Janssen Inc. v. Sandoz Canada Inc.

Janssen Inc. v. Sandoz Canada Inc.
Court (s) Database
Federal Court Decisions
Date
2022-05-31
Neutral citation
2022 FC 715
File numbers
T-549-20
Decision Content
Date: 20220531
Docket: T-549-20
Citation: 2022 FC 715
Ottawa, Ontario, May 31, 2022
PRESENT: Madam Justice Pallotta
BETWEEN:
JANSSEN INC. AND ACTELION PHARMACEUTICALS LTD
Plaintiffs
and
SANDOZ CANADA INC.
Defendant
PUBLIC JUDGMENT AND REASONS
(Confidential Judgment and Reasons Issued May 12, 2022)
Table of Contents
I. Introduction 2
II. Background 2
A. The Parties and the Nature of this Proceeding 2
B. The 770 Patent 2
C. The Circulatory System and Diseases Involving Vasoconstriction 2
III. Issues and Relevant Dates 2
IV. Evidence 2
A. Dr. Zusman (Sandoz’s Expert Witness) 2
B. Dr. Vachiery (Plaintiffs’ Expert Witness) 2
C. Dr. Chakinala (Plaintiffs’ Expert Witness) 2
D. Dr. Clozel (Plaintiffs’ Fact Witness) 2
V. The Skilled Person 2
VI. Claim Construction 2
VII. Validity 2
A. Obviousness 2
(1) The Test for Obviousness 2
(2) Introduction to Obviousness Analysis and Overview of the Parties’ Positions 2
(3) Step 1: The Skilled Person and their Common General Knowledge (CGK) 2
(a) PH/PAH and Biological Pathways 2
(b) Treatment of PAH 2
(c) CGK – Opinion of Sandoz’s Expert Witness (Dr. Zusman) 2
(d) CGK – Opinions of Plaintiffs’ Expert Witnesses (Dr. Vachiery and Dr. Chakinala) 2
(e) Analysis on CGK 2
(4) Step 2: Identify the Inventive Concept 2
(5) Step 3: Differences Between the State of the Art and the Inventive Concept 2
(a) The Parties’ Submissions 2
(b) Analysis 2
(6) Step 4: Was the Difference Obvious? 2
B. Utility 2
(1) The Experts’ Opinions 2
(2) Analysis 2
C. Overbreadth 2
D. Sufficiency of Disclosure 2
VIII. Conclusion 2
SCHEDULE A 2
SCHEDULE B 2
SCHEDULE C 2
I. Introduction
[1] The plaintiffs, Janssen Inc. (Janssen) and Actelion Pharmaceuticals Ltd (Actelion), bring this patent action against Sandoz Canada Inc. (Sandoz) pursuant to subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [PMNOC Regulations], made under the Patent Act, RSC 1985, c P-4 [Patent Act].
[2] Janssen markets the prescription medication OPSUMIT® in Canada. OPSUMIT® is a film-coated tablet containing 10mg of macitentan as the active ingredient, for the treatment of pulmonary arterial hypertension (PAH). PAH is a serious and incurable condition of high blood pressure in the blood vessels of the lungs, caused by changes to the arteries that transport deoxygenated blood from the heart to the lungs for reoxygenation. If left untreated, the high blood pressure strains the heart, leading to heart failure and death.
[3] OPSUMIT® belongs to a class of drugs known as endothelin receptor antagonists (ERAs). ERAs work by binding to endothelin receptors within the walls of blood vessels, preventing endothelin from binding to these receptors. Endothelin binding is one of the steps in the endothelin pathway, a biological pathway that causes smooth muscle cells in blood vessel walls to constrict and proliferate, forcing the heart to work harder to push blood through the narrowed and thickened arteries. By blocking the endothelin binding step, ERAs disrupt the vasoconstricting and proliferative effects of the endothelin pathway.
[4] OPSUMIT® can be prescribed alone or in combination with another class of drugs known as phosphodiesterase type-5 inhibitors (PDE5-Is). Like ERAs, PDE5-Is affect blood pressure, but they do so by enhancing the vasorelaxation and anti-proliferative effects of another biological pathway—the nitric oxide (NO) pathway. The vasorelaxation and anti-proliferative effects of the NO pathway are mediated by cyclic guanosine 3’,5’-monophosphate (cGMP). PDE5-Is work by blocking the effects of PDE5, an enzyme that breaks down cGMP.
[5] Currently, Janssen is the only company authorized by Health Canada to sell macitentan as a prescription medication. Sandoz seeks Health Canada’s approval to sell a generic prescription medication containing 10mg of macitentan as the active ingredient, for use alone or in combination with PDE5-Is. The plaintiffs allege Sandoz will infringe claims 21-31 (Asserted Claims) of Actelion’s Canadian Patent No. 2,659,770 titled “Therapeutic Compositions Comprising a Specific Endothelin Receptor Antagonist and a PDE5 Inhibitor” (770 Patent).
[6] The 770 Patent relates to macitentan in combination with a PDE5-I to treat diseases wherein vasoconstriction is involved, including PAH. Claim 21 is an independent claim of the 770 Patent that claims the use of macitentan in combination with a PDE5-I to treat a disease wherein vasoconstriction is involved. The other Asserted Claims depend directly or indirectly on claim 21 and they are narrower in scope. The dependent claims include limitations on the specific PDE5-I, the specific disease, or both.
[7] For the purposes of this proceeding only, Sandoz concedes it would infringe the Asserted Claims if it is authorized to market macitentan tablets in Canada. Sandoz defends the plaintiffs’ allegations on the basis that the Asserted Claims are invalid.
[8] Sandoz advances four grounds of invalidity. Sandoz asserts that each Asserted Claim is invalid for one or more of the following reasons: (i) the subject matter of the claim was obvious in view of what was already publicly known; (ii) the inventor had not demonstrated or soundly predicted the utility of the claimed invention; (iii) the claim is overly broad, claiming more than what the inventor actually made or disclosed; and (iv) the 770 Patent specification does not correctly and fully describe how macitentan in combination with a PDE5-I would be used to treat various diseases of vasoconstriction, failing to meet the sufficiency requirements of paragraphs 27(3)(a) and (b) of the Patent Act.
[9] For the reasons below, Sandoz has not established that the Asserted Claims are invalid based on the alleged grounds of invalidity. The plaintiffs are entitled to a declaration that Sandoz would infringe the Asserted Claims by making, constructing, or using its macitentan tablets in Canada.
II. Background
A. The Parties and the Nature of this Proceeding
[10] Janssen is a pharmaceutical company with a head office in Toronto, Ontario. Actelion is a pharmaceutical and biotechnology company with a head office in Allschwil, Switzerland. Janssen is wholly owned by Johnson & Johnson, which acquired Actelion in 2017. Both Janssen and Actelion are members of the Johnson & Johnson group of companies. Janssen is a “first person” within the meaning of subsections 4(1) and 6(1) of the PMNOC Regulations. Actelion is the registered owner of the 770 Patent and is a necessary party to this action under subsection 6(2) of the PMNOC Regulations.
[11] Sandoz is a pharmaceutical company with a head office in Boucherville, Quebec. Sandoz is a “second person” within the meaning of subsections 5(1) and 6(1) of the PMNOC Regulations.
[12] Sandoz filed an Abbreviated New Drug Submission (ANDS) with Health Canada, seeking authorization to market 10mg macitentan tablets based on their equivalent pharmaceutical and bioavailability characteristics, when compared to OPSUMIT®.
[13] The Minister of Health maintains a list of patents related to drugs that have been authorized for sale under a notice of compliance (NOC). As a condition of obtaining market authorization for its macitentan product, the PMNOC Regulations required Sandoz to address the patent list for OPSUMIT®. Sandoz served a Notice of Allegation on April 1, 2020 and the plaintiffs commenced this action in response.
[14] When this action was commenced, three patents were listed in relation to OPSUMIT®: Canadian Patent No. 2,437,675, Canadian Patent No. 2,621,273, and the 770 Patent. Canadian Patent No. 2,437,675 has expired, and Canadian Patent No. 2,621,273 is not at issue in this action. Only the 770 Patent is at issue.
[15] By commencing this action, the plaintiffs triggered a stay that prevents the Minister of Health from issuing an NOC to Sandoz for up to 24 months, that is, before May 14, 2022, in order to allow time for the action to be heard and decided.
B. The 770 Patent
[16] The 770 Patent was issued on November 18, 2014. It relates to a specific compound, referred to throughout the patent as “formula (I)”, in combination with a PDE5-I to treat diseases wherein vasoconstriction is involved. Formula (I) is identified by the following diagram of its chemical structure:
[17] There is no dispute that formula (I) is the compound now known as macitentan, the active ingredient in OPSUMIT®, and that formula (I)/macitentan is an ERA.
[18] The first paragraph of the 770 Patent specification describes the invention as relating to a product containing a compound of formula (I) in combination with at least one compound having PDE5-inhibitory properties for therapeutic use in the treatment of a disease wherein vasoconstriction in involved. Some of the Asserted Claims do not include a limitation on the disease, while others are limited to: hypertension and pulmonary hypertension (PH), PH specifically, or PAH specifically.
[19] The patent specification defines “compound having PDE5-inhibitory properties” to be a compound that meets or exceeds a threshold measurement of its ability to inhibit PDE5 according to an experimental test protocol described in the patent. Examples of such compounds are sildenafil, vardenafil, tadalafil, and udenafil. Some of the Asserted Claims do not include a limitation on the PDE5-I, and others are limited to: the four example PDE5-Is, sildenafil or tadalafil, sildenafil specifically, or tadalafil specifically.
C. The Circulatory System and Diseases Involving Vasoconstriction
[20] Vasoconstriction is the constriction of the vasculature (arteries and veins) of the circulatory system. The vasculature can be divided into two circuits that circulate blood between the body, heart, and lungs. The systemic circuit involves the left side of the heart, which pumps oxygenated blood from the heart to the rest of the body (except the lungs). The pulmonary circuit involves the right side of the heart, which pumps deoxygenated blood from the heart to the lungs for reoxygenation.
[21] The 770 Patent specification lists particular diseases said to involve vasoconstriction: hypertension, PH (including PAH), diabetic arteriopathy, heart failure, erectile dysfunction or angina pectoris. The following provides a brief description of each disease of vasoconstriction listed in the 770 Patent.
[22] Hypertension is a condition of persistently raised blood pressure in the systemic circulatory system (also known as systemic hypertension and colloquially referred to as “high blood pressure”). Long-term excessive force of the blood against the artery walls can damage the blood vessels and organs.
[23] PH is a general term that describes abnormally high blood pressure in the pulmonary circulatory system. The blood pressure in the pulmonary circulation is far lower than in the systemic circulation. Abnormally high blood pressure in the pulmonary circulation is defined hemodynamically as a mean pulmonary arterial pressure of 25 mmHg or higher.
[24] PAH is one subtype of PH. As noted above, PAH is a progressive and incurable disease where the artery walls of the lungs constrict and thicken, increasing vascular resistance to blood flow and making the right side of the heart work harder to push blood through narrowed arteries. The extra stress causes the right ventricle of the heart to enlarge and dilate. Over time, the changes become unsustainable. The right ventricle weakens, its ability to push blood out of the heart to the lungs is compromised, and eventually, the heart fails.
[25] Diabetic arteriopathy is a vascular disease caused by accelerated atherosclerosis, a condition in which plaque builds up and hardens in the arteries of diabetic patients. Over time this narrows the arteries, which limits the flow of oxygenated blood to the body.
[26] Heart failure is a disorder of cardiac performance where the heart is unable to meet the blood supply needs of the body. Patients with congestive heart failure may be breathless or fatigued during exertion, or even at rest.
[27] Erectile dysfunction is an inability to obtain and maintain a penile erection sufficient for sexual intercourse. Penile erection is dependent upon a balance between vasoconstricting and vasorelaxing forces on cavernosal smooth muscle, which requires adequate levels of cGMP. Inhibitors of enzymes that degrade cGMP, particularly PDE5-Is, aid in vasodilation and thus erection.
[28] Angina pectoris is a disorder of vascular obstruction (a narrowing or blockage) of arteries that supply the heart muscle itself, which leads to chest pain or discomfort.
III. Issues and Relevant Dates
[29] The issues in this action relate to claim construction and validity of the Asserted Claims. Infringement of the Asserted Claims is not an issue that is before the Court. Since Sandoz concedes that it would infringe the Asserted Claims for the purposes of this proceeding, the parties agree that the plaintiffs are not required to establish infringement of the essential elements of any Asserted Claims.
[30] The 11 Asserted Claims of the 770 Patent must be construed—that is, interpreted—before there is an assessment of whether they are valid: Whirlpool Corp v Camco Inc, 2000 SCC 67 at para 43 [Whirlpool]. Doing so requires that the claims be read in an informed and purposive way, from the perspective of a notional person of ordinary skill in the art or science to whom the patent is addressed (skilled person): Free World Trust v Électro Santé Inc, 2000 SCC 66 at para 44 [Free World].
[31] In this case, the parties and their expert witnesses disagree on the qualifications of the skilled person and the relevant experience and knowledge that person would bring to bear on the issues in the action. The first issue for the Court is to define the skilled person.
[32] The parties’ disagreement on the skilled person affects their respective positions on issues of validity, but it does not affect their positions on claim construction. The parties and their experts agree on what the Asserted Claims mean. However, the Court is not required to accept the parties’ or the experts’ proposed construction. Claim construction is a matter of law for the Court to decide: Whirlpool at para 61; Zero Spill Systems (Int'l) Inc v Heide, 2015 FCA 115 at para 41 [Zero Spill]. The construction of the Asserted Claims is the second issue.
[33] Sandoz alleges that each of the Asserted Claims is invalid. The claims of a patent are presumed to be valid and Sandoz bears the burden of proving invalidity on a balance of probabilities. The parties’ joint statement of issues outlines the following validity issues in respect of the 770 Patent:
(i) Obviousness: Are any of the Asserted Claims invalid on the basis of obviousness?
(ii) Utility: Are any of the Asserted Claims invalid for lack of utility (i.e. no demonstration of utility or sound prediction of utility)?
(iii) Overbreadth: Are any of the Asserted Claims invalid for overbreadth (i.e. claiming more than what the inventor made or disclosed)?
(iv) Sufficiency: Does the 770 Patent meet the sufficiency requirements of paragraphs 27(3)(a) and (b) of the Patent Act?
[34] The relevant date for construing the claims of a patent is the date the patent application was published. The application for the 770 Patent was published on March 6, 2008.
[35] The same date, March 6, 2008, is the relevant date for determining whether the Asserted Claims are invalid for (iv) failing to meet the sufficiency requirements of paragraphs 27(3)(a) and (b) of the Patent Act. For simplicity, I will sometimes refer to the publication date as March 2008 or simply 2008.
[36] The claim date (section 28.1 of the Patent Act) is the relevant date for determining whether the Asserted Claims are invalid for (i) obviousness, (ii) lack of demonstrated or soundly predicted utility, and (iii) overbreadth. The application for the 770 Patent was filed in Canada on August 28, 2007, however, the application claimed the benefit of an earlier priority date based on applications that were filed on August 29, 2006 and October 19, 2006 (the October 19, 2006 application differs from the August 29, 2006 application in that it includes additional results from experimental testing on macitentan).
[37] The parties do not allege any differences in the relevant prior art or the common general knowledge of the skilled person as of any of these dates. Consequently, it makes no difference to the result if the earliest priority date is the claim date for the obviousness analysis, and the parties have addressed the question of obviousness as of August 29, 2006. For simplicity, I will sometimes refer to this date as August 2006 or simply 2006.
[38] Similarly, the parties do not allege any material difference in assessing utility or overbreadth as of the priority date or the Canadian filing date. The parties have addressed those issues as of the Canadian filing date (August 28, 2007). For simplicity, I will sometimes refer to this date as 2007.
IV. Evidence
[39] The parties agreed on a number of facts. They provided a joint scientific primer and a joint statement of facts.
[40] The parties introduced expert evidence in support of their respective positions on claim construction and validity. Since Sandoz bears the burden on validity, the parties had agreed that Sandoz would serve its expert reports first and the plaintiffs would serve responding expert reports. Sandoz did not file a reply expert report. The trial evidence followed the same sequence, with Sandoz leading its evidence first.
[41] Sandoz relied on the evidence of one expert witness, Dr. Randall Zusman. The plaintiffs relied on the evidence of two expert witnesses, Dr. Jean-Luc Vachiery and Dr. Murali Chakinala. The plaintiffs also called Dr. Martine Clozel, the sole inventor named in the 770 Patent, as a fact witness.
[42] The following summarizes each expert witness’ qualifications and provides an overview of the witnesses’ testimony.
A. Dr. Zusman (Sandoz’s Expert Witness)
[43] Dr. Zusman is a medical doctor specializing in cardiology at the Massachusetts General Hospital (MGH) in Boston, Massachusetts. Dr. Zusman received his M.D. from the Yale University School of Medicine in 1973. He completed his internship, residencies, and chief residency at the MGH. Dr. Zusman has over 42 years of experience as a physician and clinical researcher. He was board certified in internal medicine in 1976 and cardiovascular diseases in 1983. Since 1982, Dr. Zusman has been the Director of Hypertension at the MGH Cardiac Unit. He is also an Associate Professor in Medicine at Harvard Medical School.
[44] Dr. Zusman’s clinical activities include the care of patients with hypertension, PH, PAH, hyperlipidemia, cardiovascular risk factors, and other vascular diseases. Dr. Zusman is active in professional societies including American College of Cardiology, American Heart Association, and American Society of Hypertension. He has been an editor and a member of the editorial board for several scientific journals on the topics of cardiology and hypertension.
[45] At trial, the plaintiffs objected to the admissibility of Dr. Zusman’s report and his ability to testify. The plaintiffs first notified Sandoz and the Court that they intended to raise this objection during their opening statement at trial. The plaintiffs’ objection could have disqualified Dr. Zusman from testifying at trial, and it should have been raised “as early as possible in the proceeding”, instead of the day of his scheduled testimony: Rule 52.5 of the Federal Courts Rules, SOR/98-106. Nonetheless, I allowed the plaintiffs to argue their objection following their cross-examination on Dr. Zusman’s qualifications. The plaintiffs argued that Dr. Zusman is not properly qualified to provide expert evidence in respect of the issues in this action because he does not have the requisite expertise in PH and PAH, which they contend to be the focus of the 770 Patent. While the plaintiffs presented a second argument, that the expertise as set out in Dr. Zusman’s proposed qualifications overreaches, it boiled down to the same concern: according to the plaintiffs, when Dr. Zusman’s evidence is properly narrowed to relate only to his actual expertise, there would be no purpose in having him testify because his opinion would only cover tangential issues.
[46] Sandoz argued that while the commercial embodiment of macitentan is related to PAH, the 770 Patent is broader and does not exclude one disease condition over another. The 770 Patent is about treatment of diseases of vasoconstriction, the skilled person does not change on a claim-by-claim basis, and Dr. Zusman is properly qualified to give expert evidence. He has experience treating patients with the diseases referred to in the 770 Patent, including seeing 300-400 patients a year with PH. While PAH is not the focus of his practice, it is also a rare disease: Hoffmann-La Roche Limited v Sandoz Canada Inc, 2021 FC 384 at para 139.
[47] The following morning I issued a ruling that I was satisfied Dr. Zusman had the requisite expertise and qualifications to give expert opinion evidence on the material issues in dispute. I had not yet made any determinations regarding the focus of the 770 Patent and the characteristics of the skilled person to whom the patent is addressed. I stated that the importance of any specific expertise was a question that remained to be determined. I also noted that an expert witness may be in a position to opine on what the skilled person would know or understand, even if their qualifications do not mirror those of a skilled person: Halford v Seed Hawk Inc, 2006 FCA 275 at para 17. I held that Dr. Zusman’s evidence would be necessary to assist me in deciding material issues in this case and I was satisfied that Dr. Zusman had sufficient experience in the subject matter of his opinion to find that his report and testimony were admissible.
[48] I noted that the extent of Dr. Zusman’s experience in the area of PH or PAH or the focus of his research or study were matters that could affect the weight that would be accorded to his evidence, or to parts of it.
[49] Having reviewed the proposed qualifications put forward by Sandoz, I was satisfied that Dr. Zusman was qualified to testify as an expert as follows:
Dr. Randall M. Zusman is a practicing clinical cardiologist, researcher and professor in medicine with expertise in the diagnosis, management and treatment of hypertension, pulmonary hypertension (including pulmonary arterial hypertension), diabetic arteriopathy, heart failure, erectile dysfunction and angina pectoris, and other diseases wherein vasoconstriction is involved.
Dr. Zusman has expertise in the design, conduct and evaluation of clinical trials for therapies including in diseases wherein vasoconstriction is involved. Such expertise encompasses pre-clinical testing, including the use of animal models, and clinical trials of therapies of these diseases.
[50] Dr. Zusman prepared an expert witness report dated July 29, 2021. The report sets out Dr. Zusman’s opinions on a number of specific mandates related to the qualifications and knowledge of the skilled person, construction of the Asserted Claims, and the validity of the Asserted Claims.
[51] The plaintiffs contend that a number of factors should negatively affect the weight accorded to Dr. Zusman’s opinions. According to the plaintiffs, Dr. Zusman is a relative stranger to ERAs, and has tangential knowledge of PH/PAH as a result of working with colleagues who are the true experts. They say he was evasive under cross-examination and revealed himself to be a professional witness (Dr. Zusman has testified as an expert witness in a number of other cases) and an advocate for Sandoz. The plaintiffs further submit that Sandoz’s counsel provided the documents Dr. Zusman relied on, including 39 references cited as the prior art to support his opinion on obviousness. The plaintiffs allege that, as a physician who was not active in the PAH field at the relevant time, Dr. Zusman can only conduct the obviousness analysis with hindsight, and his opinions in this regard are therefore unreliable. I consider the weight that ought to be accorded to Dr. Zusman’s evidence in the context of my analysis below.
B. Dr. Vachiery (Plaintiffs’ Expert Witness)
[52] Dr. Vachiery is a cardiologist, professor, and researcher. Dr. Vachiery received his M.D. from the Université Libre de Bruxelles in 1985 and became board certified in internal medicine in 1992 and cardiology in 1995. Dr. Vachiery has treated patients with various cardiovascular disorders since 1995 and he has specialized in PH and PAH. Currently, Dr. Vachiery is a Clinical Professor of Cardiology and Director of the Pulmonary Vascular Diseases and Heart Failure Clinic at the Hôpital Erasme – Cliniques Universitaires de Bruxelles, Belgium. He is also a member of the pulmonary vascular disease interdisciplinary network at the International Society for Heart & Lung Transplant.
[53] Dr. Vachiery has been active on a number of councils and working groups related to PH, including by serving as co-chair of the Pulmonary Hypertension Council at the International Heart and Lung Society (2002-2005), chair of the Working Group on Pulmonary Circulation and Right Ventricular Function at the European Society of Cardiology (2006-2008), chair of the Working Group on Heart Failure at the Belgian Society of Cardiology (2008-2009), chair of the Pulmonary Hypertension Council at the International Society for Heart & Lung Transplantation (2018-2020), and Task Force member and Section Editor of the European Guidelines on Pulmonary Hypertension (2009 and 2015).
[54] Sandoz did not object to Dr. Vachiery’s proposed qualifications. I was satisfied Dr. Vachiery was qualified to provide expert opinion evidence according to the proposed qualifications that were put forward by the plaintiffs:
Dr. Vachiery is a medical doctor, researcher, and clinical professor of cardiology with expertise in: (i) pulmonary hypertension (“PH”) (including pulmonary arterial hypertension (“PAH”)); (ii) the development and science of treatment of PH (including PAH); and (iii) the analysis and interpretation of data and results of pre-clinical experimentations, clinical drug trials, case reports and observational studies in the area of pulmonary medicine and cardiology, including the treatment of PAH.
[55] Dr. Vachiery prepared an expert witness report dated October 29, 2021. The report responds to Dr. Zusman’s opinions on mandates related to the skilled person, construction of the Asserted Claims, and the validity of the Asserted Claims.
[56] Sandoz contends that a number of factors should negatively impact the weight accorded to Dr. Vachiery’s opinion. His assessment of the prior art was close-minded and he was quick to dismiss any teachings that were not backed by randomized, controlled clinical trials. Furthermore, Sandoz points to Dr. Vachiery’s ongoing relationship with the plaintiffs for more than 17 years, and states that his career has been and continues to be tied to and funded by the plaintiffs. I consider the weight accorded to Dr. Vachiery’s evidence in the context of my analysis below.
C. Dr. Chakinala (Plaintiffs’ Expert Witness)
[57] Dr. Chakinala is a pulmonologist (referred to as a respirologist in Canada), professor, and researcher. He received his M.D. from Vanderbilt University in 1994 and completed his internship and residency at the University of Texas, Southwestern Medical Center between 1994 and 1997. In 2002, Dr. Chakinala completed fellowships at the Washington University School of Medicine, in Pulmonary and Critical Care Medicine, and General Medical Sciences. He is currently a professor of medicine at the Pulmonary and Critical Care Medicine Division of Washington University School of Medicine, where he is also the director of the Pulmonary Hypertension Care Center.
[58] The focus of Dr. Chakinala’s clinical practice and research as a clinician scientist is on pulmonary vascular disorders. He has been a staff physician and pulmonary consultant at Barnes-Jewish Hospital in Missouri since 2002. He is a pulmonary hypertension consultant at Washington University’s Pulmonary Fibrosis Foundation Care Center Network since 2016, and the Adult Congenital Heart Disease Center since 2017.
[59] Dr. Chakinala is a member of the American College of Chest Physicians and Pulmonary Hypertension Association, among other professional societies. He has also received awards for his work on pulmonary hypertension.
[60] Sandoz did not object to Dr. Chakinala’s proposed qualifications as put forward by the plaintiffs. I was satisfied of Dr. Chakinala’s qualifications to testify as an expert as follows:
Dr. Chakinala is a medical doctor, clinical researcher, and professor of pulmonary and critical care medicine with expertise in (i) pulmonary hypertension (“PH”) (including pulmonary arterial hypertension (“PAH”)); (ii) the development and science of treatment of PH (including PAH); and (iii) the analysis and interpretation of data and results of pre-clinical experimentation, clinical drug trials, case reports and observational studies in the area of pulmonary medicine, including the treatment of PAH.
[61] Dr. Chakinala prepared an expert witness report dated October 29, 2021. The report responds to Dr. Zusman’s opinions on mandates related to the skilled person, construction of the Asserted Claims, and the validity of the Asserted Claims.
[62] Sandoz advances similar criticisms of Dr. Chakinala’s evidence as those advanced in respect of Dr. Vachiery and argues that his evidence should be accorded less weight as a result. In addition, Sandoz argues that Dr. Chakinala made statements that were demonstrably false, gave opinions that were outside of his expertise, and opined on documents without reading them. I consider the weight accorded to Dr. Chakinala’s evidence in the analysis below.
D. Dr. Clozel (Plaintiffs’ Fact Witness)
[63] At the material times, Dr. Clozel was responsible for all pre-clinical drug development as Chief Scientific Officer, Head of Pharmacology, and Executive Vice President of Actelion. She is the sole named inventor of the 770 Patent.
[64] Dr. Clozel testified about her role in the conception of the invention of the 770 Patent and the experimental work that was conducted at Actelion prior to the filing date.
[65] Dr. Clozel also testified about her role in the development of macitentan. Her work on ERAs started at Hoffmann-La Roche (Roche) where Dr. Clozel and her team conducted research that led to the discovery of ERAs, including a compound known as bosentan. In 1997, Dr. Clozel and others left Roche to found Actelion and they continued their work in this area, including work on bosentan which was licensed from Roche. In November 2001, Actelion received regulatory approval from the U.S. Food and Drug Administration (FDA) to market bosentan (TRACLEER®) for the treatment of PAH. Bosentan was the first ERA to receive drug regulatory approval.
[66] Actelion developed other compounds with ERA activity. These included the compounds disclosed in now-expired Canadian Patent No. 2,437,675 titled, “Novel Sulfamides and Their Use as Endothelin Receptor Antagonists”, one of them being the compound now known as macitentan.
V. The Skilled Person
[67] The notional person of ordinary skill in the art or “skilled person” is a legal construct embodying a number of concepts that inform a proper approach to resolving issues in a patent action. The concepts that are relevant to the claim construction and validity issues that arise in this action are set out below.
[68] First, the skilled person possesses a level of skill and knowledge necessary to appreciate the nature and description of the invention at a technical level, and to put it into practice: Whirlpool at para 53. This is the ordinary level of skill and knowledge of the particular art or science to which the patent relates: Free World at para 44. Where a patent relates to multiple scientific or technical fields, the skilled person can comprise a team of people: Amgen Inc v Pfizer Canada ULC, 2020 FC 522 at para 172. However, the skilled person is not defined on a claim-by-claim basis: Teva Canada Limited v Janssen Inc, 2018 FC 754 at para 236, aff’d 2019 FCA 273, leave to appeal to SCC refused, 39007 (7 May 2020). The skilled person embodies the common general knowledge that is generally known and accepted in the field, and they are reasonably diligent in keeping up with advances: Pfizer Canada Inc v Teva Canada Limited, 2017 FC 777 at para 185.
[69] Second, the skilled person adopts a fair and objective approach. They have a mind willing to understand and are trying to achieve success, not looking for difficulties or seeking failure: Les Laboratoires Servier v Apotex Inc, 2019 FC 616 at para 156, citing Free World at para 44. They objectively apply the same standards to all issues, which relate to construction and validity in this case.
[70] Third, the skilled person is not inventive. They pursue reasonable and logical enquiries, and can make deductions based on the information available, but they possess no imagination or inventiveness: Jay-Lor International Inc v Penta Farms Systems Ltd, 2007 FC 358 at para 75, citing Beloit Canada Ltd v Valmet Oy, [1986] FCJ No 87, 8 CPR (3d) 289 at 294 (FCA) [Beloit].
[71] Fourth, the skilled person addresses each issue at the correct point in time. They understand any differences in the relevant skills or knowledge as of each material date, and adopt the proper temporal frame of reference to analyze the issues, without hindsight. As noted above, in this case the parties do not identify any practical differences in the prior art or the relevant skills and knowledge of the skilled person at any material time between August 29, 2006 and March 6, 2008, which simplifies the analysis. Nonetheless, the Court must guard against an ex post facto analysis and the dangers of a backward-looking perspective: Janssen Inc v Teva Canada Limited, 2020 FC 593 at para 169.
[72] Expert witnesses assist the Court by opining on the qualifications, relevant experience, and knowledge of the notional skilled person, and by providing expert evidence so as to put the Court in the position of the skilled person at the relevant time: Tetra Tech EBA Inc v Georgetown Rail Equipment Company, 2019 FCA 203 at para 88, citing Free World at para 51.
[73] In this case, the parties and their experts disagree on how to define the skilled person in respect of the 770 Patent. This disagreement only affects issues of validity, and particularly the interpretation of the relevant prior art for assessing whether any of the Asserted Claims were obvious. As noted above, the parties agree on the construction of the Asserted Claims.
[74] Sandoz’s expert witness, Dr. Zusman, opines that the 770 Patent relates to the use of macitentan administered to a patient in combination with at least one PDE5-I for the treatment of a disease wherein vasoconstriction is involved. Consequently, the skilled person is a clinician, that is, a specialist physician who would treat such diseases. Where the disease is one that involves the systemic circulation, the specialist would be a cardiologist, endocrinologist, or nephrologist, with expertise in vascular medicine. Where the disease is one that involves the pulmonary circulation, the specialist would be a cardiologist, pulmonologist, or critical care physician. According to Dr. Zusman, pulmonologists focus on pulmonary circulation, but cardiology presents an overlap because cardiologists focus on both the systemic circulation and pulmonary circulation. The clinician would have a good knowledge of the drugs and therapies to treat these diseases, including monotherapy and combination therapy, and would keep up to date with the research conducted in the field.
[75] Since the 770 Patent describes tests for PDE5 inhibitory activity and experiments of the combined effects of macitentan and certain PDE5-Is in animal models, Dr. Zusman further states that the skilled team would include a clinical or pre-clinical pharmacologist who might be a medical doctor and/or hold a Ph.D. in medicinal chemistry, pharmaceutics, or a related discipline, and have a few years of experience in the pharmaceutical industry.
[76] The plaintiffs assert that Dr. Zusman’s opinion on the skilled person ignores the 770 Patent’s focus on the treatment of PH and PAH, and is belied by his own near-immediate focus on PH and PAH in his expert report. According to the plaintiffs, Dr. Zusman broadly defines the skilled person as having expertise with diseases wherein vasoconstriction is involved because he lacks a sufficient level of expertise in PH and PAH, and his qualifications do not align with those of the skilled person.
[77] The plaintiffs’ expert witnesses, Drs. Chakinala and Vachiery opine that the skilled person for the 770 Patent would have a narrower focus. The skilled person would be a clinician—a cardiologist or pulmonologist—or a researcher who focuses their clinical and/or research interests on the treatment of patients with PH, and more specifically PAH, and who is knowledgeable about the treatment options. The skilled person would understand that the focus of the 770 Patent is on the use of an ERA (being macitentan) in combination with a PDE5-I for treating PAH. The 770 Patent specification explicitly states that the disease intended to be treated according to the invention is “more preferably” selected from hypertension and PH, in particular PH, and notably PAH.
[78] Drs. Vachiery and Chakinala state that a physician who does not have a particular focus on PH or PAH would not be a part of the skilled team because this would not be reflective of how PH or PAH is treated. In 2008 (and today) it was rare for a general cardiologist to treat PH or PAH patients—such patients were and still are referred to physicians who specialize in PH and PAH. The PH/PAH specialist would be familiar with ERAs, and understand their role in treating PH, and particularly PAH, as of the relevant dates.
[79] Also, Dr. Vachiery notes that the clinician would be part of a larger team that would include a pharmacologist, biologist or biochemist in the field of drug development who is interested in studying compounds in different animal models as part of pre-clinical development.
[80] Sandoz asserts that Drs. Vachiery and Chakinala improperly adopted a claim-by-claim approach to defining the skilled person, rather than considering the 770 Patent as a whole. Dr. Chakinala’s and Dr. Vachiery’s definitions of the skilled person are problematic because they focus solely on PH/PAH and none of the other diseases to which the 770 Patent relates.
[81] I find that the definition of the skilled person would not be limited to PH/PAH specialists. The 770 Patent is not limited to the treatment of PH and PAH. It describes the invention as being related to the treatment of a disease wherein vasoconstriction is involved. The experimental results included in the disclosure are not specific to PH/PAH. While PH and particularly PAH are a focus of the patent, I disagree the skilled team consists solely of PH/PAH specialists. A number of claims are restricted to PAH, but as Sandoz correctly points out, the attributes of the skilled person do not change on a claim-by-claim basis.
[82] Dr. Zusman acknowledges that the skilled person team includes a physician who would have a good knowledge of the drugs and therapies for treating PH and PAH, and would keep up to date with the research conducted in the field. As a rare and potentially fatal disease largely treated by specialists, I find that a physician who treats pa