Tadalafil - UK

On Nov. 01, 2017, the England and Wales Court of Appeal issued a decision in CIALIS (tadalafil) case & found that the patent for treatment of male erectile dysfunction is invalid for obviousness.

The patent, EP (UK) 1,173,181 relates to the use of tadalafil in a dosage form and is entitled "Compositions comprising phosphodiesterase inhibitors for the treatment of sexual dysfunction". The claimants, Actavis, Teva and Mylan, began these proceedings to revoke the EP’181 patent on various grounds and so clear the way for the marketing of their own products. Birss J handed down judgment on Aug 10, 2016 ([2016] EWHC 1955 (Pat)) where he found that patent is valid & infringed by claimants. Claimant appealed.

Three claims were at issue, namely claims 1, 7 and 10. Claims relate to pharmaceutical unit dosage composition comprising 1 to 5mg of tadalafil wherein maximum total daily dose is 5 mg per day for treatment sexual dysfunction. Critical issues before the court of appeal were whether the subject matter of each of claims 7 and 10 was derivable directly and unambiguously, using common general knowledge from the priority document & whether there was enablement. Court of appeal held that skilled person would not have had any difficulty making the compositions the subject of claims 7 and 10 based on disclosure of the priority document. With respect to added matter & novelty court of appeal agreed with Judge Birss J and held that patent is novel & there is no added matter.

Obviousness:

Primary reference, Daugan teaches the use of PDE5 inhibitors for the treatment of ED. Tadalafil (compound A) is specifically disclosed, its IC50 against PDE5 is given and examples of a tablet containing a 50mg dose are described. It explains that doses of tadalafil will generally be in the range of from 0.5 to 800mg daily for the average adult patient.  The differences between the disclosure of Daugan and the subject matter of claims 7 and 10 are that Daugan does not specifically disclose a 5mg daily dose of tadalafil or that such a dose is an effective treatment for sexual dysfunction.

Court held that at the start of the programme and given Daugan, the skilled team would have had no idea whether or not a 5mg daily dose of tadalafil would be a safe, tolerable and effective treatment of sexual dysfunction, still less that it would be both efficacious and have minimal PDE5 related side effects. Summarizing the position in relation to the skilled team's expectations, Judge Bliss J found that they would not have a reasonable expectation that a dose of 5mg per day (on demand) would provide a useful treatment for ED, nor any expectation at all that this would produce a clinically relevant effect but with minimal side effects. However, they would discover that this dose is both effective and has reduced side effects and this would be a surprise.

Court of appeal overturning the decision held that the claimed invention lies at the end of the familiar path through the routine pre-clinical and clinical trials' process. The skilled but non-inventive team would embark on that process with a reasonable expectation of success and in the course of it they would carry out Phase IIb dose ranging studies with the aim of finding out, among other things, the dose response relationship. It is very likely that in so doing they would test a dose of 5mg tadalafil per day and, if they did so, they would find that it is safe and efficacious. At that point they would have arrived at the claimed invention. Therefore claims 7 and 10 of EP’181 are invalid.