Teva UK Ltd and Another v Leo Pharma A/S Leo Laboratories Ltd (Third Party/Appellant)
| Jurisdiction | England & Wales |
| Judge | Sir Robin Jacob,Lady Justice King,Lord Justice Kitchin,And |
| Judgment Date | 28 July 2015 |
| Neutral Citation | [2015] EWCA Civ 779 |
| Docket Number | Case No: A3/2014/3748 |
| Court | Court of Appeal (Civil Division) |
| Date | 28 July 2015 |
[2015] EWCA Civ 779
IN THE COURT OF APPEAL (CIVIL DIVISION)
ON APPEAL FROM THE HIGH COURT OF JUSTICE
CHANCERY DIVISION (PATENTS COURT)
The Hon Mr Justice Birss
Royal Courts of Justice
Strand, London, WC2A 2LL
Lord Justice Kitchin
Lady Justice King
and
Sir Robin Jacob
Case No: A3/2014/3748
and
Henry Carr QC and Tom Alkin (instructed by Simmons & Simmons LLP) for the Defendant/Appellant and Third Party/Appellant
Daniel Alexander QC and Mark Chacksfield (instructed by Pinsent Masons LLP) for the Claimants/Respondents
Hearing dates: 18/19 May 2015
Sir Robin Jacob (giving the first judgment at the invitation of Lord Justice Kitchin):
LEO (with permission in part granted by Birss J and in part by this Court) appeals from the judgment of Birss J of 6 th October 2014 and the consequential order for revocation of Leo's patents Nos. 1 178 808 and 2 455 083. The respondent, which sought revocation, is Teva.
Henry Carr QC and Tom Alkin argued the case for LEO and Daniel Alexander QC and Mark Chacksfield that of Teva.
The sole ground of attack which succeeded before the Judge was obviousness over a prior art citation called "Turi" (US Patent 4,083,974). The Judge did not go on to consider the alternative grounds of attack, namely insufficiency and added matter.
Some Basic Legal Principles
The rule as to appeals on a finding of obviousness are well-known and were not in dispute. For an appeal to succeed, an appellant must identify at least one point of principle in respect of which the Judge erred. If that can be done, then the question is open to independent evaluation by this Court, see Biogen v Medeva [1997] RPC 1 at p.45, per Lord Hoffmann, in a passage which has been cited countless times since, and St. Gobain v Fusion Provida [2005] EWCA (Civ) 17.
The structured approach to obviousness set out in Pozzoli v BDMO [2007] EWCA Civ 588, [2007] FSR 37 is often a helpful way of approaching the question, as indeed is the problem-solution approach of the EPO in a case where the patent addresses the real problem faced by the inventor and not some different artificially constructed problem (see Actavis v Novartis [2010] EWCA Civ 82, [2010] FSR 28 at [26–34]).
Next there is the oft-cited (including in the House of Lords in Conor v Angiotech [2008] UKHL 49, [2008] FSR 28) passage from Kitchin J in Generics v Lundbeck [2007] RPC 32 at [72]:
"The question of obviousness must be considered on the facts of each case. The court must consider the weight to be attached to any particular factor in the light of all the relevant circumstances. These may include such matters as the motive to find a solution to the problem the patent addresses, the number and extent of the possible avenues of research, the effort involved in pursuing them and the expectation of success."
Finally the "obvious to try" test for obviousness has limitations:
"the notion of something being obvious to try was useful only in a case in which there was a fair expectation of success. How much of an expectation would be needed depended upon the particular facts of the case" per Lord Hoffmann in Conor v Angiotech at [42].
Application of the Principles to this Case
Psoriasis is an inflammatory skin disease affecting as much as 2–3% of the population, fortunately in the main mildly. There is no known cure but there are long term treatments to alleviate symptoms. Topical treatments were the first line of approach. This case is concerned with an ointment.
Patient compliance is an important factor, particularly for those with mild symptoms. As the Judge put it at [26]:
"Although in severe cases a patient would be likely to comply with the treatment in order to alleviate their symptoms, in the majority of cases where the psoriasis was mild and reasonably contained there would be a greater risk that a patient might not comply with the treatment if it was disruptive of their daily routine, unpleasant to apply, had adverse local side effects (e.g. irritation) or more serious side effects (e.g. skin atrophy or systemic effects)."
The key claims of the patents as amended, whose priority dates are 23 rd April 1999, for present purposes may be treated as simply being for an ointment consisting of two active ingredients, calcipotriol (a vitamin D analogue) and betamethasone (a corticosteroid, a base (e.g. Vaseline) and a commercially available solvent called Arlamol E. It was common ground that the key question was whether or not such an ointment was obvious at the priority date in April 1999.
Each active was, well before April 1999, well-established for use as the sole active in a psoriasis ointment or cream.
More particularly calcipotriol 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 betamethasone — a compound known and used topically for psoriasis before 1990.
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.
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.
Patient compliance for using both creams was thus rather complex. The compliance problem was greater for less serious cases (because people were more likely to forget a particular application) as the Judge had found.
By the mid-90s, if not before, clinicians were expressing a need for an ointment or cream containing both ingredients. Some added the view that this was not possible because of the pH problem. That in itself can be somewhat discounted because clinicians are not formulators. What cannot be discounted is that formulators must have known of the desire — the want — of clinicians for a combination product.
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.
If it were as simple as that, then it would follow that any non-aqueous non-toxic solvent would do. Just picking any one of them at random would work. It would be a mere arbitrary non-inventive choice. It would not matter which such solvent was chosen, because the expectation would be that all would work. The particular choice would be analogous to the arbitrary choice of the diameter of a plate discussed in Actavis v Novartis [2010] EWCA Civ 82, [2010] FSR 28 at [36–38].
However it was far from established that any non-aqueous non-toxic solvent would produce a stable ointment. The Judge found that "there is no proper evidence either way as to whether they [i.e. other such solvents] would work or not." Nor was it established that the skilled team would expect that any non-aqueous solvent would do. Keeping water wholly out was a known real problem.
The Judge said:
"39. The concept of apparent pH reflects the fact that skilled formulators knew that even if a non-aqueous system was chosen (such as a paraffin based ointment) in practice it was unlikely to be possible to remove all the water from a system. Even if a lab based formulation was truly dry, some water was likely to be encountered during manufacture, processing and in the product's lifetime. Thus I do not accept Professor Crowley's view that by choosing to use an ointment a skilled formulator would simply put to one side any concerns about pH dependent stability. Such considerations would always play a part.
40. However in the end the skilled formulator is an empiricist. Exactly how these various considerations will play out in practice is hard to predict in advance and always requires testing. For example that is why pre-formulation compatibility studies are always carried out."
This is an important finding. For it follows that it cannot be said that a formulator would have anything like a strong expectation that any particular non-aqueous solvent would work — would result in a product stable for both calcipotriol and betamethasone. On the contrary he would have to undergo a research project. The Judge said the use of non-aqueous solvents would be "well-worth investigating" but that is not the same as saying any particular such solvent had a fair expectation of success.
Of course in the real world formulators would be likely to start any experimental programme using non-aqueous solvents with which they were familiar and which had been used in other pharmaceutical topical formulations. They may well have started with propylene glycol because by the priority date it was used in a third of the marketed corticosteroid formulations. It had a water content of 0.2%. But it did not work as LEO themselves found out.
Teva's expert, Prof. Crowley, accepted that...
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