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13 January 2014Americas

Cellular Dynamics: cells to order

In 2007, researchers discovered how to create human stem cells from adult human tissue, tackling one of the key controversies surrounding stem cell research by eliminating the need to use human embryos.

Any type of human cell can be created from these human donor-derived induced pluripotent stem (iPS) cells, which can aid in drug development and discovery by allowing researchers to study disease function and medical efficacy in vitro.

Wisconsin-based biotechnology firm Cellular Dynamics International uses iPS cells to produce different types of human cells to defined specifications on an industrial scale, which it offers to pharmaceutical companies in the business of drug discovery.

Drug discovery

“Human cells are the best tool that has ever existed for drug discovery,” says Nicholas Seay, vice president and chief technology officer at Cellular Dynamics.

“They will decrease the use of animals and animal cells as surrogates because the ability to make human cells gets you much closer to natural human biology.

“When you’re making a drug you want it to work in the cells of a human, not in the cells of a mouse, dog or pig. Therefore the availability of a whole suite of human cells that have the appropriate biology for human cells makes drug discovery much more relevant, much more likely to work and much less likely to have toxicity,” he adds.

Cellular Dynamics holds a portfolio of about 700 patents, both in-licensed and proprietary, and works with research institutions around the world to develop new technologies. Seay’s role is to ensure that all the products Cellular Dynamics sells have freedom to operate, which in this space, he says, is “quite a complicated and expensive undertaking”.

“We worry about IP protection every day,” he says. “We have invested a lot of money in obtaining all these licences and making sure that when we sell a product our customers have the freedom to operate with it.

“We do this so that if a pharmaceutical company buys cells from us and uses them in drug discovery there is no-one around that can come against them and make a claim. That’s very important to a company discovering or working on developing a potentially valuable drug.”

When Cellular Dynamics embarks on making a new cell type, it conducts a technical survey to determine what is known about the cell type, adopts a methodology to make the cell, and then carries out a patent search to find out who has filed what in that methodology.

“We then go to the owner of the technology, usually an academic institution, to ask for a licence. In most cases so far we’ve been able to obtain what we need from the academic institutions, but there’s a cell type or two that we may have to have creative solutions for,” Seay explains.

Cellular Dynamics holds 120 patents, both domestic and international, including those pending and issued, and in total owns and licenses 700 patents that cover cells as well as methods for making, programming, differentiating and engineering them.

In October 2013, it received two US patents, one covering a method of producing iPS cells and another relating to a method by which iPS cells are differentiated into various types of blood vessel cell and blood cells. The company received a total of five patents last year, although it takes care to use any type of IP that is available to protect its innovations.

“At Cellular Dynamics we’re cognisant of IP and have been from the beginning. Everything and anything that’s available we use,” says Seay. “A large amount of our ability to do what we do resides in knowhow, and trade secrets. We have elaborate standard operating procedures and manuals for everything we do which are maintained as trade secrets and embodied in how our people do things.”

“We have invested a lot of money in obtaining all these licences and making sure that when we sell a product our customers have the freedom to operate with it.”

Seay brings his expertise from the Wisconsin Alumni Research Foundation (WARF), where as a patent attorney he helped establish the foundation’s human embryonic stem cell IP portfolio. While at WARF, Seay met University of Wisconsin-Madison researcher and Cellular Dynamics founder James Thomson, who isolated the first embryonic stem cells in 1998.

Cellular Dynamics also works with other research institutions. “There are technical collaborations and there’s IP tech transfer,” he says.

“On the IP tech transfer side, you could say we’re working with everybody. We didn’t get to 700 in-licensed technologies by sitting by ourselves. We work with major research institutions in the US, Europe, Canada and Japan.”

Stem cell challenges

Stem cells can be tricky to work with, presenting challenges to Cellular Dynamics’ licensing efforts. “If you’re not extraordinarily careful, the different way you handle the cells can yield different results,” Seay says.

“It’s not at all uncommon for people to be unable to reproduce work reported by others, when it turns out they did all the same things but they started with cells that were a little different in how they were cultured from the beginning.”

He says Cellular Dynamics is extremely rigorous in checking the technologies before establishing a licensing agreement. “While we in-license many technologies, we do not do in-license until we have seen evidence that the technology works in our hands on our platform with our cells.”

In the lab, Cellular Dynamics’ technicians must differentiate a lineage from the stem cells, then repeatedly make a large number of differentiated cells from them over a long period of time, ensuring the cells meet the same technical specification every time.

However, the iPS cell’s capacity to expand indefinitely has its advantages: “You can make as many stem cells as you want and then use them to make whatever cell type is of interest to a potential customer,” Seay says. “Our manufacturing ability is in theory, and in practice, virtually unlimited.”

Future applications

Cellular Dynamics is currently developing new tools for drug discovery, and is looking towards a time where iPS cells can have therapeutic uses. While there is an “adoption curve” with new technologies, Seay says that some Japanese companies are already planning clinical trials for iPS-derived cells, and he thinks it won’t be long before trials are underway in the US and Europe.

There has been some very speedy adoption of the technology, he says: “It’s amazing—the first human iPS cells were reported in the literature in November 2007, and we had iPS cell-derived human heart cells on the market at the end of 2009.”

He hopes the tools Cellular Dynamics is developing will introduce a new era of disease treatment, adding that there could be many other applications for Cellular Dynamics’ technology in future in the chemical space, with toxicity and environmental impact testing, as well as in food development. Interest is already picking up in this area—in January 2014 the firm signed a supply agreement with the Nestlé Institute of Health Sciences.

Cellular Dynamics now has 12 various cell types on offer, including heart cells, liver cells and neurons, and makes a variety of special cell types for customers who want a particular cell engineered in a particular way. Seay says there are many other types of human cell to explore.

“Wikipedia states there are 208 cell types in the human body. That’s probably an underestimate,” he says.

Meanwhile, the firm is working on a bank of cells derived from HLA homozygous individuals, people whose cells are suitable for transplantation in a larger number of patients without fear of rejection. “Right now we’re the only enterprise we’re aware of that is moving that direction,” Seay says.

“We like to think we’re laying the groundwork for ultimate clinical use of iPS cells to treat human disease. That day is not as far off as some may think.”