Pharma in brief - Canada: Federal Court dismisses Prohibition Application for quetiapine tablets [SEROQUEL XR®]

March 2013 Authors: Amy Grenon, Daniel Daniele

Contacts

Case: AstraZeneca Canada Inc. et al. v. Teva Canada Limited et al.

Drug: Quetiapine fumarate extended release (XR) tablets (SEROQUEL XR®)

Nature of case: Prohibition Application pursuant to PM(NOC) Regulations

Successful party: Teva Canada Limited

Date of decision: March 7, 2013

Summary

AstraZeneca Canada Inc. and AstraZeneca UK Limited (“AstraZeneca”) brought an application pursuant to section 6 of the Patented Medicines (Notice of Compliance) Regulations (the “NOC Regulations”) for an order prohibiting the Minister of Health from issuing a Notice of Compliance to Teva Canada Limited (“Teva”) in respect of AstraZeneca’s quetiapine fumarate extended release tablets (sold under the brand name SEROQUEL XR®) until the expiry of Canadian Patent No. 2,251,944 (the “’944 Patent”). SEROQUEL XR® is used to treat various psychiatric disorders, including schizophrenia, bipolar disorder and major depressive disorder.

The ‘944 Patent claims a sustained release formulation of quetiapine. The only issues of invalidity canvassed at the hearing were Teva’s allegations of obviousness and ambiguity. The Court held that Teva’s allegation that it was more or less self-evident to try to obtain a sustained release formulation of quetiapine had an “air of reality” and that AstraZeneca failed to established that Teva’s allegation of obviousness was unjustified. As such, the Court dismissed AstraZeneca’s application for a prohibition order. The Court held that it was not necessary to explore the allegation of ambiguity in detail and stated that this type of allegation is "truly a last resort, rarely, if ever, to be used."

Claim construction

The parties agreed that the ‘944 Patent claims a sustained release formulation of quetiapine hemifumarate, made up of: (i) the particular gelling agent hydroxypropyl methylcellulose [HPMC]; (ii) the hemifumarate salt of quetiapine; and (iii) one or more pharmaceutically acceptable excipients.

However, Justice Near held that this was not the end of the claim construction analysis. The Court held “[w]here, as in this case, the inventive concept of the claims is not discernible from the claims themselves because they present a bare chemical formula, the Court is directed to read the specification in the patent to determine the inventive concept of the claims”. Justice Near cautioned that this does not give the Court free rein to construe the claims as broadly or as narrowly as it wishes. The patentee is “entitled to have the question of obviousness determined by reference to his claim and not to some vague paraphrase based upon the extent of his disclosure in the description”.

The Court held the key elements of the inventive concept claimed by the ‘944 Patent are: (1) a decreased occurrence of dose dumping; and (2) a less frequent dosing regimen.

Obviousness

The Court applied the four-step guide for assessing obviousness as laid out by the Supreme Court of Canada in Apotex Inc. v. Sanofi-Synthelabo Canada Inc [Sanofi].

(i) The State of the Art and Common General Knowledge

The Court held that the skilled person would have been aware that an immediate release version of quetiapine had been studied in phase II and phase III clinical trials and would have understood that quetiapine had antipsychotic properties with a reduced tendency to cause debilitating motor and other neurological side effects. The skilled person would also have known that maintenance, long-term efficacy and tolerability are the focus in treating the chronic phases of schizophrenia and other types of psychotic disorders. The skilled person would know that less frequent dosing generally leads to better compliance with a prescribed drug regimen. Finally, a skilled person would have been aware that, while there were many gelling agent options to choose from when making a sustained release formulation with a hydrophilic matrix, HPMC was commonly used.

(ii) The Inventive Concept

The Court held that the invention of the ‘944 Patent is “a sustained release formulation of quetiapine hemifumarate, made with HPMC as the gelling agent and one or more excipients, with a view to decreasing the occurrence of dose dumping and to enabling a less frequent dosing regimen”

(iii) Difference between the Prior Art and Inventive Concept

The Court held that the difference between the prior art and the inventive concept of the claims of the ‘944 Patent is a sustained release formulation for the specific drug quetiapine.

(iv) Obvious to Try

In the fourth step of the analysis the parties agreed that the “obvious to try” test is appropriate when determining whether the differences between the inventive concept and the prior art require any degree of invention. However, the parties disagreed as to the parameters of the test.

The Supreme Court in Sanofi stated that in order to find that an invention was “obvious to try”, there must be “evidence to convince a judge on a balance of probabilities that it was more or less self-evident to try to obtain the invention. Mere possibility that something might turn up is not enough.” AstraZeneca argued that in order for an invention to be “obvious to try”, it must have been very plain that successful results would be achieved before any experimentation was carried out. Teva argued that a patent claim will be obvious if it was more or less self-evident to try to obtain the invention. Justice Near accepted Teva’s articulation of the parameters of the test.

More or less self evident - The Court found 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.

Extent, nature and effort required to achieve the invention - The Court held that it was settled law that there is no invention in discovering properties of known substances. The person skilled in the art would have known that changing the viscosity or grade of the gelling agent, such as HPMC, would adjust the dissolution rate of a sustained release formulation. Consequently, the choice of HPMC and its specific grades would have been the product of routine experimentation.

Motivation - The Court held that the issue of "motivation" was central to its obvious to try analysis. In particular, the Court considered "whether certain pharmacokinetic properties of the drug would have de-motivated the notional skilled person." The question at this stage of the analysis was whether there was a fair expectation of success. On this issue, the Court held that the pharmacokinetic properties of quetiapine (e.g. dose size, solubility, partition coefficient, metabolism and duration of action) did not teach away from a sustained release formulation. These were "paper tigers", not "lions in the path."

Actual Course of Conduct - The Court drew an adverse inference from the fact that AstraZeneca did not lead evidence as to the course of conduct leading to the invention.


Link to decisions:

http://decisions.fct-cf.gc.ca/en/2013/2013fc245/2013fc245.html (50 mg strength tablets)

http://decisions.fct-cf.gc.ca/en/2013/2013fc246/2013fc246.html (Parallel reasons for 150, 200, 300 & 400 mg strengths)

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