Lions and Tigers and Bears Oh My! SEROQUEL XR formulation patent obvious

quetiapine

On March 7, 2013, Justice Near of the Federal Court of Canada, dismissed  AstraZeneca’s  prohibition applications against Teva in respect  quetiapine fumarate and Canadian Patent No. 2,251,944.  The 944 Patent is listed on the Patent register against AstraZeneca’s SEROQUEL XR tablets. The first prohibition application was commence in respects of 50 mg tablets and the second application was in respect of 150, 200, 300 and 400 mg tablets.

The 944 Patent is generally directed to extended release formulation of quetiapine. Claims 1 and 3 of the 944 Patent read:

 1. A sustained release formulation comprising a gelling agent and 11-[4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo-[b,f][1,4]thiazepine or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable excipients.

3. The sustained release formulation according to claim 1 or 2 wherein the gelling agent is a hydroxypropyl methylcellulose.

Inventive concept 

Justice Near, after looking at the entire specification concluded that the inventive concept of the claims was the decreased occurrence of dose dumping and a less frequent dosing regime of the extended released formulation.

Obviousness

Following  the framework set out by the Supreme Court of Canada in Apotex Inc. v. Sanofi-Synthelabo, Justice Near concluded that the skilled person would have known as of the claim date of the 944 Patent that

• an immediate release version of quetiapine was in clinical trial;
• quetiapine had antipsychotic properties;
• a less frequent dosing regiment generally leads to better patient compliance; and
• hydroxypropyl methylcellulose ( HPMC), a hydrophilic matrix, was one of the most popular excipients to control drug release in tablet formulations.

Justice Near held that the determinative issue in the matter before him was whether it would have been obvious to try quetapine with known sustained released formulations. Both parties agreed that an obvious to try test was appropriate but disagreed over the how certain the skilled person must be of success. AstraZeneca submitted that the test requires that it must be obvious that successful results will be achieved. Teva, on the other hand, submitted that the skilled person needed only to have to have a fair expectation of success. Justice Near concluded that on the facts before him, Teva’s interpretation was more apt, holding:

[43] While AstraZeneca argues, as one example, that the person skilled in the art “would not be able to predict with any certainty the precise amounts and grades of HPMC to be used” (AstraZeneca’s Memo at para 75), the correct standard against which to assess obviousness is no “predict with certainty,” but rather “fair expectation of success.” Based on the evidence, I thus conclude that it was self-evident or plain that there was a fair expectation that a sustained release formulation of quetiapine using HPMC would be successful.

Justice Near also rejected AstraZeneca’s submission that the physical properties of quetiapine, would have made quetiapine a “poor candidate” for a sustained release holding:

[56] In its effort to demonstrate that Teva’s allegations of invalidity are not justified, AstraZeneca points to five characteristics of quetiapine that would have de-motivated the person skilled in the art from trying a sustained release formulation of the drug: (a) large dose size; (b) solubility;
(c) partition coefficient; (d) extent of metabolism; and (e) duration of action. I am not convinced that any of these properties taught away from a sustained release formulation. The person skilled in the art would not have viewed them as “lions in the path”, but rather as paper tigers, to use the language of Lord Justice Jacob in Pozzoli SPA v BDMO SA, [2007] EWCA Civ 588 at para 126, and echoed by Justice Arnold in Teva UK Ltd & Ors v AstraZeneca AB, [2012] EWHC 655 (Pat)

Justice Near also concluded that the availability of other sustained released formulations does not make a sustained release HPMC formulation any less obvious:

[62] The fact that there may have been a number of possible formulations, as posited by AstraZeneca, does not mean that the alleged invention is not obvious (Biovail, above, at para 100; Shire Biochem Inc v Canada (Minister of Health), 2008 FC 538, [2008] FCJ No 690 at para 79). HPMC was one of the most commonly used gelling agents. This prior art knowledge combined with the relative straightforward manner in which HPMC could be manufactured, discussed above, point to a motive to choose HPMC.

A copy of Justice Near’s Reasons for Judgment may be found here.

This is not the first litigation over the Seroquel XR formulation Patent.  As previously discussed Justice Arnold of the U.K. High Court of Justice, Chancery Division held the corresponding U.K . patent invalid notwitstanding that the  District Court of the Hague  only two weeks earlier had  found the Dutch counterpart to be non-obvious. As also previously discussed, the  U.S. District Court for the District of New Jersey held the corresponding patent to be non obvious.  In February 2013 the Court of Appels for the Ferderal Circuit affirmed the disctrct Court’s finfing of non-obvious without reasons.

Teva was represented by David Aitken and Marcus Klee.