Alex Bajjon

May 2019

Background

The patent in question (EP 1173181) related to a new dosage regime for tadalafil (marketed under the brand name Cialis®) for treating erectile dysfunction (ED). The patent is owned by ICOS and exclusively licensed to Eli Lilly.

The claims of the patent included both pharmaceutical composition claims and “Swiss-form” second medical use claims, for example:

Claim 1: A pharmaceutical unit dosage composition comprising 1 to 5mg of a compound having the structural formula [of tadalafil] said unit dosage form suitable for oral administration up to a maximum total dose of 5mg per day”

Claim 10: Use of a unit dose containing 1 to 5mg of a compound having the structure [of tadalafil] for the manufacture of a medicament for administration up to a maximum total dose of 5mg of said compound per day in a method of treating sexual dysfunction in a patient in need thereof.

Actavis argued that these claims were obvious over the first patent which describes tadalafil and its use in treating cardiovascular disorders (the “Daugan patent”). The Daugan patent disclosed the compound tadalafil and that it has a potency (IC50 value) against PDE5 of 2 nM.

Given that it was known for PDE5 inhibition to be useful in the treatment of ED, it was not disputed that at the priority date that it would have been obvious for the skilled person to take tadalafil forward into a routine pre-clinical and clinical trial programme as an oral treatment for ED, based on the disclosure of the Daugan patent.

Actavis argued that given it would have been obvious to take tadalafil into clinical trials, it would have been an inevitable result that the efficacy of tadalafil at 5mg/day would be tested (and discovered). Therefore, any surprising effect would be a mere bonus effect and as a result, the claims could not be considered non-obvious.

However, ICOS/Eli Lilly argued that due to the unpredictability of the pharmaceutical field, at the start of the trial it would not have been obvious that a 5mg/day dose of tadalafil would be effective for treating ED. In other words, there would have been no reasonable expectation of success of effectiveness of the claimed invention itself.

At first instance, Mr Justice Birss held that there would have been no reasonable expectation that a dose of 5mg/day would be effective in treating ED and hence the claims of the patent could not be considered obvious.

On appeal, this was overturned by the Court of Appeal on the basis that it would have been obvious to the skilled person to take tadalafil to clinical trials and that the invention would have been inevitably reached by testing of various dose levels during the pre-clinical and clinical trials.

This appeal to the Supreme Court was concerned with two principal issues:

1. The application of the obviousness test to dosage regime patents
2. Whether the Court of Appeal was entitled to reverse the judgment of the judge at first instance on that question in the circumstances of this case.

Obviousness

With regard to obviousness, having reviewed the relevant UK and EPO case law on the approach to assessing obviousness/inventive step, Lord Hodge gave a list of relevant factors that must be considered:

1. Whether the invention was obvious to try
2. Whether the invention was reached through routine research
3. The burden and cost of any research programme
4. The necessity for and the nature of the value judgments which the skilled team would have in the course of a testing programme
5. The existence of alternative or multiple paths of research (or was it instead a “one-way avenue”)
6. The motive of the skilled person (the skilled person does conduct clinical trials without a reason, but instead has an end target in mind)
7. Whether the results of research are unexpected or surprising
8. The need to avoid 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 – i.e. whether the benefit a mere “bonus effect”

Lord Hodge made clear that each of these factors are not necessarily decisive on their own, but instead all relevant factors must be considered before a conclusion as to the obviousness of an invention can be made.

In this case, having considered the relevant factors, it was held that it would not have been necessary for the skilled person to identify the specific dose of the invention prior to conducting the clinical trials. However, as the invention was reached by a step-by-step approach, without the benefit of hindsight, this demonstrated that the skilled person would be very likely to pursue the trials to the appoint at which they would arrive at the claimed dosage forms, without exercising any inventive activity.

Accordingly, the Supreme Court affirmed the decision of the Court of Appeal and concluded that the claims of EP 1173181 were obvious over the Daugan patent.

Role of Appellate Court

ICOS/Eli Lilly also argued that the Court of Appeal had been wrong to overturn the trial judge’s finding of non-obviousness.

On this matter, the Supreme Court noted that there is a distinction between “reversing the judge’s evaluation of the facts where the application of the legal standard involved a question of principle” (being allowable) and one which involved no question of principle but was simply a matter of degree (being unallowable).

Lord Hodge noted that an error of principle is not confined to an error as to the law, but could also cover errors in application a legal standard to the facts of a case.

In this case, although Court of Appeal did not overturn any individual findings of fact made by the trial judge, the Supreme Court held that “the Court of Appeal was entitled to treat the judge’s failure to appreciate the logical consequences of the finding as an error of principle which allowed an appellate court to carry out its own evaluation.”

Therefore, the appeal was dismissed and the patent found invalid.

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