BREAKING: Supreme Court confirms no hard line on inventive step test in finding Cialis dosage patent obvious

This morning, the UK Supreme Court delivered its decision in Actavis v ICOS [2019] USKC 15, upholding the Court of Appeal's decision that ICOS's dosage regimen patent was obvious. In doing so, the Supreme Court (in a welcome change...) has followed the previous approach of the lower courts to the question of inventive step in both the UK courts and in the jurisprudence of the EPO.

The patent in question related to tadalafil (branded as CIALIS). Tadalafil is an orally administered drug for treating sexual dysfunction. Tadalafil works in a similar way to Pfizer’s famous blockbuster drug Viagra, but with fewer side effects. The original first medical use patent for tadalafil (EP 0740668, "Daugan") and its associated SPC have both expired. The latest decision related to ICOS's patent (EP 1173181) which claimed a particular dosage regime of tadalafil. Lilly is the exclusive licensee of the patent.

In an attempt to clear the market for their own tadalafil generic, Actavis brought revocation proceedings against the ICOS/Lilly patent. Actavis argued that the claims lacked novelty and inventive step in view of the original tadalafil patent ("Daugan"). The contentious claims related to a dose regime of up to 5mg tadalafil per day. The Court of Appeal, in overturning Mr Justice Birss' decision, found the patent invalid for lack of inventive step (Actavis v ICOS [2017] EWCA Civ 1671). Particularly, it was found that the claimed dose would have been obvious for the skilled person to try (IPKat post here).

The Court of Appeal

Which route to take?

In the Court of Appeal, Lord Justice Kitchin (as then was), giving the judgment of the Court, held that the dosage regime claims of the ICOS/Lilly patent lacked inventive step in view of the original Daugan patent. Particularly, the claimed dosage regime was found to have been obvious given the standard procedures followed in clinical trials.

The Daugan patent (filed in the name of Glaxo, transferred to ICOS and exclusively licensed to Lilly) disclosed the use of tadalafil for the treatment of sexual dysfunction. The patent specified a tadalafil dose in the range of 0.5 to 800 mg per day. Daugan provided data for a 50 mg tadalafil dose. Daugan did not disclose a dose of 1 to 5 mg per day of tadalafil as an effective treatment of sexual dysfunction. The novelty of the subsequent tadalafil patent in view of Daugan was therefore not at issue.

In overturning the decision of Birss J, the Court of Appeal found, based on the findings of fact at first instance, that the disclosure in Daugan would have highly motivated a skilled person to pursue tadalafil in clinical trials. The blockbuster success of the related drug Viagra was found to have been a significant motivating factor. The question was then one of whether the skilled person would have arrived at the claimed dosage regime.

From what is currently known regarding the established dose effects of tadalafil, it was also accepted by the Court of Appeal that routine experimentation in a Phase I clinical trial would establish 500 mg and 100 mg as the maximum one off and daily chronic doses of tadalafil respectively. From such a result, it was held that routine practice would lead a skilled person to select a 50 mg dose of tadalafil for a subsequent Phase IIa efficacy study. Having established the safety and efficacy of a 50 mg dose, it was further agreed that a skilled person would then reasonably be expected to try doses of 25, 50 and 100 mg in a Phase IIb dosage study.

However, if the skilled person carried out the Phase IIb trial, subsequently published data indicated that they would have been faced with the surprising discovery of a dose plateau within the 25-100 mg tadalafil dose range. Within this range, increasing or decreasing the dose would not have significantly affected the efficacy of, or tolerance to, the drug. The question of obviousness was dependent of on what a skilled person would be expected to do in view of these data. What would it have been obvious for the skilled person to do?

The Court of Appeal reasoned that the purpose of a Phase IIb clinical trial is to establish a dose response curve. A skilled person would therefore have been expected to perform further studies using modified dose ranges. In this way, a response curve could be determined. A skilled person would thereby eventually try a dose of 5 mg or lower. In other words, it would not have been obvious to a skilled person to initially try a dose as low as 5 mg in a hypothetical Phase IIb clinical trial. However, the results from a trial using higher doses would, as a routine matter, be "very likely" (as the trial judge found) to lead the skilled person to a daily dose of 5 mg.

The Supreme Court

ICOS and Lilly appealed the Court of Appeal decision to the Supreme Court. It was submitted by Lilly that the Court of Appeal's approach to the question of obviousness of the claim went beyond the requirements of Section 3 (Inventive Step) of the UK Patents Act 1977. Section 3, it was argued, merely required a court to ask the question of whether the claimed invention was obvious to a skilled person at the priority date, having regard to the state of the art at the priority date. Evaluating the potential outcome of clinical trials should not form part of such an analysis, it was argued.["Effectively asking the statutory question without allowing the skilled person to do anything but stand still at the priority date", muses Merpel]

Lord Hodge, giving the judgment of the Supreme Court, dismissed this reasoning. Particularly, Lord Hodge found that:

"Lilly's approach would require the court to disregard the work which a skilled person would carry out after the priority date in order to implement the teaching of the Daugan patent."

Lord Hodge then went on to agree with the Court of Appeal that the dosage regime patent was obvious in view of the original tadalafil patent. Particularly, Lord Hodge agreed with the Court of Appeal that tadalafil can be used to treat sexual dysfunction and would have highly motivated a skilled person to pursue tadalafil in clinical trials.  He reasoned that, the target of the skilled person in implementing Daugan would be to ascertain the appropriate dose. It was clear to the judge that the skilled person would know this target from the outset. Lord Hodge concluded (with an impressive use of subordinate clauses):

"In this case the trial judge's findings of what would have been the sequence of tests, which did not depend upon hindsight, including the finding, which the evidence clearly justified, that the team, having found a therapeutic plateau, would be very likely to test lower doses and so come upon the dosage regime which is the subject matter of the patent". 

The Supreme Court emphasised that the law of inventive step is there to strike a balance in the patent system.  The test of inventive step is thus multifactorial and the relevant factors that may be at issue are dependent on the facts (and patent), in question. In this case, Lord Hodge listed 9 relevant factors (which, even at 9, were not said to be exhaustive).  These included:

1. Whether something is "obvious to try"
2. Whether something is "routine"
3. The burden and the cost of the research program
4. Necessity for and nature of value judgments
5. Existence of alternative or multiple paths of research 
6. Motivation of the skilled person
7. Unexpected or surprising results of research
8. Caution against hindsight and step-by-step (i.e. salami slicing) analysis
9. Bonus effects 

A particular issue at the Supreme Court was focused on the second factor, i.e. routineness.  Here, Lord Hodge stated:

“Secondly, it follows that the routine nature of the research and any established practice of following such research through to a particular point may be a relevant consideration which is weighed against the consideration that the claimed process or product was not obvious to try at the outset of a research programme. Again, it is only one of several factors to be weighed in the assessment and it has no primacy and certainly no paramount status as a consideration.”

The Supreme Court thus upheld the Court of Appeal's finding that the patent lacked inventive step and dismissed the appeal.

There were a number of intervener's in the case (including The IP Federation, whose representation included the IPKat's very own AmeriKat!), British Generic Manufacturers Association and the UK BioIndustry Association. As commented by Lord Hodge:

"Several intervener's advocated that obviousness be approached by a fact specific assessment on a case by case basis, an approach which is consistent with my approach in this judgment, and resisted recognition of any one factor as being of overriding importance, whether it be the cost and effort which pre-clinical and clinical trials entail, or the standardised but sometimes routine nature of such tests." 

Lord Hodge particularly observed that he did not believe the Supreme Court's or the Court of Appeal's judgment supported any general position that the product of well-established or routine enquiries cannot be inventive. On the contrary:

"A fortiori, efficacious drugs discovered by research involving standard pre-clinical and clinical trials should be rewarded with a patent if they meet the statutory tests."

Never-the-less, the results of clinical trials are undoubtedly more susceptible of falling on the wrong side of inventive step than other forms of subject-matter. Regulatory approval requires particular results to be obtained in a particular way, and it is therefore routine for a skilled person to follow a particular route. Consequently, in this context, patent protection often demands evidence that shows something more to prove inventiveness (i.e. surprising effect, bonus effect, overcoming technical prejudice, lions in the path, skilled person's lack of motivation, etc). 

Following from Lewison LJ's commentary in the Court of Appeal (see IPKat post here), it will be interesting to see if cases continue to be more focused on purebred obvious questions, or whether "obvious to try" assessments ever regain the foothold they were considered to have held prior to the Court of Appeal's decision.  Further, it will be interesting to see how the consideration of "obvious to try" may be applied to the inventiveness of drug candidates identified by systematic automated (and AI powered) searches of a database of likely candidates.

However, at the very least, it is welcome to have a Supreme Court decision on patent law that seems to be fully grounded in everyone's previous understanding of the law.