Speculative theory of infringement sinks tadalafil prohibition application

On February 23, 2015 Justice de Montigny released his public reasons in a third prohibition application involving Eli Lilly and Mylan in respect of Mylan’s proposed tadalafil product (for our summaries of the earlier decisions, see here and here). This application involved Canadian Patent No 2,379,948 which is generally directed to a pharmaceutical formulation comprising

• tadalafil particles with at least 90% of the particles having a size of less than 40 microns;
• about 50% to about 80% of a diluent;
• a lubricant;
• about 1% to about 5% of a hydrophilic binder; and
• a disintegrant

Non-infringement – hydrophilic binder

While the identity of the hydrophilic binder in Mylan’s proposed tablets was redacted from public reasons, it was present in an amount exceeding 5% and therefore was outside the claimed range of about 1% to about 5%.  Lilly’s expert, Dr. Bodmeier, argued that the relevant excipient is normally present in tablets between 2% and 5%  and that higher amount of the excipient in Mylan’s tablets shows that the excipient is acting both as a binder and as a solubilizer. When the standard amount of the excipient acting as solubilizer (purportedly 10% to 12%) is subtracted from the total amount of the excipient, the remainder functioning as a binder is within the claimed range.

Justice de Montigny rejected Lilly’s theory of infringement as speculative.  Specifically, Justice de Montigny held that Lilly had not established that the excipient in the amount present in Mylan’s tablets cease to provide the adhesion functionality of a binder. Further still, there was no evidence that the relevant excipient in Mylan’s tablets was, in fact, acting as a solubilizer.

Speculation, even by experts, is not evidence, and is clearly not sufficient to meet the burden of proof in infringement cases.

Non-infringement – particle size

The second issue was whether the claimed particle size distribution was to be measured before of after the tadalafil particles had been formulated into tablets. Lilly had argued that since the purpose of the 948 Patent was to provide formulations with increased bioavailability, purposive construction of the patent dictated that particle size must be measured after formulation. Justice de Montigny rejected this construction on the basis that Lilly’s construction was not supported by the language of the 948 Patent or its experts.  Based on this language, it was clear that the only construction compatible with the 948 Patent was particle size distribution of  tadalafil  before the tadalafil particles are mixed with the excipients.

Since Lilly’s expert had only provided evidence on the particle size of the tadalafil particles after being formulated into a tablets, Justice de Montigny concluded that Lilly had not discharged its burden of showing that Mylan’s allegation of non-infringement was not justified.

Obviousness

While not required in light of his finding on non-infringement, Justice de Montigny considered whether the asserted claims were obvious.  The parties agreed that the inventive concept was the improved stability and bioavailability of tadalafil achieved by reducing its particle size and combining it with specific excipients.

Lilly’s expert had argued that formulation was an iterative process and the skilled person would be presented with an infinite number of possibilities when attempting to formulate a new drug.  Furthermore, until each formulation is made and tested a skilled person would not know for certain that such a formulation would work.

Justice de Montigny held that Lilly, in requiring certainty, set the obviousness bar to high.  Rather, the proper test for obviousness only requires that the skilled person have a good reason to pursue predictable solutions or solutions that provide a fair expectation of success.  It was no answer that the skilled person had  over 200 excipients to choose from. The  preferred excipients disclosed in the 948 Patent were among the most commonly available and used excipients.  Even if the proper standard is not “fair expectation of success”, Justice de Montigny held that the invention was obvious to try according to the test set out  by the Supreme Court of Canada in Clopidogrel.  Applying these tests, Justice de Montigny concluded:

[159] For all of the above reasons, I am therefore of the view that the reduction of the particle size was an obvious route to try, even if it was not possible to be sure that taking this route would produce success. Again, the test is not whether a skilled person could have predicted the result with certainty, but rather whether there could be a fair expectation of success. Once prior art is taken into consideration, there was a finite number of approaches to improving solubility, and two of the most obvious were ruled out either because they were not available or because they had been tried without success. I accept Dr. Brittain’s conclusion that “the extent of the effort required to achieve the stated invention of the 948 Patent would have been in the category of routine testing”, both with respect to the particle size and with respect to the selection of the excipients (Brittain affidavit, paras 131-132, AR Vol 13, p 2700). Therefore, Lilly has not met its burden to establish that Mylan’s allegation of invalidity is not justified, on a balance of probabilities.

A copy of Justice de Montigny’s public Judgment and Reasons may be found here.