“The best and first application for iPSCs is really to change the paradigm of drug discovery”

The-Scientist.com, July 7, 2009, by Elie Dolgin  —    A decade ago, the United States granted a series of patents that some say changed the embryonic stem cell (ESC) field forever. The Wisconsin Alumni Research Foundation (WARF) received three broad patents related to a method for isolating human ESCs that was developed by James Thomson at the University of Wisconsin-Madison. These patents, which effectively covered all ESC lines regardless of who made them or how they are generated, were so far reaching, many critics argued, that they effectively put a stranglehold on the ESC field. Indeed, only one company-Menlo Park, Calif.-based Geron Corp.-has ever received approval from the US Food and Drug Administration to test ESC-derived products in the clinic. Companies working with ESCs “are walking on very thin ice right now,” says Jeanne Loring, director of the Scripps Research Institute’s Center for Regenerative Medicine in La Jolla, Calif., who founded the now-defunct ESC-based biotech company Arcos BioScience.

Not so for the field of reprogrammed embryonic-like stem cells known as induced pluripotent stem cells (iPSCs), which are created by turning the developmental clock back on adult or other specialized cell types through the use of viruses, plasmids, transposons, or other reprogramming factors. Now, “the pendulum has swung at the patent office toward very narrow patents” across most of biology and chemistry, says David Resnick, a patent lawyer with Nixon Peabody in Boston, Mass. “It’s extremely difficult to get a broad patent right now.” That means that no single company should obtain the same de facto monopoly over iPSCs the way WARF has for ESCs.

In the past year, more than 20 applications directly relating to iPSCs and another 50 or so involving iPSC culture methods or other indirect uses of the reprogrammed cells have been published worldwide, around half of these in the US alone. Many more patent applications have also been filed since then, notes Resnick.

IPSCs can also be tailor-made to match particular disease, ethnic, or other genetic profiles, and these cells do not require embryos-a continued source of debate. Together, all this suggests that the iPSC industry could prove much more fruitful than the ESC commercialization landscape. And because there are so many methods for obtaining iPSCs, “you have the opportunity for companies to spring up that will compete against each other to ultimately get to the same place,” says M. William Lensch, a senior scientist who studies iPSCs at Children’s Hospital Boston and the Harvard Medical School. “At the end of the day, the one that produces the best results and is the quickest and cheapest is the one you’re going to go with, and at this point it’s anyone’s guess” which company will reap the most rewards. But first, they must overcome the hurdles facing everyone as a young field strives to define itself in a wide-open space.

Induced Income

“The best and first application for [iPSCs] is really to change the paradigm of drug discovery,” says John Walker, chief executive of iZumi Bio, a South San Francisco-based biotech company focused on using reprogrammed skin cells from patients to screen for new drug compounds to treat neurodegenerative diseases, such as spinal muscular atrophy, amyotrophic lateral sclerosis, and Parkinson’s disease. “It replicates the in vivo system for your drug discovery system,” says Walker. “This is really new biology… that puts the patient at the front of the drug discovery process.”

iZumi was founded in 2007 by two venture capital firms based on three patents from Bayer Yakuhin, a Japanese subsidiary of the German chemical giant Bayer AG. In addition to these patents, iZumi has expanded its reach to include nonexclusive partnerships with Kyoto University’s Shinya Yamanaka, aimed at developing new methods for deriving high-quality iPSC lines, and with the University of California at San Francisco’s Gladstone Institute, primarily focused on developing cardiovascular therapies. Within 5 years, the company expects to have two compounds in clinical trials.

Wisconsin-based Cellular Dynamics International (CDI), which Thomson cofounded with two other UW-Madison scientists in 2005, is targeting a different market. Currently, the company sells ESC-derived heart cells to a select few large pharmaceutical companies for drug screening and predictive toxicology assays, but CDI is rapidly transitioning toward selling iPSC-based technologies, based on patents licensed from WARF and developed in-house. “We can now provide individual biology, disease models, retrospective analysis, and ethnic diversity to a portfolio where only one product would have existed” if they had stuck with only using ESCs, says Chris Kendrick-Parker, CDI’s chief commercial officer, in an email.

The ultimate goal, every company admits, is to transplant iPSCs into patients for clinical therapies. However, “transplantation therapy is far away,” says Rudolf Jaenisch, a leading iPSC researcher at the Whitehead Institute in Cambridge, Mass. “But for some cell types”-particularly blood cells, bone marrow, and insulin-producing cells-“it might be closer than others.” Even so, companies that develop the core scientific capabilities to enable the use and application of iPSCs should be “well positioned to support and capitalize on… future potential clinical applications of these exciting new cell types,” says Steven Munevar, president and CEO of Munevar & Associates, a life sciences development and commercialization company, in an email.

“It’s sort of the wild west. Everyone is just racing to develop their own technologies and it’ll have to be sorted out later on.”
-David Resnick

Several supply companies, however, are happy just to be enablers of the new technology. Big suppliers, including Invitrogen and Thermo Fisher (in partnership with Athens, Ga.-based ArunA Biomedical), are now offering “kits” tailored to perform cellular reprogramming. More specialized providers are also getting into the iPSC game. For example, Addgene, a nonprofit plasmid supplier in Cambridge, Mass., has distributed more than 6,000 reprogramming vectors to around 1,000 laboratories in the past 3 years alone. “We hand them the materials and then they’re on their own,” says Melina Fan, Addgene’s executive director.

“It’s a land grab at this time,” says Enal Razvi, a biotechnology analyst with Select Biosciences, a UK-based company that tracks life sciences market trends. “Investors are putting in small amounts of money to play a larger hand. They want to have a say at the table if and when iPSCs become a mainstay.” As a result, small biotechs are scooping up intellectual property left and right from academic researchers as well as tinkering with internal methods, which are also being patented, in the hopes of taking an early dominant position.

The IP of iPSCs ……click here to finish reading this article.. http://www.the-scientist.com/article/display/55783/

Warren Sherman, M.D., F.A.C.C., F.S.C.A.I. is Associate Professor of Clinical Medicine at Columbia University College of Physicians and Surgeons and Director of Cardiac Cell-Based Endovascular Therapies at the Center for Interventional Vascular Therapy at NewYork Presbyterian Hospital/Columbia University Medical Center.


Dr. Sherman earned his Bachelor of Science degree at Massachusetts Institute of Technology

and medical degree at the State University of New York, Upstate Medical Center. Following an internal

medicine residency at the University of Rochester, he spent three years at the Oregon Health

Sciences University as a fellow in cardiovascular diseases, where many of the cardiac procedures that

form the foundation of modern interventional cardiology originate.

In 1983, Dr. Sherman moved to Mount Sinai Hospital in New York to investigate new techniques

for treating patients with acute myocardial infarction. It was at that time that the first thrombolytics

(clot-dissolving medications) were being evaluated in patients. In 1989, he shifted to a fully clinical

role, and created the Interventional Cardiology Program at Beth Israel Medical Center in New York City.

With a deepening interest in myocardial regenerative techniques, Dr. Sherman pioneered

a technique for injecting stem cells into the heart. In Rotterdam in May 2001, he performed the first

catheter-based injection of adult stem cells into the heart of a patient with congestive heart failure

due to a previous heart attack. This technique was then brought to the U.S., where he performed

a similar procedure at Mount Sinai Hospital in April 2003. As Director of Cell Therapy at Mount Sinai

Hospital, Dr. Sherman was the principal investigator of a multicenter clinical study of autologous

skeletal myoblast injections for patients with congestive heart failure and the lead investigator on

numerous translational studies. Dr. Sherman has authored or co-authored numerous publications in

the emerging field of myocardial regeneration.

Center for Interventional Vascular Therapy

at NewYork-Presbyterian Hospital/Columbia University Medical Center

Center for Interventional Vascular Therapy

(212) 305-7060 • (212) 342-3660 (fax) • ws2157@columbia.edu



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