On 1 November 2017, the UK Court of Appeal handed down its decision in Actavis v ICOS1 in which Lords Justice Kitchen, Floyd and Lewison overturned the first instance decision of Mr. Justice Birss.
This decision is an analysis of the “obvious to try” approach to inventive step and considers the importance of the skilled team’s expectation of success when researching a novel dosage regime.
It was found that, when it comes to dosage regime studies, the skilled team’s expectation of success is effectively irrelevant because they are simply following a line of routine and uninventive enquiry which must always be carried out to establish a dose response relationship. The fact that the skilled team would very likely have tested the dose in question during routine Phase IIb studies was critical. The fact that the efficacy of that dose would have been surprising to the skilled team was irrelevant.
This decision does not rule out the patentability of dosage regimes, but one can imagine that the circumstances under which new dosage regimes will be considered inventive will be rare. This decision may also have implications for other areas of research that involve analogous routine pathways.
Eli Lilly (a co-defendant with ICOS) are now petitioning the Supreme Court for the right to appeal this decision, so this case may not be over yet.
The facts
Patent No. EP 1,173,181 contains claims to a composition comprising 1 to 5mg tadalafil in a unit dosage form suitable for oral administration up to a maximum total dose of 5mg per day for use in treating sexual dysfunction (and the swiss-style equivalent).
The appeal decision included findings on various grounds, but it is the contentious finding on obviousness that will be discussed here.
The prior art in question was a patent application (“Daugan”), which teaches the use of PDE5 inhibitors (such as tadalafil) for the treatment of erectile dysfunction and contains examples of a tablet containing a 50mg dose of tadalafil. Daugan explains that doses will generally be in the range of 0.5mg to 800mg/day for the average adult patient. Daugan does not specifically disclose a tablet containing 5mg of tadalafil, nor that such a low dose will be effective.
The first instance decision
Considering the two tests, ‘obvious to try’ and ‘reasonable expectation of success’, independently, Mr. Justice Birss found the claims to be non-obvious. While he considered it highly likely that the skilled team would include a 5mg dose in the Phase IIb studies in order to fully ascertain the dose response relationship, he felt that they would have no expectation that the minimum effective dose would be substantially lower than 25mg.
The appeal decision*
Lords Justice Kitchen, Floyd and Lewison found that Mr. Justice Birss had given too much weight to the expectations of the skilled team and too little to the routine nature of the research that resulted in the unexpected discovery.
Lord Justice Kitchen stated: “The fact that the skilled team could not make any prediction at the outset that a dose of 5mg of tadalafil per day would be safe and efficacious is of little weight because at least one of the purposes of carrying out the Phase IIb studies is to better understand the dose response relationship of the drug and so identify the appropriate dose range for the target population” [147]. According to Kitchen, the fact that the skilled team would very likely have tested the 5mg dose is the critical finding.
This view was mirrored by Lord Justice Floyd, who noted that “a patent will not be granted for an invention which, though not obvious in this a priori sense, is nevertheless an invention which would be arrived at by a line of routine and uninventive enquiry which would be carried out by a skilled team” [156].
Lord Justice Lewison agreed and concluded that an expectation of success is not an integral component of an “obvious to try” case [175].
What are the implications of this decision?
This decision will set alarm bells ringing at pharmaceutical companies, particularly those engaged in research into new and improved usages of known drugs. The judges’ comments imply that, as long as the skilled team is motivated to continue moving through the phases of clinical research and they have an expectation of successfully obtaining the type of information that each phase of clinical research is designed to provide, there can be no invention, even if the results obtained were surprising to the skilled team.
On the face of it, such a conclusion does seem to have serious implications beyond dosage regime patents as much of pharmaceutical research is routine in nature and is designed to provide a particular type of information.
The judges may have foreseen these anxieties and made several explicit statements which seemingly aim to quell these fears, at least to some degree. Lord Justice Floyd notes: “It is important not to let this approach to obviousness extend beyond its proper bounds…However, there are some steps which can be characterised as so routine that the skilled person would carry them out simply because they are routine, and irrespective of any prospect of success. An example is routine dose ranging studies in the clinical testing of a known drug” [157 & 160].
He also notes that “If the only thing which was driving the skilled team to test the 5mg dose was its level of expectation that a 5mg dose might be effective, [Mr. Justice Birss’] conclusion about expectation of success as to efficacy would be highly material…Phase IIb tests are, however, conducted with a separate objective, namely to identify a dose response…The absence of an expectation of success as to efficacy is, in these particular circumstances, not relevant” [171].
Perhaps, then, the effect of this decision will be limited to dosage regime patents and areas of research with analogous routine pathways that must be followed irrespective of any expectation of success regarding efficacy.
The judges have also made it clear that this decision does not sound a death knell to all dosage regime patents. Lord Justice Kitchen, referring to the decision of Lord Justice Jacob in Actavis v. Merck2 upon which the claimants relied in their arguments, states that “It does not establish that investigations into appropriate dosage regimens cannot yield patentable inventions. Indeed, Jacob LJ made it clear at [29] of his judgement research into new and better dosage regimens is clearly desirable and that there is no policy reason why the discovery of a novel and non-obvious dosing regimen should not be rewarded by a patent” [131].
The decision also provides a couple of hints regarding what dosage regimes might be considered patentable, including those arising from research where the skilled team was faced with a series of parallel avenues of study, without any expectation that any one of those avenues would prove more fruitful than any other [139 & 143]. Actavis v Merck2 also suggests that a novel dosage regime arising from research into a substance, where treatment for the condition with the substance had ceased to be worth investigating with any dosage regime, might be considered inventive [128]. However, one can imagine that such circumstances will be few and far between.
Based on this decision, it would seem likely that the patenting of novel dosage regimes in the UK will be significantly harder than it once was.
* The numbers in square brackets refer to the relevant paragraph numbers in the appeal decision
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Actavis Group PTC EHF & Others v (1) ICOS Corporation (2) Eli Lilly [2017] EWCA Civ 1671
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Actavis UK Ltd v Merck & Co. Inc [2008] EWCA Civ 444, [2008] RPC 26