2,379,948 / Tadalafil formulation / CIALIS
Tadalafil Formulation (NOC) concerns Lilly's ‘948 patent for a formulation of tadalafil with free drug particles of less than a specified size (40 microns in Claim 1) plus specified excipients . de Montigny J found Mylan’s allegations of non-infringement and obviousness to be justified. The decision turned entirely on the facts. As counsel for Lilly stated at one point, “a lot of it just comes down to which expert the Court is going to go with” . For the most part, the Court went with Mylan’s expert. The points of most general interest are an evidentiary point concerning provision of testing data in an NOC proceeding, and a point regarding the use of documents which are not cited in the NOA. There are also a couple of points that may be of interest in interpreting formulation claims.
There were two main issues with respect to the allegation of non-infringement. First, the claims required a binder selected from a specified group in the amount of about 1% to about 5%, by weight . The (redacted) compound from that group used by Mylan was present in more than that amount. Lilly’s expert opined that the compound was working as both a binder and a solubilizer , which presumably would bring the use as a binder within the specified range. This was rejected by de Montigny J both as being speculation , but he also remarked that “it is at least implicit in the claims that the various components of the pharmaceutical formulation for which a proportional weight is set out must be acting according to their primary purpose”  and “[e]ven if [redacted] could also assist in solubilizing tadalafil once a tablet is taken by a patient, a hypothesis that has not been proven, this could not change the fact that all of the [redacted] in the Mylan tablets acts as a binder during the production of those tablets” .
The second non-infringement issue was that Mylan alleged that the tadalafil in its formulation was larger than the specified size. Lilly argued that on a purposive construction particle size must be measured after formulation, because particle size affects bioavailability when the particle is actually taken . de Montigny J rejected this on the basis that the patent itself clearly indicated that the particle size should be measured before being combined with the excipients . Moreover, even if particle size was to be measured after formulation, Lilly’s expert’s evidence was given limited weight because the underlying data was not provided:
 Lilly’s counsel objected to any questioning on the Direction to Attend and apparently instructed Dr. Bugay not to bring the requested data on the basis that it was sent out of time and that discoveries are not held in NOC proceedings. Strictly speaking, these objections from Lilly are well grounded. However, they beg the question: why wasn’t the data provided in the first place? While I am not necessarily prepared to draw an adverse inference from the fact that Dr. Bugay disregarded the request to bring the records of his results of particle size testing, I am inclined to give less weight to his opinion in the absence of the facts upon which it is based. Dr. Bugay was clearly in possession of the data plots, as he admitted, yet did not disclose them in his affidavit or when he was cross-examined; as a result, the Court is unable to assess the reliability of his test results.
On the obviousness issue, the main problem addressed by the invention was providing adequate bioavailability of tadalafil, which is poorly soluble. Lilly’s expert was of the view that there are numerous choices to be made in drug formulation and success is not guaranteed . However, while there is a large number of excipients which might be used, there is a much smaller range of excipients which are normally used , and the particular excipients specified in the ‘948 patent “were among the most commonly available and used at the relevant time. Moreover, the weight percentage rates for those excipients in the ‘948 Patent are virtually identical to those disclosed in the leading treatises” . “Lilly’s own formulation scientists referred to them as ‘conventional excipients’ and the tablet resulting from them as ‘a conventional tablet’” . Therefore on the facts, a person skilled in the art would have had a high expectation of success in solving the solubility problem, and the invention was “obvious to try” .
The most powerful counter-argument was the apparently long course of failed attempts prior to the successful formulation -. The actual course of conduct is an important consideration in avoiding the notorious problem of hindsight bias when assessing obviousness. Nonetheless, de Montigny J gave this line of argument little weight, primarily because it was not adequately supported by the evidence: “[Lilly’s fact witness] was not involved with the research done at Glaxo, and without an affiant involved in Glaxo’s work, the Court cannot weigh the soundness of the course of conduct pursued by Glaxo” . This meant that the reasons for the initial failed formulation attempts could not be ascertained. Secondly, de Montigny J accepted Mylan’s point that the early formulators were not in the same position as the skilled reader of the patent, because much of the early formulation work had become part of the state of the art and so would have been the starting point for later work .
Finally, one procedural point of general interest is that Lilly argued that Mylan’s expert’s analysis of the common general knowledge should be disregarded because he used a number of additional documents that were not cited in the NOA . de Montigny J rejected this, saying
 [C]ounsel for Lilly was unable to provide any case law to support its view that every single document upon which Mylan intended to rely to substantiate its allegations must be disclosed in its NOA. [The true rule] is not that a second person is precluded from relying on any document not cited in the NOA, but rather that the second person may not rely on any facts not cited in the NOA. What is required by paragraph 5(3)(b) of the Patented Medicines (Notice of Compliance) Regulations from a person alleging that a patent is invalid or will not be breached is a “detailed statement of the legal and factual basis for the allegation” (emphasis added). A document cannot be assimilated to a factual basis. The spirit of that provision is that a patentee must not be taken by surprise and must have all the necessary information to confidently decide whether to resist the issuance of an NOC. Of course, if a document is the source of a new factual basis, it shall properly be excluded if it has not been disclosed in the NOA. In the case at bar, Lilly made no such argument and did not identify any improper new factual bases originating from the documents not found in the NOA.