Tuesday, March 26, 2013

When is An Extended Release Tablet "Obvious to Try"?

Tuesday, March 26, 2013
The Federal Court released a decision to dismiss an application under the provisions of the Patented Medicines (Notice of Compliance) Regulations (the PM(NOC) Regulations) to prohibit the issuance of 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 (“’944 Patent).

SEROQUEL XR is a sustained release formulation of a drug effective in treating various psychiatric disorders, including schizophrenia, bipolar disorder and major depressive disorder.

The key issue addressed in this decision is the invalidity of the ‘944 Patent on the basis of obviousness. Ambiguity was a second basis of invalidity. It however was not explored in the decision. The Court, however, stated that ambiguity is truly a last resort, rarely, if ever, to be used.


Prior to an assessment of validity the claims must be construed purposively. The construction of the claims was not at issue in this case (see paragraph [12]). With the parties agreeing that the patent at issue 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 (see paragraph [12]).

A second component of the claim construction was an assessment of the inventive concept of the claims. The Court noted that “[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”. The Court further stated that as established previously, “the entire specification, including the claims, must be considered in determining the nature of the invention”.

The Court however cautioned in paragraph [13] 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 refer. 
The Court held that 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.

Applying the four-step guide for assessing obviousness as established by the Supreme Court of Canada in Apotex Inc. v. Sanofi-Synthelabo Canada Inc [Sanofi], it was agreed that the “obvious to try” test was appropriate for the present case. It was stated in the Sanofi case that:
For a finding 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. [emphasis added]. 
There was a disagreement between the parties about the parameters of the “obvious to try” test.

AstraZeneca focused on the results of experimentation and took the position that “it must be obvious that successful results will be achieved before any experimentation was carried out”. Teva’s position was that a patent claim “will be obvious if it was more or less self-evident to try to obtain the invention”. The Court accepted Teva’s interpretation of the parameters of the test.

The Court adopted the standard laid out in Pfizer Canada v. Apotex FC 8(2009), which states that the “predictable”, and therefore obvious, solutions are equivalent to ‘solutions that provide ‘a fair expectation of success’”. The Court held 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”.

The Court further stated that “motivation” is relevant in “determining whether the skilled person has good reasons to pursue ‘predictable’ solutions or solutions that provide ‘a fair expectation of success’”. The Court agreed with Teva that there was compelling evidence in support of “motivation”, namely reducing dosing frequency and the fact that a more convenient dose regime would improve compliance (see paragraph [52]). 

The Court also assessed if certain properties of quetiapine (e.g. dose size, solubility, partition coefficient, metabolism and duration of action) would have de-motivated the skilled person from trying a sustained release formulation of the drug. The Court held that these properties did not teach away from a sustained release formulation, and stated that the skilled worker would not have viewed them as were "lions in the path”, but rather "paper tigers". (paragraph [56]).

The Court stated that, the prior art, first motivated the skilled person to find the solution of the ‘944 patent - namely, to decrease dosing frequency and the avoidance of dose dumping, and secondly clearly taught that sustained release formulations were commonly used to achieve this purpose, where HPMC being the most commonly used gelling agent.

The Court thus concluded that it was more or less self-evident to try to obtain a sustained release formulation of quetiapine using HPMC, and that the person skilled in the art would have has a fair expectation of success.

Links to decisions: 

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

By Poonam Tauh