The intense and controversial debate on the patentability of embryonic stem cells in Europe has recently entered another round. On April 17, 2013, the High Court of England, in Case  EWHC 807 (Ch) (International Stem Cell Corporation v Comptroller General of Patents), requested the Court of Justice of the European Union (CJEU) to further clarify its previous interpretation of the term "human embryo", given in landmark decision C-34/10 (Oliver Brüstle v Greenpeace e.V.; handed down on October 18, 2011) (cf. Newsletter issue of May 2011).
The new referral concerns two UK patent applications, both relating to methods of obtaining human embryonic stem cells derived from oocytes that were stimulated by parthenogenesis, that is, by activation of an oocyte in the absence of sperm. In contrast to a fertilized embryo, the cells of such activated oocyte (i.e., a parthenote) are pluripotent but not totipotent (i.e., can develop into embryonic but not extra-embryonic tissue). In other words, this parthenogenetic approach of obtaining embryonic stem cells does not involve the destruction of fertilized embryos. However, both patent applications were considered to contain subject matter being excluded from patentability (i.e., the "use of human embryos for industrial or commercial purposes") in view of the guidelines laid down in decision C-34/10.
Therein, the CJEU held that the concept of 'human embryo' pursuant to Article 6(2)(c) of the EU Biotech Directive 98/44/EC, had to be understood in a wide sense. Any human ovum must, as soon as fertilized, be regarded as a human embryo if that fertilization is such as to commence the development of a human being. However, a non-fertilized human ovum into which the cell nucleus from a mature human cell has been transplanted as well as a non-fertilized human ovum whose division and further development have been stimulated by parthenogenesis must also be classified as a human embryo since they were nevertheless capable of commencing the process of development of a human being (cf. C-34/10, point 38 of the reasoning).
Applying this ruling to the subject patent applications, the UK Patent Office took the view that a stimulated oocyte divided in a manner analogous to that of a fertilized embryo, in order to produce a parthenote, a structure that is analogous to a blastocyst from which stem cells could be obtained.
On appeal, the applicant International Stem Cell Corporation argued that the CJEU, in case C-34/10, wrongly assumed that pluripotent parthenotes were capable of commencing the process of development of a human being because pluripotent cells were only capable of developing into embryonic tissue, but not extra-embryonic (e.g. placental) tissue. In contrast, fertilized embryo cells after the first few divisions were totipotent and thus capable of developing into embryonic and extra-embryonic tissues, both of which are needed to develop into a viable human being. Parthenotes did not contain totipotent cells, even after the first few cell divisions or later stages, which means that it is incapable of developing into a human being.
The High Court apparently accepted that parthenotes and fertilized ova are not identical at any stage and agreed that if the process of development of a parthenote is incapable of leading to a human being, it should not be excluded from patentability as falling beyond the definition of a "human embryo." Notably, in his opinion in C-34/10, the competent Advocate General considered totipotent cells to be excluded from patentability but pluripotent cells not.
The High Court concluded that there was still insufficient clarity as to what was exactly meant by the CJEU in C-34/10 by the expression "capable of commencing the process of development of a human being." Therefore, the following question was referred to the CJEU (no case number assigned yet):
- Are unfertilized human ova whose division and further development have been stimulated by parthenogenesis, and which, in contrast to fertilized ova, are incapable of developing into human beings, included in the term "human embryo" under Article 6(2)(c) of the Biotechnology Directive?
A preliminary ruling of the CJEU on this issue might be expected by early next year. A decision that parthenotes not being included in the term "human embryo" would attenuate the previous ruling in C-34/10 that in effect precluded the patentability of stem cells derived from embryonic stems cells, fertilized or not.
However, in order to obtain patent protection for embryonic stem cells in Europe the situation for applicants has become even more complex due to the recent revocation of European patent 1 040 185 B1 owned by Prof. Dr. Oliver Brüstle during opposition proceedings (the oral proceedings took place on April 11, 2013; no written decision has yet been issued). The subject matter of the disputed patent relates to isolated neuronal precursor cells, processes for their preparation from ES cells and their use for therapy of neural defects.
Notably, the priority-establishing German patent application, granted as DE 197 56 864 C1, resulted in the referral of the German Federal Supreme Court (BGH) to the CJEU in C-34/10. In its final ruling (Case X ZR 58/07; handed down on November 27, 2012), the BGH revoked the patent the patent to the extent to which human embryonic stem cells were obtained by destructing human embryos, due to a violation of section 2 of the German Patent Act. However, human embryonic stem cells being obtained without the destruction of embryos were considered patentable. According to the BGH, it was sufficient in this regard that alternative methods for obtaining human embryonic stem cells exist and are apparent for the skilled person at the effective date of the patent (cf. X ZR 58/07, points 26 and 32 of the reasoning).
The BGH accepted the incorporation of a general disclaimer into the claim wording that precludes the use of human embryonic stem cells being obtained by a destruction of embryos. Intriguingly, it was not further investigated whether there are in fact other practicable ways for obtaining human embryonic stem cells.
The competent EPO Opposition Division, however, applied a much stricter approach. In view of recent Enlarged Board of Appeal decisions G1/03 and G2/10 (cf. Newsletter issues of September 2011 and August 2012) the above disclaimer was rejected as extending beyond the original disclosure, and thus contravening Article 123(2) EPC. Notably, the Opposition Division had restricted its reasoning to formal aspects and thus could avoid an assessment of ethical issues in the sense of Article 53(a) EPC that would be of particular interest to many practitioners. It remains to be seen whether the written decision includes any statement in this regard.
Hence, applicants have now to face the situation of different standards apparently being applied by national courts and the EPO, respectively, with regard to the patentability of human embryonic stem cells.
The present decision of the EPO opposition Division is still open to appeal and, according to the speculations of many observers, might result in another referral to the Enlarged Board of Appeal. The first referral concerning the "WARF case" resulted in EBA decision G2/06 (cf. Newsletter issue of January 2010). Hence, it should likely be a matter of years before (hopefully) final clarification on the patentability of stem cell matters in Europe will be obtained.
In view of these recent developments, the most critical practical implication for applicants is currently to be seen in a very careful and detailed drafting of any patent applications relating to embryonic stem cell-based technologies. Particular emphasis should be put on the inclusion of methods for obtaining human stem cells that do not involve the destruction of embryos.
Furthermore, various disclaimers should be explicitly included at least in the description in order to have appropriate fallback positions disclosed, should upcoming case law require the restriction of the claimed subject matter in a particular way. And, the use of pluripotent cells should be explicitly claimed.