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Monday, 25 November 2013

Crispr patents: when palindromic repeats can cure all ills but still cause headaches

From the CRISPR genome engineering
resources website: a glimpse of things to come
Being such an industrious intellectual property law blogger, this Kat is conscious of the fact that most of the news he gleans about exciting new developments in science and technology either comes from a speed-read of The Economist or from the highly selected facts of the cases he writes about. That's why it's comforting to know that, from time to time, some kind soul will write something for this weblog that explains or discusses some aspect of science or technology that has, or is about to have, at least a good chance of making its mark on the world of intellectual property law.  Accordingly, thanks are due to Dr Philip Webber (a partner in Dehns Patent & Trade Mark Attorneys) for giving us this insight into Crispr.  Writes Philip:
Crispr: a morality test for the IP industry?

On 6 November 2013 the Independent newspaper devoted half of its front page to an article on a new genetic technique -- Crispr -- which is being heralded as a "jaw-dropping breakthrough" in the treatment of hereditary diseases.  This technique is said to allow the engineering of the human genome at level of precision which has not previously been achieved, thus opening the doorway for the correction of human gene defects.  The more entrepreneurial scientists might look on it, however, as an enhanced method to generate new organisms.

Crispr is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats. These are short palindromic repeats of DNA which are found in bacterial genomes.  While they have been known for many years, until recently they were dismissed as being merely junk DNA, with no useful purpose.  More recently, however, it has been found that they form part of a bacterial immune system where the palindromic DNA sequences provide the bacteria with a molecular memory of viruses which have previously invaded the bacteria.  If the same virus then subsequently invades the bacteria, the bacteria use these Crispr sequences to recognise them; the viruses will then be chopped up with the bacteria's Crispr-associated (CAS) enzymes.
Jennifer A. Doudna:
scientists hope to
create a colour version
of her soon ...
The ability of this system to recognise specific DNA sequences and to cut DNA having that sequence has now attracted considerable attention from scientists around the world.  In particular, a paper published last year by Jennifer Doudna from the University of California, Berkeley (Science 17 August 2012: Vol. 337 no. 6096, pp. 816-821), showed that the Crispr/CAS system can be used with programmable double-stranded RNA"guide" molecules to make highly specific changes in bacterial genomes.  More importantly, the system has now been shown to work in the genomes of plants and animals.  The ability to make such specific changes to genomes has long been a holy grail of genetic scientists, in particular those wishing to treat gene defects in humans.  The currently-available systems often rely on genetically-engineered viruses which are modified to carry a replacement gene and to insert it into an organism's genome; but these viruses cannot be controlled with the degree of accuracy which is required for use in humans. 
The hope is, therefore, that this new Crispr system will provides genetic scientists with a tool to make defined changes to human DNA with the required degree of precision and safety to treat human diseases.  Potential targets which have already been mentioned include sickle-cell anaemia, Down's syndrome and HIV. The prospect of germ-line therapy (i.e. making inherited changes to the human genome) has also been raised, for example the prospect of correcting defective genes in IVF embryos prior to implantation.

From an IP perspective, the Crispr technique should provide patent applicants with opportunities to claim new methods of treating various human diseases, particularly those that are due to single gene defects. Patents may also be sought on the specific sequences of programmable double-stranded RNA "guide" molecules that are usable to correct specific DNA mutations or which may be used to introduce new desirable gene changes. 

Within Europe, however, the provisions of the EU Biotech Directive 98/44 need to be considered.  While Article 6(2)(c) states that:

            "uses of human embryos for industrial or commercial purposes"

are not patentable, Recital 42 confirms that this exclusion

"... does not affect inventions for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it".

However, Article 6(2)(b) excludes

            "processes for modifying the germ line identity of human beings". 

Since human embryos are indeed human beings, the provisions cited above would appear to exclude patents in the EU on processes of correcting gene defects in IVF embryos.  The ethical issues surrounding such work -- and designer babies in particular -- are also likely to be highly controversial.  It must be remembered that, while the legal and moral frameworks for the application of the Crispr technology to humans are well established in developed regions such as Europe, this is not true for all countries around the world. 

It is likely to be a number of years before the safety of the Crispr technique in humans has been fully evaluated, but this technique is likely to be embraced more quickly by the agricultural industry. The prospect of making more-defined changes in plant and animal genomes might lead to greater numbers of genetically-engineered plants and animals. 

The European Patent Office has already acknowledged the patentability of such organisms (T356/93; T19/90 [a.k.a. the oncomouse, notes Merpel]) and the plant and animal variety exclusions (Rule 27 of the European Patent Convention, EPC) are not difficult to avoid provided that "the technical feasibility of the invention is not confined to a particular plant or animal variety" (Rule 27(b) EPC). 

The morality test for genetically-engineered animals (T19/90) is also one which has only rarely been invoked (EU Biotech Directive, Article 6(2)(d)):

(d) processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting from such processes.

The pooch pouch?
One area which might particularly be opened up by the Crispr technique is that of designer pets. This could lead to the production of dogs which are small enough to fit inside Louis Vuitton handbags [why should anyone want to produce a dog, ask the Kats collectively] and glow-in-the-dark poodles.   Many might say that we need some new morality laws to help to defend us all from these. 
Philip raises some big, big issues here.  Do readers have any thoughts on them, this Kat innocently inquires.


Anonymous said...


Susan said...

Having seen the EPO go through lots of anguish on the morality of patenting genes (the relaxin case), the Harvard oncomouse and of course embryo stem cells, it's clear that it's very difficult to make moral judgments on new technology. GM plants continue to be controversial and that example demonstrates how difficult it is to have public debate about such things. Our society is composed of a diverse group of adult people aged 20 to 100 who will have very different opinions on genetically manipulating nature and in particular genetically modifying people, and they will also have different degrees of trust in the organisations that will be given the authority to carry out such manipulation. We cannot even agree on whether climate change is happening and so I wonder how as a society we can possibly have intelligent debate on genetic manipulation of people.

Ashley Roughton said...

If the EPO or whoever has difficulty making moral judgments (which on any view they are neither qualified or trained to make) and leaving aside the question of what is morality anyway, why not make life easy for the poor blighters and not vest them with that sort of decision making power? There is no justification for such a thing. As Ayer has shown and Devlin admitted, courts vested with moral authority do nothing to improve or uphold morals.


Susan said...

Ashley, we still need to decide whether or not we're going to allow a new technology to be carried out, so someone has to make a decision which will have a 'moral' component to it. For example, 'do we allow people to genetically engineer their children?' is now becoming a very urgent question.

Anonymous said...

Too late Susan.

The genie's out of the bottle.
The ship has sailed.

Any attempt now to run back the clock will only result in a black market environment in which those with means will obtain what they want and only those without means will be blocked by such 'morality.'

Ashley Roughton said...


Thank-you for engaging.

I see your point, of course. But using the law of patents as a starting point is strange since it does not stop the thing itself, merely the protection of it. Surely questions of morality are sociological and therefore ought to be jury questions. Why, one might ask rhetorically, is there no primary EU legislation stating that engineering one's children is illegal?

On another slightly allied point - I disagree with you Susan about there being something wrong with genetically engineering one's children; I hope that this does not cause offence (and I do not intend to). Whether I am right or wrong about disagreeing is not strictly relevant, what is relevant is that there are, in society, two sets of views (mine and yours). If that be the case then neither view can be said to be the view of right and therefore moral. Since - I submit - morality is sociological - what does society believe is right or wrong, then genetically engineering one's children cannot be said to immoral?


Susan said...

Ashley, a couple of points:
- whilst it does seem out of place for patent offices to have to deal with morality, I think that at the end of the day we don't have enough forums for discussions of the morality of new technology, and strangely enough having the focus of a patent application in front us may be a useful way to think about the issue. The Biotech Directive was about patent law, but allowed the European parliament to discuss many difficult issues relating to new technology. Whilst it makes the patent system less efficient, I've come to the conclusion that I would rather have patent offices think about morality and in some way add to the decision-making which we as a society need to do
- in regards to you agreeing with genetically engineering children, I hope you would accept the issue is complicated. Is it right for parents to decide to have a 2 headed child? Should parents who might have psychopathic tendencies or who are depressed or who are high on drugs a lot of the time be able to design their children as they wish? How would a child feel about being given a trait it did not want or being less intelligent or less physically attractive due to its parents' choices? Should the technology be available to all or only those who can afford it?

Ashley Roughton said...


Some very interesting thoughts to think about.

On morality, there is quite a lot of learning on it but the debate on court enforced morality was stopped in its tracks by Ayer.

I agree that the issue is complicated, not least by my own experiences (three first cousins either very ill, wiped out or dying by genetic diseases which would have been avoidable using current technologies) so there is a degree of subjectivity. I accept the examples you have given raise difficult questions. I am not sure that the argument should be conducted in completely objective terms. In saying this I am not taking a contrary position - I just say that for what it is worth.


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