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1 January 2012BiotechnologyMaryAnne Armstrong

Is there life for medical diagnostic patents after Prometheus?

On March 20, 2012, the US Supreme Court handed down the long-awaited decision in Mayo Collaborative Services v Prometheus Laboratories Inc. The Prometheus decision rocked the IP world and left people wondering whether there is any room left for patents in the medical diagnostic industry, particularly as it applies to personalised medicine.

The claims in the Prometheus patent were directed to a method of optimising therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:

(a) administering a drug providing 6-thioguanine; and

(b) determining the level of 6-thioguanine, wherein the level of 6-thioguanine less than about 230 pmol per 8x108 red blood cells indicates a need to increase the amount of said drug … and … the level of 6-thioguanine greater than about 400 pmol per 8x108 red blood cells indicates a need to decrease the amount of said drug.

The Supreme Court, in analysing the patentabilty of the Prometheus claims, emphasised that it was well-known to treat gastrointestinal disorders with thiopurine drugs, and that these drugs metabolised into 6-thioguanine. It was further well-known that patients metabolised the drugs inconsistently and that the level of 6-thioguanine could be used as a measure of whether the drug level was too high or too low.

The Prometheus claims took the well-known step of administering the drug to particular patients and the associated well-known phenomena (metabolism to 6-thioguanine and correlation of 6-thioguanine with appropriate drug levels) and recited defined parameters for concluding whether the drug level was too high or too low.

The Supreme Court noted that the claims of Prometheus set forth laws of nature (the relationship between the concentration of metabolites in the blood and likelihood that the drug will be ineffective or cause harmful sideeffects) which, by themselves, are unpatentable.

The Supreme Court then considered “whether the claims do significantly more than simply describe these natural relations. To put the matter more precisely, do the patent claims add enough to their statements of the correlations to allow the processes they describe to qualify as patenteligible processes that apply natural laws?”.

In reaching its decision, the Supreme Court discussed the earlier decisions of Diamond v Diehr and Parker v Flook. The Supreme Court considered Diehr and Flook to be two representative endpoints at opposing ends of the spectrum for determining the patentability of an invention which applies a law of nature.

The Supreme Court seemed to suggest, in comparing Diehr and Flook, that because in Diehr the steps of measuring the specific recited parameters and applying those parameters to open a rubber curing mould were novel and unobvious, the invention was patentable. The Supreme Court contrasted the Diehr invention to that of Flook, wherein it was noted that all of the parameters being measured and steps taken were conventional and well-known.

The Supreme Court further stated with regard to Flook that: “Unlike the process in Diehr, it [the claims in Flook] did not ‘explain how the variables used in the formula were to be selected, nor did the [claim] contain any disclosure relating to chemical processes at work or the means of setting off an alarm or adjusting the alarm limit’. ... And so the other steps in the process did not limit the claim to a particular application.”

“BASED ON PROMETHEUS, IT APPEARS THAT IF A CLAIM IS DIRECTED TO WHAT MAY BE TERMED CLASSIC PERSONALISED MEDICINE … SUCH A CLAIM IS LIKELY TO BE FOUND TO BE UNPATENTABLE.”

In applying the decisions of Diehr and Flook to the Prometheus claims, the Supreme Court concluded that “the steps in the claimed processes (apart from the natural laws themselves) involve well-understood, routine, conventional activity previously engaged in by researchers in the field”, and that “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.

For these reasons we believe that the steps are not sufficient to transform unpatentable natural correlations into patentable applications of those regularities”.

Since the Prometheus decision, the courts have been generally silent on this issue, probably in part because they are waiting for the Court of Appeals for the Federal Circuit (CAFC) to reconsider the decision in Ass’n for Molecular Pathology v USPTO (Myriad). On April 30, 2012, the CAFC requested that supplemental briefs be filed in Myriad, taking into consideration the Prometheus decision. Oral arguments are scheduled in Myriad on July 20, 2012.

However, the US district court for the District of Columbia rendered a decision in Smartgene Inc v Advanced Biological Laboratories shortly after the Prometheus decision. The claim in Smartgene was directed to a method for personalised medicine and recited steps of:

(a) providing patient information to a computing device comprising a first knowledge base … of therapeutic treatment regimens; a second knowledge base comprising a plurality of expert rules for evaluating and selecting a therapeutic treatment regimen … and a third knowledge base comprising advisory information;

(b) generating a ranked listing of the treatment regimens; and

(c) generating advisory information. Thus, the claims in Smartgene were broader than even those in Prometheus, with the Smartgene claims not being limited to a specific disease or specific evaluation parameters. The court in Smartgene held the claims to be invalid under 35 USC §101, in view of the Prometheus decision.

Unfortunately, based on the Prometheus decision, it appears that if a claim is directed to what may be termed classic personalised medicine, (ie, taking known parameters and known treatment options and optimising that treatment based on an analysis of the known parameters), such a claim is likely to be found to be unpatentable. However, the Supreme Court did not preclude patents for diagnostic methods per se.

It is worth noting that the Supreme Court stated: “We need not, and do not, now decide whether were the steps at issue here less conventional, these features of the claims would prove sufficient to invalidate them. For here, as we have said, the steps add nothing of significance to the natural laws themselves. Unlike, say, a typical patent on a new drug or a new way of using an existing drug, the patent claims do not confine their reach to particular applications of those laws.”

It is clear that diagnostic methods using new and novel reagents and/or equipment (ie, diagnostic methods that are tied to a new product) remain patentable following the Prometheus decision. The more difficult question that remains to be resolved is whether inventions directed to diagnostic methods, which rely on newly discovered physiological relationships but are not connected to a new product, are patentable.

The decision by the Supreme Court appeared to emphasise the fact that the natural relationships, as well as the treatments, diseases, etc, set forth in the Prometheus claims were all well-known.

However, what remains unanswered for now is what about newly discovered relationships, which are applied in a specific way? If the invention is somehow tied to a newly discovered process or a new correlation (ie, a newly appreciated ‘law of nature’), which is specifically applied in a new and novel way, the invention may be patentable.

For example, if the correlation between 6-thioguanine and drug efficacy/side-effects was newly discovered by the Prometheus inventors and the claims recited steps that involved more than what the Supreme Court termed “apply[ing] the law”, the invention could have been said to be more like the invention in Diehr than the one in Flook.

It appeared to be important to the Supreme Court that the claims in Diehr relied on measuring parameters in a way that was not previously appreciated and further, that there was a specific recited application (ie, opening the mould).

In Prometheus, if the correlation between 6-thioguanine and drug efficacy/side-effects had not been previously appreciated and the claims recited more than simply monitoring the 6-thioguanine levels and had recited, for example, (a) specifically measuring 6-thioguanine at certain time points; and (b) adjusting the drug dosage in a specific way, the claims could have been argued to be more like those in Diehr than those in Flook.

So, in going forward, it appears to be important that the claims contain newly discovered subject matter (even if that subject matter is a law of nature) and recite a specific and defined application of that newly discovered subject matter.

MaryAnne Armstrong, PhD, is a partner at Birch Stewart Kolasch & Birch, LLP. She can be contacted at: maa@bskb.com

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