EXAMINATION OF HUMAN EMBRYONIC STEM CELL INVENTIONS IN EUROPE
It is now a little over a year since the decision of the CJEU was handed down in the case of Brüstle v. Greenpeace e.V. (C-34/10)1. This decision was a disappointment to many in the legal and scientific communities because of its apparent restriction on the scope of patentable inventions in the human embryonic stem cell field. I report herein on progress to date: we have now had a decision from the UKIPO concerning one meaning of “embryo” and clear indications from the EPO of its emerging practice in applying the morality provisions of the EPC to pending patent applications and to patents under opposition. What are now the key battlegrounds?
Concern and apprehension have been rife for patentees and practitioners alike in light of the Brüstle decision, which set out the CJEU’s decision as to what is and what is not excluded from patentability by the morality provisions of the Biotech Directive. Even now, little is known for certain as to how the respective patent offices in Europe will in practice interpret the decision. Perhaps that ultimate pleasure will fall to the new Unitary Patent Court? The interpretation does not significantly affect new inventions but is critical to a swathe of granted patents and pending applications, representing the high water mark of filings in this field. While snippets of individual examples of examination practice are emerging, the interpretation to date has been principally carried out at the EPO at the Examining Division level. No case has yet reached the Technical Board of Appeal (TBA). In some respects the interpretation has become more difficult with time and further references to the CJEU can be contemplated. For now, I am reviewing experiences to date of how examination practice is developing, with an eye on areas of controversy for the future.
UKIPO – revised practice note
Starting with matters closest to home, it can on the one hand be proudly said that the UKIPO has already issued a definitive, revised practice note covering inventions involving human embryonic stem cells (hESCs)1. This note reproduces the definition of “embryo” from the Brüstle decision and indicates that the UKIPO practice will now recognise as unpatentable “where the implementation of an invention requires the use of cells that originate from a process which requires the destruction of a human embryo”. On the other hand, however, the note indicates that, also to be regarded as unpatentable, are inventions that require “the use of a human embryonic stem cell line the establishment of which originally required the destruction of a human embryo” (emphasis added).
This latter part of the practice note is disappointing to practitioners, as most regard the question of whether hESCs from a cell line represent non-patentable starting material for inventions as being, to date, undecided.
Thus, while the UKIPO approach was previously applauded for its reasonableness, compared with that of the EPO, this position now seems at least temporarily reversed. In my eyes, the UKIPO’s stated position is more restrictive than it could be.
UKIPO – one meaning of “embryo”
The UKIPO has also issued a decision in the International Stem Cell Corporation Case3, which hinged not on whether an embryo was destroyed nor by whom the destruction took place but on the definition of the term “embryo”.
In that case, a non-fertilised human ovum had been stimulated to divide by parthenogenesis. Recall the Brüstle decision held that this would represent a human embryo, provided such were capable of commencing the process of development of a human being.
The facts of the case were fairly particular. Whilst parthenogenesis had indeed been used to activate a human ovum, there was a biological limitation preventing development into a human being.
The UK Hearing Officer nevertheless held that the subject matter of the invention was unpatentable because the stimulated ovum was indeed capable of commencing the process of development into a human being even if it were not able to complete that process. One analogy used is that the embryo train had gone into its tunnel (even if it would never emerge).
This case is currently under appeal and I imagine one argument to be advanced will be that the process of development into a human being cannot be said to commence in respect of a structure that is incapable of developing into a human being. The decision to date has been at the Hearing Officer level and, with several layers of appeal yet to come, is perhaps understandably conservative. Whilst it is always hazardous to predict in advance the outcome of such matters, the prospects for success at appeal seem at first sight good.
EPO – a less detailed practice note
In contrast to that of the UKIPO, the modified practice note seen in the EPO Guidelines for Examination is rather non-committal as to the extent to which its examination practice has changed. The EPO guidance emphasises that, in considering the morality of a patent application, the entire teaching of the application, not only the claim category and wording, must be taken into account and that a critical element is to establish whether products such as stem cell cultures are obtained exclusively by the use, involving the destruction, of a human embryo. No explicit mention is made of hESC lines.
EPO – revised examination criteria
So, how are our patent applications actually being examined at present by the EPO? I identify two elements.
The first element is this: it seems that a practice has evolved wherein three categories of inventions relating to hESCs have been identified as being unpatentable:-
- “Direct, destructive use of human embryos”, for example, derivation by the inventor of cells from a human embryo, generating hESCs which are the product the subject of the claim or are used to derive the product.
- “Indirect, destructive use of human embryos”, for example, derivation of hESCs by destruction of an embryo and the preparation of a cell line from those cells, that is then used by a third party as the starting material for the products the subject of the claim.
- “Non-destructive, direct use of human embryos”, for example, extraction of a cell from an eight-cell blastocyst and use of that cell as starting material for a product the subject of the claim, even though the remaining seven-cell containing structure may be regarded as a viable embryo that has not been destroyed.
- The above analysis allows for the identification of a fourth, and allowable, category which following the EPO’s new approach may be characterised as:-“Non destructive, indirect use of human embryos”, for example, extraction of a cell from an eight-cell blastocyst, use of that cell to derive a hESC line and then use of that line by a third party to derive products the subject of the claim.
- This approach pleasingly identifies clearly patentable subject-matter and corresponds to that outlined in the last CIPA journal article covering this decision4. The current EPO position differs only in that examination reports issued to date (to my knowledge) indicate that the first date accepted as rendering available hESC lines representing non-destructive, indirect use of human embryos, thus representing patentable starting material, is 10 January 2008. The previous article argued for a date of 23 August 2006. Let us just leave it that this is another aspect which practitioners will regard as, to date, undecided.
The second element is that in raising objections against claims in this area, examiners will choose whichever from a number of passages, whether obiter or ratio decidendi, and whether from the Brüstle decision or the WARF decision (G 2/06)5 fits with their purpose. Thus I have seen objections that subject matter is unpatentable because:
- carrying out the invention requires destruction of an embryo, regardless of the nature of the products obtained or claimed (WARF);
- the implementation of the invention requires the destruction of human embryos (Brüstle); or
- there has been use [of human embryos] as base material whatever the stage at which that takes place (Brüstle).
- Any one of these three (and there may be more) prongs on its own catches the patentee.
Are the EPO examining divisions construing this exception to patentability too broadly? This practice is despite yet another decision, in T1199/08: “Method of cryopreserving selected sperm cells”, holding inter alia that “according to established case law, any exception to patentability must be construed narrowly”.
I suspect examiners and practitioners have at least one thought in common: a decision is needed at TBA level.
EPO – disclaimer practice
EPO practice in relation to disclaimers may also be confused at the moment. The principle is that a disclaimer can be used to cut subject matter from the monopoly of the claims, though no more than is “necessary either to restore novelty or to disclaim subject-matter excluded from patentability for non-technical reason” (G 1/03)6.
We should not forget that the relevant EPC wording is that European patents shall not be granted in respect of biotechnological inventions which, in particular, concern the following:
- “(c) uses of human embryos for industrial or commercial purposes”.
- Imagine my surprise when the reaction from the Examining Division was not to approve this apparently unobjectionable (to my mind) phrasing but to object in the terms:
- “… the wording of the disclaimer […] is open to interpretation”;
- “… it is unclear what is actually excluded from the claims”; and
- “Indeed, it must be clear from the wording of the claims that the use of human embryonic stem cells is excluded”.
- Is EPO practice now to ask for insertion of a disclaimer that goes beyond the exception to patentability set out in the EPC? Surely to do so would indeed be more than “necessary either to restore novelty or to disclaim subject-matter excluded from patentability for non-technical reason”.
I can foresee an opposition to a patent granted following that practice: the first objection will be that the claim amendment is contrary to Article 123(2) EPC, because there is no basis for the disclaimer: none in the specification and the wording goes beyond the wording of the exception to patentability. The next objection will be that removing the disclaimer, or even going back to the wording of the exception to patentability, would be contrary to Article 123(3) EPC.
One wonders how many European patents are out there already with ill-advised disclaimer language?
Patentability – key battlegrounds for the future
So, where is the focus of the patentability debate to be?
A reminder: we are only arguing over a portion of history
As an important note, I am reminded of a question put at a recent conference: what impact will the EPO’s stance on patenting in this technology area have on research? Let’s construe the question: what impact on future research? The answer should be: almost none. The first battleground is for those patents filed from around January 1996 (invention of hESCs) until around May 2003 (when the first hESC lines became available); the next is from then until August 2006 (or January 2008 – see undecided point mentioned above) when hESCs became available indirectly from non-destructive embryo manipulation techniques, i.e. from patentable starting material. Those new hESC lines are available today. It is only a portion of the past that we are fighting over.
Exceptions to patentability
First, it needs to be established that exceptions to patentability are to be construed narrowly. The TBA case law says this repeatedly. We can go back to the intention of the legislator: was it intended that in this specific technology area and in no other exceptions to patentability should be broadly construed? There is no basis for such a reading of the history of the law in this area.
Embryo destruction: why and by whom?
Next to be considered is the nexus between the embryo destruction and the making of the invention. Is it relevant that these separate steps, for the steps are indeed separate, be carried out by unconnected individuals? One hESC line may be deposited and used by many subsequent research teams; that is after all the point of depositing a line, so that others can access the line without the need to derive their own cells (and thus without the requirement for embryo destruction by those accessing the deposited cells and making an invention). A cell line may be deposited for one purpose and then accessed by an unrelated researcher for another purpose – is that relevant?
Let us not forget the context of the WARF decision: embryos were to be destroyed and used to generate hESCs by one and the same individual essentially at a stroke. Where these separable steps are indeed separated by time and personnel the chain is broken; the requirement for the inventor to destroy an embryo has ceased. The process of deriving and depositing publically accessible hESC lines should be regarded as providing starting material for patentable inventions.
Prohibition against immoral implementation
Thirdly, are morals not to be judged by the standards of today? In vitro fertilisation is now a routine procedure. It results in embryo destruction, inevitably, as part of the process. Yet the EPO grants patents for products related to such processes and I would venture that the use of these infertility treatments and the grant of such patents is regarded by most as morally acceptable de nos jours.
The Brüstle decision used a fascinating term, in declaring immorality where the implementation of the invention requires the destruction of human embryos. To my mind, “implementation” refers to activities downstream of making an invention, including activities carried out by others long after the filing date. The step of making an invention in the stem cell field requires at that point in time no commercial use of the embryos, no industrial use as such, no trade in embryos. But were a medicine to be mass-produced, say, 15 years hence, now that really would represent commercial and/or industrial activity. Such implementation of the invention, to the extent that it entailed embryo usage or trade in embryos, is presumably the activity that the legislator intended to be unpatentable. I would find this interpretation of the legislation perfectly sensible. As morals change so an invention regarded as immoral on conception could later become acceptable, and vice versa. Article 53 EPC states that patents shall not be granted in respect of (a) inventions the commercial exploitation of which would be contrary to ‘ordre public’ or morality. The test (as per WARF) is currently applied at the filing date – the wrong point in time – but the right time is during implementation.
As it is, the EPO’s reading of the law has multiple unintended consequences, if the test remains as to date enunciated, namely inventions are unpatentable if, at the filing date, embryo destruction is required at whatever stage of making an invention or the invention requires use of an embryo as base material at whatever stage in making the invention. In vitro fertilisation processes are caught. Certain contraceptive methods and devices are caught. The test does not look at how an invention is used today but at how the invention was made in the dim and distant past. Even induced pluripotent stem cells (iPS cells) are arguably caught (iPS cells are pluripotent and behave like hESCs but may be derived without involving embryos e.g. they can be derived from human skin; to culture these cells requires media that supports growth of pluripotent cells; to obtain such media required essential research on hESCs; those hESCs came from embryos, and hence the chain back to embryo destruction is completed). The current test must be wrong.
How then to codify the test for morality in patenting? Perhaps not in reams of paper but in a gut feeling, quoting Ernest Hemmingway, Death in the Afternoon:
“About morals, I know only that what is moral is what you feel good after and what is immoral is what you feel bad after”.
Within the last few weeks (at the time of writing) interim six-month data from the first patient cohort in a Phase I/II clinical trial for treatment of spinal injury using stem cells to restore severed nerves have been released, showing considerable gains in sensory function in two of the three patients compared to pre-transplant baselines. That sort of news should make us as a society feel good. Patents should not be denied to the science underlying these breakthroughs.
- C-34/10 Brüstle v. Greenpeace e.V.
- “Inventions involving human embryonic stem cells” UKIPO practice note, 17 May 2012. http://www.ipo.gov.uk/p-pn-stemcells-20120517.htm
- BL O/316/12 International Stem Cell Corporation
- “The death of stem cell patents? – No: a regrettable decision but an exaggerated rumour” by David E Eyre and George W Schlich. CIPA Journal. November 2011, 681-685. https://www.schlich.co.uk/CJEUbrustle.php
- G 2/06 Use of embryos/WARF
- G 1/03 Disclaimer/PPG