Third Time’s a Charm: Tadalafil Use Patent Invalidated in Summary Trial

Canadian Patent No. 2,226,784 is generally directed to a pharmaceutical composition containing tadalafil or its physiologically acceptable salts or solvates for the treatment of erectile dysfunction.

Prior Mylan and Apotex PM(NOC) Applications

In 2012, Mylan served a Notice of Allegation challenging the validity of the 784 Patent on the bases of lack of promised utility and obviousness-type double patenting. A year later, Apotex served a separate NOA challenging to the validity of the 784 Patent on the bases of double patenting and that the 784 Patent failed to teach the skilled person how to make the claimed hydrates of tadalafil.

In 2015, the Federal Court held that Mylan’s and Apotex’s validity allegations were not justified and issued prohibition orders in Mylan tadalafil and Apotex tadalafil. Subsequent appeals were dismissed. As a result of these applications, the launch of generic tadalafil products for the treatment of erectile dysfunction was delayed until the expiry of the 784 Patent in July 2016.

Plaintiffs’ 2016 Infringement Actions

After the expiry of the 784 Patent, Lilly started a number of separate patent infringement actions against Teva, Pharmascience, Mylan and Apotex in respect of a number of tadalafil patents that were ultimately narrowed down to just two: the 684 Patent, generally directed to low dose unit formulations of tadalafil, and the 540 Patent, generally directed to a process for preparing tadalafil, asserted only against Apotex.

In July 2019, Lilly was granted leave to amend their pleadings to add new claims of springboarding and stockpiling infringement of the 784 Patent on the condition that the trial in respect of the 784 Patent not disrupt or postpone the trials on the 684 and 540 Patents, scheduled to start later that year.

As previously reported here, Lilly’s infringement actions in respect of the 684 Patent were dismissed in a common hearing, with Justice St-Louis holding that the asserted claims were invalid for, among other things, lack of novelty in light of the 784 Patent.  Shortly thereafter, Lilly’s infringement action against Apotex in respect of the 540 Patent was similarly dismissed by Justice St-Louis.

Defendants’ Summary Trial

Shortly after the decisions on the 684 and 540 Patents were released, the Defendants brought a joint motion for summary trial seeking to dismiss Lilly’s actions in respect of the 784 Patent. Unlike Apotex’s earlier focus on solvates/hydrates of tadalafil, the Defendants summary trial motion alleged that the extreme conditions that would be required to make a salt of tadalafil would inevitably degrade tadalafil, such that any salt made under these extreme conditions would not be considered “physiologically acceptable”. As a result, the Defendants argued that each of the asserted claims were invalid for overbreadth, insufficiency and inutility.

Construction

The key construction issues in the summary trial were (a) whether “salt”, properly construed, includes non-ionic “co-crystals”; and (b) whether “physiologically acceptable salt” was an essential element of the asserted claims.

Lilly’s expert, Dr. Byrn, gave evidence that the skilled person in 1997 would understand “salt” to include co-crystals. Based on this definition, Dr. Byrn relied on a post-art Chinese patent purportedly disclosing tadalafil salicylate, tadalafil mandelate and tadalafil napthalendisulfonic acid as proof that salts of tadalafil could be made under conventional conditions.

Justice St-Louis rejected Dr Byrn’s proposed construction, holding:

[100] It is clear that in 1997, the POSITA would have understood a salt to involve a transfer of proton. Salt consisted of a negatively charged species, called and anion that electronically interacts with a positively charged species, called a cation. In 1997, the POSITA would not have included cocrystals in the definition of salt.

Justice St-Louis also held that “physiologically acceptable” was an essential element of each asserted claim and that the skilled person would understand this term to mean more than just that the salt was non-toxic:

[92] I thus find that POSITA, armed with the common general knowledge of 1997, would have understood a “physiologically acceptable” salt certainly required the salt be non-toxic and to not cause harm. However, I find the POSITA would also have understood that the salt needed to be stable and pure, not degraded.

Overbreadth

Justice St-Louis held that overbreadth is a question of fact as to what the inventor actually invented. If the evidence establishes that the inventor did not invent what is claimed, that claim is invalid.

Based on her construction, Justice St-Louis accepted the Defendants’ expert evidence that physiologically acceptable salts of tadalafil cannot be made such that the named inventor never invented any physiologically acceptable salt of tadalafil:

[120] As I conclude that it is more probable than not that physiologically acceptable salts of tadalafil cannot be made I conclude, as the Defendants argue, that such a salt was not invented. The Asserted Claims therefore claim broader than what was invented and are thus invalid for overbreadth.

Insufficiency

Based again on her construction, and applying the two-step sufficiency analysis set out by the Supreme Court of Canada in Teva sildenafil, Justice St-Louis concluded that a physiologically acceptable salt must be enabled by the disclosure. Justice St-Louis then concluded the skilled person would have to complete a research project to try and find a physiologically acceptable salt of tadalafil such that the asserted claims were also invalid for insufficiency of disclosure.

Inutility

Justice St-Louis accepted that (a) the named inventor did not have a factual basis to predict that a physiologically acceptable salt of tadalafil could be made; (b) the named inventor did not have an articulable and sound line of reasoning for this prediction; and (c) no factual basis or articulable line of reasoning is disclosed in the 784 Patent. Nevertheless, in light of her findings on overbreadth and insufficiency and the potential impact of the decision of the Supreme Court of Canada in AstraZeneca, Justice St-Louis made no finding on whether the asserted claims lack utility.

Justice St-Louis therefore granted the Defendants’ Summary Trial and dismissed each infringement action as it relates to the 784 Patent.

The Defendants’ summary trial was led by Aitken Klee. Scott Beeser and Jonathan Stainsby represented Teva; Marcus Klee and Aleem Abdulla represented Pharmascience and Riva.

A copy of the public judgment and reasons may be found here.