Cellular Dynamics and Mount Sinai Sign Licensing Agreement

GenomeWeb.com, May 29, 2009

Cellular Dynamics International (CDI), the startup company formed by Dr. James Thomson of the University of Wisconsin at Madison, has signed a licensing agreement with Mount Sinai Medical School in New York City.

The exclusive licensing agreement will allow CDI to produce cardiac cells with technology that was originally developed by Dr. Gordon Keller, who served as a professor of gene and cell medicine at Mount Sinai School of Medicine (MSSM) from 1999 to 2006, and after whom the Keller Laboratory at MSSM is named. Currently Dr. Keller directs the McEwen Centre for Regenerative Medicine at the University Health Network in Toronto. The license will allow for the differentiation of human pluripotent stem cells into cardiovascular progenitor cells which can then be further differentiated into more specialized cell lineages such as cardiomyocytes, endothelial cells and vascular smooth muscle cells. The various cardiac cells would then be used for pharmacological drug screening.

CDI, which Dr. Thomson and 3 of his colleagues founded in 2004, has already been selling heart cells to Roche and a number of other pharmaceutical companies for the toxicity testing of drugs. This new licensing agreement significantly increases CDI's patent portfolio.

This is not the first licensing agreement between CDI and an academic institution, although it is the first that CDI has formally disclosed. The agreement is considered to be unique in a number of ways, not the least of which is its exclusivity, a condition which is rarely granted by academic institutions and which is thought to have cost CDI consideraly more than a nonexclusive licensing agreement would have cost. A senior representative of CDI indicated that the announcement of further licensing agreements could be expected in the near future.

According to Dr. W. Patrick McGrath, executive director of MSSM's Office of Technology and Business Development (OTBD), "The Mount Sinai School of Medicine is pleased that CDI has selected MSSM's technology for the production and use of cardiomyocytes and other cardiac cells. OTBD believes that CDI is well qualified to take the final steps to commercially develop MSSM's translational research into products and services that will benefit the drug development process and, ultimately, cardiac patients worldwide."

As Chris Kendrick-Parker, chief commercialization officer and one of the vice presidents of CDI, adds, "We believe that CDI's pluripotent stem cell technology will be the pharmaceutical industry's platform of choice for identifying drug candidates and their probability of success in predictive toxicology. This exclusive license provides CDI complete freedom to operate in our quest to efficiently and effectively produce and provide cardiomyocytes and other cardiac cells for screening purposes. Furthermore, this license strengthens our growing patent portfolio and makes us a preferred collaborator and provider to pharma and biotech companies developing predictive toxicology tools to aid the industry."

As Dr. Thomson has often explained in the past, the most immediate application of pluripotent stem cells is not so much in cell-based therapies for the treatment of actual diseases and injuries, but rather in drug testing and development. Until a number of scientific obstacles are overcome, merely one of which is the danger of teratoma (tumor) formation, pluripotent stem cells carry too many risks to be used as actual clinical therapies. Pluripotent stem cells include not only embryonic stem cells but also the more recently developed iPS (induced pluripotent stem) cells, which, by official definition of pluripotency, are required to form teratomas. Adult stem cells, by sharp contrast, which are multipotent instead of pluripotent, do not, by definition, carry any risk of teratoma formation.

As Mr. Kendrick-Parker further explains, "This gives us multiple methods to arrive at the end goal of making fully functional terminal tissues from pluripotent cells, and really gives us the freedom to operate through a variety of methods to generate large quantities of cardiomyocytes as a tool. We've tried to basically create a portfolio of patents that allows us to use the most efficient means necessary to arrive at those cell types, and to have choices to arrive at the best population of cells for our customers. This helps us make sure that we have a marked advantage in this area, and that our customers know that when they do business with us they are unencumbered."

Curiously, a certain amount of ambiguity seems to have been built into this news announcement, as neither this nor other related news articles specify the exact source of these newly generated cardiac cells. In other words, nowhere was it mentioned whether the cardiac cells are to be generated from human embryonic stem cells (hESCs) or from induced pluripotent stem (iPS) cells, the latter of which are of adult somatic cell origin. Similarly, the news announcement as posted on the website of CDI merely states that the newly generated cardiac cells are produced from "human pluripotent stem cells (hPSCs)", which could be either of embryonic or of adult cell origin, and even the company's official announcement also stops short of specifying the precise source of these hPSCs. However, a further examination of the description of "human cardiac cytotoxicity screening" on CDI's website reveals that these hPSCs are of adult, not embryonic, cell origin, as they are derived from iPS (induced pluripotent stem) cells, not from embryonic stem cells. More precisely, the CDI website displays the following statement: "CDI's cardiomyocytes are differentiated from hPSCs that are reprogrammed to their pluripotent state from adult cells, thus avoiding the controversial and ethical issues surrounding embryonic stem cells." This is further verified by Mr. Kendrick-Parker's statement that, "There are a lot of different institutions where we think if we can industrialize the process of making iPS cells, then there is a business to be had in the generation of those materials." Despite the fact that Dr. Keller's specialty is in the derivation of cardiovascular progenitor cells from embryonic stem cells, therefore, this particular licensing application of the IP that Dr. Keller developed would seem to be intended for cells that are of adult somatic, not embryonic stem cell, origin.

Such a point is not insignificant, especially in light of the fact that Dr. James Thomson, one of the founders of CDI and CDI's Chief Scientific Officer, is renowned throughout the world for having been the first person ever to isolate an embryonic stem cell in the laboratory, first from a nonhuman primate in 1995 and then from a human in 1998. Known as "the father of embryonic stem cell science", Dr. Thomson is credited with having spawned the entire field of embryonic stem cell research, and the mere mention of his name invokes sincere reverence from embryonic stem cell scientists throughout the world. Yet on numerous occasions, Dr. Thomson himself has emphasized the point that iPS cells hold greater medical potential than embryonic stem cells, and furthermore, unlike embryonic stem cells, iPS cells are created from adult somatic (ordinary, non-stem cell) cells, and are therefore derived without the need for embryos at all. In fact, Dr. Thomson and his colleagues in his laboratory at the University of Wisconsin at Madison were also co-developers of iPS cell technology, although this fact is often overshadowed by Dr. Thomson's earlier, more dramatic pioneering work in embryonic stem cell research. However, the fact that CDI is now investing so heavily in research that involves iPS cells, not embryonic stem cells, is further evidence for the greater medical usefulness and commercial priority of iPS cells over embryonic stem cells. Why, exactly, this rather crucial and fundamental point was never explicitly clarified in any of the news announcements, however, is anyone's guess.

CDI has plans that extend beyond cardiovascular progenitor cells, as Mr. Kendrick-Parker explains that the company is developing projects "for a variety of different cell types that run the gamut of tools that are required for pharmacology and toxicity testing." Still, however, the final goal of CDI's stem cell R&D, regardless of the specific types of cells that are involved, is for purposes of drug screening - and the profitable commercialization of drug screening tools - not for the development of cell-based clinical therapies.

Specific terms of the licensing agreement have not been disclosed.