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iZumi Bio's Pact with Kyoto U May Help Bolster Firm's Position as Early Leader in iPSC Tech

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California-based biotech startup iZumi Bio said last week that it will collaborate with Kyoto University's Center for iPS Cell Research and Application to explore using induced pluripotent stem cells to develop new drug-discovery tools and cell-based therapies, particularly in the area of neurological disorders.

The announcement comes approximately one month after iZumi acquired from German pharma giant Bayer rights to what it believes to be a seminal patent application related to methods for inducing pluripotent stem cells. The deal also follows by about a year iZumi licensing from San Francisco's Gladstone Institutes certain patents related to the use of iPSCs in cardiovascular disease as part of a research partnership between the two organizations.

Kyoto University also was awarded a patent in Japan last September related to inducing PSCs from human cells. It is widely considered to be the first such patent awarded in the world, though it is predated by Bayer's iPSC application in Japan.

iZumi does not have a license to that patent, and last week's agreement with the Center for iPS Cell Research and Application, also known as CiRA, does not necessarily imply that it will obtain one, iZumi CEO John Walker told BTW last week.

"It's truly a collaboration between the two entities, and we haven't released any financial details from that standpoint," Walker said. "It is not research that one lab is conducting versus the other; it was intended to be a joint collaboration."

In addition, he said, there is no overlap per se between iZumi's collaboration with Kyoto University and its relationship with the Gladstone Institute or its licensing deal with Bayer.

However, the company, based in South San Francisco, Calif., does appear to be amassing pertinent IP and allying itself with key players in what is shaping up to be a complicated IP landscape surrounding iPSCs.

"You want to be careful trying to build your company only on IP," Walker told BTW. "It's important to have an ability to operate and continue to practice your science, and we believe we clearly have that."

According to Walker, iZumi was founded in 2007 as a culmination of discussions between Shinya Yamanaka, director of CiRA and professor of stem cell biology at Kyoto's Institute for Frontier Medical Sciences, and Beth Seidenberg, a partner at Bay Area life-sciences venture-capital firm Kleiner Perkins Caulfield and Byers.

Yamanaka, who also has a joint appointment at the Gladstone Institute, had been working with Seidenberg to identify commercial opportunities in the area of stem cells and regenerative medicine.

KPCB, along with Highland Ventures, co-led a $20 million financing round in iZumi last summer to specifically explore such opportunities based on breakthrough work that Yamanaka was conducting in iPSC induction.

Under the collaboration announced last week, iZumi and CiRA will exchange part of their representative human iPS cell lines derived by various methods. The organizations will conduct comparison and characterization studies independently, but will share their results to determine which methods produce the most appropriate iPS cell lines for drug screening and development, and those most suitable for cell-based therapy, they said.

iZumi and CiRA said that they are able to take skin cells from a diseased patient with known genotypic and phenotypic information and reprogram the cells to behave similarly to human embryonic stem cells. The iPS cells can then be changed into various cell types using directed differentiation, they said, and transformed into cell-based, disease-specific assays to identify small molecules, biologics, or other agents for drug discovery.

"We are moving forward with the application [of iPSCs] to drug discovery and development," Walker said. "We're really looking at driving [the technology] more aggressively downstream to [create] cell-based disease phenotypes that would replicate as much as possible human disease in an assay form, and allow us to … shift the way that drug discovery is done to using patients at the front of the cycle."

In a statement issued last week, former US Vice President Al Gore, who is a partner at KPCB, endorsed the collaboration. "Stem-cell research holds great promise for the creation of new therapies that could revolutionize the treatment of disorders such as Parkinson's disease, diabetes, and muscular dystrophy," Gore said.

"The discovery that iPS cell technology brings — that 'stem-cell like' cells can be generated from a small amount of human skin rather than from embryos — opens a new door for stem cell research and its application to therapeutic discovery," Gore added.

Walker said that iZumi's collaboration with CiRA will initially focus on three neurological disorders: Parkinson's disease, spinal muscular atrophy, and amyotrophic lateral sclerosis.

Last June, the company also said it had established a research collaboration and licensing agreement with the Gladstone Institute, in which iZumi is partnering with the laboratory of Deepak Srivastava to investigate using iPS cells to develop discovery assays and treatments for cardiovascular disorders, in particular calcific aortic valve disease.

Who Owns the IP in iPSCs?

Yamanaka's lab will be at the center of the iZumi-CiRA collaboration. In 2006, Yamanaka and colleagues successfully induced iPS cells in mice using four transgenes delivered into fibroblasts via retroviral vectors, which was widely believed to be the first work of its kind.

In November 2007, Yamanaka's lab reported that it had also generated human iPS cells — as did human embryonic stem-cell pioneer James Thomson at the University of Wisconsin-Madison, who was able to generate similar cells using different genetic factors.

The breakthroughs, which were published in the same week, immediately prompted the scientific community to explore how the technology might be used in developing drug-discovery tools and cell-based therapeutics, as companies such as Cascade LifeSciences and Fate Therapeutics announced that they had begun amassing university IP for exactly that reason (see BTW, 12-3-2007).

The announcements also ignited immediate debate over which organization would control pertinent intellectual property surrounding the method for human iPS cell induction — a debate that was intensified last September when Japan used a fast-track procedure to grant Kyoto University a domestic patent on human iPSCs based on Yamanaka's work.

However, in June 2007, unbeknownst to most of the general public and scientific community at the time, Bayer's Japanese branch had applied for a patent in Japan to protect a technique that can generate iPSCs based on the work of then-employee Kazuhiro Sakurada.

The Bayer patent application is still under review in Japan and other countries. In the meantime, however, Yamanaka made Seidenberg and others at iZumi aware of Sakurada's work, Walker said, and last month iZumi licensed the IP portfolio from Bayer, betting on the idea that it may become the seminal IP in the field.

"What I think people are not aware of is that a pharma company such as [Bayer], where this work was done, usually doesn't publish quite as quickly as would an academic institution," Walker said. While Bayer did not publish Sakurada's work, it did file patents on it, and it is those patents that have been assigned to iZumi, he added.

"We feel we have some very important precedent to [Yamanaka and Thomson's] work, and it really became the founding IP of the company," Walker said. And with the CiRA research agreement, iZumi "also now believes that we have the lead in establishing the application of cellular reprogramming in a new paradigm for drug discovery and development," he added.

However, Walker cautioned that it is far too early to know who will end up owning the seminal iPSC patents, or whether such patents will even exist, as only Kyoto University has an actual patent in hand, and even then only in Japan. No related patents have been issued in the US and Europe.

"It's really hard to say who will prevail at the end of day," Walker said. "We are hoping to assemble as much IP as possible and …move the technology much further downstream in drug discovery, so we will establish new IP as we move our programs forward.

Walker added that because of the huge amount of work being done in the area of iPSCs, "you’re going to see a lot of IP created as a result. As to whether or not there will exist a patent similar to what [the Wisconsin Alumni Research Foundation] has been able to establish around human embryonic stem cells, for example, I don't know.

"But we do believe we will have a dog in that hunt if in fact that is part of what is argued out at some point," he added.

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