Brüstle v Greenpeace (C-34/10): The End For Patents Relating to Human Embryonic Stem Cells in Europe? Author: Dr Stephen Blance

Brüstle v Greenpeace (C-34/10): The End For Patents Relating to Human Embryonic
Stem Cells in Europe?

Author: Dr Stephen Blance                                                      Peer Reviewer: Dr Jon Broughton

1. Summary

1.1 The article will outline the major implications of the recent ruling of the CJEU in relation to the
patentability of inventions relating to human embryonic stem cells. The background to the referral and
the questions referred are set out along with the opinion of the Advocate General and ruling of the
Court. Finally, the issues this ruling raises for the future of patenting invention in this field in Europe
are discussed.

2. Background

2.1 On 18 October 2011 the Court of Justice of the European Union (CJEU) issued its eagerly
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anticipated decision in Brüstle v Greenpeace (C-34/10) concerning the patentability of inventions
relating to the use of human embryonic stem cells (hESC). The CJEU has ruled that inventions
involving hESC derived from the destruction of a human embryo are unpatentable. Scientific,
religious and environmental groups have keenly awaited this decision given the likely profound
implications for the patentability of inventions in this field.

2.2 The decision results from a referral to the CJEU by the German Court (Bundesgerichtshof) in
relation to German Patent DE19756864 (Brüstle) granted in 1999. This patent, filed in 1997, related
to isolated and purified neural precursor cells derived from embryonic stem cells and their use for the
treatment of neural disorders such as Parkinson’s disease. Greenpeace brought an action for the
annulment of the Brüstle patent arguing that the claims directed to precursor cells obtained from
hESC contravened the morality provisions of German patent law. The German Court considered that
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the decision was dependant on interpretation of Article 6 of the Biotech Directive 98/44 , upon which
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the morality provisions of the German statute are based . This states, among other things, that uses
of human embryos for industrial or commercial purposes shall be considered unpatentable.

3. Questions referred

3.1 In light of this the German Court referred three questions to the CJEU for a preliminary ruling:

3.2 Question 1

1
  http://curia.europa.eu/
2
  Directive 98/44/EC Article 6
1. Inventions shall be considered unpatentable where their commercial exploitation would be contrary to ordre public or
morality; however, exploitation shall not be deemed to be so contrary merely because it is prohibited by law or regulation.
2. On the basis of paragraph 1, the following, in particular, shall be considered unpatentable:
(a) processes for cloning human beings;
(b) processes for modifying the germ line genetic identity of human beings;
(c) uses of human embryos for industrial or commercial purposes;
(d) processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial
medical benefit to man or animal, and also animals resulting from such processes.
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  Section 2, paragraph 2 No. 3 PatG (German Patent Act) a patent shall not be granted for the use of human embryos for
industrial or commercial purposes.

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3.2.1 What is meant by the term “human embryos” in Article 6(2)(c) of Directive 98/44/EC? Does it
include all stages of the development of human life, beginning with the fertilisation of the ovum, or
must further requirements, such as the attainment of a certain stage of development, be satisfied?

3.2.2 Does this also include: (1) unfertilised human ova into which a cell nucleus from a mature
human cell has been transplanted; (2) unfertilised human ova whose division and further development
have been stimulated by parthenogenesis?

3.2.3 Are stem cells obtained from human embryos at the blastocyst stage also included?

3.3 Question 2

3.3.1 What is meant by the expression “uses of human embryos for industrial or commercial
purposes”? Does it include any commercial exploitation within Article 6(1) of the Directive, especially
use for the purposes of scientific research?

3.4 Question 3

3.4.1 Is an invention considered unpatentable in relation to Article 6(2)(c) of the Directive even if the
use of human embryos does not form part of the technical teaching claimed, but is a necessary
precondition of its application, where it concerns a product whose production necessitates the prior
destruction of human embryos or because the patent concerns a process which requires a base
material obtained by destruction of human embryos?

4. Advocate General’s Opinion

4.1 In March 2011 the Advocate General (AG) Yves Bot issued his preliminary opinion in response to
the questions referred by the Bundesgerichtshof. The AG’s opinion provided clarification of the
meaning of Article 6(2)(c) of Directive 98/44/EC, and controversially argued that even inventions
making use of hESC from long established cell lines were unpatentable on moral grounds.

4.2 In this opinion, the AG provided useful guidance as to what constitutes a human embryo. He
pointed out that Directive 98/44 itself gives no definition of the concept of a human embryo, because
of this, the AG indicates that he took guidance from the legislation of the Member States, the
provisions of the directive (even though this does not provide a direct definition), and current scientific
information.

4.3 The AG points out that legislation of the Member States is not very helpful due to the lack of any
consensus as to when a human embryo comes into existence, therefore, was quickly dismissed. To
help in defining what a human embryo is, the AG draws on the wording of the Directive itself. He
argues that this provides an important indication of what should be defined when considering what
constitutes a patentable invention.

4.4 Specifically, the AG refers back to Article 5 of Directive 98/44/EC which states that “The human
body at the various stages of its formation and development………cannot constitute patentable
inventions”. In light of the Article 5 exclusion, he concludes that the question to be answered in
relation to patentability is - what stage of development of the human body must be given the legal
categorisation of embryo? He argues that this must be considered in conjunction with the
requirement that patent law must be applied so as to respect the fundamental principles safeguarding
the dignity and integrity of the person.

4.5 Turning to current scientific understanding, the AG states that it is “universally accepted” that
development from conception begins with a few cells, which exist in their original state for only a few
days. The AG concludes that these totipotent cells, no matter how they are produced, represent the

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first stage of the human body and as such must be legally categorised as embryos and so excluded
from patentability. This assertion that it does not matter how the totipotent cells are produced leads
the AG to the view that not only must totipotent cells produced after fertilisation be excluded from
patentability, but unfertilised ova into which a cell nucleus from a mature cell has been transplanted
(nuclear transfer), and unfertilised ova which are stimulated to divide by parthenogenesis, must also
be excluded because these cells also constitute embryos.

4.6 The AG then turns his attention to pluripotent cells present in the blastocyst. The AG argues that
since the blastocyst, from which the pluripotent cells are derived, develops from the totipotent cells it
is itself one of the aspects of the development of the human body and constitutes one of its stages
and so must accordingly be categorised as an embryo. This in itself is not contentious.

4.7 He also accepts that pluripotent cells in isolation cannot themselves develop separately into a
complete human being and so cannot individually be considered as constituting an embryo
[paragraph98].

4.8 However, he points out that Directive 98/44/EC accepts that the principle of dignity and integrity of
the person must be considered in relation to patentability and that this extends to the human body at
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any stage of its formation or development (Recital 16) .

4.9 In light of this, the AG concludes that because pluripotent stem cells are removed from the
blastocyst, which itself is categorised as an embryo, resulting in its destruction, patentability of the
pluripotent stem cells must be excluded for reasons of morality and ordre public.

4.10 This is the case even if the description does not contain any reference to the use of human
embryos, but if the application of the technical process necessitates the prior destruction of human
embryos or their use as a base material.

4.11 It is important to note here that the AG provided no indication of when the prior destruction
necessary for application of the technical process needs to occur. Therefore, it was unclear from the
Ag’s opinion whether the use of long established stem cell lines would fall within this exclusion.

4.12 An indication that perhaps the AG did consider such cell lines are within the scope of the
exclusion is found in paragraph 103 of the opinion which stated that “it is not possible to ignore the
origin of this pluripotent cell. It is not a problem in itself that it comes from some stage in the
development of the human body provided only that its removal does not result in the destruction of
that human body at the stage of its development at which the removal is carried out.”

5. Decision of the Court

5.1 Subsequent to the AG’s opinion, the CJEU issued its decision on 18 October 2011. This in large
part followed the conclusions reached in the AG’s opinion. The answers given to the referred
questions are set out below and followed by a brief analysis of the reasons given by the Court in
reaching their decision.

5.2 Ruling on Question 1 - What is meant by the term “human embryos”? – the CJEU decided that:

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   Recital (16) Whereas patent law must be applied so as to respect the fundamental principles safeguarding the
dignity and integrity of the person; whereas it is important to assert the principle that the human body, at any stage in
its formation or development, including germ cells, and the simple discovery of one of its elements or one of its
products, including the sequence or partial sequence of a human gene, cannot be patented; whereas these principles
are in line with the criteria of patentability proper to patent law, whereby a mere discovery cannot be patented;

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5.2.1 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:

5.2.2 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’;

5.2.3 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.

5.3 Ruling on Question 2 - What is meant by “uses of human embryos for industrial or commercial
purposes”? – the CJEU decided that:

5.3.1 The exclusion from patentability concerning the use of human embryos for industrial or
commercial purposes set out in Article 6(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.

5.4 Ruling on Question 3 - What is the extent of exclusion for the use of human embryos? – the CJEU
decided that:

5.4.1 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.

6. Analysis of the Decision

6.1 Question 1

6.1.1 In coming to its decision in relation to the first question, the CJEU bore in mind that the definition
of a human embryo is a very sensitive social issue in many Member States and can differ
significantly. However, it indicates that in relation to European Union law the meaning and scope of
the term human embryo must be given a uniform and independent interpretation. The CJEU further
specified that in relation to the present reference it 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 Directive
98/44/EC.

6.1.2 In this regard, the CJEU points out that the preamble to the Directive states that although it
seeks to promote investment in the field of biotechnology, use of biological material originating from
humans must be consistent with regard for fundamental rights and, in particular, the dignity of the
person. The context and aim of the Directive thus show that the European Union legislature intended
to exclude any possibility of patentability where respect for human dignity could be affected. It follows
that the concept of ‘human embryo’ within the meaning of Article 6(2)(c) of the Directive must be
understood in a wide sense.

6.1.3 The CJEU therefore agreed with the AG’s opinion that any 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.

6.1.4 They further concurred that the classification must also apply to a non-fertilised human ovum
into which the cell nucleus from a mature human cell has been transplanted and a non-fertilised

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human ovum whose division and further development have been stimulated by parthenogenesis. The
decision states that although those organisms have not, strictly speaking, been the object of
fertilisation they are capable of commencing the process of development of a human being, and so
must be excluded from patentability.

6.1.5 As regards stem cells obtained from a human embryo at the blastocyst stage, the CJEU decided
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 and, therefore, are included
within the concept of “human embryo” within the meaning and for the purposes of the application of
Article 6(2)(c) of the Directive.

6.1.6 The decision thus agrees with the opinion of the AG and provides clarification of the meaning of
the term human embryo as used in Article 6(2)(c) of Directive 98/44/EC.

6.1.7 It appears that this final conclusion has been included to account for future scientific
developments which would allow pluripotent embryonic stem cells to be manipulated such that they
could develop into a human being and thus become human embryos within the meaning of the
Directive.

6.2 Question 2

6.2.1 In relation to the second question the CJEU makes the important point that the purpose of the
Directive is not to regulate the use of human embryos in the context of scientific research. It is limited
to the patentability of biotechnological inventions. Therefore the decision does not per se affect the
ability to undertake such research which is determined by national laws in each Member State.

6.2.2 It concludes that, although the aim of scientific research must be distinguished from industrial or
commercial purpose, the use of human embryos for the purposes of research which constitutes the
subject-matter of a patent application cannot be separated from the patent itself and the rights
attaching to it i.e. the commercial purpose.

6.2.3 It further confirms the view of the EPO that inventions for therapeutic or diagnostic purposes
which are applied to the human embryo and which are useful to it avoid exclusion from patentability.

6.3 Question 3

6.3.1 In relation to the third question, the CJEU concluded that 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. They consider that this
must also relate to the use of a human embryo within the meaning of Article 6(2)(c) of the Directive.

6.3.2 Importantly, and most controversially, the final sentence of paragraph 49 of the Decision states
that: “The fact that destruction [of a human embryo] 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”.

6.3.3 It is how this statement is interpreted by the EPO and the national courts which determine
whether any further European patents based on hESC technology are granted and whether any such
patents currently in force in Europe will be enforceable.

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7. Discussion

7.1 When considering the decision of the CJEU its interplay with the decision of the Enlarged Board of
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Appeal of the EPO in G2/06 issued in November 2008 must be addressed. This decision relates to a
referral to the Enlarged Board in relation to a patent in the name of Wisconsin Alumni Research
Foundation (WARF) whose claims were directed towards primate embryonic stem cell cultures. In this
case the Enlarged Board was asked to decide if the EPC forbids the patenting of claims directed to
products (human embryonic stem cell cultures) which - as described in the application - at the filing
date could be prepared exclusively by a method which necessarily involved the destruction of the
human embryos from which the said products are derived, if the said method is not part of the claims?
It was also asked to decide whether it is of relevance that after the filing date the same products could
be obtained without having to recur to a method necessarily involving the destruction of human
embryos (eg derivation from available human embryonic cell lines)?

7.2 The Enlarged Board decided that if production of a claimed product necessarily involved the
destruction of a human embryo its patentability was to be denied under Rule 28(c), which is identical
to Article 6(2)(c) 98/44/EC, because it relates to the use of human embryos for industrial or
commercial purposes. Furthermore, the board stated that it was of no relevance that the same
products could be obtained without having to recur to a method necessarily involving the destruction
of human embryos after the filing date.

7.3 Subsequent to this decision the EPO adopted the pragmatic practice of allowing patents directed
towards products derived from hESC where their filing date is after 9 May 2003. This is the date
when human embryonic cell lines were deposited at the US National Institute of Health by the Israel
Institute of Technology. This has been based on the reasoning that since hESC were available that
did not necessarily involve the destruction of a human embryo the patents should escape the
exclusion. There has been some dispute at the EPO regarding whether this date should be
considered the earliest date at which hESC lines were available, with applicants in cases with an
earlier filing date arguing that this is not the correct cut off point. There is at least one appeal pending
in relation to this. This case will give the EPO an early opportunity to provide guidance on how it will
apply the ruling of the CJEU.

7.4 The decision of the CJEU appears to go further than that of the Enlarged Board in stating that the
exclusion extends to inventions 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.

7.5 As discussed above the passage in paragraph 49 of the decision states that “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”. Reading the words of this passage
literally, it appears that this could be very problematic for inventions which involve, directly or
indirectly, the use of such human embryonic stem cells. The CJEU appear to be adopting the position
that even if a hESC line has been established and used for a number of years and the use of this is
not regarded as immoral or illegal in a Member State, the fact that at some stage in its development a
human embryo was destroyed means that any subsequent inventions are unpatentable.

7.6 In relation to the EPO, it should be noted that this is not a member of the European Union and so
is not bound by the decision of the CJEU. However, in the case of biotechnology, the EPO have
incorporated the Biotech Directive (98/44/EC) directly into the EPC. In light of this it would seem likely
that the EPO will take account of the decision of the CJEU. Indeed, in the President’s Blog posted on

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    http://www.epo.org/law-practice/case-law-appeals/pdf/g060002ex1.pdf

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3 November 2011, Benoît Battistelli, President of the EPO stated that “If the judges rule in favour of a
restrictive interpretation of biotech patentability provisions, the EPO will immediately implement it”.

7.7 It is understood that the EPO has recently issued internal guidance to the Examiners indicating
that the CJEU decision should be applied to all cases relating to human embryonic stem cells which
will now need to be either amended to disclaim the unpatentable subject matter or will be refused.

7.8 It is also understood that the UKIPO is considering the implications of the decision of the CJEU
and are not waiting for the referring German Court to issue its ruling. Therefore, it is likely that
pending UK applications will similarly need to be amended to remove the unpatentable subject matter
or will be rejected.

7.9 A further commercial question which must be considered in relation to granted patents in this
area, particularly for academic institutes and smaller enterprises, is are granted patents relating to
hESC worth the paper they are written on? In the current financial climate, patentees may consider
that it is not worth the expense of paying renewal fees to maintain what may be an unenforceable
right in states where the CJEU decision is binding.

7.10 However, it may not all be doom and gloom. Where it is possible to perform an invention without
a human embryo ever having been destroyed, perhaps through the use of Induced Pluripotent Stem
cell techniques, or through the use of non-destructive techniques for generating hESCs the invention
may fall outside the exclusion. This is because this invention will not have involved the destruction of
a human embryo at any stage. Although, in relation to the use of non-destructive techniques for
generating hESCs, it must be noted that the decision states that the exclusion extends to the use of
human embryos as “a base material” and therefore, if this language is construed in a restrictive
manner, the mere use of an embryo, whether it is destroyed or not may mean that the subject matter
is considered excluded. It will be interesting to see how the various jurisdictions interpret this
language.

7.11 This decision may mean that companies redouble their efforts in the area of IPS and non-
destructive technology because if a simple reliable and reproducible method of obtaining such cells
can be developed this could now be incredibly valuable.
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7.12 IPS technology was first described by Yu et al in 2007 and non-destructive techniques for
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obtaining hESCs were first described by Klimanskaya et al 2006 . It will be interesting to see whether
the EPO and national courts will consider it necessary to specifically show that a non-destructive or
IPS technique was used to produce the hESC or cell line, or whether they will take the position,
similar to that of the EPO after the WARF decision, that for applications filed after the appropriate date
the existence of such non-destructive techniques will be sufficient to overcome the exclusion.

7.13 It is also not clear, if it is required to show that non-destructive techniques were used, what level
of evidence will be required to show that an embryo used was not destroyed? Will it be sufficient to
show that the technique used to produce the hESC did not result in the destruction of the embryo, or
will it be necessary to show that the embryo used to produce the hESC was not subsequently
destroyed?

7.14 Finally, there has been a great deal of consternation in the stem cell community following this
decision with eminent scientists indicating that this could lead to the end of stem cell research in
Europe because European patents will not be available for the results. However, it should be
remembered that patents would still be available in other jurisdictions for research undertaken in

6
 : Junying Yu, Maxim A. Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer L. Frane, Shulan Tian, Jeff Nie,
Gudrun A. Jonsdottir, Victor Ruotti, Ron Stewart, Igor I. Slukvin, James A. Thomson (2007) Science, 21 Dec, Vol. 318 no. 5858
pp. 1917-1920. (Published Online: Nov 20, 2007).
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  Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R. (2006) Nature, Nov 23; 444:481-5. (Published Online: Aug 23, 2006).

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Europe. Furthermore, if the position becomes such that patents in relation to inventions involving the
use of hESC are not available in Europe, research will be able to be undertaken without being
encumbered by the existence of competitors’ patents and the requirement for licences. Therefore, if
research continues to be undertaken in this important area this may possibly make Europe the
location of choice.

For further information please contact:

Dr Stephen Blance
Tel: +44 118 950 9937
Email: steve.blance@avidity-ip.com

The information provided in this document is, of course, of a general nature and should not be
considered as legal advice; if you have any specific questions, please contact us as set out above.

© Avidity IP Ltd March 2012

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