Patentability of stem cells in Europe

Introduction

Stem cell research is giving scientists the power to create new tools which might one day be used to repair or replace tissues, for example, to repair spinal cord injuries, to treat diabetes, Parkinson's disease, osteoporosis and heart attacks. However, one technically favoured source of human stem cells is the early human embryo, and such embryos are destroyed when the stem cells are removed. This raises significant moral and ethical questions regarding whether society is willing to accept the sacrificing of such embryos, if necessary, for research and/or therapeutic uses.

These moral and ethical questions are also of significance to the patenting of materials derived from human embryos since the patent systems in Europe, at least, contain provisions which prohibit the patenting of inventions which are deemed to be immoral or unethical. However, there is significant concern that recent legislative events may have the effect of driving research on stem cells derived from human embryos out of the EU.

The patent system

Patents are granted to inventions that are novel, inventive and capable of use in any form of industry. The grant of a patent gives the patent owner the right to prevent others from exploiting the invention for a set period of time (generally up to 20 years) in the country for which the patent has been granted. In return for this, the patent owner must make full details of the invention available to the public, so at the end of the patent life, the public is free to use the invention.

In Europe, two patent systems co-exist. Under the European Patent Organisation, which is administered by the European Patent Office (EPO), patents are granted which may cover up to 38 European states. In addition to this, each of the individual European states has its own patent system. The patent laws of the European Patent Organisation and the individual European states are based on the same principles, although minor differences do exist. 

An attempt to harmonise these patent laws further was made through the adoption by the European Parliament in 1998 of a Directive on the Legal Protection for Biotechnological Inventions (Directive 98/44/EC, generally known as the ‘Biotech Directive’). The member states of the EU were obliged to implement all of the provisions of the Biotech Directive in their national laws and most have done this (although some member states have not implemented all of the provisions).

Despite the fact that the EPO was not bound by the Biotech Directive (the EPO is not a member state of the EU or an EU organisation), the rules of the European Patent Convention (EPC) have been amended to incorporate a number of the provisions of the Biotech Directive.

Patenting of cells

The patentability of cells is assessed in the same manner as any other invention, that is, for a patent to be granted, the cells must be novel, inventive and capable of use in industry.

Cells are deemed to be novel if they have been isolated or purified from their natural environment or reproduced outside the body. This issue is clarified by Recitals 20-21 of the Biotech Directive which state specifically that isolated forms of such cells are in principle patentable:

'(20) Whereas, therefore, it should be made clear that an invention based on an element isolated from the human body or otherwise produced by means of a technical process, which is susceptible of industrial application, is not excluded from patentability, even where the structure of that element is identical to that of a natural element, given that the rights conferred by the patent do not extend to the human body and its elements in their natural environment;

 (21) Whereas such an element isolated from the human body or otherwise produced is not excluded from patentability since it is, for example, the result of technical processes used to identify, purify and classify it and to reproduce it outside the human body, techniques which human beings alone are capable of putting into practice and which nature is incapable of accomplishing by itself;'

The invention must also be inventive, that is, not obvious to a person who is skilled in the relevant area of technology; and capable of use in any kind of industry.

Immoral inventions are not patentable

The EPC and the patent laws of most European states contain provisions that do not permit the patenting of inventions which are immoral or contrary to public order. An often-quoted example of an immoral invention is a letter bomb. The Biotech Directive refers to a number of inventions which are considered to be immoral; these include processes for cloning human beings.

Under the Biotech Directive, non-human animal cells and non-embryonic human cells are in general not considered to fall within the provisions against the patenting of immoral inventions. Such cells (including stem cells) may therefore be patented provided that they fulfil the patentability criteria mentioned above.

Patentability of human embryonic stem cells

Whilst the Biotech Directive does not contain any specific references to the patenting of human embryonic stem cells, there are some provisions in the Biotech Directive which have been interpreted as having an indirect effect on whether or not these cells can be patented. In particular, the Biotech Directive prohibits the patenting of ‘uses of human embryos for industrial or commercial purposes’ on grounds of morality. The scope of this exclusion has been interpreted differently by different patent offices.

EPO approach

As far as the EPO is concerned, questions about the extent of this exclusion from patentability were raised by the Examining Division and Technical Board of Appeal of the EPO in Wisconsin Alumni Research Foundation’s EP patent application (EP 96903521.1).  These questions were then referred to the highest legislative body of the EPO, i.e. the Enlarged Board of Appeal, for a decision on this matter. The Enlarged Board of Appeal took written submissions on these questions from all concerned parties in October 2007 and also oral submissions from Wisconsin Alumni Research Foundation (WARF) and the President of the EPO in June 2008. Their decision issued in November 2008.  The Enlarged Board decided that inventions which require the destruction of human embryos in order to put them into practice fall within the 'uses of embryos for industrial or commercial purposes' exclusion laid down in the Biotech Directive. As such, they ruled essentially that WARF’s invention was immoral if it required the destruction of a human embryo. However, since that decision the EPO appears to be allowing patents where a deposited stem cell line is used.

UK approach

The UK Intellectual Property Office (UK IPO) has taken a different line from the EPO. In a Practice Notice issued in April 2003, the UK IPO stated that it will distinguish between inventions that relate to totipotent stem cells on the one hand (that is, cells which are individually capable of producing an entire human body) for which patents are not being granted and pluripotent or multipotent stem cells on the other (that is, cells which are not individually capable of producing an entire human body) for which patents are being granted. The UK IPO revised their practice in February 2009 to take account of the above-mentioned EPO Enlarged Board WARF decision. Thus, the UK IPO will now not grant patents on processes for obtaining stem cells from human embryos or for stem cells which can only be obtained via the destruction of human embryos.

EU approach

The patentability of inventions which require the use of human embryos is also currently being considered by the Court of Justice of the European Union (CJEU). This case  centres around a German patent which was filed in 1997 by Oliver Brüstle and which relates to isolated and purified neural precursor cells for use in the treatment of neural defects. 

After the grant of the Brüstle patent, Greenpeace eV applied to the German courts to have the patent declared invalid on the grounds that, at the filing date of the patent in 1997, the neural precursor cells were only obtainable from human embryonic stem cells, that those stem cells could only be obtained via the destruction of human embryos and hence that the patent was immoral under the rules of the Biotech Directive (as discussed above). A key issue in this case is the definition of the term 'human embryo' and whether it covers all stages of human development, including human blastocysts (from which embryonic stem cells are obtained) or whether it only covers later stages of development (such as when the fertilised ovum is implanted into a uterus). The German court (the Bundesgerichtshof, i.e. the Federal Court of Justice in Germany) decided that it needed further guidance on the interpretation of the term 'human embryo' and hence, in January 2010, it referred a number of questions on this matter to the CJEU. 

In March 2011, a legal advisor to the CJEU (Advocate General M. Yves Bot) published his preliminary Opinion on the questions which had been referred to the CJEU. In his Opinion, the term 'human embryo' did indeed cover all of the early stages of human development after the fertilisation of the human ova, and all other similar cells which had the capability of forming a complete human being. Under this definition, all stem cell inventions which require the destruction of human embryos at any stage would be considered to be immoral.

Potential conflict between CJEU and EPO

The Opinion of the Advocate General appears to extend significantly the exclusion on patentability beyond the current practice of the EPO. 

Following the WARF decision, the EPO's view has been that inventions are not deemed to be immoral if the invention is based on human material which is obtainable without necessitating the destruction of a human embryo.  For example, if the invention involves the use of a human embryonic stem cell line and such cell lines were readily available at the filing date of the patent application, then the invention could be put into practice at the filing date without destroying human embryos, and hence the invention is potentially patentable.

However, in his Opinion, the Advocate General stated (paragraphs 109-110 of the Opinion):

"... inventions relating to pluripotent stem cells can be patentable only if they are not obtained to the detriment of the embryo... 

These cells are removed from the human embryo at the blastocyst stage and they necessarily entail the destruction of the human embryo".

Concern has been expressed by some that the Opinion proposes that all inventions relating to human pluripotent stem cells should be deemed to be unpatentable and that an invention is not patentable if a human embryo is destroyed at any stage, even if the destruction occurred far upstream of the invention and is not described in the patent application. It would also potentially mean that inventions using a deposited and publicly available stem cell line might be unpatentable. This lack of clarity is currently causing much concern to some European researchers and investors working in the area of human stem cells. The Advocate General's advice thus seems to go beyond the position taken by previous bodies, such as the EPO, that have looked at this issue in the past.

Final decision of the CJEU

The CJEU's decision on this matter is expected in a few months. The CJEU does not have to follow Advocate General's Opinion, but in practice the CJEU follows the Opinions in the most cases. 

Whatever the decision of the CJEU, its interpretation of the term 'human embryo' and the other points that it rules upon will be binding on the national courts (and hence, indirectly, on the national Patent Offices) of the EU member states. 

The CJEU decision may not, however, be directly binding on the EPO (because the EPO is not an EU organisation), even the rules of the EPO include the 'uses of embryos' exception to patentability which was imported from the Biotech Directive; these rules also require the EPO to take account of the Biotech Directive 'as a supplementary means of interpretation' when considering the EPO's rules.

Summary

Stem cell technology has the potential to revolutionise the way that certain diseases are treated. However, currently a favoured source of stem cells is from early human embryos and the use of such embryos raises significant moral and ethical questions.

The European Patent Organisation and the individual European states have patent laws which allow for the patenting of inventions relating to cells, including stem cells, provided that the inventions are novel, inventive and capable of use in industry. These laws also prohibit the patenting of inventions which are immoral.

In a landmark decision, the highest legislative body of the EPO has made a ruling on the patentability of inventions which can only be put into practice by destroying human embryos.  It decided essentially that the commercial exploitation of such inventions is immoral. The highest EU court (i.e. the Court of Justice of the European Union, CJEU) is currently considering the same issue, although concerns have been expressed by some that the CJEU decision might have a significantly wider effect than the EPO decision, and effectively render most human stem embryonic cell inventions unpatentable.

Basic research into the uses of stem cells is developing at a rapid pace, and indeed much research in this area is funded by the EU. However, significant capital investment is needed to convert this basic research into marketable products that are both safe and efficacious. This investment will not occur unless the companies/research institutions which are carrying out this research are given the prospect of recouping their initial investment via the patent system.

The purpose of the patent system is to encourage innovation and the production of inventions that benefit society. Ultimately, therefore, it is up to society to decide whether it wishes to encourage future stem cell research, if necessary, by clarifying the patent laws in this area; or whether such inventions should fall within the category of inventions which society deems to be immoral.

CIPA Life Sciences Committee
10 May 2011