Leo Pharma (a/s Leo Laboratories Ltd) v Sandoz Ltd

Anticipation by inevitable result requires proof that every relevant way of carrying out the prior-art teaching would produce the patented subject matter. A result that is thermodynamically favoured is insufficient where kinetic factors and seeding may affect whether it forms. In an empirical field, experimental outcomes cannot be assumed from an imprecisely defined programme. For obviousness, an investigation is not obvious merely because it might be included in a research programme. The relevant question is whether there was a fair expectation of success. A limited check for hydrate formation may itself be obvious where an aqueous pharmaceutical formulation makes that issue relevant, but the invention remains non-obvious if the check would not, on the evidence, be expected to discover the claimed hydrate.

Leo owned a patent for calcipotriol monohydrate and pharmaceutical preparations containing it. Sandoz conceded infringement but counterclaimed for revocation, alleging lack of novelty and obviousness.

The principal prior art was an acne-treatment patent disclosing a suspension cream containing calcipotriol and instructing the reader to mill it to a specified particle size. Sandoz argued that carrying out that disclosure would inevitably produce calcipotriol monohydrate, or that the skilled team would discover and use the monohydrate through wet milling, regulatory work, hydrate checks, polymorph screening or routine crystallisation experiments.

The central issues were whether the prior art disclosed the invention by inevitable result and whether the claimed invention was obvious in light of the prior art and common general knowledge.

1. Outcome. No claim of the patent was invalid. The action succeeded and Sandoz’s counterclaim was dismissed.

2. Novelty. The relevant disclosure had to disclose subject matter which, if performed, would necessarily infringe. Where anticipation depended on an inevitable result and the prior art could be performed in more than one way, each relevant way had to be shown, on the balance of probabilities, to produce the same result. The instruction to mill in the prior-art suspension-cream example disclosed dry milling, not wet milling.

3. The experimental repetition relied on starting material likely to contain trace monohydrate seeds. Since seeding could affect conversion in the aqueous cream, the experiment was not a true repetition of the prior art. The alternative experiment-free case also failed. Although the cream conditions made monohydrate thermodynamically favoured, that did not establish that crystallisation would inevitably begin or that the hydrate would be kinetically favoured.

4. Obviousness. The court applied the structured approach in Pozzoli v BDMO SA, [2007] EWCA Civ 588, and [2007] FSR 37. The “obvious to try” reasoning required a fair expectation of success, assessed in the circumstances of the case.

5. Full polymorph screening was not an obvious step. However, a skilled team developing an aqueous suspension cream would recognise that it should investigate hydrate formation as part of stability or regulatory work. That did not make the invention obvious because the evidence did not establish that the limited investigation would probably discover the monohydrate. Wet milling was an obvious variant of the prior-art example, but it did not guarantee production of the monohydrate. The inherently unpredictable nature of crystallisation therefore defeated the obviousness attacks.