Posted: March 29th, 2019
Actavis Group PTC EHF and others (Respondents) v ICOS Corporation and another (Appellants)  UKSC 15 – 27 March 2019
The UK Supreme Court has agreed with the Court of Appeal that a dosing regimen patent was invalid for lack of inventive step.
The case concerns EP 1,173,181 (“EP’181”) owned by ICOS and exclusively licensed to Eli Lilly (together referred to as “Lilly”) for tadalafil (marketed by Lilly as Cialis) for the treatment of erectile dysfunction (“ED”). The claims of EP’181 in question were both Swiss-form and EPC 2000 claims for the dosing regimen of 1 to 5mg of tadalafil per day for the treatment of ED.
At first instance Birss J had found EP’181 to be valid and infringed. The Court of Appeal reversed the decision, finding EP’181 to be invalid for lack of inventive step. In their opinion, it would have been obvious to the skilled team to arrive at the surprisingly low (but effective) dose using routine dose ranging studies.
Lilly appealed the decision, leading to the Supreme Court reviewing the English court’s approach to inventive step, in particular the “obvious to try” test.
Common General Knowledge and the Prior Art
It was of central importance to Actavis’ case that the development of new drugs follows a well-established four phase programme of pre-clinical and clinical trials.
The key prior art document, “Daugan”, disclosed that doses of tadalafil would generally be in the range of from 0.5 to 800mg daily for the average patient.
Obvious to try?
Before Birss J, Actavis had submitted that in light of Daugan it would be obvious at the priority date for the notional skilled team to take tadalafil forward into routine pre-clinical and clinical trials as an oral treatment for ED. While costly and time-consuming, the trials would involve nothing more than routine work and no inventive effort was required. In the course of the programme to establish tadalafil as a safe and effective treatment for ED, a 5mg dose would be one of the doses used as it was obvious to determine the lowest dose at which the drug was effective. Standard dose-ranging studies would lead to the claims in EP’181.
Lilly’s response was that the discovery of the dosage regime was the result of costly and unpredictable research which was entitled to patent protection. Secondly, at the start of the programme it was not obvious to try a low dose such as 5mg per day as there was no reason to think that tadalafil would be effective at that dosage.
Lord Hodge, giving the only judgment with whom the other Justices (Lady Hale, Lord Kerr, Lord Sumption and Lord Briggs) agreed, ran through 10 factors which the court should consider when assessing obviousness in such a case:
1. Whether at the priority date something was “obvious to try”, in other words whether it was obvious to undertake a specific piece of research which had a reasonable or fair prospect of success.
2. The routine nature of the research and whether there was any established practice of following such research through to a particular point.
3. The burden and cost of the research programme.
4. The need for and the nature of the value judgments which the skilled team would have in the course of the research programme.
5. The existence of alternative or multiple paths of research as these will often be an indicator that the invention is not obvious.
6. The motive of the skilled team.
7. The fact that the results of research which the inventor actually carried out are unexpected or surprising as this may point to an inventive step.
8. The courts have repeatedly cautioned against the use of hindsight.
9. Whether a feature of a claimed invention is an added benefit in a context in which the claimed innovation is obvious for another purpose.
10. The nature of the invention.
The Supreme Court concluded that the skilled team’s task in this case was to implement Daugan. Their target would be to ascertain the appropriate dose, which would usually be the lowest effective dose. The pre-clinical and clinical trials involved routine procedures and normally progressed in Phase IIb to the discovery of the dose-response relationship.
Birss J’s findings of what would have been the sequence of the tests, included the finding that having found a therapeutic plateau, the skilled team would be very likely to test lower doses and so come upon the dosage regime in question.
The Supreme Court found that the lack of an expectation of efficacy at a 5mg dose is a factor of little weight if, as was found, the skilled team would be very likely to study such a dose in the search for a dose response relationship.
Further, the Court of Appeal was entitled to treat the judge’s failure to appreciate the logical consequences of his finding, namely that it was very likely that the skilled team would continue the testing – as an error of principle which allowed an appellate court to carry out its own evaluation. As such, the Supreme Court was satisfied that the Court of Appeal was entitled to interfere with Birss J’s assessment of inventive step and to hold that EP’181 was invalid for lack of inventive step.
A copy of the judgment can be found here.
Sarah Turner and Amy Crouch, Simmons & Simmons LLP