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Dosage regime relief!

11 April 2019

A unanimous decision by the Supreme Court is being hailed as a relief for innovators in the pharmaceutical sector, and confirms that novel and inventive dosage regimes are patentable.

Tadalafil (Cialis) is a second in class PDE5 inhibitor for the treatment of erectile dysfunction. This use of tadalafil was first disclosed in EP 0839040 (the Daugan patent), which was published in 1997. Daugan contained an example in which 50 mg of tadalafil was provided as a tablet.

ICOS Corporation obtained the Daugan patent and took tadalafil forward into clinical trials, with the aim of developing an oral treatment for erectile dysfunction. In 1999 ICOS Corporation filed a US provisional patent application for a new dosage of tadalafil for treating erectile dysfunction. In particular, ICOS was seeking to protect a dosage of 1-5 mg per day and a European patent was granted as EP1173181 in 2003.

The validity of EP(UK) 1173181 was subsequently challenged by a number of generic drug manufacturers on several grounds including a lack of inventive step. However, the judge at first instance found the claims to be inventive, concluding that, amongst other things, it was surprising that a 5 mg/day dose was therapeutically effective (given the 50 mg dose described in the Daugan patent) and resulted in minimal side effects.

The generic drug manufacturers appealed this decision and, in a judgement that alarmed many in the pharmaceutical industry, the Court of Appeal found the patent to be invalid due to a lack of inventive step. In short, the Court of Appeal was of the view that the skilled person would have tested a 5mg dose of tadalafil as part of the dose-ranging studies routinely performed and required in Phase IIb of clinical trials. The Court of Appeal judgement included a statement that “in a case which involves routine pre-clinical and clinical trials, what would be undertaken as part of that routine is unlikely to be innovative”.

ICOS Corporation subsequently appealed to the Supreme Court, arguing that the claims of EP(UK) 1173181 were inventive and that the Court of Appeal was not entitled to reverse the decision of the judge at first instance.

The Supreme Court unanimously dismissed the appeal, finding that the Court of Appeal was justified to differ its assessment of obviousness and that the Court of Appeal’s assessment was correct. In particular, the Supreme Court took account of expert testimony provided during the first instance proceedings, which stated that, having identified a therapeutic plateau between 25 mg and 100 mg it would have been a “no brainer” to test lower doses, including 5 mg, in order to establish a dose response relationship as part of the Phase IIb study.

However, following interventions by a number of pharmaceutical sector bodies, Lord Hodge stated in the Supreme Court judgement that he “[did] not construe the judgements of the Court of Appeal as supporting any general proposition that the product of well-established or routine enquiries cannot be inventive” and took care to emphasise that “there is no policy reason why a novel and inventive dosage regime should not be rewarded by a patent”.

This provides welcome clarity for the pharmaceutical sector, indicating that new dosage regimes resulting from clinical trials can be considered inventive and worthy of patent protection.

 

Dr Helen Henderson

If you require further information on anything covered in this briefing, please contact Helen Henderson (hhenderson@withersrogers.com; +44 117 925 3030) or your usual contact at the firm. This publication is a general summary of the law. It should not replace legal advice tailored to your specific circumstances.

© Withers & Rogers LLP, April 2019