By Kevin E. Noonan --
The sanctimony continues over the U.S. Patent and Trademark Office re-examination of the Thomson stem cell patents. This time, it is an article by Constance Holden in the April 13, 2007 issue of Science. Although refreshingly factual, it manages in ways both frank and subtle to create the (false) impression that stem cell patenting is a bad idea.
The primary alleged offenses are two: first, that these patents impede scientific research, and second that commercial licenses are too high. The first allegation is supported by complaints from scientists about the material transfer agreements (MTAs) associated with licensing stem cells covered by the Thomson patents from the Wisconsin Alumni Research Foundation (WARF). Although the article acknowledges that "[m]ost scientists doing basic stem cell research in academic or government labs are minimally restricted by WARF's current policies, which require them to pay only $500 for a batch of Wisconsin cells," the process is burdened by too much "red tape." (This allegation is preciously illustrated by a toll booth labeled "WARF" through which nonprofit researchers can pass, but they are festooned with said red tape.) These allegations ignore the fact that the agreement used by WARF was developed with the participation of the National Institutes of Health (NIH) and is consistent with (and in some ways, more lenient than) MTAs commonly used between university tech transfer offices. It also ignores the amount of time and effort WARF spends in training recipients of its cells, which are notoriously difficult to handle and propagate to retain their "stemness." Also unspoken is any acknowledgement that WARF's program (in conjunction with the NIH) has permitted stem cell scientists in federally funded laboratories to continue to do their work in the face of the Bush administration's restrictive prohibitions on stem cell science. Significantly, WARF imposes no restrictions on patenting or publishing the results of basic academic research.
Martin Pera (at right) from the University of Southern California complains that "WARF's grip on 'basic platform technology critical to the future development' of the field is bound to impede progress," but that hasn't stopped him from obtaining three of his own human stem cell patents: U.S. Patent Nos. 6,875,607; 7,011,822; and 7,112,437. These patents claim:
Claim 1 of the '607 patent: A method of modulating the differentiation of undifferentiated, pluripotent human embryonic stem (hES) cell in culture, comprising providing a fibroblast feeder layer which has been selected based on its ability to induce differentiation of undifferentiated, pluripotent human embryonic stem (hES) cells in culture, and growing said undifferentiated, pluripotent human embryonic stem (hES) cells on said fibroblast feeder layer, wherein said fibroblast feeder layer modulates the differentiation of said undifferentiated, pluripotent human embryonic stem (hES) cell in culture.
Claim 1 of the '822 patent: A method of transplanting human ES derived neural progenitor cells in into a host, said method comprising: obtaining undifferentiated or pluripotent human embryonic stem cells; culturing the cells in the presence of serum free medium supplemented with B27 and growth factors comprising EGF and bFGF to obtain neural progenitor cells comprising expressed markers of primitive neuroectoderm and neural stem cells; and injecting the neural progenitor cells into the central nervous system of the host.
Claim 1 of the '437 patent: A method of producing a human neural progenitor cell from a human ES cell, said method comprising: obtaining a source of an undifferentiated human ES cell; and culturing the ES cell in the presence of an antagonist of a BMP mediated default pathway of extra embryonic endoderm differentiation to differentiate the ES cell to a progenitor cell, wherein said progenitor cell lacks at least one marker of said undifferentiated ES cell; and culturing the progenitor cell in a neural progenitor cell culture medium to obtain a neural progenitor cell.
The owner of these patents, ES Cell International of Singapore, provides the same human embryonic stem cells provided by WARF, but at a cost of $6,000. Licensing terms for these patents and whether any licenses are available or have been granted are unknown, but the company is "underpinning its position in the stem cell biotechnology arena through aggressive implementation of its Patent and Intellectual Property Strategy" according to its website.
Predictably, the loudest complaints come from commercial interests, who cite licensing fees of (gasp!) "up to $400,000," according to Jonathan Auerbach of GlobalStem, Inc. (GlobalStem is reported to have avoided the Thomson patents by using stem cells having abnormal karyotypes.) Unspoken is the reality that these types of licensing fees are not particularly onerous for a commercial concern, particularly when licensing a patented reagent as potentially valuable as a stem cell. Also common are the types of "reach through" provisions for products made using stem cells contained in WARF's commercial licenses; since the commercial entities will typically be selling such products (be they 
biochemicals produced by the cells or differentiated cells or tissues made from stem cells), it would be unrealistic (and inequitable) for a company to obtain the cells for a simple licensing fee and insulate its commercial products from royalty obligations. Similar considerations apply to the complaints of Robert Lanza (at left) of Advanced Cell Technologies, Inc. (ACT), that WARF requires a $5,000 fee when ACT sells stem cells to third parties. Mr. Lanza ignores the fact that most MTAs preclude ownership, much less transfer, of the material by the licensee, or that ACT's cells benefit from being within the Federal government's stem cell ban as a result of WARF's provenance over these cell lines. (Unmentioned in the article is ATC's market cap
of $42M.) Mr. Lanza complains that WARF exclusively licensed the Thomson patents to Geron Corporation for certain indications, but gives no reason (because there really are no reasons) why this isn't a commonplace consequence of patent licensing.
The immediate fate of the Thomson patents will take at least until the end of the year, when the U.S. Patent and Trademark Office is expected to determine whether any of the Thomson patent claims are patentable after considering WARF's responses to the first round of Office Actions in both the ex parte and inter partes interferences.
For additional Patent Docs coverage concerning stem cells, please see:
- "It's Time to Stop the Hypocrisy over Stem Cell Patents - Part I" - April 17, 2007
- "WARF Stem Cell Patent Claims Rejected in Re-examination" - April 3, 2007
- "NIH Chief Dissents on Federal Stem Cell Funding Ban" - March 20, 2007
- "Stem Cells a Go! in California" - February 28, 2007
- "Limitations on the Usefulness of Adult Stem Cells" - February, 28, 2007
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