Guest post by Paul Cole, European Patent Attorney, Lucas & Co.
How is the Prometheus invention viewed by the EPO, and what are the differences between the reasoning of EPO appeal boards and of the US Supreme Court concerning patent eligibility?
An indication is that the EPO granted EP-B-1114403 (Seidman) which corresponds to US 6355623 and has a main claim that reads:
An in vitro method for determining efficacy of treatment of a subject having an immune-mediated gastrointestinal disorder or a non-inflammatory bowel disease (non-IBD) autoimmune disease by administration of a 6-mercaptopurine drug, comprising
determining in vitro a level of 6-thioguanine in a sample from said subject having said immune-mediated gastrointestinal disorder or said non-inflammatory bowel disease (non-IBD) autoimmune disease,
wherein said treatment is considered efficient if the level of 6-thioguanine is in the range of about 230 pmol per 8x108 red blood cells to about 400 pmol per 8x108 red blood cells.
The above claim is not an outlier. The forward references of the '633 patent include US 7524851, whose equivalent EP-B-1695092 has a main claim that reads:
A method for monitoring azathioprine therapy in an individual, said method comprising
measuring the level of 6-thioguanosine diphosphate and 6-thioguanosine triphosphate in a sample from said individual, and
calculating a concentration ratio of 6-thioguanosine triphosphate to 6-thioguanosine triphosphate and 6-thioguanosine diphosphate,
wherein a concentration ratio greater than 0.85 is indicative of superior clinical responsiveness to azathioprine therapy, and wherein a concentration ratio less than 0.85 is indicative of inferior clinical responsiveness to azathioprine therapy.
In a communication dated 26 October 2007 and available in the EPO's online file the Examining Division decided that the '851 claim was novel and inventive based on the technical effect of improved therapeutic efficiency. In accordance with EPO practice, from that effect a technical problem based on the Seidman disclosure as starting point could be reconstructed which was to provide an improved method of monitoring azopurine therapy.
If the '403 patent had been challenged e.g. in an opposition the EPO would have been bound to follow established case law and hold that the claimed method was patent-eligible firstly because it is carried out on a sample from the subject and secondly because an in vitro measurement is made, see the Enlarged Appeal Board decision in G 3/08 PRESIDENT'S REFERENCE in which the long-standing practice of the Appeal Boards was approved. An argument that the "wherein" features should be disregarded for assessment of novelty or inventive step taking into account the exclusions under art. 52 EPC as a mere discovery or mere presentation of information would have been likely to fail because, as seen above, improvement in therapeutic efficiency is treated at least at first instance as a technical effect.
The CAFC in its opinion on remand of 17 December 2010 reasoned in broadly similar terms to what would be expected from an EPO Appeal Board dealing with patent-eligibility. It held that treatment and optimization formed part of an inherently patent-eligible treatment protocol (opinion, page 20) and continued:
We agree with the district court that the final "wherein" clauses are mental steps and thus not patent-eligible per se. However, although they alone are not patent-eligible, the claims are not simply to the mental steps. A subsequent mental step does not, by itself, negate the transformative nature of prior steps. Thus, when viewed in the proper context, the final step of providing a warning based on the results of the prior steps does not detract from the patentability of Prometheus's claimed methods as a whole. The data that the administering and determining steps provide for use in the mental steps are obtained by steps well within the realm of patentable subject matter; the addition of the mental steps to the claimed methods thus does not remove the prior two steps from that realm.
As to the overall significance of the "wherein" clauses in the context of the claim as a whole, the CAFC appears to have accepted that they helped define a technical result (opinion at pp.22-23):
Although the wherein clauses describe the mental processes used to determine the need to change the dosage levels of the drugs, each asserted claim as a whole is drawn to patentable subject matter. Although a physician is not required to make any upward or downward adjustment in dosage during the "warning" step, the prior steps provide useful information for possible dosage adjustments to the method of treatment using thiopurine drugs for a particular subject. Viewing the treatment methods as a whole, Prometheus has claimed therapeutic methods that determine the optimal dosage level for a course of treatment. In other words, when asked the critical question, "What did the applicant invent?," Grams, 888 F.2d at 839 (citation omitted), the answer is a series of transformative steps that optimizes efficacy and reduces toxicity of a method of treatment for particular diseases using particular drugs.
From a European standpoint the key ruling of the Supreme Court is that the reasoning of the CAFC and the EPO Appeal Boards should not be followed. Its reasons are set out in the slip opinion pp. 20-21:
Third, the Government argues that virtually any step beyond a statement of a law of nature itself should transform an unpatentable law of nature into a potentially patentable application sufficient to satisfy §101's demands… The Government does not necessarily believe that claims that (like the claims before us) extend just minimally beyond a law of nature should receive patents. But in its view, other statutory provisions—those that insist that a claimed process be novel, 35 U. S. C. §102, that it not be "obvious in light of prior art," §103, and that it be "full[y], clear[ly], concise[ly], and exact[ly]" described, §112—can perform this screening function.
This approach, however, would make the "law of nature" exception to §101 patentability a dead letter …
What role would laws of nature, including newly discovered (and "novel") laws of nature, play in the Government's suggested "novelty" inquiry? Intuitively, one would suppose that a newly discovered law of nature is novel. The Government, however, suggests in effect that the novelty of a component law of nature may be disregarded when evaluating the novelty of the whole… But §§102 and 103 say nothing about treating laws of nature as if they were part of the prior art when applying those sections. Cf. Diehr, 450 U. S., at 188 (patent claims "must be considered as a whole").
If the CAFC/EPO approach is to be abandoned, what is the alternative? The rule followed by the Supreme Court is that the claimed combination of features must amount to significantly more than the natural law itself and that limiting the law to a particular technological environment or adding insignificant post-solution activity does not suffice. The Court was aware of the need for caution and warns in its opinion:
The Court has recognized, however, 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.
In effect the Mayo rule corresponds to the "contribution approach" suggested at first instance in the UK in Merrill Lynch's Application  R.P.C. 1 which was to consider whether the inventive contribution resided only in excluded matter. That approach also has its difficulties and it was rejected by the UK Court of Appeal in Genentech's patent  R.P.C. 147 where it was observed that:
Such a conclusion, when applied to a discovery, would seem to mean that the application of the discovery is only patentable if the application is itself novel and not obvious, altogether apart from the novelty of the discovery. That would have a very drastic effect on the patenting of new drugs and medicinal or microbiological processes.
The Supreme Court acknowledges that the rule ought not to be interpreted to cover newly discovered first or subsequent medical indications for a known substance (slip opinion at page 18):
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, however, less than clear by what logic new drugs escape the rule in Mayo but the Prometheus test is caught by that rule. For example, nitroglycerin was first synthesized in 1847 and was used as an explosive. In 1878 it was introduced as a treatment for angina by Dr William Murrell. Suppose Dr Murrell had claimed a pharmaceutical composition for the treatment of angina or other heart conditions comprising nitroglycerin and a pharmaceutically acceptable carrier or diluent. The anti-angina activity of nitroglycerin could be regarded as a mere phenomenon of nature "though just discovered", the reference to treatment of cardiac disorder could be a mere limitation to a particular technological environment and formulation into tablets or other forms for convenient administration to the patient could be regarded as an insignificant post-solution activity since the incorporation of active ingredients into tablets or other dosage forms was well known long before 1878. The pharmaceutical composition claim which is in standard form for a first medical indication would block research into further formulations and further medical indications for nitroglycerin. Indeed, blocking further development was an objection raised in the 1790's to James Watt's patent for a steam engine. It might be said that the hypothetical Murrell claim confines the reach of what has been discovered to the particular application of pharmaceuticals but it might equally be said that the Prometheus claim confines the reach of what has discovered to the particular application of a blood test for metabolites of drugs of a particular family. If there is a distinction, arguably it is no more than pragmatism.
Such a conclusion is consistent with the arguments of Robert Sachs in Part III of his Guest Post, where he singles out relative terminology and conclusory statements. A question expressed as "doing significantly more" or "adding enough" is a matter of degree rather than of kind, and provides no unequivocal forward guidance. Indeed the Supreme Court accepted the limitations of its guidance (slip opinion at page 24) where it said:
In consequence, we must hesitate before departing from established general legal rules lest a new protective rule that seems to suit the needs of one field produce unforeseen results in another.
Perhaps the wisest course is to take the opinion at its word and accept that beyond disapproving the CAFC/EPO approach Mayo makes no new rule and does nothing positive to explain what is patent-eligible and what is not.
Paul Cole wrote more on the topic in a recent guest post on Warren Woessner's blog Patents4Life.