The judgment confirms that inventions that use human embryonic stem (hES) cell lines obtained by destruction of a human embryo are unpatentable in the European Economic Area (EEA).
The referral to the CJEU arose from an appeal in the German Federal Court of Justice by inventor Oliver Brüstle relating to the scope of the exclusion from patentability of “uses of human embryos for industrial or commercial purposes” conferred by Article 6(2)(c) of Community Directive 98/44 (also known as the “Biotech Directive”) covering inventions in the field of biotechnology. Three questions were referred, which related to the interpretation of the term “human embryo” (Question 1), whether “for industrial … purposes” covers use for purposes of scientific research (Question 2), and whether the exclusion covers inventions that relate to products whose production the prior destruction of human embryos or to processes for which such a product is needed as base material (Question 3).
In answer to Question 1, the CJEU stated that the following three types of organism fall within the meaning of the term “human embryos”:
- any human ovum after fertilisation,
- any non-fertilised human ovum into which the cell nucleus from a mature human cell has been transplanted, and
- any non-fertilised human ovum whose division and further development have been stimulated by parthenogenesis.
The CJEU failed to provide an exact definition of a “human embryo” in its answer. However, paragraph 37 of the judgment suggests that an organism is a “human embryo” if it is “capable of commencing the process of development of a human being”. The CJEU held that it was up to the German court to determine whether in the light of scientific developments, the particular cell used in Brüstle’s patent (a stem cell obtained from a human embryo at the blastocyst stage) constitutes a “human embryo”. Thus, it will be for individual courts to determine whether organisms other than the three specific types recited in the answer to Question 1 fall within the definition of a “human embryo”.
In answer to Question 2, the CJEU found in the affirmative that:
The exclusion … also covers the use of human embryos for purposes of scientific research, only use for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it being patentable.
Thus, the CJEU found that inventions that relate to the use of a human embryo for research are excluded by the Biotech Directive. However, inventions which are useful to a human embryo are not excluded from patentability. Thus, methods directed to treating a defect identified during IVF that use a human embryo, for example, would not fall within the exclusion.
The answer to Question 3 has caused the most discussion in the scientific community. The CJEU held that:
Article 6(2)(c) … excludes an invention from patentability where the technical teaching which is the subject matter of the patent application requires the prior destruction of human embryos or their use as base material, whatever the stage at which that takes place and even if the description of the technical teaching claimed does not refer to the use of human embryos.
Significantly, this means that inventions that make use of established hES cell lines that were generated by destruction of a human embryo are not patentable, even if destruction of the human embryo occurred long before the effective filing date of the invention.
The term “base material” is further described in the judgment as a product that has been obtained by destruction of a human embryo. However, the specific wording of the answer to Question 3 is not so limited and simply refers to “use” of human embryos as base material. The extent of the exclusion is thus open to interpretation by individual courts and the European Patent Office (EPO), as outlined below.
Are all hES cell inventions excluded?
If the answer to Question 3 is interpreted narrowly, the judgment does not explicitly exclude from patentability inventions that use hES cells/hES cell lines whose generation did not require the “destruction” of a human embryo (referred to hereafter as “hES cells/hES cell lines obtained by non-destructive methods”). There is, however, some room for interpretation of the word “destruction”. If “destruction” is equated with non-viability, then it would be significant that technology allegedly already exists to make hES cell lines whilst preserving the viability of the donor embryo (for example, see Klimanskaya et al., 2006, Nature, 444:481-485 and Y. Chung, et al., Cell Stem Cell, 2, 113-117, 2008).
Thus, it may be that inventions that can be practised using hES cells/hES cell lines obtained by non-destructive methods would not necessarily be excluded from patentability, but it is likely that claims will need to be limited in scope so that they do not also encompass hES cells/hES cell lines generated using destructive methods.
Where description of established cell lines obtained by non-destructive methods or description of the non-destructive methods is not contained in the patent application as filed, it will be necessary to convince the EPO and at least UK courts that such technology would have been part of the skilled person’s common general knowledge at the effective filing date in order to meet the requirements for sufficiency of disclosure. Thus, when drafting applications, include description of non-destructive techniques, and uses of hES cell lines that have been generated without destroying embryos, together with examples of such hES cell lines that are publicly available at the effective filing date to avoid having to rely on the skilled person’s common general knowledge. In order to avoid the exclusion, the cells obtained from the human embryo by the non-destructive method should not themselves be considered by the national court or the EPO to be “human embryos”.
If the answer to Question 3 is interpreted broadly, any inventions that have used a human embryo at any stage would be excluded and so all inventions that use hES cells/existing hES cell lines (including those obtained by non-destructive methods) will not be patentable. Anecdotally, it seems that EPO examiners are already adopting this harsher line following the judgment.
It will be necessary to wait for the Technical Boards of Appeal of the EPO and individual courts to issue decisions on this point before we know how the exclusion will be interpreted. It is very possible, of course, that the judgment will be interpreted differently in different states. An additional complication for industry, of course, is that it is very unusual for relevant court cases to arise so this uncertainty is likely to continue into the future.
The judgment may feasibly even impact on claims to products (such as cell culture media or to compounds for inducing differentiation) where in order to put the invention into practice, the product would be used with a human embryo/hES cell/hES cell line. Indeed, the answer to Question 3 indicates that it is necessary to look at “the technical teaching which is the subject matter of the patent application” to determine whether the invention is excluded, not just the claims. To attempt to address this possibility, when drafting applications to products that do not contain human embryos/hES cells/hES cell lines but whose exploitation may use human embryos/hES cells/hES cell lines, include description in the application of non-excluded uses. It remains to be seen whether the presence in the description of the excluded uses in addition to the non-excluded uses will render such inventions unpatentable.
Changes to EPO practice
Following the “WARF” decision of the Enlarged Boards of Appeal of the EPO (G 2/06), the EPO’s policy has been not to grant claims directed to products which, at the filing date of the patent could be prepared exclusively by a method which necessarily involved the destruction of the human embryos from which the said products are derived, even if the said method is not part of the claims. However, if at the filing date of the patent, the invention could be practised using an established hES cell line, the EPO’s policy since the WARF decision has been not to exclude such claims from patentability, even if the established hES cell line was made by destruction of a human embryo. The EPO now has to refuse such claims as well and preliminary indications are that EPO examiners are requiring disclaimers to all hES cells/hES cell lines to be added, no matter how they were obtained.
As mention above, there is room for interpretation as to whether the exclusion encompasses all hES cell/hES cell line inventions or only those inventions that involved destruction of a human embryo. In view of this, there is potential for a “trap” if a disclaimer that has no basis in the application as filed is inserted in a claim and is found post-grant to disclaim more than is excluded from patentability. In situations where it is not possible to remove such a disclaimer post-grant without extending the scope of protection of the granted claims, the patent concerned will be invalid unless the claim concerned is deleted. Consequently, when drafting new applications, it will be advantageous to include basis for disclaimers to uses of human embryos and to uses of hES cells/hES cell lines to ensure there is basis for any disclaimers that are required to avoid the possibility of this “trap”. It may also be advantageous to include basis for disclaimers to uses of hES cells/hES cell lines generated by destruction of a human embryo, subject to the considerations below. Even if hES cells/hES cell lines obtained by non-destructive methods are not explicitly excluded by the judgment, drafting claims to such non-excluded embodiments may prove problematic. Recitation in a claim of using an hES cell/hES cell line obtained by a non-destructive method may still be excluded if the EPO or national court considers such a recitation also to encompass hES cells obtained by destructive methods by virtue of such cells having the same characteristics as the recited cells. Thus, it may be necessary to limit claims to (use of) specific examples of existing hES cell lines obtained by non-destructive methods. Whether the application as filed refers to such existing hES cell lines would therefore become relevant to the assessment of patentability. Applicants/proprietors will need to decide whether claims limited to specific existing hES cell lines have any commercial value. Similarly, the usefulness of limited disclaimers, which disclaim only hES cells/hES cell lines generated by destructive methods, is questionable. If such a disclaimer is seen to encompass any hES cells/hES cell lines having the characteristics of such hES cells/hES cell lines, such disclaimers are likely to encompass also hES cells/hES cell lines generated without destruction of a human embryo. Consequently, inserting a limited disclaimer may have the same effect as inserting a disclaimer to all hES cells/hES cell lines.
Relevance of effective filing date
Looking at the effective filing date of a particular application/patent will help in assessing whether the claimed invention is patentable.
Effective filing date before date “X”
Applications/patents whose technical teaching encompasses the use of hES cells/hES cell lines and whose effective filing date is before non-destructive methods of generating hES cells were publicly available will not be patentable (applications) or will be invalid (patents). There is likely to be some debate as to the exact date when such technology was available (hence the date is referred to as “X” above) but it is arguable from the publications mentioned above that such a method has been publicly available since at least 23rd August 2006.
Effective filing date on or after date “X”
If courts and the EPO adopt a narrow interpretation of the answer to Question 3, applications/patents whose effective filing date is on or after the date on which non-destructive methods became publicly available may be able to avoid the exclusion by arguing that the invention can be practised without making use of the excluded hES cells/hES cell lines. It may be that only applications having basis for limiting the claims to specific hES cell lines generated by the non-destructive methods are patentable. If a broad interpretation of the answer to Question 3 is adopted, the effective filing date will be irrelevant as all hES cell inventions will not be patentable.
Claims using human embryos
Applications/patents having claims that encompass the use of “human embryos”, as defined in the CJEU’s answer to Question 1, will not be patentable (applications) or will be invalid in EEA member states (granted patents), unless the invention is for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it. This will be the case, irrespective of the effective filing date.
Amendment of applications/patents
Applicants/proprietors should consider amendment of applications/patents to exclude the excluded subject matter where this is possible. For example, claims should be limited to carve out the excluded subject matter, for example by way of a disclaimer, by a positive limitation or by deletion of the offending claims. Early amendment of granted patents is advisable rather than waiting until it becomes imperative to have to enforce the claims and use of the EPO’s central limitation procedure should be considered.
Where amendment or argumentation is not possible, applicants/proprietors should assess whether it is worthwhile continuing to maintain cases that will ultimately be unenforceable.
Effect in EPC contracting non-EEA states
Patents will not automatically be invalid in EPC contracting states that are non-EEA member states unless the courts in those states decide to follow the CJEU’s interpretation of the law. Such countries include Albania, Switzerland, Croatia, Monaco, the Former Yugoslav Republic of Macedonia, Serbia, San Marino, Turkey, Bosnia and Herzegovina and Montenegro. For such states, applicants wanting to obtain broader protection than available via the EPO route (assuming the EPO follows the CJEU’s judgment) may want to consider pursuing protection down the national route if it becomes evident that there will be a divergence in practice.
Effect on Biotech industry
Some see the judgment as representing a blow to innovation in Europe, as they consider it will disincentivise biotechnology and pharmaceutical companies from investing in research involving hES cells and so set back research in these areas that many consider vital to human health. On the flip side, by abolishing patent protection in EEA member states for inventions that necessarily involved destruction of a human embryo or for inventions which use human embryos, the general scientific community will be able to use such technology without fear of patent infringement.
For companies wanting to protect their hES cell-based therapeutics in Europe and for whom patent protection is no longer available, data exclusivity remains an option and so the judgment is not a death knell for hES cell-based commercial research in Europe. Many companies already use adult stem cells, umbilical cord stem cells or induced pluripotent cells (iPS cells) for their research and the judgment will not affect such technologies unless at some stage during those processes a “human embryo” is made. Thus, the judgment may not have as far reaching effects as some have feared.