Eli Lilly Canada Inc. v. Apotex Inc.

Eli Lilly Canada Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2015-09-11
Neutral citation
2015 FC 1016
File numbers
T-1599-13
Decision Content
Date: 20150911
Docket: T-1599-13
Citation: 2015 FC 1016
Ottawa, Ontario, September 11, 2015
PRESENT: The Honourable Madam Justice Gleason
BETWEEN:
ELI LILLY CANADA INC.
Applicant
and
APOTEX INC. AND
THE MINISTER OF HEALTH
Respondents
and
ICOS CORPORATION
Respondent Patentee
PUBLIC JUDGMENT AND REASONS
(Confidential version of Judgment and Reasons issued August 26, 2015)
[1] In this application, the applicant, Eli Lilly Canada Inc. [Lilly], seeks an order under section 6 of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [the PMNOC Regulations] to prohibit the respondent, the Minister of Health [the Minister], from issuing Notices of Compliance [NOCs] to the respondent, Apotex Inc. [Apotex], for approval to sell generic versions of CIALIS and ADCIRCA until after the expiry of the Canadian Patent 2,379,948 [the 948 Patent] on April 26, 2020. Lilly markets CIALIS principally for the treatment of erectile dysfunction [ED] and ADCIRCA for the treatment of pulmonary arterial hypertension [PAH].
[2] The active pharmaceutical ingredient in both CIALIS and ADCIRCA (as well as Apotex’ generic versions of them) is a substance known as tadalafil. Tadalafil was discovered at Glaxo Laboratories and was first claimed in Canada in a patent that expired in January of 2015 (Canadian Patent 2,181,377 or the 377 Patent). Glaxo initially collaborated with ICOS Corporation on the development of tadalafil, which was found to be poorly soluble in water. When the collaboration between Glaxo and ICOS ended, Lilly partnered with ICOS to develop a tablet version of tadalafil.
[3] The 948 Patent, the patent in suit in this case, is a formulation patent for tadalafil that claims formulations with a reduced particle size and certain excipients to address tadalafil’s poor water solubility.
[4] The 948 Patent is listed against both CIALIS and ADCIRCA on the Patent Register maintained by the Minister under sections 3 and 4 of the PMNOC Regulations. Apotex was therefore required to address the 948 Patent to obtain NOCs and did so in two Notices of Allegation [NOAs], dated August 16, 2013 (CIALIS) and August 21, 2013 (ADCIRCA), which it served on Lilly. In response, Lilly commenced the present application for prohibition on September 27, 2013.
[5] Although Apotex raised several additional claims in its NOAs, by the time the matter was argued only three of them remained, namely, whether Apotex’ products infringe the 948 Patent and whether the 948 Patent is invalid for obviousness or lack of utility.
[6] Justice de Montigny ruled on the same obviousness issue as arises in this case in the context of another prohibition application brought by Lilly against another generic company, Mylan Pharmaceuticals ULC, in his decision in Eli Lilly Canada v Mylan Pharmaceuticals ULC, 2015 FC 178, 251 ACWS (3d) 124 [Mylan Tadalafil III] and found that Mylan’s obviousness allegation was justified. In addition, in Mylan Tadalafil III Justice de Montigny was faced with a claim of non-infringement by Mylan that is very similar to the position taken by Apotex in this application. Justice de Montigny ruled that Mylan’s generic product did not infringe the 948 Patent. As a result, Justice de Montigny dismissed Lilly’s prohibition application in Mylan Tadalafil III.
[7] Lilly has appealed Justice de Montigny’s decision in Mylan Tadalafil III to the Federal Court of Appeal. Mylan has also appealed Justice de Montigny’s earlier decision in Eli Lilly Canada v Mylan Pharmaceuticals ULC, 2015 C 17, 249 ACWS (3d) 191 [Mylan Tadalafil I] in which he granted Lilly’s prohibition application with respect to the Canadian Patent 2,226,784 [the 784 Patent], which principally claims the use of tadalafil to treat ED. Both of these appeals are still pending before the Federal Court of Appeal.
[8] Apotex asserts that the decision of Justice de Montigny in Mylan Tadalafil III renders the present prohibition application by Lilly against it an abuse of process within the meaning of paragraph 6(5)(b) of the PMNOC Regulations and therefore says that this application should be summarily dismissed.
[9] Thus, the issues that arise for determination in this matter are the following:
1. Should this application be dismissed as an abuse of process?
2. Do Apotex’ generic products infringe the 948 Patent?
3. Is the 948 Patent invalid for obviousness? and
4. Is the 948 Patent invalid for lack of utility?
[10] For the reasons set out below, I have determined that in the rather unique circumstances of this case, this application is not an abuse of process and accordingly may be pursued by Lilly. I have also concluded that Apotex’ products do not infringe the 948 Patent, that its allegation of obviousness is justified but that its allegation of non-utility is not justified. I have therefore determined that this application must be dismissed.
I. Is it an abuse of process for Lilly to pursue this application? [11] Turning to the first of these issues, the starting point for analysis of the abuse of process allegation is paragraph 6(5)(b) of the PMNOC Regulations, which recognizes this Court’s discretion to stay prohibition applications brought under section 6 of the Regulations where they are “redundant, scandalous, frivolous or vexatious” or “otherwise an abuse of process in respect of one or more patents”. In Sanofi-Aventis Canada v Novopharm Ltd, 2007 FCA 163, 59 CPR (4th) 416 [Sanofi Ramipril], the Federal Court of Appeal held that it is an abuse of process, within the meaning of paragraph 6(5)(b) of the PMNOC Regulations, for a patent holder to re-litigate the same allegation(s) that it was unsuccessful on in a previous prohibition application involving a different generic company, even if the allegations are differently worded in the Notices of Allegation in the two files or even if the patent holder seeks to call better or more detailed evidence in the second file. In writing for the majority in Sanofi Ramipril, Justice Sexton determined that allowing re-litigation by a patent holder in such circumstances would constitute an abuse of process because the patent holder is seeking to collaterally attack the earlier decision and, in that case, permitting it to do so created an undesirable risk of conflicting judgments as the earlier award involved a factual determination and was therefore not binding in the subsequent case. Justice Sexton also held that allowing the re-litigation would lead to a waste of judicial resources and would possibly encourage patent holders to divide their cases and engage in serial litigation of the issues, which constituted further indicia of an abuse of the Court’s process. He thus held that the second prohibition application brought by Sanofi in that case should have been dismissed as an abuse of process. However, in so holding, he noted that there might well be circumstances where fairness would require a different result but found that the case before him was not such a case.
[12] It is important to note that by the time Sanofi Ramipril was decided by the Federal Court of Appeal, a final decision had been made in the earlier prohibition application brought by Sanofi as its appeal to the Federal Court of Appeal and application for leave to appeal to the Supreme Court of Canada in the earlier application had been dismissed. This was not the case when the motion to dismiss was first heard and, by reason of the fact that the application for leave to appeal to the Supreme Court was still pending when the motion to dismiss the second application was first decided, Prothonotary Milczynski initially declined to dismiss Sanofi’s second prohibition application in Sanofi-Aventis Canada v Novopharm, (Order of Prothonotary Milczynski, May 8, 2006, Court File No. T-1965-05).
[13] Apotex argues that the decision of the Federal Court of Appeal in Sanofi Ramipril should be applied in the instant case and that Lilly’s prohibition application should be dismissed as Lilly is seeking to re-litigate the same obviousness issue that was dismissed by Justice de Montigny in Mylan Tadalafil III and cannot do so because it is an abuse of process.
[14] Lilly disagrees and submits that there is an important distinction between this case and Sanofi Ramipril because in the case at bar an appeal of the earlier decision it lost is still pending. It points to both the decision of Prothonotary Milczynski in Sanofi Ramipril and to the subsequent decision of Prothonotary Tabib in Eli Lilly Canada v Novopharm, 2008 FC 513, 327 FTR 1 as being circumstances where a motion to dismiss was heard while an appeal of an earlier decision was pending and notes that both prothonotaries in both instances declined to dismiss the subsequent prohibition applications.
[15] In Eli Lilly Canada v Novopharm, Prothonotary Tabib offered detailed and thoughtful reasons for her refusal, noting that the key consideration in the exercise of discretion as to whether to dismiss a subsequent application for prohibition under the PMNOC Regulations while an appeal of the earlier decision is pending is the potential effect of the appeal on the subsequent application. In that case, she determined that allowing the second prohibition application to proceed would not amount to an abuse of process as the concerns noted by the Federal Court of Appeal in Sanofi Ramipril did not arise.
[16] More specifically, Prothonotary Tabib found that there was little risk of possible conflicting judgments as the pending appeal in that case was likely to have been decided before the second prohibition application was decided. She also found that unfairness to Lilly would result if the second prohibition application were dismissed as it would be prejudiced if it were successful on the appeal. She further noted that this chain of events would likely lead to more litigation as, if she dismissed the second prohibition application and the appeal were successful, there would need to be an application to set the dismissal aside, which could well result in a judge being required to decide the second prohibition in an even shorter time frame.
[17] Finally, Prothonotary Tabib found that the best means of ensuring consistency in decision making would have been to stay the second prohibition application, pending a final determination of the appeal of the first unsuccessful prohibition application, but noted that this option was not open to the Court under the PMNOC Regulations in the absence of consent from the parties due to the statutory deadlines applicable to the disposition of prohibition applications. In this regard, section 7 of the PMNOC Regulations provides for a 24 month stay, following the filing of a prohibition application, during which the Minister is prohibited from issuing an NOC to the generic company for the drug that is referenced in the prohibition application. Unless the parties to the application consent to an extension of that deadline, the Minister is free to issue the NOC at the end of the 24 month period. Prothonotary Tabib found that, failing consent to an extension of the 24 month period, the next best means of ensuring consistency was through the dismissal of Novopharm’s motion for dismissal as Lilly had agreed that it would discontinue the second prohibition application if it were ultimately unsuccessful on appeal. Through this agreement, consistency of result was assured.
[18] As Apotex correctly submits, there is one significant difference in the facts that were before Prothonotary Tabib and the facts in the instant case. In that case, unlike the present, it was likely that the appeal of the refusal to issue a prohibition order would have been decided before the second application was argued. While this fact made it easier to conclude that the second application was not an abuse of process (because there was minimal risk of conflicting decisions), I do not believe that the different timing in the present case should lead to a different result than in Eli Lilly Canada v Novopharm.
[19] In this regard, I note that the decision on whether to dismiss an application like the present as being abusive is a discretionary one: paragraph 6(5)(b) of the PMNOC Regulations confirms that I may dismiss this application if I find it to be an abuse of process. In exercising my discretion in this case, I believe the key issue for consideration involves determination of which party will be more severely prejudiced by a negative determination on the dismissal request.
[20] In my opinion, it is Lilly who would be more severely prejudiced if I dismiss this application, as it will lose its ability to have the present application heard on the merits. This will be to its severe prejudice if it succeeds before the Federal Court of Appeal in its appeal of Justice de Montigny’s decision in Mylan Tadalafil III.
[21] In this regard, the appeal of Justice de Montigny’s decision in Mylan Tadalafil III has not yet been heard and will not be heard before the 24 month statutory stay expires in this case on September 27, 2015 but may well be decided before the expiry of the 784 Patent in July of 2016. The pending appeal in Mylan Tadalafil III is therefore unlikely to be dismissed for mootness.
[22] In the event Lilly is successful in its appeal of Justice de Montigny’s decision in Mylan Tadalafil III, it would be impossible for this Court to set aside a dismissal of this application and re-examine the prohibition application before September 27, 2015. Therefore, if I grant Apotex’ dismissal request, Lilly will lose its opportunity to seek an order of prohibition in respect of the 948 Patent in the context of Apotex’ request for NOCs. However, if it wins its appeal, it probably would have been entitled to an order of prohibition in the instant case.
[23] It is no answer to say, as Apotex argues, that Lilly could still maintain an infringement action and obtain damages as Lilly will have lost the benefit of the statutory stay under the PMNOC Regulations, which is an important strategic advantage. In addition, in the event Lilly succeeds in its appeal in Mylan Tadalafil III, Apotex may enjoy an undeserved competitive advantage over Mylan if I dismiss this application as Apotex would be entitled to obtain an NOC for its ADCIRCA product and for its generic version of CIALIS in 2016 once the 784 Patent expires whereas Mylan’s entitlement to an NOC for its CIALIS product would depend on the outcome of Lilly’s pending appeal and potentially also on the outcome of any subsequent application for leave to the Supreme Court of Canada. This is not only unfair but is precisely the sort of potential conflicting result that ought to be avoided as an abuse of process.
[24] On the other hand, Apotex will not lose its ability to argue this case, even if I were to grant the prohibition application, as it can appeal my decision and still have the full opportunity to argue its position and to seek to have the prohibition application dismissed on the merits by the Federal Court of Appeal. Moreover, Apotex could have avoided any cost and inconvenience associated with the pursuit of this application while the appeal in Mylan Tadalafil III is pending by simply agreeing to a stay and an extension of the 24 month time limit for the issuance of the NOCs it seeks. However, it was not prepared to do so.
[25] Thus, Lilly will be much more severely impacted than Apotex if this application is dismissed summarily. Accordingly, in my view, fairness requires that Lilly be allowed to pursue this prohibition application.
[26] Many other courts have reached similar conclusions and held that it is not an abuse of process for a party to maintain a second action or application while the first determination is being appealed as a decision under appeal is not a final decision for purposes of application of the abuse of process or issue estoppel doctrines (see, e.g., Novopharm Ltd v Eli Lilly and Co, [1999] 1 FC 515 at paras 29-32, [1998] FCJ No 1634 (FCTD); Wells v Canada (Minister of Transport) (1993), 48 CPR (3d) 308, 63 FTR 213 (FCTD); Cardinal v R (1991), 47 FTR 203, 29 ACWS (3d) 723 (FCTD) (rev’d in part on other grounds (1993), 164 NR 301, 72 FTR 309); Starlight v Canada, 2001 FCA 342 at para 4, [2001] FCJ No 1685; Nordic Laboratories Inc v Deputy MNR (1996), 113 FTR 168 at paras 23-28, [1996] FCJ No 1067 (FCTD)).
[27] Indeed, in most instances where a prior decision is being appealed, the second case that involves the same issue is simply stayed pending the final determination of the appeal in the first case, which allows for the preservation of the parties’ rights and avoids unnecessary litigation and the risk of conflicting decisions. Given the provision of section 7 of the PMNOC Regulations and the unwillingness of the parties to agree to a stay in this case, that option was unfortunately not available to me. Thus, the fairest option is to refuse Apotex’ dismissal request.
[28] While this may result in unnecessary litigation (in the event the appeal in Mylan Tadalafil III is dismissed), this is preferable to the unfairness that would result to Lilly if this dismissal request were granted. I therefore determine that Lilly’s pursuit of this prohibition application while its appeal in Mylan Tadalafil III is pending is not an abuse of process and that I accordingly will not summarily dismiss this application.
II. The 948 Patent [29] I turn now to the merits of this application and begin by review of the relevant portions of the 948 Patent.
[30] The 948 Patent is entitled “ß-Carboline Pharmaceutical Compositions” and notes in its opening paragraph that the field of the invention claimed in the Patent relates to the formulation of ß-carboline compounds “formulated in a manner providing uniform potency, and desirable stability and bioavailability characteristics” (948 Patent, p 1).
[31] The next section of the Patent describes the background to the invention and discusses three other patents: the U.S. versions of the 377 Patent, the 784 Patent and the Butler U.S. Patent No. 5,985,326 [the Butler Patent]. The 377 Patent claimed a number of ß-carboline compounds, including, notably, tadalafil, and the 784 Patent claimed the use of these compounds for the treatment of ED. The Butler Patent discloses a method for the preparation of tadalafil as a co-precipitate with hydroxypropyl methylcellulose phthalate and the manufacture of the co-precipitate into tablets.
[32] After describing these previous Patents, the 948 Patent goes on to state that studies revealed problems with the co-precipitate formulation, which included “difficulties in generating precisely reproducible lots” and the fact that maximum blood concentration of tadalafil was only achieved in 3 to 4 hours, “with the average time for onset of a therapeutic effect as yet not precisely determined” (948 Patent, p 2). The Patent states that a formulation that allows for “a more rapid attainment of maximum blood concentration, along with a greater prospect for rapid onset of therapeutic effect” is desirable as patients prefer a more immediate effect (at pp 2-3 of the Patent).
[33] After discussing the background to the invention, the 948 Patent then summarizes the invention and states that it is a pharmaceutical formulation comprised of tadalafil, in free drug form, where the particle size has been reduced, “in admixture with a diluent, a lubricant, a hydrophilic binder selected from the group consisting of a cellulose derivative, povidone, and a mixture thereof, a disintegrant selected from the group consisting of crospovidone, croscarmellose sodium, and a mixture thereof, and, optionally, microcrystalline cellulose and/or a wetting agent … [and] optionally … additionally … a second diluent” (at p 4 of the Patent). The most preferred pharmaceutical formulation is stated to comprise “about”:
(a) 1 to 5, and preferably about 2 to 4% by weight of tadalafil in a free drug form, where the particle size is milled so that at least 90% of the particles have a particle size of less than about 40 microns;
(b) 50 to 85% by weight and preferably about 50 to 75% by weight of lactose;
(c) 0.25 to about 2% by weight of magnesium stearate;
(d) 1 to 5% by weight of hydroxypropylcellulose;
(e) 3 to 15% by weight of croscarmellose sodium;
(f) 0 to 40% by weight of microcrystalline cellulose; and
(g) 0 to 5% by weight of sodium laurel sulphate.
(948 Patent, pp 4, 8).
[34] The 948 Patent defines or further discusses several terms used in it. The relevant ones for purposes of this application are “free drug”, “water-soluble diluent”, “hydrophilic binder” and “microcrystalline cellulose” (or MCC).
[35] “Free drug” is defined as meaning solid particles of tadalafil as opposed to tadalafil embedded in a co-precipitate (p 5 of the Patent). A “water-soluble diluent” is defined as referring to compounds typically used in the formulation of pharmaceutical tablets to impart bulk and is stated as including (but not being limited to) sugars, polysaccharides, polyols, cyclodextrins and mixtures thereof (p 6 of the Patent). A “hydrophilic binder” is said to act as an adhesive to hold the tablet together (p 9 of the Patent). Possible hydrophilic binders falling within the group of cellulose derivatives are listed to include hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxyethylcellulose and hydroxybutyl methylcellulose (at p 10 of the Patent). Finally, the Patent notes that MCC is present in the formulations claimed at 0 to about 40% by weight and “can serve multiple functions in the formulation, e.g., a disintegrant and/or a second diluent in addition to the water-soluble diluent” (at p 11 of the Patent). This section of the disclosure also states that the invention claimed in the 948 Patent provides improved dissolution and in vivo absorption as well as improved stability over prior formulations (at pp 12–13 of the Patent).
[36] The 948 Patent then goes on to describe the technique to be used to formulate tablets as well as preferred dosage forms. It contains 13 non-limiting examples, showing different formulations of the invention claimed in the Patent.
[37] The 948 patent contains 33 Claims; those in issue in the present case are Claims 1-4, 7-8, 11-15, 17-21, 23-31 and 33.
[38] Claim 1 is the only independent claim. It claims a pharmaceutical formulation comprising tadalafil, provided as free drug and comprising particles wherein at least 90% of the particles have a particle size of less than about 40 microns; about 50 to 85% by weight of a water-soluble diluent; a lubricant; about 1 to 5% by weight of a hydrophilic binder selected from the group consisting of a cellulose derivative, povidone, and a mixture thereof; and a disintegrant selected from the group consisting of croscarmellose sodium, crospovidone, and a mixture thereof.
[39] Claims 2 to 8, 10 to 15 and 17-18 claim specific components of the formulation of Claim 1. Claims 19 to 21 claim a tablet comprising the formulation of Claim 1. Claims 23 to 25 claim specific particle sizes of the formulation in Claim 1. Claims 26 to 29 claim tablets comprising the formulation of Claim 1 where the compound is present in an amount of about 10 mg, 1 to 5 mg, 2.5 mg and 20 mg per tablet, respectively. Finally, Claims 30, 31 and 33 claim the use of the formulation and the tablets to treat sexual dysfunction and, specifically, ED.
[40] The Claims at issue in this application are reproduced in full in the Annex to these Reasons.
III. The Witnesses [41] Lilly tendered evidence of a law clerk (merely to introduce the relevant documents as exhibits), of two fact witnesses (Drs. Kral and Pullman) and two experts (Drs. Goldstein and Bodmeier). Apotex tendered an affidavit from Duane Terrill, the Associate Director, Regulatory Affairs at Apotex, to explain the background to the application, an affidavit of a law clerk, to produce additional documents, and an expert affidavit from Dr. Mumper.
[42] Dr. Pullman is a clinical pharmacologist formerly employed by Lilly. He is the co-inventor of another tadalafil patent, the 2,371,684 Patent (which was the subject of another prohibition application in Eli Lilly Canada v Mylan Pharmaceuticals ULC, 2015 FC 125, 249 ACWS (3d) 863). Dr. Pullman was involved in the clinical trials of tadalafil and in his affidavit introduces several clinical studies undertaken by Lilly.
[43] Dr. Martha Kral is one of the inventors of the 948 Patent and was a Research Advisor at Lilly. Her affidavit reviews the formulation work for tadalafil, both before and during her involvement, and recounts the work leading up to the invention claimed in the 948 Patent. She appends several studies to her affidavit, including studies done at Glaxo, as well as formulation and clinical studies conducted at Lilly.
[44] Dr. Bodmeier is a professor of pharmaceutical technology at the College of Pharmacy at Freie Universität in Berlin, Germany. He obtained his Ph.D. from the University of Texas in Austin and teaches and researches pharmaceutical sciences, including in respect of formulation and use of excipients. He has held numerous editorial positions for various journals in the pharmaceutical area and has published approximately 170 scientific papers in refereed journals and 10 book chapters on a variety of pharmaceutical topics, including in relation to formulation of poorly water-soluble drugs. Dr. Bodmeier was Lilly’s expert on both infringement and validity in Mylan Tadalafil III. In his affidavit in this case, he opines on the invalidity issues (including those that are no longer at play) and the non-infringement issue. He offers the opinion that Apotex’ generic versions of CIALIS and ADCIRCA infringe the 948 Patent and that the Patent is not invalid for obviousness or lack of utility.
[45] Dr. Goldstein is a urologist and the only clinician to give evidence in this proceeding. He was the Co-Director of the Laboratory for Sexual Medicine Research at the Boston University School of Medicine from 1981 to 2005 and the editor-in-chief of the International Journal of Impotence Research from 2001 to 2004. From 2004 to 2014 he was the editor-in-chief of the Journal of Sexual Medicine and is currently the editor-in-chief of the Journal of Sexual Medicine Reviews. He is currently a consultant and is also the Director of Sexual Medicine and a Clinical Professor of Surgery at the Alvarado Hospital and the University of California, San Diego. He has belonged to numerous professional organizations and has written broadly in areas associated with sexual dysfunction, with nearly 300 peer-reviewed papers, multiple book chapters and research awards from national and international organizations. In his affidavit, Dr. Goldstein offers an opinion on utility with respect to Claims 30, 31 and 33 of the 948 Patent and is of the view that the promise of these Claims has been demonstrated through the clinical studies Lilly filed and, accordingly, that these Claims are not invalid for inutility.
[46] Finally, Dr. Mumper is a pharmaceutical scientist, similar in profile to Dr. Bodmeier. He is the John A. MacNeill Distinguished Professor and Vice Dean at the University of North Carolina’s Eshelman School of Pharmacy and has a Ph.D. in Pharmaceutical Science. He has held several other academic appointments, served on the editorial boards of several leading publications in pharmaceutics and has published and spoken widely on various pharmaceutical topics. Prior to taking up the role of professor, Dr. Mumper worked in industry (for an innovator drug company) and was actively engaged in drug formulation, including in respect of poorly water-soluble drugs. In his affidavit, Dr. Mumper offers opinions on patent construction, infringement, utility and obviousness and takes the position that the Apotex products do not infringe the 948 Patent and that the Patent is invalid because the promised utility was neither demonstrated nor soundly predicted and the invention claimed was obvious.
IV. Do Apotex’ generic products infringe the 948 Patent? [47] With this background in mind, it is now possible to turn to the examination of whether the Apotex products infringe the 948 Patent. As an antecedent to this analysis, it is first necessary to construe the relevant Claims in the 948 Patent and determine their essential elements as infringement occurs when there is replication by the infringer of one or more of the essential elements of the patented invention (Free World Trust v Électro Santé Inc, 2000 SCC 66 at para 31, [2000] 2 SCR 1024; Whirlpool Corp v Camco Inc, 2000 SCC 67 at paras 43-45, [2000] 2 SCR 1067 [Whirlpool]).
A. Construction of the 948 Patent and determination of the essential elements of Claim 1 [48] In reviewing the claims of the 948 Patent, it is sufficient to limit the discussion to Claim 1, the only independent claim in the 948 Patent as, if this Claim is not infringed, none of the following dependent claims may be infringed. With one exception, the parties agree as to the essential elements of Claim 1 of the 948 Patent. These are:
(a) tadalafil in free drug form;
(b) with 90% of the tadalafil particles having a particle size of less than about 40 microns;
(c) about 50 to 85% by weight of a water-soluble diluent;
(d) a lubricant;
(e) about 1 to 5% by weight of a hydrophilic binder selected from the group consisting of a cellulose derivative, povidone, and a mixture thereof; and
(f) a disintegrant selected from the group consisting of croscarmellose sodium, crospovidone, and a mixture thereof (Bodmeier affidavit, para 82; Mumper affidavit, para 85).
[49] They disagree, however, on the meaning that should be ascribed to the term “about”. On one hand, Lilly and Dr. Bodmeier assert that the term means plus or minus 10 percent. Thus, they would read “about 1 to about 5%” as including an amount between 0.9% to 5.5% and “about 50 to about 85%” as including an amount between 45 and 93.5% (which they round up to 94%) (Bodmeier affidavit, paras 72, 86, 90). Apotex and Dr. Mumper, on the other hand, reject this reading and instead take the position that “about” means “approximate” and posit that the inventor used the word “about” in the 948 Patent to avoid a hard cut-off line so as to allow for small variations of quantities in the formulation, which invariably occur (Mumper affidavit, paras 96-101). They thus say that the amount by which an excipient may vary will be much less than the 5 to 9 % range posited by Lilly and Dr. Bodmeier with respect to the bounds of the infringing range of a water-soluble diluent (Mumper affidavit, paras 135-136).
[50] Of the two positions, I prefer that of Dr. Mumper and Apotex for three reasons. First, it makes much more sense. “About” does mean approximate and it strains credulity to think that a range of “about 50 to 85%” means between 45 and 94% – if that is what was meant, why not simply say so? In short, 45 is not approximately 50 nor is 93.5 or 94 approximately 85. Second, Dr. Bodmeier offers no justification for his selection of the plus or minus 10% interpretation, which, therefore, appears to have been selected to favour a finding of infringement. (He does note at para 72 of his affidavit that the plus or minus 10% calculation applies to the drug content of pharmaceutical dosage forms but provides no explanation of why a regulatory requirement for allowable variances in the generally very small amount of the active pharmaceutical ingredient in a tablet should apply to the interpretation of the amounts set out by the inventor in the 948 Patent.) Third, and most importantly, I discount Dr. Bodmeier’s credibility as I find he has tailored his evidence in this case to favour the result sought by Lilly.
[51] In this regard, in his affidavit, Dr. Bodmeier offered the view that the invention claimed in the 948 Patent was not obvious as there was “no guarantee that any of the options would work to result in a usable formulation” (at para 249 of the Bodmeier affidavit). This was the key statement in his affidavit, summarizing his conclusion on obviousness. Dr. Bodmeier made an identical statement in his affidavit in the Mylan Tadalafil III case.
[52] In Mylan Tadalafil III, Justice de Montigny rejected Dr. Bodmeier’s evidence in part because he found that Dr. Bodmeier set the bar too high for the test for obviousness. Justice de Montigny found as follows at para 150 in Mylan Tadalafil III:
[T]he test is not whether a skilled person would know for certain that a formulation would work or whether there is a guarantee that particular formulations would work, as suggested by Dr. Bodmeier in his affidavit [citations omitted]. This would set the bar too high. The test, rather, is whether the skilled person had good reason to pursue predictable solutions or solutions that provide a “fair expectation of success”.
[53] Justice Barnes also discounted similar evidence from Dr. Bodmeier in Janssen v Teva Canada Limited, 2015 FC 184 at para 101 for the same reason.
[54] At the outset of his cross-examination in this case, which occurred just days after the release of the confidential version of Justice de Montigny's decision in Mylan Tadalafil III, Dr. Bodmeier indicated that he wished to change the word “guarantee” in paragraph 249 of his affidavit in this case to the word “expectation” so the paragraph would read as follows:
There is no expectation [as opposed to guarantee] that any of the options would work to result in a usable formulation. In other words, it is not self-evident that it would be possible to obtain a workable formulation that provided an early onset of action.
[55] Dr. Bodmeier explained during his cross-examination that he made the decision to change this word in his affidavit through discussions with counsel because it was “a language issue” and he did not understand the word “guarantee” to mean 100%, but rather thought it meant a little more than a 50% likelihood of success. When he learned through discussion with counsel that this is not what the word “guarantee” in fact meant, he says he decided to change it to “expectation” to reflect what he says he originally meant, namely, that there was not more than a 50% likelihood that any of the options would result in a usable formulation (Bodmeier cross-examination, Application Record [AR] pp 8843-48).
[56] Counsel for Lilly submits that this change should not be viewed as an illegitimate attempt by Dr. Bodmeier to alter his evidence, prompted by the need to avoid a similar determination to that made by Justice de Montigny, but, rather, should be viewed as a mere correction that results from the fact that English is not Dr. Bodmeier’s first language. I reject this submission. Not only is there no evidence to support it, I find it unbelievable that Dr. Bodmeier – who completed his Ph.D. in Texas and who, according to his curriculum vitae, has written and spoken on scientific issues countless times in English – would not know the difference in meaning between the words “guarantee” and “expectation”. I therefore believe that the change was an attempt to adjust his evidence to avoid a conclusion unfavourable to Lilly, which is not how an independent expert ought to conduct himself.
[57] If I am wrong in this and Dr. Bodmeier’s English is so poor that he cannot distinguish between “guarantee” and “expectation”, then his command of the language is such that it is not suitable for him to be providing expert testimony to this Court. I therefore determine that where there is a conflict between the evidence of Dr. Bodmeier and Dr. Mumper, Dr. Mumper’s evidence is to be preferred. I accordingly conclude that the word “about”, as used in Claim 1 of the 948 Patent means “approximately” and not plus or minus 10%.
B. Non-infringement [58] Apotex asserts that its generic versions of CIALIS and ADCIRCA do not infringe the 948 Patent as they do not contain approximately 50 to 85% by weight of a water-soluble diluent nor approximately 1 to 5% by weight of a hydrophilic binder selected from the group consisting of a cellulose derivative, povidone, or a mixture thereof.
[59] Drs. Mumper and Bodmeier concur that the composition of the Apotex generic tablets (as disclosed in its Abbreviated New Drug Submissions [ANDSs], filed in support of its request for NOCs) is as follows:
Apotex Component
Apotex’ Stated Function
Mg/
Unit
Dose
(20mg)
% w/w
(20 mg)
Mg/
Unit
Dose
(10mg)
% w/w
(10mg)
Mg/
Unit
Dose
(5mg)
%
w/w
(5mg)
Mg/
Unit
Dose
(2.5mg)
% w/w
(2.5mg)
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(Bodmeier affidavit, para 80, AR p 354; Mumper affidavit, para 145, AR p 7533)
[60] The only binder listed in the Apotex formulations is [redacted]. Both parties concur that [redacted] is not a cellulose derivative nor povidone, and therefore does not come within the 948 Patent’s definition of a “hydrophilic binder”, which is defined as including hydrophilic binders selected from the group consisting of a cellulose derivative, povidone, and a mixture thereof (Mumper affidavit, para 148; uncontradicted by Bodmeier). Therefore, if one accepts that the excipients in the Apotex tablets perform the functions Apotex claims they perform, the Apotex products do not contain approximately 1 to 5% by weight of a hydrophilic binder because [redacted] is not a hydrophilic binder of the type claimed in the Patent.
[61] Moreover, even if it were, the amount present in the Apotex tablets falls outside the essential weight range of approximately 1 to 5% claimed in Claim 1 of the 948 Patent. The tablets contain approximately [redacted], which Dr. Mumper says is not equivalent to being “about” 5% and which also, incidentally, falls outside Dr. Bodmeier’s plus or minus 10% range (Mumper affidavit, paras 152-155). Thus, if the excipients in the Apotex products perform the functions listed in Apotex’ ANDSs, they are missing an essential element of Claim 1, namely, the presence of approximately 1 to 5% by weight of a hydrophilic binder selected from the group consisting of a cellulose derivative, povidone, and a mixture thereof.
[62] The Apotex formulations on their face also do not contain approximately 50 to 85% by weight of a water-soluble diluent if the excipients perform the functions Apotex claims they perform. Apotex lists [redacted] diluents in its ANDSs, namely [redacted] and [redacted]. There is no dispute that [redacted] is not water-soluble but that [redacted] is (Bodmeier affidavit, para 86; Mumper affidavit, paras 174-75). The Apotex formulations contain only approximately [redacted]. This falls well below the amounts required by Claim 1 of the 948 Patent of approximately 50 to 85%. Thus, for this reason as well, if the excipients in the Apotex tablets perform the functions that Apotex alleges they perform, the Apotex products do not infringe the 948 Patent.
[63] Lilly and Dr. Bodmeier, however, say that the excipients in the Apotex formulations do not in fact perform the functions Apotex claims and, therefore, that its products infringe the 948 Patent. More specifically, Dr. Bodmeier asserts that the Apotex products contain the required am