Background

What does the term ‘human embryo’ as used in Article 6(2)(c) of European Directive 98/44/EC mean?

In Europe, patents shall not be granted in respect of biotechnological inventions which concern uses of human embryos for industrial or commercial purposes (Article 6(2)(c) of Directive 98/44/EC).

The UK High Court has referred a question to the Court of Justice of the European Union (CJEU) following an appeal by International Stem Cell Corporation (ISCC) against a decision of the UK Intellectual Property Office (UKIPO) that the subject matter in two related applications are excluded from patentability under the provisions corresponding to Article 6(2)(c) of European Directive 98/44/EC. The patent applications relate to human embryonic stem cells isolated from oocytes activated by parthenogenesis, which is the development of an embryo from an unfertilised oocyte (GB0621068.6 concerns the production of human stem cells from such parthenotes; GB0621069.4 concerns human synthetic corneas and corneal tissues derived from such parthenotes). The claimed methods of producing stem cell lines and the claimed stem cell lines (GB0621068.6), and the claimed methods of producing synthetic corneas or corneal tissue and the claimed synthetic corneas or corneal tissue (GB0621069.4), were deemed by the UKIPO to constitute uses of human embryos for industrial or commercial purposes and thus excluded from patentability.

The development of a human being starts with fertilisation of an oocyte. Within several days after fertilisation, the so-called ‘blastocyst’ forms which comprises an inner cell mass surrounded by an outer layer of cells. During normal embryonic development, cells that are produced in the very first few divisions are totipotent (capable of differentiating into both embryonic and extra-embryonic tissues). At the blastocyst stage, the developmental potential of the inner cell mass has become restricted to embryonic tissues (pluripotent), while the outer layer of cells can give rise to extra-embryonic tissues, such as the placenta.

Three years ago, the CJEU addressed the meaning of the term ‘human embryo’ in the heavily reported Brüstle case (C-34/10). There, the CJEU held that ‘any human ovum must, as soon as it is fertilized be regarded as a human embryo since fertilization is such as to commence the process of development of a human being’. Further ‘any human ovum after fertilisation, any non-fertilised human ovum into which the cell nucleus from a mature human cell has been transplanted, and any non-fertilised human ovum whose division and further development have been stimulated by parthenogenesis constitute a ‘human embryo’ within the meaning of Article 6(2)(c).’.

During prosecution of the applications, ISCC was confronted with the objection that the applications are not patentable as the inventions disclosed constitute uses of human embryos that are not patentable under the standards established in Brüstle by the CJEU. ISCC argued that Brüstle should not apply as the inventions concern parthenogenetically activated oocytes not ‘capable of commencing the process of development of a human being’ in contrast to an embryo created by fertilisation of an ovum which can do so due to genomic imprinting.

The question referred 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 the Directive 98/44 on the Legal Protection of Biotechnological Inventions?”

The opinion of the Advocate General

The opinion of the Advocate General Villalon is that unfertilised human oocytes whose division and further development have been stimulated by parthenogenesis should be excluded from the definition of ‘human embryos’ in the sense of Article 6(2)(c) of the Directive.

It appears to be accepted that parthenotes of several species, which contain only maternal DNA in contrast to a fertilised embryo, cannot develop to term. This is understood to be because there is a need for the presence of paternal DNA for the development of extra embryonic tissues necessary for normal embryonic development, so-called ‘genomic imprinting’. In particular, human parthenotes have been shown not to develop beyond a blastocyst-like structure and are therefore not ‘capable of commencing the process of development of a human being’. That said, the barrier of genomic imprinting might be surmountable by genetic manipulation, even though this has so far not been proven in human beings.

The Advocate General appears to recognise that according to Brüstle, the notion of ‘human embryo’ under Article 6(2)(c) of the Directive must be understood in a wide sense, but the ‘process of development of a human being’ cannot merely be ‘commenced’ but must be understood as a process that can result in complete development.

The Advocate General opines that the Brüstle decision was based on incomplete scientific information, for the Court was not aware that, without undergoing substantial genetic manipulation, a parthenote is unable to develop into a human being. However, in consideration of the possibility of the future development of genetic manipulation techniques able to make parthenotes obtained from human ova capable of developing into human beings, the Advocate General advises the CJEU to give the following, conditional answer:

“Unfertilised human ova whose division and further development have been stimulated by parthenogenesis are not included in the term ‘human embryos’ in Article 6(2)(c) of Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions as long as they are not capable of developing into a human being and have not been genetically manipulated to acquire such a capacity.”

Practice Pointers

It is important to note that the Advocate General’s opinion is just that, an opinion. It is not binding on the CJEU but is considered persuasive so we await the Court’s decision in due course.

In the meantime, it appears prudent to ensure that when drafting or amending claims relating to parthenotes to consider language ensuring that there is no possibility of the subject matter being capable of developing into a human being. In this regard, it is interesting to note that ISCC amended their claims before the UKIPO to try to exclude stem cells capable of developing into a human being and any method in which the issues associated with genomic imprinting may be overcome, for example:

“A method of producing a pluripotent human stem cell line comprising…
.. and wherein … the oocyte genome lacks paternal imprinting …”

It will be very interesting to see if these amendments are persuasive.