the purification approach from IMV-focused to EEV-preserving

Inventive Principle:
Principle #35Parameter changes

2Device complexity

If traditional purification methods are used, then process simplicity is maintained, but animal-derived products remain in the final composition

Engineering Contradiction:
Improveprocess simplicityVSAvoidanimal-derived products
Core Design Contradiction:
Device complexityVSObject-generated harmful factors

Solution Approach 1:

The process extracts and removes animal-derived contaminants through sequential filtration steps, taking out harmful substances while preserving the therapeutic EEV particles

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The method uses disposable filtration membranes and single-use filtration cassettes that can be discarded after one use, eliminating the need for extensive sterilization and validation procedures while ensuring removal of animal-derived products

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Reliability

If EEV particles are retained in the composition, then therapeutic efficacy is enhanced, but purification process complexity increases

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidpurification process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The filtration system performs multiple functions simultaneously: depth filtration removes large particulates, microfiltration retains EEV particles while allowing buffer exchange, and diafiltration removes contaminants - all within a unified process framework

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The process performs preliminary concentration and clarification steps before the main purification phase, preparing the sample in advance to facilitate easier and more efficient EEV retention during subsequent filtration steps

Inventive Principle:
Principle #10Preliminary 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

The process yields a high-titer EEV composition with enhanced therapeutic and prophylactic efficacy, as demonstrated by improved survival rates and tumor regression in animal models, showcasing the potential of EEVs in cancer treatment and other therapeutic applications.

Implementation Method 1

The culture media and the packaging cells are subjected to a depth filtration step, allowing the withdrawal of the cellular debris

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 2

The virus-containing filtrate is then subjected to a microfiltration step, allowing the concentration of the poxviruses

Methodology Applied
Scientific EffectMicrofiltration: Semipermeable Membrane

Implementation Method 3

The poxviruses are then purified by subjecting the concentrated virus to a diafiltration step

Methodology Applied
Scientific EffectDiafiltration: Semipermeable Membrane

Data Source

PatentEP2530161B1Process for producing poxviruses and poxvirus compositions
Publication Date: 2018.03.28 TRANSGENE SA
  • EP2530161B1 patent drawingFigure 1
  • EP2530161B1 patent drawingFigure 2
  • EP2530161B1 patent drawingFigure 3

AI summary

The present invention relates to compositions and pharmaceutical compositions comprising poxviruses and more particularly extracellular enveloped viruses. The present invention also relates to a process for producing poxviruses and poxviruses obtained thereof. Moreover, the present invention also relates to the use of said poxvirus and said composition for the preparation of a medicament.