Canadian Federal Court considers whether Teva's COPAXONE second medical use patents were obvious-to-try (Teva v Pharmascience)

A recent Canadian Federal Court decision (Teva v Pharmascience, 2020 FC 1158) adds yet further nuance to the critical question of when a second-medical use patent application should be filed. One option is to file as soon as the clinical trial gets under way, to avoid the very fact of the clinical trial itself becoming prior art (see IPKat: Untested hypothesis in a clinical trial protocol destroys novelty of a method of treatment claim in Australia (Mylan v Sun Pharma). However, filing a patent too early, in the absence of convincing clinical data from a pivotal trial, runs the risk of an insufficiency attack. Instead, you could wait until the results of a clinical trial are in and argue that the success of the trial was non-obvious. If you are lucky, the trial might even demonstrate an unexpected level of efficacy that would further support inventive step. However, such an approach runs the risk of invalidation on the grounds of obviousness. After all, it may be argued, given the substantial resources were put into a clinical trial, surely there must have been some expectation of success?

Case Background

Navigating second-medical use 
patent validity

Teva has a number of patents relating to the use of glatiramer acetate for the treatment of multiple sclerosis (MS). Teva's branded glatiramer acetate product, COPAXONE, has been marketed in Canada since the mid 1990s and has been a substantial revenue generator for Teva. COPAXONE was originally authorised for administration as a 20 mg daily dose. In 2016, COPAXONE 40 mg administered three times a week, was also approved in Canada. 

A generic version of glatiramer acetate, GLATECT 20 mg, has been marketed by the Canadian based Pharmascience since 2017. The Canadian infringement action related to Pharmascience's marketing authorisation request for GLATECT 40 mg. Teva submitted that GLATECT 40 mg would infringe two of their second-medical use Canadian patents for glatiramer: CA 2702437 and CA 2760802. Pharmascience counterclaimed that the patents were invalid. One patent related to a MS patient sub-group, the other to the 40 mg/3x per week dosage regime. 

To assess inventiveness, the Canadian Federal Court followed the direction of the Canadian Supreme Court in Sanofi (2008 SCC 61) by applying the Windsurfer/Pozzoli test familiar to UK patent attorneys. The last step of Windsurfer/Pozzoli includes an assessment of whether the claimed invention would be "obvious-to-try" in view of the prior art and common general knowledge of the skilled person. 

The patient sub-group patent (CA 2702437)

CA 2702437 was a second medical use patent directed to the treatment of a subset of MS patients. The patent particularly claimed glatiramer acetate for the use of delaying the onset of full MS in patients who have experienced a first clinical attack suggestive of MS. These patients are termed Clinically Isolated Syndrome (CIS) patients. Teva filed the patent in 2007 following the positive results of their phase III clinical trial for the use of glatiramer acetate in the CIS MS patient subgroup (NCT00666224). 

The difference between the prior art and the claimed invention was the lack of any prior art data for the efficacy of glatiramer acetate in delaying MS onset in CIS patients. Pharmascience argued that the use of glatiramer to treat CIS MS patients would have been obvious-to-try. Pharmascience particularly cited the summary of Teva's Phase III clinical trial and a number of journal articles in which the success of the pivotal trial was confidently predicted. 

Teva argued in response that there were no clinical data in the prior art supporting the use of glatiramer acetate in the CIS MS patient subgroup. It was argued that the vague hopes and suggestions by the authors of obscure journal articles could not, in the absence of such data, deprive a second-medical use claim based on data from a Phase III clinical trial of inventiveness. Teva further submitted that the Phase III clinical trial results on which the patent was based demonstrated an even greater efficacy than might have been expected. 

The Federal Court was, however, unpersuaded by Teva's arguments. The Judge found that there was, if not a strong consensus, at least a prevailing view at the priority date that glatiramer acetate might be used to treat CIS MS patients. The Judge was further persuaded by evidence that other Phase III clinical trials in the same patients, for unrelated drugs, had been successful. As such, the Judge reasoned, treatment of this subgroup of patients with glatiramer acetate would have been strongly considered by the skilled person at the priority date. 

The Judge, citing previous Canadian case law, also dismissed the argument that the presence of an unexpected technical effect ("golden bonus" Janssen v Teva, 2015 FC 184) could rescue a claim that was obvious to try, given that "if a patentee obtains a workable formulation, the later discovery of one of its inherent characteristics does not add anything inventive to what had already been discovered" (para. [594], citing 2012 FC 410). The Canadian case law on this point seems at odds with both the UK and EPO case law, both of which permit an unexpected technical effect to provide inventive step (Case Law of the Boards of Appeal, I-D-10; and Actavis v ICOS [2019] USKC 15). 

The claim was therefore found to have been obvious-to-try at the priority date, and as such was found invalid. 

The dosage regime patent (CA 2760802)

CA 2760802 is a dose regime patent claiming the use of 40 mg of glatiramer acetate, administered subcutaneously three times a week with at least one day between injections, for the treatment of MS. Spacing the injections throughout the week was said to reduce injection-site irritation.   

The key prior art identified by Pharmascience was a small pilot open-label clinical trial demonstrating the efficacy of 20 mg glatiramer acetate every other day in MS patients (e.g. Fletcher et al. 2002). The prior art also included the results of Teva's Phase II clinical trial demonstrating the superior efficacy of 40 mg compared 20 mg daily dose of glatiramer acetate (e.g. Rovaris et al. 2006), together with the associated pending PCT patent application (subsequently abandoned). Critically, however, the prior art also included data from the follow-on Phase III trial demonstrating the similar efficacy of 20 mg and 40 mg daily doses of glatiramer acetate (Comi et al.). 

The difference between the state of the art and the claimed invention was that the prior art did not specify administration of 40 mg glatiramer acetate every other day, three times a week. Pharmascience submitted that the skilled person would be aware of the problem associated with injection-site irritation, and would be motivated to reduce this. Thus, it was argued, the disclosures of the clinical effectiveness of 40 and 20 mg glatiramer acetate every other day and the administration of other drugs to treat MS three times a week, would motivate a skilled person to try the administration of 40 mg every other day, three times a week. 

With regards to the obviousness of the dosage regime patent, however, the Judge did not agree with Pharmascience. The Judge particularly found that Pharmascience's argument was based on an unjustified mosaicking of the prior art. The skilled person, the Judge found, would not be aware of all of the prior art necessary for the mosaic, such as the patent application and the brief conference abstract describing the results of the non-pivotal Phase II clinical trial. Even if the skilled person were to read the prior art, they would dismiss some of the disclosures as unjustified based on the available evidence (e.g. a phase II as opposed to a phase III clinical trial). Finally, on the basis of expert evidence, the Judge was not convinced that a skilled person would believe that reducing dose frequency would necessarily increase patient compliance, given the complexity of the factors involved. 

Teva's dosage regime patent was therefore upheld, and the infringement action against Pharmascience was granted. Pharmascience has appealed the decision. 

Final thoughts

This Canadian case is yet another reminder of how nuanced the factors in decision of when to file a patent application for a second medical use may be. The resulting patent's validity will depend not only on the facts of the case, but the jurisdiction you happen to be in. A particular lesson one might draw from this Canadian case is the importance of the disease or indication involved, and the perceived likelihood of success of clinical trials in that disease. Following a successful trial, evaluating what the pre-trial expectation of success must necessarily run the risk of using hindsight. Traversing the gap between sufficiency and obviousness is this field is therefore not a trivial under-taking.