INNsight article by Alexander Robinson , August 2015

In a judgment handed down on 28 July (Teva v Leo [2015] EWCA Civ 779), the Court of Appeal in London overturned an earlier finding of obviousness in respect of two patents owned by Leo Pharma A/S. In doing so the Court of Appeal has reaffirmed the principle that an invention is not obvious under English law merely by way of being obvious to try; rather, there must also be a reasonable expectation of success associated with the test.

Background

Leo Pharma A/S is the proprietor of two European patents (EP 1178808 and EP 2455083) relating to an ointment comprising two active ingredients, calcipotriol (a vitamin D analogue) and betamethasone (a corticosteroid), together with a commercially available non-aqueous solvent called Arlamol E (a polyoxypropylene 15 stearyl ether).

Each active ingredient was known for use in the treatment of psoriasis by topical application in an aqueous ointment or cream. It was common among clinicians to co-prescribe calcipotriol and betamethasone for the treatment of psoriasis. However, it had not been possible to make a formulation containing both actives, because calcipotriol and betamethasone are each only stable within certain, non-overlapping, pH ranges. The two actives therefore needed to be prescribed in separate formulations. It was desirable to find a way to co-administer the two actives to improve patient compliance. Leo solved this problem by using the nonaqueous solvent, Arlamol E. Leo’s coadministration formulation, marketed as “Dovobet ointment”, had enjoyed considerable commercial success as a treatment for psoriasis.

The decision at first instance

Teva challenged Leo’s patents in the UK, asserting that they were obvious over the common general knowledge and a US prior art document, “Turi” (US patent 4,083,974), which disclosed a topical cosmetic preparation comprising the solvent polyoxypropylene 15 stearyl ether and a corticosteroid.

In the first-instance decision of the High Court (Teva v Leo [2014] EWHC 3096 (Pat))Mr Justice Birss held that the “person skilled in the art” would be a team comprising a skilled clinician and a skilled formulator.  The skilled clinician would be aware that a co-administration formulation would be likely to improve patient compliance.  In the judge’s opinion, the idea of a fixed-dose composition of calcipotriol and a corticosteriod such as betamethasone would have been obvious to the skilled clinician.  The common general knowledge of the skilled formulator would include the fact that calcipotriol and betamethasone were stable at different pH values.  To the skilled formulator it would have been a matter of common general knowledge to aim for a non-aqueous formulation comprising both active ingredients in order to address the pH incompatibility problem.

The real issue, in the judge’s view, was identifying a suitable solvent. The skilled formulator would have carried out compatibility tests on “a number” (given as being typically 10 – 20) of non-aqueous solvents as a “routine screening”. The “Turi” document disclosed the relevant non-aqueous solvent, Arlamol E, which was used by Leo, but this was conventionally used as an emollient in cosmetic products. Turi’s idea was to use Arlamol E as a solvent in pharmaceutical preparations with anti-inflammatory steroids.

Leo argued that regulatory considerations would discourage the skilled formulator from using Arlamol E, since it was not a widely-used pharmaceutical excipient. The judge acknowledged that the skilled formulator may never have heard of the particular solvent disclosed in Turi, that there was no evidence of the solvent’s utility with calcipotriol, and that the solvent did not have a well established track record in pharmaceutical formulations. Nevertheless, in his opinion, this “would not be sufficient to put the formulator off including it in the test”. There was no reason on the basis of the available evidence to assume that it would not work. He concluded that “based on what the skilled formulator knew about it at the time there was a sufficient prospect of a positive result in the tests with this compound to make it worth testing” and that the patents were obvious.

The decision on appeal

The Court of Appeal, in a judgment delivered by Sir Robin Jacob, disagreed with the trial judge, holding that he had erred in principle in his assessment of obviousness.
Sir Robin noted that it was “far from established that any non-aqueous non-toxic solvent would produce a stable ointment”: there was no guarantee that an arbitrarily-chosen non-aqueous solvent would be expected to work.   There was no strong expectation in the mind of the skilled formulator that any particular solvent would result in a stable product.   In the opinion of the Court of Appeal, “having the property of being non-aqueous was a necessary, but well short of sufficient, condition.  Finding [a solvent which would work] 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.” 

Sir Robin also noted that the trial judge’s opinion that the skilled formulator would find it obvious to try the Turi solvent, despite its unfamiliarity, was “rather odd” as this amounted to “saying that the notional person skilled in the art would be different from the real person skilled in the art”, which was contrary to established legal principles that the notional skilled person is captive to “the real prejudices and practices” of those skilled in the art.

In the Court of Appeal’s opinion, the judgment at first instance effectively said that “the idea of including [Arlamol E] as part of a research project amounted to obviousness”.  However, the “obvious to try” standard requires a higher expectation of success: as noted in the St Gobain v Fusion Provida case, “Mere possible inclusion of something within a research programme on the basis you will find out more and something might turn up is not enough.  If it were otherwise there would be few inventions which were patentable.” There was no “reasonably optimistic expectation” from Turi that Arlamol E would produce a stable formulation; finding that it really did “was an invention and an advance in human knowledge”.

Finding that the trial judge had erred in principle, the Court of Appeal reconsidered the question of obviousness, this time finding that both patents were non-obvious.

Summary

The Court of Appeal’s decision is important in that it reaffirms the principle that a finding of obviousness cannot rest solely upon an invention being “obvious to try”, but rather that there should be “a fair expectation of success”.   Although it may have been obvious or routine to include the invention described in the patent as part of a research programme, this does not automatically render the invention itself obvious unless there was also a reasonable expectation that the invention would succeed.  As noted in Conor v Angiotech [2008] UKHL 49, the level of “expectation of success” which is needed to establish a finding of obviousness will depend upon the particular facts of any given case.

Teva have 28 days from the decision of the Court of Appeal to seek permission to appeal the judgment to the Supreme Court and it remains to be seen whether permission will be sought.  Meanwhile, both of the patents in dispute also remain under opposition at the European Patent Office and it may be some time before a final decision is reached in those proceedings.

Note: a more detailed version of the original article published by Dehns which is available [here]