The Supreme Court dismissed an appeal by the owner and exclusive licensee of a patent for a 1 to 5 mg dose of tadalafil, the active ingredient in Cialis, and held that the patent lacked an inventive step. An earlier patent had already disclosed tadalafil as a treatment for erectile dysfunction, and routine dose-ranging trials would very likely have led a skilled team to test 5 mg and find it safe and effective. The unexpected reduction in side effects was an added benefit, not an invention.
The dosage patent
Tadalafil, sold as Cialis, treats erectile dysfunction by inhibiting the enzyme PDE5. It works in essentially the same way as sildenafil, sold as Viagra, but is more selective. An earlier patent, the Daugan patent, had already disclosed tadalafil for that use. It suggested a daily range of 0.5 mg to 800 mg and gave a 50 mg tablet as an example, but it did not identify an appropriate dosage regime. It was not disputed that a skilled team reading Daugan would have taken tadalafil into ordinary pre-clinical and clinical trials.
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The patent under challenge, EP(UK) 1,173,181, was owned by ICOS and exclusively licensed to Eli Lilly. It claimed a unit dose of 1 to 5 mg, taken by mouth, up to a maximum of 5 mg a day. The claims in dispute were purpose-limited: claim 7 covered that dosage form for treating sexual dysfunction, and claim 10 was a Swiss-form claim covering use of the dose in making a medicine for that treatment. Lilly said the invention was the discovery that so low a dose was effective and caused minimal side effects, so the drug could be taken daily rather than only in anticipation of sexual activity.
The trial and the Court of Appeal
Generic manufacturers, including Actavis, Teva and Mylan, sought revocation. The issue was obviousness under section 3 of the Patents Act 1977: whether, at the priority date, the claimed dose would have been obvious to a skilled but uninventive team. That team comprised a clinical pharmacologist and a urologist.
Birss J found that the team would follow the standard trial pathway. A first efficacy study would use 50 mg. The first on-demand dose-ranging study would use 25, 50 and 100 mg, not 5 mg. Those doses would unexpectedly be equally effective, revealing a therapeutic plateau. Further testing was not inevitable, because at least 25 mg was already safe, tolerable and effective, but it was very likely, and a further study would include 5 mg. The team would not expect 5 mg to work or to reduce side effects. Discovery of the drug’s half-life would also lead them to study daily dosing. Standing back, the judge held that 25 mg a day was obvious but that 5 mg a day was not, so claim 7 involved an inventive step.
The Court of Appeal did not reject those primary findings. Kitchin LJ, with whom Floyd and Lewison LJJ agreed, held that the judge had not followed them through. Dose-ranging studies are intended to find how effect changes with dose. While the results remained on a plateau, that relationship had not been found, so the team would very likely test 5 mg and find it safe and effective. The surprise and the fewer side effects came from routine work; the reduction in side effects was a bonus. Claim 1, which was not limited to a treatment purpose, was also obvious. Lord Hodge understood Lilly not to challenge that conclusion. The Supreme Court appeal concerned claims 7 and 10, and whether the Court of Appeal could reverse the judge.
Why the low dose was obvious
Lord Hodge, with whom Lady Hale, Lord Kerr, Lord Sumption and Lord Briggs agreed, treated obviousness as one fact-specific question. The court may consider the uninventive steps needed to implement an earlier patent. It does not ask only what a skilled person could already do. The English Windsurfing/Pozzoli questions and the European Patent Office’s problem-and-solution approach are aids, not formulae, and neither requires the exact dose to have been foreseen before testing.
Relevant considerations may include whether a test was obvious to try, whether the work was routine, its cost, value judgments, alternative lines of inquiry, motive, unexpected results and the need to avoid hindsight. None is automatically decisive. A dosage regime can be patented, but a new dose will usually be obvious because investigating dosage, commonly in search of the lowest effective dose, is standard practice. An appeal court may not simply reweigh the factors. It may intervene for an error of principle, or where the conclusion is outside the range of reasonable disagreement.
The error was the failure to follow the finding that further testing was very likely. That finding, supported by Lilly’s expert’s description of a lower-dose test as a “no brainer”, left little weight in the size of the reduction from the known doses, the absence of an expectation that 5 mg would work, the surprise when it did, or the judgment about whether to continue. The team would continue because the dose-ranging study was unfinished.
Daugan had to be treated as both disclosing and enabling the use of tadalafil. On the judge’s own sequence of tests, the team would reach the claimed dose. Daily administration was not a separate invention: it followed from the half-life found in Phase I, and claims 7 and 10 also covered on-demand use up to 5 mg a day. An inventive concept must apply to every embodiment relied on. The fewer side effects were an added benefit of a dose that was obvious for another purpose, and that bonus could not found a patent.
Lord Hodge was not persuaded that the European problem-and-solution approach would necessarily have produced a different result: the problem was to identify an appropriate dose, and the team would have completed the dose-ranging work for that reason. Foreign decisions were of limited help because the evidence and findings differed. He also rejected any general rule that routine testing cannot produce an invention. A novel dosage regime, or a drug found through standard tests, may still be patented if the statutory conditions are met. On these facts, the low-dose claims were not.
Verdict: The Supreme Court unanimously dismissed the appeal. The Court of Appeal had been entitled to hold the dosage patent invalid for lack of an inventive step. The alternative challenges based on priority, anticipation and added matter did not need to be decided.
Source: Actavis Group PTC EHF and others v ICOS Corporation and another [2019] UKSC 15
