Plant-Based Monoclonal Antibody Purification Platform

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Solution Overview

Problem

Current monoclonal antibody production methods, particularly mammalian-based systems, are complex, costly, and inefficient, requiring specific protocols for each antibody type, extensive testing, and virus inactivation steps, which limits scalability and rapid response to diseases.

Innovation Solution

A standardized plant-based monoclonal antibody purification platform using transient gene expression in plants, followed by a multi-step chromatography process involving affinity, ion exchange, and multimodal columns, eliminating the need for virus inactivation and reducing testing and regulatory compliance costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mammalian-based monoclonal antibody production methods are used, then antibodies can be produced with high specificity and affinity, but the production process becomes complex, costly, and requires extensive virus inactivation and testing steps

Engineering Contradiction:
Improveantibody specificity and affinityVSAvoidproduction process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies universality by using a standardized plant-based production platform that can produce multiple different monoclonal antibodies through a single, consistent process. The same plant expression system and purification protocol are used across different antibody projects, eliminating the need for separate process development and validation for each antibody, thus reducing overall complexity while maintaining reliability.

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

Solution Approach 2:

The patent uses copying by implementing a standardized, replicated production platform across different facilities and projects. The same plant-based expression system, vector constructs, and purification methods are copied and applied universally, reducing the need for unique process development for each antibody and simplifying regulatory compliance through consistent manufacturing practices.

Inventive Principle:
Principle #26Copying

2Reliability

If mammalian-based monoclonal antibody production methods are used, then antibodies can be produced with high specificity and affinity, but production costs increase due to extensive testing and virus inactivation requirements

Engineering Contradiction:
Improveantibody specificity and affinityVSAvoidproduction cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses copying by implementing a standardized, replicated production platform across different facilities and projects. The same plant-based expression system, vector constructs, and purification methods are copied and applied universally, reducing the need for unique process development for each antibody and simplifying regulatory compliance through consistent manufacturing practices.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent applies this principle by using transient gene expression in plants rather than establishing permanent transgenic cell lines. The plant cells are infected with viral vectors that express the antibody temporarily, allowing for rapid production without the need for long-term cell line maintenance, characterization, and cryopreservation infrastructure, thereby reducing overall manufacturing costs.

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

3Manufacturing precision

If specific purification protocols are developed for each antibody type, then purification effectiveness is optimized, but the overall production system becomes less scalable and more costly

Engineering Contradiction:
Improvepurification effectivenessVSAvoidproduction scalability
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent applies universality by using a standardized plant-based production platform that can produce multiple different monoclonal antibodies through a single, consistent process. The same plant expression system and purification protocol are used across different antibody projects, eliminating the need for separate process development and validation for each antibody, thus reducing overall complexity while maintaining reliability.

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

4Reliability

If mammalian cell systems are used for antibody production, then high antibody quality is achieved, but the response time to disease outbreaks is delayed due to complex process setup and validation

Engineering Contradiction:
Improveantibody qualityVSAvoidresponse time to disease outbreaks
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-establishing standardized plant-based expression systems and purification protocols that are ready for immediate deployment. The plant expression platforms are pre-validated and can be rapidly activated upon identification of a target antibody, eliminating the time-consuming process of cell line development, characterization, and process validation required for mammalian systems, thus enabling faster response to disease outbreaks.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies this principle by using transient gene expression in plants rather than establishing permanent transgenic cell lines. The plant cells are infected with viral vectors that express the antibody temporarily, allowing for rapid production without the need for long-term cell line maintenance, characterization, and cryopreservation infrastructure, thereby reducing overall manufacturing costs.

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

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 approach simplifies and streamlines monoclonal antibody production, reducing development and production costs, ensuring reliable and scalable production of high-quality antibodies, and enabling rapid response to diseases with uniform and potent antibody products.

Implementation Method 1

an affinity column, a second ion exchange column, and a third multimodal column for removal of extraneous compounds

Methodology Applied
Scientific EffectAffinity chromatography: Adsorption

Implementation Method 2

a first affinity column, a second ion exchange column, and a third multimodal column

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 3

a first affinity column, a second ion exchange column, and a third multimodal column for removal of extraneous compounds

Methodology Applied
Scientific EffectMultimodal chromatography: Adsorption

Implementation Method 4

extraction and clarification, filtrate generation

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentEP3092002B1Method of purifying monoclonal antibodies
Publication Date: 2019.09.25 KENTUCKY BIOPROCESSING LLC
  • EP3092002B1 patent drawingFigure 1
  • EP3092002B1 patent drawingFigure 2
  • EP3092002B1 patent drawingFigure 3

AI summary

A new platform method to purify plant-based monoclonal antibodies is provided. Such a method includes an antibody purification platform that involves a standardized procedure for the production of a wide array of different antibodies within a simplified context. The versatility of the overall purification process accords a one-size-fits-all approach for myriad antibody products and includes plant tissue harvesting, extraction and clarification, filtrate generation, a succession of column chromatography procedures, and buffer exposure to provide the desired monoclonal antibodies in proper filtered and purified form for further incorporation and/or use within medicaments and other formulations. Thus, the purified monoclonal antibodies produced thereby such a method are also encompassed within this invention.