• Human Embryonic Stem Cells: EPO Provides Guidance on the Line Between Parentability and Immorality

    Human embryonic stem cells (hESCs) are considered by medical practitioners and researchers to be of significant importance as they are ‘pluripotent’ - they are capable of differentiation into any of approximately 200 unique cell types. As such, they are potentially useful in regenerative medicine, cell therapies, tissue replacement or as cell development research tools. hESCs are derived from early stage human embryos; they are isolated from the inner cell mass of the embryo at less than 14 days from conception.

    Rule 28(c) EPC prohibits grant of a European patent in respect of biotechnological inventions which concern, in particular, uses of human embryos for industrial or commercial purposes, thereby implementing Article 6(2)(c) of the EU Biotechnology Directive. On 25th November 2008 the Enlarged Board of Appeal at the European Patent Office gave it’s ruling in the case of the Wisconsin Alumni Research Foundation (WARF) application concerning the extent to which Rule 28(c) EPC applies to claims directed to stem cell products. WARF filed a patent application in 1996 with claims directed to a purified preparation of primate ESCs and a method of isolating primate ESCs. Rule 29(2) EPC states that an element isolated from the human body may constitute a patentable invention. hESCs are isolated from the human body, and are therefore potentially patentable. However, at the time of filing, the WARF application only described a method that included thedestruction of human embryos.

    During examination, claims to a cell culture of primate (including human) embryonic stem cells were refused on the grounds that a hESC product necessarily involved a ‘use’ of human embryos for industrial or commercial purposes, and this was a contravention of Rule 28(c) EPC. When WARF appealed the decision, the EPO referred a question to the Enlarged Board of Appeal (EBA), asking whether Rule 28(c) EPC forbids the patenting of claims directed to products that are prepared exclusively with a method that necessarily involves the destruction of human embryos, if the method is not a part of the claim.

    Rule 28 EPC gives examples of inventions that are not patentable under Article 53(a) EPC because they are deemed contrary to morality. WARF argued as there is no European consensus concerning the moral issues surrounding hESCs, they should not be excluded from patentability. WARF accepted that human embryos themselves are excluded from patentability under Rule 28(c) EPC, but argued that hESC cultures are not themselves embryos and therefore should be patentable.

    The EBA asked the President of the EPO to comment. The President accepted that hESC cultures were not themselves embryos. Nevertheless, she argued that WARF’s technical contribution to the art involved the use of human embryos for industrial and commercial purposes, and that an invention includes not only the claimed subject matter but also the methods used by the Applicant to produce the invention.

    In the end, the EBA ruled (in Decision G2/06) that claims to inventions, which at the time of filing the application required the destruction of human embryos, are not allowable. Even where the method steps resulting in the destruction of human embryos are not included in the claim, the EBA stated that “A claimed new and inventive product must first be made before it can be used” and that the manufacture of the product was therefore relevant. As the only described manufacture of the WARF hESC culture necessarily involved the destruction of human embryos as an integral part, even though the claims are directed to the resultant product, the invention fell within the prohibition of Rule 28(c) EPC.

    Our comment

    The impact of this decision on patentability of human stem cells per se may not be particularly broad, which is good news for applicants. The question put to the EBA was somewhat narrow, and the decision merely states that Rule 28(c) EPC ‘…forbids the patenting of products which at the filing date could be prepared exclusively by a method necessarily involving the destruction of human embryos from which said products are derived…’ (emphasis added). This is a very case-specific decision. It does not, for example, clearly address the broader question of use of human embryos. There will be numerous cases to which the G 2/06 will simply not be relevant.

    Since the WARF application was filed, new methods have been developed for the production of stem cell lines that do not require the use of human embryos. These include ‘reprogramming’ techniques in which differentiated cells (such as skin cells) are induced to revert back to the pluripotent state, resulting in ‘induced pluripotent stem cells’. In this regard, it is noted that G 2/06 specifically states that ‘…this decision is not concerned with the patentability in general of human stem cells or human stem cell cultures.’ Accordingly, G 2/06 does not prevent the patenting of stem cell inventions that do not involve the use of human embryos.

    By focusing the decision on the destruction of embryos, the EBA has provided no direction as to whether hESCs prepared using methods in which the embryos remain viable would be allowable. Recently, techniques have been reported which purport to generate hESCs from human embryos without embryo destruction (Young Chung et al., 2008, Cell Stem Cell, Volume 2, Issue 2, 113-117). A patent application (WO/07/130664) filed in 2007 by Robert Lanza, the inventor of this method, includes a claim to ‘A human ES cell line derived from a human embryo but without destroying the human embryo produced by (a method)’. It will be interesting to see how the EPO will handle such a claim.

    Following the WARF decision, it is clear that the EPO will not grant claims to inventions that necessarily involve the destruction of human embryos. It is worth noting, however, that in 2003 the UK Intellectual Property Office issued a Practice Notice indicating that in principle it will grant claims directed to human embryonic pluripotent stem cells, although it will not grant claims directed to human tutipotent cells or methods of obtaining stem cells from human embryos. This Practice Notice has not yet been rescinded, leaving open the possibility that claims may still be obtained directed to human embryonic pluripotent stem cells in the UK.

    Our advice for applicants in the light of this decision is:

    • Where possible, applications should include a sufficient disclosure of at least one method by which the stem cells involved in the application can be produced without using human embryos.
    • If the invention necessarily involves the use of human embryos, where possible applicants should provide a disclosure of a method of production that does not involve the destruction of those human embryos.
    • For inventions involving the use of human embryos, Applicants should consider filing in the UK as well as at the EPO; The limitations of this decision has not been adopted in the UK.