The IP Picture for iPS Cells
(as published in BIO IT World)
The regenerative medicine field has seen an intense effort in recent years to find new strategies for creating stem cells without the use of embryos. An exciting recent advance has been the generation of induced pluripotent stem (iPS) cells which are derived from somatic cells, rather than embryos, through a process of “de-differentiation.” The ability to reprogram somatic cells into pluripotent stem cells, which in turn can generate virtually any cell type, opens the door to customized therapies using a patient’s own cells.
The first reports of iPS cell derivation, published in 2006 and 2007 by the groups of Shinya Yamanaka, Rudolf Jaenisch (Whitehead Institute), and James Thomson, involved the overexpression of four transcription factors: Oct4 and Sox2 with either Klf4 and c-Myc (in mouse cells) or with Nanog and Lin28 in human somatic cells. Numerous reports since then have expanded upon these seminal findings, using normal and diseased somatic cells as a starting source. Not surprisingly, several biotech companies are attempting to commercialize iPS cell technologies. These include iPierian which has a formal collaboration with Yamanaka; Fate Therapeutics which was co-founded by Jaenisch; and Cellular Dynamics International, which was co-founded by Thomson.
The relative technical ease and the robustness of iPS cell generation methods suggest that the technical and cost barriers to market entry may be relatively low. For this reason, effective intellectual property (IP) protection will be more important for successful commercialization than in some other fields. A handful of groups are vying for the first and, more importantly, the broadest patent protection typically awarded to pioneers in a nascent technology. Some of the first iPS cell patents have already been granted in the US, Japan and the UK.
The first iPS cell patent, Japanese Patent 2008-131577, based on Yamanaka’s work, was issued to Kyoto University on September 2, 2008. The patent claims priority to December 2005 and covers iPS cell generation methods using reprogramming factors. Similar subject matter is being pursued but has not yet been patented in the US or Europe.
A second iPS cell patent, UK Patent 2450603, based on the work of Kazuhiro Sakurada, was issued to iPierian on February 10, 2010. The patent claims priority to June 2007 and covers iPS cell generation methods using the reprogramming factors Oct4, Sox2, and Klf4, but not c-Myc. (Myc-independent reprogramming methods reflect an improvement aimed at reducing the risk of tumor formation from iPS cells, therefore making iPS cells more clinically attractive.) Similar subject matter is being pursued but has not yet been patented in Europe and Australia. Both of these patents took advantage of relatively recent “fast-track” prosecution routes in Japan and the UK.
A third iPS cell patent, US Patent 7,682,828, based on the work of Jaenisch, was issued to the Whitehead Institute on March 23, 2010, and is exclusively licensed to Fate Therapeutics. This patent claims priority to November 2003, predating the first published reports of iPS cell generation by almost three years. It covers compositions of somatic cells that harbor an exogenous reprogramming factor and a selectable marker under the control of an endogenous “pluripotency” promoter such as an Oct4 or Sox2 promoter. Such cells may be useful for the identification of new reprogramming factors that co-operate with or replace known factors.
The commercial value of patents related to regenerative medicine will hinge on what ultimately proves to be clinically efficacious. The rapidly evolving iPS cell field continues to advance as groups vie to develop and identify the most clinically efficacious and robust methods and compositions. For example, the first-generation transgenic methods discussed above have been replaced with protein transduction methods or substitution of reprogramming factors with chemical compounds. Other groups have generated neuronal and pancreatic cells through a process of “trans-differentiation”, which involves expression of factors from differentiated, rather than pluripotent, cells and presumably does not require de-differentiation to a pluripotent stage. At first glance, these methods and their resultant cells would not appear to be encumbered by iPS cell patents requiring expression of exogenous early, rather than late, factors and transition through an immature, pluripotent state.
It remains to be seen which of the known stem cell types will be the most clinically successful and whether any one stem cell type will be universally applicable. Consequently, it is also unclear which of the related patents will be the most commercially valuable. However, the intense interest in this field and the resulting fast-paced technological advancements will generate new IP niches that will in turn be exploited commercially by existing or new players.