Patenting Stem Cells of Human Origin ATRIP Conference, Tokyo, 2003 In the wake of the Commission’s first report on the 1998 Directive on the legal protection of biotechnological inventions......what is the legal and ethical position regarding patenting stem cells of human origin?......is Article 6 as clear or true to its aims as it could be?......what lessons can be learned for future bioethical debacles concerning patenting in Europe? Dr. Graeme Laurie Co-Director, AHRB Research Centre for Studies in Intellectual Property and Technology Law, School of Law, University of Edinburgh

The EC Biotechnology Directive 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. 2. 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. 3. The industrial application of a sequence or a partial sequence of a gene must be disclosed in the patent application. 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.

While reiterating, once again, the substantial economic, scientific and social benefits that can accrue from biotechnology... Majority of member states had failed to implement Directive; 8 now referred to the ECJ (July 2003) Commission is satisfied with terms of Articles 5 and 6 after C-377/98 Kingdom of the Netherlands v Council of the European Union and the European Parliament (2001) Further areas of research: –scope to be given to patents related to sequences or partial-sequences of genes isolated from the human body; –potential patenting of human stem cells and cells lines obtained from them. Commission Report COM (2002) 545 final, 7 October 2002

Stem Cell Controversy Stem cells have two unique properties : –They can divide and multiple more or less indefinitely without differentiation –They can be manipulated to differentiate into particular specialised cells Adult stem cells – research/use for 40 years; animal embryonic stem cells first isolate in 1981; human embryonic stem cells first isolated in 1998 Unique moral status of the embryo – at the moment we must both use and destroy a human embryo to establish (pluripotent) embryonic stem cells Realm of regulation : limits imposed to varying degrees – from outright ban (Austria) to permissive use for research (UK). N.B. Commission funding for FP6 only on pre-existing IVF embryos; cf – Parliament view in April In US, federal funding only available for pre-existing stem cells lines (9 August 2001) Is the prospect of patenting stem cells a step too far?

Stem Cell Patenting By 2002 over 2000 applications world-wide; over 500 on embryonic stem cells. More than 30% of all stem cell applications and 25% on embryonic stem cells granted (European Group on Ethics in Science and New Technologies (EGE) 2002) Currently pending before EPO: U.S. WARF patent —the isolation, culture and proliferation of human embryonic stem (ES) cells and derived cell lines. How broad is this likely to be? Expert Group established by the Commission. The ‘Edinburgh’ Patent (EPO, Opposition Proceedings, July 2002): –Patent entitled ‘isolation, selection & propagation of animal transgenic stem cells’ –Did this extent to humans? Might it lead to human reproductive cloning? –Opposition Division required amendment of patent to exclude human and animal embryonic stem cells –Rule 23(d)(c) – ‘uses of human embryos for industrial or commercial purposes’ – Does this mean that human embryonic stem cells are not patentable under the 1998 Directive? Embryonic stem cells are not embryos and never can be Their use is not the use of embryos as such

Further guidance on patenting stem cells EGE and UK PO - what is excluded? EARLY STAGE INTERFERENCES – Processes for cloning an embryo – expressly prohibited by Article 6 Processes for obtaining stem cells from an embryo – direct use of the embryo (Art.6) Totipotent human cells – a breach of Article 5; stem cells are not developed from embryos at this stage Isolated stem cells – too close to human origin. But why would Article 5 not apply (isolated stem cells do not exist naturally)? Also no identified use; industrial application Unmodified stem cells – too broad a monopoly; potentially wide range of undescribed uses; industrial application – not an issue about embryos per se

Ethical Justifications 1.Concerns are not always about the embryo – a.breadth of patents is a general issue b.also demonstrates that ethical concerns permeate all of patent law and can be accommodated without recourse to morality provisions 2.Only early interventions are excluded – a logical progression? a.We have a narrow and literal interpretation of the provision of Article 6 (processes for cloning; uses of embryos), but b.Sine qua non is that we must use and destroy an embryo before later products and processes become patentable, so c.Do these interpretations uphold the spirit of Article 6?

How clear and effective is Article 6? What is the rationale behind Article 6? - to respect human dignity, and - to guard against instrumentalisation of the human body (ECJ (2001)/COM (2002)) Are these criteria met from an ethical perspective? Production of embryonic stem cells is a continuum - the prohibition on patenting early stage interventions does not detract from the fact that later patent possibilities mean that there is every incentive to create stem cells - which necessarily involves the use (and destruction) of an embryo Indeed, the availability of a patent is a good (economic) reason to pursue embryonic stem cell research (rather than fetal or adult stem cell research) So, subtle and narrow distinctions about the scope of the exclusions do not necessarily respect the dignity of embryos nor prevent their use towards ends other than their own.

Options? BROAD VIEW - Exclude embryonic stem cell patents? Problems of competitiveness, loss of benefits and also definition; where do you stop? NARROW VIEW - What is an ‘embryo’? Is a cloned organism an ‘embryo’? PRAGMATISM OVER ETHICS - Patent Office is concerned only with (i) the instant application and (ii) whether commercial exploitation of the invention is immoral. Questions about the wider impact of the patent are not relevant. ETHICS OVER PRAGMATISM - (i) respect for human dignity cannot be compartmentalised, broader impact of patent grant is also an ethical issue, (ii) the EGE has called for independent ethical evaluation of patent applications in controversial areas: a possible option for reform? These views tend to polarise the debate…

Options? ETHICAL PRAGMATISM - Difficulties arise because of failure to distinguish between objections to the invention itself and objections about its commercial exploitation. A. If we accept the permissibility of embryo research, is there anything objectionable of a different order about granting patents over derived products? - Free availability? Undermines the need for a balance - Commercial reality of (stem cell) research - Patent scope B. If we do not accept the permissibility of embryo research, then a fortiori, patenting is also unacceptable. Indeed, legal prohibition can be a more balanced measure of an invention’s unacceptability than the exclusions in Article 6. C. What if law is silent: ‘the prospect of patenting leads to offensive practices’ ? - Edinburgh patent is a pre-emptive moral judgment embodied in ‘precedent’ - Cf, EU funding of stem cell research and rapidly changing laws (Spain)? - Impact on future research if patenting is questionable?

Patenting Stem Cells of Human Origin What lessons can we learn? Embryonic Stem Cells are but the first in a long line of controversial applications It is far from certain that Article 6 provides us with sufficient clarity or consistency of approach: our ethical approach is unprincipled We should seek to separate out: ethical objections to science per se (probably best dealt with entirely outside patent system; and latter should not pre-empt former) ethical concerns about scope of monopoly (an appropriate question for the patent system) Science may save us from current problems - new techniques to produce stem cells not involving the creation of an embryo - ( e.g. parthenogenesis)......but this is no answer to the issues facing the European patent lawyer.