Janssen Inc. v. Pharmascience Inc.

Janssen Inc. v. Pharmascience Inc.
Court (s) Database
Federal Court Decisions
Date
2022-08-23
Neutral citation
2022 FC 1218
File numbers
T-1441-20, T-558-22
Decision Content
Date: 20220823
Docket: T-1441-20
T-558-22
Citation: 2022 FC 1218
Ottawa, Ontario, August 23, 2022
PRESENT: The Honourable Mr. Justice Manson
BETWEEN:
JANSSEN INC. and JANSSEN PHARMACEUTICA N.V.
Plaintiffs
and
PHARMASCIENCE INC.
Defendant
PUBLIC JUDGMENT AND REASONS
(Confidential Judgment and Reasons issued August 23, 2022)
I. Introduction
[1] This proceeding involves two patent infringement actions – Court File Nos. T-1441-20 and T-558-22 – pursuant to subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 (the “Regulations”).
II. Background
A. The Parties
[2] The Plaintiffs are Janssen Inc., a corporation headquartered in Toronto, and Janssen Pharmaceutica N.V., a corporation headquartered in Belgium (collectively, “Janssen”). Janssen Inc. is a “first person” as defined in the Regulations, and Janssen Pharmaceutica N.V. 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”).
[3] The Defendant, Pharmascience Inc. (“Pharmascience” or “PMS”), is a generic pharmaceutical company headquartered in Montréal. Pharmascience is a “second person” in accordance with the Regulations.
B. 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 1970s, 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 (first generation) antipsychotics block D2 receptors in the brain and work well against positive symptoms of schizophrenia. However, they are also associated with a high incidence of severe adverse side effects called extrapyramidal symptoms, which typically involve motor control issues (such as muscle spasms, muscle rigidity, restlessness, and jerky movements).
[10] Atypical (second generation) antipsychotics entered the market in the 1990s, and act on both dopamine and serotonin receptors. Atypical antipsychotics are associated with a far lower incidence of extrapyramidal symptoms.
[11] As stated above, 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 no 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 prolonged drug exposure.
C. The Invention Story
[13] In the early 1990s, Janssen started working on a long-acting injectable paliperidone formulation for the treatment of schizophrenia. Around 2003, a global research team to support this development was labelled the Paliperidone Palmitate Compound Development Team (PP CDT).
[14] 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.
[15] Dr. An Vermeulen, a pharmacometrician at Janssen, was actively involved in the development of the dosage regimen for paliperidone palmitate. Initial multi-dose studies conducted at Janssen indicated that, among other things, once monthly injections patients would only reach steady-state plasma concentrations of paliperidone after four to five months. In 1999, Dr. Vermeulen designed a Phase I study, BEL-7, which compared two different loading dose regimens: (1) administering a double dose on Day 1 with monthly dosing thereafter; and (2) administering the same dose on Day 1 and Day 8 with monthly dosing thereafter. All doses were administered intramuscularly in the gluteal muscle. The BEL-7 study showed that the second loading dose regimen with fixed doses on Day 1 and Day 8 and monthly doses thereafter resulted in steady-state plasma concentrations within the first month.
[16] Following Phase I clinical trials, Dr. Vermeulen developed a population pharmacokinetic model to assist in making informed dosing decisions and support dosing regimen selections. In 2003, Janssen moved forward with the Phase II study SCH-201 based on the results of the BEL-7 study and Dr. Vermeulen’s modeling. The SCH-201 study tested fixed doses of 50 and 100 milligram equivalent (mg-eq.) administered in the gluteal muscle on Days 1, 8, and monthly thereafter.
[17] Based on the success of SCH-201, Janssen designed two Phase III 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 muscle. These studies were conducted from December 2004 to March 2006, and June 2005 to June 2006, respectively.
[18] 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 III clinical trials. At this time, the PSY-3003 and PSY-3004 studies 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 III studies and propose improvements to the dosing regimen.
[19] To assist in revising the dosing regimen, Dr. Vermeulen developed a new population pharmacokinetic model using clinical data from over 1,200 patients. She used this model to evaluate several different dosing regimens by simulating the plasma concentrations of a virtual, representative patient population.
[20] 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.
[21] In 2006, Dr. Vermeulen 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 population pharmacokinetic model for Janssen’s long-acting injectable paliperidone palmitate formulation.
[22] In February and December 2007, advisory board meetings were held with representatives of Janssen (including Drs. Gopal (attended both meetings), Vermeulen (attended the February meeting), and Samtani (attended the February meeting)) and external advisors (including Dr. Ereshefsky (attended the December meeting)). The objectives of the meetings were to review and obtain feedback on the clinical trial data and planned submissions to regulatory authorities. At that time, the proposed dosing regimen included: 1) a 150 mg-eq. dose administered in the deltoid muscle on Day 1 of treatment, 2) a second dose in the range of 25 to 150 mg-eq. in either the deltoid or gluteal muscle starting on Day 8, and 3) monthly doses thereafter.
[23] The advisors were of the view that the use of a 150 mg-eq. dose for most of the patients was a risk and a more acceptable regimen would be to start with 100 mg-eq. The reluctance to accept a 150 mg-eq. starting dose was due to two concerns: 1) safety (overdosing) concerns and 2) the acceptability of regulatory authorities. In light of the feedback, Janssen went forward with an initial new drug application that had a 100 mg-eq. starting dose, including other refinements to the regimen.
[24] Dr. Samtani built a new model using data from over 1,400 patients, comprising 15,000 samples from Phase I, II, and III studies. The development and validation took approximately six months, and took into account a wide range of covariates and paliperidone palmitate’s absorption and elimination process. Once complete, simulations were ran to guide optimization of the paliperidone palmitate-dosing regimen.
[25] 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 muscle, 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 III 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 dose of INVEGA®, an extended release oral tablet of paliperidone.
[26] Dr. Samtani also used his model to develop recommended flexible tolerance intervals for the timing of the second loading dose and subsequent maintenance dose injections, or “dosing windows.” 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 affecting safety and efficacy. Based on modeling and clinical data, Dr. Samtani also determined the appropriate downward dose adjustments for renally impaired patients – a 100 mg-eq. dose on Day 1 followed by a 75 mg-eq. dose on Day 8, both in the deltoid, and monthly doses thereafter of 50mg-eq. in either the deltoid or the gluteal muscle.
[27] While Janssen did not receive the results of the PSY-3007 study until after December 19, 2007 (the first priority date for the 353 Patent), Dr. Samtani had developed this regimen using his population pharmacokinetic model and confirmed the safety and efficacy of the regimen (at least in part) using the PSY-3007 results.
D. The 335 Patent
[28] The 335 Patent is titled “Prolonged-Release Injectable Suspensions of Paliperidone Palmitate and Dosage Forms and Delivery Systems Incorporating Same.”
[29] 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.
[30] The 335 Patent contains 63 claims – each of which is asserted in the two actions in this proceeding. Claims 1, 2, 17, 18, 33, 34, 49, and 50 are independent claims.
[31] The 335 Patent relates to dosing regimens for long-acting injectable paliperidone palmitate formulations for treatment of schizophrenia and related disorders, and teaches 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.
[32] In order to rapidly achieve therapeutic blood plasma concentrations, the 335 Patent teaches a “loading dose” regimen, wherein a specific dose is administered on Day 1 and a different specific dose is administered on Day 8 – both in the deltoid muscle. The “loading dose” regimen is followed by a “maintenance dose” regimen comprised of doses of paliperidone palmitate administered monthly thereafter, in either the deltoid or the gluteal muscle.
[33] The dosing regimen incorporates “dosing windows” of ± 2 days for the second loading dose, and ± 7 days for the monthly maintenance doses.
[34] The claims of the 335 Patent break down into four sets:
Claims 1 to 16 relate to prefilled syringes adapted for administration according to the claimed dosing regimens;
Claims 17 to 32 relate to a use of a “dosage form” according to the claimed dosing regimens;
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; and
Claims 49 to 63 relate to a “dosage form” adapted for administration according to the claimed dosage regimens.
[35] The claimed dosing regimen for non-renally impaired psychiatric patients in need of treatment for schizophrenia is defined in claims 1, 17, 33, and 49:
A first loading dose of 150 mg-eq. of paliperidone palmitate administered into the deltoid muscle on Day 1 of treatment;
A second loading dose of 100 mg-eq. of paliperidone palmitate administered into the deltoid on Day 8 ± 2 days; and
Maintenance doses of 75 mg-eq. of paliperidone palmitate administered into the deltoid or gluteal muscle monthly ± 7 days after the second injection.
[36] The claimed dosing regimen for renally impaired patients, as defined in claims 2, 18, 34, and 50 follows the same dosing schedule, dosing windows, and injection sites, but with loading doses of 100 mg-eq. and 75 mg-eq., and maintenance doses of 50 mg-eq.
E. INVEGA SUSTENNA®
[37] The 335 Patent is listed on the Patent Register maintained by the Minister of Health pursuant to the Regulations in respect of Janssen’s paliperidone palmitate suspension, marketed under the brand name INVEGA SUSTENNA®, in dosage strengths of 50 mg/0.5 mL (i.e. 50 mg-eq.), 75 mg/0.75 mL, 100 mg/1 mL, and 150 mg/1.5 mL.
[38] The product monograph for INVEGA SUSTENNA® sets out dosing regimens falling within the claims of the 335 Patent.
F. Litigation History
(1) Court File No. T-353-18: Janssen Inc. v. Teva Canada Ltd.
[39] Janssen has previously asserted claims 1 to 48 of the 335 Patent against Teva Canada Ltd. in Court File No. T-353-18 (Janssen Inc. v. Teva Canada Ltd., 2020 FC 593 [Teva Paliperidone]).
[40] In Teva Paliperidone, I determined, among other things, the Person of Ordinary Skill in the Art (POSITA), the Common General Knowledge, and the construction of claims 1 to 48 of the 335 Patent – the details of which will be set out in the relevant sections below.
[41] While the appeal of Teva Paliperidone is currently pending, the POSITA and construction of claims 1 to 48 of the 335 Patent are not at issue in these proceedings.
(2) Court File No. T-455-20: Janssen Inc. v. Pharmascience Inc.
[42] On February 28, 2020, Pharmascience served a Notice of Allegation and Detailed Statement in respect of its Abbreviated New Drug Submission (ANDS) No. 236094 in regards to the 335 Patent and seeking approval to market and sell in Canada 50, 75, 100, and 150 mg-eq. doses of a proposed pms-PALIPERIDONE PALMITATE product, a generic version of Janssen’s INVEGA SUSTENNA® product.
[43] In response, Janssen commenced an infringement action under subsection 6(1) of the Regulations on April 8, 2020 in Court File No. T-455-20. On October 2, 2020, the action in respect to ANDS No. 236094 was discontinued on consent.
(3) Court File No. T-1441-20: Janssen Inc. v. Pharmascience Inc.
[44] On October 16, 2020, Pharmascience served a Notice of Allegation and Detailed Statement in respect of its ANDS No. 244641 in regards to the 335 Patent and seeking approval to market and sell in Canada |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| doses of its proposed pms-PALIPERIDONE PALMITATE, a generic version of Janssen’s INVEGA SUSTENNA® product.
[45] Pharmascience alleges that the 335 Patent is invalid or void and would not be infringed by the making, constructing, using, or selling of a proposed pms-PALIPERIDONE PALMITATE as set out in ANDS No. 244641.
[46] In response, Janssen commenced an action (File No. T-1441-20) against Pharmascience pursuant to subsection 6(1) of the Regulations on November 27, 2020. Janssen is seeking:
A declaration that the making, constructing, using, or selling of pms-PALIPERIDONE PALMITATE by Pharmascience in accordance with ANDS No. 244641 would infringe claims 1 to 63 of the 335 Patent, directly and/or indirectly;
A permanent injunction restraining Pharmascience (as well as its subsidiaries and affiliates) from:
Making, constructing, using, or selling the pms-PALIPERIDONE PALMITATE in Canada;
Offering for sale, marketing, or having the pms-PALIPERIDONE PALMITATE marketed in Canada;
Importing, exporting, distributing, or having the pms-PALIPERIDONE PALMITATE distributed in Canada; and
Otherwise infringing or inducing others to infringe the 335 Patent.
If Pharmascience makes, constructs, uses, or sells the pms-PALIPERIDONE PALMITATE before the expiry of the 335 Patent, damages or an accounting of Pharmascience’s profits, as Janssen may elect, resulting from Pharmascience’s infringing activities in respect of the 335 Patent;
Janssen’s costs of this action; and
Any other relief that this Honourable Court deems just.
[47] On January 26, 2021, Pharmascience brought a motion for summary trial on the grounds that the pms-PALIPERIDONE PALMITATE, made in accordance with ANDS No. 244641, does not contain an essential element (i.e. the 75 mg-eq. dose) of any of the 63 claims of the 335 Patent and, therefore, cannot infringe the 335 Patent.
[48] In Janssen Inc. v. Pharmascience Inc., 2022 FC 62 [PMS Paliperidone], I found that Janssen had shown, on a balance of probabilities, that Pharmascience’s proposed pms-PALIPERIDONE PALMITATE in accordance with ANDS No. 244641 will induce infringement of the 335 Patent. More specifically, based on the evidence, there appear to be several instances in the product monograph of the proposed pms-PALIPERIDONE PALMITATE that would influence prescribers to prescribe the claimed dosing regimen leading to direct infringement of the 335 Patent.
[49] Thus, Janssen’s action was not dismissed and was allowed to proceed on Pharmascience’s defence of alleged invalidity as described herein.
[50] The appeal of the PMS Paliperidone summary trial is currently pending.
[51] Since all 63 claims of the 335 Patent are at issue in Court File No. T-1441-20, claims 49 to 63 have been construed – the details of which will be set out in the relevant section below.
(4) Court File No. T-553-22: Janssen Inv. v. Pharmascience Inc.
[52] On January 29, 2022, Pharmascience served a Notice of Allegation and Detailed Statement in respect of its ANDS No. 251767 in regards to the 335 Patent and seeking approval to market and sell in Canada |||||||||||||||||||||||| of its proposed pms-PALIPERIDONE PALMITATE, a generic version of Janssen’s INVEGA SUSTENNA® product.
[53] In the Statement of Claim, Janssen asserts that the letter served on them was not a proper Notice of Allegation as Pharmascience failed to comply with the Regulations. However, this is not an issue in these proceedings.
[54] Pharmascience alleges that the 335 Patent is invalid or void, but does not contest infringement by the making, constructing, using, or selling of a proposed pms-PALIPERIDONE PALMITATE as set out in ANDS No. 251767.
[55] In response, Janssen commenced an action (Court File No. T-558-22) against Pharmascience pursuant to subsection 6(1) of the Regulations on March 14, 2022. Janssen is seeking:
A declaration that the making, constructing, using, or selling of pms-PALIPERIDONE PALMITATE by Pharmascience in accordance with ANDS No. 251767 would infringe claims 1 to 63 of the 335 Patent, directly and/or indirectly;
A permanent injunction restraining Pharmascience (as well as its subsidiaries and affiliates) from:
Making, constructing, using, or selling the pms-PALIPERIDONE PALMITATE in Canada;
Offering for sale, marketing, or having the pms-PALIPERIDONE PALMITATE marketed in Canada;
Importing, exporting, distributing, or having the pms-PALIPERIDONE PALMITATE distributed in Canada; and
Otherwise infringing or inducing others to infringe the 335 Patent.
If Pharmascience makes, constructs, uses, or sells the pms-PALIPERIDONE PALMITATE before the expiry of the 335 Patent, damages or an accounting of Pharmascience’s profits, as Janssen may elect, resulting from Pharmascience’s infringing activities in respect of the 335 Patent;
Janssen’s costs of this action; and
Any other relief that this Honourable Court deems just.
III. Issues
[56] As stated above, at the motion for summary trial dealing solely with the issue of infringement, Janssen’s action was not dismissed, a finding of infringement was made, and this action has proceeded on the basis Pharmascience’s defence of alleged invalidity of the 335 Patent.
[57] The Parties have filed a Joint Statement of Issues:
Whether any of the claims of the 335 Patent are invalid on the basis of obviousness, pursuant to section 28.3 of the Patent Act, RSC 1985, c P-4; and
Whether any of the claims of the 335 Patent are invalid on the basis of lack of patentable subject matter (i.e. as a method of medical treatment) under section 2 of the Patent Act.
IV. Analysis
A. The Experts and Fact Witnesses
(1) Janssen’s Fact Witnesses
(a) An Vermeulen, PhD
[58] Dr. Vermeulen is a named co-inventor of the 335 Patent. She is currently the Clinical Pharmacology and Pharmacometrics Therapeutic Area Head for Immunology at Janssen.
[59] Dr. Vermeulen received her PhD in Pharmaceutical Sciences from the University of Ghent, with a focus on pharmacokinetics.
[60] Dr. Vermeulen was a credible witness and gave evidence on her work in the development of pharmacokinetic models to guide decision-making, design clinical trials, and support dose regimen selection and adaptation of the formulation and dosing regimens for Janssen’s paliperidone palmitate injectable as described above in the invention story.
(b) Srihari Gopal, MD
[61] Dr. Gopal is a named co-inventor of the 335 Patent. Though no longer employed by or associated with Janssen, at the time of signing his affidavit he was Senior Director (Head of Development, Psychiatry) at Janssen Research & Development LLC.
[62] Dr. Gopal obtained his medical degree from Rutgers University before completing two medical residencies: one in association with the Department of Surgery at the University of Illinois, College of Medicine and the other in association with the Department of Family Medicine at the Baylor College of Medicine in Texas. Dr. Gopal also has a Masters of Health Science in association with the Clinical Research Training Program at Duke University in North Carolina.
[63] Dr. Gopal was a credible witness and gave evidence about his role in the development of the paliperidone palmitate one-month long-acting injectable formulation, as well as his understanding of the studies completed before his employment at Janssen. Dr. Gopal became involved with the PP CDT during the Phase III trials as described above in the invention story.
[64] On consent, the final paragraph of Dr. Gopal’s affidavit was removed in response to an objection raised by Pharmascience.
(c) Mahesh Samtani, PhD
[65] Dr. Samtani is a named co-inventor of the 335 Patent. He is currently Senior Director, US Pharmacometrics Head at Janssen.
[66] Dr. Samtani received his PhD in Pharmaceutical Science from the State University of New York. A portion of his PhD thesis was on pharmacokinetic and pharmacodynamic modeling of aqueous suspensions of a corticosteroid with long-acting properties.
[67] Dr. Samtani was a credible witness and gave evidence about his role in the development of a population pharmacokinetic model that would be suitable for submissions to regulatory authorities and would aid in optimizing the dosing regimen for paliperidone palmitate as described above in the invention story.
(2) Pharmascience’s Fact Witnesses
(a) Horatiu Lazar
[68] Mr. Lazar is a Marketing and Sales Data Analyst at Pharmascience. He described how the IGVIA (formerly, IMS) data (which provides pharmaceutical sales and prescription data for paliperidone palmitate products from 2021) cited in Dr. Jeffries expert report was prepared.
[69] Mr. Lazar was not examined and his affidavit was entered into evidence as read.
(b) Nathaniel Frank-White
[70] Mr. Frank-White is a Records Request Processor at the Internet Archive, which provides the Wayback Machine service. He provided screenshots of a Johnson & Johnson webpage that linked to webcasts and documents of public conferences and events held by the company from June 7, 2007 to January 22, 2008, including the Credit Suisse investors meeting transcript.
[71] Mr. Frank-White was not examined and his affidavit was entered into evidence as read.
(3) Janssen’s Expert Witnesses
(a) Dr. Pierre Chue
[72] Dr. Chue is a Medical Doctor with specialized training in the field of psychiatry. He holds several clinical, research, and teaching positions with Alberta Health Services and the University of Alberta. Dr. Chue’s practice focuses on the treatment of adult patients with mental illness, including schizophrenia and schizoaffective disorder.
[73] Dr. Chue obtained his Bachelor of Medicine, Bachelor of Surgery (MBBCh) from the Welsh National School of Medicine.
[74] Dr. Chue was qualified as an expert in the diagnosis and treatment of schizophrenia and schizoaffective disorder. This expertise includes the clinical use of injectable depot medications, such as paliperidone palmitate (i.e. INVEGA SUSTENNA®), as well as oral antipsychotic medications.
[75] Pharmascience raised a preliminary objection to portions of Dr. Chue’s testimony under Rule 248 of the Federal Court Rules, SOR/98-106. Pharmascience objected to any testimony regarding the prescribing practices of Canadian physicians because a Janssen corporate representative had previously refused to answer whether they had any information about the prescribing practices of Canadian physicians during discovery.
[76] As I have previously ruled in related proceedings, testimony regarding the practices and knowledge of other physicians is hearsay, neither reliable nor necessary, and, as such, given little to no weight (Teva Paliperidone at paragraph 52).
[77] Dr. Chue testified to the issues of obviousness and method of medical treatment. Dr. Chue was somewhat obstructionist during cross-examination, and did not give straightforward answers to many simple questions. Nevertheless, the weight of his evidence, when of value, is considered below.
(b) Larry Ereshefsky, PharmD
[78] 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.
[79] Dr. Ereshefsky obtained his PharmD from the University of Southern California 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, teaching courses in psychiatric therapeutics and clinical pharmacology.
[80] 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.
[81] Dr. Ereshefsky was qualified as an expert in:
Clinical pharmacology, particularly in the clinical pharmacology of antipsychotic drugs;
Evaluating the pharmacokinetics, pharmacodynamics, bioequivalence, drug-drug interactions, and pharmacogenetics of antipsychotic drugs, including long-acting injectable (depot) antipsychotic drugs;
The clinical use of antipsychotic drugs, including designing, implementing, monitoring, and modifying treatment plans for patients using antipsychotic dugs (including long-acting injectable antipsychotic drugs) for treatment pf psychiatric disorders, including schizophrenia, schizoaffective disorder, and schizophreniform disorder;
Clinical trial design and implementation, including clinical trials for drugs used in the treatment of psychiatric disorders, including schizophrenia, schizoaffective disorder, and schizophreniform disorder;
Translational psychopharmacology, including the evaluation of preclinical (animal) data and models and the extrapolation of preclinical date to predict pharmacokinetic and pharmacodynamic parameters in humans; and
The evaluation of toxicology and safety signals, including in translating preclinical and clinical trial data into design strategies incorporating patient assessments/biomarkers and in exploring exposure limits.
[82] Dr. Ereshefsky testified to the issues of obviousness and method of medical treatment. He suffered some credibility issues in providing several unreasonable opinions, related to evidence on the issue of obviousness, as discussed in more detail below.
(4) Pharmascience’s Expert Witnesses
(a) Joel Jeffries, MD
[83] Dr. Jeffries was appointed as Staff Psychiatrist at the Centre for Addiction and Mental Health from 1998 until May 2021, when he retired from active clinical practice. Among other teaching roles, Dr. Jeffries has been an Associate Professor of Psychiatry and Pharmacy at the University of Toronto since 1978, and claims more than 50 years of experience in psychiatry. Dr. Jeffries received his medical degree from the University of Dublin.
[84] Dr. Jeffries was qualified as an expert in the field of psychiatry, including in the diagnosis, monitoring, and treatment of patients with schizophrenia and related disorders, including long-acting injectables and depot formulations. He is also an expert in the prescribing practices of psychiatrists and the standard of practice of psychiatrists and physicians treating patients with schizophrenia and related disorders.
[85] Dr. Jeffries provided his opinion on the issue of method of medical treatment. He suffered some credibility issues, having provided inconsistent statements and sometimes seemed confused or unable to follow relatively straight-forward questions. Dr. Jeffries has also never prescribed INVEGA SUSTENNA®. As stated above for Dr. Chue’s testimony, any testimony provided by Dr. Jeffries reflecting other physicians prescribing practices gathered from discussions with colleagues is hearsay and is given little or no weight.
(b) Pardeep Gupta, PhD
[86] Dr. Gupta is a Professor of Pharmaceutics and Burroughs Wellcome Chair in the Department of Pharmaceutical Sciences at University of the Sciences in Philadelphia. He is also the Director of Industrial Pharmacy Laboratory at Philadelphia College of Pharmacy, University of the Sciences in Philadelphia. He teaches on the topics of injectable and non-injectable pharmaceutical formulations, drug diffusion, controlled drug delivery, pharmaceutical rate processes, drug stability, bioavailability and pharmacokinetics.
[87] Dr. Gupta received his PhD in Pharmaceutics and Physical Chemistry from the University of Wisconsin – Madison. His research was focussed on study of the biological variables that affect bioavailability of drugs and his graduate education in pharmaceutical sciences involved extensive course work and research projects in the area of drug formulation, chemical modifications of drugs and pharmacokinetics.
[88] Dr. Gupta was qualified as an expert in the field of drug dissolution, drug formulation, and drug delivery systems, including nanoparticle-based injectables. He is also an expert in the bioavailability and pharmacokinetic trials and is familiar with pharmacokinetic modelling.
[89] Dr. Gupta provided his opinion on the issue of obviousness. He suffered some credibility issues in failing to agree to or admit simple, straightforward propositions. Dr. Gupta has also never conducted or designed a clinical trial or pharmacokinetic trial in humans.
B. Claim Construction
[90] Claim construction is a matter of law for the Court (Whirlpool Corp.v. Camco Inc., 2000 SCC 67 at paragraph 61). 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 paragraphs 25, 35, and 36; Excalibre Oil Tools Ltd. v. Advantage Products Inc., 2016 FC 1279 at paragraph 119).
[91] The principles of claim construction were summarized by the Federal Court of Appeal in Tearlab Corporation v. I-Med Pharma Inc., 2019 FCA 179 at paragraphs 30 to 34:
[30] The general principles of claim construction are now well established and were set out by the Supreme Court in three cases (Whirlpool at paras. 49-55; Free World Trust v. Électro Santé Inc., 2000 SCC 66, [2000] 2 S.C.R. 1024 at paras. 31-67 [Free World Trust]; Consolboard Inc. v. MacMillan Bloedel (Sask.) Ltd., 1981 CanLII 15 (SCC), [1981] 1 S.C.R. 504 at p. 520 [Consolboard]). These principles can be summarized as follows.
[31] The Patent Act promotes adherence to the language of the claims, which in turn promotes fairness and predictability (Free World Trust at paras. 31(a), (b) and 41). The words of the claims must, however, be read in an informed and purposive way (at para. 31(c)), with a mind willing to understand (at para. 44). On a purposive construction, it will be apparent that some elements of the claimed invention are essential while others are non-essential (at para. 31(e)). The interpretative task of the court, in claim construction, is to separate and distinguish between the essential and the non-essential elements, and to give the legal protection to which the holder of a valid patent is entitled only to the essential elements (at para. 15).
[32] To identify these elements, the claim language must be read through the eyes of a POSITA, in light of the latter’s common general knowledge (Free World Trust at paras. 44-45; see also Frac Shack at para. 60; Whirlpool at para. 53). As noted in Free World Trust:
[51] …The words chosen by the inventor will be read in the sense the inventor is presumed to have intended, and in a way that is sympathetic to accomplishment of the inventor’s purpose expressed or implicit in the text of the claims. However, if the inventor has misspoken or otherwise created an unnecessary or troublesome limitation in the claims, it is a self-inflicted wound. The public is entitled to rely on the words used provided the words used are interpreted fairly and knowledgeably. [Emphasis in the original.]
[33] Claim construction requires that the disclosure and the claims be looked at as a whole “to ascertain the nature of the invention and methods of its performance, … being neither benevolent nor harsh, but rather seeking a construction which is reasonable and fair to both patentee and public” (Consolboard at p. 520; see also Teva Canada Ltd. v. Pfizer Canada Inc., 2012 SCC 60, [2012] 3 S.C.R. 625 at para. 50). Consideration can thus be given to the patent specifications to understand what was meant by the words in the claims. One must be wary, however, not to use these so as “to enlarge or contract the scope of the claim as written and … understood” (Whirlpool at para. 52; see also Free World Trust at para. 32). The Supreme Court recently emphasized that the focus of the validity analysis will be on the claims; specifications will be relevant where there is ambiguity in the claims (AstraZeneca Canada Inc. v. Apotex Inc., 2017 SCC 36, [2017] 1 S.C.R. 943 at para. 31; see also Ciba at paras. 74-75).
[34] Finally, it is important to stress that claim construction must be the same for the purpose of validity and for the purpose of infringement (Whirlpool at para. 49(b)).
[92] The relevant date for construing the claims is the publication date: June 19, 2009.
[93] As stated above, the construction of all 63 claims of the 335 Patent and the POSITA have been previously determined and are not at issue in these proceedings.
[94] The essential elements of claim 1 are (Teva Paliperidone at paragraph 145):
Prefilled syringes containing a depot formulation of paliperidone as paliperidone palmitate formulated as an aqueous nanoparticle suspension;
For administration by intramuscular injection to a psychiatric patient in need of treatment for schizophrenia, schizoaffective disorder, or schizophreniform disorder;
Wherein the prefilled syringes are adapted for administration in accordance with the following dosing regimen:
A first loading dose of about 150 mg-eq. of paliperidone injected into the deltoid on treatment Day 1;
A second loading dose of about 100 mg-eq. of paliperidone injected into the deltoid on treatment Day 8 ± 2 days;
Continuous maintenance doses of 75 mg-eq. of paliperidone injected into the deltoid or gluteal monthly ± 7 days thereafter.
[95] The essential elements of claim 2 are the same, except that the patient in need of treatment must have renal impairment, and the claimed dose amounts are about 100 mg-eq., 75 mg-eq., and 50 mg-eq., respectively (Teva Paliperidone at paragraph 146).
[96] The essential elements of the claims are conjunctive. The first claim set requires the combination of multiple prefilled syringes of varying dosage amounts adapted for administration in accordance with the claimed dosing schedule and injection sites. The claimed invention is a dosing regimen, not simply dosage forms (Teva Paliperidone at paragraphs 147).
[97] Claims 3 through 14 depend from claims 1 and 2, and include further specific formulation limitations. Claims 3 through 14 incorporate the dose amounts, dosing windows, and injection sites from independent claims 1 and 2 (Teva Paliperidone at paragraph 128).
[98] Claim 15 further limits any of claims 1 to 14 to administration to a psychiatric patient in need of treatment for schizophrenia only. Claim 16 is similar, but limited to psychiatric patients in need of treatment for schizoaffective disorder only (Teva Paliperidone at paragraph 129).
[99] Claims 1 to 16 comprise “product” claims (Teva Paliperidone at paragraphs 145 to 147).
[100] Claims 17 to 32 effectively mirror claims 1 to 16, except that they are directed towards “use of a dosage form of paliperidone as paliperidone palmitate” rather than prefilled syringes (Teva Paliperidone at paragraph 148).
[101] Claims 17 and 18 claim the same dosing regimen as claims 1 and 2. Claims 19 to 30 include the same formulation limitations as claims 3 to 14. Claims 31 and 32 are identical to claims 15 and 16 except for the claims upon which they depend (Teva Paliperidone at paragraph 149).
[102] Where the s