Janssen Inc. v. Teva Canada Ltd.

Janssen Inc. v. Teva Canada Ltd.
Court (s) Database
Federal Court Decisions
Date
2020-05-05
Neutral citation
2020 FC 593
File numbers
T-353-18
Decision Content
Date: 20200505
Docket: T-353-18
Citation: 2020 FC 593
Ottawa, Ontario, May 5, 2020
PRESENT: The Honourable Mr. Justice Manson
BETWEEN:
JANSSEN INC.
Plaintiff
and
JANSSEN PHARMACEUTICA N.V.
Plaintiff
(Defendant by Counterclaim)
and
TEVA CANADA LIMITED
Defendant
(Plaintiff by Counterclaim)
PUBLIC JUDGMENT AND REASONS
I. Introduction
[1] This is a patent infringement action pursuant to subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [the Regulations]. The Plaintiffs are Janssen Inc, a corporation headquartered in Toronto, and Janssen Pharmaceutica NV, a corporation headquartered in Belgium [collectively Janssen].
[2] Janssen Inc is a “first person” as defined in the Regulations, and Janssen Pharmaceutica NV is a party to this action pursuant to subsection 6(2) of the Regulations as the registered owner of Canadian Patent No. 2,655,335 [the 335 Patent]. Janssen Inc is authorized by Janssen Pharmaceutica NV to sell INVEGA SUSTENNA® (paliperidone palmitate) in Canada.
[3] The Defendant, Teva Canada Ltd [Teva] is a generic pharmaceutical company headquartered in Toronto. Teva filed an Abbreviated New Drug Submission [ANDS] with Health Canada, seeking approval to sell its own paliperidone palmitate product in Canada. On January 9, 2018, Teva served Janssen with a Notice of Allegation pursuant to the Regulations, prompting the commencement of this action.
II. Background
A. Technical Background
(1) Schizophrenia and Related Disorders
[4] Schizophrenia is a debilitating, lifelong disease estimated to afflict over 300,000 Canadians. Symptom onset typically manifests as a psychotic breakdown, and often occurs when the afflicted individual is in their early to mid-twenties.
[5] Schizophrenia is characterized by “positive” symptoms such as hallucinations, delusions, and disorganized behaviour, and “negative” symptoms such as apathy, lack of motivation, and social withdrawal. Diagnosis takes place once symptoms persist for at least six months after onset, and must include the presence of at least two characteristic symptoms for a significant portion of time during a one month period.
[6] Schizophreniform disorder requires the presence of characteristic symptoms for at least one month, but less than six months. Schizoaffective disorder requires similar diagnostic criteria to schizophrenia, with an additional mood element such as major depressive episodes, manic episodes, or both. Unless otherwise indicated, references to “schizophrenia” in these reasons should be understood to mean schizophrenia, schizophreniform disorder, and schizoaffective disorder.
[7] The underlying mechanism causing schizophrenia symptoms is abnormal dopamine functioning in certain parts of the brain. Since the 1970’s, researchers have been aware that effective antipsychotic medications act by blocking dopamine at the D2 receptor.
(2) Treatment of Schizophrenia
[8] Antipsychotic drugs are the cornerstone of schizophrenia treatment and management. They can be broken down into two classes: (1) typical (first generation) antipsychotics; and (2) atypical (second generation) antipsychotics.
[9] Typical antipsychotics block D2 receptors in the brain, and work well against positive symptoms of schizophrenia. However, they are also associated with high incidence of severe adverse side effects called extrapyramidal symptoms, typically involving motor control symptoms such as muscle spasms, muscle rigidity, restlessness, and jerky movements.
[10] Atypical antipsychotics entered the market in the 1990s, and act on both dopamine and serotonin receptors. Atypical antipsychotics have a far lower propensity to cause extrapyramidal symptoms.
[11] Because schizophrenia is incurable and requires life long management with antipsychotic medications, adherence to a treatment regimen is critical. Many schizophrenia patients take oral antipsychotics and are responsible for administering their own medication. A leading cause of relapse is non-adherence, where patients do not take their antipsychotic medication as prescribed, or at all. Rates of non-adherence amongst individuals with schizophrenia are very high.
[12] One strategy to ensure treatment adherence is the use of long acting formulations of antipsychotics. One type of long acting formulation is intramuscular injections of antipsychotic drugs, known as “depot formulations” or “long acting injectables”. Once injected, the drug releases from the injection site slowly, providing the patient with a prolonged dose of the drug.
B. The 335 Patent
[13] The 335 Patent is titled “Prolonged-Release Injectable Suspensions of Paliperidone Palmitate and Dosage Forms and Delivery Systems Incorporating Same.”
[14] The 335 Patent issued from an application filed in Canada on December 17, 2008, claiming priority from United States Patent Application No. 61/014,918, filed on December 19, 2007. The 335 Patent was laid open on June 19, 2009, issued on September 6, 2016, and has not expired. It contains 63 claims, and Janssen alleges infringement of claims 1 to 48 [the Asserted Claims].
[15] The invention relates to dosing regimens for long acting injectable paliperidone palmitate formulations for treatment of schizophrenia. The goal of the invention was to develop a dosing regimen that ensures an optimum plasma concentration-time profile for treating patients with paliperidone. The inventors targeted a plasma concentration exposure range of 7.5 to 40 ng/mL of paliperidone after injection, to ensure efficacy and minimize adverse side effects.
[16] In order to rapidly achieve therapeutic blood plasma concentrations, the patent teaches a “loading dose” regimen comprising doses of paliperidone palmitate administered on day 1 and day 8 in the deltoid muscle, followed by a “maintenance dose” regimen comprising doses of paliperidone palmitate administered monthly thereafter, in either the deltoid or gluteal muscle.
[17] The dosing regimen incorporates “dosing windows” of ± 2 days for the second loading dose, and ± 7 days for the monthly maintenance doses. The dosing windows build flexibility into the regimen without impacting therapeutic effect.
[18] The Asserted Claims of the 335 Patent break down into three sets:
i. claims 1 to 16 relate to prefilled syringes adapted for administration according to the claimed dosing regimens;
ii. claims 17 to 32 relate to a use of a “dosage form” according to the claimed dosing regimens; and
iii. claims 33 to 48 relate to use of paliperidone as paliperidone palmitate in the manufacture/preparation of a “medicament” adapted for administration according to the claimed dosing regimen.
[19] The claimed dosing regimen for non-renally impaired psychiatric patients in need of treatment for schizophrenia, as defined in claims 1, 17, and 33 consists of:
i. A first loading dose of 150 mg-eq of paliperidone palmitate administered into the deltoid muscle on day 1 of treatment;
ii. A second loading dose of 100 mg-eq of paliperidone palmitate administered into the deltoid on day 8 ± 2 days;
iii. Maintenance doses of 75 mg-eq of paliperidone palmitate administered into the deltoid or gluteal muscle monthly ± 7 days after the second injection.
[20] The claimed dosing regimen for renally impaired patients, as defined in claims 2, 18, and 34, follows the same dosing schedule, dosing windows, and injection sites, with loading doses of 100 and 75 mg-eq, and maintenance doses of 50 mg-eq.
C. The Invention Story
[21] Janssen started working on a long acting injectable paliperidone formulation in the early 1990s, forming a global research team to support its development. Around 2003, this team was labelled the Paliperidone Palmitate Compound Development Team [PP CDT].
[22] The primary goals of the PP CDT were to optimize the formulation of the paliperidone palmitate injection for monthly delivery, evaluate the safety and efficacy of paliperidone palmitate for the treatment of schizophrenia and other disorders, and to develop dosing regimens for the drug that would achieve regulatory approval.
[23] Dr. An Vermeulen, a pharmacometrician at Janssen, was actively involved in developing the dosage regimen for paliperidone palmitate. Initial multi-dose studies conducted at Janssen indicated that with once monthly injections, patients would only reach steady-state plasma concentrations of paliperidone after 4-5 months. In 1999, Dr. Vermeulen designed BEL-7, a phase 1 study comparing two different loading dose regimens: (1) administering a double dose on day 1 with monthly dosing thereafter; and (2) administering the same dose on days 1 and 8 with monthly dosing thereafter. All doses were administered in the gluteal. BEL-7 showed that the second loading dose regimen with fixed doses on days 1 and 8, and monthly thereafter, resulted in steady state plasma concentrations within the first month.
[24] Following phase 1 clinical trials, Dr. Vermeulen developed a population pharmacokinetic [popPK] model to assist in making informed dosing decisions and support dosing regimen selections. Based on the results of BEL-7 and Dr. Vermeulen’s modeling, Janssen moved forward with a phase 2 study—SCH-201—in 2003, testing fixed doses of 50 and 100 mg-eq on days 1, 8, and monthly thereafter. Based on the success of SCH-201, Janssen designed two phase 3 studies, PSY-3003 and PSY-3004, to investigate fixed doses of 25, 50, 100, and 150 mg-eq administered on days 1, 8, and monthly thereafter into the gluteal. These studies were conducted from December 2004 to March 2006, and June 2005 to June 2006, respectively.
[25] In April 2006, Dr. Srihari Gopal joined Janssen as a Project Physician on the Clinical Team subgroup of the PP CDT. He was assigned responsibility for ongoing paliperidone palmitate phase 3 clinical trials. At this time, PSY-3003 and PSY-3004 were either complete or nearing completion. The results of these studies were unexpectedly disappointing, and led to the creation of a special task force, including Drs. Vermeulen and Gopal, to troubleshoot problems identified following the phase 3 studies and propose improvements to the dosing regimen.
[26] To assist in revising the dosing regimen, Dr. Vermeulen developed a new popPK model using clinical data from over 1200 patients. She used this model to evaluate different dosing regimens by simulating the plasma concentrations of a virtual but representative patient population.
[27] The task force eventually identified a “treatment by country” interaction in patients from the United States that was determined to be the result of high body mass index. The task force then focused on adjusting the dose regimen for future trials to overcome the issue.
[28] In 2006, Dr. Vermuelen moved to a new position within Janssen. Dr. Mahesh Samtani took over her role on the PP CDT in February 2007. He was tasked with developing a new popPK model for Janssen’s long acting injectable paliperidone palmitate formulation.
[29] Dr. Samtani used Dr. Vermeulen’s model as a starting point, and built a new model using data from over 1400 patients, comprising 15,000 samples from phase 1, 2, and 3 studies. His model took into account a wide range of covariates and paliperidone palmitate’s complex absorption and elimination process. It took approximately six months to build and externally validate the model, and once it was complete, he ran simulations to guide optimization of the paliperidone palmitate dosing regimen.
[30] Dr. Samtani used his model to establish a dosing regimen comprised of loading doses of 150 mg-eq on day 1 and 100 mg-eq on day 8, injected into the deltoid, and maintenance doses of 75 mg-eq monthly thereafter injected into either the deltoid or gluteal muscle. Based on modeling, simulation, and the results of a further phase 3 study, PSY-3007, the team was confident that this dosing regimen was safe and effective, did not require oral supplementation, brought patients to steady state plasma concentration within one week, and matched the plasma concentrations of patients taking 6 mg oral doses of extended release paliperidone.
[31] While Janssen did not receive the PSY-3007 results until after the 353 Patent claim date, Dr. Samtani had developed this regimen using his popPK model, and confirmed the safety and efficacy of the regimen in part using the PSY-3007 results.
[32] Dr. Samtani also used his model to develop recommended dosing windows, that is, flexible tolerance intervals for the timing of the second loading dose and subsequent maintenance dose injections. He determined that dosing windows of ± 2 days for the second loading dose, and ± 7 days for the monthly maintenance doses would maintain therapeutic plasma concentrations without impacting safety and efficacy. Based on modeling and clinical data, Dr. Samtani also determined the appropriate downward dose adjustments for renally impaired patients.
III. Issues
[33] At the outset of trial, three primary issues remained: infringement, and invalidity on the bases of obviousness and unpatentable subject matter. During the course of the trial, Teva withdrew its plea of unpatentable subject matter, leaving only obviousness and infringement in dispute.
[34] The remaining issues are:
Are the Asserted Claims of the 335 Patent invalid for obviousness?
Will Teva directly infringe or induce infringement of the 335 Patent if it comes to market with its paliperidone palmitate product?
[35] For the reasons that follow, I find that:
The Asserted Claims are not obvious, and are valid.
Teva will directly infringe claims 1 to 16 and 33 to 48 of the 335 Patent if it comes to market with its paliperidone palmitate product in accordance with its ANDS. Claims 17 to 32 will not be directly infringed, and Teva will not induce infringement of any of the Asserted Claims.
IV. Fact Witnesses
A. Janssen’s Fact Witnesses
(1) An Vermeulen, PhD
[36] Dr. Vermeulen is a named co-inventor of the 335 Patent. She is currently a Senior Scientific Director and Fellow in Janssen’s Quantitative Sciences Consulting Group.
[37] Dr. Vermeulen joined Janssen Pharmaceutica NV in 1992 as a scientist, and joined the Pharmacometrics Department as a Pharmacometrician in 2001. In this role, she was responsible for developing pharmacokinetic models, popPK models, and population pharmacodynamic models. Dr. Vermeulen used models to guide decision making, design clinical trials, and support dose regimen selection and adaptation.
[38] Dr. Vermeulen gave evidence on her work in the development of the formulation and dosing regimens for Janssen’s paliperidone palmitate injectable.
(2) Mahesh Samtani, PhD
[39] Dr. Samtani is a named co-inventor of the 335 Patent. He is currently a senior director at Janssen Research & Development, involved in all stages of drug development. He joined the PP CDT in February 2007 as a pharmacometrician.
[40] Dr. Samtani gave evidence on his work in the development of the paliperidone palmitate dosing regimen, however his credibility was called into question. He was obstructionist on cross-examination, and did not give straightforward answers to many simple questions. Dr. Samtani was clearly very impressed with his own modeling work.
(3) Srihari Gopal, MD
[41] Dr. Gopal is a named co-inventor of the 335 Patent. He is currently Senior Director (Head of Development, Psychiatry) at Janssen Research & Development. He is also the current team leader of the PP CDT, having initially joined the team as a clinician in 2006.
[42] Dr. Gopal gave evidence about his role in the development of the paliperidone palmitate one month long acting injectable formulation.
[43] Dr. Gopal took several unreasonable positions on cross-examination. He was presented with a 2014 Janssen publication where he is listed as an author, describing a study where the dosing regimen used was 150 mg-eq on day 1 in the deltoid, 100 mg-eq on day 8 in the deltoid, followed by a monthly maintenance doses in the range of 25 to 150 mg-eq in either the deltoid or gluteal muscle. Dr. Gopal stated that reference to a range of maintenance doses was likely due to a “cut and paste” error, and as of the publication date of the paper a maintenance dose range was “definitely not the company position.”
[44] Despite the clear description of the maintenance dose range, and acknowledging that he and his co-authors would have reviewed the paper, Dr. Gopal maintained that Janssen did not recommend any maintenance dose other than 75 mg-eq at that time.
[45] Similarly, counsel for Teva produced a 2009 paper co-authored by Dr. Gopal for submission to Health Canada and the United States Food and Drug Administration that states “[g]ood clinical practice is to individualize treatment based upon clinical symptoms. Individualization of the dose of paliperidone palmitate can begin as early as Day 36, the time corresponding to the third injection.” Despite acknowledging that he was familiar with the document, and the document had been submitted to the regulatory authorities, Dr. Gopal testified that this statement is not correct.
[46] Further, Dr. Gopal stated during examination for discovery that any of the maintenance doses work, depending on patient needs and the prescribing physician’s choice. Janssen decided to recommend a single dose to provide guidance to the physician as to which dose to start with, and 75 mg-eq was selected based on the average maintenance dose for oral paliperidone, as well as the common maintenance dose of paliperidone palmitate used in the flexible dose studies. The read-ins from Dr. Gopal’s discovery paint a different picture of Janssen’s company position on the maintenance dose than the one he gave on cross-examination.
[47] Dr. Gopal’s inconsistent positions on cross-examination as compared to statements made during discovery and in papers he co-authored weakened his credibility.
B. Teva’s Fact Witnesses
(1) David Boughner
[48] Mr. Boughner is the Senior Director of Commercial Management for Teva. He provided evidence that Teva does not market to doctors, and with the exception of product monographs [PMs], does not market its generic products generally.
V. Expert Witnesses
A. Janssen’s Expert Witnesses
(1) Ofer Agid, MD
[49] Dr. Agid is a medical doctor with specialized training in psychiatry. He is a psychiatrist and clinician scientist in the Schizophrenia Program at the Centre for Addiction and Mental Health [CAMH] in Toronto, with a particular focus on diagnosis, treatment, and management of psychotic disorders, including schizophrenia.
[50] Dr. Agid obtained his medical degree at the Hebrew University in Jerusalem, Israel in 1992. He completed a psychiatry residency with the Israeli Psychiatric Association in 1999, and joined CAMH in 2001 as a post-doctoral fellow in clinical research.
[51] In addition to his clinical roles at CAMH, Dr. Agid previously served as a committee member on the CAMH Pharmacy and Therapeutics Committee, which is responsible for creating, reviewing, and implementing policies and procedures in respect of drug products at the hospital. Dr. Agid also carries out schizophrenia research in association with CAMH and the University of Toronto, and is an Associate Professor of Psychiatry at the University of Toronto.
[52] Dr. Agid was qualified as an expert in the diagnosis, treatment, and management of psychotic disorders, including schizophrenia, schizoaffective disorder, schizophreniform disorder, and treatment-resistant schizophrenia, and the nature and clinical use of antipsychotic drugs, including INVEGA SUSTENNA, for the treatment of psychotic disorders, including schizophrenia, schizoaffective disorder, schizophreniform disorder, and treatment-resistant schizophrenia. While he opined on the prescribing practices of physicians in Canada with respect to antipsychotic drugs for these indications, his evidence on this issue is given only limited weight as being for the most part hearsay.
[53] He gave evidence on issues of claim construction, infringement, and obviousness.
[54] On cross-examination, Dr. Agid suffered from two credibility issues. First, he seemed to take contrary positions between his expert report and cross-examination. He repeatedly took the position that the claims allow for treatment using only a single maintenance dose. This position is inconsistent with his report, where he states that treatment must be continuous due to the untreatable nature of schizophrenia.
[55] He was steadfast in his interpretation that the skilled clinician could understand the claims to include only a single maintenance dose, despite the plain claim language that the maintenance doses are adapted for intramuscular administration according to a continuous schedule having a monthly ± 7 days dosing interval.
[56] Second, Dr. Agid maintained that the dosing regimen described in the 335 Patent was the “optimized and standardized” regimen. When pressed by counsel for Teva, Dr. Agid pointed to claim 1 of the patent as support for this position. However, the examples and preferred embodiments in the patent describe numerous different dosing regimens. Dr. Agid could not point to anything in the disclosure that supported his position that the claimed dosing regimen is an “optimized and standardized” dosing regimen.
[57] In addition to these two credibility issues, Dr. Agid admitted that physicians would focus on the “Dosage and Administration” section of a PM, including both Janssen and Teva’s paliperidone palmitate PMs. This admission tends to undermine his position that practicing clinicians would interpret the Teva PM as recommending a maintenance dose of 75 mg-eq based on the entirety of the document.
(2) Barrett E. Rabinow, PhD
[58] Dr. Rabinow is a consultant in the field of pharmaceutical sciences. He obtained his PhD in physical-organic chemistry from the University of Chicago in 1974, and completed postdoctoral work in electrochemistry at the University of Chicago, and clinical chemistry at the National Institute of Health in Chicago.
[59] From 1977 to 2016, Dr. Rabinow worked as a scientist for Baxter Healthcare Corporation, in the areas of parenteral products and sterile fluids, including troubleshooting manufacturing problems and developing nanosuspension drug formulation platforms.
[60] Dr. Rabinow was qualified as an expert in pharmaceutical formulation development and manufacturing, including with respect to liquid formulations for parenteral administration and the preparation and use of suspensions and nanosuspensions in formulations and dosage forms, including injectable dosage forms. This expertise includes excipient selection, and the analysis and characterization of physical and chemical properties of nanosuspension pharmaceutical formulations, including pH, particle size distribution, viscosity, and isotonicity.
[61] Dr. Rabinow opined on formulation aspects of the 335 Patent, and infringement by Teva.
(3) Richard Jones
[62] Mr. Jones is a pharmacist, and is currently the Regional Director of Pharmacy Services at the Vancouver Island Health Authority.
[63] He was qualified as an expert in drug formulary management, including the process and considerations involved in listing a drug product on the hospital drug formulary; and pharmacy practice and medication management in a hospital setting, including prescribing methods, drug dispensing practices and pharmacy clinical practise processes. His evidence was focused on the use of generic PMs in pharmacy practice, hospital formulary management, and pharmacy drug dispensing practices.
[64] Mr. Jones was a credible witness. At times, he appears to have overstated the involvement of the pharmacist in the prescribing process, which is a task within the mandate of the clinician, but overall his testimony was credible and helpful in establishing the role of the pharmacist in the prescription process, as well as the availability of specific drugs within a hospital formulary.
(4) Robert Bies, PharmD, PhD
[65] Dr. Bies is an Associate Professor at the School of Pharmacy and Pharmaceutical Sciences at the State University of New York at Buffalo, an Adjunct Associate Professor at the Department of Pharmacology and Therapeutics at the Roswell Park Cancer Institute, and an Adjunct Associate Professor of Clinical Pharmacology at the Indiana University School of Medicine. His research area focuses on pharmacokinetic and pharmacodynamic mathematical modeling and simulation techniques.
[66] Dr. Bies obtained his PharmD from the University of Texas in 1994, and received his PhD in pharmacology from Georgetown University in 1998. He completed postdoctoral studies at the Center for Drug Development Sciences at Georgetown University between 1998 and 2000. From 2006 to 2016, Dr. Bies served as a research scientist at the CAMH, providing pharmacometric modeling support to investigators studying antipsychotics.
[67] Dr. Bies was qualified as an expert in pharmacometrics, including:
● Developing, selecting, and utilizing pharmacokinetic, pharmacodynamic, and population pharmacokinetic and pharmacodynamic mathematical models of drugs, including antipsychotic drugs;
● Application of pharmacometric approaches to psychiatry; and
● Analyzing simulations from pharmacokinetic, pharmacodynamic, and population pharmacokinetic and pharmacodynamic mathematical modeling, including for therapeutic response modeling of antipsychotic drugs.
[68] Dr. Bies testified to the issue of obviousness and the course of conduct of the inventors, and he was a credible witness. At times he seemed somewhat evasive on cross-examination, however this appears to have arisen from his desire to be precise in answering questions.
(5) Larry Ereshefsky, PharmD
[69] Dr. Ereshefsky is a clinical pharmacologist and Certified Psychiatric Pharmacist with over 40 years of experience as a clinician, scientist, and investigator in developing treatments and clinical methodologies for neurodegenerative and psychiatric disorders, including schizophrenia.
[70] Dr. Ereshefsky obtained his PharmD from the University of Southern California in 1976 and completed his residency in psychiatric pharmacy/psychopharmacology at the University of Southern California – Los Angeles County Medical Center. Now retired, he was a Professor of Pharmacy, Psychiatry, and Pharmacology at the University of Texas from 1977-2003, teaching courses in psychiatric therapeutics and clinical pharmacology.
[71] As Associate Director of the Clinical Research Unit at San Antonio State Hospital, Dr. Ereshefsky oversaw the clinical care and conduct of numerous clinical trials in the development of atypical antipsychotics and new therapies for schizophrenia and other disorders.
[72] Dr. Ereshefsky was qualified as an expert in:
● Clinical pharmacology, particularly clinical pharmacology of antipsychotic drugs;
● Evaluating the pharmacokinetics, pharmacodynamics, bioequivalence, drug-drug interactions, and pharmacogenetics of antipsychotic drugs, including depot antipsychotics;
● Clinical use of antipsychotic drugs, including designing treatment plans for patients;
● Clinical trial design and implementation, particularly for schizophrenia drugs;
● Translational psychopharmacology, including evaluation of preclinical data and models to predict pharmacokinetic and pharmacodynamic parameters in humans;
● Evaluation of toxicology and safety signals.
[73] Dr. Ereshefsky testified to the issue of obviousness and the course of conduct of the inventors. He was a credible witness.
B. Teva’s Expert Witnesses
(1) Richard F. Bergstrom, PhD
[74] Dr. Bergstrom is an Adjunct Professor of Medicine at the Indiana University School of Medicine in the Clinical Pharmacology Division of the Department of Medicine. He obtained his PhD in Pharmaceutical Chemistry (Pharmacokinetics) from the University of Michigan in 1980.
[75] Dr. Bergstrom worked at Eli Lilly and Company between 1973 and 2008, primarily as a pharmacokineticist. In this role, he was responsible for many projects involving the design and evaluation of pharmaceutical dosage forms and formulations, including depot formulations for intramuscular injection. His role in these projects was to use his pharmacokinetic expertise to assist in designing dosage forms, formulations, and dosing regimens.
[76] Dr. Bergstrom was qualified as an expert on issues relating to bioavailability, pharmacokinetics, and pharmacodynamics, including in the development of pharmaceutical formulations, including depot formulations.
[77] Dr. Bergstrom opined on the issue of obviousness of the dosing regimen aspects of the claims, and overall he was a credible witness. However, at times he was evasive on questions relating to obviousness, and took unreasonable positions with respect to how the skilled pharmacokineticist would understand some of the clinical trial information cited in his own report. In his report, he suggested that phase 3 clinical trials were indicative that development of a dosing regimen was in its final stages; however, on cross-examination he suggested that the clinicaltrials.gov website does not always accurately list phase 1, 2, and 3 trials, and downplayed the importance of phase 3 clinical trials.
[78] Despite his view that the development of the dosing regimen would have been routine, Dr. Bergstrom acknowledged on cross-examination that depot formulation development is a long and difficult process because the doses are given infrequently, and it takes a long time to assess this type of trial. Further, phase 3 trials are not always successful, so ongoing phase 3 trials do not necessarily indicate that drug development is nearing completion
(2) Adil Virani, PharmD
[79] Dr. Virani is a Clinical Associate Professor at the University of British Columbia’s Faculty of Pharmaceutical Sciences, and a Manager of Pharmacy Services for Lower Mainland Pharmacy Services. He has been a licensed pharmacist since 1992, and trains medical and pharmacy students on topics relating to mental health, substance abuse, and pain management.
[80] Dr. Virani obtained his PharmD from the University of British Columbia in 1997. He has extensive clinical experience in evidence-based practices, specifically psychopharmacology in pediatric and adult disorders. He has experience treating patients with various psychiatric conditions with antipsychotic medications, including INVEGA SUSTENNA.
[81] Dr. Virani was qualified as an expert in psychopharmacology, the listing of drugs on hospital formularies, and hospital pharmacy management. His evidence was focused on the use of PMs in pharmacy practice.
[82] Dr. Virani’s evidence was helpful to the Court. He answered questions clearly on cross-examination, and was not evasive. He did not advocate for any position, but gave evidence as to how he understands and uses PMs, and the role of pharmacists in the prescription and verification process.
[83] During cross-examination, Dr. Virani stated that in a collaborative healthcare setting such as a hospital, pharmacists may review and change a physician’s prescription if the pharmacist is of the opinion that the dose is not appropriate for the patient in question. This aligns closely with Mr. Jones’ testimony that a pharmacist may actively question a physician on their choice of dose; a point that counsel for Teva attempted to minimize in cross-examination.
[84] That said, Dr. Virani agreed that pharmacists do not prescribe medicine in the traditional sense, and a hospital pharmacist could not write a prescription to be filled outside the hospital.
(3) James Simm, MD
[85] Dr. Simm is the Medical Director at the PACT Logan Winnipeg Regional Health Authority. His responsibilities in this role include directing a community outreach team for patients with severe, persistent mental illness, including schizophrenia. He obtained his medical degree from the University of Manitoba in 1995.
[86] In past positions, Dr. Simm has directed outpatient clinics for patients with schizophrenia, attended to patients admitted to the hospital with schizophrenia, and directed an inpatient unit caring for patients with both addictions and mental illness. Dr. Simm is also an Associate Professor at the University of Manitoba. His responsibilities in this role include teaching clinical skills to medical students and supervising psychiatry residents who are training in addiction psychiatry.
[87] Dr. Simm gave evidence on the use of PMs in clinical practice and his paliperidone palmitate prescribing practices. He was a credible witness.
(4) Glen Kwon, PhD
[88] Dr. Kwon is a Professor at the School of Pharmacy at the University of Wisconsin-Madison and an adjunct Professor in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta. His responsibilities include teaching pharmacy students about the use and manufacture of injectable drug depots.
[89] Dr. Kwon obtained his PhD from the University of Utah in 1991, and completed postdoctoral studies in bioengineering at Tokyo Women’s Medical College. His current research focuses on polymeric nanotechnology for drug delivery, including studying drug solubilization, controlled drug release, and drug targeting for injectables.
[90] Dr. Kwon was qualified as an expert in the development of pharmaceutical formulations, including injectable formulations. He was a credible witness, acknowledging that his expertise was limited to the formulation aspects of the 335 Patent. He opined that the formulation aspects of the Asserted Claims were obvious at the relevant date.
(5) Suzanne Allain, MD
[91] Dr. Allain is a staff psychiatrist at St. Joseph’s Hospital and Thunder Bay Regional Hospital in Thunder Bay. Her clinical work is largely focused on inpatient treatment of patients with schizophrenia and related diseases.
[92] Dr. Allain obtained her MD from the University of Toronto in 1988, and completed a residency in psychiatry at the University of British Columbia in 1993. She is an Associate Professor at the Northern Ontario School of Medicine, an Adjunct Professor in the Department of Psychiatry at Western University, and an Assistant Professor in the Department of Psychiatry at the University of Toronto.
[93] Dr. Allain was qualified as a psychiatrist who specializes in the treatment of schizophrenia, schizoaffective disorder, and schizophreniform disorder, particularly in patients with chronic or treatment resistant disease. She gave evidence on the use of PMs in clinical practice, and her paliperidone palmitate prescribing practices.
[94] Dr. Allain was a credible witness. She stood steadfast in her opinion that the claimed maintenance dose must be administered on a “continuous” monthly schedule.
VI. Claim Construction
[95] Claim construction is a matter of law for the judge (Whirlpool Corp v Camco Inc, 2000 SCC 67 at para 61 [Whirpool]). Where the judge can construe the patent as it would be understood by a skilled person, expert evidence is not required (Pfizer Canada Inc v Canada (Minister of Health), 2007 FC 446 at paras 25, 35-36; Excalibre Oil Tools Ltd v Advantage Products Inc, 2016 FC 1279 at para 119).
[96] The principles of claim construction in Canadian patent law were laid out by the Supreme Court of Canada in Whirlpool and Free World Trust (Whirlpool, above, at paras 49-55; Free World Trust v Électro Santé Inc, 2000 SCC 66 at paras 44-54 [Free World Trust]). These principles are as follows:
i. Claims are to be read in an informed and purposive way, with a mind willing to understand and viewed through the eyes of the skilled reader, as of the date of publication, having regard to the common general knowledge;
ii. Adherence to the language of the claims allows them to be read in the manner in which the inventor is presumed to have intended, and in a way that is sympathetic to accomplishing the inventor’s purpose, which promotes both fairness and predictability;
iii. The whole of the specification should be considered, in order to ascertain the nature of the invention, and the construction of the claims must be neither benevolent nor harsh, but instead should be reasonable and fair to both the patentee and the public; and
iv. On a purposive construction, the claim language will 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 knowledge of the worker skilled in the art to which the patent relates as of the patent publication date.
[97] The relevant date for construing the claims is the publication date: June 19, 2009.
A. Person of Ordinary Skill in the Art [POSITA]
[98] The POSITA is a worker of ordinary skill in the art to which the invention relates who possesses the ordinary amount of knowledge incidental to that particular trade (Consolboard Inc v Macmillan Bloedel (Saskatchewan) Ltd, [1981] 1 SCR 504 at 523). The POSITA may be a team of persons with different skills (Teva Canada Limited v Janssen Inc, 2018 FC 754 at para 66 [Teva Canada], aff’d 2019 FCA 273).
[99] The parties’ experts agreed that the POSITA team includes a clinician with experience treating schizophrenia, and a pharmaceutical formulator. In addition to these team members, Janssen’s experts opined that the POSITA includes a pharmacometrician and a clinical pharmacologist. Teva’s experts opined that the POSITA additionally includes a pharmacokineticist, but not a pharmacometrician or clinical pharmacologist.
[100] Janssen submits that because Figures 1-3 and Example 7 in the 335 Patent relate to popPK modeling, the POSITA should include a pharmacometrician with expertise in developing this type of model. As explained by Dr. Bies, a pharmacokineticist would not necessarily have expertise in developing popPK models.
[101] I agree that the 335 Patent disclosure includes figures and results based on popPK modeling, however the invention is not directed towards developing popPK models. The POSITA is a team “sufficiently versed in the art to which the patent relates to enable them on a technical level to appreciate the nature and description of the invention” (Whirlpool at para 53). Accordingly, the POSITA need only understand the figures and features of paliperidone’s pharmacokinetics identified using the models, a skill set the pharmacokineticist would possess. Expertise developing popPK models is not required to understand the 335 Patent.
[102] That said, the parties ultimately appear to agree on this point. Teva submits that the POSITA has skills related to “pharmacokinetics and pharmacodynamics, including modeling” and Teva further relies on the testimony of Dr. Bies—Janssen’s expert pharmacometrician—for evidence that the skilled person would have known how to build a popPK model. The Court is satisfied that the POSITA would have had sufficient expertise to both develop and interpret the results of popPK models.
[103] The knowledge and skills of Janssen’s “clinical pharmacologist” and Teva’s “pharmacokineticist” largely overlap. As acknowledged by Dr. Ereshefsky on cross-examination, a POSITA team comprised of a clinician, formulator, and pharmacokineticist would possess the relevant skills and knowledge of the clinical pharmacologist as defined by him.
[104] Having considered the expert testimony on the composite POSITA, I find that the POSITA team is comprised of a clinician, a pharmaceutical formulator, a pharmacometrician, and a pharmacokineticist.
[105] The clinician POSITA would have a medical degree and at least three to five years of experience treating patients with psychotic disorders, including schizophrenia and its related disorders. The clinician would understand the diagnosis, pathophysiology, treatment, and management of these disorders, and would be aware of antipsychotics available to treat these disorders, including their mec