A recent change in EPO practice allows for European patent applications requiring the use of human embryonic stem cell (hESC) lines to avoid the morality exclusion of Article 53(a) EPC, provided the effective date of the application is on or after 5 June 2003.
By way of background, according to Article 53(a) EPC, European patents shall not be granted for inventions “the commercial exploitation of which would be contrary to “ordre public” or morality”. Rule 28(c) EPC explicitly identifies “the use of human embryos for industrial or commercial purposes” as falling within this exception to patentability.
In decision G2/06 by the enlarged board of appeal, Rule 28(c) EPC was interpreted as prohibiting claims directed to products which “at the filing date could be prepared exclusively by a method which necessarily involved the destruction of the human embryos”. The enlarged board also noted this requirement extended beyond what was explicitly required by the claims, to all steps necessary to perform the invention (including the initial derivation of a cell line).
This provides the rationale for inventions requiring hESC lines being excluded from patentability under Article 53(a) EPC, when such cell lines could only have been obtained via the destruction of a human embryo at the effective date. The reasoning has been applied in inter alia, technical board of appeal decision T 2221/10.
However, the question arises, precisely what is considered a human “embryo”? Furthermore, are sources of hESCs available which did not, at any stage, result from the destruction of such an embryo? Finally, if so, when are such sources accepted as having been first disclosed in the art?
The wording of EU Directive 98/44/EC on the legal protection of biotechnological inventions has been implemented into the EPC through Rule 28(c). It is furthermore stated in the EPC that the Directive is to be used as “a supplementary means of interpretation” in the case of biotechnological inventions (Rule 26(1)), although it is not legally binding. Therefore, opinions of the Court of Justice of the European Union (CJEU) on the Directive are considered relevant to the interpretation of the EPC, and have been followed by the boards of appeal.
Firstly, in decision C-34/10 the CJEU agreed with an opinion of the Bundesgerichtshof that an isolated cell taken from a blastocyst was not to be considered an “embryo”. As a consequence, in decision T 1441/13, the EPO technical board of appeal initially found that the date on which a method for obtaining hESC lines without the destruction of a human embryo became available in the art was in February 2008. This was the publication of Chung et al. (2008)1 in Cell Stem Cell; in which viable hESC cultures were established after the non-destructive removal of blastomeres from early-stage embryos. The authors noted in particular that “to date, the derivation of all [hESC] lines has involved destruction of embryos”.
However, by contrast, in decision C-34/10 it was also indicated that a parthenote is to be considered an embryo within the meaning of Directive 98/44/EC.
Parthenogenesis is a method of artificially stimulating cell division in unfertilized ova using a series of chemical stimuli. The resulting cells (“parthenotes”) lack paternal DNA and, as a result, stop development at an early stage of embryogenesis. This is largely because gene expression signatures from the paternal or maternal chromosomes are often complementary. Therefore, most often both copies of the gene are required for development. A parthenote comprising two silenced copies of a maternal gene will not express the gene; consequently the parthenote is not able to undergo development into a human being. Parthenotes can therefore only be described as pluripotent cells. They can differentiate into almost any cell lineage in isolation, but lack totipotency, which cells require in order to undergo embryonic development.
In view of the above, the opinion of the CJEU in C-34/10 on parthenotes has been criticised as being technically inaccurate. Subsequently, following a referral from the UK High Court, the CJEU presented the amended view in decision C‑364/13 that “an unfertilised human ovum whose division and further development have been stimulated by parthenogenesis does not constitute a ‘human embryo’”.
The issue was furthermore considered by a technical board of appeal of the EPO in T 1808/13. In this instance, the Board considered several publications in the proceedings and concluded that a 2007 publication (Revozova et al.2) provided the first disclosure of hESC lines being successfully derived from parthenotes, and therefore without the destruction of a human embryo.
However, the EPO has recently established a new, earlier, date, when they consider the first such disclosure to have occurred. This is 5 June 2003, the publication date of WO 2003/046141 in the name of Advanced Cell Technology Inc. The EPO have since begun citing this date in examination proceedings as the first disclosure of a method in which hESC lines are obtained without the destruction of a human embryo at any stage.
Therefore, provided a European application has an effective date on or after 5 June 2003, the skilled person is considered to be able to obtain hESC lines necessary to work the invention via the disclosure of WO 2003/046141. As a result, inventions claimed in such an application will not be considered to contravene Article 53(a) EPC.
Explicit reference to hESC lines being derived from parthenotes, or WO 2003/046141, is not required in the description for Article 53(a) EPC to be satisfied, as the non-destructive method is considered available in the art to the skilled person. However, from our experience it is necessary to clearly indicate any examples making use of hESC lines obtained from destructive methods as being “reference examples”, and not illustrative of the invention.
The opinions of the boards of appeal in T 1808/13 and T 1441/13 also demonstrate an interesting interaction between decision G 2/10 by the enlarged board of appeal and the interpretations of Article 53(a) EPC discussed above.
It is now established practice that an “undisclosed” disclaimer (not expressly worded in the application as filed) may be used in a claim to carve out subject-matter excluded from patentability, for example under Article 53(a) EPC. This may be done without adding subject-matter beyond the application as filed and contravening Article 123(2) EPC. However, in decision G 2/10 it was established that, for the purpose of Article 123(2) it is also necessary to evaluate whether the subject-matter remaining in a claim after said disclaimer is disclosed to the skilled person in the application as filed, when accounting for common general knowledge.
Take, for example, the disclaimer in either a product or method claim requiring hESC cell lines: “wherein the human embryonic stem cell line has not been obtained by means of a process in which human embryos are destroyed” (as used in T 1441/13). Whether or not the subject-matter of the claim remaining after the disclaimer is disclosed in the application as filed (a product/method requiring a hESC line obtained without the destruction of a human embryo), is entirely dependent on the effective date of the application.
Prior to 5 June 2003, the method of WO 2003/046141 is not available to the skilled person. Therefore a hESC line obtained without destroying a human embryo is deemed not to have existed in the art. Consequently, the subject-matter of the claim remaining after the disclaimer is not disclosed (either explicitly or implicitly) to the skilled person in the application as filed, and contravenes Article 123(2) EPC. Such a claim is also considered unworkable (as the skilled person cannot obtain such a hESC line), and is therefore also insufficient at the effective date, in contravention of Article 83 EPC.
If the effective date is on or after 5 June 2003, an “undisclosed” disclaimer is no longer necessary to avoid Article 53(a) EPC, due to the availability of WO2003/046141.
Accordingly, there is relatively little practical advice which can be given in respect of inventions requiring hESC lines and agreement with Article 53(a) EPC. At present, whether or not Article 53(a) is contravened hinges on the effective date of the application. If this is on or after 5 June 2003, applicants should take care to indicate that examples using hESC lines obtained from destructive methods are not encompassed by the invention. Nevertheless, it is certainly positive for applicants to now have reasonable legal certainty over what are now considered by the EPO to be ethically acceptable sources of human embryonic stem cells.
1 Chung Y et al. (2008) Human Embryonic Stem Cell Lines Generated without Embryo Destruction. Cell Stem Cell 2008, 2(2), 113-117.
2 Revazova et al. (2007) Patient-Specific Stem Cell Lines Derived from Human Parthenogenetic blastocysts. Cloning and Stem Cells, 9 (3), 2007, 432-449.