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.