Eli Lilly Canada Inc v Mylan Pharmaceuticals ULC, 2015 FC 125

This Federal Court (“FC”) decision dealt with an application to prohibit the issuance of a Notice of Compliance (“NOC”) until the expiry of an existing patent. The respondent successfully argued that the existing patent was invalid on the grounds of lack of utility for having made a promise of utility that could not be demonstrated nor soundly predicted, was anticipated by a previous patent of the applicant that claimed an overlapping dosage range, and was also therefore made obvious by the same previous patent. This decision is being appealed by the applicant.

Background

Mylan Pharmaceuticals (“Mylan”), one of the respondents, sought a NOC for a generic version of tadalafil, a drug used to treat erectile dysfunction (“ED”). Eli Lilly (“Lilly”), the applicant, applied for an order prohibiting the issuance of the NOC to Mylan until the expiry of Canadian Patent No. 2,371,684 (the “‘684 Patent”). The ‘684 Patent claims a dosage form of tadalafil and claims its use to treat ED.

Mylan argued that the ‘684 Patent was a selection patent, contending that it had never had its utility demonstrated or soundly predicted either at the filing date or presently. Alternatively, Mylan submitted that if the ‘684 Patent was not interpreted as a selection patent, then the claimed invention was anticipated by Canadian Patent No. 2,226,784 (the “’784 Patent”), and was clearly obvious.

The FC was required to construct the ‘684 Patent and then determine whether the following three allegations were justified:

1. Is the allegation that the ‘684 Patent is invalid for lack of utility justified?
2. Is the allegation that the claims are invalid for anticipation by the ‘784 Patent justified?
3. Is the allegation that the claims are invalid for obviousness justified? [82]

The FC dismissed the application for an order prohibiting the issuance of the NOC as the applicant failed to establish the validity of the ‘684 Patent on a balance of probabilities. The respondent was successful in alleging that the ‘684 Patent lacked utility, was anticipated and was obvious. Lilly has appealed.

‘684 Patent

This case is one of three prohibition applications by Lilly relating to its tadalafil patents. Tadalafil was claimed and disclosed in Canadian Patent No. 2,181,377 (the “’377 Patent”), which was published in 1995. [4] The use of tadalafil for the treatment of ED was claimed and disclosed in the ‘784 Patent, which was published in 1997. [4]

The ‘684 Patent came about as a result of research into the side effects of sildenafil, the main compound in Viagra, which is also used for the treatment of ED. Some of the side effects of sildenafil include, but are not limited to, high rates of flushing, blue-green vision, headaches, back pain, rhinitis and conjunctivitis. [6-7]

The ‘684 Patent claimed a dosage form of tadalafil of less than 20mg to treat ED, with separate claims to various specific dosage forms. It was filed in Canada on April 26, 2000 and has a priority date of April 30, 1999. [13] Lilly sold the drug under the brand name CIALIS, in a unit dosage form protected by the ‘684 Patent.

Selection Patent

Mylan attempted to argue that the patent is a selection patent. A selection patent refers to “a patent where a single element or segment is selected from a group, based on a particular feature of the element that provides an advantage not shared by the larger group.” [105] It is similar to other patents and is governed by the same legal principles.

The FC did not interpret the ‘684 Patent as a selection patent. There was nothing in the ‘684 Patent to suggest that the promised advantage of reduced side effects was peculiar to the claimed dosage range and to the exclusion of other doses.

Utility

Central to the utility analysis is the promise of a patent, which as stated by the Federal Court of Appeal in Sanofi-Aventis v Apotex, 2013 FCA 186, “is the standard against which the utility of the invention described in the patent is measured”. Lilly contended that the promise of the ‘684 Patent was that the claimed doses were effective and that they would have less side effects than sildenafil when used by patients for the treatment of ED. [86] Mylan argued that the ‘684 Patent’s promise went beyond Lilly’s construction, and that it promised that the claimed doses would provide an improvement over sildenafil by reducing three side effects – flushing, vision abnormalities, and the negative effects associated with co-administration with nitrates – to clinically insignificant levels. [86] Lilly attempted to read down the promise, but the FC disagree, finding that the promise of the ‘684 Patent was “not merely to lower the incidence of adverse side effects as compared to sildenafil, but to minimize them significantly or even to eliminate them.” [100]

The FC thus agreed with Mylan’s construction of the promise, holding that Lilly’s construction would go against the clear language of the patent. [92] There were explicit statements throughout the patent that promised more than a marginal improvement over sildenafil.

The FC found that as of the filing date, the promised utility had not been demonstrated. Furthermore, the FC found that the promised utility could not be predicted by a person skilled in the art. Lilly did not attempt to establish predicted utility and the FC held that it should not have even tried as there was no factual basis for such a prediction as there was no evidence to support a sound prediction. [116] The disclosure of the ‘684 Patent was not complete and the FC noted that the only study provided that compared one of the side effects between the compounds showed no difference, calling the study “very sketchy.” [139]

The FC also agreed with Mylan that at the time the application was being heard neither demonstrated nor predicted utility of the ‘684 Patent had been established.

Consequently, the FC found that the ‘684 Patent lacked utility, as the promise of the Patent was neither demonstrated, nor soundly predicted at the filing date and at present.

Anticipation

After finding that the ‘684 Patent was not a selection patent, the FC was required to consider whether the ‘684 Patent was anticipated by the ‘784 Patent. As set out by the Supreme Court in Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61, a patent will be invalid for anticipation if the essential elements of the claimed invention have been disclosed and where the disclosure enables the claimed invention. [145]

The ‘784 Patent disclosed:

• unit dosage forms of tadalafil, such as tablets or capsules, in the dosage range from 0.2 to 400 mg;
• with the unit dosage form suitable for oral administration; and
• for use in treating male ED. [148]

The doses of tadalafil in the ‘684 Patent, ranging from 1 to 20 mg, are entirely within the dosage range disclosed in the ‘784 Patent. The FC therefore held that the ‘784 Patent disclosed all the essential elements of the ‘684 Patent and provided the skilled person with enough information to allow him or her to perform the invention claimed in the ‘684 Patent without undue burden. [149] Therefore, the ‘684 Patent was anticipated by the ‘784 Patent.

Obviousness

Mylan alleged that if the ‘684 Patent was not interpreted as a selection patent, then the claimed invention was clearly obvious because it was anticipated by the ‘784 Patent.

The FC used the four-part test for obviousness laid out by the Supreme Court in Sanofi-Synthelabo:

1. Identify the notional “person skilled in the art” and the relevant common general knowledge of that person;
2. Identify the inventive concept claimed in the patent;
3. Identify the differences between the common general knowledge and the inventive concept;
4. Do those differences require a degree of invention, or are they more or less self-evident?

The analysis focused mainly on whether it was more or less self-evident that the lower and narrower doses of tadalafil in the ‘684 Patent would be effective in treating ED and would result in reduced side effects. The FC found that it was more or less self-evident that a skilled person in the art would look for a minimal effective dose and a maximum tolerated dose. [172] The FC thus found that the ‘684 Patent was invalid for obviousness.

Commentary

Patentees should be wary to not overstate promises of utility in their patents. When a promise is not clearly and unequivocally expressed in the claims of a patent, a court will construe the promise within the context of the patent as a whole. Promises must be supported by articulate and reliable evidence to prevent the possibility of a patent being deemed invalid in the future.

This is not the first time that Lilly has been on the losing side of a battle regarding the manufacture and distribution of generic versions of drugs. In response to the courts invalidating two of its other pharmaceutical patents (Zyprexa and Strattera) for lack of utility, Lilly initiated legal proceedings against Canada, alleging violation of the North American Free Trade Agreement (“NAFTA”). Lilly contends that the courts, in invalidating the Zyprexa and Strattera patents, relied on the promise of utility doctrine, an allegedly elevated utility requirement that is not found in other jurisdictions and that Lilly argued is inconsistent with Canadian jurisprudence on utility. Lilly believes that the courts have imposed a heightened evidentiary burden for demonstrating utility, straying from prior jurisprudence. The issue to be determined is what the minimum basic intellectual property principles are regarding utility, which NAFTA countries must adhere to. The nine day hearing of Lilly’s NAFTA challenge is scheduled for May 30, 2016. The outcome of the challenge may affect the case discussed above and the way courts address utility in the future.