By Kevin E. Noonan —

Last Thursday, the European Court of Justice rendered a decision in International Stem Cell (ISCO) Corporation v. Comptroller General of Patents, Designs and Trademarks (UK) that significantly modified the landscape for human embryonic stem cell (hESC) patenting, by holding that prohibitions against patents on hESCs only apply to such cells derived from embryos that had the potential to develop into a human being.  This left as patent eligible in Europe hESCs produced from "parthenotes," embryos stimulated to decide (and produce hESCs) without fertilization.

The case was brought by ISCO over the UK government's rejection of these two patent applications:

• Application GB0621068.6, entitled 'Parthenogenetic activation of oocytes for the production of human embryonic stem cells', claiming methods of producing pluripotent human stem cell lines from parthenogenetically-activated oocytes and stem cell lines produced according to the claimed methods, and

• Application GB0621069.4, entitled 'Synthetic cornea from retinal stem cells', claiming methods of producing synthetic cornea or corneal tissue, which involve the isolation of pluripotent stem cells from parthenogenetically-activated oocytes, and product-by-process claims to synthetic cornea or corneal tissue produced by these methods.

ISCO appealed a decision by a Hearing Officer of the United Kingdom Intellectual Property Office, affirmed by the High Court of Justice (England and Wales), Chancery Division (Patent Court) that the claims of ISC's patent application are unpatentable under the proscription of the ECJ against hESC patenting in its earlier Brüstle (C‑34/10, EU:C:2011:669) decision.  It will be remembered that in 2011 the ECJ held that hESCs are not patent-eligible subject matter on the grounds that stem cell patents were "contrary to ethics and public policy" because they required "industrial use" of human embryos, the position originally taken by the ECJ advocate-general, Judge Yves Bot.  That case was brought by Greenpeace in German federal court over a German patent to the University of Bonn involving methods for deriving neural cells from hESCs (DE 197568664 C1).  The German federal court ruled for Greenpeace in 2006, and the university appealed to the German supreme court.  That court decided that it needed to refer the question to the ECJ, since German law was closely patterned on European Union guidelines for biotechnology patenting.  In the ECJ's decision in 2011, "human embryo" was interpreted broadly:

[A]ny human ovum must, as soon as fertilised, be regarded as a "human embryo" within the meaning and for the purposes of the application of Article 6(2)(c) of the Directive, if that fertilisation is such as to commence the process of development of a human being.

And the ECJ further decided that a "totipotent" or "pluripotent" human embryonic stem cell falls within the definition of a human embryo, deciding that these cells' capacity to develop into many or all human tissues was sufficient for them to qualify as a "human embryo."  Even the use of established hESC lines fell within the scope of that proscription, according to the ECJ, because the production of the claimed product (hESC) "necessitates the prior destruction of human embryos" by "the removal of a stem cell from a human embryo":

Accordingly, [] an invention must be regarded as unpatentable, even if the claims of the patent do not concern the use of human embryos, where the implementation of the invention requires the destruction of human embryos.  In that case too, the view must be taken that there is use of human embryos within the meaning of Article 6(2)(c) of the Directive.  The fact that destruction may occur at a stage long before the implementation of the invention, as in the case of the production of embryonic stem cells from a lineage of stem cells the mere production of which implied the destruction of human embryos is, in that regard, irrelevant.

The ECJ in the most recent action considered again the application of the meaning of 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 (OJ 1998 L 213, p. 13).  This issue arose as a Question Presented by the UK court to the ECJ, as follows:

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 … ?

ISCO distinguished the Brüstle decision on the grounds that the basis for the ECJ's decision in the Brüstle case was that the hESCs were "capable of commencing the process of development which leads to a human being."  ISCO argued that its cells did not satisfy that requirement, because ISCO's cells "cannot undergo such a development process."  Thus, ISCO argues that these cells should be capable of being patented under the Biotechnology Directive (Directive 98/44).

The Comptroller also identified the Brüstle decision as controlling, and maintained that "the key issue is what the Court meant in the judgment in Brüstle [] by organism 'capable of commencing the process of development of a human being just as an embryo created by fertilisation of an ovum can do so.'"  The judgment notes that the Comptroller admitted that "the written observations lodged with the Court in that case [Brüstle] may have inaccurately presented the scientific and technical background relating to parthenogenesis."

In its decision*, the ECJ set forth its understanding of the question asked by the national court to be "whether Article 6(2)(c) of Directive 98/44 must be interpreted as meaning that an unfertilised human ovum whose division and development to a certain stage have been stimulated by parthenogenesis constitutes a 'human embryo' within the meaning of that provision."  The Court concluded that the basis for the Brüstle decision was to prohibit patenting of embryos, or cells derived from embryos that are "'capable of commencing the process of development of a human being."  However, here the parthenogenetic human embryos did not have that capability (being limited to development to the blastocysts stage) and thus these embryos and hESC's derived from them did not satisfy the criterion relied upon by the Brüstle court to exclude those cells from patent eligibility.  As stated in the judgment, "where a non-fertilised human ovum does not fulfil that condition, the mere fact that that organism commences a process of development is not sufficient for it to be regarded as a 'human embryo', within the meaning and for the purposes of the application of Directive 98/44," wherein "[b]y where such an ovum does have the inherent capacity of developing into a human being, it should, in the light of Article 6(2)(c) of that directive, be treated in the same way as a fertilised human ovum, at all stages of its development."

The Court's opinion was framed as an answer to the national court's referred question:

In view of the foregoing considerations, the answer to the question referred is that Article 6(2)(c) of Directive 98/44 must be interpreted as meaning that an unfertilised human ovum whose division and further development have been stimulated by parthenogenesis does not constitute a 'human embryo', within the meaning of that provision, if, in the light of current scientific knowledge, that ovum does not, in itself, have the inherent capacity of developing into a human being, this being a matter for the national court to determine.

And its judgment, binding throughout the EU, was worded as follows:

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 must be interpreted as meaning that an unfertilised human ovum whose division and further development have been stimulated by parthenogenesis does not constitute a 'human embryo', within the meaning of that provision, if, in the light of current scientific knowledge, it does not, in itself, have the inherent capacity of developing into a human being, this being a matter for the national court to determine.

Whether parthenogeneticly produced hESCs are useful for anything other than laboratory research will determine whether this decision does anything to limit the extent to which the Brüstle decision impedes progress in hESC-dependent areas like human regenerative medicine.

*  The judgment of the Grand Chamber of the Court, made up of Judges Skouris (President), Lenaerts (Vice-President), Tizzano, Silva de Lapuerta, Ilešič and Vajda (Presidents of Chambers), Rosas, Borg Barthet, Malenovský, Toader, Safjan (Rapporteur), Šváby and Biltgen.  Also represented before the Court were representatives of the governments of Poland, France, Portugal, Sweden, the United Kingdom and the European Commission.