By guest blogger Doug Calhoun
On 20 March the Supreme Court of the United States (SCOTUS) issued a decision unanimously allowing an appeal by the Mayo Clinic and declaring invalid two patents that a lower court had found Mayo to be infringing: (see here)
The background to the invention is described on the web page of one of the inventors: (see here)
In Yves ThÃ©oret’s own words:
‘[We study] the relationships that exist between concentrations of medications and their metabolites (medication transformation products) in plasma and blood cells, and therapeutic response, according to genetic characteristics of individuals or a given population (French Canadians, Amerindians, American Blacks, Asians). These characteristics (or polymorphisms) can translate into a deceleration or an acceleration in the enzymatic transformation of medication and/or an amplification or reduction in medicated response on specific tissue sites. By determining these various variables, it is possible to individualize and optimise therapeutic treatment while minimizing toxic effects.’
‘Our studies with thiopurines (6-mercaptopuirine or Purinethol; azathioprine or Imuran) administered to children have made it possible to validate this axiom. Thus, patients with an activity deficiency of a particular transferase enzyme (thiopurine methyltransferase) have higher concentrations of active metabolites (nucleotides of 6-thioguanine) and a higher percentage of therapeutic response than patients who do not have reduced enzymatic activity. The sex and age of the patient are also determining factors when it comes to the pharmacokinetics of the medication and therapeutic response. Facing the obvious impracticality of performing pharmacokinetics (measuring the concentration of the medication and its metabolites per unit of time) on all drugs administered to children with various ailments, we also study the possible relationships between the intensity of the drug dose (quantity administered per unit of time) and the therapeutic response as evaluated by various parameters (white blood cell count, gastric acidity, hepatic enzymes). Specialized software makes it possible to determine these relationships.’
In the words of the patents, the invention ‘provides a method of optimising therapeutic efficacy of 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder’ — the goldilocks level of dosage.
The SCOTUS decision (pages 5 and 6) focused on one representative claim (claims define the invention of a patent — the rest is background):
‘A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:
(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and
(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder,
wherein the level of 6-thioguanine less than about 230 µmol per 8×108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject, and
wherein the level of 6-thioguanine greater than about 400 µmol per 8×108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.’
The decision then went on to analyse the claims. On page 11 it came to the conclusion:
‘… the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.’
Going back a step, SCOTUS was making a determination of whether or not the invention claimed was patent eligible – whether it fitted within the definition of an invention:
‘Any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof.’
But then SCOTUS went on (from page 2) to consider if it was nevertheless excluded under any of the three judge-made exclusions to patent eligibility: ‘phenomena of nature, mental processes and abstract intellectual concepts.’ It focused on the first of these exclusions. The balancing act it said it was performing was to exclude patents for the ‘basic tools of scientific and technological work’ – while at the same time recognising ‘that too broad an interpretation of this exclusionary principle could eviscerate patent law. For all inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas.’
The premise (Page 8) on which SCOTUS came to the conclusion that the patents were invalid was:
‘Prometheus’ patents set forth laws of nature–namely, relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm.’
This is a breathtaking extrapolation. Go back up and read Dr. ThÃ©oret’s first paragraph. There is a huge variability between people, based on their genetic make up, causing different rates of metabolising the thiopurines they are taking. The relationships are hardly ‘laws of nature’ within the meaning given in earlier SCOTUS decisions referred to in this one. Determining that a particular range of metabolites in the blood for a particular disorder is the goldilocks range is hardly going to pre-empt a ‘basic tool of scientific and technological work’.
What is a law of nature? One example is that nothing can travel faster than the speed of light (except maybe neutrinos between Geneva and northern Italy!). I think a definition most scientists could agree on is that it is an hypothesis that has not been disproved by so much experimentation that it is generally agreed to be correct. But remember the scientist’s lament, ‘a beautiful hypothesis – ruined by an ugly fact.’
SCOTUS justices generally deal with matters concerning the interpretation of the constitution. And a training in and understanding of science is not a prerequisite to being appointed. But a lack of understanding of science, or a wilful overlooking of what a law of nature is to a scientist, has led to this decision. And there is no appeal from here.
And who is the winner? The Mayo Clinic:
Although it is a non-profit organisation, it brings in handsome sums of money and any premium it might have had to pay for the Prometheus diagnostic kits will hardly make what it charges its patients any cheaper.
And the losers?
Prometheus Laboratories will now lose its exclusivity in marketing the diagnostic kits used to carry out the patented method. The patents were due to expire in seven years time, so its investment in commercialising the invention will have to be recouped in competition with suppliers who have contributed nothing to getting the science from the lab to the market place.
But the real losers are Ste-Justine’s hospital (the French language children’s hospital in Montreal — my home town) and the taxpayers of Quebec who fund the public health system that Ste-Justine’s is a part of. They will lose the royalty income stream the patents were generating.
And where does this leave the Myriad Genetics gene patents appeal pending before SCOTUS?
One commentator has speculated that SCOTUS will refer that case back to the appeal court that held the ‘gene’ claims to be valid. But in 2011 SCOTUS referred Mayo v Prometheus back to them — and the CAFC did not change its mind.
Watch this space.
~ Doug Calhoun