Plant-based protein expression offers high yields and easy harvesting but has been held back by a lack of funding and the ubiquity of mammalian and bacterial systems, says Leaf Expression Systems.
UK-based contract biopharmaceutical development firm Leaf Expression Systems has appointed Simon Saxby, a former executive at contract manufacturing organizations (CMOs) Recipharm and Cobra, as its CEO.
Leaf Expression Systems offers the production of proteins, antibodies and vaccines through its Hypertrans expression system, based on tobacco plants.
Saxby’s immediate focus will be forging “both risk sharing and straight commercial relationships to produce proteins, vaccines and complex biomolecules that are either too expensive or too difficult to produce in other expression systems, like mammalian cell culture systems,” he told BioProcess Insider, in order to raise the firm’s profile and demonstrate its tech platform.
“We will also be working with clients and partners to establish Hypertrans and Leaf as the technology and partner of choice for production of their new molecules, and especially when there is the need for a rapid response to disease outbreaks, like Zika or Ebola, allowing big pharma to focus on longer term solutions to these outbreaks.”
According to Saxby, plant-based systems offer high yields of biologics while avoiding some of the pitfalls of mammalian and microbial platforms.
“The plants grow rapidly, infiltration is a simple process, and within a week or two of the plants being infiltrated we are able to harvest and purify the products,” he said, adding Leaf’s Hypertrans platform produces meaningful quantities of proteins, vaccines or biomolecules within 12 weeks of receiving the sequences from clients.
“In common with other plant-based systems we also offer the advantage of not using any animal-based products in the manufacturing process – either upstream or downstream – removing a considerable regulatory concern over product purity and potential adventitious infection of patients.”
But despite the advantages, there is only one biotherapeutic made using a plant-based expression system commercially available: Protalix Biotheraputics/Pfizer’s Elelyso (taliglucerase alfa), made from transgenic carrot cell suspensions, was approved in 2012 to treat Gaucher disease.
“Despite plant-based technologies being around for many years, there has been significant underfunding for research and development of plant-based systems as industry has focused on improving the safety profiles and yields from mammalian and bacterial processes,” Saxby said.
Furthermore, “because all of the first biologic drugs were produced in either mammalian or bacterial systems, and because pharma and biotech developed these systems to meet the understandably strict regulatory requirements, switching to plant-based systems posed too much of an economic and financial risk.”
There are others looking to reach Protalix’s success with a plant-based approval, such as Brazil’s Axis Biotec, which is looking to make a biosimilar of Humira (adalimumab) using tobacco plants, and Medicago, a firm developing biologics and vaccines.
“When additional plant produced therapeutics receive regulatory approval, e.g. Medicago’s ‘flu vaccine which is currently in Phase III trials, I expect the landscape for plant-based drug manufacture will change significantly.”
Leaf’s expression system is based on the gene of interest being cloned into the Hypertrans system.
“This clone is transferred to a bacterium (Agrobacterium tumefaciens) which naturally transfers DNA to plant cells,” Saxby explained. “The bacteria are introduced into the plant leaf and the gene of interest is transferred from the bacteria to the plant cells. The plants are grown for several days to allow the gene of interest to produce protein and then leaves are harvested. Following harvest, proteins are extracted and purified from the plant material.”
But for industry to move to disruptive plant-based tech, Saxby told us that there has to be a commercial as well as a good scientific reason, something his new firm claims to be able to offer.
“We will accelerate client R&D programs – enabling them to either move products from research into the development programs quicker or helping them fail products earlier,” he said.
He continued, saying such accelerated R&D programs increases the throughput of client research and development organizations.
“Finally – accelerating a programme that helps to get a product to market quicker brings significant commercial value by extending the patent life of the product.”