Merck & Co. Inc. v. Apotex Inc.

Merck & Co. Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2005-05-26
Neutral citation
2005 FC 755
File numbers
T-884-03
Decision Content
Date: 20050526
Docket: T-884-03
Citation: 2005 FC 755
Ottawa, Ontario, this 26th day of May, 2005
Present: The Honourable Mr. Justice Richard Mosley
BETWEEN:
MERCK & CO., INC.
and
MERCK FROSST CANADA & CO.
Applicants
- and -
APOTEX INC.
and
THE MINISTER OF HEALTH
Respondents
REASONS FOR ORDER AND ORDER
[1] Osteoporosis is a disease that results in bone fragility and increased risk of fractures. Fractures are the main clinical consequence of the disease and their incidence increases with age. Osteoporosis is more common in women than in men. A woman who reaches the age of 50 has a 50% chance of suffering an osteoporotic fracture in the remaining part of her life.
[2] Osteoporotic fractures cause severe and chronic pain, spinal deformity, and height loss, disability and a significant reduction in the quality of life. Women who have sustained one osteoporotic fracture often live in fear of suffering another fracture. In addition, osteoporotic fractures are associated with increased mortality. Given the widespread incidence and severity of osteoporosis, there is a strong incentive among pharmaceutical companies to develop new and effective therapies to reduce or reverse the effects of this disease.
[3] Through patent protection, Canadian society has chosen the pragmatic policy of granting patent monopolies to those individuals or companies who assume the risk of developing such new therapies, providing always that they are truly inventive. Considering the high price to consumers of allowing a monopoly, however, Canadian society also has a strong interest in limiting the length of time that an inventor can benefit from market exclusivity. As noted by Justice Binnie in Whirlpool Corp. v. Camco Inc., [2000] 2 S.C.R. 1067 at para. 37:
It is common ground that the bargain between the patentee and the public is in the interest of both sides only if the patent owner acquires real protection in exchange for disclosure, and the public does not for its part surrender a more extended monopoly than the statutory 17 years from the date of the patent grant (now 20 years from the date of the filing of the patent application). A patentee who can "evergreen" a single invention through successive patents by the expedient of obvious or uninventive additions prolongs its monopoly beyond what the public has agreed to pay.
[4] At its core, the issue in this case is whether the patentee has been granted an unjustified extended monopoly in relation to an unquestionably very effective osteoporosis treatment, through an uninventive change to the dosage regime by which it is administered to patients.
Nature of the proceedings
[5] This application was brought on May 29, 2003 under section 6 of thePatented Medicines (Notice of Compliance) Regulations, SOR/93-133 by Merck & Co. Inc. and Merck Frosst Canada & Co. (collectively hereafter "Merck") in response to a Notice of Allegation ("NOA") sent by Apotex Inc. ("Apotex") on February 25, 2003. The Minister of Health ("the Minister") is a party to this proceeding because the Minister could have issued a Notice of Compliance (NOC) allowing Apotex to market their generic drug had Merck not disputed the NOA by bringing this application. The Minister made no submissions, either in writing or in oral argument.
[6] Merck's application is for an order of prohibition against the Minister preventing the issuance of a NOC until after the expiry of the Canadian Letters Patent No. 2,294,595 ("the '595 patent"). Commencement of the application for prohibition triggers a 24-month "statutory freeze" that stops the Minister from issuing a NOC unless and until the application is dealt with by the court: paragraph 7(1)(e) and subsection 7(4) of the Patented Medicines (Notice of Compliance) Regulations. Argument in this matter was heard in the twenty-third month.
[7] The '595 patent, entitled "Method for Inhibiting Bone Resorption", was issued for Merck's osteoporosis drug, alendronate monosodium trihydrate ("alendronate" ), a member of the bisphosphonate class of bone resorption inhibitors. Alendronate is sold by Merck under the trade name of FOSAMAX® for, amongst other formulations, a once weekly administration of 70 mg tablets. Apotex wants to market a generic version of alendronate for once weekly 70 mg administration.
[8] Apotex does not dispute that its drug formulation would infringe Merck's patent, if that patent is valid. However, Apotex contends that Merck should never have been issued a patent for the once weekly alendronate tablet. Apotex submits that the patent was anticipated by the prior art; was obvious in view of the prior art to those skilled in the art; lacked utility or was insufficient and ambiguous; and was directed to a method of medical treatment. If any one of these allegations is supported by the evidence, the '595 patent is invalid.
Osteoporosis and the problem of bone resorption
[9] I have relied upon my understanding of the evidence provided by both parties' expert witnesses for the non-contentious descriptions of the nature of osteoporosis, the problem of bone resorption and the operation of bisphosphonates set out in these reasons.
[10] Bone renews itself continuously in a process called bone remodelling. Bone remodelling is carried out by basic multicellular units consisting of osteoclasts and osteoblasts, both generated in bone marrow. Osteoclasts remove old bone by a process called bone resorption, while osteoblasts form a new organic matrix at the site of resorption, which subsequently mineralizes or calcifies by a process called bone formation. Normally, the rate of bone resorption is equal to the rate of new bone formation, but in certain situations, the processes become unbalanced, resulting in various clinical conditions.
[11] Osteoporosis is caused by an imbalance between bone resorption and bone formation. Bone resorption outpaces bone formation, resulting in net bone loss and destruction of bone architecture. In women, this is partly due to the increase in bone resorption that follows the loss of estrogens at menopause. If the bone resorption activities of the osteoclasts can be suppressed by some means (without significantly inhibiting bone formation by the osteoblasts), the progress of the disease can be slowed. Alendronate has proven to be an effective therapy to accomplish the suppression of osteoclast resorption activities.
[12] Another skeletal disorder for which alendronate has proven effective as a therapy is Paget's disease. Paget's is a skeletal disease that affects one or more bones. The disease progresses slowly and leads to changes in the shape and size of affected bones and to skeletal, joint and vascular complications. In Paget's disease, there is an increase in the number and size of osteoclasts in affected sites while the rest of the skeleton remains normal. The typically very large osteoclasts induce excessive bone resorption which is associated with an increased recruitment of osteoblasts to the remodelling sites. The result is increased bone formation and therefore an overall increase in the rate of bone remodelling.
Bisphosphonates and dosing regimes
[13] Bisphosphonates are a class of compounds that have the ability to inhibit bone resorption. Bisphosphonates do not occur in nature. The first bisphosphonates were synthesized in the 19th century by German chemists. They were initially used in industrial and other non-medical settings - such as water softening and anti-scaling applications - because they are useful for inhibiting the formation of crystals. However, it was also known by the 1970s that bisphosphonates such as clodronate, pamidronate and etidronate can be useful in inhibiting bone resorption and treating bone resorption diseases, such as Paget's disease.
[14] The bioavailability of bisphosphonates is low, so a relatively large amount must be taken compared to the amount that will actually be absorbed by the gastrointestinal tract. However, once absorbed, they remain in the body for a relatively long time - up to two weeks. Bisphosphonates, therefore, have a relatively long half-life and do not degrade quickly in the human body. Bisphosphonate compounds are inherently corrosive and their oral use has long been associated with adverse gastrointestinal side effects.
[15] A number of patents have issued, both in Canada and abroad, in relation to discoveries about the bone resorption properties of bisphosphonates and more specifically, for alendronate. The "base" patent application, disclosing the use of alendronic acid as a therapy for inhibiting bone resorption was filed in 1983 (claiming priority back to 1982) by Instituto Gentili SpA, a company later acquired by Merck. Alendronate sodium was subsequently developed by Merck as an effective form of the compound with fewer adverse side effects.
[16] Canadian Patent Number 2,018,477 ("the '477 patent") was published by Merck in 1990 to cover a 10 mg oral dosage form of alendronate sodium on a daily dosing basis for the treatment of osteoporosis and a 40 mg daily unit for Paget's disease. Also in 1990 and in 1991, alendronic acid and alendronate were the subject of patents issued in the United States (U.S. patents 4,922,007 and 5,019,651). Similar patents were applied for in other jurisdictions. Alendronate in tablet form is described in U.S. patent 5,358,941 issued in 1994.
[17] In 1995, Merck received a NOC from the Minister and began marketing alendronate tablets in Canada in a 10 mg daily dosage form for the treatment of osteoporosis. To avoid gastrointestinal side effects, the dosing regime was strict. The daily tablets were to be taken at least one-half hour before the first food, beverage or medication of the day, with a full glass of plain water only and the patient was to remain upright for at least 30 minutes thereafter.
[18] It is common ground between the parties that noncompliance with Merck's dosing instructions for taking alendronate was a major cause, for a small proportion of patients, of significant adverse side effects. They differ on whether the more common effects were "pill esophagitis", a local injury to the esophagus caused by prolonged contact of the pill with the mucosal lining, or "acid reflux", a backing up of the stomach contents into the esophagus possibly leading to "Gastro-esophageal Reflux Disease" or "GERD".
[19] As a result of reports of these problems, in 1996 Merck sent what has been referred to in the evidence as a "Dear Doctor" letter that advised physicians in prescribing alendronate to emphasize to their patients the importance of following the dosing instructions and to inform them of a change in the instructions: that patients should not lie down after taking it until they had eaten the first food of the day.
[20] By 1997, the tablets were widely prescribed in Canada and abroad and while the Dear Doctor letter had led to a pronounced reduction in GI side effects, they continued to be a problem for some patients. Suggestions were put forward, by clinical researchers and others, internal and external to Merck, for solutions to address this problem. The solution seized upon by Merck and for which it received protection through the '595 patent is the subject of these proceedings.
[21] Merck argues that this was not a case of "evergreening" a soon-to-expire patent. Merck did not create the problem of GI side effects. It was faced with the problem when it became apparent from the clinical reports and responded to it by finding an inventive solution for which a patent was properly issued.
The patent in issue
[22] Merck's application was filed in Canada on July 17, 1998. The '595 patent claims priority from US provisional applications 60/053, 351 and 60/053, 535, filed on July 22 and July 23, 1997 and the UK patent applications 9717590.5 and 9717850.3, both filed in August 1997. Both parties accept the July 22, 1997 priority date. The '595 patent issued on August 21, 2001. Merck received marketing approval for FOSAMAX® 70 mg tablets from Health Canada in 1997.
[23] The U.S. patent number 5,994,329 ("the U.S. '329 patent"), the UK patent number 0 998 292 ("the U.K. '292 patent"), the Australian patent number 741818 ("the Australian '818 patent") and the European patent number EP-B-998292 cover substantially the same subject matter as the '595 patent. These patents have all been found to be invalid in those jurisdictions: Merck & Co., Inc. v. Teva Pharmaceuticals USA, Inc. 395 F.3d 1364 (2005 US App.), rev'ing 288 F.Supp. 2d 601 (2003 U.S. Dist. Del.); Teva Pharmaceutical Industries Ltd. et al. v. Istituto Gentili SpA et al., [2003] All E.R. (D) 153 (H.C.J.), aff'd [2003] All E.R. (D) 62 (C.A.); Arrow Pharmaceuticals Ltd. v. Merck & Co., Inc. 2004 FCA 1282 (F.C.A. - N.S.W.).
[24] The United States Court of Appeals for the Federal Circuit held the claims of the patent at issue invalid on the ground of obviousness in view of the prior art. Applications for a rehearing by the panel and for a rehearing en banc were denied on April 21, 2005. Merck has given notice that it will seek certiorari before the U.S. Supreme Court. The Court of Appeal in England upheld a trial level decision invalidating the comparable U.K. patent on the grounds of anticipation, obviousness and method of treatment. The earlier base patent was also found invalid. The Federal Court of Australia found Merck's Australian patent to be uninventive, as it simply altered a dosage regime and was anticipated by several pieces of prior art at issue in these proceedings.
[25] These decisions are in no way binding upon me and I have been alert to the significant differences in patent law between the jurisdictions. Nonetheless, I have found them helpful, particularly the U.K. and Australian revocation proceedings, for shedding light on the history and chronology of events in the development of Merck's alendronate patents. While the issues are not identical, having regard to the differences in law, the substantive evidence was largely the same in each of these cases.
The claims
[26] In Biovail Pharmaceuticals Inc. v. Canada (Minister of National Health and Welfare) 2005 FC 9 at paragraph 15, Justice Harrington summarized the principles drawn from two recent patent claim construction decisions of the Supreme Court of Canada: Free World Trust v. Électro-Santé Inc., [2000] 2 S.C.R. 1024 and Whirlpool Corp. v. Camco Inc., supra. A patent is notionally addressed to a person skilled in the art or science of the subject-matter and is to be read as such a person would have read it when it first became public. Claims are to be read in an informed and purposive way to permit fairness and predictability and to define the limits of the monopoly. It is only such novel features that the inventor claims to be essential that constitute the "pith and marrow" of the claim. "The key to purposive construction is therefore the identification by the Court with the assistance of the skilled reader, of the particular words or phrases in the claims that describe what the inventor considered to be the "essential" elements of his invention" (Whirlpool, supra at paragraph 45).
[27] The claims at issue in this case are for a 70 mg tablet of alendronate for oral administration weekly for the treatment of osteoporosis. Both parties acknowledge that neither oral treatment with alendronate nor its use in the treatment of osteoporosis is new. What is claimed as novel is the fact that a large once weekly dosage of alendronate has fewer adverse side effects when compared to the adverse side effects associated with an equal amount of alendronate taken daily over a one-week period. Merck argues that this was surprising and inventive, and was not obvious or anticipated by the prior art.
[28] Merck now submits, and Apotex does not dispute, that of the patent's 177, the relevant claims are numbers 35, 87, and 139.
Claim 35:
Use of a bisphosphonate according to any one of Claims 19 to 34 wherein said mammal is a human.
Claim 87:
A pharmaceutical composition according to any one of Claims 71 to 86 wherein said mammal is a human.
Claim 139:
A bisphosphonate according to any one of Claims 123 to 138 wherein said mammal is a human.
Read with the claims from which they depend, these claims are as follows:
Claim 35:
Use of alendronate monosodium trihydrate in the manufacture of a medicament for treating osteoporosis in a human wherein said medicament is adapted for oral administration as a unit dosage form comprising about 70 mg on an alendronic acid active basis according to a continuous schedule having a once-weekly dosing interval.
Claim 87:
A pharmaceutical composition useful for treating osteoporosis in a human comprising a pharmaceutically effective amount of alendronate monosodium trihydrate in association with a pharmaceutically acceptable carrier wherein said alendronate monosodium trihydrate is adapted for oral administration as a unit dosage form comprising about 70 mg on an alendronic acid active basis according to a continuous schedule having a once-weekly dosing interval.
Claim 139:
Alendronate monosodium trihydrate for use in an orally administrable unit dosage form comprising about 70 mg on an alendronic acid active basis in treating osteoporosis in a human in accordance with a continuous schedule having a once-weekly dosing interval.
[29] Each of these claims covers a 70 mg unit oral dosage of alendronate monosodium trihydrate for the treatment of osteoporosis in humans. Claim 35 addresses the use of alendronate in the manufacture of the dosage form; claim 87 addresses the dosage form per se, and claim 139 addresses alendronate for use in the dosage form.
[30] While Apotex submits that the scope of the asserted claims can be read more broadly than Merck has proposed, there is no dispute in these proceedings that they cover Merck's FOSAMAX® product or that they would cover the product Apotex wishes to market, described as follows in the NOA:
...tablets for oral administration comprising alendronate monosodium trihydrate ("AMT") in strengths of 70 mg (on an alendronic acid active basis) for treatment and prevention of osteoporosis and treatment of Paget's disease, the oral administration being according to a continuous schedule having a periodicity of once a week for the 70 mg tablet for the treatment and prevention of osteoporosis.
[31] In Biovail, supra Justice Harrington noted:
To overclaim is to lose everything. If the inventor underclaims, the court will not broaden the monopoly in the interests of the "spirit" thereof. This often, as in this case, results in layers of claims, each limitation serving as a potential safety net so that if the broadest claims fall, the monopoly may be saved in part by the more modest claims.
The '595 patent is also written in layers. However, it is not the broadest claims that are in issue here, but claims more limited and specific, in particular, those that describe the 70 mg alendronate tablet for once weekly administration. In this NOC proceeding, Apotex is not concerned to attack every claim of the '595 patent, but only those that stand in the way of it selling a generic product that would otherwise infringe certain of the claims.
[32] The parties agree that there is nothing novel in the use of oral bisphosphonates, including alendronate, to treat osteoporosis. It is only the proportionally higher dose and frequency of dosing to meet the goal of reducing adverse gastrointestinal side effects - 70 mg once per week - that is alleged to be the patentable subject-matter.
Burden of proof
[33] Applications under the Patented Medicines (Notice of Compliance) Regulations are administrative proceedings for the purpose of determining whether the Minister may issue a NOC. Merck is required to establish, on a balance of probabilities, that the allegations in Apotex's NOA are not justified. In establishing that the allegations are not justified, the Applicants are entitled to rely upon the statutory presumption of validity found in subsection 43(2) of the Patent Act R.S.C. 1985, c. P-4; Eli Lilly and Co. v. Apotex Inc. (1995), 60 C.P.R. (3d) 206 at 216 (F.C.T.D.), aff'd (1996), 66 C.P.R. (3d) 329 (F.C.A.); Bayer Inc. v. Canada (Minister of National Health and Welfare) (2000), 6 C.P.R. (4th) 285 (F.C.A.).
[34] Apotex, having made the allegations in the NOA, has the burden of putting sufficient evidence "in play" to present issues for examination: Eli Lilly & Co. v. Nu-Pharm Inc., [1996] F.C.J. No 904 (F.C.A.); (1996), 69 C.P.R. (3d) 1.
[35] As reiterated by the Federal Court of Appeal in Procter & Gamble Pharmaceutical Canada Inc. et al v. Genpharm Inc. et al, 2004 (FCA) 393 (F.C.A.), the evidentiary burden on a generic pharmaceutical firm alleging patent invalidity in a prohibition application remains proof on a balance of probabilities.
[36] If this court finds that the allegations in the Notice of Allegation are not justified, it must grant an order prohibiting the Minister from issuing an NOC until after the expiration of the '595 Patent: Patented Medicines (Notice of Compliance) Regulations, subsection 6(2).
Evidence
[37] Several volumes of evidence were filed by the parties to this application. In support of its application, Merck initially submitted affidavits from the following individuals:
Professor Socrates E. Papapoulos, a Professor of Medicine, Consultant Physician and the Director of Bone and Mineral Research at the Department of Endocrinology and Metabolic Disease of the Leiden University Medical Centre in Holland, tendered as a witness able to interpret the '595 patent and comment on the knowledge of the skilled practitioner in the field (or as an expert in bisphosphonates and clinical osteoporosis treatment - as found in the US Dist. Ct.).
Dr M. Brian Fennerty, Professor of Medicine and the Section Chief of Gastroenterology at the Department of Internal Medicine, Section of Gastroenterology at Oregon Health & Science University in Portland, Oregon, tendered as an expert gastroenterologist;
W.H. Guy Saheb, Director of Regulatory Affairs for Merck Frosst Canada & Co. who attached various documents related to the status of alendronate in Canada.
[1] Apotex submitted affidavits from the following individuals:
Professor Juliet Elizabeth Compston, Professor of Bone Medicine, Department of Medicine, University of Cambridge School of Medicine and Honorary Consultant Physician, Addenbrooke's Hospital, Cambridge, tendered as an expert in bone physiology and disease;
Dr. Richard B. Mazess, Emeritus Professor of Medical Physics at the University of Wisconsin, Madison (retired) and until 2000, Chair, President and Chief Executive Officer of Lunar Corporation, Inc., described as the major provider of medical diagnostic systems for the assessment of osteoporosis and metabolic bone diseases and for orthopedic applications. Also a consultant to the pharmaceutical industry in relation to osteoporosis drugs, and the author and editor of Lunar's publication, Lunar News. Tendered as an expert in the diagnosis and treatment of bone diseases, particularly osteoporosis and renal osteodystrophy and to provide direct evidence of events occurring in 1996 and 1997;
Dr. David Markowitz, is a physician specializing in gastroenterology and an Assistant Professor of Clinical Medicine at Columbia University, New York, tendered as an expert in gastroenterology;
Dr. Michael Mayersohn is a Professor of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, tendered as an expert in pharmacokinetics, biopharmaceutics and pharmaceutics;
Dr. Robert S. Langer is the Kenneth J. Germeshausen Professor of Chemical and Biomedical Engineering at MIT; Department of Chemical Engineering, Whitaker College of Health Sciences, Technology and Management; and the Harvard-MIT Division of Health Sciences and Technology, tendered as an expert in pharmaceutics and pharmaceutical formulation technology, including the formulation of bisphosphonate drugs;
David Weissburg is an independent business consultant who was a marketing and sales employee from July 1994 to February 2001 at the Lunar Corporation;
Franco A. Tassone is an employee of Parcels Inc., the copy service for the United States District Court for the District of Delaware. He was asked to obtain copies of publicly available documents from the U.S. trial of Merck & Co., Inc. v. Teva Pharmaceuticals USA, Inc., supra and attached them to his affidavit.
[2] Merck was given leave to file reply evidence and did so with the following affidavit:
Gerald Devlin is Senior Attorney, Intellectual Property Litigation for Merck & Co. Inc., with primary responsibility for the coordination of the Merck alendronate litigation worldwide. He attaches various affidavits and cross-examination transcripts from the Australian proceedings in Arrow Pharmaceuticals Ltd. v. Merck & Co., Inc., supra; excerpts from the trial transcripts in the U.K. proceedings in Teva Pharmaceuticals Industries Ltd. v. Istituto Gentili SpA, supra and from the U.S. trial in Merck & Co., Inc. v. Teva Pharmaceuticals USA, Inc., supra; as well as a deposition transcript from the proceedings in the U.S. trial.
Merck Motion to Strike Apotex Affidavits
[3] At the outset of the hearing of this application, Merck renewed a motion to strike Apotex affidavits. An initial motion to strike the Tassone, Weissburg and Mazess affidavits was decided by Prothonotary Lafrenière on June 21, 2004. He ruled that the relief sought was premature, in the absence of special circumstances, and that evidentiary determinations should be left to the applications judge. The motion was dismissed without prejudice to Merck to seek leave to file reply evidence. Leave to file reply evidence was granted in a further order by the Prothonotary on July 13, 2004 resulting in the filing of the Devlin affidavit described above.
[41] Merck filed a fresh motion on April 6, 2005 seeking to have struck, in addition to the three affidavits addressed in the June 2004 motion, the affidavits of Drs. Langer and Mayersohn. I gave an oral ruling on the motion before proceeding to hear the merits of the application.
[42] Merck argued that the impugned affidavit evidence should not be admitted primarily on the grounds that:
1. the Apotex affiants were not properly qualified to give opinion evidence in the several areas of knowledge to which they deposed.
2. The evidence given was not relevant to the determination of the issues that are before the court in this NOC proceeding.
[43] Applying the principles enunciated by the Supreme Court of Canada in R. v. Mohan [1994] 2 S.C.R. 9 at para. 17, namely: (a) relevance; (b) necessity in assisting the trier of fact; (c) the absence of any exclusionary rule; and (d) a properly qualified expert, I concluded that the opinion evidence proffered by Apotex was admissible.
[44] Relevance is a threshold requirement for any evidence. Logically relevant evidence may be excluded if its probative value is overborne by its prejudicial effect, if the time required is not commensurate with its value or if it can influence the trier of fact out of proportion to its reliability (Mohan at para. 18).
[45] Expert evidence, to be necessary, must likely be outside the experience and knowledge of a judge or jury and must be assessed in light of its potential to distort the fact-finding process. Necessity should not be judged by too strict a standard. Expert evidence can be excluded if it falls afoul of an exclusionary rule of evidence separate and apart from the opinion rule itself, such as the hearsay rule (Mohan at paras. 21-23).
[46] There are no specific credentials that potential experts must have in order to be admitted
as experts by the Court. Opinion evidence may be given by a witness "who is shown to have acquired special or peculiar knowledge through study or experience in respect of the matters on which he or she undertakes to testify" (Mohan at para. 27). This echoes statements by the court in R. v. Marquard, [1993] 4 S.C.R. 223 at para. 35, citing R. v. Beland, [1987] 2 S.C.R. 398 at para 16, holding that "[t]he only requirement¼ is that the expert witness possesses special knowledge and experience going beyond that of the trier of fact".
[47] As Sopinka, Lederman and Bryant state in The Law of Evidence in Canada (1992) at 536-7,
The admissibility of [expert] evidence does not depend upon the means by which that skill was acquired. As long as the court is satisfied that the witness is sufficiently experienced in the subject matter at issue, the court will not be concerned with whether his or her skill was derived from specific studies or by practical training, although that may affect the weight to be given to the evidence.
[48] With respect to Drs. Langer and Mayersohn, Merck did not object to these affidavits when it brought its earlier motion. It contends that the weakness of their qualifications relevant to the issues in this proceeding only became apparent on cross-examination. Merck now objects to the reception of their evidence as they are not medical doctors and argues that the issues upon which they were asked to provide expert opinions, as characterized by Merck, relate solely to the medical fields of gastroenterology and endocrinology.
[49] I do not agree with Merck's contention that these two witnesses were asked to comment on matters beyond their expertise. Dr. Langer's relevant and very impressive qualifications are as an expert with respect to pharmaceutical technology involving the formulation of drugs, including bisphosphonate drugs. His opinion is tendered with respect to formulation issues and thus does not exceed his expertise in pharmaceutics.
[50] Dr. Mayersohn's qualifications are as an expert in pharmacokinetics, biopharmaceutics and pharmaceutics. His testimony about the equivalence of 70 and 80 mg of alendronate due to the low bioavailability of the drug was never questioned on cross-examination. Apotex objected to Merck questioning this evidence in oral argument as contravening the rule in Browne v. Dunn (1893), 6 R. 67 (H.L.). I was satisfied the evidence was highly relevant, uncontradicted and admissible.
[51] Dr. Mazess's affidavit primarily describes events surrounding the publication of his views on alendronate in the newsletter Lunar News produced by the corporation he had founded to manufacture and distribute bone densitometry equipment used in the diagnosis and treatment of skeletal disease. Merck objects to Dr. Mazess's being permitted to comment on the evidence of Drs. Papapoulos and Fennerty as he is not a physician. It also objects to the relevance of his testimony about meetings and correspondence between Dr. Mazess and Merck representatives concerning dosing regimens for bisphosphonates. Finally, it submits that his writings in Lunar News speak for themselves and he should not be explaining their meaning.
[52] Dr. Mazess, through his academic and business careers, has gained considerable knowledge about bone diseases, particularly osteoporosis. While he is not qualified to treat patients, that does not preclude him, in my view, from commenting on treatment regimes for bone disorders. It is apparent from the record that his utterances in the Lunar News carried considerable weight in the pharmaceutical and clinical worlds. Drs Papapoulos and Fennerty comment at length on his writings in their evidence. There was ample reason, in my view, to think that Dr. Mazess' comments on their evidence would be helpful in determining the issues in this matter.
[53] With regard to Dr. Mazess' evidence about correspondence and meetings with Merck staff, I was satisfied that it was relevant and admissible. Merck is correct that, as possible prior art references, his writings in Lunar News must speak for themselves. However, I was also satisfied that he could properly give evidence as to the background and context of those writings. Accordingly, his evidence was admissible subject to argument about its weight.
[54] The Weissburg affidavit does not contain expert opinion evidence but rather describes events and hearsay statements made by others. Apotex relies upon those statements not for their truth but for the fact they were made. As determined by the Supreme Court of Canada in R. v. Khan, [1990] 2 S.C.R. 531 and subsequently applied to civil cases by a number of courts, hearsay is not inadmissible if found to be credible and reliable: e.g., Dye v. Morehouse (1999), 45 C.P.C. (4th) 329 (B.C.S.C.), E.S. v. D.M. (1996), 143 Nfld. & P.E.I.R. 192 (Nfld. S.C.). I allowed this evidence for the limited purpose of establishing that certain events occurred and statements were made and not for the truth of the contents of those statements.
[55] Attached to the Tassone affidavit are copies of documents filed by the defendant in the U.S. District Court proceedings. Apotex' object in submitting this material was, in part, to refute Drs. Papapoulos' and Fennerty's evidence that the prior art references included in the NOA would not have been relied upon to demonstrate the safety of high doses of alendronate in osteoporosis patients. Included in the Tassone material is Merck's submission to the United States Federal Drug Administration ("FDA") for approval of the 70 mg dosage of FOSAMAX®, which indicates that Merck relied upon the same prior art references to show that a dose of that size would be safe and effective.
[56] Merck objected to its reception on the ground that the attached documents had not been proven or authenticated for the purpose of this proceeding in accordance with Canadian evidentiary requirements for documents from foreign courts: section 23, Canada Evidence Act R.S. 1985, c. C-5 ("CEA"). Further, Merck argued that the submission of some six volumes of evidence from the U.S. proceedings was an impermissible attempt to enlarge upon the allegations in the NOA. Merck conceded that if the Tassone affidavit was inadmissible, the same was true of the attachments to the Devlin affidavit which consisted, similarly, of evidence from a foreign case.
[57] Dr. Yates, the principal named inventor of the '595 patent, was no longer an employee of Merck when this application was initiated and refused to provide evidence, according to the Devlin affidavit. Merck seeks to introduce portions of his evidence from the Australian, United Kingdom, and United States proceedings, through Mr. Devlin's affidavit, to reply to the evidence of Dr. Mazess and Mr. Weissburg about a meeting they attended with Merck principals, including Dr. Yates, on May 21, 1997. Mazess and Weissburg had given evidence about that meeting in the Australian case similar to their evidence in this proceeding. According to Mr. Devlin, the other Merck participants either had no recollection of the discussion or were unavailable to provide evidence. Thus Merck submits, the relevant portions (paragraphs 94-116) of Dr. Yates' affidavit in the Australian proceedings, dated March 22, 2004, are the best evidence it has to dispute Dr. Mazess' and Mr. Weissburg's accounts of what was said at the May 1997 meeting.
[58] Dr. Yates was cross-examined on his affidavit in the Australian proceeding and that testimony was also attached to the Devlin affidavit. I note that at paragraphs 70-73 of his reasons for judgment, Judge Gyles of the Federal Court of Australia, accepted the evidence of Dr. Mazess and Mr. Weissburg as to what transpired at the May 1997 meeting, also tested under cross-examination, and rejected that of Dr. Yates as implausible. Dr. Yates' evidence was accepted in the U.S. District Court proceeding and he was described as "fair" by Justice Jacob in the U.K. proceedings. Nonetheless, Justice Jacob found that Merck's own contemporaneous documents were a more significant record of what was known by Merck staff, including Yates, in 1996-97. Those documents, including internal e-mail and correspondence, are reproduced in detail in Justice Gyles' reasons and led to his finding that it "stretches credulity" that Dr. Yates was unaware of the content of the Lunar News articles tabled at that meeting.
[59] In this proceeding, I was not satisfied that I could accord any greater weight to the Yates' evidence than that given it by Justice Gyles.
[60] Turning to the Tassone affidavit, in my view, it was improper for Apotex to use that means to submit evidence filed in a foreign proceeding as evidence in this case. Authentication by a clerk employed by a copying service does not meet the requirements of CEA section 23. The attachments to the affidavit constituted six volumes of material. Apotex made no real effort to explain how most of this material would be relevant and admissible. Even if it was properly authenticated, the question of its relevance and admissibility had to be established: Merck & Co., Inc. v. Apotex Inc., [1998] 3 F.C. 400 (T.D.).
[61] I accept that section 23 is not the sole procedure by which foreign evidence can be proven. Relevance and admissibility can be established by other means, particularly where there is no doubt about the authenticity of the appended material: Suchon v. Canada (2002), 291 N.R. 250. There was no real doubt of authenticity in this case. But I think it was unnecessary and excessive to dump the U.S. trial evidence into the record in this manner and accordingly, I ruled that most of it was inadmissible. I would strongly discourage any repetition of this practice.
[62] Several documents attached to the Tassone and Devlin affidavits were identified in the course of the examination of other affiants in these proceedings. I was satisfied that their authenticity had been sufficiently established. Accordingly, I allowed any document, so identified, to be relied upon as evidence by both parties to this application. Just one proved to be of any significance: Merck's new drug submission to the US Food and Drug Administration (FDA) concerning the 70 mg formulation.
[63] Apotex questions the credibility and reliability of Merck's principal witnesses, Drs. Papapoulos and Fennerty, and argues that both selectively reviewed the prior art references, advancing information helpful to Merck's case, while ignoring that which would be unhelpful. Apotex points to the near identity of much of their affidavit evidence, their long-standing and continuing roles as Merck consultants, and contends that neither has the necessary independence required of an expert witness. For these reasons, Apotex argued, less weight should be accorded their evidence.
[64] Expert evidence presented to the Court should be, and should be seen to be, the independent product of the expert, uninfluenced as to form or content by the exigencies of litigation: Whitehouse v. Jordan [1981] 1 All ER 267 (H.L.) at 276. I had little difficulty coming to the conclusion in reading the evidence in this case that where there was a conflict between the evidence of the Merck witnesses and the Apotex witnesses, I preferred the latter. While Dr. Papapoulos is eminently well qualified in his field, I found his evidence, as it was characterized by Justice Jacob in the UK proceedings, to be "rigid" and "extreme" when he was confronted on cross-examination with prior art references inconsistent with Merck's position. As for Dr. Fennerty, it was apparent from his truculence in answering questions on cross-examination that he had crossed the line between independence and advocacy. I accorded little weight to his evidence.
[65] Merck argues that the evidence of those who were directly engaged in the skilled art at the relevant times should be preferred. In this case, it argues, the skilled arts are medical treatment for osteoporosis and gastroenterological conditions and, thus, the Court should give greater weight to the evidence of those who practised in those fields at