Takeda Canada Inc. v. Apotex Inc.

Takeda Canada Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2024-02-07
Neutral citation
2024 FC 106
File numbers
T-151-22
Decision Content
Date: 20240207
Docket: T-151-22
Citation: 2024 FC 106
Toronto, Ontario, February 7, 2024
PRESENT: The Honourable Madam Justice Furlanetto
BETWEEN:
TAKEDA CANADA INC.
Plaintiff
and
APOTEX INC.
Defendant
and
TAKEDA PHARMACEUTICAL COMPANY LIMITED AND TAKEDA PHARMACEUTICAL USA, INC.
Defendants/Patent Holders
PUBLIC JUDGMENT AND REASONS
(Confidential Judgment and Reasons issued January 23, 2024)
I. Overview [1] This judgment arises from a patent infringement action brought under subsection 6(1) of the Patented Medicines (Notice of Compliance Regulations), SOR/93-122 [PMNOC Regulations]. The patent at issue is Canadian Patent No. 2,570,916 [916 Patent]. The innovative drug relating to the action is DEXILANT®, which is used to treat heartburn associated with gastroesophageal reflux disease [GERD], as well as to heal damage to the esophagus from stomach acid.
[2] Takeda Canada Inc. [Takeda] is the “first person” in accordance with the PMNOC Regulations. Takeda Pharmaceuticals USA, Inc. is the registered owner of the 916 Patent and is a party to the action pursuant to subsection 6(2) of the PMNOC Regulations. Takeda claims that the making, constructing, using or selling by the Defendant, Apotex, Inc. [Apotex], of its dexlansoprazole oral dose capsules in strengths of 30 mg and 60 mg [Apotex Product] in accordance with Apotex’s Abbreviated New Drug Submission [ANDS] Control Number 256485 will infringe at least one of claims 1, 5-8, 10-11 and 16 [Asserted Claims] of the 916 Patent. Apotex denies infringement and asserts in defence that the Asserted Claims are invalid for anticipation, obviousness, inutility, insufficiency, overbreadth, ambiguity and/or as unpatentable subject-matter.
[3] For the reasons that follow, I find that the action should be dismissed as the Asserted Claims of the 916 Patent are not infringed and are also invalid for failure to meet the disclosure requirements under subsection 27(3) of the Patent Act and to provide proper disclosure of the factual basis and line of reasoning to support a sound prediction of utility.
II. Background [4] The 916 Patent is listed on the Patent Register in association with the medicine dexlansoprazole, which is the R-enantiomer of lansoprazole.
[5] Dexlansoprazole is one of a group of compounds known as proton pump inhibitors [PPIs] that function by inhibiting the gastric hydrogen potassium pump, known as the H+/K+ ATPase [proton pump] found in cells in the lining of the stomach. Activation of the proton pump results in the formation of gastric acid which decreases the pH in the stomach. PPIs react with acid to form a compound that inhibits the proton pump through covalent bonding. The result is a decrease in the gastric acid level and a corresponding increase in the pH in the stomach.
[6] Dexlansoprazole is the active ingredient in Takeda’s product DEXILANT®. DEXILANT® is a pulsatile release formulation sold in capsule form that includes two types of delayed-release beads containing dexlansoprazole. The dexlansoprazole is released from the dosage form in two discrete pulses, with one of the types of delayed release beads designed to release drug after it reaches the proximal small intestine and the second type of delayed release bead designed to release drug in the distal region of the small intestine, several hours later.
[7] Takeda obtained a Notice of Compliance [NOC] and began selling DEXILANT® in Canada in 2010. At the time DEXILANT® entered the Canadian marketplace it was the sixth PPI available, with the market already including other PPIs, namely omeprazole, esomeprazole, lansoprazole, pantoprazole (and pantoprazole magnesium) and rabeprazole, which were sold as single release formulations for treating GI disorders related to increased and delocalized gastric acid.
[8] This action initially alleged infringement of two patents listed on the Patent Register – the 916 Patent and Canadian Patent No. 2,671,369 [369 Patent]. However, by letter dated June 12, 2023, Takeda advised the Court that it would not be pursuing the allegations in respect of the 369 Patent. At trial, Takeda confirmed that it had abandoned its infringement claim with respect to the 369 Patent and that there were no issues for the Court to determine with respect to the 369 Patent.
III. The 916 Patent [9] The 916 Patent is entitled “Pulsed Release Dosage Form of a PPI”. It is the national phase entry of a Patent Co-operation Treaty patent application filed on June 1, 2005, which is based on a United States priority patent application, filed on June 16, 2004. The application for the 916 Patent was published on January 26, 2006 and will expire on June 1, 2025. It names two inventors: Dr. Majid Vakilynejad (a pharmacokineticist) and Dr. Rajneesh Taneja (a formulator).
[10] Page 1 of the 916 Patent identifies the technical field of the invention of the 916 Patent as relating to PPIs and in particular, dosage forms containing multiple doses of a PPI.
[11] The Background to the 916 Patent describes PPIs as a class of pharmaceutical compounds that inhibit gastric acid secretion by inhibiting the proton pump. It notes that PPIs rapidly degrade in acidic environments and therefore that dosage forms containing PPIs are generally designed to protect the PPI from the acidic environment of the stomach and to release the PPI in the upper small intestine.
[12] The Background explains that PPIs have a prolonged therapeutic effect that does not directly correlate with serum concentrations of these drugs and their relatively short pharmacokinetic [PK] half-life. It further explains that despite the prolonged therapeutic effect of PPIs, some patients on PPI therapy experience a nocturnal breakthrough event where the secretory activity of the proton pump returns. The Background states that there is no currently known solution to nocturnal breakthrough effects and that there is a need for a dosage form containing a PPI that can provide a full day of therapeutic effect while being administered on a once-a-day basis.
[13] The Summary of the Invention [Summary] describes the invention of the 916 Patent as dosage forms comprising a PPI that is released as a first and a second dose in an amount sufficient to raise the plasma concentration of the PPI to at least 100 ng/mL. The Summary explains that release of the PPI may occur as discrete pulses where the pulses are separated by a pre-selected period of time or alternatively, may be separated by little or no time delay and released continuously. The Summary states that the invention also provides “methods of treating gastrointestinal disorders with the dosage forms”.
[14] In the Detailed Description [Description], the 916 Patent teaches the person skilled in the art [PSA] that the PK properties of the PPI can be used to mitigate the nocturnal breakthrough phenomenon so that a single oral dosage form can be taken once a day. First, it teaches that alleviation of nocturnal breakthrough is a function of the concentration of the PPI in the patient; and second, it teaches that there is a threshold concentration that must be surpassed in a second dose of the PPI before a therapeutic effect is achieved (916 Patent, Ex1, 2a:8-17):
It has unexpectedly and surprisingly been discovered that the breakthrough phenomenon can be mitigated through appropriate use of pharmacokinetic properties of these drugs to establish effective concentrations of the PPI. In particular, it has been found that it is not sufficient merely to provide an additional dose of PPI sometime after a first daily dose and before nighttime. The appropriate means for alleviating the breakthrough phenomenon is a function of the concentration of the PPI in a patient. Applicants have discovered that there is a threshold concentration of these drugs that must be surpassed in a second dose of the PPI before a therapeutic effect is achieved. Moreover, the first and the second dose can be administered in a single oral dosage format that can be taken once a day to alleviate nocturnal breakthrough events.
[15] The invention is described as providing a dosage form where each of the first and second dose of PPI is “in an amount sufficient to achieve a therapeutic effect and thereby alleviate the nocturnal breakthrough phenomenon” (916 Patent, Ex1, 2a:18-21). The Description teaches that each dose of PPI should raise the plasma level of PPI to at least 100 ng/mL, preferably above 200 ng/mL, more preferably above 300 ng/mL, even more preferably above 400 ng/mL, and most preferably above 500 ng/mL (916 Patent, Ex1, 3:1-5). The 916 Patent notes that “those skilled in the art can readily determine the milligram amounts of any particular PPI that should be included in the first and second dose of the PPI to raise patient plasma levels to the thresholds” (916 Patent, Ex1, 3:5-7).
[16] The PSA is told that the benefits of the invention are not limited to a particular type of dosage form and that the dosage forms of the invention can exist as either controlled release dosage forms or pulsed release systems. Controlled release dosage forms are described as including matrix systems, osmotic pumps and membrane controlled systems. Pulsed release systems are described as generally comprising a first drug release and second drug release separated by a predetermined period of time or site of release. The 916 Patent notes that this may include a combination of an immediate release and extended release formulation and can include particle or granule systems where distinct populations of drug containing particles are used to achieve the pulsed release with different coating polymers targeted to release the drug at different points in time or location (916 Patent, Ex1, 10:23-11:3).
[17] The 916 Patent teaches that when a pulsed release dosage form is employed, the first and second pulses of the drug should each be sufficient to increase the plasma level concentration above the threshold level (916 Patent, Ex1, 12:4-6). The 916 Patent explains that due to decreasing absorption in the downstream portions of the gastrointestinal [GI] tract, it is preferred to load dosage forms with PPI such that the second dose of PPI is higher than the first dose (916 Patent, Ex1, 12:25-27). The 916 Patent teaches a second dose that is at least 10% more, more preferably at least 50% more, even more preferably at least 100% to 200% more, and most preferably at least 200% to 900% more than the first dose (916 Patent, Ex1, 12:27-31). The 916 Patent states that a PSA would be able to formulate oral dosage forms containing a PPI that is released in accordance with the threshold concentrations (916 Patent, Ex1, 11:28-30).
[18] The 916 Patent teaches that any PPI can be used in the dosage form as well as their respective enantiomers (916 Patent, Ex1, 2a:22-27). It refers to lansoprazole or an enantiomer or salt thereof such as R-lansoprazole (dexlansoprazole) as a PPI of the invention (916 Patent, Ex1, 2:24-25). The 916 Patent states that the dosage forms may be tested empirically in animal and/or human models (916 Patent, Ex1, 13:27-28).
[19] The 916 Patent includes two examples. The first example refers to mathematical modelling based on plasma concentration data from administration of single intravenous [IV] doses of lansoprazole in humans. The example refers to using the IV data to model the pharmacological effect “using a sigmoid Emax model”, and modelling PK using a two compartment model with a PK compartment linked to a separate effect compartment. The example refers to the modelling first establishing “the pharmacokinetic characteristics of lansoprazole”, then “the relationship between drug plasma concentration and intragastric pH”, and then “pharacodynamic [sic] parameter estimates” (916 Patent, Ex1, 14:24-26). The results of the modelling are depicted graphically in Figure 1 of the patent, which is described as showing the relationship between plasma concentration at steady-state and gastric pH and as establishing that the threshold concentration of “approximately 100 ng/mL should be attained for purposes of attaining a minimum change in the desired pharmacological effect from baseline.” (916 Patent, Ex1, 14:32-15:2).
[20] The second example is a site of absorption study that measures the extent to which lansoprazole was absorbed at different sites in the GI tract (916 Patent, Ex1, 15:5). The 916 Patent states that Example 2 shows that “[t]he rate and extent of absorption for lansoprazole from the distal small intestine [is] less than that obtained for the proximal intestine” and that “[t]he extent of absorption was reduced when lansoprazole was directly delivered to the colon.” (916 Patent, Ex1, 17:1-3).
IV. Issues [21] The following issues were identified by the parties as being those in dispute for this action:
The construction of the Asserted Claims, and specifically, the meaning to be given to the elements: “a first and a second dose” and “threshold concentration”;
Whether the making, constructing, using or selling of the Apotex Product in accordance with ANDS Control Number 256485 would infringe the Asserted Claims?
Whether Canadian Application No. 2,499,574 [574 Application] anticipates the subject-matter defined by the Asserted Claims, contrary to paragraph 28.2(1)(b) of the Patent Act?
Whether the subject-matter defined by the Asserted Claims would have been obvious on the claim date of June 16, 2004 to a PSA, contrary to section 28.3 of the Patent Act?
Whether a practical utility relating to the subject-matter of the Asserted Claims was not soundly predicted by the 916 Patent’s Canadian filing date of June 1, 2005?
Whether the 916 Patent fails to correctly and fully describe the invention and its operation or use as contemplated by the inventors, contrary to subsection of 27(3) of the Patent Act?
Whether the Asserted Claims are broader than either the invention made by the named inventors of the 916 Patent or the invention disclosed in the specification of the 916 Patent?
Whether the Asserted Claims fail to define distinctly and in explicit terms the subject-matter of the invention for which an exclusive privilege or property is claimed, contrary to subsection 27(4) of the Patent Act? and
Whether the Asserted Claims claim patentable subject-matter, as required by section 2 of the Patent Act?
V. Witnesses [22] Five experts gave testimony at the trial of this action; two experts gave evidence for Takeda (Dr. Robert J. Timko and Dr. David Armstrong) and three experts for Apotex (Dr. Colin Rowlings, Dr. Neal Davies and Dr. Peter Kahrilas).
[23] As a preliminary matter, I note that Apotex challenged the admissibility of much of Takeda’s expert evidence. While I have determined that the expert evidence should not be rendered inadmissible, I have concerns with certain aspects of Takeda’s expert evidence and attribute those aspects limited weight as set out further below. A summary of these findings follows.
A. Takeda’s Experts [24] Dr. Robert J. Timko - Dr. Timko obtained his Ph.D. from Rutgers University in 1979, specializing in dissolution, formulation development, and physical pharmacy. He is currently the Founder and President of RhoTau Pharma Services LLC, a pharmaceutical and regulatory sciences consulting firm. Dr. Timko has over 45 years experience working in pharmaceutical formulation and process development for new chemical entities, generics, and consumer (over-the-counter) products, including 30 years with AstraZeneca. He was admitted as an expert in pharmaceutical formulation, with expertise in respect of the design, development, manufacture and analysis of pharmaceutical dosage forms.
[25] Dr. Timko delivered three expert reports in the proceeding. His first report opined on claims construction and infringement. The second report opined on the validity of the 916 Patent, including the issues of sufficiency and overbreadth and responded to the expert report of Dr. Rowlings on those issues. The second report also commented on documents relating to DEXILANT® and whether DEXILANT® was covered by the claims of the 916 Patent. The third report replied to certain comments made by Dr. Rowlings and Dr. Davies on infringement.
[26] Dr. Timko was unable to comment on the full scope of Dr. Rowlings’ and Dr. Davies’ critiques of his infringement analysis. During cross-examination, he acknowledged that he did not read the whole of their reports, but only those aspects to which he responded. His evidence therefore did not benefit from a full understanding of the completeness of Dr. Rowlings’ and Dr. Davies’ comments.
[27] In final argument, Apotex challenged the admissibility of Dr. Timko’s infringement opinion, asserting that he had employed a novel untested methodology. In his infringement analysis, Dr. Timko identified certain individual plasma concentration curves amongst the bioequivalence test data on the Apotex Product that, in his view, showed that the dexlansoprazole within the Apotex Product was released as two distinct pulses. To determine the amount of dexlansoprazole present in each of the asserted doses (or pulses), Dr. Timko identified a proposed transition point between the two asserted releases and then estimated the “area under the curve” [AUC] for each proposed pulse using the trapezoidal mathematical integration method. The amount of dexlansoprazole in each proposed dose was then determined from the estimated AUC exposure values using the total, starting dose amount.
[28] Apotex asserts that Dr. Timko’s analytical approach is a novel testing methodology that does not meet the reliable foundation test laid down by the U.S. Supreme Court in Daubert v Merrell Dow Pharmaceuticals, Inc, 509 US 579 (1993) [Daubert] and cited with approval by the Supreme Court of Canada [SCC] in R v J-LJ, 2000 SCC 51 [J-LJ] at paras 33-35. In J-LJ, the SCC identified four factors that must be considered when evaluating whether a novel test methodology will be accepted by the Court as admissible evidence: 1) whether the theory or technique can be and has been tested; 2) whether the theory or technique has been subjected to peer review and publication; 3) the known or potential rate of error or the existence of standards; and 4) whether the theory or technique used has been generally accepted.
[29] While I accept many of the concerns raised by Dr. Davies and Dr. Rowlings as to the approach taken by Dr. Timko in his analysis, and while I find that the cross-examination further undermined Dr. Timko’s approach, in my view these issues are best addressed as a matter of weight, rather than admissibility.
[30] First, I do not accept that Dr. Timko has introduced a new methodology as that term was intended in Daubert. His analysis does not involve the development of a new protocol or experimental procedure, but rather involves an attempt to adapt known analytical techniques (i.e., AUC and trapezoidal method) to a new context - that of determining whether the dose amounts claimed are found in the Apotex Product. Indeed, Apotex’ expert Dr. Davies referred to AUC in his scientific primer as a known PK parameter, reflecting “the total exposure of the body to the drug” and discussed the trapezoidal method for determining AUC (Davies, Ex32, para 91). As discussed further below, while the approach taken by Dr. Timko was shown to have flaws, Apotex’ criticisms do not, in my view, engage the Daubert principles.
[31] Second, while Apotex argues that Dr. Timko’s analysis taints the whole of his infringement opinion such that his full report should be rendered inadmissible, I do not accept that it extends this far. The determination of the dose amounts of dexlansoprazole is but one part of Dr. Timko’s infringement assessment. It is clear that Dr. Timko is an expert in his field and that he has provided some useful information for the Court’s consideration. I do not accept that the whole of his report is subject to concern for admissibility.
[32] Third, I consider Apotex’ argument to arise too late in the day to be dealt with as an admissibility objection. In my view, this type of admissibility argument should have been raised with the Court as soon as Dr. Timko’s evidence was received so that the Court could have considered the proper approach to be taken and whether a voir dire would benefit its gatekeeper role (Rule 52.5(1), Federal Courts Rules). As noted in White Burgess Langille Inman v Abbott and Haliburton Co, 2015 SCC 23 [White Burgess], one of the key objectives in the Court’s gatekeeping role is to streamline the process and balance relevance, reliability and necessity as against time, prejudice and confusion (at paras 16, 24). By Apotex waiting to raise its concerns, this balancing exercise can no longer serve the same objective.
[33] Dr. David Armstrong - Dr. Armstrong has practiced gastroenterology in the United Kingdom [UK] and Canada since 1983. He is also a Professor of Medicine at McMaster University. He obtained his medical degree from Cambridge in 1977 and completed post-graduate work at King’s College Hospital Medical School. He is certified by medical boards in Canada and the UK and is a member of many medical associations relating to gastroenterology, including the American Gastroenterological Association [AGA]. He has also served as a peer reviewer for several academic publications. Dr. Armstrong was admitted as an expert in the use of PPIs in clinical, research and hospital settings and the treatment of gastric acid disorders, including the use of PPIs from the 1990s to present, including the knowledge, trends, and biases held by physicians during this period. Dr. Armstrong was asked to respond to Dr. Kahrilas’ and Dr. Davies’ review of the 916 Patent and their analyses on inventiveness, and to Dr. Davies opinion on anticipation. He was also asked to provide his opinion on the issue of utility and to respond to Dr. Kahrilas and Dr. Davies on this issue. Dr. Armstrong further commented on the properties and benefits of DEXILANT®.
[34] In final argument, Apotex objected to the admissibility of Dr. Armstrong’s report on the basis that he had failed to fulfill his overriding duty as an expert. As set out in White Burgess at paragraph 32, an expert has an overriding duty to the Court to provide their evidence impartially, independently and without bias. The expert’s opinion must reflect an objective assessment of the questions at hand; it must be the product of the expert’s independent judgment, uninfluenced by the party who retained the expert or the outcome of the litigation; and must not unfairly favour one party’s position over another. This overriding duty is reflected in the Expert Code of Conduct, which is discussed in Rule 52.2, and attached as a Schedule to the Federal Courts Rules.
[35] Apotex points to candid admissions by Dr. Armstrong that he did not read prior art on which his comments relating to obviousness and anticipation were based, instead relying on the summaries provided by Takeda’s counsel. On cross-examination, Dr. Armstrong acknowledged that in view of this reliance he had made inaccurate statements in his report as to the content of prior art, and in particular with respect to the examples of the 574 Application and the disclosure in prior art documents, WO 03061584 A2 [WO 584] and WO 0124777 A1 [WO 777]. He admitted to relying upon information from counsel in an “unconfirmed”, “unsubstantiated” and “unverified” manner and that he was not surprised by certain inaccuracies in his opinion that were brought to his attention during cross-examination. With respect to the 574 Application, Dr. Armstrong admitted that if he had taken greater care to understand this reference that he would have written certain aspects of his opinion differently. He acknowledged that he should have read the entirety of the prior art documents to provide his opinions.
[36] I agree that Dr. Armstrong’s evidence on the prior art is tainted by the select reading taken, which reflects Takeda’s interpretation of the references, thereby putting the impartiality and independence of his related opinions in question. The issue before the Court is whether Dr. Armstrong’s evidence should be rendered inadmissible in view of these concerns or whether it should be dealt with as a matter of weight.
[37] In Biogen Canada Inc v Taro Pharmaceuticals Inc, 2020 FC 621; aff’d on appeal 2022 FCA 143, Justice Manson considered the issue of impartiality in the context of a patent infringement action. In that case, cross-examination revealed that approximately one hundred paragraphs of the expert’s report had been copied verbatim from the Notice of Allegation, which the expert acknowledged he had never reviewed. Justice Manson found that this activity cast significant doubt as to the impartiality and independence of the expert, but dealt with these concerns as a matter of weight rather than rendering the evidence inadmissible:
[44] As a preliminary point, the parties’ key witnesses’ evidence was uniformly weakened on cross-examination. Given the inconsistencies of evidence, advocacy, and unreasonable positions taken by Drs. Oh and Leist for Biogen, and Drs. Ebers and Bailey for the Defendants, unless otherwise specified, the Court gives limited weight to their expert opinion evidence.
[...]
[70] Dr. Ebers’ report was also far from impartial. Biogen highlighted approximately one hundred paragraphs of his report that were copied nearly verbatim from Taro’s NOA, which Dr. Ebers acknowledged he had never reviewed.
[71] It is certainly permissible for counsel to help an expert prepare his or her report (Moore v Getahun, 2015 ONCA 55 at paras 55, 64). Counsel may even point the expert to relevant prior art, as long as the expert reviews and confirms the content of his or her report, as the choice of prior art is entirely in the hands of the party alleging obviousness (Ciba Specialty Chemicals Water Treatments Limited’s v SNF Inc, 2017 FCA 225 at para 60). It is quite another story for an expert to do little or no independent research and accept, verbatim, large portions of a NOA prepared by legal counsel which the expert has never seen, let alone reviewed. This crosses the line of propriety and puts into real doubt the impartiality and independence of the expert; key aspects of the expert’s duty to the Court (White Burgess Langille Inman v Abbott and Haliburton Co, 2015 SCC 23 at paras 26-32).
[38] Similarly, in Rovi Guides, Inc v Bell Canada, 2022 FC 1388 [Rovi], Justice Lafrenière admitted the expert report in question despite finding that significant portions of the report were unequivocally plagiarized. Justice Lafrenière held there would be severe prejudice to Rovi in disqualifying its only technical expert, that far outweighed any prejudice to Bell in treating the criticisms of the expert’s report as a matter of weight:
[107] However, what happened in this case went well beyond collaboration, consultation, wordsmithing or editing. It was word-for-word copying of a technical expert’s opinions and conclusions on key issues before this Court, all done without any attribution. It is plagiarism pure and simple. Plagiarism is wrong whether it is intentional or not.
[108] A critical distinction must be drawn between counsel assisting an expert in framing their reports in a way that is comprehensible and responsive to the pertinent legal issues in a case and leading, or be seen to have led, an expert to express a particular opinion. The latter crosses the line of propriety and puts into real doubt the impartiality and independence of the expert: White Burgess Langille Inman v Abbott and Haliburton Co, 2015 SCC 23 [White Burgess] at paras 26-32. It also brings into question what other “assistance” may have been given to the expert in drafting their report. The expert’s opinion “must be independent in the sense that it is the product of the expert’s independent judgment, uninfluenced by who has retained him or her or the outcome of the litigation” (White Burgess at para 32).
[...]
[111] In Abbott Laboratories v Canada (Minister of Health), 2006 FC 76, aff'd 2009 FCA 94 [Abbott Laboratories] at para 19, Associate Judge Martha Milczynski, then called Prothonotary, set out the proper approach to determine whether or not an expert should be disqualified. In that case, the plaintiff expressed concern that a proposed expert of one of the defendants had received some confidential information of the plaintiff, thereby placing the expert in a potential conflict of interest. Prothonotary Milczynski stated that there must be an objective review of the facts and circumstances in each case and listed various factors to be analyzed in conducting the review. For the purpose of the present case, the following factors are relevant:
̶̶ whether the expert knew he or she was relying on plagiarized information;
̶ the nature of the plagiarized information;
̶ the risk of prejudice arising to either the party challenging the expert or to the party seeking to retain the challenged expert; and
̶ the interests of justice and public confidence in the judicial process.
[112] After balancing all of the above factors, I conclude that Mr. Wahlers should not be disqualified as a witness. The circumstances in the present case are different than those in Anderson. In Anderson, the expert report prepared by a family physician was found to be plagiarized and the physician was found to have lied about it. The judge also concluded that the expert was biased, unqualified and not independent. The primary reason the expert was disqualified was because he did not have the appropriate expertise, which is not the case here.
[113] While the second factor identified above militates in favour of disqualification, I find there would be a severe prejudice to Rovi to disqualify its only technical expert, one that far outweighs any prejudice to the Defendants.
[114] It remains that Mr. Wahlers lack of candour and his apparent indiscriminate adoption of another expert’s opinions or conclusions, albeit unknowingly, raise serious concerns in my mind as to whether Mr. Wahlers has fulfilled his duty to the Court to provide an independent opinion. The problem is compounded by the fact that, contrary to what is asserted by Rovi, Mr. Wahlers was unable to defend many of his opinions at trial.
[...]
[118] Despite my strong reservations as to Mr. Wahlers’ credibility, independence and impartiality, it would not be just to reject his reports or testimony out of hand. There are, after all, some aspects of his evidence that are not controversial and prove useful and reliable. The concerns raised by the Defendants go to weight to be given to Mr. Wahlers’ evidence, rather than to its admissibility. Just to be clear, I have looked upon Mr. Wahlers’ evidence with great skepticism.
[39] Applying the principles set out in Rovi, and considering the potential prejudice to Takeda as Dr. Armstrong was Takeda’s primary expert on validity and only expert who responded to Apotex’ experts Dr. Davies and Dr. Kahrilas on validity issues, I prefer to deal with his evidence as a matter of weight. While it was revealed that Dr. Armstrong did not complete a full reading of the references, it is clear that he had the requisite expertise to give evidence and that he was willing to concede the shortcomings in the approach he had taken. In my view, these concessions established that Dr. Armstrong was not functioning as an advocate for Takeda. As was the case in Rovi, even with these difficulties and others highlighted during cross-examination, Dr. Armstrong’s views were still of value to the Court on certain technical issues. Indeed, even Apotex relied on Dr. Armstrong for specific points within its argument, acknowledging in oral submissions that they had cited to Dr. Armstrong various times.
B. Apotex’ Experts [40] Dr. Colin Rowlings - Dr. Rowlings obtained his Ph.D. from the University of Iowa in 1989, specializing in pharmaceutics. He is currently the Senior Vice President of Gossamer Bio Inc. He has over 34 years experience working in the pharmaceutical industry primarily on small-molecule, new chemical entity development, encompassing a variety of dosage forms. He has contributed to multiple product approvals and has significant experience in the field of oral modified release dosage forms, including pulse release dosage forms and the use of enteric coatings. Dr. Rowlings was admitted as an expert in the field of pharmaceutical sciences, pre‑formulation, formulation development and analytical testing, with specific expertise in oral modified release dosage forms (extended release formulations, pulsatile release formulations, gastro-retentive formulations, and mini-tablet and pellet formulations), characterization of excipients, and the design, interpretation and application of site of absorption studies. His expertise includes analysis and interpretation of PK and pharmacodynamic [PD] data from studies conducted for the purpose of developing oral formulations.
[41] Dr. Rowlings provided two reports: a first report opining on claims construction, anticipation, obviousness, overbreadth, sufficiency and ambiguity; and a second report opining on the issue of infringement and responding to Dr. Timko’s evidence on this issue.
[42] Overall, I found Dr. Rowlings to be a forthright and fair witness who was knowledgeable about pharmaceutical formulation and whose testimony assisted the Court. He conceded points that were against the interests of Apotex where it was evident that he should do so. For the most part, I rely heavily on Dr. Rowlings’ evidence with one reservation relating to his obviousness analysis, where he admittedly reviewed prior art references in an effort to “find” certain elements in the claims. In my view, this suggests a degree of hindsight in the approach taken to the references such that the Court must consider his evidence on this issue with some caution.
[43] Dr. Neal Davies - Dr. Davies is a pharmacologist and registered pharmacist with over 25 years experience in drug development, pharmacokinetics, drug delivery and pre-clinical and clinical pharmaceutical sciences. He obtained his Ph.D. from the University of Alberta in 1996, specializing in pharmacokinetics. He is currently a Professor in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta and is also a Fellow in the Canadian Academy of Health Sciences. Dr. Davies has significant experience in the analysis of plasma profiles and the use of PK models. His work focuses on drug development, pharmacokinetics and drug delivery, as well as on basic and clinical pharmaceutical sciences. Dr. Davies was admitted as an expert in the fields of pharmacology, pharmacokinetics (including drug absorption, distribution, metabolism and excretion), pharmacodynamics and pharmaceutical sciences, with specific expertise in PK/PD modelling, designing and interpreting PK/PD studies, analytical techniques to measure drug concentration, drug development, drug delivery and formulations, determining appropriate dosages in animals and humans, chirality of drugs, gastrointestinal disorders and PPIs. Like Dr. Rowlings, Dr. Davies provided two reports. His first report opined on claims construction, anticipation, obviousness, utility, overbreadth, insufficiency and ambiguity. His second report opined on the issue of infringement and responded to Dr. Timko’s evidence on this issue.
[44] Dr. Davies is undoubtedly a very knowledgeable witness. He gave helpful information on pharmacology, pharmacokinetics, pharmacodynamics, including PK/PD modelling and how the PSA would read and understand Example 1 of the 916 Patent. He was the only true pharmacokinetics expert in the proceeding and the only expert who understood all facets of the effect compartment modelling that was used by the inventors. While I found Dr. Davies to be very knowledgeable, at times I found him to be unnecessarily difficult when answering straight-forward questions and to be fixated on problems which made him unable to respond meaningfully to questions directed at understanding the significance of some of his comments. I had difficulty with his testimony regarding the calculation of the dose amounts from the 574 Application where I found he read the examples without trying to understand them in a practical way. In that instance where the evidence was in conflict with Dr. Rowlings, I preferred the evidence of Dr. Rowlings. I have highlighted these matters further in my analysis below.
[45] Dr. Peter Kahrilas - Dr. Kahrilas is a gastroenterologist with 40 years of clinical experience treating patients with acid-related disorders, such as GERD. He also conducts research and is a Professor of Medicine at Northwestern University where he has worked since 1999. His research concerns esophageal physiology and pathophysiology with a focus on motility disorders and GERD. Dr. Kahrilas is certified by several medical boards in the United States [US] and is a fellow of a number of medical organizations, including the AGA. Dr. Kahrilas was admitted as an expert in the field of gastroenterology with specific expertise in the diagnosis and treatment of patients with esophageal disorders, such as GERD and esophageal motility disorders. Dr. Kahrilas provided a single expert report, offering opinions on claims construction, obviousness and utility.
[46] Dr. Kahrilas was a knowledgeable witness who provided clear and straight-forward answers, giving his responses simply and directly even if answers were not in Apotex’ favour. I found Dr. Kahrilas’ evidence to be helpful and where it conflicted with that of Takeda’s experts, I preferred the evidence of Dr. Kahrilas unless otherwise stated below. Similar to Dr. Rowlings, the only reservation I had with Dr. Kahrilas’ evidence related to his approach to the third part of the obviousness analysis and his review of prior art references in an effort to “find” elements in the claims. I discuss this concern in greater detail below.
C. Fact Witnesses [47] Three fact witnesses gave evidence at trial. The first fact witness, Dr. Majid Vakilynejad, is one of the inventors of the 916 Patent. His evidence provided background on the proposed invention and Examples 1 and 2 of the 916 Patent. The remaining two fact witnesses, Jason Goodfield and Rose Guthrie, are current and former employees of Takeda who spoke to the introduction and impact of DEXILANT® on the Canadian market. Apotex objected to the admissibility of certain aspects of the Goodfield and Guthrie evidence on the basis that it was hearsay, opinion evidence, or contrary to Rule 248 of the Federal Courts Rules. I address these objections and provide a brief summary of the fact evidence below.
[48] In addition to Takeda’s fact witnesses, Apotex introduced one fact witness affidavit from Julie Szirtes, the Director of Clinical Research and Development at Apotex. Ms. Szirtes provided an affidavit attaching several documents relating to |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||| submitted as part of Apotex’s ANDS that compared the 60 mg Apo-dexlansoprazole capsules to the 60 mg DEXILANT® capsules.
(1) Dr. Vakilynejad [49] Dr. Vakilynejad joined Takeda Abbott Pharmaceuticals (TAP) in September 2000 and began investigating the PPI, lansoprazole, in late 2001. His role was as a member of the Drug Metabolism and Pharmacokinetics group. Dr. Taneja, the other co-inventor, worked in a separate department and was part of the formulation group. At the time, several PPIs including lansoprazole were already on the market; however, none were able to provide patients with a full day of therapeutic relief. To address nocturnal breakthrough events, Dr. Vakilynejad was asked by D