Patenting of human genes and their uses in diagnostic tests Patenting of human genes and their uses in diagnostic tests Prof Sigrid Sterckx, Ghent University Dr Julian Cockbain, European Patent Attorney, Gent and Oxford Oxford, 24 June 2015

Translation Patents can assist translation (getting science into practice) or it can hinder it. Diagnostic tests are a perfect example of both. Analyte patents (eg BRCA/Myriad) can hinder Platform patents (ie new equipment or way of finding the analyte) can help. I’m tempted to say PCR, but HCy is a better example. So don’t accept a gung-ho argument on either side to readily

Monopoly Patents (that is monopolies) are a bad thing, a restraint on free trade They are NOT a right They need to be justified They need to be in the interests of the society They must not damage the interests of society

The ‘natural’ What is out there in nature, is ours freely to use Products, phenomena, and laws of nature should be free to all men, the exclusive property of no-one Water, elements, minerals, trees, gravity, relativity, microbes, and genes OTHERWISE further research and development is stifled – risking lives or even the climate of our planet This has been a consistent feature of US Supreme Court law – the need to avoid patents which inhibit further discovery or preempt any use of the building blocks of nature.

Purpose The purpose of patents (now) is to encourage investment in the development of new technologies It was not always so: - to avoid loss of technology (Venice) - to repay the sovereign’s favorites (UK) - to introduce new industry, and taxes and jobs (UK) - to keep Ben Franklin happy (US)

Purpose Despite screams to the contrary, the purpose was NEVER to confirm a ‘natural right’ or a ‘human right’ or to ‘reward’ or ‘encourage’ invention

Natural products Many, if not most, of our drugs and our diagnostic tests are, or are founded on, natural products – peptides, oligonucleotides, lipids, other biochemicals, and the like A very recent example – teixobactin, an antibiotic from a soil-dwelling bacterium

The balance Give a short term (20y) monopoly But for ‘inventions’ which meet the requirements, the standard gatekeepers of novelty, non- obviousness, utility, and sufficiency of disclosure

The gatekeepers aren’t enough For newly found natural materials, e.g. genes or biochemical markers, the normal gatekeepers are ineffective – being newly found they meet the novelty (and usually non-obviousness) hurdles since those involve comparison with the known

Patent-eligibility EPC and 35 USC contain further ‘patent-eligibility’ barriers. Art 52(2) EPC – certain things, like ‘discoveries’ and ‘computer programs’ are simply not inventions 35 USC 101 requires inventions to fall into particular categories, e.g. compositions of matter or processes, to be patent-eligible

USA A gene, a DNA molecule, is a ‘composition of matter’ surely? There can be no doubt that the 35 USC 101 patent-eligibility hurdle is overcome surely? Not so – US Supreme Court considers that natural products, laws and phenomena are open to all, the property of none. However…

Parke-Davis v Mulford A patent for ‘purified’ adrenalin (as compared to ground up adrenal glands) In 1911, SDNY Judge Learned Hand found this ‘for every practical purpose a new thing commercially and therapeutically. That was a good ground for a patent.’

‘Isolated’, ‘purified’, ‘tweaked’ Thus for a century the practice of many patent offices was generally (not always) that a natural product was patent-eligible if claimed in a way it did not exist in in nature, e.g. ‘an isolated DNA molecule comprising the sequence TTCCAA…’ Novobiotic do this with teixobactin: ‘An isolate X, or an enantiomer, diastereomer, tautomer, or pharmaceutically-acceptable salt thereof...’

Diamond v. Chakrabarty In its famous 1980 decision which opened the floodgates to the patenting of lifeforms in the US, the 1950s comment that anything under the sun made by man should be patent-eligible was repeated. From then interpretation of 35 USC 101 changed little (and genetics based medicine developed hugely) until three Supreme Court decisions from 2012, 2013 and 2014

The trio Mayo v. Prometheus – dose-optimising diagnostic tests (2012) AMP v. Myriad – isolated human DNA (2013) Alice v. CLS – financial transaction risk mitigation (2014) (OK, and In re Bilski (2010) – business methods)

The development? Diamond v. Chakrabarty – arguably novelty, i.e. a difference, over the natural is enough. A ‘marked’ difference was clearly enough. Mayo v. Prometheus – combining the natural with the conventional was not enough, there needs to be an inventive concept. AMP v.Myriad – Novelty was not enough, there had to be an inventive act Alice v. CLS – Simply combining the excluded natural with a conventional component would eviscerate the excusion of the natural making patent-eligibility dependent on the patent attorney’s drafting skill

The result Isolated, extracted, etc naturally occuring genetic fragments and other materials (e.g. teixobactin) are not patent-eligible in the US. cDNA is, but it isn’t clear why given the references to acts of invention and inventive concepts Most recently, the US Patent Office and courts have been vigorously applying the position laid out in Mayo, AMP and Alice, e.g. the rejection by the CAFC of a patent to a dianostic test for paternal DNA in maternal blood on 12 June 2015 in Ariosa v Sequenom (plus Ox Uni)

Europe Europe went the other way. The exclusion of ‘discoveries’ is rendered at least partly toothless since Art 52(3) EPC restricts the exclusion to the specified thing (discovery, computer program, etc) ‘as such’ and since the ‘Computers’ Technical Board of Appeal of the EPO (3.5.01) has had its way…

Art 52(2)/(3) per (a) a discovery is not a discovery as such if it has a technologial effect when in use, e.g. a gene when it is operating as part of a protein producing exercise. (b) a discovery is not a discovery as such if it is claimed in combination with anything else (or uncombined etc), e.g. as a plant, it is uprooted.

European Biotech Directive The ‘anything added or removed’ approach of was also set in stone, to the delight of industry, in Art 5 of the Biotech Directive which effectively adopted the position of the EPO Examination Guidelines. Elements isolated from the human body are patent-eligible even if they are identical to the elements as they existed in the body – human genes are patent-eligible as long as the patent attorney drafts the claim properly – the teixobactin claims mentioned earlier are OK. Europe is following the now-discredited Judge Learned Hand.

Relaxin Before the Directive came into force, the EPO Opposition Division in Relaxin/HOWARD FLOREY had applied the EPO Guidelines to uphold the patent (to DNA encoding a human protein, and to synthetic versions of that protein). On appeal, the Appeal Board simply followed the Directive which followed the Guidelines… See T-272/95

Australia In passing, essentially the same claims as in AMP v Myriad were found valid by the Australian appeal court last year – the isolated DNA was a manner of manufacture in line with long established Australian case law. The supreme court (Federal Court of Australia Full Court) agreed to hear the appeal and did so on June Result awaited late this year, but to my mind likely to go Myriad’s way. DN suspects the full length gene claims might fail for lack of material benefit.

A way out? If a computer program is not an invention, can the same program become an invention simply by being put on a standard disc? If a gene sequence or a plant or mineral as it occurs in nature is a discovery, does it cease to be a discovery when it is put into a standard environment under which it can be studied? Art 52(1) EPC reserves patents for ‘inventions’ and the EPC does not state that anything that passes the prior art based ‘inventive step’ test of Art 56 is an invention. We need to learn from the Supreme Court with its ‘preemption concern that undergirds [its 35 USC] 101 jurisprudence’ (Justice Thomas, Alice v CLS)

THE END Thanks for listening