Federal Court Upholds Pfizer’s Polymorph Patent for the Depression Drug PRISTIQ as Inventive and Useful

Federal Court Upholds Pfizer’s Polymorph Patent for the Depression Drug PRISTIQ as Inventive and Useful

Pfizer Canada Inc v Teva Canada Limited, 2017 FC 777

Innovator pharmaceutical companies have been criticized for seeking questionable patents on purportedly new or improved versions of drugs that are already on the market to effectively lengthen the market exclusivity period for the original drug. Polymorph patenting may be an example of such a practice. A polymorph is a crystalline form of a drug that may have improved qualities such as more stability and reduced side effects.

This case is concerned with the Canadian Patent No. 2,436,668 (“the ‘668 Patent”), which covers the depression drug PRISTIQ marketed by Pfizer Canada Inc. (“Pfizer”). [1] Pfizer applied to the Federal Court (“FC”) and was granted an Order of prohibition to prevent Teva Canada Limited (“Teva”) from being issued a Notice of Compliance under the Patented Medicines (Notice of Compliance) Regulations. [6] This Order prevents Teva from marketing or selling its generic version of PRISTIQ until the expiration of Pfizer’s ‘668 Patent.

The FC rejected Teva’s allegations that Claims 8, 9, 33, 43 and 44 of the ‘668 Patent are obvious and lack utility. Following a heavily fact-dependent obviousness analysis, the FC found that the Skilled Person at the time would not have been able to predict the novel crystalline form taught by the ‘668 Patent, but rather would have envisioned a large research program to come to the claimed invention. [246-249] The FC also found the subject-matter of the invention claimed in the patent as useful. [347]

The Polymorph Patent – From I ODV Succinate

The ‘668 Patent, entitled “Novel Succinate Salt of O-Desmethyl-Venlafaxine” (ODV), was issued in Canada in May 2009 and describes Form I ODV succinate – a particular crystalline form of a particular salt of ODV. [15] Form I ODV succinate is the specific active pharmaceutical ingredient in Pfizer’s PRISTIQ and acts to inhibit serotonin and norepinephrine reuptake for the treatment of depression. [15]

The prior art includes EFFEXOR and the extended release version EFFEXOR XR, also marketed by Pfizer for the treatment depression. [22] Importantly, EFFEXOR and EFFEXOR XR contain venlafaxine and, upon administration, require the body to convert it to the pharmacologically active ODV. [16-17] The problem with venlafaxine at the time was that no solid-state form of ODV itself was stable enough to be safely stored. [28] As such, research was conducted to solve this problem which culminated in the development of the crystalline solid described in the ‘668 Patent. [33-34]

Teva challenged the validity of the ‘668 Patent on the grounds of obviousness and lack of utility in regard to Claims 8, 9, 33, 43 and 44. [2] Claims 8 and 9 describe the novel composition matter, Form I ODV succinate (the “Composition of Matter Claims”). Claims 33, 43 and 44 depend on Claims 8 and 9, and relate to the use of Form I ODV succinate for treatment of depression and sustained release formulations (the “Use Claims”). [160]

Use Claims and Composition of Matter Claims are Not Obvious

The FC held that Teva’s allegation of obviousness is not justified because the inventive concepts of the Composition of Matter Claims and the Use Claims were not obvious and were not obvious to try. [162] The FC focused on whether the new composition of matter could have been predicted, and what the nature was of the research efforts involved.

The FC determined the gap between the state of the art and the inventive concepts of the Composition of Matter Claims to be the new composition of matter, Form I ODV succinate. [229] Further, since the prior art taught that every new solid form had its own set of unknown and unpredictable properties, [231] the FC considered the gap between state of the art and the inventive concept of Claim 33 to be the use for the treatment of depression [234], and that of Claims 43 and 44 to be sustained release formulations with reduced side effects. [237]

The FC considered expert evidence and found that the Skilled Person would not have been able to arrive directly and without difficulty at the inventive concept. [246] The Skilled Person was considered to not have been able to predict whether a compound is capable of polymorphism, the different polymorphs that may exist, or the characteristics of such hypothetical polymorphs. [196] The FC accepted expert evidence that such predictions would have required an extremely large number of potential experiments. [196] Essentially, the Skilled Person would have envisioned a research program as opposed to research that is routine in nature. [249]

The ‘obvious to try’ test was warranted for further analysis given that pharmaceutical experimentation was involved in this case. [251-252] The FC found that it was not more or less self-evident to the Skilled Person that what is being tried – to arrive at the solution of Form I ODV succinate – ought to work. [304-305] The FC rejected Teva’s expert evidence proposing the idea that a routine salt screen could have identified a salt form such as ODV succinate, because the expert statement was contradicted on cross-examination. [260-261] The FC did not consider there to be a finite number of predictable solutions, [264] and the amount of effort required to achieve the invention was considerable, including pro-drug experimentation, salt screening, polymorph screening, in vitro and in vivo testing. [276, 279] The FC considered the course of conduct in this case to entail a research program that is more than routine experimentation. [301] Further, the FC found no evidence of motivation in the prior art that points in the direction of the ‘668 Patent. [282] For all these reasons, the FC concluded that the inventive concept was not obvious to try. [303-304]

The Utility Requirement was Satisfied

After the FC heard this case, a new test for utility was released in the decision AstraZeneca Canada Inc v Apotex Inc, 2017 SCC 36. The new test provides that in considering whether that subject matter is useful, a single useful use is sufficient to meet the utility requirement, even if multiple uses are disclosed. In contrast, the utility analysis would have previously involved discussion of the Promise Doctrine, on which Teva’s allegations of inutility were entirely based. [335]

The FC determined the subject matter of Claims 8, 9, 33, 43 and 44 to be Form I ODV succinate, [327, 336] and that all these claims met the utility threshold. [346] Claims 8 and 9 were considered useful in offering solid-form stability, [328-330] and Claim 33 in providing a treatment for depression. [340] The FC also found Claims 43 and 44 to be useful because the sustained release formulations led to reduced side effects, when compared with previous immediate release formulations. [342]

Commentary

The FC ruled that Teva’s allegations of obviousness and inutility were not justified. Perhaps the most significant take-away from this case is its unfortunate timing for Teva. The Promise Doctrine was struck down by the Supreme Court of Canada between this case having been heard and the judgment having been rendered, leaving the generic drug-maker with only the obviousness argument to advance. The analysis for obviousness turned on the opposing opinions offered by pharmaceutical experts. The judge was more persuaded by Pfizer’s expert, while Teva’s expert made concessions at the hearing that weakened its position. [261] It should be noted that this judgment was released as part of a pair of decisions that resulted in the FC issuing two Orders of prohibition against the generic makers, Teva and also Apotex (see Pfizer Canada Inc v Apotex Inc, 2017 FC 774, PCK Reporter summary available Here). Both Teva and Apotex appealed.

CSP