Thursday, February 26, 2015

Gliclazide Dosage Form Patent Obvious and Not Infringed

Les Laboratoires Servier v Apotex Inc / gliclazide (NOC) 2015 FC 108 Roy J
            2,629,670 / gliclazide / DIAMICRON MR

In Gliclazide Dosage Form Roy J dismissed Servier’s application for an order of prohibition, primarily on the basis of non-infringement [147], though he went on to hold the patent to be obvious and lacking in utility. The findings of non-infringement and obviousness turned largely on the facts and do not raise any novel legal issues, but the discussion of utility is noteworthy for holding explicitly that the factual basis for demonstrated utility must be disclosed in the patent. This post discusses the first points, and tomorrow’s will discuss utility.

Gliclazide is a known compound used for treating diabetes. The original dosage form was a breakable immediate release tablet [4]. Subsequently, a modified (slow) release tablet was developed, but it was not breakable [5]; some modified release formulations should not be broken, as dividing the tablet will alter the release profile. The invention of the ‘670 patent is related to a breakable modified release table with an identical dissolution profile whether or not it has been subdivided [70]. It was not disputed that the essential elements of claim 1 of the ‘670 patent are to a “gliclazide, a cellulose derivative which provides the modified release of the active ingredient, a binder and, once subdivided, that the gliclazide tablet has an identical dissolution profile to that of the whole tablet” [101]. The other asserted claims were variations on this theme [80].

There was dispute as to whether Apotex’ product had a binder: Apotex argued that it’s product was held together by compression, without a separate binder, while Servier argued that the cellulose derivative that was present in Apotex' product can serve both as a binder and a modified release matrix [113], [116]. There was also dispute as to whether the “identical dissolution profile” referred to the profile measured in vitro or in vivo. Apotex prevailed on both these point, which turned primarily on the terms of the patent itself. Without going into the details, I will simply say that Roy J’s analysis on these issues struck me as entirely sound.

The finding of non-infringement followed almost directly from the claim construction. There are two points of some general interest. First, Servier argued that Apotex’ evidence of its manufacturing process, which goes to the point that it tablets were held together by compression, without a binder, was inadmissible because it was not disclosed in the NOA [133]. Roy J rejected this on basis “that Apotex did not have to anticipate the position Servier chose to take,” which is to say the position that the patent should be construed to that the cellulose derivative could serve a dual purpose [133]. Roy J at [136] quoted the FCA 2005 FCA 270 [16]: “A second person [the generic] should not be required to anticipate every theory of possible infringement, however speculative, in the detailed statement supporting its allegations.”

The second point of some interest is that Servier argued that the fact that Apotex had obtained regulatory approval by showing bioequivalence with Servier’s product showed that Apotex’ product must have had an identical in vivo dissolution rate [141]. Roy J rejected this on the basis that even if that is true, the patent, properly construed, speaks to in vitro dissolution rate [142]. So, while infringement in NOC proceedings is often conceded, regulatory approval using the patentee’s product as a comparator, does not necessarily imply infringement of a patent covering that product.

The obviousness aspect of the Roy J’s decision turned straightforwardly on the facts: “[185] In my opinion, Apotex has in effect shown that the skilled worker would have been able to combine the mosaic of prior art into the claimed invention. The step was not high. The gap was not broad.”

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