Israeli drug developer Protalix Biotherapeutics has licensed technology for producing acetylcholinesterase and variants thereof in plants for a variety of therapeutic and preventative applications from the Hebrew University of Jerusalem and Cornell University’s Boyce Thompson Institute for Plant Research, Protalix said last week.
Hebrew University stands to reap the most financial reward from the deal because it has an ownership stake in all the pertinent intellectual property, while BTI is only an assignee on one core patent. In addition, Hebrew University will be involved in developing future Protalix products based on the technology, officials close to the deal said last week.
Under the terms of the agreement, Protalix has licensed a portfolio of patents related to methods for producing the mammalian enzyme acetylcholinesterase, or AChE, in transgenic plants, from Boyce Thompson and from the Yissum Research and Development Company, the tech-transfer arm of Hebrew University.
The core patent, US No. 6,770,799, entitled “Expression of recombinant human acetylcholinesterase in transgenic plants,” resulted from collaborative research between scientists at both institutions and thus is owned by both.
In addition, Protalix licensed several patents that stemmed from research conducted solely at Hebrew University, and thus fell under the authority of Yissum.
Hermona Soreq, dean of the faculty of science at Hebrew University and the only inventor common to all of the licensed patents, characterized and cloned genetically engineered versions of the AChE gene in her lab in the early 1990s.
More recently, Soreq’s lab published several scientific articles related to the activity of AChE genetic variants, which is what piqued Protalix’s interest in licensing the technology.
It’s a natural variation [of AChE],” Soreq told BTW last week. “We’ve cloned the AChE gene and demonstrated that it undergoes splicing, and under various disease and stress conditions it produces this particular variant that appears to be associated with a boost in the proliferation of blood cells needed under certain diseases — the brain’s reaction to traumatic conditions, for instance; or protection from organophosphate poisoning.”
Meanwhile, a few years ago Soreq’s lab collaborated with Charles Arntzen’s lab at Boyce Thompson. Arntzen, who is well-known for his work producing mammalian cells in plant systems, also worked on the project with his postdoc Tasfrir Mor, who earned his PhD at Hebrew University.
Soreq said that Hebrew University sent Boyce Thompson the various molecules and genes associated with AChE, and Arntzen and Mor developed a method for producing the protein in plants.
Protalix, based in Carmiel in northern Israel, is focused on developing recombinant therapeutic proteins that it expresses and manufactures through its own proprietary plant cell-based expression system. Thus the work being done by Soreq and colleagues was a natural fit for Protalix, Yossi Shaltiel, the company’s executive vice president of research and development, told BTW last week.
“We were trying to locate several new projects, and we obviously went through all the companies that are attached to the universities in Israel,” Shaltiel said. “During this search, we found this project, and they had already showed feasibility in plants, which is similar to our system, so it was a good fit.”
Protalix’s main therapeutic candidate is a recombinant protein for enzyme replacement therapy in Gaucher disease. The deal with Hebrew University and BTI is a bid to expand its therapeutic pipeline and even enter new markets, such as biodefense, according to Shaltiel.
“Biodefense is really the first application,” Shaltiel said. “It is really simple to develop and we understand that. The other applications will be a lot more complicated and take some more time.”
Soreq agreed that biodefense was “probably the most immediate need and immediate justification of financing,” but added that she believes Protalix’s platform combined with her lab’s technology holds great promise in a variety of application areas, primarily because of AChE’s role in the human nervous system.
Soreq said that the protein’s potential application in treating organophosphate poisoning is also a very important goal.
“We have shown that this protein seemingly has an advantage over anything else that was tried before,” to treat organophosphate poisoning, she said, adding that organophosphate poisoning is common because of the use of insecticides, and “is a threat because of terrorism and nerve gasses that are used in war.”
“Hebrew University [has] a lot of expertise in this area, though, and we will obviously use it.”
Soreq also said that the protein in its natural form is extremely scarce, “so there is little hope to produce it from any natural source. Plus, you don’t want to pull these human proteins from natural sources because of the contamination danger. Working with Protalix is a great opportunity, and I’m very pleased.”
Financial terms of the agreement were not disclosed. However, Soreq confirmed that she would receive royalties on future products based on the licensed IP.
In addition, Hebrew University and Soreq stand to gain the most from the deal because they are both named as inventors or assignees on all of the pertinent patents, and because Protalix and Hebrew University will continue to collaborate on the development of potential therapeutic or preventative products based on the licensed technology.
“Further development will be done with Hebrew University, but likely [not with] Boyce Thompson,” Protalix’s Shaltiel said. “The research will be done in Protalix’s labs. Hebrew University [has] a lot of expertise in this area, though, and we will obviously use it.”
Nava Swersky Sofer, president and CEO of Yissum, told BTW that Yissum stands to gain the most from future product royalties, although that figure was “hard to quantify at this time” because of the multiple-market potential of the AChE technology. Sofer declined to comment on which of the various markets had the most potential.
Sofer also said that in 2006, Yissum had total revenues of $40 million, $30 million of which were due to royalty payments and licensing fees. The remaining $10 million was a result of industry-sponsored research.
Boyce Thompson, which is an affiliate of Cornell University, certainly has a smaller stake in the deal, but any financial benefit it receives will be independent of Cornell.
“We’re an affiliate, technically speaking, but we’re also a separate entity with our own separate endowment,” Paul Debbie, director of the Center for Gene Expression Profiling and manager of patents and licensing at BTI, told BTW. “But we’re not a subsidiary of Cornell. The IP that I manage here is solely BTI IP.”
Debbie added that BTI at times does have IP that overlaps with Cornell, because some BTI researchers have joint appointments at both entities. In those cases, Cornell is responsible for managing the IP.
BTI does not disclose its licensing metrics publicly. Debbie said that the deal with Protalix and Hebrew University is an example of how research with commercial potential can pay dividends several years down the road, even after that research has been curtailed.
“At Boyce Thompson, a lot of our research has been in the area of producing mammalian proteins from plant cells, but it’s not the focus of what we’re doing now,” Debbie said. “When Charlie Arntzen was here, we definitely had a lot of research on plant-based vaccines, and these are older IP that came from that era.”