Parthenotes and Patentability
In an eagerly awaited decision, the CJEU today provided some pre-Christmas cheer to those struggling with patentability of stem cell-related inventions in Europe.
The CJEU have confirmed the preliminary view of the Advocate General (AG) that unfertilised human ova whose division and further development have been stimulated by parthenogenesis (parthenotes) are not to be included in the term ‘human embryos’. Accordingly, cells of this type, and inventions that make use of them, are eligible for patent protection in Europe.
The decision may also offer a lifeline to many older stem cell-related cases currently pending before the EPO. The EPO had previously viewed morally acceptable human stem cells as having first been made available on 10th January 2008, and thus patent applications relating to human embryonic stem (hES) cells with a priority date on after this date can in many cases be permitted. Since stem cells derived from parthenotes were available earlier than this, today’s decision may mean that the objections regarding non-patentable subject matter may no longer apply to some cases filed before this date.
How is one to understand the term “capable of commencing the process of development of a human being”? Does an unfertilised ovum have the inherent capacity of developing into a human being? Answers to these questions are fundamental to the understanding of the meaning of the term “human embryos” in the European Directive (98/44/EC) on the legal protection of biotechnological inventions (the Directive).
This has most recently been considered by the CJEU in International Stem Cell Corporation (ISCO) v Comptroller General of Patents, Case C-364/13. Following on from the AG Opinion in July 2014, the CJEU has agreed with the AG that parthenotes are not included in the term ‘human embryos’ under the Directive, and are hence patentable. The case will now go back to the UK High Court for a final decision on the specific facts of that case.
C-364/13 - Background
In June 2013, the UK High Court referred a single question to the CJEU.
“Are unfertilised human ova whose division and further development have 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/EC* on the Legal Protection of Biotechnological Inventions?”
The Directive states that “…uses of human embryos for industrial or commercial purposes” are considered unpatentable. Furthermore, the UK Patents Act 1977, which implements the Directive, states that “…uses of human embryos for industrial or commercial purposes” are not patentable inventions.
In fact, this question posed by the UK High Court, was almost identical to the questions that the CJEU answered three years ago in the “Brüstle” case. The point of significance was clarification of whether the Brüstle prohibition really applied to parthenotes, which in contrast to fertilised ova, contain only pluripotent cells and are therefore incapable of developing into human beings. The Brüstle decision explicitly stated in paragraphs 36 and 38 that human parthenotes were considered to be non-patentable ‘human embryos’ per se, but this finding was based upon seemingly flawed logic, hence the need for a further referral to clarify the matter.
ISCO filed two patent applications at the UKIPO, one was entitled ‘Parthenogenetic activation of oocytes for the production of human embryonic stem cells’, and claimed methods of producing pluripotent human stem cell lines from parthenogenetically-activated oocytes and stem cell lines produced according to the claimed methods. The other, entitled ‘Synthetic cornea from retinal stem cells’ claimed methods of producing synthetic cornea or corneal tissue involving the isolation of pluripotent stem cells from parthenogenetically-activated oocytes as well as synthetic cornea or corneal tissue produced by these methods. Parthenogenesis refers to the development of an egg without fertilisation. Both applications were objected to on the basis that the inventions disclosed constituted the use of human embryos, even though these were unfertilised. It was maintained by the UKIPO that these were not patentable under the standard established by the Brüstle decision.
However, ISCO argued that the standard in Brüstle should not apply, as the inventions in question related to parthenogenetically-activated oocytes, which would not be capable of commencing the process of human development. When confronted with research which suggested parthenogenetic mice had been born live, ISCO argued that those mice had been subject to further extensive genetic manipulation. ISCO then amended their patent claims to exclude any such method of manipulation by introducing the word “pluripotent” before “human stem cell line”. Even still, the UKIPO refused the applications in 2012, which ISCO appealed to the UK High Court.
ISCO argued that the Brüstle test was intended to only exclude organisms capable of developing into a human being. In fact, the UK High Court itself was of the opinion that if the parthenogenetically-activated oocytes at issue are incapable of developing into a human being, they should not be regarded as human embryos; pluripotent cells per se should not be excluded from patentability. This would strike the appropriate balance between encouraging biotechnological research by way of patent law and respect for the dignity and integrity of the person, which the Directive was intended to achieve.
The AG Opinion
In light of the question asked of the CJEU by the UK High Court, written observations were submitted by ISCO, France, Poland, Portugal, Sweden, the United Kingdom and the Commission. On 29 April 2014 the Court held a hearing, during which ISCO, the United Kingdom, France, Sweden and the Commission made observations. ISCO, France, Sweden, the United Kingdom and the Commission considered parthenotes not to be ‘human embryos’ in the sense of Article 6(2)(c) of the Directive. Portugal also supported this reading of the formula of the Court, but emphasised the risk of further manipulation of a parthenote leading to its viability. Poland, however, argued that in the interest of safeguarding human dignity, even though parthenotes cannot, according to current understanding, develop into human beings, they initially undergo the same stages of development as a fertilised ovum, namely cell division and differentiation, and hence constitute human embryos.
The AG chose to take a closer look at what the Court in Brüstle meant, regarding whether an unfertilised ovum had the inherent capacity of developing into a human being; that Court did not distinguish parthenotes. But the AG noted that the decisive criterion that should be taken into account for determining whether an unfertilised ovum is a human embryo hence 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. In was apparent in this case, that a parthenote does not, per se, have the required inherent capacity of developing into a human being and hence as such does not constitute a ‘human embryo’.
The AG did make one caveat regarding a parthenote, in theory, being manipulated genetically in such a way that it can develop to term and thus into a human being. Where the parthenote is manipulated in such a way that it actually obtains the respective capacity, it can no longer be considered a parthenote and it cannot be, consequently, patented.
In today’s decision, the CJEU have confirmed the AG’s position that unfertilised human ova whose division and further development have been stimulated by parthenogenesis are not included in the term ‘human embryos’ of the Directive, as long as they are not capable of developing into a human being and have not been genetically manipulated to acquire such a capacity.
Ramifications of the Decision
As well as providing a clear indication that inventions directly relating to the use of parthenotes are eligible for patent protection in Europe, the CJEU’s decision may also benefit many patent applications that relate to stem cells more broadly.
In light of the Brüstle decision, the EPO had adopted 10th January 2008 as being the first date on which human embryonic stem cells from a morally acceptable source (i.e. one not requiring the destruction of human embryos) had been made available. This date represented the online publication of Chung et al.’s paper disclosing the non-destructive generation of hES cells from isolated blastomeres. The EPO considered that patent applications relating to hES cells filed prior to 10th January 2008 could not be put into practice without violating the Directive, and so would reject these as failing to comply with the EPC’s morality provisions; those filed later might be considered patentable, depending on the specific facts of the case.
The decision that parthenotes, which lack the inherent capacity to develop into a human being, should not be viewed as representing a “human embryo”, indicates that human pluripotent stem cells from other sources lacking this capacity should also be excluded from the definition of an embryo. While the earliest definitive date on which such cells have been made available has not yet been determined, it is clear that this precedes the present 10th January 2008 “cut off”. Accordingly, while of course each case will be decided on its individual facts, patent applications filed at a time when such sources of human pluripotent stems cells were available, but before the previous January 2008 date, may now have a much greater chance of being considered to represent patentable subject matter before the EPO and national courts.
We eagerly await further developments in this area. It is yet to be seen how well aligned the practice of the EPO in granting patents on the one hand, and the national courts and the CJEU in assessing validity on the other hand, will be. Nonetheless, it is refreshing to see a development in the jurisprudence which expands the scope for patentability in this contentious area.