Pharma update: tadalafil patent invalidated

The District Court of The Hague has invalidated ICOS’ patent EP 1 173 181 B3 (‘EP ‘181’) claiming a dosage range of tadalafil for the treatment of sexual dysfunction.

Icos Corporation (‘Icos’), an Eli Lilly and Company subsidiary, distributes the medicinal product Cialis® containing tadalafil for the treatment of sexual dysfunction in adult men. EP ‘181 relates to tadalafil for the treatment of sexual dysfunction in a dosage range of 1-5 mg.

Teva Pharmaceuticals Europe B.V. (‘Teva’) initiated invalidity proceedings before the District Court of The Hague. It argued that EP ‘181 should be invalidated because it contained added subject matter, and for lack of novelty and inventive step.

In its judgment of 14 March 2018, the Court invalidated the Dutch part of EP ’181 due to lack of inventive step. The Court reasoned that in light of the closest prior art (Daugan), the skilled person would embark on clinical trials, in the reasonable expectation to find an effective and safe dosage of tadalafil. The data obtained from the phase 1 clinical tests would lead the skilled person to conduct a dose ranging study (phase IIb). The question was whether 5 mg would be part of such phase IIb study. The Court agreed with Teva that, based on mathematical calculations comparing the data from Daugan and the phase 1 clinical trial, with the known data regarding sildenafil (Viagra®), the skilled
person would also test 5 mg.

According to the Court, referring to the decision of the UK Court of Appeal, the skilled person would still eventually arrive at a dosage of 5 mg, even if he would not have immediately included a dosage of 5 mg in the phase IIb study. The skilled person would test 25, 50 and 100 mg and find that they were equally efficacious, but the lowest dosage caused the least side effects. Therefore, he would test even lower dosages and, having found that a daily dosage of 10 mg was equally efficacious but caused even fewer side effects, it was obvious to test 5 mg. The Court held that, even though it may not have been predictable at the outset that a dose of 1-5 mg was safe and efficacious, all the skilled person had to do to arrive at the claimed dosage of 1-5 mg, was to merely perform several non-inventive steps. For the skilled person this entails nothing more than walking down a ‘one-way-street’. EP ‘181 thus lacked inventive step and was invalidated as a result. The Court did not address the other invalidity arguments asserted by Teva.

Pending these proceedings, Icos initiated interim relief proceedings against Teva, Sandoz and Mylan for introducing their generic products on the Dutch market. Those interim relief proceedings were suspended awaiting the outcome in the invalidity proceedings. It is to be expected that Icos’ request for an injunction in the interim relief proceedings will be rejected due the Court’s decision in the invalidity proceedings.

Similar proceedings have been conducted in other countries, including the UK, Germany and Belgium. The UK Court of Appeal and the German Bundespatentgericht also invalidated the UK and German parts of the patent due to lack of inventive step. In the UK, this matter is currently pending before the Supreme Court. In Belgium, the Court of Appeal in Brussels decided to refuse an injunction in PI proceedings as it considered it likely that the patent lacked inventive step. Final relief proceedings are still pending.