Friday, June 13, 2014

Evergreening Patent Held Invalid by the FCA

Pharmascience Inc v AstraZeneca Canada Inc / NEXIUM (NOC) 2014 FCA 133 Pelletier JA: Sharlow, Mainville JJA rev’g 2012 FC 1189, 105 CPR(4th) 267 O’Keefe J
            2,290,531 / esomeprazole / NEXIUM

In Pharmascience / NEXIUM the FCA held that O’Keefe J at first instance had erred in law in failing to apply the correct legal standard to the question of the burden of proof of utility [38], [42]. The FCA therefore reviewed the evidence de novo [43], and concluded that AstraZeneca had not satisfied the onus of showing that Pharmascience’s allegations of lack of utility was unjustified [43], [58]. Consequently, the application for a prohibition order was dismissed. Though there is no hint of it in the decision, I suspect that the FCA’s approach to the utility question was motivated by the “evergreening” nature of the 531 patent.

The patent claims an enteric coated formulation comprising (es)omeprazole*, an enteric coating, and a separating layer, in which the separating layer is hydroxypropyl methylcellulose (HPMC) with a specified cloud point (CP) [FC 13], [14]. The separating layer is used to prevent reactions between the API and the enteric coating which may lead to problems such as discoloration [FC 33]. HPMC was known in the prior art for use in the separating layer, and the technical contribution disclosed by the patent lay in the discovery that use of HPMC with the specified CP results in a higher release rate for the API [FC 47], and that there is variation in CP between batches of HPMC. The practical advantage of this is that if each batch of HPMC is checked for CP prior to tableting, and only batches with the specified CP are used, discard of the final product for failure to meet regulatory requirements for API release rate requirements will be reduced, thus reducing costs [FC 98, 100], [531 p4].

The utility point turned essentially on the question of whether it was true that the specified CP gives a higher release rate. But ignore this question for the moment. Suppose it is true, and the patent was valid. The result would be that a generic which produced a version of NEXIUM using what I understand to be the old method – that is, not by screening batches of HPMC for CP, but simply by using whatever came through the door and then screening the final product for release rate – would nonetheless infringe the patent. This is because the patent does not claim a method of production comprising screening HPMC for CP, and using only batches with the specified CP; it claims the pharmaceutical composition as such.** Assume it is true, as the patent asserts, that there is batch variation in HPMC. Because of that batch variation, even a generic using the old method would produce at least some lots of tablets which fall within the claims of the patent. The net result is that a technical contribution which provides a cost reduction in the production of esomeprazole tablets could be used to entirely block sales of such tablets, even if the production method did not take advantage of the technical teaching of the patent.

In the FC, this point was addressed largely via the argument that the 531 patent is not an invention because it merely verifies the properties of HPMC. O’Keefe J responded that

[176] On review of the evidence and the ‘531 Patent, I agree with AstraZeneca that the patent provides more information than merely identifying inherent physiochemical properties of a known substance. Rather, as submitted by AstraZeneca, the patent delves into batch-to-batch variations of a single low viscosity HPMC product and a property that can be tested to ensure consistent release of omeprazole in accordance with the marketing standard.

While it is all true (at least on the evidence as found by O’Keefe J), the problem is that the patent does not claim such an invention. The patentee is entitled to claim the practical embodiment of the new information it provides, and so the inventors would have been entitled to claim a method comprising testing for batch variation prior to tableting. But instead the patent claimed the formulation itself, even, on its face, if produced under the previously known method. Similarly, AstraZeneca argued that:

[100] When properly construed, the patent does not merely contribute a verification of the CP but also teaches that by selecting low viscosity HPMC above the claimed CP, a pharmaceutical formulator can reduce the amount of product discard that does not meet omeprazole release specifications. This was a surprising and unexpected teaching offering a substantial advantage.

The patent taught that, but it is not enough to teach a new invention; that invention must also be claimed. To my mind, this case is like the classic case of BVD Co [1937] SCR 441, in which the patentee invented and disclosed a good invention, but failed to claim it.

From a policy perspective, the patentee should be entitled to the exclusive right to exploit the advantage provided by its invention. In this case, the practical advantage is reduced production costs. What the 531 patent should give AstraZeneca is the right to compete against generics using a lower cost process, so it can afford to undercut the generics and still make a profit. The technical advance disclosed in the patent does not justify a monopoly on the production of enteric coated esomeprazole. (I should say that none of this has anything to do with the degree of ingenuity involved in the patent. It may require a stroke of genius to devise a new production method that reduces costs by 1%. The patent reward should be commensurate with the benefit to society, not with the degree of ingenuity.)

It may be that I haven’t fully understood the facts or the proper construction of the patent, as the case was not argued in exactly the way I have discussed, and consequently many of these issues were not discussed. But it does seem clear that a minor technical advance was being used to block competition in the market for enteric esomeprazole. This seems to be a true example of evergreening, in the pejorative sense. While the FCA took a stringent approach in its utility analysis, I would not read too much into that analysis beyond a desire to strike down what appears to be clearly a bad patent.

*Note: the 531 patent covers formulations of both omeoprazole and esomeprazole. The FC decision states that Pharmascience’ ANDS compared its capsultes to AstraZeneca’s NEXIUM, which is esomeprazole [3]. The FCA, on the other hand, says that the order sought was to prohibit an NOC “to Pharmascience for its version of the drug omeprazole “ [1], and the FCA also states that “Losec is a commercially marketed formulation of enteric coated esomeprazole, the (-) enantiomer of omeprazole.” [15]. As I understand it, LOSEC is omeoprazole, not esomeprazole. I take it that the FC was right that the case is really about esomeprazole. Nothing turns on this error by the FCA, but comparing the FC and FCA decisions can be confusing unless this point is kept in mind.

**In addition to claiming the formulation itself, the patent also claims the process of manufacture using HPMC of the specified CP, but it does not specify prior selection of the HPMC prior to tableting, so that again, the old method would infringe. This is as I construe the claims; the issue was not addressed in the decisions

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