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Tobacco as a medicine maker

By Josh Shepherd

There are literally hundreds of square yards of vibrant green tobacco plants in the huge growing facilities at Kentucky BioProcessing (KBP) in Owensboro. Even for a Kentuckian accustomed to the sight of commercial tobacco, the plants in this facility are nothing farmers outside of Daviess County have ever seen.

Kentucky BioProcessors in Owensboro induces a strain of tobacco native to New Zealand to produce specialty proteins for pharmaceutical uses such as a potential treatment for Ebola.
Kentucky BioProcessors in Owensboro induces a strain of tobacco native to New Zealand to produce specialty proteins for pharmaceutical uses such as a potential treatment for Ebola.

“The variety of tobacco that we use in our production facilities is not native to Kentucky,” said founding CEO Hugh Haydon. The species, Nicotiana Benthemiana, does not grow well in this region outside of the highly controlled, laboratory environment KPB maintains in its facility.

“N. Bethemiana is indigenous to New Zealand and Australia. That’s where it was first catalogued,” Haydon said. “It is not grown commercially anywhere for any purpose other than what we do with it.”

But because Kentuckians understand how to cultivate the broad-leafed member of the nightshade family, this non-North America tobacco species is now the foundation of KBP’s emergence as an industry leader in the commercial production of plant-based proteins for the biopharmaceutical industry.

KBP earned media attention in October for dedicating all its operations toward producing monoclonal antibody proteins for an experimental Ebola treatment created by its primary client, San Diego-based Mapp Biopharmaceuticals. There was national attention regarding that treatment, ZMapp, which was used on an emergency basis to treat healthcare providers infected with the Ebola virus. ZMapp has shown promise in early trials with primates, according to Mapp, but results are not yet scientifically conclusive.

KBP’s primary business model involves its expertise with bio-pharma applications of the tobacco plant. KPB uses N. Benthamiana as a platform to produce specific types of proteins that fill clients’ needs. The company is a member of a research partnership whose aim is, using a tobacco-grown protein, to develop a gel that prevents HIV transmission.

Tobacco strain “photocopies” proteins

“Photocopying is a reasonable analogy to describe what the plant does,” the KBP executive explained. “You have a target protein that our client wishes to reproduce. It has a certain genetic makeup. You reproduce that genetic makeup in the laboratory, then you introduce that into the plant.”

Tobacco biology does much of the rest.

“People have assumed that we take something out that is native to the tobacco plant, but that is a misconception of the business. Rather, we introduce something into the plant, a protein or a chemical, that the tobacco plant then reproduces at a rapid rate,” Haydon said. “We have the ability to produce a wide variety of proteins. It just depends on what we engineer in our labs to put into the plant.”

KBP allows a plant to approach the point where it has so much foreign material within it that it can no longer sustain itself, then employees harvest the plant and begin extracting and purifying the protein or chemical it produced.

This bio-pharma protein production method is a unique niche for KBP, Haydon said. Few others in the world are doing research and development with this species of tobacco plant. The standard method for bio-production uses mammalian, or animal-based, proteins grown in large reactors.

“That is a much, much larger sector of the industry,” Haydon said. “Compared to other systems that produce bio-pharmaceutical proteins and related chemical material, we’re not very large.”

Faster and safer than animal systems

KBP’s production speed also differentiates it from others in its industry. Because of the biology it works with and the type of gene expression it does, KBP’s system can be faster than a mammalian cell system, Haydon said.

“The concept is to have a purified protein in the hands of our clients much more quickly than in another system,” he said.

In October, Kentucky BioProcessors began putting all of its capacity into production of a monoclonal antibody protein created for use in a potential Ebola virus treatment developed by San Diego-based Mapp Biopharmaceuticals.
In October, Kentucky BioProcessors began putting all of its capacity into production of a monoclonal antibody protein created for use in a potential Ebola virus treatment developed by San Diego-based Mapp Biopharmaceuticals.

Additionally, plant-produced protein has less risk of some pathogen influencing and compromising the final product, he said. Plants are not susceptible to the same types of viruses as mammalian cells. Therefore, plant-based proteins are cleaner, faster and a culturally advantageous process, he added.

N. Benthamiana tobacco grows quickly and in three to four weeks reaches a stage at which foreign materials can be introduced for reproduction using current good manufacturing processes, or cGMP, Haydon said.

Federal cGMP quality regulations apply to the entire biopharmaceutical industry, whether protein production is via plants or mammalian cells. The cGMP designation indicates a company demonstrates proper control of its processes. It is an indication also, according to Haydon, that KBP is committed to continuous improvement of production methods and quality controls.

“Our service has a wide variety of applications,” he said.

One of those is production of monoclonal antibody proteins, according to a Mapp Pharmaceuticals report. In addition to Ebola infections, these proteins have shown potential as a treatment against Marburg and Junin viruses, ricin and equine encephalitis. There are also potential uses in the prevention of HIV and other infectious diseases, according to Mapp.

Picking up where a start-up left off

KPB was formed in 2005, Haydon said. Part of its technology and part of the facility it occupies was acquired from a California company, Biosource, that had sought to capitalize on Kentucky’s tobacco experience.

Recognizing the potential tobacco plants presented as a plant-made pharmacueticals production platform, Biosource in the late 1980s established a start-up named Large Scale Biology. It hoped to tap not only local tobacco farming know-how but the extensive research scientists had been conducting at the University of Kentucky and University of Louisville.

In late 2005, however, the potential of the industry had not produced parallel financial development, and Large Scale Biology ceased operations then filed for bankruptcy. This opened the way, though, for the founding of KBP.

“That company had set up an operation in Owensboro to do something similar to what we do, and they chose to set it up in Owensboro primarily because of the local knowledge and expertise regarding the managing and handling of the tobacco plant,” Haydon said. “We’ve added significantly to the technology and to the facility to build the business that we’ve built.”

Recognizing the long-range business potential, individual investors partnered with Owensboro Health, known then as the Owensboro Medical Health System, to continue the pioneering work that had been started.

“Owensboro Health supported the company with a vision toward economic development in the Daviess County region and investing its resources into an area that could result in improved public health,” Haydon said.

The goals of KBP and Owensboro Health meshed well enough to prompt the independent healthcare system to commit to a multimillion-dollar investment in KBP to buy the remains of Large Scale Biology, he said.

KBP soon developed mutually beneficial relationships with a number of clients, but those with Mapp Biopharmaceuticals and Icon Genetics are its most successful and productive to date, according to Haydon.

In 2014, Reynolds American, the parent company of R.J. Reynolds Tobacco Co., acquired Owensboro Health’s interests in KBP.

“Reynolds American continues to invest in promising new technologies involving tobacco,” Haydon said. “We are a company that is redefining how breeds of tobacco can contribute to the health of the global population. Their acquisition of the company has had a positive impact for KBP and is beneficial to what we are trying to accomplish.”

 Josh Shepherd is a correspondent for The Lane Report. He can be reached at [email protected]