Merck Sharp & Dohme Corp. v. Pharmascience Inc.

Merck Sharp & Dohme Corp. v. Pharmascience Inc.
Court (s) Database
Federal Court Decisions
Date
2022-04-11
Neutral citation
2022 FC 417
File numbers
T-419-20
Decision Content
Date: 20220411
Docket: T-419-20
Citation: 2022 FC 417
Toronto, Ontario, April 11, 2022
PRESENT: The Honourable Madam Justice Furlanetto
BETWEEN:
MERCK SHARP & DOHME CORP.
AND MERCK CANADA INC.
Plaintiffs
and
PHARMASCIENCE INC.
Defendant
PUBLIC JUDGMENT AND REASONS
(Identical to the Confidential Judgment and Reasons
Issued on March 28, 2022)
[1] This judgment arises from a patent infringement action brought under subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [PMNOC Regulations]. The patent at issue is Canadian Patent No. 2,529,400 [400 Patent]. The innovative drug relating to the action is JANUVIA®, which is used to treat type 2 diabetes.
[2] Merck Canada Inc. is the “first person” in accordance with the PMNOC Regulations. Merck Sharp & Dohme Corp. is the registered owner of the 400 Patent and is a party to the action pursuant to subsection 6(2) of the PMNOC Regulations.
[3] The Plaintiffs [collectively, Merck] claim that the making, constructing, using or selling by the Defendant Pharmascience Inc. [PMS] of its sitagliptin phosphate tablets in strengths of 25 mg, 50 mg, and 100 mg in accordance with PMS’ Abbreviated New Drug Submission will infringe at least one of claims 4-7, 19, 20, 22, 24 and 26 [Asserted Claims] of the 400 Patent. PMS asserts in defence that the 400 Patent is invalid for obviousness and/or insufficiency.
[4] The parties agreed to a stipulation that the only issue to be adjudicated at trial was the validity of the 400 Patent. The stipulation provided that should the court find any of the Asserted Claims of the 400 Patent to be valid, the Order sought by the Plaintiffs in the action should issue with the relief requested by the Plaintiffs.
[5] For the reasons that follow, I find the Asserted Claims of the 400 Patent valid and that the relief sought should be ordered accordingly.
I. Background
[6] The 400 Patent is listed on the Patent Register in association with the medicine sitagliptin phosphate monohydrate. Sitagliptin exists as a dihydrogen phosphate salt in crystalline monohydrate form in the tablets sold as JANUVIA®. Sitagliptin is the active ingredient in the drug product.
[7] In type 2 diabetes, cells develop insulin resistance such that the presence of insulin in the blood does not stimulate cells to take up glucose, or the pancreas does not produce enough insulin to overcome the resistance. Thus, glucose accumulates in the blood.
[8] Sitagliptin inhibits dipeptidyl peptidase-4 [DPP-4, DP-IV or DPP-IV], an enzyme that degrades one of the peptides (Glucagon-Like Peptide-1 [GLP-1]) that stimulates the secretion of insulin. This inhibitory effect modulates the level of insulin and glucose in the blood. Sitagliptin acts only when glucose is elevated in the bloodstream, thereby reducing the risk of hypoglycemia caused by low glucose levels.
[9] In 2006, JANUVIA® became the first DPP-4 inhibitor approved by the United States Food and Drug Administration [FDA] for the treatment of diabetes. It was approved by Health Canada in 2007.
[10] This action initially alleged infringement of three patents - the 400 Patent, as well as two other patents listed on the Patent Register in association with sitagliptin phosphate monohydrate – Canadian Patent Nos. 2,536,251 [251 Patent] and 2,450,740 [740 Patent]. However, the allegations in respect of the 251 Patent and 740 Patent were discontinued prior to trial.
[11] The 740 Patent is the corresponding Canadian national phase patent of Patent Co‑operation Treaty [PCT] patent application WO 03/004498 [WO498]. WO498 discloses a genus of compounds that includes the chemical compound now known as sitagliptin. It specifically exemplifies sitagliptin, amongst other compounds, both as a free base and hydrochloride salt and refers to other salts and crystalline forms as being within its scope. WO498 is referenced in the 400 Patent as discussed further below.
[12] The 400 Patent is directed to the dihydrogenphosphate [DHP] salt of sitagliptin and its crystalline monohydrate form, a process for making the DHP salt of sitagliptin as a crystalline monohydrate, its formulation as a pharmaceutical composition and its use to treat diseases affected by the inhibition of DPP-4, such as type 2 diabetes.
II. Witnesses
[13] Seven experts gave testimony at the trial; three experts were called by PMS and four by Merck. The parties agreed to stipulations as to the expertise of all expert witnesses.
A. PMS Experts
[14] Dr. Vassil Elitzin obtained his Ph.D. from Stanford University in 2004, specializing in the synthesis of naturally occurring chemical compounds. He is currently the Director of Chemistry, Manufacturing and Controls and Chief Chemist at LI-COR Biosciences. He was previously a principal scientist in the Chemical Development group at GlaxoSmithKline. His work focuses on the development of active pharmaceutical ingredients and dosage forms from discovery to commercialization. Dr. Elitzin was admitted as an expert in synthetic organic chemistry and compound characterization, with particular expertise in developing, making, and characterizing different salt and crystalline forms of compounds.
[15] Dr. Elitzin provided an opinion on whether the Asserted Claims of the 400 Patent would have been obvious to the person skilled in the art [PSA]. He also reviewed some of Merck’s internal documents and provided an opinion on the course of conduct taken by the inventors towards obtaining the DHP salt of sitagliptin and the crystalline monohydrate.
[16] PMS highlights Dr. Elitzin’s experience in industry; however, he was not active in industry at the relevant date for assessing obviousness of the 400 Patent. His observations as to what was happening at the time are limited to his understanding from the literature and from lectures attended during his Ph.D. studies. While in general I found Dr. Elitzin’s testimony to be helpful to the Court, as highlighted below, he was selective in accepting statements from leading authorities as to the common general knowledge in the art, some of which came from publications he had relied on for his own report. I have therefore approached his evidence in those areas with caution and in some instances have preferred the evidence of Merck’s experts over that of Dr. Elitzin in those areas.
[17] Dr. Mark Hollingsworth is an Emeritus Research Professor at Kansas State University. He has worked in academia since 1987, first as an Assistant Professor in the Chemistry Department at the University of Alberta, then as an Assistant Professor in the Chemistry Department at Indiana University, and later as an Associate Professor in the Chemistry Department at Kansas State University, where he worked from 1998 to August 2021 when he retired. He has taught and lectured extensively on solid state chemistry and the characterization of crystalline forms. Dr. Hollingsworth was admitted as an expert in organic chemistry, particularly solid state organic chemistry, including the characterization of the solid state of organic compounds and their properties, with expertise in analytical techniques for characterizing organic solids and the crystallization of organic solids. He was further qualified as an expert in the fields of crystal growth and crystal engineering with expertise in analytical techniques for characterizing organic solids and the crystallization of organic and inorganic compounds, including by x-ray crystallography.
[18] Dr. Hollingsworth provided opinions on claims 4-7, 19, 20 and 24 of the 400 Patent and on the elements of the test for obviousness relating to those claims, both before and after a review of some of Merck’s internal documents. He also analyzed Merck’s raw data files relating to the x-ray powder diffraction [XRPD] characterization work done during Merck’s polymorph screening and provided an analysis of this work, including with respect to the limitations found in claims 5-7 of the 400 Patent. I found Dr. Hollingsworth to be a knowledgeable and credible witness.
[19] Dr. James E. Foley is a retired clinical research director with experience in drug development relating to diabetes treatments. He has worked in the field of diabetes since the 1970s and began working on DPP-4 inhibitors in 1995. Dr. Foley was involved in the evaluation of the Novartis candidate drug DPP-728 as a DPP-4 inhibitor in patients, and in the clinical development and profiling of LAF-237 (vildagliptin) as a DPP-4 inhibitor. Dr. Foley was admitted as an expert in pharmacology and drug development, including specifically the history of development of DPP-4 inhibitors as a treatment for diabetes. He was further admitted as having expertise in drug discovery and development, and in lead compound identification.
[20] Dr. Foley provided background on the development of Novartis’ DPP-728 and vildagliptin compounds as DPP-4 inhibitors. He gave opinions on claims 22 and 26 of the 400 Patent and on the elements of the test for obviousness as it related to those claims. I found Dr. Foley to be a knowledgeable and credible witness.
B. Merck Experts
[21] Dr. James Wuest is a Professor of Chemistry at the Université de Montréal where he has worked since 1981. He is also the Canada Research Chair in Molecular Materials. He was previously an Assistant Professor of Chemistry at Harvard University and a Research Fellow at Harvard Medical School. Dr. Wuest specializes in molecular design and synthesis of solid state forms, including salt forms, crystalline forms and their polymorphs. He has extensive experience synthesizing compounds and characterizing their resulting structures and properties. Dr. Wuest was admitted as an expert in molecular design and synthesis, with particular expertise in solid state organic chemistry, including the characterization of the solid state of organic compounds and their properties, with expertise in analytical techniques for characterizing organic solids and the crystallization of organic compounds.
[22] Dr. Wuest provided opinions on claims 4-7, 19, 20, 22 and 24 of the 400 Patent and whether those claims would have been obvious at the relevant date. He also responded to the opinions of Drs. Elitzin and Hollingsworth.
[23] PMS highlights that Dr. Wuest has never worked on a drug development team. I note that this criticism also applies to PMS’ own expert, Dr. Hollingsworth. While Dr. Wuest’s opinions, like those of Dr. Hollingsworth, must be considered with this limitation in mind, where opinions relate to scientific principles and information that can be assessed from knowledge of the techniques used and literature available at the time, it does not diminish the weight to be attached to the opinions.
[24] PMS further highlights that Dr. Wuest has testified in a number of cases for innovators, including some for Merck, and was retained in litigation in the U.S. relating to the corresponding patent to the 400 Patent. It suggests that Dr. Wuest has ties to Merck because Dr. Wuest has met Merck’s inventor Dr. Wenslow and had planned to give a lecture at Dr. Wenslow’s company. I find these criticisms unpersuasive. Dr. Wuest does not receive any financial support for his research from Merck. His involvement in past litigation is not uncommon for an accomplished scientist in the field and he is not currently involved in the U.S. proceeding on the corresponding 400 Patent. As made clear during his cross-examination, Dr. Wuest has not discussed this litigation or sitagliptin with Dr. Wenslow and his lecture at Dr. Wenslow’s company is unrelated to the litigation. There is no basis on the evidence before me to suggest that Dr. Wuest is not an independent, unbiased witness.
[25] In general, I found Dr. Wuest to be a knowledgeable witness who was of assistance to the Court. However, his view of certain background passages in the 400 Patent relating to inhibitory activity appeared strained and his positon as to whether he could speak to issues involving the potency of compounds and their therapeutic use unclear. I have therefore approached his evidence on those issues with caution.
[26] Dr. Martyn C. Davies is an Emeritus Professor and pharmaceutical consultant who recently retired from the University of Nottingham where he served in various roles, including as the Head of the Pharmaceutical Sciences and Pharmacy School. He has worked for many years as a consultant and has significant practical experience developing, formulating and characterizing pharmaceutical formulations and advanced drug delivery systems. Dr. Davies was admitted as an expert in pharmaceutical formulation and drug delivery, including with respect to pre-formulation assessment, formulation design and development, manufacture, characterization, testing and analysis, including for solid oral dosage forms.
[27] Dr. Davies provided an opinion on the issue of obviousness with respect to claims 4-7 and 22 of the 400 Patent from the perspective of the skilled formulator. He also responded to the opinion of Dr. Elitzin on those claims from this perspective.
[28] PMS highlights Dr. Davies history with pharmaceutical litigation on behalf of innovators. It also suggests that Dr. Davies attempted to bolster the evidence of other Merck witnesses during his testimony. PMS refers to two passages during Dr. Davies cross-examination where Dr. Davies refers to testimony of other Merck witnesses when addressing a question asked. In one instance, the testimony refers to Dr. Wenslow and in the other instance Dr. Wuest. While I agree with PMS’ criticism of the first instance, the second instance appeared to result from Dr. Davies being asked about an area not covered by his expertise. In any event, I do not consider these two passages to pervade the remaining testimony provided by Dr. Davies. In my view, Dr. Davies was a knowledgeable witness and I consider his testimony to be of assistance to the Court.
[29] Dr. Richard E. Lewanczuk is an endocrinologist and the Senior Medical Director of Health System Integration for Alberta Health Services. He has held various roles in that organization since the 1990s. He is also a professor of medicine and physiology at the University of Alberta with a research background in diabetes, hypertension, chronic disease management, therapeutic natural products, and drug-disease interactions. Dr. Lewanczuk was admitted as an expert in internal medicine and endocrinology with extensive expertise in managing and treating type 2 diabetes. Dr. Lewanczuk was further qualified as an expert in the conduct of clinical trials for pharmaceutical agents for use in the treatment of type 2 diabetes.
[30] Dr. Lewanczuk provided background on type 2 diabetes and the history of different therapies used to treat type 2 diabetes, including the role and impact of JANUVIA® and other Merck drug products. Dr. Lewanczuk was also asked to respond to Dr. Foley’s opinions regarding obviousness and claims 22 and 26 of the 400 Patent.
[31] PMS criticizes Dr. Lewanczuk for failing to disclose that he had received honoraria from Merck for sitting on an advisory panel and giving a lecture. This information was readily acknowledged by Dr. Lewanczuk on cross-examination, where he clarified that honoraria from pharmaceutical companies are common and thus are not included in his CV due to the abundance in which they are provided. Dr. Lewanczuk confirmed that he had never received research support from Merck. I do not consider the omission of the honoraria to affect Dr. Lewanczuk’s credibility or suggest any form of bias. Overall, I viewed Dr. Lewanczuk as a forthright witness who readily acknowledged and helped to clarify these omissions.
[32] PMS also criticized Dr. Lewanczuk for providing views on salt selection and whether sitagliptin was previously disclosed in the prior art, when this evidence was admittedly outside of his expertise. I agree that there were a few instances where Dr. Lewanczuk strayed outside his expertise, principally when seeking to respond to comments on these same issues made in Dr. Foley’s report. I have not given those aspects of his opinion any weight when reaching my decision.
[33] While I consider Dr. Lewanczuk’s report to have went into unnecessary detail in certain areas, his comments on claims 22 and 26 and his response to Dr. Foley’s opinion on those claims were of assistance to the court.
[34] Dr. William R. Roush is the Executive Vice President of Chemistry of IFM Therapeutics where he is responsible for leading drug discovery medicinal chemistry research activities. He has over 40 years of experience in organic and medicinal chemistry and is an Emeritus Professor of Chemistry at the Scripps Research Institute. Between 2005-2017 he was the former Executive Director of Medicinal Chemistry in the Drug Discovery Division of Scripps’ Translational Research Institute where he directed research for optimizing drug candidates for drug discovery projects internal to Scripps. Prior to 2017, he also acted as a consultant to pharmaceutical and biotechnology companies. Dr. Roush was admitted as an expert in organic and medicinal chemistry, and specifically in the areas of synthesis and characterization of organic compounds. Dr. Roush was further qualified as having expertise in drug discovery and development and in lead compound identification.
[35] Dr. Roush was asked to opine on the 400 Patent and whether the PSA would have chosen to investigate sitagliptin or any of its salts as a potential DPP-4 inhibitor for treating type 2 diabetes as of June 24, 2003, without having the benefit of the 400 Patent. He was also asked to respond to Dr. Foley. In doing so, he provides opinions on claims 4, 22 and 26 of the 400 Patent and whether claims 22 and 26 are obvious. In providing these opinions, Dr. Roush conducts a prior art search and reviews the steps a medicinal chemist would take to identify a lead candidate for drug development.
[36] PMS asserts that Dr. Roush has extensive ties to brand pharmaceutical companies. It highlights that at the relevant date Dr. Roush was in academia and not in industry. PMS criticizes Dr. Roush for asserting that he had acquired some expertise on DPP-4 inhibitors after preparing his report and for dedicating a portion of his report to the success of JANUVIA®, while admittedly having no personal knowledge of that success.
[37] I agree these are critiques that can be made of Dr. Roush’s evidence. However, I do not agree that Dr. Roush presented as a biased witness or that these critiques establish that the substance of Dr. Roush’s evidence is not credible. Further, I do not consider Dr. Roush’s comments on the process involved in lead candidate identification to be affected by the date of his experience. The bigger problem the Court has with Dr. Roush’s evidence is that aspects of it are from the perspective of the medicinal chemist who is evaluating and directing Structure Activity Relationship [SAR] studies on compounds of the prior art to advance the next stages of research. As will be discussed further below, this is not a focus of the 400 Patent. While I will need to consider whether the PSA would be motivated to move from WO498 to the inventive concept of the 400 Patent, I do not consider a separate medicinal chemist to be a necessary member of the skilled team interpreting the 400 Patent. As such, certain aspects of Dr. Roush’s evidence are not relevant to my analysis.
C. Fact Witnesses
[38] There were two fact witnesses introduced by the Plaintiffs. The first, Christine Vincent, is a law clerk with the solicitors for the Plaintiffs. She provided an affidavit attaching several documents obtained from Health Canada’s website associated with generic submissions involving sitagliptin. The affidavit also attached pleadings from the Merck Sharp & Dohme Corp v JAMP Pharma Corporation T-667-20 proceeding. The significance of these pleadings to the present action was not made known to the Court through the Plaintiffs’ submissions. Ms. Vincent’s affidavit was accepted and it was agreed that she would not be cross-examined.
[39] The second fact witness, Dr. Robert M. Wenslow, is one of the inventors of the 400 Patent. Dr. Wenslow was the discovery representative for the Plaintiffs and, on agreement of the parties, was the only inventor examined under Rule 237(4) of the Federal Courts Rules, SOR/98‑106 [Federal Courts Rules].
[40] Dr. Wenslow joined Merck in 1997 as a Senior Research Chemist in the Process Research & Development Department. At the time of sitagliptin’s development, Dr. Wenslow led a team of scientists in the Physical Measurements group, which was then part of the Analytical Research department, and directly supervised the work of his co-inventors Drs. Russell Ferlita and Alex Chen, as well as Yaling Wang.
[41] The Physical Measurements Group formed part of the broader multi-disciplinary DPP-4 project team that was involved in sitagliptin’s development. The primary responsibility of the Physical Measurements Group was to perform solid state characterization of candidate drug compounds, including XRPD, solid state nuclear magnetic resonance [NMR] spectroscopy, differential scanning calorimetry [DSC] and thermogravimetric analysis [TGA]. As a lead member of the group, Dr. Wenslow regularly discussed and collaborated with the broader DPP-4 project team and reviewed research reports and data generated on sitagliptin, including those of the remaining co-inventors Drs. Karl Hansen, Ivan Lee, Stephen Cypes and Vicky Vydra.
[42] As admitted by Dr. Wenslow, he was not directly assigned to the sitagliptin project until March/April 2002, around the time the phosphate salt was chosen for further development (Trial Transcript [TT], Volume [V]4, Page [P]:349 Line [L]:8-13; TT V5, P:190 L:18). As one of his primary responsibilities upon joining the group, he reviewed the development work up to that point and had discussions with other members of the DPP-4 group to familiarize himself with the work that had been completed prior to his joining the project (TT V4, P:349 L:16 – P:350 L:1).
[43] Dr. Wenslow provided an overview of the invention story, both through oral testimony and through affidavit evidence, including with reference to various documents outlining the history of the invention. PMS accepted all but one of the documents as being authentic and the vast majority for the truth of their contents by way of joint agreement of the parties.
[44] While it was not disputed that Dr. Wenslow could appear at trial and submit an affidavit introducing those documents covered by the agreement, large portions of the content of his affidavit were hotly contested as being hearsay, improper opinion evidence, covering subject matter beyond the pleadings, and/or being contrary to rules 232 and 248 of the Federal Courts Rules. In light of the timing of these objections, and on the basis of their nature and number, which in many cases included parsing words and/or sentences from within paragraphs, it was determined that the Court would benefit from hearing Dr. Wenslow’s full oral testimony at trial and that the admissibility of the objected to portions of his affidavit evidence would be dealt with as a preliminary matter as part of this decision. Time was reserved for argument on the motion to take place at the close of the evidence. The parties also agreed that counsel for PMS would provide an update after Dr. Wenslow testified as to whether any objections would be withdrawn. However, in the end, the motion was not narrowed. Instead, PMS sought to add additional objections arising from Dr. Wenslow’s oral testimony. PMS was directed to identify the additional objections and the impugned portions of the affidavit to which they related.
[45] As determined by oral ruling during argument on the motion, after-the-fact objections to direct testimony not related to impugned portions of the affidavit were rejected as it was viewed that the failure of PMS to raise the objection during the testimony precluded Merck from properly responding to the objections at the relevant time and potentially curing any deficiency: Teva Canada Ltd v Pfizer Canada Inc, 2017 FC 526 (Venlaflaxine 2) at paras 32- 42. Answers given on cross-examination were also rejected as being improper objections as such answers were elicited by PMS directly. The remaining objections are set out in the Appendix attached to this decision. The Appendix lists the original objections to the affidavit, along with the objections to the asserted related oral testimony and provides my specific dispositions on each. Below, I provide some general comments on the four primary grounds of objection raised.
(1) Hearsay
[46] Hearsay evidence is evidence that is adduced for its truth without the contemporaneous opportunity to cross-examine the declarant: R v Khelawon, 2006 SCC 57 [Khelawon] at para 35. Hearsay evidence is presumptively inadmissible unless it falls under one of the recognized exceptions to the hearsay rule: Khelawon at paras 2, 34, and 42; Pfizer Canada Inc v Teva Canada Limited¸ 2016 FCA 161 [Venlafaxine] at paras 86-87.
[47] Hearsay evidence may also be admitted under the principled approach if the party adducing it can establish it is necessary and reliable: Khelawon at paras 42; Coldwater First Nation v Canada (Attorney General), 2019 FCA 292 [Coldwater] at para 48. A statement is reliable if there is no real concern about whether the statement is true because of the circumstances in which it was made, or if the circumstances allow its truth and accuracy to be sufficiently tested (Khelawon at paras 61-63), such as if it is supported by contemporaneous documentary evidence (Coldwater at para 49-50). Necessity is a flexible criterion and is not to be equated with the unavailability of a witness: Khelawon at para 78; Coldwater at para 53. The nature and practical exigencies of a proceeding can impact the evaluation of necessity (Coldwater at paras 54-55), such as avoiding an impracticably large number of affidavits or witnesses, and the resulting promotion of speed and efficiency (Coldwater at para 59; R v Baldree, 2013 SCC 35 [Baldree] at para 72). One criterion may have an impact on the other (Khelawon at paras 46 and 77) such that if the reliability of the impugned evidence is sufficiently established, the necessity requirement can be relaxed (Baldree at para 72).
[48] This modern approach to hearsay recognizes that evidence may be admissible from departmental supervisors or individuals who take on an oversight role and although not performing all of the work, have enough personal knowledge to testify about the conduct, activities and events that have taken place: Coldwater at paras 42-46.
[49] PMS argues that much of Dr. Wenslow’s evidence consists of statements made about work performed by others or their state of mind and reasoning processes. It asserts that Dr. Wenslow had a limited supervisory role that is insufficient to allow him to testify broadly about the conduct, activities, and events in Merck’s sitagliptin development process. It contends that if Merck wanted this evidence admitted, it needed to call other inventors or Merck employees as witnesses.
[50] Merck argues that much of the impugned evidence is not hearsay as it arises from Dr. Wenslow’s personal knowledge gained in his supervisory capacity. It asserts that the impugned evidence is admissible under the principled approach to hearsay.
[51] As set out further in the Appendix, the majority of the objections made based on hearsay cannot succeed, as they are either not hearsay and/or are admissible under the principled approach to hearsay. I find that Dr. Wenslow’s role within the team was such that he functioned in a larger supervisory capacity that allows him to speak about many aspects of the team’s experimental work. Moreover, as to reliability, the impugned statements generally refer to information from documents that have already been accepted by PMS as being admissible for the truth of their contents without further proof, or which raise facts that have otherwise already been admitted into evidence.
[52] As to necessity, it is difficult to reconcile the inconsistent position taken by PMS to agree to accept Dr. Wenslow’s testimony as the only testimony of the invention story for the purpose of discovery, while asserting it is now insufficient for trial. In some instances if PMS’ objections were to prevail, they would result in PMS reading-in certain facts from discovery as its evidence, while requiring Merck to introduce those same facts through additional witnesses. The PMNOC Regulations seek to promote efficiencies and to avoid the impracticality of a large number of affidavits or witnesses where such testimony is not required. The overly technical position taken by PMS, splitting and parsing sentences, where the reliability of the impugned statements are supported by contemporaneous documents or other evidence runs contrary to the fundamental guidelines set out in section 6.09 of the PMNOC Regulations.
(2) Opinion Evidence
[53] The general rule is that a fact witnesses must limit their testimony to the facts of which they are aware and not to inferences or opinions drawn from those facts: White Burgess Langille Inman v Abbott and Haliburton Co, 2015 SCC 23 at para 14. This rule applies unless the witness is in a better position than the trier of fact to form the conclusions made, the conclusions are ones that a person of ordinary experience can make, the witness has the experiential capacity to make the conclusions, or where giving opinions is a convenient mode of stating facts too subtle or complicated to be narrated as facts: Toronto Real Estate Board v Commissioner of Competition, 2017 FCA 236 at para 79. The line between fact and opinion is not always clear: Graat v The Queen, [1982] 2 SCR 819 at 835.
[54] PMS objects to all or part of 26 paragraphs of Dr. Wenslow’s affidavit and related oral testimony on the basis that he is providing impermissible opinion evidence. PMS asserts that Dr. Wenslow gives unhelpful, and potentially misleading opinion evidence that does not meet the limited and narrow exceptions for a fact witness. Merck asserts that many of the alleged objections relate to factual evidence regarding the observations and conclusions drawn by Merck employees at the time. Merck argues that if any opinion evidence is provided, it is admissible because Dr. Wenslow is well positioned to provide that evidence and has the experiential capacity to do so.
[55] The majority of the statements alleged to be opinion set out the reasoning behind the choices made by the DPP-4 development team and are admissible for this purpose. While some of the statements are technical in nature, this does not automatically negate the statements, especially where such statements reflect the understanding of the development team at the time. In some cases, Dr. Wenslow adds “gloss” to his description of events. However, in most cases such comments are not of such a character that would mislead the Court or be prejudicial to PMS and do not warrant the exclusion of the evidence. Such comments can most effectively be dealt with by considering the weight to be given to the statement. With few exceptions, the objections made in this category are dismissed.
(3) Beyond the Pleadings
[56] Relevance is a threshold requirement for the admission of evidence. Evidence is relevant if it tends to establish a fact in issue. To succeed on showing that evidence should be excluded for relevance, the moving party must show that the evidence is “obviously irrelevant”: Coldwater at para 14. PMS has failed to do so in this case.
[57] The impugned evidence is relevant to the obvious to try analysis and the inventor’s course of conduct. While all of the details of Merck’s invention story were not specifically pleaded in Merck’s Reply, the evidence is clearly responsive to the issues in the proceeding and to PMS’ evidence. The objections in this category accordingly have been dismissed.
(4) Rule 232 and 248 Objections
[58] Rules 232 and 248 aim to avoid a party being prejudiced by the late disclosure of documents and to prohibit “trial by ambush”: Airbus Helicopters, S.A.S. v Bell Helicopter Textron Canada Limitée, 2017 FC 170 at para 81; Apotex Inc v Sanofi Aventis, 2010 FC 481 at para 6. Rule 248 only applies where a party fails to produce documents, or refuses to answer a proper question and later seeks to introduce such evidence at trial: Human Care Canada Inc v Evolution Technologies Inc, 2018 FC 1302 [Human Care] at paras 60-61; Pollard Banknote Limited v BABN Technologies Corp, 2016 FC 883 at para 215. The Court retains the discretion to admit evidence that is given in violation of rule 248.
[59] In general, where a party seeks to introduce evidence that is perceived as being inconsistent with testimony given on discovery, the correct approach is to present the inconsistency to the witness through cross-examination: §16.178, Sidney N Lederman, Alan W Bryant and Michelle K Fuerst, ed, Sopinka, Lederman and Bryant: The Law of Evidence in Canada, 5th ed (Toronto, LexisNexis Canada, 2018); JD Irving Limited v Siemens Canada Limited, 2016 FC 69 at para 43.
[60] PMS raises 14 objections under rules 232 and 248. One of these objections is to an email that was not disclosed prior to Dr. Wenslow’s discovery or in response to undertakings. The email chain confirms the date certain experiments were conducted. This information is not controversial in light of the admission into evidence of other details relating to those experiments in documents that have been accepted as being admissible for the truth of their contents. As a result, I see no prejudice to admitting the document.
[61] The remainder of the rule 248 objections fall into three groups. The first group relate to subject matter that was not refused during discovery, but rather relate to statements that PMS perceives as being inconsistent. These are not appropriate for a rule 248 objection. The second group are based on refusals to very specific points that have only a tenuous connection to the evidence being objected to. The third group relate to objections that lack foundation or were not sufficiently particularized in PMS’ submissions.
[62] In addition to the formal objections raised to Dr. Wenslow’s evidence, PMS also seeks an adverse credibility finding against Dr. Wenslow. It asserts that this finding is separate and distinct from the issue of admissibility, yet sits “hand in glove” with these admissibility objections. It argues that Dr. Wenslow has not acknowledged that his evidence is grounded in hearsay and that his affidavit is based on information and belief. Pursuant to Rule 81(2) of the Federal Courts Rules, PMS asserts that an adverse inference must be drawn as Merck has not provided evidence from persons having personal knowledge of material facts.
[63] While evidence was not provided by those who conducted the experiments, as set out earlier in my decision, in most instances I consider Dr. Wenslow to have sufficient knowledge through his interaction within the DPP-IV development team to be able to provide the evidence given. Such evidence outlines the invention story supported by the contemporaneous documents, accepted as being admissible for the truth of their contents. I find such evidence to be credible and any elaborations given shall be addressed through weight.
III. Issues
[64] The following issues were identified in the parties’ Joint Statement of Issues as being those in dispute for this action:
Obviousness: As of the claim date (June 24, 2003), would the subject matter defined by the Asserted Claims have been obvious and/or obvious to try to a PSA?
Insufficiency: Does the 400 Patent satisfy the requirements of subsections 27(3)(a) and (b) of the Patent Act, R.S.C., 1985, c. P-4 (the Patent Act)?
[65] In addition to these issues raised by the parties, and before determining the validity of the 400 Patent, the Court must construe the Asserted Claims of the 400 Patent. In order to do so, the Court must put the 400 Patent in context by determining whether it is a selection patent and by defining the PSA of the 400 Patent.
IV. The 400 Patent
[66] The 400 Patent is entitled “Phosphoric Acid Salt of a Dipeptidyl Peptidase-IV Inhibitor”. It is the national phase entry of a PCT application filed on June 18, 2004 based on a US priority patent application, filed June 24, 2003. The 400 Patent will expire on June 18, 2024.
[67] The Field of the Invention, at page 1 of the 400 Patent, states that the invention of the 400 Patent relates to the DHP salt of the compound 4-oxo-4-[3-(trifuoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine, now known as sitagliptin, which is a potent inhibitor of DPP-4. It explains that the DHP salt and its crystalline hydrates are useful for the treatment and prevention of diseases and conditions for which an inhibitor of DPP-4 is indicated, in particular type 2 diabetes, obesity and high blood pressure. It also states that the invention further concerns pharmaceutical compositions comprising the salt and crystalline hydrates and processes for preparing them.
[68] The Background to the 400 Patent refers to several articles relating to DPP-4 inhibition for the treatment of type 2 diabetes. It also refers to Merck & Co’s prior patent application WO498 as disclosing a class of compounds that are potent inhibitors of DPP-4 and to the disclosure of 4-oxo-4-[3-(trifuoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine within this class.
[69] The summary of the invention characterizes the invention as the DHP salt of 4-oxo-4-[3-(trifuoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine and its crystalline hydrates; in particular, the crystalline monohydrate. It explains that the DHP salt and crystalline hydrates have advantages in the preparation of pharmaceutical compositions, such as “ease of processing handling, and dosing”. They also exhibit “improved physical and chemical stability, such as stability to stress, high temperatures and humidity, as well as improved physicochemical properties, such as solubility and rate of solution”, which make them particularly suitable for pharmaceutical dosage forms. The section states that the invention further concerns “pharmaceutical compositions containing the novel salt and hydrates as well as methods for using them as DP-IV inhibitors, in particular for the prevention or treatment of Type 2 diabetes, obesity, and high blood pressure.”
[70] The Detailed Description includes as structural formulas (I), (II) and (III) respectively, depictions of the monobasic DHP salt of 4-oxo-4-[3-(trifuoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine in its racemic, R-enantiomer and S-enantiomer forms.
[71] The 400 Patent teaches that the monobasic DHP salt of 4-oxo-4-[3-(trifuoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine is a 1:1 salt with one molar equivalent of mono-protonated compound to one molar equivalent of DHP anion. It also teaches that the salts of the compounds of each of formulas (I), (II) and (III) can be crystalline monohydrates. The crystalline monohydrate of the R-enantiomeric form (structural formula (II)) of sitagliptin DHP salt is the form of the medicine used in JANUVIA®.
[72] The 400 Patent teaches that the DHP salt of structural formulas (I) – (III) in its crystalline monohydrate form can act as an active pharmaceutical ingredient and exhibits pharmaceutic advantages and enhanced chemical and physical