Professor Edward Rybicki was introduced at the Entrepreneurship Development in Higher Education (EDHE) Lekgotla 2022 as the scholar whose research, combined with that of the unit he heads, has the largest patent portfolio at the University of Cape Town (UCT), and the largest vaccine-related portfolio in Africa.

Despite this success, Rybicki, Director of the Biopharming Research Unit at UCT, became entrepreneurial quite by chance. In fact, he credits his success to luck – both good and bad.

“The bad luck you get when the NRF (National Research Foundation) stops funding you, and the good luck was the opportunity and the agility that got me out of my comfort zone to do something different — mainly by diversifying the funding source,” he said. “I’ll show you how happy accidents can happen and lead you into a life like this,” he said, leading into his presentation, Entrepreneurship Research for the Marketplace, at the 6th annual EDHE Lekgotla 2022, which Nelson Mandela University hosted in Gqeberha from 19 to 21 July.

“I started out in plant virology in 1981. I ended up getting into plant biotechnology,” said Professor Rybicki, who has been an NRF A-rated scientist – a rating given to researchers recognised by their peers as leading in their field – since 2011. He spoke remotely from his Cape Town base.

From useless to useful patents

When he moved into plant biotechnology in the 1990s with his colleague, Professor Jennifer Thomson, they thought they would create something useful. So, they made virus-resistant tobacco. “It turned out to be probably the most useless patent we ever took up,” he said.

Then he had an NRF “intervention”, as he put it, in his research in 1999 when they took his funding level from a couple of R100 000 rand a year to 1/10th of that, before reducing it to zero, in two years. His wife, Professor Anna-Lise Williamson, “a very practical person”, he said, suggested he do something useful. “So, I married plant biotechnology and human biology and got into vaccines via the South African AIDS Vaccine Initiative and the Innovation Fund so that the next set of patents were HPV (Human Papillomavirus, some of which can cause cancer) and HIV vaccines.

The unit that creates hopeful monsters

This led to the formation of the Biopharming Research Unit at UCT, which now has patents on animal vaccines, enzymes, antibodies, and processes to do with technology. “It is research intensive. In other words, it’s early-stage biotechnology. It is also student centered. We train a lot of students, generate early-stage products — hopeful monsters, things that could end up being made by somebody, that we try and patent,” he said.

Funding ranges from the Strategic Health Innovation Partnerships (SHIP), an initiative of the South Africa Medical Research Council and the Department of Science and Innovation, through the private Poliomyelitis Research Foundation (PRF), which funds virology research, to foreign companies such as Medicago from Canada and Zip Solutions from Spain — “the kinds of people you meet by presenting work at foreign conferences”, he said.

His Unit’s aim is to make high value biologics and reagents in plants for sale to industry, that is, complicated biological compounds that could be used as therapies or vaccines or reagents. They also potentially provide a service for researchers wanting small amounts of protein and transfer technology and expertise to manufacturing partners, to eventually make reagents, vaccines and therapeutics for animal, and then human disease agents.

You cannot sell what you haven’t protected

“Why and how do we do these things? We had a really good idea. We did some nice research and ended up with a product. And you might earn money for yourself, your group, and the institution because that’s how our South African patent law works. Your invention may actually be used,” said Professor Rybicki.

But he cautions: “Did you talk about it? Nobody else will want it if it isn’t protected and it is disclosed”.

The university’s role

Researchers generate research and UCT spins out companies to leverage the UCT-generated intellectual property (IP), which it licenses through its Research Contracts and Innovation office (RC&I). Professor Rybicki has been working with the office for 25 years, and, together, have built a good relationship. “We now understand what they want; they facilitate us getting that out into the universe,” he said.

Their spin-out company is called Cape Biopharms, a plan-based production platform which makes a variety of recombinant proteins for biomedical research. Initially it focused only on commercialising Professor Rybicki’s research unit’s biotech, but it has now become entrepreneurial in it is own right and has expanded rapidly. They make plant-made proteins by hydroponic vertical farming and contributed to the making of approved CoViD-19 rapid diagnostic test kits.

The Biopharming Research Unit has generated 17 patent families, about 47 issued patents, all except two done by UCT.

The snobbery around applied vs pure research

Professor Rybicki said applied research is a swear word among certain people. “People in the ivory towers on the hills like UCT, look at you and say ‘but you’re doing applied research, not pure research’. Who gets money to do pure research, today?” he asked.

He said the snobbery about it is phenomenal but incorrect because you can publish really good work out of applied research, which alerts people to what you do, and then patent it. Industry or bodies such as the Technology Innovation Agency (TIA) provide funding. Patenting it involves writing it up like an academic paper and submitting it with a disclosure form to the university’s IP office.

The secret is not to publish the research or even talk about it in public until it has been protected.

Life after the patent

Professor Rybicki does not paint a picture of instant glory after patenting a product. He said getting a patent can mean committing to a several-years-long project of seeing the same thing again and again. “And again, it goes to different countries for registration as a patent because different patent attorneys take issue with the same thing, or different things, in different countries. So, you end up seeing the same work over, possibly, 15 years.”

For an incentive, at UCT, researchers get an inventor mug, and the RC&I Office takes a photograph to honour the achievement, he said, displaying on a PowerPoint slide, a picture of his, holding his novel coffee cup in November 2010. But of even bigger value is the licensing income generated. “This is a very under-appreciated mode of exploitation of intellectual property,” he said. He showed another slide, of licensing income at UCT, between 2001 and 2013, where in 2010 the income jumped by R3-million in a single year. “That was one patent from our lab, licensed by a big multinational pharma company that brought in one big chunk of money and then yearly tranches of money after that, until they actually gave the patent up,” he said.

That type of patent had an interesting trajectory, he said. The company gave up the patent for papilloma virus research because it was too restrictive for them. It was promptly taken up by Medicago from Canada for another six years at least until they stopped funding it as well. “But we got 10 years of licensing income from a patent that nobody ever made a vaccine out of — something that we can’t do in South Africa. Because we don’t have the facilities to make the vaccine, we’re having to license this sort of thing outside of the country. That, hopefully, will change very soon,” he said.

What UCT’s Biopharming Research Unit patents

“There’s money coming in for molecular biotechnology in Africa right now that may completely revolutionise the face of science in Africa,” he said of the type of research they do.

The Unit engineered resistance in maize, making GMO (genetically modified organism) maize for maize streak virus, which he said is “the single most important viral pathogen in Africa”. It took them 20 years to do, and “ended up big, getting money from industry to research making transgenic plants”. The unit also published good papers on it, referring particularly to one by the lead researcher Dionne Shepherd, Maize streak virus-resistant transgenic maize: a first for Africa, published in the Plant Biotechnology Journal in August 2007.

It was patented, funded by and licensed to one company, then taken over by another, which decided it was an African disease and too small for their interest. “So, it sits on the shelf again. But it’s still there. We retain IP for people to license if and when they have interest in developing this in Africa, for Africa,” he said.

In the last 20 years, some of their patented research relates to human papillomavirus (HPV) proteins, avian influenza, human rotavirus proteins, bluetongue virus proteins, African horse sickness proteins, beak and feather disease virus for parrots, and various antibodies.
“It is a specialised field that we got into, 25 years ago, and we’ve managed to progress every year, with a large team of people. We have generated good international collaborations, a fantastic crop of PhDs, postdocs and technicians, thanks to The Good Wife who told me originally to do something useful,” said Professor Rybicki.

Q&A

This is an edited account of the discussion.

Professor Keolebogile Motaung (left), Director: Technology Transfer and Innovation, Durban University of Technology, who facilitated the session, asked: I see that three of your patents are for the SARS (severe acute respiratory syndrome) virus, caused by a coronavirus. Is that for CoViD-19? When was this licensed, given the stress there was about a CoViD vaccine? What is the situation, regarding this vaccine?

Professor Rybicki: The main problem with South Africa and vaccines is that we have no facility to manufacture them, other than the Biovac Institute in Cape Town for one very specific kind of bacterial vaccine. There is no other vaccine manufacturer. The CoViD-19 vaccine originating from South Africa is under licence to someone else.

We have been exploring ways to produce vaccines in a plant setup which we’ve been trying to get established for about 15 years. It might now be possible to make small batches of vaccines in South Africa using plant-based technology, with hopefully some expansion because it is one of the easiest things to scale up. We can’t divulge who we are licensing to, yet, but once that materialises, they will gear up to do full-scale manufacturing in Cape Town by the end of next year, hopefully using some of our technology to get off the ground.

Gillian Anstey is a contract writer for Universities South Africa.

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