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Introduction
Recent advancement in biotechnology [1] has necessitated grant of patent on living things, which was traditionally granted primarily for mechanical ‘inventions’. [2] This has generated considerable legal and ethical debate, as it means that now living materials (e.g., a plant or an element isolated from the human body [3] ) can be appropriable as property by others to make profit. The controversy is acute particularly on patents relating to human embryonic stem cells that require the deliberate necessary destruction of an otherwise viable embryo for their production and has the potential to develop into whole human beings. The European Biotechnology Directive [4] (hereinafter, the Directive) gave expression to some of these concerns by introducing certain ethical exclusions from patentability. The paper considers the scope of such exclusions in relation to patents involving human embryonic stem cells.
Stem cells
Stem cells are cells with properties to differentiate into various types of mature cells found in all vertebrate animals, including human beings. This ability to divide into further identical or different cell types are thought to contain the prospect of tissue repair necessary in the treatment of many debilitating diseases like Parkinson's, Alzheimer's, diabetes, stroke, spinal cord injuries and bone diseases. They are also key research tools for gaining important scientific knowledge about embryonic development e.g., birth defects and screening drugs for pharmaceutical companies, instead of animal models.
Stem cells can be derived from early embryos, aborted foetuses and adult tissues (from living or deceased donors). According to their development potential, they can be divided into three types: i) totipotent stem 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. [5]
Criteria for patent
Patents are granted in respect of inventions, i.e., technological improvements, great and small, which contain at least some scintilla of inventiveness over what is previously known. [6] It gives the inventor or the applicant an exclusive right to control commercial exploitation of the invention by others for a maximum of 20 years from application, thus enabling the applicant to recoup investment, which is mostly very large in biotechnological research. In return, there is a requirement for the disclosure of the detailed description of the invention in the patent specification for the information of the rest of industry and any others interested.
European patent law
The European Patent Convention (EPC) is the authoritative legal instrument on patent protection in Europe. [7] Thus a European patent must meet the validity specified in the EPC. According to article 52(1) of the EPC, a patent may be granted in all European countries provided that there is an “invention" (a concept which is not defined) and that invention is patentable that is: it must be novel (or not “anticipated) it must involve an inventive step (i.e., not obvious to anyone familiar with the field concerned) [8] it must be capable of industrial application [9] and further taking into account articles 52-57 of the EPC, it must not fall “as such" within any of the categories of subject-matter specifically excluded.
Patentability of stem cells
Patent on stem cells may involve either products (stem cells themselves) or processes involved in their isolation, culture or modification. They could also be for newly isolated stem cells, undifferentiated stem cell lines, differentiated stem cell lines or genetically modified stem cell lines.
However, for a long time, the EPC did not include detailed guidelines with regard to the patenting of inventions based on the use of ‘living’ material or elements from human origin. Neither, the case law of the European Patent Office (EPO) was extensively developed on this point. The Directive resulted to end this legal vacuum.
The Directive
The Directive resulted to establish legal certainty in the protection of biotechnological inventions within the EU. The Directive does not introduce a new set of substantive patentability requirements, neither does it change the existing conditions. According to article 3(1) of the Directive, biotechnology patents have to meet the same substantive patentability requirements as other inventions, which requirements are governed by national patent law.
The directive proclaims as a general rule the patentability of biological material. [10] As to the patentability of human material, article 5(1) of the Directive stipulates “the human body, at the various stages of its formations and development, and the simple discovery of one of its elements, including the sequence or partial sequence of a gene, cannot constitute patentable inventions." The reason for this exclusion from patentability is found in recital 16 of the Directive, which underlines that the human body and its elements, including germ cells cannot be patented as they are mere discovery and so not in line with the patentablity criteria of an ‘invention’.
Further, article 5(2) reads, “an element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element". This raises the question as to what extent the article applies to human stem cells. In this connection, in Case C-377/ 98, Kingdom of the Netherlands v European Parliament [11] , the Court of Justice, applying recitals 20 and 21 of the Directive held that only inventions which combine a natural element with a technical process enabling it to be isolated or reproduced for an industrial application can be the subject of an application for patent. Hence, the touchstone to decide whether or not elements from human origin are patentable or not, whether they are to be considered as discoveries or not, lies in the technical intervention – the isolation, purification or reproduction of the element – techniques which human beings alone are capable of putting into practice and which nature is incapable of accomplishing by itself. Thus human stem cells as they appear in their natural environment would not be considered patentable, whereas human stem cells which have been isolated, identified and reproduced outside the human body would not be excluded from patentablility.
Exclusions on grounds of morality
Article 5 of the Directive is further specifically subject to the provisions of Article 6 of the Directive clause 1 of which provides that inventions shall be considered unpatentable where their commercial exploitation would be contrary to ordre public or morality. This article closely resembles article 53(a) of the EPC which stipulates that European patents shall not be issued in respect of inventions the publication or exploitation of which would be contrary to public policy or morality. [12]
The role and meaning of the above morality exclusion under the EPC was first considered in the 1989 Harvard/Onco-mouse [13] decision. The case concerned the patentability of mice that had been genetically modifed so that they would develop cancer: a result it was hope would be useful in cancer research. The patent was granted on utilitarian ground that likely benefit to cancer research outweighs the suffering to the animal. The same utilitarian approach was adopted in 1991 when the EPO warned the pharmaceutical company UpJohn that it would not accept an application to patent a mouse into which a gene had been introduced such that the mouse would lose its hair in experiments to cure hair loss. [14] In weighing up the benefit that flowed from the invention as against the harm suffered by the mice, the EPO asserted that the invention was immoral and thus would not be patentable.
However, prior to the Directive, the EPC did not contain a specific provision concerning the admissibility of patents on human material. In view of the question of the patentability of biological material in general and human stem cells in particular, the other relevant provision other than article 53(a) was article 53(b) which states that European patents shall not be granted in respect of plant or animal varieties or essentially biological processes for the production of plants or animals, which provision does not apply to microbiological processes of the products thereof. Thus article 53(b) of the EPC did not give a clear-cut answer, to the question whether or not human stem cells could be subject of patent protection.
By contrast, the Directive goes into detail to specify what is contrary to “ordre public" and morality in the biotechnology sector, namely Article 6(2) provides in particular that the following are considered to be 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 and
(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." [15]
Recital 38 of the Directive, stresses that the purpose of the list is “to provide national courts and patent offices with a general guide to interpreting the reference to “ordre public" and morality …and obviously cannot presume to be exhaustive". Of the above, (a) and (c) are relevant for the purposes of this paper as they relate to human embryonic stem cells.
Processes for cloning (art. 6(2)a)
R ecital 40 of the Directive states that there is a consensus within the Community that intervention in the human germ line and the cloning of human beings offends against ordre public and morality and it is therefore important to exclude unequivocally processes for modifying the germ line genetic identity of human beings and processes for cloning human beings from patentablity. This exclusion, however, raises various questions. The first question is whether the exclusion of therapeutic or reproductive cloning is envisaged. An answer can be found in Recital 41 from the Directive which defines human cloning as “…as any process, including techniques of embryo splittings, designed to create a human being with the same nuclear genetic information as another living or deceased human being." This points in the direction of the exclusion of reproductive cloning, but not of therapeutic cloning.
In a ‘therapeutic cloning’ a nucleus from a cell of the patient to be treated is inserted into an enucleated egg cell. The ‘pseudoembryo’ so formed may be caused to divide to the blastocyst stage from which a stem cell line may be isolated. The importance of this is that the stem cell line may be used to treat the patient without the risk of rejection inherent in the use of stem cell lines derived from IVF embryos. The problem is that the first steps in this process are identical to what would be done (and may already have been done) for reproductive cloning. Consequently, research in therapeutic cloning might be paving the way for developments in reproductive cloning. Thus overall, it is questionable whether it was appropriate to have this ethical exclusion in a situation where withholding a patent does not prevent commercial exploitation. [16]
The second question is what is to be understood by ‘human being’? The Directive does not offer any definition. Current national legislations employ differing definitions of ‘human being’ which might lead to a different scope of the exclusion in the different member states. In fact, it has been suggested that the scope of the exclusion will depend on how ‘human being’ is defined. [17] In particular, ‘human being’ may be defined in such a way as not to include human embryos and embryonic tissue. Further, it should be noted that the EPO declared that methods in a cloning process which fused human and pig cells were contrary to morality. As a consequence the applicants did not pursue the application any further. [18] As such, it seems that even if the cloning of human embryos was not caught by Article 6(2)(a) it would fall under the general prohibition in Article 52(a) of the EPC or Article 5 of the Directive.
Use of human embryo (art. 6(2)c)
With regard to article 6(c), question arises whether the Directive envisages the exclusion of the use of embryos for research purposes. It is possible that there can be inventions with a combined commercial and therapeutic purpose. Recital 42 of the Directive stipulates in this regard that the exclusion of human embryos for industrial or commercial purposes in any case does not affect “inventions for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it", which are not excluded from patentablity. This does not make clear what the fate of an invention would be which has both combined commercial and therapeutic purpose.
Further it is not clear whether the production of embryonic stem cell lines from human embryos constitute commercialisation of human embryos. Clearly, if someone were to invent a technique for using embryos directly to produce a commercial product (e.g. an anti-cancer drug,) no one could deny that this would represent the commercialisation of human embryos.
However, the European Patent Office has in the past granted patents covering human embryonic stem cells and methods involving them. Of major interest has been a patent granted to Edinburgh University in December 1999. This was before the Directive was inserted in the EPC and took effect.
The 'Edinburgh' patent was 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, there was widespread public agitation as it was believed to enclose human cloning methods and 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.
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) of EPC (article 6(2)c of the Directive). To answer this question the Division relied on Rule 23e(1) of the EPC (article 5(1) of the Directive) 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 decision was that human embryonic stem cells per se are not patentable under Rule 23d(c).
By contrast, in April 2003, the UK Patent Office issued a practice note [19] setting out its position 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). Hence, stem cells (with the exception of totipotent cells) are patentable in the UK.
The position taken by the UK office has much to commend it whereas the position taken by the EPO is regrettable. 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. [20] Furthermore, it is in contradiction to the approach now adopted by the UK Office which violates the purpose of the Directive that came into existence with a view to harmonise the laws relating to biotechnological inventions within the EC.
Conclusion
The scientific exploration of nature benefits mankind through discoveries concerning animate and inanimate matter. Where such discoveries are the basis of inventions which can be developed into industrial processes and products there is no reason in law or in principle to deny patent protection for such inventions unless they are grossly contrary to public policy and morality. In this regard, the exclusions from patentability as contained in articles 5 and 6 of the Directive seem to strike a good balance. But there needs to be further guidelines as to the interpretation of particular phrases in the said articles such as ‘human being’, ‘therapeutic cloning’, ‘use of human embryo for industrial and commercial purpose’ and so on.
With regard to the human embryonic stem cells, the position taken by the European Patent Office in the Edinburg University case is regrettable when there are important scientific reasons for developing such cells. This would certainly handicap EU countries in the development of stem cell medicine.
Overall it was probably not a good idea to include these ethical exclusions in the patenting process. It would exert enormous pressure on the patent office without the benefit of suitable advice from qualified ethicists. Further, it would also result in conflicting decisions between national patent offices of the EU. A better option is perhaps to regulate these issues like human cloning, embryo research, etc. by European or national law clearly stipulating what is and is not permissible.
Bibliography
Acts, Conventions and Directives
1. The Patent Act 1977 (UK)
2. Directive 98/44/EC on the Legal Protection of Biotechnological Inventions
3. European Patent Convention 1977
Articles
1. Crespi, Stephen, Biotechnology patenting: the wicked animal must defend itself, European Intellectual Property Review, Volume 17, 1995, pp. 431-441.
2. Curley, Duncan and Sharples, Andrew, Patenting Biotechnology in Europe: The Ethical Debate Moves On, European Intellectual Property Review, Volume 24, 2002, pp. 565-570.
3. Dwyer, Deirdre, Beyond Autonomy: The Role of Dignity in ‘Biolaw’, Oxford Journal of Legal Studies, Volume 23, 2003, pp.319-331.
4. Llewelyn, Margaret, The legal protection of biotechnological inventions: an alternative approach, European Intellectual Property Review, Volume 19, 1997, pp. 115-127.
5. Nott, Robin, “You Did It!": The European Biotechnology Directive At Last, European Intellectual Property Review, Volume 20, 1998, pp. 347-351.
6. Sampson, Timothy, Achieving Ethically Acceptable Biotechnology Patents: A Lesson from the Clinical Trials Directive, European Intellectual Property Review, Volume 25, 2003, pp. 419-425.
7. Sherman, Brad, Patent law in a Time of Change: Non-obviousness and Biotechnology, Oxford Journal of Legal Studies, Volume 10, 1990, pp. 278-287.
8. Thumm, Nikolaus, Ethical considerations raised by biotechnology patents, The Institute for Prospective Technological Studies Report, No. 51, 2001, pp. 20-25.
9. Vossius, Volker, Patent protection for animals: Onco-mouse/Harvard, European Intellectual Property Review, Volume 12, 1990, pp. 250-254.
Books
1. Bentley, Lionel and Sherman, Brad, Intellectual Property Law, Oxford University Press, 2002.
2. Cornish, William and Llewelyn, David, Intellectual Property: Patents, Copyright, Trade Marks and Allied Rights, London: Sweet & Maxwell, 5 th edition, 2003.
Reports
1. Opinion No. 16 on the Ethical Aspects of Patenting Inventions involving Human Stem Cells , European Group on Ethics in Science and New Technologies to the European Commission, 2002.
2. Overwalle, Geeertrui Van, Study on the Patenting of Inventions Related to Human Stem Cell Research, European Group on Ethics in Science and New Technologies to the European Commission, 2001.
[1] Biotechnology is the “engineering" of genetic material towards practical ends such as medical and veterinary advances, modified crops and improved animal breeds.
[2] Some “industrial" processes have traditionally used the capacities of living matter to make products, as with yeasts in brewing and baking. Yet for a long period, there had been an embargo on patents for things found in nature. For example, it is only i n 1980, that the US Supreme Court overturned its previous case law to allow the granting of a patent on living matter, namely an oil degrading bacterium ( Diamond v. Chakrabarty 65 Law Ed. (2d) 144 (1980), SC (US). Since then, there is a standing practice for patenting biotechnological inventions on living matter, for instance micro-organisms, genes and cell lines including human ones such as cancer cell lines.
[3] In a famous U.S. case, the California Supreme court held that John Moore, patient whose doctor obtained a patent on a cell line retrieved from his spleen had no property rights over cells that were once taken from his body.
[4] Directive 98/44/EC of the European Parliament and of the Council on the Legal Protection of Biotechnological Inventions.
[5] For details see, Overwalle, Geeertrui Van, Study on the Patenting of Inventions Related to Human Stem Cell Research, European Group on Ethics in Science and New Technologies to the European Commission, 2001, pp. 8-12.
[6] Cornish, William and Llewelyn, David, Intellectual Property: Patents, Copyright, Trade Marks and Allied Rights, London: Sweet & Maxwell, 5 th edition, 2003, p. 7.
[7] Since 2002, there are now 30 countries participating in the system. Cornish, Ibid., at p. 125.
[8] Thus a simple discovery cannot constitute a patentable invention. One of the main difficulties regarding patenting in biotechnology, is the ability to distinguish between a simple discovery which is not patentable and an invention as such, which is patentable.
[9] In this respect, medicine and agriculture are considered to be “industry".
[10] Article 3(1) of the Directive. For the purposes of the Directive, article 2(1)(a) defines biological material as “any material containing genetic information and capable of reproducing itself or being reproduced in a biological system.
[11] (2002) 33 I.I.C. 722, ECJ.
[12] The concept refers mainly to the respect of human dignity, which is at the roots of human rights and is mentioned in Article 1 of the Charter of Fundamental Rights.
[13] [1990] EPOR 4.
[14] See Bentley, Lionel and Sherman, Brad, Intellectual Property Law, Oxford University Press, 2002, p.407.
[15] These are now mirrored in Rule 23d, Implementing Regulations to the EPC (introduced by (1999) OJEPO 437).
[16] In fact, recital 14 of the Directive states, “a patent for invention does not authorise the holder to implement that invention, but merely entitles him to prohibit third parties from exploiting it for industrial or commercial purposes".
[17] Bostyn, S., The patentability of genetic information carriers, Intellectual Property Quarterly, p. 1,11.
[18] Patent applications for the cloning of embryos (including human embryos) as well as mixed-species embryos from pigs and humans <http://dailynews.yahoo.com.h/nm/200001006/humanpig_1.html> 27 Oct. 2000.
[19] See, UK Patent Office Practice Note 2003 at http://www.patent.gov.uk/cgi-bin/
[20] One example is the US patent awarded to the Wisconsin Alumni Research Foundation (WARF), for human pluripotent stem cells derived from spare embryos created for infertility treatment. That patent gives WARF control over who may work with its five stem cell lines and for what purpose.
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