Patenting embyronic stem cells - influence of recent jurisprudence on (Belgian) stem cell research
Patenting embyronic stem cells - influence of recent jurisprudence on (Belgian) stem cell research
Patenting embryonic stem cells -influence of recent jurisprudence on (Belgian) stem cell research
Debaere, M1; Iserentant, D1,2; Pappaert, K3 ; Paemen, L3
1Ghent University, 2VIB, 3De Clercq & Partners
Abstract: In October 2011, the Court of Justice of the European Union ruled that procedures relating to human embryonic stem cells or human embryonic stem cell lines are excluded from patentability if they required the destruction of a human embryo. This EU ruling consequently has affected the practice of the European Patent Office and has caused a lot of confusion in the scientific community. In this study, we evaluated the impact of current patent debate on the universities, companies, suppliers and public funding authorities that are engaged in stem cell research. Therefore, interviews were taken of the actors in both the Benelux and the United Kingdom. We also performed several database searches in order to map the influence of the EU ruling on the filing and examination of European patent applications and we compared the obtained results with the patenting of human embryonic stem cell-based inventions in the U.S. and the patenting of induced pluripotent stem cell-based inventions in Europe. We conclude that there have been a lot of misconceptions about the influence of the EU Court’s recent decision and that a vocal minority is awaiting the European Patent Office to take a conclusive position in this matter. Furthermore, it is of great importance that human embryonic stem cell research is to be continued, irrespective of the progress made in induced pluripotent stem cell research.
The use of human embryonic stem cells used to require the destruction of a human embryo in order to obtain the pluripotent stem cells. This traditional requirement has been – worldwide – an ethical and legal sticky point through 15 years by now. Several European countries have yet acquired a favorable regulatory framework for the conduct of embryonic stem cell research; however, the patentability of human embryonic stem cell-related inventions is a crucial factor in determining whether the many potential cell therapies will move from academic laboratories via the industry to the patient.
Patenting embryonic stem cells at the European patent Office (EPO) previously relied on EPO’s Board of Appeal decision in the WARF case , which stipulated that biotechnological inventions are excluded from patentability only if the invention necessarily involved the destruction of a human embryo at the time of filing a patent application. The decision of the European Court of Justice in the Brüstle v. Greenpeace case , however, goes far beyond the former practice of the EPO by judging that biotechnological inventions are non-patentable if the invention was obtained via human embryo destruction at any point in time. This ruling needed to be implemented at the EPO and triggered great concerns towards the scope of patent protection available for human embryonic stem cell-based inventions. Nevertheless, the controversial patent held by Prof. Dr. Brüstle was challenged both at national and at European level, the latter which is still ongoing in the Brüstle v. Geron case .
Interviews were taken of the academic institutions, companies and public funding agencies that are all involved in the field of stem cell research and are located in either the Benelux or United Kingdom. The key aspects of discussion include changes in research strategy, changes in intellectual property strategy or difficulties in search of financial support.
Additionally, database searches were performed in order to map the impact of the EU decision on the filing frequency and examination of European stem cell patent applications, in order to juxtapose data on embryonic stem cell patenting in Europe v. the U.S. and in order to juxtapose data on embryonic v. induced pluripotent stem cell patenting.
Our small-scale survey study reveals that the use of stem cells derived from human embryos is mainly practiced in academic scientific research and barely applied in stem cell companies. In this observation, the EU judgment does not play a role as a causative factor, but rather represents an extension of the issues that have hampered the progress of human embryonic stem cell research. That is why the Belgian and Dutch companies’ interest in embryonic stem cells has generally been lagging and academic scientists have expressed their frustrations at the non-scientific problems surrounding this research field. Acquiring financial support for the conduct of research using a human embryonic stem cell-based strategy has not been problematic, however, from the moment that an economic purpose is mentioned, those chances become strongly reduced.
Quote from a research scientist at Vrije Universiteit Brussel (Belgium):
"Our request to financially support the human embryonic stem cell-based research project has been deferred as no industrial partner could have been found to collaborate with bearing in mind the non-patentability. The only option left is to present a similar project for non-economic purposes, by which is meant that the project should be tailored to the treatment of an orphan disease."
While the influence of the EU judgment cannot be supported with numerous examples of failed R&D projects, because few R&D attempts have so far been carried out in this relatively new scientific field, we have now come to a point that human embryonic stem cell-based applications are ready to be commercially developed (cf. Pluriomics was launched in 2011) and scrutinized in clinical trials (cf. ACT published preliminary clinical trial results in 2012). This statement was echoed by the CEO at Cell Therapy Catapult Centre, who has adopted a wait-and-see attitude in view of the patentability of human embryonic stem cells in Europe.
Quote from a translational research expert at Cell Therapy Catapult Centre (United Kingdom):
"We will choose the best strategy to obtain intellectual property rights for our future human embryonic stem cell-based inventions, either via patent protection or trade secret protection. At this moment we are not looking for ways to get around the Court’s judgment, we are just awaiting the decision of the Opposition Division of the EPO in the Brüstle v. Geron case."
At this time, the EU judgment has resulted in far-reaching objections to any claim that insinuates the destruction of a human embryo and in numerous claim amendments. Furthermore, we have seen that stem cell patent applications at the EPO are delayed in proceeding to the grant of a patent and become temporized in anticipation of the final outcome in the Brüstle v. Geron case. It is far too early to draw conclusions in terms of European patent filings in the year in which the EU Court delivered its judgment, however, current public information reveals that the EU decision will be responsible for another hitch in the evolution of embryonic stem cell patenting and, although the actual judgment was not a direct cause, the whole patent discussion regarding human embryonic stem cell inventions can be held in connection with the exponential increase in European patent filings pertaining to induced pluripotent stem cells (see Figure 1).
Because patent law in the U.S. does not comprise an explicit morality clause and the U.S. Patent and Trademark Office (USPTO) has adopted a less restrictive stance towards the patentability of human embryonic stem cell-based inventions, we juxtaposed the number of patent families regarding embryonic stem cells as well as the number of granted patents thereof at the USPTO and at the EPO. As can be seen in Figure 2, there is not a significant difference between Europe and the U.S. in terms of patent filings or patent grants relating to embryonic stem cells, however, this observation is probably due to an unfavorable regulatory framework which has hobbled, for a long time, human embryonic stem cell research in the U.S.
There have been a lot of misconceptions about the impact of EU Court’s recent decision in the Brüstle v. Greenpeace case. Its consequences turn out to be not as dramatic as was primarily feared; the EU judgment does not equal the end of implementing embryonic stem cell research in Europe, nor has it caused a flight of scientists from Europe. It did, however, brought about hurdles in acquiring public funding for human embryonic stem cell-based research with an economic purpose, modifications in the ratio of patent v. trade secret protection, and delays in either the filing or examination process of stem cell patent applications at the EPO. These effects merely represent the present level of uncertainty for patenting human embryonic stem cells in Europe and send out a negative message that impedes the development and marketing of potentially life-saving therapies, but therefore are not necessarily definite; as Europe used to attract companies because of the strong regulatory framework (cf. Pfizer Neusentis Unit, UK, 2008) and is currently struggling with patenting issues, the United States offers an attractive environment for the commercialization of cell therapies whilst they have only recently been tackling its restrictive regulatory framework. This is understood by the researchers who have set their hopes on potential appeal proceedings in the Brüstle v. Geron case, whereby it is likely that the Boards of Appeal of the EPO will take a position towards the patentability of human embryonic stem cells in Europe. It is said by EPO examiners that the method called "single blastomere biopsy" may resolve some of the non-scientific problems of human embryonic stem cells seeing that this technique enables the isolation of stem cells from a human embryo whilst the embryo remains viable.
Furthermore, it is concluded that the conduct of induced pluripotent stem cell research cannot be continued at the expense of human embryonic stem cell research. Both stem cell sources are of great importance to clarify all the mechanisms behind the character of "pluripotency" and each one holds the potential to be used in clinical applications. It is not yet known which one will eventually be the most effective stem cell source for clinical use, nevertheless, they should be explored complementary rather than substitutive and (the development of) a cell therapy in the benefit of patients with life-threatening diseases should not be driven by politics and public opinion.
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3. Geron. Notice of opposition against EP1040185 [Internet]. 2006. Available from: https://register.epo.org/espacenet/application;jsessionid=069FDA8A75135…
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