What is really meant by the term ”human embryo” as used in Article 6(2)(c) of the Biotech Directive (98/44/EC)? Are parthenotes to be considered as embryos and what is meant by “capable of commencing the process of development to a human being”?
Following an appeal by International Stem Cell Corporation (“ISCC”) against a decision that the subject matter sought protection for in two related applications is excluded from patentability as it relates to human stem cell, the UK High Court has referred a question to the Court of Justice of the European Union (“CJEU”). The subject matter of these patent applications relates to human embryonic stem cells (hESCs) isolated from oocytes activated by parthenogenesis, which is the initiation of embryogenesis without fertilization through the activation of an oocyte by artificial means in the absence of a sperm.
During normal embryonic development, the first few cell divisions give rise to cells that are totipotent (capable of differentiating into both embryonic and extra-embryonic tissues, such as the placenta). Already when the embryo consists of 100-200 cells and makes up a hollow sphere called the blastocyst, the developmental potential of a central group of cells called the inner cell mass has become restricted to embryonic tissues (pluripotent), while the outer layer of cells gives rises to extra embryonic tissues.
Scientific studies have shown that parthenotes of several species, which in contrast to fertilized embryos only contain maternal DNA, cannot develop to term. This is because paternal DNA is required for the development of extra embryonic tissues necessary for normal embryonic development. In particular, human embryos have been shown not to develop beyond a blastocyst-like structure. And, in contrast to a fertilized ovum, in the first few cell divisions after activation the cells of a parthenote are only pluripotent, not totipotent.
The CJEU gave guidance in the Oliver Brüstle v Greenpeace case (C-34/10) as to what is the correct interpretation of Article 6(2)(c), saying that the concept “human embryo” must be understood in a wide sense. Accordingly, “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”. Also, any artificially manipulated ovum capable of commencing the process of development of a human being just as an embryo created by fertilization must be regarded as a “human embryo”. Hence, any human ovum after fertilization, any non-fertilized human ovum into which the cell nucleus from a mature human cell has been transplanted and any non-fertilized human ovum whose division and further development have been stimulated by parthenogenesis constitute a “human embryo” within the meaning of Article 6(2)(c).
In the case at hand, ISCC argued that it was necessary to establish what the CJEU meant by “capable of commencing the process of development of a human being”. According to ISCC, the question is whether it means “commencing a process of development which leads to a human being” or whether this applies also to processes that are incapable of leading to a human being. ISCC submitted that the test adopted by the CJEU was clearly directed at the first alternative and therefore their inventions should not be excluded from patentability as their embryos never develop past the blastocyst-like structure. They argued that CJEU incorrectly assumed that parthenotes were capable of commencing the process which leads to the development of a human being. ISCC also pointed to the reasoning of the Bundesrichtgehof following the ruling of the CJEU in Brüstle, interpreting the CJEU judgment as permitting the use of hESC derived from non-viable embryos.
The Comptroller General of Patents (the UK patent office) argued that the test applied by the CJEU might refer only to the start of the process of development and did not require its completion and the birth of a viable human being. In doing so, he pointed for example to the phrase “as soon as fertilized”, as well as to similarities between early development of parthenotes and viable embryos. However, the Comptroller agreed that it was unclear whether the Brüstle test turned on commencing the process of development, or commencing the process capable of creating a viable human being.
The Deputy Judge decided a further reference was justified, based on the different factual matrix (the evidence before the CJEU was that parthenotes have the potential to create a human being whereas in the present data was presented showing that this is not the case) combined with the insufficient clarity of the test applied by the CJEU in Brüstle.
Like the Advocate General in Brüstle, the Judge considered that a distinction should be made between totipotent cells and pluripotent cells. He emphasized that parthenotes and fertilized ova are not identical at any developmental stage. In his view, if the process of development is incapable of leading to a human being, as in the case of parthenotes, then it should not be excluded from patentability as a “human embryo”. Also, the Judge repeated well known concerns of the biotech industry and academia and concluded with stating that the total exclusion from patent protection of the fruits of stem cell research would be “to the detriment of European industry and public health”.
It appears as if the last word on stem cell patenting has not been said…
Joanna Applequist, Associate
The question to be referred:
“Are unfertilized human ova whose division and further development have been stimulated by parthenogenesis, and which, in contrast to fertilized 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 case: International Stem Cell Corporation v Comptroller General of Patents, Patents Court, London, UK, 17 April 2013, Case No.  EWHC 807 (Ch)