Three years after the landmark Brustle ruling, the CJEU is poised to revisit the scope of exclusion on industrial and commercial uses of “human embryos” in Article 6(2) (c) of the EU Directive on Biotechnological Inventions. This time, the referral is from a national court of first instance, the Chancery Division (Patents Court) of the UK High Court of Justice Court. In the Opinion of Advocate General Cruz Villalon, whilst the question raised by the UK court is “virtually identical” to the questions raised in the Brustle reference of the German Federal Court of Justice (BGH), the answer should be different.
One of the questions raised by the BGH in Brustle was whether the term ‘human embryo’ encompassed ‘unfertilised human ova whose division and further development have been stimulated by parthenogenesis’ (parthenotes). In Brustle, the Grand Chamber of the CJEU held that parthenotes fell within the scope of exclusion of Article 6(2) (c) because the term ‘human embryo’ had to be given an autonomous meaning in EU law and should be “be understood in a wide sense” to include any human ovum, as soon as fertilised “… since that fertilisation is such as to commence the process of development of a human being.” The criterion of whether an organism is “capable of commencing the process of development” (the ‘commencement’ test) was relied upon by the UK intellectual Property Office to reject two patent applications by International Stem Cell Corporation (ISC) relating to human embryonic stem cell lines produced by parthenogenesis activation of ova. In its appeal, ISC argued that the Brustle exclusion should not extend to parthenotes because such organisms are incapable of developing into human beings. In this light, the UK High Court raised the following question for a preliminary ruling: “Are unfertilised human ova whose division and further development has been stimulated by parthenogenesis, and which, in contrast to fertilised ova, contain only pluripotent cells and are incapable of developing into human beings, included in the term ‘human embryos’ in Article 6(2)(c) of Directive 98/44 on the Legal Protection of Biotechnological Inventions?”.
France, Sweden and the Commission submitted that, in the current state of science, parthenotes cannot be considered identical to embryos at any stage of their development and parthenogenesis cannot be regarded as a technique capable of commencing the process of development. Portugal expressed concern about the risks of further genetic manipulation and would have left the decision to national courts. The UK submitted that the critical factor was the capacity of the cell itself and not its capacities after genetic manipulation (para. 60). By contrast, Poland submitted that, even though parthenotes cannot develop into human beings according to current scientific understanding, nonetheless respect for human dignity requires that they should be treated as human embryos as they “initially undergo the same stages of development as a fertilised ovum (para. 60).
The analysis of Advocate General Cruz Villalon proposes to read into the Grand Chamber’s ‘commencement’ rule in Brustle a functional equivalence test, so that the decisive criterion which should be taken into account for determining whether an unfertilised ovum is a human embryo is “whether that unfertilised ovum has the inherent capacity of developing into a human being, i.e. whether it really constitutes the functional equivalent of a fertilised ovum.” (at para. 73). On this basis, the mere possibility that a parthenote could be genetically manipulated so that it can develop to term and into a human being does not change the fundamental character of the parthenote before manipulation. According to current scientific knowledge parthenotes do not have the capacity to develop into human beings but “where the parthenote is manipulated in such way that it actually obtains the respective capacity, it can no longer be considered a parthenote and it cannot be, consequently patented.” (at para. 77).
In reaching his conclusion that parthenotes are not human embryos, Cruz Villalon proceeded on the basis that the Directive was not to be a “law of bioethics” but concerns biotechnological patents (at para. 38). On the other hand, given the sensitivity of the ethical issues raised by new biotechnologies, the Directive opens a space for ethical and moral considerations to be addressed under the umbrella of Article 6. Reiterating the views of the earlier EU Courts judgments in the Netherlands and Italy cases, Cruz Villalon noted that the list of moral exclusions in Article 6(2)(c) is illustrative and not exhaustive. It represents a ‘no-go’ zone that is common to all Member States. But the list does not imply that Member States could not prohibit patentability on the basis of other moral considerations (para. 43). This analysis, Cruz Villalon hopes “… will enable the Court of Justice to give the referring court a more exact answer which might prevent further references.” (para. 34).
The hope might yet prove overoptimistic in the light of the rapid pace of scientific advances in genetic engineering and the conceptual difficulties in establishing the ‘inherent’ scientific properties of an organism at any given point in time. Cruz Villalon’s analysis is consistent with the view of the BGH in its application of the Brustle ruling in its decision of 27th November 2012 ( X ZR 58/07). The BGH upheld the validity of Oliver Brustle’s national German patent 197 56 864 in an amended form, on the grounds that “The embryos from which the stem cells described in E8 and E9 were extracted had, by the time they were extracted, lost that capability without any outside influence. The removal of cells from such organisms should not therefore be considered a use of embryos.” (at para. 34). By contrast, the Opposition Division of the European Patent Office (EPO) revoked the European counterpart of the German patent in independent proceedings on 11th April 2013, partly in reliance on the decision of its own Enlarged Board of Appeal which issued guidance on moral exclusions relating to embryonic stem cells in the Warf case (G2/06). Opposition proceedings to the European Brustle patent granted by the EPO on 22nd February 2006 had been filed by US company Geron. According to the EPO, the European Brustle patent was revoked on the grounds that the amended application covered subject matter not disclosed in the original application. On the other hand, Oliver Brustle was granted a US patent on 28th June 2011 (US7968337 B2). Evidently, there remains significant elasticity in the scientific, moral and legal standards applied by patent offices and courts in Europe and beyond to determine whether or not a human embryo is sufficiently implicated in an application to preclude the grant of a patent.
More generally, Cruz Villalon’s approach has the merit of recalling the distinction drawn by the EU Court in the Netherlands and Italy cases as between inventions which the Directive requires all Member States to exclude from patentability (namely the illustrative list including ‘industrial and commercial uses of human embryos’ in Article 6(2)(c)) and other inventions on which there is no moral consensus in the EU. As noted in an FP6 study conducted in 2006, where an invention does not fall within the specific exclusion in Article 6(2)(c) but, in the view of some Member States, should be morally excluded from patentability, these States may rely on the general exclusion in Article 6(1) to preclude patentability within their territories (subject to the limitations in Article 27 of TRIPS).
Thus, even if ‘parthenotes’ do not fall within the Brustle definition of a ‘human embryo’ States, like Poland may still rely on Article 6(1) to exclude patents on parthenotes within their territory. Cruz Villalon’s approach is therefore an important reminder that the Directive includes a flexible framework on moral exclusions on patents in recognition of the diversity of moral cultures on sensitive matters in Europe. On the other hand, the Opinion leaves intact and indeed could be read as reinforcing the Brustle autonomous definition of a human embryo and the requirement that it should be given a ‘wide’ meaning which precludes the grant of patents on any products/therapies reliant on human embryonic stem cells which were originally obtained through destruction of a human embryo, irrespective of how far removed the application may be from the original derivation of the cell line. As noted before, the definition relies on the application of a unitary concept of human dignity to the human embryo which is at odds with the legal reality in Europe.
The practical implication of the Opinion and the Brustle ruling thus remains that hESC based regenerative therapies are unpatentable in Europe. This arguably includes, for instance, hESC based therapies developed by European researchers at the UCL Institute of Ophtamology to treat incurable diseases of the eye and the cornea. By contrast, if the EU Court follows the Opinion of the Advocate General, International Stem Cell, a US based company, will be able to secure patent protection on its application GB06210694 entitled ‘Synthetic cornea from retinal stem cells’ claiming methods of producing corneal tissue involving the isolation of pluripotent stem cells from parthenotes. Thus, a company which has relied on methods circumventing the Brustle ruling will be able to secure patents whilst others in Europe which have been developing promising therapies for crippling diseases based on decades of hESC research will have to fall back on commercial secrecy. This continues to be a worrying prospect for the commercialization of European research on health and innovation and ultimately for patients in Europe.
See Aurora’s earlier piece: EU Ban on Stem Cell Patents: Intended and Unintended Consequences