The Supreme Court has confirmed that a patent for a dosage regime of a drug used to treat erectile dysfunction (ED) was obvious over the prior art.
A patent is invalid for lack of inventive step if the invention claimed in it was obvious to a person skilled in the art having regard to the state of the art at the priority date (section 3, Patents Act 1977).
In Pozzoli SPA v BDMO SA, the Court of Appeal formulated questions to assess obviousness:
• Identify the person skilled in the art, and then identify the relevant common general knowledge of that person.
• Identify the inventive concept of the claim in question.
• Identify what, if any, differences exist between the matter cited as prior art and the inventive concept of the claim.
• Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention? (the Pozzoli questions) (www.practicallaw.com/6-374-1001).
In Actavis UK Ltd v Merck & Co Inc, the Court of Appeal held that there was no policy reason why a novel non-obvious dosage regime, which was the product of expensive and unpredictable research, should not be rewarded with a patent of a Swiss-form claim (www.practicallaw.com/4-382-2625).
Tadalafil is a drug, used to treat ED, which followed the blockbuster drug sildenafil (VIAGRA). L was the exclusive licensee of two patents related to the dosage of the drug Tadalafil and its formulation.
The dosage patent claims doses of 1-5 mg of Tadalafil up to a maximum total dose of 5mg per day and discloses that such doses exhibit fewer side effects than sildenafil whilst retaining efficacy.
Tadalafil is marketed for the treatment of ED in unit doses of 10mg and 20mg for on-demand administration and in unit doses of 2.5mg and 5mg for daily administration. Sildenafil is marketed on demand at doses of 25mg, 50mg and 100mg.
Four pharmaceutical companies (together, A) applied to revoke L's patents to clear the way to market Tadalafil. Patent protection for Tadalafil itself had expired. A alleged that the patents were not entitled to the claimed priority and were invalid for lack of novelty and inventive step, as well as for added matter and insufficiency. L counterclaimed for infringement.
The High Court held that some patent claims were not entitled to priority and were invalid as lacking novelty, but that other claims were novel and not obvious over the relevant prior art and were not invalid for added matter (www.practicallaw.com/2-633-7924). A appealed.
The Court of Appeal reversed the High Court decision on obviousness. A appealed.
L argued that the correct question to be asked when assessing obviousness was whether at the priority date, before the skilled team embarked on any testing, it was obvious in the light of the prior art that a 5mg daily dose of Tadalafil would be safe and effective with minimal side effects for sexual dysfunction. That is, was it obvious to try a low dose of 5mg because there was a reasonable expectation of success at the outset, before any testing (the "obvious to try" test). L argued that this was in line with the Pozzoli question requiring identification of the inventive concept of the claim. This approach would exclude any consideration of whether the steps required to reach the invention were routine.
A argued that, on the basis of the fundamental principles of patent law, a patent should not cover subject matter which was already in the skilled person's repertoire, such as products or processes which the skilled person was already able to make or do. The claimed low dose of Tadalafil was the result of a familiar and routine path of pre-clinical and clinical research, in which each step was likely to follow the outcome of the prior step.
The Supreme Court upheld the Court of Appeal's assessment of obviousness and held that the patent was invalid for lacking an inventive step.
The court provided guidance on the correct approach to assessing obviousness. Here, the obviousness argument was based on prior art which disclosed the use of Tadalafil for the treatment of ED, giving a 50mg dose as a formulation example.
The court rejected L's arguments and held that it was not necessary for the skilled team to identify in advance of the clinical testing the specific dose which is the subject of the claim. Instead, the court relied on the High Court's findings that the skilled team, having embarked on Phase IIb dose ranging studies and identified a therapeutic plateau at doses of 10mg and above, would very likely test a 5mg dose given that the aim of a dose ranging study is to identify a dose as low as possible consistent with effectiveness. The claim was therefore obvious.
The court also dismissed L's argument that daily administration was a technical effect of the patent, given that the claims cover both on-demand and daily dosing and any inventive concept must apply to all embodiments falling within the claims. Also, the fact that the claimed dosing regime had an added benefit of reduced side effects was merely that, an added benefit, and did not preclude the claims from being obvious.
This decision confirms that patents for new dosage regimes for known drugs are unlikely to involve an inventive step, given the standard testing regime required to meet regulatory requirements for marketing authorisation. It also makes the "obvious to try" test, with its likelihood of success requirements, of less importance in these circumstances.
In considering the factors to be assessed following the Pozzoli approach, the court recognised the nature of the invention as the overriding factor. While the decision confirms Actavis v Merck, which showed that novel non-obvious dosage regimes may in appropriate cases be patentable, it also points out that in the case of a dosage regime patent the target of the skilled person's research is largely pre-determined. The skilled person aims for a dose as low as possible consistent with effectiveness: this is normally the appropriate dosage regime and consequently is an obvious one. This decision therefore confirms existing patent case law, without the controversy that recent Supreme Court patent decisions, such as Actavis v Eli Lilly, have caused.
Case: Actavis Group PTC EHF and others v ICOS Corporation & and another  UKSC 15.
First published in the May 2019 issue of PLC Magazine and reproduced with the kind permission of the publishers. Subscription enquiries 020 7202 1200.