CJEU Stem Cell Patents: Brüstle v Greenpeace (C-34/10)

The case relates to a German patent granted to neuroscientist Oliver Brüstle in 1999 for a method for turning mammalian ES cells into neurons. Greenpeace filed a nullity action with the Federal Patent Court arguing that claims to neural precursor cells derived from hESC contravened the morality provisions of German patent law. The German Federal Court of Justice (BGH) then referred questions on the interpretation of the Biotech Directive¹ to the CJEU.

According to Article 6 of the Biotech Directive, "uses of human embryos for industrial and commercial purposes" shall be considered unpatentable.

The questions referred to the ECJ related to three main issues:

1. the meaning and scope of the term 'embryo' and whether blastocysts, embryos made by somatic cell nuclear transfer/cloning or parthogenically activated embryos, fall within this definition;
2. the meaning and scope of exclusion of 'industrial and commercial uses' in Article 6(1) of the Biotech Directive; and
3. the extent to which the exclusion on 'uses' of human embryos for industrial and commercial purposes applies

The Court ruled as follows (the ruling itself appears in bold, followed by comments):

1. The meaning of the term 'embryo'

Article 6(2)(c) of the 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:

• 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';
• it is for the referring court to ascertain, in the light of scientific developments, whether a stem cell obtained from a human embryo at the blastocyst stage constitutes a 'human embryo' within the meaning of Article 6(2)(c) of Directive 98/44.

The Court pointed out that the definition of human embryo is a very sensitive social issue in many member states and that the Court is not called upon to broach questions of a medical or ethical nature, but must restrict itself to a legal interpretation of the relevant provisions of the Biotech Directive.

However, with reference to the preamble of the Biotech Directive it stated that one of the aims of the Directive was that "patent law must be applied so as to respect the fundamental principles safeguarding the dignity and integrity of the person". It considered that the context and aim of the Directive was that European Union legislature should exclude any possibility of patentability where human dignity could be affected. It then concluded that the concept of 'human embryo' according to Article 6 of the Directive should be understood in a wide sense.

The Court went on to consider that any fertilised human ovum should be considered as 'human embryo' if that fertilisation is such as to commence the process of development of a human being. The term also includes a non-fertilised human ovum into which the cell nucleus from a mature human cell has been transplanted (for example by somatic cell nuclear transfer), and a non-fertilised human ovum whose division and further development have been stimulated by parthenogenesis.

With regard to stem cells obtained at the blastocyst stage, the Court indicated that it is for the referring court to ascertain, in the light of scientific developments, whether they are capable of commencing the process of development of a human being.

This part of the ruling is perhaps superfluous at present because stem cells obtained from a blastocycst are pluripotent and do not have the capacity to develop into a human being. However, the Court appears to be mindful that in the future, this situation may change with advances in the technological field. They have therefore avoided stating as a general rule that pluripotent cells are not regarded as human embryos. Instead the test is whether the cell, or collection of cells, is capable of subsequent development into a human being.

2. The meaning of term 'industrial and commercial uses'

The exclusion from patentability concerning the use of human embryos for industrial or commercial purposes set out in Article 61(2)(c) of Directive 98/44 also covers the use of human embryos for purposes of scientific research, only use for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it being patentable.

The Court pointed out that, as supported by recital 14 of the preamble to the Directive, the rights attaching to a patent are, in principle, connected with acts of an industrial or commercial nature. Thus the use of human embryos for scientific research which is the subject matter of a patent application cannot be distinguished from industrial and commercial use and is encompassed by the exclusion.

It also confirmed that, in accordance with recital 42 of the preamble to the Directive, the exclusion does not affect inventions for therapeutic and diagnostic purposes which are applied to the embryo and are useful to it.

3. The extent of the exclusion

Article 6(2)(c) of Directive 98/44 excludes an invention from patentability where the technical teaching which is the subject matter of the patent application requires the prior destruction of human embryos or their use as base material, whatever the stage at which that takes place and even if the description of the technical teaching claimed does not refer to the use of human embryos.

The Brüstle patent relates to neural progenitor cells and processes for their production from embryonic stem cells. There is no specific mention of using human embryos, but, in view of the date in question, it must be assumed that embryonic stem cells were obtained from a blastocyst and that in doing so, the blastocyst was destroyed.

The Court confirmed that the fact that the use of human embryos is not specifically mentioned does not affect the patentability of the invention: if the implementation of the invention requires the destruction of human embryos, the invention must be regarded as unpatentable.

This avoids the situation where an applicant can avoid the exclusion from patentability set out in Article 6(2)(c) of the Biotech Directive merely by ensuring the language of the claim avoids mention of the method of isolation of embryonic stem cells.

An important consideration is how the ruling given by the CJEU in this case fits with the decision of the Enlarged Board of Appeal of the European Patent Office (EPO) in the case G2/06 which was issued on 25 November 2008². G2/06 related to a patent application from the Wisconsin Alumni Research Foundation (WARF) which described a method for obtaining embryonic stem cell cultures from primates. It was held that a patent cannot be granted for an invention which necessarily involves the use and destruction of human embryos.

G2/06 effectively precludes patent protection for old patent applications for which the only technology available for the generation of hESC involved destruction of a blastocyst. However, stem cell technology has moved on and there are now other ways of making stem cells which may not necessarily involve the destruction of an embryo. Moreover, human embryonic stem cells lines are now publicly available, which are suitable as a starting point for many stem-cell based inventions.

Following G2/06 an unofficial interim practice has arisen at the EPO. Patent applications which post-date the deposit of cell lines by the Israel Institute of Technology, Technicon, at the US National Institutes of Health in May 2003 have a good chance of escaping the exemption on the grounds that, as deposited human embryonic stem cells lines were available, it was not necessary to destroy a human embryo as part of the practice of the claimed invention.

There are, however, ongoing disputes at the EPO as to the precise date on which hESC lines were available to the public according to EPO case law and practice, and at least one pending appeal on an application which pre-dates the May 2003 date mentioned above.

The decision of the CJEU in relation to the third question appears to be in line with G2/06, as it confirms that an invention is excluded from patentability where the technical teaching which is the subject matter of the patent application requires the prior destruction of human embryos or their use as a base material.

This would appear to mean that inventions where the technical teaching no longer requires the prior destruction of a human embryos (ie, where an established human embryonic stem cell line may be used) would be outside the scope of the exemption.

However, the phrase "whatever the stage at which [the destruction of a human embryo] takes place" does introduce some ambiguity. It may be that, because it was necessary to destroy an embryo in order to make the deposited stem cell line, and downstream product of the cell line is also excluded from patentability.

If, however, it is possible to put the invention into effect without ever destroying a human embryo, for example if the date of the patent application is late enough that alternative technologies were available, then the invention may be outside the scope of the exclusion.

It will be interesting to see whether the EPO continues its current practice of considering patent applications relating to stem cells which were filed after May 2003 to be outside the exemption due to the availability of deposited human embryonic stem cells lines, or whether the significance of this date needs to be reassessed.

Footnotes:

1. European Parliament and Council Directive 98/44/EC of 6 July 1988 on the legal protection of biotechnological inventions
2. G2/06: Official Journal EPO 5/2009, 306.

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Full text of decision: Brüstle v Greenpeace C-34/10