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“Probably, likely, or definitely” selection patent anticipated, obvious and not infringed

Valganciclovir

Valganciclovir

On July 12, 2012, Justice Kane of the Federal Court released the public Reasons for Judgment in Hoffman-La Roche’s prohibition application against Apotex in respect Canadian Patent No 2,154,721, listed on the Patent Register against Roche’s valganciclovir product, VALCYTE. Justice Kane found Apotex’s allegations of anticipation, obviousness and non-infringement of claim 4 were justified.

Background

The 721Patent is generally directed to a mono-L-valine prodrug ester of ganciclovir and its pharmaceutically acceptable salts. A significant disadvantage of ganciclovir recognized in the prior art was its limited oral bioavailability.

Inventive Concept and Selection Patent

A contentious issue between the parties was the proper characterization of the inventive concept of the invention. Justice Kane, concluded that the 721 Patent is not a selection patent and rejected the inventive concept proposed by both parties, instead holding that the inventive concept was “the invention of valganciclovir, a stable prodrug with low toxicity and improved bioavailability of ganciclovir.”

Anticipation

Justice Kane found that EP 329 disclosed the invention claimed in the 721 Patent. While EP 375 329 preferred bis-esters, it disclosed both mono- and bis-esters, including valganciclovir. Justice Kane noted that the decision of the Supreme Court of Canada in Sanofi-Synthelabo, reviewed by Justice Hughes in Abbott clarithromycin, had relaxed the earlier stringent test for anticipation. Justice Kane rejected Roche’s submission that the test required that person carrying out the disclosure would necessarily infringe the claim, holding:

[211] I do not share the view that the word “necessarily” was inadvertently omitted and that it should be read into the principle. As noted by Justice Hughes, the civil burden of proof on a balance of probabilities applies. The “would necessarily infringe” standard is arguably not different from “would infringe” given that the civil standard of proof on a balance of probabilities applies. It is clear that Justice Hughes is providing guidance in #7 that if the person carrying out the disclosure, which need not be an exact description, would infringe the claim on a balance of probabilities, then the claim is anticipated.

Applying the test in Sanofi-Synthelabo and the principles set out by Justice Hughes in Abbott clarithromycin, Justice Kane found that 721 Patent teaches the mono-L-valine ester of ganciclovir and a skilled person would engage in routine, non-inventive chemistry to arrive at valganciclovir.

Obviousness

The parties agreed on the test for obvious but disagreed how it ought to be applied, particularly with in respect of the “obvious to try” parameters. Following the test set out in Sanofi-Synthelabo, Justice Kane found that prior art teaching that valacyclovir, the L-valine prodrug had better oral bioavailability than acyclocvir was highly relevant and persuasive and when combined with EP 329 provided a limited number of predictable solutions to improve the bioavailability of ganciclovir:

[340] The encouraging results of valaciclovir would have led the inventor to try to do the same for ganciclovir to improve its bioavailability while maintaining its other ad-vantages. This research would have been combined with the knowledge of EP 329 which disclosed both the mono- and bis- esters, and although it only exemplified or tested the bis-esters, it had shown increased bioavailability over ganciclovir. There were two paths to pursue. Given that EP 329 had taken the bis and mono path and claimed improved bioavailability, and the acyclovir research had taken the mono path with strongly encouraging results of improved bioavailability, it would have been more or less self-evident that adding the mono-L-valine ester to ganciclovir would also result in increased bioavailability over ganciclovir.

[353] The four-part test to determine whether the invention is obvious, including the factors to be considered to determine whether it was “obvious to try” the invention, all point in the same direction. All of the factors that apply in the present case point to the conclusion that the invention was obvious to try. There was a clear motivation to pursue the invention. There were a limited number of predictable solutions to pursue. The addition of the mono-L-valine ester to ganciclovir to improve its bioavailability was more than mere speculation; it was self-evident that it ought to work based on the acyclovir research and on the prior art. While testing and research would be required, it would not be long or arduous for the skilled person armed with the common general knowledge of the day.

Non-infringement

Claim 4 of the 721 Patent is specifically directed to crystalline valganciclovir and its pharmaceu-tically acceptable salts. Justice Kane held that Apotex’s NOA, was not limited to the allegation that Apotex’s valganciclovir hydrochloride would not be crystalline when sold. Justice Kane re-jected Roche’s submission that the Court should draw an adverse inference from Apotex’s failure to provide samples for testing. Finding that Roche had failed to rebut the presumption that the Apotex Product is amorphous an non crystalline, Justice Kane found Apotex’s allegation of non-infringement of claim 4 to be justified.

A copy of the public Reasons for Judgment may be found here.