The patents concern ointments for the topical treatment of psoriasis. Calcipotriol (a vitamin D analogue) had been introduced with success by LEO in 1991 and rapidly become well-known and widely used. But it was not as potent as the steroids, including in particular the corticosteroid betamethasone – a compound known and used topically for psoriasis before 1990. LEO's ointment was a combination of two active ingredients (calcipotriol and betamethasone) in an emollient (Croda's Arlamol E, a PPG-15 Stearyl Ether).
The judgement (per Sir Robin Jacob) explains the technical problem:
13. Each ingredient has a different beneficial effect and so patients were often prescribed two topical products, one containing calcipotriol and the other betamethasone. One might use one in the morning and the other in the evening or one after another on successive days.
14. But what could not be done was to use them at the same time. Patients had to be warned that they could not be applied together. The reason was that each of the ingredients was unstable save in a narrow range of pH: alkali for calcipotriol and acid for betamethasone. The mono-creams used an aqueous solvent buffered to a pH which gave stability for the active concerned. The pHs for stability did not overlap.
17. Now there was a way, in theory, that the problem might be solved. Everyone knew that you can only have a pH at all, acid, neutral or alkali, if water is present. So theory would suggest that the way forward was to produce a dual product containing no water – which boils down to the use of a non-aqueous solvent. If you could do that then in theory the mixture of active ingredients would be stable.
Sir Robin was not convinced. He said:
24. … that to the skilled person, identifying a non-aqueous solvent which would actually work to produce a stable ointment, was not easy. Having the property of being non-aqueous was a necessary, but well short of sufficient, condition. Finding one was a research project. And that was because there was no sufficient expectation of success. Yes, a particular candidate might work, but it was far from certain that it would.
Consequently, Sir Robin considered the patents inventive and reversed the first instance decision.
Interestingly, Sir Robin agreed with the decision of EPO Opposition Division (Appeal at the EPO is pending) on inventiveness (and also added matter and sufficiency) saying:
39. I add that I am not surprised that the EPO Opposition Division, even though supplied with the Judge's judgment, rejected Teva's opposition. It said:
"[3.3.1]… The purpose of the invention in the contested patent is to provide a stable combination therapy for psoriasis (sebopsoriasis and seborrhoic dermatitis) comprising components A and B. The skilled man would then start looking for documents disclosing combination therapies and see which are the challenges presented by the fact of combining both active agents.
D22 [Turi] does not have the same purpose of the invention. D22 [Turi] is directed to provide a composition comprising corticosteroids (monotherapy) for treating anti-inflammatory diseases. Nothing is said either about a possible combination of corticosteroids with a vitamin D analogue or about the compatibility problems that said combination would present. D22 [Turi] discloses a composition having a similarity in the composition because two of the three components are present, namely component B and C. However its suitability for the purpose of the invention is not disclosed. There is neither an indication of combining the corticosteroid with a vitamin D analogue and nor a link between said non-disclosed combination with the incompatibility problem addressed in the patent in suit. Thus, D22 [Turi] could not qualify as the closest prior art."
"The skilled person would not start from D22 [Turi] and combine its teaching with the common general knowledge resulting in a non-aqueous composition comprising components A, B and C for the topical treatment of psoriasis. Pointing the selection of Arlamol E as obvious in view of D22 is a conclusion going beyond what the skilled person would have objectively inferred from the prior art, without the benefit of hindsight knowledge of the invention. In D22 the problem was neither mentioned or even suggested and considering D22 as the closest prior art is merely the result of an ex-post facto analysis." (emphasis added)