Hoffmann-La Roche Limited v. Sandoz Canada Inc.

Hoffmann-La Roche Limited v. Sandoz Canada Inc.
Court (s) Database
Federal Court Decisions
Date
2021-05-12
Neutral citation
2021 FC 384
File numbers
T-896-19, T-897-19, T-898-19, T-899-19
Decision Content
Date: 20210512
Dockets: T-896-19
T-897-19
T-898-19
T-899-19
Citation: 2021 FC 384
Ottawa, Ontario, May 12, 2021
PRESENT: The Honourable Mr. Justice Manson
BETWEEN:
HOFFMANN-LA ROCHE LIMITED AND INTERMUNE, INC.
Plaintiffs
and
SANDOZ CANADA INC.
Defendant
JUDGMENT AND REASONS
Contents
I. Introduction 4
II. Background 5
A. The 654 and 997 Patents 5
B. Treatment of Idiopathic Pulmonary Fibrosis 6
C. Initiation of the Current Actions 7
D. Prior Art 7
III. Issues 8
IV. Summary of Results 9
V. Expert Witnesses 10
A. Roche’s Experts 10
(1) Dr. Martin Kolb 10
(2) W. Neil Palmer 12
(3) Slava Zlydennyy 13
B. Sandoz’s Experts 14
(1) Susanne Picard 14
(2) Dr. R. Andrew McIvor 15
VI. Fact Witnesses 17
A. Roche’s Witnesses 17
(1) Robert James Aleksandr Baker 17
(2) Dr. Williamson Bradford 17
B. Sandoz’s Witness 18
(1) Kim Ly 18
VII. Evidentiary Issues 18
A. Ms. Ly’s Evidence 19
B. Mr. Baker’s Evidence 21
VIII. Claims Construction 22
A. Person of Skill in the Art 24
B. Common General Knowledge 26
(1) IPF Treatment: 654 and 997 Patents 26
(2) Managing Adverse Effects: 654 and 997 Patents 27
(3) Drug Induced Liver Toxicity: 997 Patent 28
(4) Prior Art 29
C. Construction of the Asserted Claims 30
(1) 654 Patent 30
(2) 997 Patent 33
(3) Essential Claim Elements 36
(4) Structure of the 654 and 997 Asserted Claims 37
IX. Infringement 42
A. Direct Infringement 42
B. Induced Infringement 43
(1) The Act of Infringement by the Direct Infringer 46
(2) Influence 47
(3) Knowledge 52
X. Validity 53
A. Anticipation of the 654 Patent 53
B. Double Patenting of the 997 Patent 54
C. Obviousness of the 654 and 997 Patents 57
(1) 654 Patent 59
(2) 997 Patent 67
D. Skill and Judgment / Patentability of the 654 and 997 Patent 70
(1) 654 Patent 74
(2) 997 Patent 75
E. Alternative Invalidity Claims 77
(1) Utility/Sound Prediction 77
(2) Over claiming 80
(3) Insufficiency 81
(4) Ambiguity 82
XI. Conclusion 82
XII. Costs 83
XIII. Appendix A – List of Asserted Prior Art 84
I.
Introduction
[1] This proceeding involves four patent infringement actions (T-896-19, T-897-19, T-898-19 and T-899-19), under subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [the “Regulations”].
[2] The Plaintiff Hoffmann-La Roche Limited is a “first person” under the Regulations. It is a Canadian corporation, which markets and distributes pirfenidone capsules and tablets, under the brand name ESBRIET® [respectively, “ESBRIET Capsules” and “ESBRIET Tablets”].
[3] The Plaintiff InterMune, Inc. [InterMune] is the owner of Canadian Patents Nos. 2,667,654 [654 Patent] and 2,709,997 [997 Patent] and is a party to this action under subsection 6(2) of the Regulations. It is a corporation pursuant to the laws of Delaware in the United States of America.
[4] The Defendant Sandoz Canada Inc. [Sandoz] has an office located in Boucherville, Quebec. It is seeking approval to sell its own pirfenidone capsules and tablets in Canada [the “Sandoz Products”], based on a comparison to ESBRIET.
[5] The Plaintiffs [collectively, “Roche”] claim that the making, using, importing, offering for sale, selling and/or exporting of Sandoz’s pirfenidone tablet [the “Sandoz Tablet”] and capsule [the “Sandoz Capsule”], and that in accordance with Sandoz’s Abbreviated New Drug Submissions [the “Sandoz ANDSs”], will infringe and/or induce infringement of the 654 and 997 Patents.
[6] Sandoz challenges both the claim of infringement and the validity of the 654 and 997 Patents. Collectively, Sandoz asserts the following basis of invalidity for either the 654 or 997 Patent: anticipation (654 Patent only), double patenting (997 Patent only), obviousness, unpatentable subject matter/method of medical treatment, lack of utility/lack of sound prediction, insufficiency of disclosure, overbreadth, and/or ambiguity (654 Patent only).
II. Background
A. The 654 and 997 Patents
[7] The 654 and 997 Patents are listed on the Patent Register. They generally relate to the use of pirfenidone in the treatment of idiopathic pulmonary fibrosis [IPF].
[8] The 654 Patent, entitled “Method of Providing Pirfenidone Therapy to a Patient”, claims the use of pirfenidone in a dose escalation regimen that eliminates or minimizes adverse events. It has 32 claims.
[9] The 654 Patent was issued to InterMune on December 13, 2016 from an application having a filing date of December 18, 2007. It was published on June 26, 2008 and claims priority from United States application (US 60/870,593), filed on December 18, 2006.
[10] The 997 Patent, entitled “Pirfenidone Treatment for Patients with Atypical Liver Function” claims the use of a full therapeutically effective dose of pirfenidone to a patient, after this patient has exhibited a grade 2 abnormality in one or more biomarkers of liver function, following treatment with pirfenidone. The 997 Patent has 11 claims.
[11] The 997 Patent was issued to InterMune on March 27, 2012 from an application having a filing date of November 9, 2009. The application of the 997 Patent was published on May 14, 2010 and claims priority from United States applications (US 61/113,107, US 12/428,393, US 12/488,228, US 61/228,943, US 12/553,292), the earliest of which was filed on November 10, 2008.
B. Treatment of Idiopathic Pulmonary Fibrosis
[12] IPF is a rare, chronic and incurable lung disease. It is characterized by progressive scarring (or fibrosis) of the lungs, but of an unknown (or idiopathic) cause. This fibrosis stiffens the inner lung walls and widens the distance between the air pockets in the lungs and the blood stream. Overtime, this reduces the oxygen supply to the IPF patient’s body. IPF patients progressively lose lung function until death, typically within 3 to 5 years, or a successful lung transplant.
[13] In 2012, pirfenidone, marketed as ESBRIET, became the first drug in Canada approved for the treatment of IPF. It was made available to IPF patients in 2013. Its role is to improve progression-free survival of patients with this chronic lung disease.
C. Initiation of the Current Actions
[14] As referenced above, Roche markets and sells ESBRIET Capsules (267 mg) and ESBRIET Tablets (267 mg and 801 mg). Sandoz seeks approval for the Sandoz Products from Health Canada for the same indications as ESBRIET and on the basis of a comparison to ESBRIET, as specified in the Sandoz ANDSs. The Sandoz Capsules will be available in a strength of 267 mg. The Sandoz Tablets will be available in strengths of 267 mg and 801 mg.
[15] Sandoz further will have a Patient Support Program [the “Sandoz PSP”] that offers services to patients that are taking the Sandoz Products, including reimbursement navigation, financial assistance, clinical support, educational support and co-ordination for patients. Sandoz’s current intention is that any patient enrolled in the Sandoz PSP will be enrolled through their healthcare professional. Sandoz will further make the Sandoz Product Monographs [Sandoz PMs], a Healthcare Professionals Checklist [HCP Checklist] and a Patient Brochure available on a website and to physicians and pharmacists, through its PSP [the “Sandoz Materials”].
[16] Sandoz served Roche with four Notices of Allegation [NOAs] pursuant to the Regulations, dated April 16, 2019, which led to the commencement of these actions.
D. Prior Art
[17] Several prior art references have been relied upon by Sandoz in attacking the validity of the 654 and 997 Patents, including academic articles, a patent, website printouts, a drug label and industry guidance. For clarity, prior art has been labeled throughout this decision generally using keywords and the year, as consistently used by the parties. The alleged prior art, as listed in chronological order, includes: Raghu 1999, Walker&Margolin 2001, Bowen 2003, Azuma 2005, ClinicalTrials.gov 2006, Babovic-Vuksanovic 2006, FDA Guidance for Industry 2007, 646 Patent (2007), Pirespa Label 2008. The prior art is described in greater detail below, in the relevant sections related to validity. A complete list of references is included in Appendix A.
[18] Sandoz further relies on several additional studies as part of its validity attack, specific to its obvious to try argument related to the 654 Patent. These studies concern the actual course of conduct of the named inventor and of other third parties regarding pirfenidone. In light of my findings on obviousness below, these additional studies do not change the result and need not be discussed further.
III. Issues
[19] The parties have filed a Joint Statement of Issues:
What is the proper claim construction of the 654 Asserted Claims 1, 3, 5, 7, 8, 10, 12 and 14 to 18 and 997 Asserted Claim 11, as dependent on claim 10, which is further dependent on claims 1 to 9?
Did Sandoz directly infringe and/or induce infringement by others in respect of the Sandoz Capsules (T-896-19, T-898-19) and Sandoz Tablets (T-897-19, T-899-19)?
Are the 654 Asserted Claims 1, 3, 5, 7, 8, 10, 12 and 14 to 18 and the 997 Asserted Claim 11 (as dependent on claim 10) invalid on the basis of anticipation (654 Patent only), double patenting (997 Patent only), obviousness, unpatentable subject matter/method of medical treatment, lack of utility/lack of sound prediction, insufficiency of disclosure, overbreadth, and/or ambiguity (654 Patent only)?
What is the appropriate remedy?
What costs should be awarded?
IV. Summary of Results
[20] In summary, my conclusions are as follows:
Sandoz will not directly infringe the 654 Asserted Claims 1 , 3, 5, 7, 8, 10, 12 and 14 to 18 or the 997 Asserted Claim 11;
Sandoz will induce infringement of the 654 Asserted Claims 1, 3, 5, 8, 10, 12 and 14 to 17;
Sandoz will not induce infringement of the 654 Asserted Claims 7 and 18;
Sandoz will not induce infringement of the 997 Asserted Claim;
The 654 Asserted Claims are not invalid on the basis of anticipation;
The 997 Asserted Claim is invalid on the basis of obviousness double patenting;
The 654 and 997 Asserted Claims are invalid on the basis of obviousness;
The 654 and 997 Asserted Claims are invalid as methods of medical treatment; and
Invalidity of the 654 and 997 Asserted Claims has not been established on the basis of: (i) utility; (ii) over claiming; (iii) insufficiency; or (iv) ambiguity (654 Patent only).
V. Expert Witnesses
A. Roche’s Experts
(1) Dr. Martin Kolb
[21] Dr. Kolb is a practicing clinical respirologist at St. Joseph’s Healthcare in Hamilton, Ontario. He is also the Division Director for Respirology in the Department of Medicine and the Moran Campbell Chair in Respirology Medicine at McMaster University. Dr. Kolb is a researcher, with a focus on IPF.
[22] Dr. Kolb received his Doctor of Medicine from Julius-Maximillian University of Würzburg in 1992. He further received an Acknowledgement of Internal Medicine Specialty and an Acknowledgement of Respiratory Medicine Specialty from the Bavarian Medical Association in 2002. He also obtained a Privatdozent (equivalent to a PhD) in 2003 from Julius-Maximillian University.
[23] Dr. Kolb runs a specialty clinic, the Interstitial Lung Disease [ILD] Clinic at the Firestone Institute for Respiratory Health [Firestone Institute]. Dr. Kolb is also the Research Director at the Firestone Institute. The ILD Clinic is one of the highest volume clinics for ILD patients in Canada, including IPF patients. Dr. Kolb estimates that he has seen and treated over a thousand patients with IPF, including several hundred with pirfenidone, since 2004.
[24] In these actions, Dr. Kolb was qualified as a practicing clinical respirologist and researcher with expertise in: (i) the diagnosis, management and treatment of respiratory conditions including IPF, including the management of adverse effects of drug therapies; and (ii) the development of treatments, including involvement in clinical trials of therapies for IPF.
[25] Dr. Kolb authored four expert reports which, in broad terms, addressed his claim construction, infringement and responding validity mandates.
[26] Dr. Kolb was a credible witness. Dr. Kolb’s previous and ongoing work with InterMune and Hoffmann-La Roche Limited has not impacted his ability to assist this Court impartially. On cross-examination, Dr. Kolb reconciled discrepancies between his current opinion on the described climate surrounding IPF treatment in 2006 and 2008 and his own publications, which were more contemporaneous to the relevant dates in this action. His reconciliation of these differences did not impact his overall credibility. However, any inconsistency has been assessed and weighted accordingly below.
(2) W. Neil Palmer
[27] Mr. Palmer is the Founder, Senior Strategic Adviser and President Emeritus of PDCI Market Access Inc. [PDCI], an Ottawa-based pricing and reimbursement consultancy for pharmaceutical companies, established in 1996. Mr. Palmer has worked in the field of health care utilization and costs for more than 30 years (1988 to 2020).
[28] Mr. Palmer was qualified as a pharmaceutical industry consultant with expertise in the Canadian pharmaceutical marketplace, in particular, pharmaceutical product pricing and market access, such as price regulation, reimbursement policies (including in relation to products with restricted listings, for example, exceptional access products), interchangeability, and the listing of drug products on public and private drug plan formularies.
[29] Mr. Palmer provided a general description of the pharmaceutical marketplace in Canada and of the reimbursement regimes relevant to pirfenidone. He opined that the Sandoz Products would be funded based on the same criteria as ESBRIET, at a lower cost, and would be designated as interchangeable with ESBRIET.
[30] On cross-examination, Mr. Palmer admitted that he has no experience in the preparation of PMs. He further acknowledged that a generic drug price could be the same, lower or higher than the net price for a brand name drug, after rebates.
(3) Slava Zlydennyy
[31] Mr. Zlydennyy has been a practicing pharmacist for over 12 years. He graduated with a Bachelor of Science in Pharmacy from the University of Toronto in 2007. Mr. Zlydennyy has worked at the Markland Wood Pharmacy, his main practice site, since 2008. He is further involved in the teaching and training of pharmacy students.
[32] Mr. Zlydennyy was qualified in these actions as a registered pharmacist with the Ontario College of Pharmacists, with expertise in the community pharmacy practice in Ontario, including the dispensing of medications and counselling patients regarding the same.
[33] Mr. Zlydennyy provided an overview of the steps a community pharmacist would take upon receiving a prescription to dispense a drug to a patient. He further described the interchangeability and substitution policies that apply to dispensing generic drugs in Ontario. Mr. Zlydennyy opined that a pharmacist would typically dispense the lower cost generic drug product, notably the Sandoz Products, assuming that: (1) ESBRIET Capsules and Tablets are interchangeable with the Sandoz Capsules and Tablets; (2) the Sandoz Products will be reimbursed by public and private drug plans for the same criteria as ESBRIET; and (3) the Sandoz Products will be the lower cost product. Mr. Zlydennyy’s opinion does not change if the assumptions further include the presence of patient support programs for the Sandoz Products and ESBRIET.
[34] It is Mr. Zlydennyy’s opinion that most community pharmacists would have no prior experience with dispensing pirfenidone when the Sandoz Products are launched. He believes that many pharmacists (especially those that are not familiar with pirfenidone) would review the Sandoz PMs, Sandoz HCP Checklist and Sandoz Patient Brochure prior to dispensing the Sandoz Products.
[35] While Mr. Zlydennyy was a credible witness, I have considered several limitations with his evidence: Mr. Zlydennyy has no particular experience with dispensing pirfenidone and his scope of expertise was limited to the community pharmacy setting in Ontario.
B. Sandoz’s Experts
(1) Susanne Picard
[36] Ms. Picard is an occasional replacement pharmacist and the President of SPharm Inc., which she founded in 2000. SPharm Inc. provides regulatory consulting services, including to the pharmaceutical industry. Ms. Picard was awarded a Bachelor Degree of Pharmacy (1990) and a Masters in Hospital Pharmacy (1991) from the University of Montreal.
[37] Ms. Picard was qualified as a regulatory consultant in the pharmaceutical industry with expertise in Canadian pharmaceutical regulatory affairs, including: (i) the preparation and filing of various regulatory submission types, including New Drug Submissions and Abbreviated New Drug Submissions with Health Canada, including the preparation of PMs for brand name and generic drugs; (ii) the relevant regulations and guidelines for preparing PMs; and (iii) Health Canada’s regulatory approval process for brand name and generic products. The parties agreed that Ms. Picard’s expert report would be taken as evidence in these proceedings, without oral testimony.
[38] Ms. Picard opined that Health Canada would not have allowed Sandoz to omit or remove from the Sandoz PMs the following information, provided in the ESBRIET PM: (i) “Indications and Clinical Use”; (ii) “Skin” under “Warnings and Precautions”; (iii) “Recommended Dose and Dosage Adjustment” and “Recommendations in Case of ALT, AST, Bilirubin Elevations” under “Dosage and Administration”; and (iv) “Usual adult dose” under “Part III: Consumer Information”. In Ms. Picard’s opinion, it would have been necessary for Sandoz to include the same clinical information in the Sandoz PMs as provided in the ESBRIET PM in order for Sandoz to receive a Notice of Compliance from Health Canada for pirfenidone.
(2) Dr. R. Andrew McIvor
[39] Dr. McIvor is a staff respirologist at the Firestone Institute, St. Joseph’s Healthcare and a Professor of Medicine at McMaster University since 2005. Dr. McIvor obtained a Bachelor of Medicine, of Surgery, and of Obstetrics from Queen’s University [Queen’s] in Belfast, Northern Ireland in 1984. He further received a Doctor of Medicine degree from Queen’s in 1994.
[40] Dr. McIvor is an author, contributor and editor and is involved in teaching. He has previously held medical practices in Toronto and Halifax from 1994 to 2005, and has prior teaching experience from the University of Toronto and Dalhousie University. Dr. McIvor estimates that he has treated approximately 300 patients with IPF.
[41] Dr. McIvor was qualified as a practicing clinical respirologist and researcher with expertise in: (i) the diagnosis, management and treatment of respiratory conditions, including IPF, including the management of adverse effects of drug therapies; and (ii) the development of treatments including involvement in clinical trials of therapies for IPF.
[42] Dr. McIvor’s mandates include, in broad terms, his opinions on construing the 654 and 997 Asserted Claims, validity and non-infringement.
[43] Overall, Dr. McIvor was a credible witness, although his testimony was weighted having regard to raised inconsistencies and overstatements. For example, he acknowledged during cross-examination that he had no personal knowledge of the number of IPF patients being treated at the IDL Clinic, despite offering an assumption to this effect. Considering the relative rarity of IPF as a chronic lung disease, I do not find that Dr. McIvor’s current practice and research, which focus on areas other than IPF, adversely affect the weight of his opinion other than as specifically indicated below.
VI. Fact Witnesses
A. Roche’s Witnesses
(1) Robert James Aleksandr Baker
[44] Mr. Baker is an articling student with counsel for Roche. He was asked to undertake two tasks involving the tallying of the number of patients who were recorded to have experienced photosensitivity reactions or rashes in InterMune’s CAPACITY clinical trials. To complete these tasks, he wrote a Python application. For the reasons stated below, this evidence can be given no weight.
(2) Dr. Williamson Bradford
[45] Dr. Bradford is the named inventor of the 654 Patent and a co-inventor of the 997 Patent. Dr. Bradford has an MD from the University of North Carolina and a PhD in epidemiology from Berkeley School of Public Health. He joined InterMune around 2001 to lead the IPF program and has previous drug development industry experience. Dr. Bradford and his team were responsible for the design of the CAPACITY studies, two phase III studies of pirfendidone in IPF. Dr. Bradford testified about InterMune’s IPF program, including his work on pirfenidone and the course of conduct leading to the inventions of the 654 and 997 Patents.
[46] Dr. Bradford was a challenging witness. While his recollection of documents led in chief remained relatively intact, Dr. Bradford claimed an imperfect memory in relation to those documents led in cross-examination. He was obstructionist at times and attempted to anticipate counsel’s direction in asking questions during cross-examination, which resulted in evasiveness and a failure to answer straight-forward questions. He had to be reminded by the Court that his role was to answer those questions posed by counsel to the best of his abilities. Dr. Bradford failed to recognize the 654 and 997 Patents in issue, in respect of which he is a named inventor. Overall, his evidence can be given limited weight.
B. Sandoz’s Witness
(1) Kim Ly
[47] Ms. Ly is a law clerk with counsel for Sandoz. Her affidavit introduced various webpages from clinicaltrials.gov and www.internetarchive.com (Internet Archive / Wayback Machine), in an effort to demonstrate how certain information was obtained on these websites regarding the listing of a phase III study of pirfenidone in IPF patients, sponsored by InterMune. Ms. Ly’s evidence is inadmissible in these proceedings for the reasons stated below.
VII. Evidentiary Issues
[48] The parties seek to introduce evidence from their respective counsel’s firms. They each submit that such evidence is admissible in the case of non-controversial or objective matters. However, the evidence the parties seek to introduce in this case, through their respective law firms, relates to the probative value of the prior art. The evidence of both Ms. Ly and Mr. Baker fail to meet the requirements of the best evidence rule, and on the basis of the reasons below, are respectively inadmissible or should be given no weight in this case.
A. Ms. Ly’s Evidence
[49] During the proceeding, Roche objected to the admissibility of Ms. Ly’s affidavit and testimony. Ms. Ly’s evidence was put forward in order to establish the authenticity of a printout, ClinicalTrials.gov 2006. ClinicalTrials.gov 2006 purports to be a website listing for a phase III study of pirfenidone in IPF patients, sponsored by InterMune. It is entitled “Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis”.
[50] Dr. McIvor relies on the printout of www.ClinicalTrials.gov 2006 as he understands it would have appeared on October 9, 2006, as prior art, which he claims would have formed part of the state of the art. Ms. Ly’s evidence was intended to support the admissibility of this printout, by providing evidence regarding how the information was obtained via www.clinicaltrials.gov and www.internetarchive.com, using Wayback Machine.
[51] Sandoz submits that Ms. Ly’s affidavit and testimony is objective evidence, which can be appropriately submitted by counsel. Sandoz asks this Court to also take notice of the asserted general reliability of using Wayback Machine and corroborative evidence offered by Ms. Ly. Further, Roche’s expert, Dr. Kolb, has responded to www.ClinicalTrials.gov 2006, rendering any admissibility concerns irrelevant.
[52] While I note the case law suggesting that Wayback Machine is generally reliable for retrieving information indicating the state of a website in the past, Sandoz has failed to establish the authenticity of the printout in this case, pursuant to section 31.1 of the Canada Evidence Act, RSC, 1985, c C-5 [Canada Evidence Act]. Ms. Ly had never worked for Internet Archive, nor has any experience in web-based archiving. She retrieved the printout as instructed by counsel for Sandoz. On cross-examination, the evidence demonstrated that the information contained in the printout was captured at different points in time. As such, the October 9, 2006 date could not be established. Further, it could not be established that the prior art, as contained in the printout, was publicly available at the relevant time.
[53] Further, Sandoz has failed to meet the requirements of the best evidence rule in section 31.2 of the Canada Evidence Act and Rule 81 of the Federal Courts Rules, SOR/98-106. The affidavits of law clerks do not meet the requirements of Rule 81. No reasoning was provided as to why a witness from InterMune was not called to testify to this fact in issue, at the time the evidence was entered and submissions were heard. Sandoz attempted to submit reasoning after the fact, which is not accepted by this Court (ME2 Productions, Inc v Doe, 2019 FC 214 at paras 120-122).
[54] I do not accept Sandoz’s argument that this evidence is objective and therefore appropriately submitted through counsel. Ms. Ly’s affidavit and testimony is being proffered to establish the authenticity of prior art. For the reasons above, this evidence is inadmissible.
[55] Lastly, while I find it problematic that Dr. Kolb has addressed www.ClinicalTrials.gov 2006 in his responding expert report for the 654 Patent, I accept Roche’s position that this was done under the assumption the Court may find that www.ClinicalTrials.gov 2006 was available on October 9, 2006 as shown on the printout.
B. Mr. Baker’s Evidence
[56] Sandoz has objected in turn to the evidence of Mr. Baker, an articling student with counsel for Roche. Mr. Baker testified to a counting exercise he undertook in relation to documents in evidence. Specifically, the counting exercise related to the number of patients in InterMune’s CAPACITY trials which experienced a photosensitivity reaction or rash. Instructions for this tallying exercise were initially devised by Dr. Kolb, who was asked by counsel for Roche whether it would be possible to assess the incidence of photosensitivity reaction adverse events in the treatment arms of both CAPACITY studies, prior to December 18, 2007. Dr. Kolb used the generated results of this exercise to conclude that, “[a]s compared to Raghu 1999 and Azuma 2005, which reported 24% and 43.8% photosensitivity rash, respectively, the incidence of photosensitivity reaction (including photosensitivity rash) in the CAPACITY studies was significantly reduced”.
[57] Roche argues that Mr. Baker’s affidavit is restricted to non-controversial matters. Mr. Baker did not interpret the documents in question, rely on hearsay or make any judgment call. Mr. Baker’s counting exercise was further carried out on documents the parties had agreed were authentic and admissible and Sandoz was fully able to explore Mr. Baker’s methods on cross-examination.
[58] I find that Mr. Baker’s evidence should be given no weight owing to inaccuracies inherent in the tallying method used. On cross-examination, it became evident that differences in how photosensitivity reactions are recorded, possible spelling mistakes in the recorded information and whether or not the reactions are attributed to pirfenidone could create inconsistencies in the tallies, as performed. Roche argues that the tallies are consistent with the final results reported after the completion of the CAPACITY trials, as noted by Dr. Kolb. I am not satisfied this establishes the reliability of this evidence in this case.
[59] Moreover, this evidence is inconsistent with the requirements of the best available evidence rule. I do not find that this evidence is “non-controversial”. It is not properly submitted through counsel for Roche.
VIII. Claims Construction
[60] This Court must purposively construe the claims of the 654 and 997 Patents, defining the scope of the patent holder’s monopoly (Whirlpool Corp v Camco Inc, 2000 SCC 67 at paras 43, 49 [Whirlpool]). This is a question of law, which precedes consideration of the issues of infringement and validity (Whirlpool, above at para 49(b)). The following principles further underlie the claim construction exercise (Tearlab Corporation v I-MED Pharma Inc, 2019 FCA 179 at paras 30-34; Whirlpool at paras 31, 49-55; Free World Trust v Électro Santé Inc, 2000 SCC 66 at paras 44-54 [Free World Trust]; Consolboard Inc v MacMillan Bloedel (Sask) Ltd, [1981] 1 SCR 504 at 520 [Consolboard]):
Claims are to be read in an informed and purposive way with a mind willing to understand, viewed through the eyes of the person of skill in the art [POSITA] as of the relevant date, having regard to the common general knowledge;
Adherence to the language of the claims allows them to be read in the manner the inventor is presumed to have intended, and in a way that is sympathetic to accomplishing the inventor’s purpose, promoting fairness and predictability;
The whole of the specification should be considered to ascertain the nature of the invention, and the construction of the claims must be neither benevolent nor harsh, but should instead be reasonable and fair to both the patentee and the public; and
On a purposive construction, the claim language may show that some elements are essential while others are non-essential. The identification of claim elements as essential or non-essential is made on the basis of the common general knowledge of the POSITA to whom the patent relates as of the relevant date.
[61] The parties disagree on two aspects of the claims construction: (i) whether the claims are purposively construed as “use” claims or are properly categorized as Swiss-style, German-style and product for use claims; and (ii) the construction of the term “incidence” in claims 7 and 18 of the 654 Patent.
[62] The relevant date for the purpose of claims construction is the respective publication dates, or June 26, 2008 for the 654 Patent and May 14, 2010 for the 997 Patent (Whirlpool at paras 53-54).
A. Person of Skill in the Art
[63] Each patent in issue is construed through the eyes of the POSITA, the notional person to whom the 654 and 997 Patents respectively relate. This person, while unimaginative and uninventive, has an ordinary level of competence and knowledge incidental to the field to which the patent relates and a mind willing to understand the specification addressed to them (Free World Trust, above at para 44).
[64] The parties and their experts disagree on how specialized the POSITA is in this person’s understanding and involvement with IPF. Sandoz argues that the POSITA “could have been involved in a clinical trial as site investigators. i.e. executing a clinical trial designed by leading IPF experts”. Roche, however, asks this Court to favour Dr. Kolb’s evidence to the effect that in the 2006 to 2008 timeframe, IPF treatment was not as specialized as it is today, when the majority of patients at the time would have been seen by community respirologists or internists in remote areas.
[65] The parties and their experts unnecessarily emphasize the specialized nature of the POSITA. Based on the evidence, the experts have agreed to the qualifications of the POSITA, as follows:
The POSITA, in relation to the 654 and 997 Patents, is a physician, with specialized training in the treatment of respiratory disorders. This would include respirologists or internists in remote areas. The POSITA would further possess several years of practical experience treating IPF patients in a clinical setting. However, considering the rarity of IPF, specific experience could be a relatively small portion of the POSITA’s practice.
As part of their experience with IPF, the POSITA would further be able to manage the possible side effects of available IPF therapies. This would include the management of drug-induced liver toxicity.
While the skilled person would not be capable of designing IPF clinical trials, they would have generally been aware of such studies, as described in the common general knowledge section below.
[66] The parties agree that the characteristics of the POSITA are the same for both the 654 and 997 Patents.
B. Common General Knowledge
[67] The common general knowledge is derived from a common sense approach to the question of what would be known to an appropriately skilled person that could be found in real life, who is good at his or her job (Eli Lilly and Company v Apotex Inc, 2009 FC 991 at para 97, aff’d in 2010 FCA 240, citing General Tire & Rubber Co v Firestone Tyre & Rubber Co, [1972] RPC 457 (UKHL) at 482-483). Dr. Kolb did not dispute Dr. McIvor’s description of the common general knowledge of the POSITA on the following aspects, in relation to the 654 and 997 Patents, which I accept as follows.
[68] The experts have opined on the POSITA’s common general knowledge in 2006, 2008 and 2010. There were no changes to the POSITA’s common general knowledge as it relates to this time period.
(1) IPF Treatment: 654 and 997 Patents
[69] As of 2006 and up to 2008, the common general knowledge included that IPF was an incurable disease, causing patients to progressively lose lung function. This usually occurred over the course of a few years, until death or a successful lung transplant. No drug had been proven to reverse or slow down the progression of IPF. However, during this time, prednisone-based combination therapy and supportive treatments remained the standard of care for IPF patients, although associated with considerable side effects.
[70] Pirfenidone was one of many IPF therapies under investigation. At the relevant time, pirfenidone was only available through a clinical trial and the results of its effectiveness were promising, but inconclusive. The POSITA would have been generally aware of any planned or ongoing phase III clinical trials of investigational drugs for IPF and curious about the main findings of published IPF study results.
(2) Managing Adverse Effects: 654 and 997 Patents
[71] As of 2006 and up to 2008, the POSITA would have been aware that patients were monitored for adverse effects (also called “side effects” or “adverse events”) during clinical trials of investigational drugs used in the treatment of lung disease, including IPF. These adverse effects were typically identified before a drug came to market and would be included in published clinical studies and drug labelling.
[72] Adverse effects could determine the standard dosing of a drug, creating an upper dosing limit in a drug’s effective therapeutic range or “therapeutic window”. To maximize efficacy, doses were often selected at or near the maximum-tolerated dose from clinical trials.
[73] Adverse effects were managed with varying strategies, depending on their type, for example, gastrointestinal [GI] upset, nausea, fatigue, drowsiness, dizziness, headache and photosensitivity rash. With the exception of photosensitivity rash, these adverse effects were relatively common.
[74] Administration strategies were known to reduce common adverse effects. However, they would be balanced with patient compliance considerations. These included: (i) administering smaller doses more frequently (although, 4 or more doses per day would be inconvenient for the patient); (ii) starting at a low dose and gradually increasing to the target dose (i.e. “dose escalation” to develop tolerance and reduce the likelihood of GI upset and nausea); (iii) reducing the dose; and (iv) administering the dose with food (although, this was not a uniformly applicable strategy). Photosensitivity was a less common drug adverse effect, which would have been managed by educating patients to avoid and protect themselves from prolonged sun exposure.
(3) Drug Induced Liver Toxicity: 997 Patent
[75] The common general knowledge in 2006 and up to 2008 also applies in 2010, in relation to the 997 Patent. In addition to the above, and specifically in relation to the 997 Patent, in 2008 and up to 2010, the POSITA would have been aware of the potential for pirfenidone to cause drug-induced liver toxicity. Elevations in liver biomarkers may be indicative of liver injury. These biomarkers include alanine transaminase [ALT] and/or aspartate transaminase [AST] and bilirubin, for example.
[76] Patients in clinical trials would have been monitored for symptoms of liver injury and regularly tested for elevations in liver biomarkers. If a patient presented with symptoms of liver dysfunction, such as jaundice or hepatitis, the patient would also be tested for elevations in liver biomarkers. The POSITA would have experience monitoring patients and treating drug-induced liver toxicity, using classification systems for elevations in liver biomarkers.
[77] Such classification systems would often grade elevations in liver biomarkers on a five-point scale, including grades: (0) normal, (1) mild, (2) moderate, (3) severe, (4) life-threatening, and (5) fatal. Grading designations were made by determining whether a patient’s levels of liver biomarkers were within the “upper limit of normal” [ULN] or within certain multiples of the ULN.
[78] If a patient experienced an elevation in ALT and/or AST, the POSITA would have generally chosen from among the following strategies: (i) continue treatment at the same dose (and monitor); (ii) reduce the dose (and monitor); (iii) temporarily stop the drug, and restart it when the biomarker returned to normal (i.e. re-challenging following a drug holiday); and/or (iv) permanently discontinue the drug. Determining which choice to make involved balancing the potential toxicity of the therapy (for which biomarkers would provide an estimate of the degree of risk) against the benefit of the drug.
(4) Prior Art
[79] The experts agree that two of the key referenced prior art formed part of the common general knowledge at the relevant time in relation to both the 654 and 997 Patents; Raghu 1999 and Azuma 2005, which are discussed below.
C. Construction of the Asserted Claims
(1) 654 Patent
[80] As it relates to the 654 Patent, Roche initially alleged infringement or induced infringement of claims 1, 3, 5, 7 to 8, 10, 12 and 14-32 (with some discrepancies in asserted claims between the T-896-19 and T-897-19 actions). However, at closing, the 654 Asserted Claims were reduced to independent claims 1, 3, 5, 8, 10 and 12 and dependent claims 7 and 14 to 18.
[81] Dr. Kolb and Dr. McIvor agree that the 654 Asserted Claims relate to a method of providing pirfenidone, a known compound, for the treatment of IPF in a patient. The independent 654 Asserted Claims 1, 3, 5, 8, 10 and 12 broadly relate to a dose escalation regimen of pirfenidone. The 654 Asserted Claims can be divided into two subsets, including those that specify certain limitations (claims 1, 3 and 5) and those that do not (claims 8, 10 and 12). They are reproduced for reference:
1. Use of pirfenidone in conjunction with food for treatment of idiopathic pulmonary fibrosis in a patient in need thereof, at a first oral daily dosage of 801 mg as one capsule comprising 267 mg of pirfenidone three times a day for seven days followed by a second oral daily dosage of 1602 mg as two capsules each comprising 267 mg of pirfenidone three times a day for a further seven days followed by a third oral daily dosage of 2403 mg as three capsules each comprising 267 mg of pirfenidone three times a day.
…
3. Use of pirfenidone in the manufacture of a medicament for use for treatment of idiopathic pulmonary fibrosis in a patient in need thereof, in conjunction with food, wherein the medicament is