Phaeodactylum Tricornutum Vectors for Therapeutic Antibody Secretion

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for producing monoclonal antibodies (mAbs) in CHO cells are inefficient, leading to heterogeneous glycosylation, proteolytic degradation, high manufacturing costs, and contamination risks, while alternative systems like tobacco plants require significant infrastructure and microalgae face low production yields.

Innovation Solution

A nucleotide construct in Phaeodactylum tricornutum (P. tricornutum) encoding therapeutic monoclonal antibodies, using the V-ATPase C promoter/FcpA terminator pair and heterologous signal peptides, enhances secretion and production yields.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If CHO cells are used for mAb production, then human-like glycosylation is achieved, but production costs increase and product heterogeneity occurs

Engineering Contradiction:

Improveglycosylation homogeneityVSAvoidmanufacturing cost

Core Design Contradiction:

Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent changes the host cell type from CHO cells to microalgae P. tricornutum, fundamentally altering the biological system parameters. This substitution maintains human-like glycosylation capabilities while eliminating the high costs associated with mammalian cell culture, including complex media requirements and contamination risks.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If CHO cells are used for mAb production, then significant protein excretion is achieved, but contamination risk with viruses and prions increases

Engineering Contradiction:

Improveprotein production amountVSAvoidvirus and prion contamination risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent employs microalgae as a disposable, single-use expression system that eliminates the need for expensive, complex mammalian cell culture infrastructure. Microalgae cells are naturally resistant to human viruses and prions, providing inherent biosafety without requiring extensive purification and quality control steps.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Ease of manufacture

If microalgae are used for mAb production, then production costs decrease, but production yield is low

Engineering Contradiction:

Improvemanufacturing costVSAvoidmAb production yield

Core Design Contradiction:

Ease of manufactureVSProductivity

Solution Approach 1:

The patent optimizes multiple parameters including promoter selection (using strong constitutive promoters like rbcS and psbA), signal peptide engineering (testing various heterologous and endogenous signal peptides), and culture condition optimization (light intensity, temperature, nutrient composition) to maximize mAb secretion yield in microalgae.

Inventive Principle:

Principle #35Parameter changes

4Ease of manufacture

If tobacco plants are used for mAb production, then production costs decrease, but infrastructure requirements increase

Engineering Contradiction:

Improvemanufacturing costVSAvoidinfrastructure complexity

Core Design Contradiction:

Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent employs microalgae that can be cultured in self-contained photobioreactors or open pond systems, eliminating the need for complex greenhouse infrastructure, soil preparation, and plant transformation facilities required by tobacco plants. The system uses sunlight or artificial light for photosynthesis-driven biomass production, reducing operational complexity.

Inventive Principle:

Principle #25Self-service

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 system achieves high and homogeneous production of therapeutic antibodies like Trastuzumab and Rituximab, overcoming the limitations of CHO cells and providing a cost-effective, virus-resistant, and scalable production method.

Implementation Method 1

A nucleotide construct in Phaeodactylum tricornutum (P. tricornutum) encoding therapeutic monoclonal antibodies, using the V-ATPase C promoter/FcpA terminator pair

Methodology Applied

Scientific EffectTranscription:

Implementation Method 2

A nucleotide construct in Phaeodactylum tricornutum (P. tricornutum) encoding therapeutic monoclonal antibodies

Methodology Applied

Scientific EffectTranslation:

Implementation Method 3

using the V-ATPase C promoter/FcpA terminator pair and heterologous signal peptides, enhances secretion and production yields

Methodology Applied

Scientific EffectSecretion:

Implementation Method 4

Culture media is estimated to be much lower (0.002 US$ per liter) that is especially true for photosynthetic microalgae for which sunlight drives the production of biomass

Methodology Applied

Scientific EffectPhotosynthesis: Photosynthesis

Data Source

PatentUS20250277228A1Production of therapeutic antibodies by the microalgae phaeodactylum tricornutum

Publication Date: 2025.09.04 UNIVERSITE DE ROUEN NORMANDIE

AI summary

Monoclonal antibodies represent the most rapidly growing category of the recombinant therapeutic protein pipeline, with more than 85% of the therapeutic indications. The present invention proposes novel vectors that have been optimized so as to produce high levels of monoclonal antibodies when transfected in the microalgae Phaeodactylum tricornutum, as well as optimized culture conditions of said microalgae cells. Altogether, the present invention provides new systems for producing high amounts of monoclonal antibodies, functional fragments or derivatives thereof, in microalgae.