The UK Patents Court has held that a formulation patent for an ophthalmic solution is invalid for obviousness having applied, for the first time, the factors established in recent Supreme Court precedent 1
Allergan’s patent relates to bimatoprost, a treatment for glaucoma which reduces the build-up of pressure inside the eye, known as Intra-Ocular Pressure (IOP). The patent concerned a formulation of bimatoprost at a lower concentration than previous products (0.01% compared to 0.03%), in combination with a higher concentration of a preservative called benzalkonium chloride (BAK, at 0.02% compared to 0.005%), embodied in Allergan’s product marketed as LUMIGAN. The driver for the reduced concentration of bimatoprost related to the dose-dependent adverse side-effect of bimatoprost, called conjunctival hyperemia (otherwise known as “red-eye”).
Aspire and Accord sought to launch generic versions of LUMIGAN and did not dispute that their products fell within the scope of the patent. Hence, the case concerned only invalidity; in particular whether the patent was obvious and/or insufficient (though given the finding of obviousness, the latter was not addressed in the judgment in any great detail).
The main prior art (Laibovitz) disclosed a Phase 2 dosing study, comparing the safety and efficacy of bimatoprost at varying concentrations (0.003%, 0.01% and 0.03%) with another agent, timolol. The date of this study – 2001, a few years before the 2005 priority date – was the reason that a preservative was not used, as preserved formulations were not available at the time the study was conducted. The results of the Laibovitz study showed that, although the lower concentration was effective, the higher concentration had the most advantageous safety profile. The authors concluded that further clinical evaluation of the higher 0.03% concentration was warranted.
Mr Justice Arnold referred to the Supreme Court’s recent review of the law of obviousness in Actavis v ICOS, commenting that the “overall tenor” of Lord Hodge’s leading judgment was to confirm the approach previously adopted by the courts, as summarised in his list of factors.
Arnold J then said “it is sufficient to note five points” in this case, inferring that the longer list of factors set out by the Supreme Court does necessarily need to be fully assessed in each case. This makes sense, as of course only a subset may apply to the facts or arguments of a particular case. To paraphrase, the 5 points noted were:
- The endorsement (but not a mandate) of the approach set out in Windsurfing / Pozzoli.
- The endorsement of considering the facts of each case and the weight to be attached to any particular factor in light of all the relevant circumstances.
- The relevance of whether something was “obvious to try”, including the balance between the need for a likelihood of success versus that there may be experiments that are obvious, even if there is no expectation of success due to the nature of the experiment.
- The existence of alternatives may be evidence that an invention is not obvious. Interestingly, Arnold J added here that he took this to be an endorsement by Lord Hodge that what matters is whether the invention was obvious from a technical point of view, not whether it would be commercially obvious to implement it.
- The endorsement of motive being a relevant consideration.
One argument concerned Arnold J’s point 4, as Allergan argued that the cost of repeating Laibovitz (the motivation for which was accepted by both sides) would be “enormous”. Arnold J rejected this argument, adding that another obvious course of action would be to just repeat the 0.01% and 0.03% arms of the study. In any event, Arnold J repeated his statement in point 4 above that cost is not a relevant factor as it has no effect on whether the repeat would be obvious from a technical point of view.
As a result, the key question became whether, when repeating Laibovitz, the inclusion of the preservative BAK would be an obvious choice from a technical point of view. Arnold J held that it would be obvious to use a preserved formation when repeating the study, as the only reason preserved formulations were not used in Laibovitz is because they were not yet available. Since BAK was the most commonly used preservative at the priority date, it was an obvious choice. Furthermore, it was obvious to try BAK at 0.02%, being one of a range of concentrations already used in other commercially available products.
Arnold J added that, even if it was not obvious to include BAK as a preservative, it was obvious to include it as a penetration enhancer; it was deemed to be common general knowledge that BAK could act as a “corneal penetration enhancer” to increase bioavailability of bimatoprost, which would be relevant to improve its efficacy at a lower (0.01%) concentration. As such, the patent was obvious.
It is interesting, with respect to Allergan’s argument on the cost of repeating Laibovitz, that one of the Supreme Court’s factors that Arnold J did not refer to when selecting five points in particular (set out above) was Lodge Hodge’s third factor that:
“…the burden and cost of the research programme is relevant. But the weight to be attached to this factor will vary depending on the particular circumstances. This appeal concerns a pharmaceutical patent claiming as an invention a dosage regime. The cost and effort involved in bringing a drug to market through pre-clinical and clinical trials are notorious.”
This may therefore be an early indication that the courts will need to debate further as to the weight attributed to this factor versus approaching obviousness from a purely technical stance; the latter having been more strongly weighted and emphasised by Arnold J in this case.
1 Allergan, Inc & Anor v Aspire Pharma Ltd  EWHC 1085
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