A stem cell is a cell that displays two properties. When it divides by mitosis the daughter cells can either enter a path leading to a fully differentiated cell or remain a stem cell, thus ensuring that the pool of stem cells is not 'used up'. There are three types of cell defined by their development potential. These are (i) totipotent cells which are only found in the fertilised egg and the first four or so cells of a blastocyst and which have the potential to develop into whole human beings, (ii) pluripotent stem cells which are also isolated from embryos and have the potential to make any differentiated cell in the body but cannot develop into a whole human being and (iii) multipotent stem cells which can only differentiate into a limited number of tissue types and can be found in adult humans and animals or in embryos.

The articles of the EU Directive which are relevant to the patentability of the various cells are Articles 5(1), 6(2)c and 6(1) which read as follows:

Article 5(1)
The human body, at the various stages of its formation and development, and the simple discovery of one of its elements, including the sequence or partial sequence of a gene cannot constitute patentable inventions.

Article 6(2)c
The following in particular shall be considered unpatentable:
c) uses of human embryos for industrial or commercial purposes.

Article 6.1
Inventions shall be considered unpatentable where their exploitation would be contrary to ordre public or morality.

In September 1999, Articles 5(1) and 6(2)c were incorporated into the European Patent Convention (EPC) as new Rules 23e(1) and 23d(c) respectively. The provisions of Article 6(1) already existed in the EPC as Article 53a. The relevant articles of the Directive have also been incorporated into the national laws of UK, Denmark, Finland, Greece, Ireland, Spain and Portugal but due to political dissension, not into the laws of the other EU member states at present.

Since the UK is obliged to follow the provisions of the Directive, the UK Patent Office specifically considered its position on patenting stem cells in April 2003. It issued a practice note which sets out the Office's position as regards the patentability of processes for obtaining stem cells, human totipotent cells and human embryonic pluripotent stem cells. The notice confirms that the UK Office will not grant patents for processes for obtaining stem cells from human embryos since it regards such processes as excluded by virtue of the prohibition of uses of human embryos for industrial or commercial purposes. Neither will it grant patents for human totipotent cells since they have the potential to develop into an entire human body.

However, the UK Office has decided that human embryonic pluripotent stem cells which arise from further division of totipotent cells and do not have the potential to develop into an entire human body, can be patented. It is considered that these do not fall within the specific exclusions of Article 5(1) or 6(2)c of the Directive and neither should they be rejected on other unspecified moral grounds under Article 6(1). The Practice Note states that:

Although there is some opposition in the United Kingdom to research involving embryonic stem cells, a number of reports from influential UK political, medical and scientific bodies in recent years have emphasised the enormous potential of stem cell research including embryonic stem cell research, to deliver new treatments for a wide range of serious diseases. This indicates that on balance the commercial exploitation of inventions concerning human embryonic pluripotent stem cells would not be contrary to public policy or morality in the United Kingdom.

Thus, stem cells (with the exception of totipotent cells) are patentable in the UK providing they can satisfy the other criteria for patentability i.e. novelty, inventive step and so on. Regrettably, the European Patent Office does not seem to be taking the same approach. European patents covering human embryonic stem cells and methods involving them have been issued. Of major interest has been a patent granted to Edinburgh University (EP-B-0695351) in December 1999. Because this patent would have been accepted prior to September 1999 when the implementing regulations of the European Patent Convention were adapted to the EU Directive, the specific prohibitions of the Directive would not have been considered during the prosecution.

The 'Edinburgh' patent is concerned with methods of isolating, enriching and selectively propagating animal stem cells and was granted with claims to the general method of selecting cells, to cell mixtures, including stem cells, transfected with the marker gene and to a method of making a transgenic animal by introducing the transfected cells into a blastocyst. The claims were not restricted to using the method with any particular stem cells. Following grant the patent was opposed by fourteen parties, all with, among other things, ethical objections to the patent and a full written Decision was issued by the Opposition Division on 21st July 2003.

Although the claims of the patent were not limited with respect to the type of stems cells, the technology was exemplified only with mouse embryonic stem cells. The Opponents were able to convince the Opposition Division with technical evidence that there were serious doubts as to whether the stem cell selection procedure would work with embryonic stem cells from sources other than mouse, in particular with human embryonic stem cells. The claims therefore, were held insufficient so far as embryonic stem cells were concerned. However, the Division further held that the Opponents had not discharged their burden of proof that the invention would not work with stem cells other than embryonic stem cells. Thus, the patent was maintained with amended claims, including claims to stem cells per se, having a disclaimer to embryonic stem cells.

The Opposition Division went on to consider whether, in the absence of a disclaimer, the claims would have contravened new Rule 23d(c) prohibiting the patenting of “uses of human embryos for industrial and commercial purposes.

To answer this question the Division relied on Article 5(1) (EPC Rule 23e(1)), which confirms that the human body at its various stages of formation and development cannot be patented. They reasoned that this rule prohibits the patenting of human embryos. Thus, if Rule 23d(c) was also intended to exclude only the patenting of human embryos it would be redundant over Rule 23e(1). Therefore, the rule must be intended to exclude something over and above just the human embryo. It was thus decided:

In consequence, Rule 23d(c) EPC, in order to have a purpose exceeding the one of Rule 23e(1) has to be interpreted broadly to encompass not only the industrial or commercial use of the human embryos but also human ES cells retrieved therefrom by destruction of human embryos.

Therefore, the decision is that human embryonic stem cells per se are not patentable under Rule 23d(c). This is a very unsatisfactory outcome since, should the EPO continue to follow it, it would put Europe at a commercial disadvantage in the field compared to the US where over 100 patents covering human embryonic stem cells have already been granted. Furthermore, it is in contradiction to the approach now adopted by the UK Office.

Edinburgh have now filed an Appeal against the decision of the Opposition Division and requested that claims very similar to those originally granted be maintained. However, a decision on this is not expected for at least a year. The appeal is on the grounds that the Patentee considers that the Opposition Division did not consider sufficiency with regard to the technical contribution to the art, but had their opinion shaded by the moral issues and also, that the correct assessment of whether the work on mouse ES cells could be extrapolated across species was not performed. The patentee has also appealed against the decision to construe the claims as excluded from patentability under Rule 23d (c) EPC because they consider that this exclusion, which should be interpreted narrowly, was viewed too broadly, and that the Opposition Division exceeded its mandate.

Contact: Claire Baldock
Telephone: +44 20 7430 7500
E-mail: cbaldock@boult.com