SLIDE Within the context of human ESCs biovalue as such is still highly prospective rather than real as embryonic-derived products are still, to use an appropriate phrase, in their infancy. Most as this slide shows relate to the use of hESCs as a source of tissue to test the toxicity of new pharmaceutical compounds, and indeed in the UK, the Medical Research Council and Department of health recently established the Stem Cells For Safer Medicine (SC4SM) programme to fund experimental work to do precisely this. I have listed some of the main centres internationally that are developing these sorts of techniques and products, including one just down the road in Redfern .
Within the context of hESC there have been some interesting developments. Here I make a number of important observations about patent activity we have found that reflects the intellectual property response of companies to the moral position taken by the EPO in Munich. The EPO does not make a distinction between embryonic cells as toti compared with pluri-potent. This means that cell lines are seen to be able to generate whole persons, not just specific organs. While in the US The United States Patent and Trademark Office (USPTO) has, to date, granted over 50 patents that claim human embryonic stem (hES) cells in their title and front pages. These include patents on culture methods, differentiated cells derived from hES cells and even hES cells per se . By contrast, the European Patent Office (EPO) has not granted a single patent that makes direct hES cell claims. This reflects the major constraints imposed by the European Patent Convention (EPC), which prohibits the patenting of the &quot;human embryo&quot; on moral grounds As I note here – despite the Federal constraint on hESC research in the US, ironically it is easier to get a patent there than in Europe. One other point to note is that we can see the emergence of patent thickets that serve to secure commercial monopolies in the area: WARF is trying t do this with new IPS cells.
This slide simply gives you an idea of patenting by private compared with public (university/research organisation) sectors, here a UK/US regional comparison. It is quite interesting to note that despite the long-standing complaint about British universities being entrepreneurially weak the proportion of patents they are filing is much higher than the US, though in absolute terms is still of a lower number of course.
SLIDE – Overall, as Bergman and Graff have recently argued, we can say that the patent landscape is highly complex. ‘ Stem cell lines and preparations, stem cell culture methods and growth factors show the most intense patenting activity but also have the most potential for causing bottlenecks, with component technologies expected to show high degrees of interdependence while being widely needed for downstream innovation in stem cell applications’. This complexity makes for real difficulties among firms trying to secure some niche in the market, especially smaller ones, who have to embark on a considerable amount of cross-licensing to be able to make any headway with their product.
Innovation and health technologies: celling science? Professor Andrew Webster, Director SATSU, University of York and of UK SCI KITE Seminar Series February 4 2009
‘ Skin replacement opens million dollar markets’ , Health Care Industry July 1992
‘ The firm's "conservative revenue model" predicted first-year Dermagraft sales of $37 million and 1998 sales of $125 million. An aggressive model estimated sales of $280 million by 1998.’ Market estimates for tissue-engineered products have been very promising, ranging from 80 billion € for the USA alone (MedTech Insight, 2000) to 400 billion € worldwide (Langer & Vacanti, 1993). More moderate estimates still calculated a global market of 3.9 billion € by 2007 (Business Communication Company, 1998) or of 270 million € by 2007 for skin products alone (MedMarket Diligence, 2002). The reality provides much lower figures with world-wide sales of tissue-engineered products probably not surpassing 60 million € in 2002. Source: IPTS, 2003
Current world-wide sales Total sales $1.3b Source: M. LYSAGHT et.al. 2008 (TE, vol 14)
Japan Tissue Engineering Co., Ltd. (J-TEC) Est: February 1, 1999 Capitalization: 5,543.45 million yen
The number of firms has remained stable over the last five years, but a high level of turnover
Sub-sectoral structure is slowly changing following shift to stem cells in early 2000s
Relatively mature, but problem with firm growth
Healthy number of products, but relatively poor sales apart from a few dominant ones
Narrow development pipeline
Few collaborations with large firms
The Gartner Curve Gartner ‘hype cycles’ are said to distinguish hype from reality, so enabling firms to decide whether or not to enter the market
Technology Push: Beginning the 2 nd Half of the Gartner Curve? Stage of Development Visibility Technology Trigger Peak of Inflated Expectations Trough of Disillusionment Slope of Enlightment Plateau of Productivity 1980 Early TE research (MIT) 1985 Term “TE” coined 1986 ATS & Organogenesis founded 1988 SyStemix founded 1992 Geron founded 1997 First cell therapy FDA approved (Carticel ) 1997 Dolly the sheep 1998 Human ESCs first derived 1998 Plan to build human heart in 10 years 1999 First TE product FDA approved (Apligraf) 1999 TE bladders in clinic 1999 Intercytex founded 2000 Time Magazine: TE No. 1 job 2001 Bush “partial ban” on HESCs 2001 Dermagraft FDA approved 2001 TE blood vessel enters clinic 2001 Ortec FDA approved 2001: 3000 jobs, 73 firms, mkt cap > $3B 2002 ISSCR founded 2002 ATS + Organogenesis file Chapter 11 2003 UK Stem Cell Bank set up 2005 CIRM founded 2006 Carticel - 10,000 patients 2006 hESCs derived without harming embryo 2006 Batten’s Disease trial 2006 Reneuron file IND for stroke trial 2007 Apligraf - 200,000 patient therapies 2007 Mouse fibroblast to mESCs 2007 Intercytex start Phase 3 ICX-PRO 2007 Osiris Named Biotech Co. of the Year 2008 Geron expected to file IND - spinal cord Synthetic Biology?? (Source: Paul Martin)
Patent applicants are going via national offices such as the UKIPO to file and secure patents on pluripotent lines, short-circuiting the EPO in Munich which conflates toti and pluri potent lines
So, ironically, it is much easier to obtain patent protection on hESCs in the US than in Europe.
Most recent data on stem cell patents reveals a dramatic growth in the number of stem cell patent applications suggesting the field is ripe for the emergence of a stem cells ‘patent thicket’ and blocking monopolies
Patents in hESC domain 25% 75% USA 47% 53% UK 31% 69% Globally Public sector Private sector
‘ The technical content of the patent landscape is highly complex. Stem cell lines and preparations, stem cell culture methods and growth factors show the most intense patenting activity but also have the most potential for causing bottlenecks, with component technologies expected to show high degrees of interdependence while being widely needed for downstream innovation in stem cell applications.’ (Source Bergman and Graff, Nature biotech 2007)
What were/are the difficulties faced by TE innovation?
What sort of business model: e.g. ‘product’ or ‘service’ based (akin to ‘cryovial products’ vs IVF clinic)
Allogeneic vs autologous therapies?
Different business models: Allogeneic products amendable to large-scale manufacturing at single sites Autologous therapies more of a service industry, with a heavy emphasis on local or regional cell banking.
Medical knowledge is much more than the appliance of science
Other forms of knowledge are key and are only produced in particular clinical settings e.g. experience of disease, routines and protocols, practice style, complementary technologies, assessment of cost-benefit