The interplay between CRISPR and the Biotech Directive
Current understandings of gene-editing are that the proper or most likely fruitful and efficient approach concerns ‘correcting’ cells which, in turn, means editing their genetic codes in some respects. The most obvious strategy for gene-editing is to target totipotent cells, ie, those cells which remain differentiated as part of the development process or, more colloquially, the building blocks. Totipotent cells can be found in embryos and are often known as embryonic stem cells. The use and exploitation of such cells is regulated to some degree as far as human embryonic cells are concerned.
How does our current framework function in a patent context? At present, schedule A2 of the UK Patents Act 1977 tells us that processes for modifying the germ line genetic identity of human beings and uses of human embryos for industrial or commercial purposes are not patentable. What those words have been construed as meaning is something quite different.
In Oliver Brüstle v Greenpeace (2012), the Court of Justice of the European Union made it clear that the equivalent of paragraph 3(d) of schedule A2 in the Biotech Directive does not merely prohibit the patenting of methods which expressly stipulate the use of human embryos for industrial or commercial purposes. The court added that the prohibition extends to patenting methods which necessarily require, but do not claim, the use of human embryos for industrial or commercial purposes, whether or not that requirement is expressed in the claims of the patent or patent application.
Clear biotech boundaries
The rule is stark and is hard to detect from the language of the Biotech Directive, but at least there are clear boundaries. It does not extend to methods concerning or products derived from cells which, although part of the germ line, are something less than totipotent (such as unfertilised eggs which are incapable of developing into human beings—see International Stem Cell Corp v Comptroller General of Patents, Designs and Trade Marks).
Further, the use of a totipotent human embryonic stem cell implies that the embryo must be destroyed. If a few cells are shaved off here and there and the embryo remains viable and vital then the embryo has not been used in a destructive sense. In T 1441/13 (Embryonic stem cells, disclaimer/Asterias), a European Patent Office technical board of appeal was clear that if in any patent application a claim was made to a method which might be performed by using a human embryo, that would then invalidate a patent application because of the human embryo use exception.
If in any patent application a method could be performed which disclaimed use of a human embryonic stem cell, and there were methods which worked and performed the task in that way (ie, not involving the use of human embryonic stem cells), that would then vindicate the patent application.
The Brüstle case represents an extensive ban, but it is only part of a system concerning research into human embryo stem cells; in other parts of the control mechanism, as governed in the UK by the Human Fertilisation and Embryology Act 1990, the position is less absolute and more discretion-based. The scope and depth of research is ruled by a genetic regulator, the Human Fertilisation and Embryology Authority, with considerably more latitude in its discretion.
CRISPR: a powerful tool
CRISPR (clustered regularly interspaced short palindromic repeats) is a powerful tool which can, in principle, change people’s DNA. This implies that the technique can be used to (1) knock out a gene function; (2) edit a gene; (3) repress or interfere with (short of knock-out) a pathway; and (4) increase gene expression in a targeted way.
The technology has gained recognition only in the last five years or so, and it is in a nascent stage, but it has a great deal of potential as a gene-editing tool. That potential has good and bad sides. The good is that it could save lives and stop people from being born with lifelong and life-threatening congenital conditions—for instance, cystic fibrosis, the pathogenesis of which we now know is about neither cysts nor fibrosis, is a debilitating genetic condition which stops certain cells from sweating chloride ions and water through pores or transport proteins.
“Embryonic stem cell research continues, is sanctioned by the genetic regulator and involves—to the point of positive encouragement—doing the very things the patent system seeks to discourage.”
The disease and its pathways are well understood. The genetic defect is well researched and (for most instances of the disease) if one could, all one needs to do is add three nucleotides. The argument seems, to this author, to go one way.
On the other hand what is to stop us from making monsters or, more realistically, making value judgements about perfection?
Is a person more beautiful or better because they have a particular hair colour, nose shape and so on? Who makes that judgement? Why should it be down to one person? Is diversity not the key to our success as a civilisation and social development? In this respect the arguments are ambiguous. It could be that the best approach, given the clear conflict between morality and advancement, is the current approach of our genetic regulator—tread carefully and slowly. However, treading carefully and slowly is not the way that the Biotech Directive has chosen.
How have patents directed to CRISPR fared? The answer is a squabble, but there has been no statement of principle that CRISPR-based inventions are not patentable in any circumstances. The squabble arises because of the dying embers of a US interference action and a spat over inventorship between east and west coast universities in the US.
Such squabbles will become increasingly rare as the 2011 America Invents Act, which heralds the beginning of a first-to-file system in the US, starts to take hold. No CRISPR patent application has (yet) fallen foul of the Biotech Directive on the basis of the human embryo use exception.
Legislative problems
The principal difficulty faced by our legislators is that they have not thought about or debated in any democratic sense the playoff between a discretion-based regime of genetic regulation and the more absolute patent system which has been delivered to us. Indeed the existence of a discretion-based system and an absolute rule-based system, devoid of any regard for technical advancement or understanding side-by-side, seems baffling, although coordination is not something our legislators have ever been good at; their interests are too short term. If ever there was an argument for a second unelected, legislative debating chamber, this is it.
The problem is that the consequences for advancement or innovation are too important or costly to ignore. In any objective and organised debate on the subject one might have found proponents for the current system providing evidence that our current patent system (which discourages the exploitation of embryos) will achieve, or indeed has achieved ex post facto, something that genetic regulation has, or could, not.
There is no such evidence, not least because the regulatory system has not been found wanting. The evidence, such as it is, seems to suggest that the system has failed to achieve its objectives. Embryonic stem cell research continues, is sanctioned by the genetic regulator and involves—to the point of positive encouragement—doing the very things the patent system seeks to discourage.
The effect of this is to say that only academics with no commercial object in mind (a dying breed) or those who are good at generating secrets (and keeping them) will benefit. The effect of this is, so far as commercial entities are concerned, to cause process research to abound at the expense of product research since processes are easier to conceal than products. Whether this is optimal is something that no-one has ever investigated, but just by pure reasoning alone, it can’t be.
One argument in favour of the Biotech Directive is that it may serve to stop the powerful genetic research lobby from getting the upper hand with the genetic regulator. This argument, if even sustainable, is likely to be short-lived. The genetic regulator, which in the UK was around for some time before the Biotech Directive took hold, has withstood such pressure and looks robust enough to do so in the future.
There is a disconnect, one which needs to be resolved, this author suggests, by abolishing the Biotech Directive and leaving it to the genetic regulator to maintain standards. This, after all, is a consistent approach since methods for working embryos can be protected in a variety of ways such as with confidential information, copyright and the various design rights floating around the European intellectual property system—none of which has human embryo exploitation exceptions.
Even then, if the means of protection won’t work or human embryo exploitation is carved out of the other rights around, there is still a means of protection by keeping processes secret anyway. The Dutch did this for years in relation to food processing technologies and it seemed to work for them.
Ashley Roughton is a consultant barrister at Nabarro. He can be contacted at: a.roughton@nabarro.com
