Eli Lilly Canada Inc. v. Mylan Pharmaceuticals ULC et al., (2015) 474 F.T.R. 256 (FC)

• Judge: de Montigny, J.
• Court: Federal Court (Canada)
• Case Date: February 02, 2015
• Jurisdiction: Canada (Federal)
• Citations: (2015), 474 F.T.R. 256 (FC);2015 FC 125

Eli Lilly Can. v. Mylan Pharmaceuticals (2015), 474 F.T.R. 256 (FC)

MLB headnote and full text

Temp. Cite: [2015] F.T.R. TBEd. FE.039

Eli Lilly Canada Inc. (applicant) v. Mylan Pharmaceuticals ULC and The Minister of Health (respondents) and ICOS Corporation (respondent/patentee)

(T-298-13; 2015 FC 125)

Indexed As: Eli Lilly Canada Inc. v. Mylan Pharmaceuticals ULC et al.

Federal Court

de Montigny, J.

February 2, 2015.

Summary:

Eli Lilly Canada Inc. (Lilly) applied for an order to prohibit the issuance of a Notice of Compliance to Mylan Pharmaceuticals ULC (Mylan) for a generic version of tadalafil (CIALIS), until after the expiration of the Canadian Patent 2,371,684 (the '684 Patent). Tadalafil was used to treat erectile dysfunction (ED). The '684 Patent was directed to a unit dosage form of tadalafil. By the time the '684 Patent was filed, sildenafil (VIAGRA) had been approved for the treatment of ED. Mylan submitted that the '684 Patent was a selection patent and that its utility was neither demonstrated nor soundly predicted; that the claimed invention was anticipated by Canadian Patent No. 2,226,784 (the '784 Patent), listed against CIALIS; and was clearly obvious.

The Federal Court dismissed Lilly's prohibition application. The Court did not interpret the '684 Patent as a selection patent. The following allegations of invalidity regarding the '684 Patent were justified: (1) it lacked utility, as the promise of the Patent was neither demonstrated nor soundly predicted at the filing date, and was still not met; (2) it was anticipated by the '784 Patent, as the dosages claimed in the '684 Patent were entirely within the range disclosed in the '784 Patent; and (3) it was obvious that a unit dose of 1 to 20 mg would be effective in treating ED and would lead to a better side effect profile than sildenafil.

Food and Drug Control - Topic 1108.2

Drugs - New drugs - Notice of compliance - Prohibition order (incl. compensation by first person) - Eli Lilly Canada Inc. (Lilly) applied for an order to prohibit the issuance of a Notice of Compliance to Mylan Pharmaceuticals ULC (Mylan) for a generic version of tadalafil (CIALIS), until after the expiration of the Canadian Patent 2,371,684 (the '684 Patent) - The '684 Patent was directed to a unit dose of 1 to 20 mg of tadalafil for the treatment of erectile dysfunction (ED) - Mylan submitted that the '684 Patent was a selection patent and that its utility was neither demonstrated nor soundly predicted; that the claimed invention was anticipated by the Canadian Patent No. 2,226,784 (the '784 Patent), listed against CIALIS; and was clearly obvious - By the time the '684 Patent was filed, sildenafil (VIAGRA) had been approved for the treatment of ED - Sildenafil was marketed in doses of 25 mg, 50 mg, and 100 mg - The Federal Court dismissed Lilly's prohibition application - The following allegations of invalidity regarding the '684 Patent were justified: (1) it lacked utility, as the promise of the Patent was neither demonstrated nor soundly predicted at the filing date, and was still not met; (2) it was anticipated by the '784 Patent, as the dosages claimed in the '684 Patent were entirely within the range disclosed in the '784 Patent; and (3) it was obvious that a unit dose of 1 to 20 mg would be effective in treating ED and would lead to a better side effect profile than sildenafil.

Patents of Invention - Topic 17

Patents of invention - General - Selection patents (incl. what constitutes) - The Federal Court stated that "[a] selection patent is not different in nature from any other patent; it is merely a way of describing a patent ... . In the field of chemical patents (which includes, of course, pharmaceutical compounds), 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. For example, one patent may claim a group of compounds, and then a subsequent patent - the selection patent - claims a selection from that group based on some 'special property of an unexpected character'" - After reviewing the conditions that must be satisfied for a selection patent to be valid, the Court stated that "[c]haracterizing a patent as a selection patent does not make it prima facie more or less valid ... but merely informs the analysis of other bases for invalidity, ie novelty, obviousness, sufficiency and utility." - See paragraphs 105 and 106.

Patents of Invention - Topic 17

Patents of invention - General - Selection patents (incl. what constitutes) - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - The use of tadalafil for the treatment of ED was claimed and disclosed in the '784 Patent - The dosages claimed in the '684 Patent were entirely within the range disclosed in the '784 Patent - By the time the '684 Patent was filed, sildenafil (VIAGRA) had been approved for the treatment of ED - Sildenafil was marketed in doses of 25 mg, 50 mg, and 100 mg - The Federal Court was not convinced that the '684 Patent was a selection patent - "While the dosage range claimed is much narrower compared to the broad range disclosed in the '784 Patent and the improvement over sildenafil is said to be a characteristic of the entire dosage range of 1 to 20 mg, there is nothing in the specification (let alone in the claims themselves) to the effect that the promised advantage is peculiar to this particular dosage range to the exclusion of any other unit dose. ... The patentee clearly claims that a dosage range of 1 to 20 mg provides a substantial advantage over sildenafil in treating ED, but does not assert that a larger number of unselected doses do not possess the same advantage. That being an essential characteristic of a selection patent, I am therefore of the view that the '684 Patent is not a selection patent." - See paragraphs 108 and 109.

Patents of Invention - Topic 1030

The specification and claims - Construction of a patent - "Person skilled in the art" - Eli Lilly Canada Inc. (Lilly) applied for an order to prohibit the issuance of a Notice of Compliance to Mylan Pharmaceuticals ULC (Mylan) for a generic version of tadalafil (CIALIS), until after the expiration of the Canadian Patent 2,371,684 (the '684 Patent) - Tadalafil was used to treat erectile dysfunction (ED) - The '684 Patent was directed to a unit dosage form of tadalafil - Mylan submitted that the '684 Patent was a selection patent and that its utility was neither demonstrated nor soundly predicted; that the claimed invention was anticipated by Canadian Patent No. 2,226,784, listed against CIALIS; and was clearly obvious - The Federal Court described the "person skilled in the art" as a person or a drug development team having expertise in areas that were relevant to drug dosing, such as pharmacology and/or pharmacokinetics, physiology, dose ranging and safety assessment of candidate therapeutics and with experience in the treatment of ED - See paragraphs 83 and 160.

Patents of Invention - Topic 1589

Grounds of invalidity - Lack of "inventive ingenuity" (obviousness) - Particular patents - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - Sildenafil (VIAGRA) was known to treat ED by the same mechanism of action as tadalafil, and was marketed in doses of 25 mg, 50 mg, and 100 mg - The Federal Court held that the '684 Patent was invalid for obviousness - It was obvious, as of the priority date, that a unit dose of 1 to 20 mg would be effective in treating ED and would lead to a better side effect profile than sildenafil - The Court preferred the opinion of an independent expert witness that there was a well-established approach to the process of determining an appropriate dose - "Having started with an unnecessarily high dose, the tadalafil team cannot claim to have 'surprisingly' found that they could use a lower dose. I find, therefore, that a person skilled in the art would have likely designed an initial dose escalation study to start at approximately 5 mg of tadalafil and move up to approximately 50 mg; as a result, there was a finite number of predictable solutions. ... There is no evidence as to the extent and amount of effort required to achieve the invention, but on the basis of the relative potency and relative molecular weight of sildenafil and tadalafil, and of the ordinary course of drug development, there was a finite number of predictable solutions." - See paragraphs 162 to 172.

Patents of Invention - Topic 1605

Grounds of invalidity - Anticipation - Particular patents - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - An allegation of invalidity was that the '684 Patent was anticipated by the '784 Patent because the claimed invention was disclosed and enabled by the '784 Patent - The Federal Court held that the allegation was justified - "The '784 Patent disclosed: (1) unit dosage forms of tadalafil, such as tablets or capsules, in the dosage range from 0.2 to 400 mg; (2) with the unit dosage form suitable for oral administration; and (3) for use in treating male ED. ... [A]ll of the essential elements of the claims of the '684 Patent are disclosed in the '784 Patent. ... When a second patent is not interpreted as a selection patent, its advantages do not factor into the inquiry of anticipation and need not be disclosed in a previous patent to be anticipated. Not only did the '784 Patent disclose all the essential elements of the '684 Patent, but it also provides the skilled person with enough information to perform the invention claimed in the '684 Patent without undue burden." - See paragraphs148 and 149.

Patents of Invention - Topic 1653

Grounds of invalidity - Anticipation by prior patent - What constitutes anticipation - The Federal Court stated that, pursuant to s. 28.2 of the Patent Act, "a patent will be invalid for anticipation if the essential elements of the claimed invention were disclosed in such a manner that it became available to the public more than one year before the filing date, and were enabled to a skilled person ... [T]he disclosure does not have to be an exact description of the claimed invention; the disclosure must be sufficient so that, when read by a person skilled in the art and willing to understand what is being said, it can be understood without trial and error ..." - See paragraph 145.

Patents of Invention - Topic 1721

Grounds of invalidity - Lack of utility and operability - General (incl. "promise of the patent") - The parties differed on the promised utility of the patent at issue - The Federal Court preferred the opinions of the respondents' experts on the construction of the promise, because they were more in line with the wording of the patent - The language of the disclosure made it clear that the promised improvement when it came to adverse side effects was not just marginal but significant - The applicant's experts read down the promise based on irrelevant considerations - "Such an approach is clearly unacceptable: a clear promise cannot be narrowed down to fit what has been demonstrated, otherwise utility would never be an issue." - See paragraphs 86 to 96.

Patents of Invention - Topic 1721

Grounds of invalidity - Lack of utility and operability - General (incl. "promise of the patent") - The patent at issue was directed to a unit dosage form of tadalafil (CIALIS), including the use of that unit dosage form for the treatment of erectile dysfunction - The parties differed on the promised utility of the patent - The promise targeted three side effects, one of which related to the negative effects associated with co-administration with nitrates - According to the patentee ("Lilly"), the patent spoke in terms of preference, and did not rule out the possibility of a contraindication - The Federal Court stated that "[i]t is no doubt true that contraindications are regulatory matters, and I accept Lilly's argument that a patentee cannot promise that which it has no control over. Yet, the language of a patent cannot be ignored and a patentee can make an explicit promise that a contraindication is unnecessary even if, at the end of the day, this is a matter primarily for regulators. This is precisely what was done here. ... Having made an explicit promise of a specific result in the Patent, the patentee has made the contraindication not only a regulatory issue, but also a patent issue." - See paragraphs 97 to 99.

Patents of Invention - Topic 1721

Grounds of invalidity - Lack of utility and operability - General (incl. "promise of the patent") - The Federal Court discussed the "general rule that the promise should be construed within the context of the patent as a whole ... when the promise is not 'clearly and unequivocally' expressed in the claims of the patent." - In the case at bar, the claims of the subject patent related to the unit dosage forms of tadalafil (CIALIS) to treat erectile dysfunction, and did not "clearly and unequivocally" set out a promise - For that reason, the claims of the patent could not be the exclusive focus for the construction of the promise - See paragraphs 101 to 103.

Patents of Invention - Topic 1721

Grounds of invalidity - Lack of utility and operability - General (incl. "promise of the patent") - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - Sildenafil (VIAGRA) was known to treat ED by the same mechanism of action as tadalafil, and was marketed in doses of 25 mg, 50 mg, and 100 mg - Sildenafil's side effects included high rates of flushing, blue-green vision and an interaction with nitrates that caused a drastic drop in blood pressure - A ground of invalidity regarding the '684 Patent was that it lacked utility, as the promise of the Patent was neither demonstrated nor soundly predicted - The parties disagreed not only as to the side effects to be considered, but also the extent of the side effect reduction promised by the '684 Patent - The Federal Court concluded that "the promise of the '684 Patent is not merely to lower the incidence of adverse side effects as compared to sildenafil, but to minimize them significantly or even to eliminate them. This is true for all three side effects that are the focus of the '684 Patent, but more particularly with respect to the co-administration of tadalafil with nitrates; this is the inescapable conclusion that one must draw from the statement that a contraindication is unnecessary when tadalafil is administered as a unit dose of about 1 to about 20 mg." - See paragraph 100.

Patents of Invention - Topic 1721

Grounds of invalidity - Lack of utility and operability - General (incl. "promise of the patent") - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - Sildenafil (VIAGRA) was known to treat ED by the same mechanism of action as tadalafil, and was marketed in doses of 25 mg, 50 mg, and 100 mg - A ground of invalidity regarding the '684 Patent was that it lacked utility, as the promise of the Patent was neither demonstrated nor soundly predicted - The Federal Court held that the allegation of invalidity was justified - "[T]he '684 Patent promises that the claimed unit doses of 1 to 20 mg of tadalafil, when administered to patients for the treatment of ED, will be effective and provide an improvement over sildenafil by minimizing significantly or eliminating three side effects (flushing, vision abnormalities, and the negative effects associated with co-administration with nitrates)" - The Patent failed to meet the promise of reducing the effects of the nitrate interaction significantly (or to a clinically insignificant level), such that a contraindication of tadalafil and nitrates was not necessary - As of the filing date, there was no demonstration or sound prediction of any improvement in nitrate interaction of the claimed doses of tadalafil over sildenafil - See paragraphs 110 to 123.

Patents of Invention - Topic 1723

Grounds of invalidity - Lack of utility and operability - Chemical products and substances intended for food and medicine - [See fifth Patents of Invention - Topic 1721 ].

Patents of Invention - Topic 1724

Grounds of invalidity - Lack of utility and operability - Doctrine of sound prediction - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - Sildenafil (VIAGRA) was known to treat ED by the same mechanism of action as tadalafil, and was marketed in doses of 25 mg, 50 mg, and 100 mg - Sildenafil's side effects included an interaction with nitrates that caused a drastic drop in blood pressure - A ground of invalidity regarding the '684 Patent was that it failed to meet the promised utility: (1) nitrate interaction had not been reduced to "clinically insignificant levels" because tadalafil was absolutely contraindicated with nitrates; and (2) there was no improvement in the nitrate interaction over sildenafil - The Federal Court agreed that as of the filing date, the promise of minimizing significantly or eliminating the negative side effects associated with co-administration with nitrates was neither demonstrated nor soundly predicted - The only study dealing with the co-administration of tadalafil with organic nitrates that was available at the time was far from sufficient to establish that a contraindication was unnecessary, as stated in the Patent - What was "most troubling" was that the undisclosed part of the study demonstrated no statistically significant difference between tadalafil and sildenafil - See paragraphs 111 to 115 and 127 to 136.

Patents of Invention - Topic 1724

Grounds of invalidity - Lack of utility and operability - Doctrine of sound prediction - The Federal Court stated that "utility can also be soundly predicted if not demonstrated by the time of filing. At least three requirements must be met for sound prediction to be established: 1) there must be a factual basis for the prediction; 2) the inventor must have at the date of the patent application an articulable and 'sound' line of reasoning from which the desired result can be inferred from the factual basis; and 3) there must be proper disclosure" - See paragraph 137.

Patents of Invention - Topic 1724

Grounds of invalidity - Lack of utility and operability - Doctrine of sound prediction - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - Sildenafil (VIAGRA) was known to treat ED by the same mechanism of action as tadalafil, and was marketed in doses of 25 mg, 50 mg, and 100 mg - According to the patentee, a person skilled in the art could conclude the invention was soundly predicted by reviewing only the disclosure of the '684 Patent - The Federal Court disagreed - "[A] skilled person could not have soundly predicted that unit doses of 1 to 20 mg of tadalafil would provide an improvement in the nitrate interaction over sildenafil. Not only is there no factual basis for the prediction and no articulable and sound line of reasoning from which the desired result can be inferred from the factual basis, but the '684 Patent does not even provide a proper disclosure. ... This failure is clearly unacceptable in a Patent that promises not only efficacy in treating ED, but also a better side effect profile as against sildenafil, and a patentee should not be able to benefit from a partial, if not misleading, disclosure." - See paragraphs 138 to 140.

Patents of Invention - Topic 1724

Grounds of invalidity - Lack of utility and operability - Doctrine of sound prediction - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - Sildenafil (VIAGRA) was known to treat ED by the same mechanism of action as tadalafil, and was marketed in doses of 25 mg, 50 mg, and 100 mg - According to the patentee, a person skilled in the art could conclude the invention was soundly predicted by reviewing only the disclosure of the '684 Patent - The Federal Court disagreed, and went on to state that "[e]ven if utility could have been soundly predicted at the filing date, the '684 Patent must be voided if, as of today, the clinical evidence indicates that tadalafil does not significantly improve over sildenafil with respect to nitrate interactions. ... [A]s of today, there is no improvement in nitrate interaction of tadalafil over sildenafil, when considering the incidence of a significant drop in blood pressure. Moreover, to the extent that there is any difference between tadalafil and sildenafil, tadalafil is contraindicated with nitrates for a longer period of time (48 hours vs 24 hours) because of its longer half-life. Therefore, even as of today, the '684 Patent fails to meet the promise of providing any significant improvement in the nitrate interaction as compared to sildenafil." - Based on that finding, even if the Court had accepted the patentee's narrow construction of the promise (a reduction of side effects compared to sildenafil), that promise was neither demonstrated nor soundly predicted - See paragraphs 141 to 144.

Patents of Invention - Topic 1725

Grounds of invalidity - Lack of utility and operability - Particular patents - The subject patent (the '684 Patent) was directed to a unit dose of 1 to 20 mg of tadalafil (CIALIS) for the treatment of erectile dysfunction (ED) - Sildenafil (VIAGRA) was known to treat ED by the same mechanism of action as tadalafil, and was marketed in doses of 25 mg, 50 mg, and 100 mg - Sildenafil's side effects included an interaction with nitrates that caused a drastic drop in blood pressure - A ground of invalidity regarding the '684 Patent was that it failed to meet the promised utility: (1) nitrate interaction had not been reduced to "clinically insignificant levels" because tadalafil was absolutely contraindicated with nitrates; and (2) there was no improvement in the nitrate interaction over sildenafil - The patentee claimed that direct comparative testing between tadalafil and sildenafil (both PDE5 inhibitors) was not necessary: (1) reasonable comparisons could have been made on the basis of readily available data in the published literature at the time of the '684 Patent application filing, and (2) direct head to head studies with PDE5 inhibitors were rare - The Federal Court stated that "[t]his is an astonishing argument to make for a patentee promising that his product is an improvement over another one on the market. One would expect, on the contrary, that the most critical piece of evidence to support such a promise would be a direct comparison of the two compounds in clinical studies using similar methodologies." - In the end result, the Court held that the allegation of invalidity was justified - See paragraph 125.

Cases Noticed:

Pfizer Canada Inc. et al. v. Apotex Inc. et al. (2007), 319 F.T.R. 48; 2007 FC 971, refd to. [para. 46].

Eli Lilly Canada Inc. v. Mylan Pharmaceuticals ULC et al. (2015), 473 F.T.R. 1; 2015 FC 17, refd to. [para. 84].

Apotex Inc. and Novopharm Ltd. v. Wellcome Foundation Ltd., [2002] 4 S.C.R. 153; 296 N.R. 130; 2002 SCC 77, refd to. [para. 84].

Eli Lilly Canada Inc. et al. v. Novopharm Ltd. (2010), 405 N.R. 1; 2010 FCA 197, refd to. [para. 84].

Apotex Inc. v. Sanofi-Aventis (2013), 447 N.R. 313; 2013 FCA 186, refd to. [para. 85].

AstraZeneca Canada Inc. et al. v. Apotex Inc. et al. (2014), 457 F.T.R. 227; 2014 FC 638, refd to. [para. 96].

Fournier Pharma Inc. et al. v. Canada (Minister of Health) et al. (2012), 413 F.T.R. 277; 2012 FC 741, refd to. [para. 101].

Alcon Canada Inc. et al. v. Apotex Inc. et al. (2014), 459 F.T.R. 255; 2014 FC 699, refd to. [para. 101].

Sanofi-Synthelabo Canada Inc. et al. v. Apotex Inc. et al., [2008] 3 S.C.R. 265; 381 N.R. 125; 2008 SCC 61, refd to. [para. 105].

I.G. Farbenindustrie A.G.'s Patents, Re (1930), 47 R.P.C. 289 (Ch. D.), refd to. [para. 105].

Abbott Laboratories et al. v. Canada (Minister of Health) et al. (2008), 337 F.T.R. 17; 2008 FC 1359, affd. (2009), 387 N.R. 347; 2009 FCA 94, refd to. [para. 145].

Tennessee Eastman Co. et al. v. Commissioner of Patents, [1974] S.C.R. 111, refd to. [para. 154].

Imperial Chemical Industries Ltd. v. Commissioner of Patents (Can.), [1986] 3 F.C. 40; 67 N.R. 121 (F.C.A.), refd to. [para. 154].

Statutes Noticed:

Patent Act, R.S.C. 1985, c. P-4, sect. 28.3 [para. 156].

Counsel:

Jamie Mills, Adrian Howard and Chantal Saunders, for the applicant and the respondent patentee;

Sana Halwani, Andrew Moeser and Zarya Cynader, for the respondent, Mylan Pharmaceuticals ULC.

Solicitors of Record:

Borden Ladner Gervais, LLP, Ottawa, Ontario, for the applicant and the respondent patentee;

Gilbert's LLP, Toronto, Ontario, for the respondent, Mylan Pharmaceuticals ULC;

William F. Pentney, Deputy Attorney General of Canada, Toronto, Ontario, for the respondent, The Minister of Health.

This application was heard on October 20-23, 2014, at Ottawa, Ontario, before de Montigny, J., of the Federal Court, who delivered the following judgment and reasons, dated February 2, 2015.