Medexus Pharmaceuticals Inc. v. Accord Healthcare Inc.

Medexus Pharmaceuticals Inc. v. Accord Healthcare Inc.
Court (s) Database
Federal Court Decisions
Date
2024-03-26
Neutral citation
2024 FC 424
File numbers
T-1007-20
Decision Content
Date: 20240326
Docket: T-1007-20
Citation: 2024 FC 424
Toronto, Ontario, March 26, 2024
PRESENT: Madam Justice Pallotta
BETWEEN:
MEDEXUS PHARMACEUTICALS INC., MEDEXUS INC. and MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH
Plaintiffs
(Defendants by Counterclaim)
and
ACCORD HEALTHCARE INC. AND
INTAS PHARMACEUTICALS LTD.
Defendants
(Plaintiffs by Counterclaim)
PUBLIC JUDGMENT AND REASONS
(Identical to the Confidential Judgment and Reasons issued
on March 14, 2024)
TABLE OF CONTENTS
I. Introduction 3
II. Issues and Determinative Issue 4
III. Background on Methotrexate 7
IV. 662 Patent and Asserted Claims 8
V. Evidence 11
A. Dr. Massarotti (plaintiffs’ expert witness) 12
B. Dr. Sinko (plaintiffs’ expert witness) 13
C. Mr. Harington (plaintiffs’ expert witness) 15
D. Mr. Will (plaintiffs’ fact witness) 16
E. Dr. Mark Jansen and Dr. Matthijs Janssen (plaintiffs’ fact witnesses) 17
F. Dr. Roth (defendants’ expert witness) 18
G. Dr. Rue (defendants’ expert witness) 20
VI. Admissibility of Dr. Jansen’s and Dr. Janssen’s Testimony 21
VII. Principles: Skilled Person and Common General Knowledge 25
VIII. Claim Construction 27
IX. Validity 33
A. Skilled Person 33
(1) The parties’ submissions 33
(2) Analysis 35
B. Common General Knowledge 40
(1) The parties’ submissions 40
(2) Analysis 40
C. Obviousness 51
(1) Legal Principles 51
(2) The parties’ submissions 53
(3) Step 1: The skilled person and their CGK 58
(4) Step 2: Inventive concept 58
(5) Step 3: Differences between the State of the Art and the Inventive Concept 68
(6) Step 4: Are the Differences Obvious? 72
D. Other invalidity grounds 82
(1) Anticipation 82
(2) Ambiguity 83
(3) Utility, Insufficiency, Overbreadth 91
X. Damages 94
XI. Conclusion 98
SCHEDULE A 100
I. Introduction
[1] In this patent action the plaintiffs seek remedies for the defendants’ alleged infringement of Canadian Patent No 2,659,662 titled “Concentrated Methotrexate Solutions” (662 Patent). The opening paragraph of the 662 Patent states:
The present invention relates to concentrated methotrexate solutions. In particular, the present invention relates to the use of methotrexate in the production of a parenterally administered medicament for the treatment of inflammatory autoimmune diseases, wherein the methotrexate is present in a pharmaceutically acceptable solvent at a concentration of more than 25 mg/ml. The invention also relates to a ready-made syringe and a carpule containing such a pharmaceutical solution formulation, as well as a pen injector comprising such a carpule and/or a ready-made syringe.
[2] The plaintiff medac Gesellschaft für klinische Spezialpräparate mbH (medac), owner of the 662 Patent, manufactures Metoject® pre-filled (or ready-made) syringes containing a 50 mg/ml methotrexate solution for parenteral administration. Specifically, Metoject® syringes are approved for subcutaneous injection and can be prescribed to treat severe disabling rheumatoid arthritis and psoriasis/psoriatic arthritis, which are inflammatory autoimmune diseases (IADs). Rheumatoid arthritis mainly affects synovial joints. Psoriasis mainly affects the skin and can develop into psoriatic arthritis.
[3] Metoject® syringes are offered as 7.5, 10, 12.5, 15, 17.5, 20, 22.5 and 25 mg doses of methotrexate. For example, a 10 mg dose syringe would contain 0.2 ml of a 50 mg/ml methotrexate solution for injection and a 25 mg dose syringe would contain 0.5 ml of a 50 mg/ml methotrexate solution for injection.
[4] The plaintiffs Medexus Inc and Medexus Pharmaceuticals Inc claim relief as licensees of the 662 Patent. Medexus Inc marketed Metoject® products in Canada until it merged with Medexus Pharmaceuticals Inc in 2021. Since then, medac has licensed Medexus Pharmaceuticals Inc to market and sell Metoject® products in Canada.
[5] The defendant Accord Healthcare Inc (Accord), a subsidiary of Intas Pharmaceuticals Ltd (Intas), received Health Canada approval to market methotrexate products for subcutaneous injection based on a comparison to medac’s Metoject® products. Accord received approval to market syringes pre-filled with a 50 mg/ml methotrexate solution in 2019 (Accord Products), and it received approval to market injector devices pre-filled with a 50 mg/ml methotrexate solution in 2022 (Methofill Products). Intas is the manufacturer of these products.
II. Issues and Determinative Issue [6] The plaintiffs assert that the defendants infringe claims 1 to 10, 18 to 22, 35, and 39 of the 662 Patent (Asserted Claims), including by importing and selling Accord Products and Methofill Products in Canada.
[7] The defendants contend they are not liable for patent infringement because each of the Asserted Claims is invalid. The defendants allege that the subject matter of the Asserted Claims is not inventive and that medac has claimed a monopoly for what amounts to an obvious extension of its existing methotrexate product line. The defendants also allege that some or all of the Asserted Claims are invalid because their subject matter was anticipated, insufficiently disclosed, overbroad, or ambiguous, or because utility was not supported across the full scope of the claim. The defendants counterclaim for a declaration that the 662 Patent claims are, and always have been, invalid and of no force or effect.
[8] Just before the commencement of trial, the defendants conceded that the Accord Products and the Methofill Products would infringe the Asserted Claims if they are valid. As a result of the concession, the plaintiffs did not lead evidence to establish that the Accord Products and Methofill Products fall within the scope of the Asserted Claims. There are no non-infringement issues before the Court, apart from validity.
[9] Consequently, the issues in this action relate to claim construction, validity, and the remedy for infringement of any valid Asserted Claims.
[10] The only point of claim construction in dispute relates to the meaning of the term ‘about 50 mg/ml’ in claims 3 and 20 of the 662 Patent.
[11] The defendants bear the onus of establishing that the Asserted Claims are invalid. They advance the following grounds of invalidity:
anticipation (claims 1-6);
obviousness;
ambiguity (claims 3, 20 and their dependent claims);
lack of demonstrated or soundly predicted utility across the full scope of the claims;
insufficiency; and
overbreadth.
[12] Schedule A to these reasons is a list of scientific references the parties relied on, including 22 references the defendants pleaded as prior art. Where I refer to a reference in these reasons, I use the short form notation identified in bold text in Schedule A.
[13] If the defendants infringe at least one valid Asserted Claim, the plaintiffs ask the Court to award monetary relief for past infringement and an injunction to prevent future infringement. With respect to monetary relief, the plaintiffs elected damages instead of an accounting of the defendants’ profits. The plaintiffs seek an award of damages to compensate them for lost Metoject® profits resulting from the defendants’ sales of infringing products.
[14] For the reasons below, the Asserted Claims are invalid for obviousness. Obviousness is the determinative issue in the action and the defence fully succeeds on this basis.
[15] It is not necessary to address the other invalidity grounds. However, I will address the other invalidity grounds to the extent they relate to the narrowest Asserted Claim the defendants were required to invalidate to succeed in their defence. In view of the defendants’ concession that they would infringe all Asserted Claims, no purpose would be served by deciding whether claims 1-6 are invalid for anticipation. Ambiguity affects the narrowest Asserted Claim. I will address ambiguity in detail because it overlaps with claim construction, and because two expert witnesses addressed it in some detail and were cross-examined at length on this ground. I will address utility, insufficiency, and overbreadth to the extent these grounds affect the narrowest Asserted Claim; however, the analysis is brief in view of my findings on obviousness.
III. Background on Methotrexate [16] Methotrexate has a long history of use as a medication—since about the 1950s.
[17] Methotrexate was first used to treat certain forms of cancer. It belongs to a class of chemotherapeutic agents known as antifolates, which inhibit cell proliferation by antagonizing folic acid and interfering with the synthesis of tetrahydrofolate. Tetrahydrofolate is involved in a variety of intracellular processes including the synthesis, repair, and replication of DNA.
[18] By the 1980s, clinical trials had established methotrexate’s effectiveness in treating IADs—that is, diseases characterized by inflammation caused by the body’s immune system attacking its own cells. Methotrexate soon became a standard treatment for rheumatoid arthritis, psoriasis, and other IADs.
[19] When used to treat IADs, methotrexate is prescribed at lower doses than those typically used for cancer treatment. At lower doses methotrexate acts as an immunosuppressant, but even today, its mechanism of action in this regard is not fully understood. At the doses used to treat IADs, methotrexate is classified as a disease modifying anti-rheumatic drug (DMARD). DMARDs modify the body’s inflammatory response in a different way than steroids or non-steroidal anti-inflammatory drugs. DMARDs can slow the progression of the disease.
[20] Patients on methotrexate for IADs typically remain on methotrexate indefinitely, taking the drug weekly in the form of orally administered tablets or injections of a solution containing the prescribed dose.
IV. 662 Patent and Asserted Claims [21] The 662 Patent was filed in Canada on July 20, 2007 with an earlier claimed priority filing date based on a German patent application filed on July 21, 2006. The application for the 662 Patent was published on January 24, 2008. The 662 Patent issued on January 20, 2015.
[22] As noted above, the 662 Patent specification states the invention relates to concentrated methotrexate solutions, and in particular, the use of methotrexate in the production of a parenterally administered medicament for the treatment of IADs wherein the methotrexate is present in a pharmaceutically acceptable solvent at a concentration of more than 25 mg/ml. In an especially preferred embodiment, the methotrexate is present in a pharmaceutically acceptable solvent at a concentration of about 50 mg/ml.
[23] Parenteral administration refers to routes of administration that avoid the gastrointestinal tract. While the 662 Patent does not define ‘parenteral’, it states the medicament is administered by intravenous, intramuscular, or subcutaneous injection. Subcutaneous administration is an injection into the tissue immediately below the skin. A preferred embodiment of the 662 Patent provides that the methotrexate solution is in a form suitable for subcutaneous self-administration by the patient and all Asserted Claims include a limitation of subcutaneous administration.
[24] The 662 Patent specification states the medicaments of the invention are directed to the treatment of all IADs that can reasonably be treated with methotrexate; for example, rheumatoid arthritis, juvenile arthritides, vasculitides, collagenoses, Crohn’s disease, colitis ulcerosa, bronchial asthma, Alzheimer’s disease, multiple sclerosis, Bechterew’s disease, joint arthroses or psoriasis, as well as psoriasis arthritis and in particular plaque-type psoriasis vulgaris. The specification states the medicaments are especially preferred for the treatment of rheumatoid arthritis, including juvenile arthritides, such as specifically the oligoarthritic and polyarthritic forms of juvenile arthritis.
[25] The Asserted Claims are independent claims 1 and 18 and dependent claims 2-10, 19-22, 35, and 39, as they directly or indirectly depend from one another. The same Asserted Claims are advanced against the Accord Products and the Methofill Products.
[26] Claim 1 relates to the use of methotrexate to produce a subcutaneously administered medicament for the treatment of IADs where the methotrexate is present in a solvent at a concentration greater than 30 mg/ml. Claim 18 relates to a ready-made syringe comprising a methotrexate formulation for subcutaneous administration where the concentration of methotrexate is greater than 30 mg/ml. The dependent claims add limitations on methotrexate concentration, methotrexate dosage, the solvent, disease indications, and/or aspects of administration.
[27] The Asserted Claims in the 662 Patent read as follows (independent claims are shown in bold text):
1. Use of methotrexate for the production of a subcutaneously administered medicament for the treatment of inflammatory autoimmune diseases, wherein the methotrexate is present in a pharmaceutically acceptable solvent at a concentration of more than 30 mg/ml.
2. Use according to claim 1, wherein the methotrexate is present at a concentration of more than 30 mg/ml to 100 mg/ml.
3. Use according to claim 2, wherein the methotrexate is present at a concentration of about 50 mg/ml.
4. Use according to any one of claims 1 to 3, wherein the pharmaceutically acceptable solvent is selected from water, water for injection purposes, water comprising isotonization additives and sodium chloride solution.
5. Use according to any one of claims 1 to 4, wherein the inflammatory autoimmune disease is selected from rheumatoid arthritis, juvenile arthritides, vasculitides, collagenoses, Crohn's disease, colitis ulcerosa, bronchial asthma, Alzheimer's disease, multiple sclerosis, Bechterew's disease, joint arthroses, or psoriasis.
6. Use according to claim 5, wherein the inflammatory autoimmune disease is rheumatoid arthritis.
7. Use according to any one of claims 1 to 6, wherein the medicament is present in a form suitable for patient self-administration.
8. Use according to any one of claims 1 to 7, wherein the medicament is contained in an injection device for a single application.
9. Use according to claim 8, wherein the injection device contains a dosage of 5 to 40 mg.
10. Use according to claim 8 or 9, wherein the injection device is a ready-made syringe.
…
18. Ready-made syringe, comprising a pharmaceutical solution formulation of methotrexate with a concentration of more than 30 mg/ml in a pharmaceutically acceptable solvent for subcutaneous administration.
19. Ready-made syringe according to claim 18, wherein the methotrexate is present at a concentration of more than 30 mg/ml to 100 mg/ml.
20. Ready-made syringe according to claim 19, wherein the methotrexate is present at a concentration of about 50 mg/ml.
21. Ready-made syringe according to any one of claims 18 to 20, comprising a dosage of 5 to 40 mg.
22. Ready-made syringe according to any one of claims 18 to 21, wherein the pharmaceutically acceptable solvent is selected from water, water for injection purposes, water comprising isotonization additives and sodium chloride solution.
…
35. Use according to claim 9, wherein the injection device contains a dosage of 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 27.5, 30.0, 32.5, 35.0, 37.5 or 40.0 mg, of methotrexate.
…
39. Ready-made syringe according to claim 21, comprising a dosage of 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 27.5, 30.0, 32.5, 35.0, 37.5 or 40.0 mg, of methotrexate.
V. Evidence [28] The parties agreed on many facts. They provided a joint scientific primer and a joint statement of facts.
[29] The parties introduced expert evidence in support of their respective positions on claim construction and validity. The plaintiffs had served a report by an expert witness who opined on claim construction and infringement, but they elected not to call that witness at trial in view of the defendants’ concession on infringement. For the same reason, the defendants did not rely on a report by one of its experts, Peter Rue, on the issue of infringement. While it is often the case that a defendant will lead evidence first when validity is the main issue for determination, the trial schedule was set before the defendants withdrew their non-infringement defence and the plaintiffs led their evidence first.
[30] The plaintiffs called three expert witnesses: Elena Massarotti, Patrick J Sinko, and Andrew Harington. The plaintiffs also called three fact witnesses: the inventor Heiner Will, as well as Mark Jansen and Matthijs Janssen, who are authors of a prior art reference the defendants rely on. The defendants raised evidentiary objections to the testimony of Drs. Jansen and Janssen, arguing their testimony is irrelevant, improper, and prejudicial because it was expert opinion rather than fact evidence.
[31] The defendants called two expert witnesses: Johannes Roth and Peter Rue. They did not call an expert witness on damages.
[32] The following provides an overview of each side’s witnesses and their evidence.
A. Dr. Massarotti (plaintiffs’ expert witness) [33] Dr. Massarotti is a rheumatologist, professor, and researcher. Dr. Massarotti received her MD from Tufts University School of Medicine in 1984 and completed her internship and residency in internal medicine at New England Medical Center (which later became Tufts Medical Center) from 1984 to 1987. From 1988 to 1990, Dr. Massarotti completed a fellowship in Rheumatology/Immunology at New England Medical Center, and from 1990 to 1991 she was the Chief Medical Resident. Dr. Massarotti held several positions related to rheumatology at Tufts Medical Center between 1993 and 2007, including director of clinical rheumatology training, acting division chief of rheumatology, and clinical director of rheumatology.
[34] Dr. Massarotti is board certified in internal medicine and in rheumatology and a member of the American College of Rheumatology. She is an Associate Professor at Harvard Medical School and an Associate Physician at Brigham and Women’s Hospital. At the hospital, Dr. Massarotti is the director of clinical trials for the Lupus Center and a co-director of the Clinical Trials Center at the Division of Rheumatology. Dr. Massarotti is active in academia, serving as an ad hoc reviewer for several medical journals, serving on the executive committee of the Lupus Nephritis Trials Network, and publishing peer-reviewed articles, review articles, book chapters, and abstracts, including reports of clinical trials, epidemiologic studies, and clinical observations in the areas of autoimmune disease.
[35] The plaintiffs proposed that Dr. Massarotti was qualified to provide expert opinion evidence as:
A physician, associate professor of medicine, and clinical researcher with expertise in (1) rheumatology, (2) the treatment of patients suffering from inflammatory autoimmune diseases with methotrexate, and (3) the analysis and interpretation of experimental results, including from pre-clinical and clinical trials in clinical rheumatology, in the area of inflammatory autoimmune diseases, including rheumatoid arthritis.
[36] The defendants did not object to Dr. Massarotti’s proposed qualifications and I was satisfied she was qualified to provide expert opinion evidence according to the plaintiffs’ proposed qualifications.
[37] Dr. Massarotti’s expert report dated September 8, 2022 sets out her opinions on specific mandates related to the qualifications and knowledge of the skilled person, construction of the Asserted Claims, and the validity of the Asserted Claims. Confidential and public versions of her report were marked as trial exhibits. Her report was taken as read.
B. Dr. Sinko (plaintiffs’ expert witness) [38] Dr. Sinko is a pharmaceutical consultant, registered pharmacist, professor, and researcher. Dr. Sinko earned a Bachelor of Science degree in pharmacy from the College of Pharmacy, Rutgers University in 1982 and he received a PhD in pharmaceutics from the College of Pharmacy, University of Michigan in 1988. From 1988 to 1991, Dr. Sinko was a Research Scientist at the University of Michigan and Therapeutic Systems Research Labs. Dr. Sinko has been a Professor in the Department of Pharmaceutics at Rutgers University’s College of Pharmacy since 1991 and was appointed Distinguished Professor in 2007. Dr. Sinko has held several positions in academic publishing, including a current position as Editor-in-Chief (Biopharmaceutics) for the journal Pharmaceutics and a previous position as Section Editor for the European Journal of Pharmaceutical Sciences.
[39] Dr. Sinko is a member of the American Association for the Advancement of Science, American Association of Pharmaceutical Scientists, American Association of Colleges of Pharmacy, American College of Clinical Pharmacy, American Diabetes Association, American Society of Microbiology, and the Controlled Release Society. In 2003, he was elected as a fellow of the American Association of Pharmaceutical Scientists for being internationally recognized as an expert in biopharmaceutics and drug delivery.
[40] Dr. Sinko has authored, edited, and published articles in scientific journals, books, and chapters, including publications relating to injectable formulations. He has consulted for pharmaceutical and biotechnology companies and he has experience formulating injectable dosage forms including intradermal, subcutaneous, and intramuscular injections.
[41] The plaintiffs proposed that Dr. Sinko was qualified to provide expert opinion evidence as:
A professor, researcher, and registered pharmacist with expertise in (1) pharmaceutical science and formulation, including first-hand experience with a wide range of drugs and dosage forms, including the use of methotrexate, and (2) formulating drug delivery systems, including for subcutaneous, intramuscular, and intravenous injectable dosage forms.
[42] The defendants did not object to Dr. Sinko’s proposed qualifications and I was satisfied he was qualified to provide expert opinion evidence according to the plaintiffs’ proposed qualifications.
[43] Dr. Sinko’s expert report dated September 9, 2022 sets out his opinions on the qualifications and knowledge of the skilled person, construction of the Asserted Claims, and the validity of the Asserted Claims. Confidential and public versions of Dr. Sinko’s report were marked as trial exhibits. His report was taken as read.
C. Mr. Harington (plaintiffs’ expert witness) [44] Mr. Harington is a Chartered Professional Accountant, Chartered Financial Analyst charterholder, and Chartered Business Valuator. Mr. Harington earned a Bachelor of Commerce degree from the University of Cape Town in 1991, as well as a Bachelor of Commerce (Honours) degree in Financial Accounting and a Post Graduate Diploma in Accounting from the University of Cape Town in 1992. In South Africa, Mr. Harington was registered as a Chartered Accountant in 1995. In Canada, he was registered as a Chartered Accountant in 1998, a Chartered Financial Analyst in 2002, and a Chartered Business Valuator in 2005. Currently, Mr. Harington is a principal at The Brattle Group. Mr. Harington has experience in the valuation of businesses, intellectual property, and financial damages quantification. He has prepared investigative accounting and damage quantification reports for proceedings in the Federal Court and Ontario Superior Court.
[45] Mr. Harington is the lead author of the 2018 edition of Calculating Monetary Remedies in Intellectual Property Cases in Canada – a Reference Book of Principles and Case Law. He co-authored two earlier monographs published in 2012: Damages Calculations in Intellectual Property Cases in Canada and Accounting of Profits Calculations in Intellectual Property Cases in Canada.
[46] The plaintiffs proposed that Mr. Harington was qualified to provide expert opinion evidence as:
A Chartered Professional Accountant, Chartered Financial Analyst charterholder, and Chartered Business Valuator who is qualified to provide expert evidence on investigative and forensic accounting, business valuation, and quantification of financial remedies, including accounting of profits in patent infringement disputes.
[47] The defendants did not object to Mr. Harington’s proposed qualifications. I was satisfied he was qualified to provide expert opinion evidence according to the plaintiffs’ proposed qualifications.
[48] Mr. Harington’s June 10, 2022 expert report sets out his opinions on quantifying the plaintiffs’ lost profits due to the defendants’ sales. Significant parts of Mr. Harington’s report refer to solicitor’s eyes only (SEO) confidential information. SEO confidential and public versions of Mr. Harington’s report were marked as trial exhibits. His report was taken as read.
D. Mr. Will (plaintiffs’ fact witness) [49] Mr. Will is the sole inventor named in the 662 Patent. He has been employed at medac since 1984 and he was managing director of medac’s autoimmune group at the material times. Mr. Will testified about his roles at medac, the invention story, his role in the development of the Metoject® product, and medac’s business relationships regarding the product. He introduced a number of exhibits including medac documents that are written in German. Documents in the German language were entered as a three-part trial exhibit comprising the German document, the English translation of the document, and the translator’s affidavit. There was a pre-trial process for exchanging and raising any issue with certified translations of German documents and neither party raised an issue with the English translations of documents that were marked as trial exhibits.
[50] Although Mr. Will’s first language is German, he speaks English well. The parties agreed to have a German translator present throughout Mr. Will’s testimony in chief and cross-examination to provide assistance when needed. Mr. Will requested assistance from the interpreter from time to time, but for the most part Mr. Will testified capably in English.
E. Dr. Mark Jansen and Dr. Matthijs Janssen (plaintiffs’ fact witnesses) [51] Dr. Mark Jansen is a hospital pharmacist and clinical pharmacologist. Dr. Matthijs Janssen is a retired rheumatologist.
[52] Drs. Jansen and Janssen were working in their respective fields before 2006 and they are co-authors (together with a third author, Elsbeth Nagtegaal) of an academic article published in the scientific journal Pharmaceutisch Weekblad in 1999. The article is titled (translation) “Intramuscular and subcutaneous administration in rheumatoid arthritis, Methotrexate outside the clinic” and discusses intramuscular or subcutaneous injection as an alternative to oral methotrexate in the treatment of inflammatory autoimmune diseases. Jansen 1999 is one of the references discussed in the expert reports and there is no dispute that it is a prior art reference that could have been located by the skilled person. The original Dutch article was entered as a trial exhibit together with an English translation and translator’s certificate.
[53] The defendants brought a motion to exclude Drs. Jansen and Janssen from testifying on the basis that their evidence would be inadmissible. I declined to rule on admissibility before hearing the evidence.
[54] Drs. Jansen and Janssen each testified about the Jansen 1999 article, as well as their personal knowledge and experience relating to the preparation and use of methotrexate solutions at the material times. The latter included evidence about aspects of the state of the art, as well as answers to questions asking whether Drs. Jansen and Janssen had considered increasing the concentration of methotrexate solutions or creating a new methotrexate formulation.
[55] My admissibility ruling is in the next section of these reasons.
F. Dr. Roth (defendants’ expert witness) [56] Dr. Roth is a pediatric rheumatologist, professor, and researcher. Dr. Roth received his MD from the University of Tuebingen in 1996 and then completed a residency in pediatrics and a fellowship in pediatric rheumatology. From 2001 to 2007, Dr. Roth practiced as an academic pediatric rheumatologist at Charité University and completed his habilitation, which is an extended PhD thesis under the German academic system. Since 2007, Dr. Roth has been Chief of the Division of Pediatric Dermatology and Rheumatology at the Children’s Hospital of Eastern Ontario and a professor of pediatrics at the University of Ottawa’s Faculty of Medicine.
[57] Dr. Roth’s clinical practice includes diagnosis, treatment, and management of patients. While his clinical practice is focussed on pediatric rheumatic diseases, he also treats adult patients over the age of 18 when they have not yet been transitioned to a rheumatologist who treats adult patients.
[58] Dr. Roth is active in academia, having published numerous peer-reviewed papers, abstracts, and book chapters primarily in the field of pediatric rheumatology. Dr. Roth has acted as both a principal investigator and co-investigator in clinical trials, including trials related to rheumatology.
[59] The plaintiffs did not object to Dr. Roth’s proposed qualifications. I was satisfied Dr. Roth was qualified to provide expert opinion evidence according to the proposed qualifications that were put forward by the defendants:
Dr. Johannes Roth is an academic and clinical pediatric rheumatologist who has expertise in the diagnosis, treatment, and management of autoimmune disorders including in particular both juvenile and adult rheumatic diseases such as rheumatoid arthritis and juvenile idiopathic arthritis. Dr. Roth also has expertise in the prescribing, dosing, and administration of methotrexate to patients.
[60] Dr. Roth prepared an expert report dated June 10, 2022. The report sets out Dr. Roth’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. Confidential and public versions of Dr. Roth’s report were marked as trial exhibits and taken as read.
G. Dr. Rue (defendants’ expert witness) [61] Dr. Rue is a pharmaceutical consultant. Dr. Rue earned a Bachelor of Science degree in 1973 and a PhD in pharmacy in 1978 from the University of Aston in Birmingham. He worked in the Formulation Development Department of the Beecham Pharmaceuticals Research Division of Burgh Heath from 1977 to 1980. Dr. Rue was employed at the Pharmaceutical Research Department of Glaxo Group Research of Ware, England from 1980 to 1995 and headed the Pharmaceutical Development Department from 1990 to 1995. Dr. Rue was a visiting professor at the University of Aston from 2001 to 2017, teaching solid dosage form modules as part of the Masters program in pharmacy.
[62] Dr. Rue is a member of the Royal Pharmaceutical Society of Great Britain. He has co-authored academic publications, including publications related to pharmaceutical formulations and compositions, and is a named inventor on a number of pharmaceutical patents.
[63] The plaintiffs did not object to Dr. Rue’s proposed qualifications. I was satisfied Dr. Rue was qualified to provide expert opinion evidence according to the proposed qualifications that were put forward by the defendants:
Dr. Peter J. Rue is a pharmaceutical consultant who has expertise in drug development, pharmaceutical formulation, and drug delivery, including in the design and development of liquid pharmaceutical formulations and injectable pharmaceutical formulations.
[64] Dr. Rue prepared an expert report dated June 1, 2022. The report sets out Dr. Rue’s opinions on mandates related to the qualifications and knowledge of the skilled person, construction of the Asserted Claims, and the validity of the Asserted Claims.
[65] The defendants had served a second expert report from Dr. Rue, on infringement. In view of their concession on infringement, the defendants did not rely on Dr. Rue’s second report.
[66] The defendants sought leave to introduce a third expert report from Dr. Rue dated October 26, 2022, to reply to Dr. Sinko’s expert opinion on the issue of ambiguity. In a decision dated December 14, 2022 (2022 FC 1734), I granted the motion in part. At trial, the defendants tendered a redacted copy of Dr. Rue’s third report that only included the paragraphs I had found to be proper reply evidence, namely, paragraphs 1-4, 6-8, 10-11, the first sentence of paragraph 12, paragraphs 16-22, and the first sentence of paragraph 23.
[67] Confidential and public versions of Dr. Rue’s first report, as well as the redacted copy of his third report (which did not contain any confidential information), were marked as trial exhibits and taken as read.
VI. Admissibility of Dr. Jansen’s and Dr. Janssen’s Testimony [68] On the first day of trial, the defendants brought a motion to exclude Drs. Jansen and Janssen from testifying, on grounds that their testimony would be irrelevant, improper, and prejudicial. The defendants argued the proposed testimony would be irrelevant because Drs. Jansen and Janssen were being put forward to testify about their personal knowledge and experience with methotrexate, but the question of obviousness is an objective assessment based on expert evidence of the skilled person’s perspective and assessment of the prior art. The defendants also argued the proposed testimony would be improper and prejudicial because it would be tantamount to expert opinion tendered under the guise of fact evidence, without complying with procedural safeguards for opinion evidence. They noted that Drs. Jansen and Janssen have expertise similar to that of the experts in this case and would be testifying about issues addressed in the experts’ reports. The defendants argued the proposed testimony would prejudice the Court’s fact finding process as it would overlap with the parties’ expert evidence and render it impossible to extricate determinations properly made on the expert evidence from those improperly made based on Dr. Jansen’s or Dr. Janssen’s testimony.
[69] In response, the plaintiffs argued that the evidence: (i) should be judged by its content (Dow Chemical Canada ULC v Nova Chemicals Corporation, 2015 ABQB 401 at para 25) as fact evidence within Dr. Jansen’s and Dr. Janssen’s personal knowledge and experience, and not judged by whether these witnesses have the same expertise as the experts or would give testimony that relates to issues addressed in the expert reports; (ii) would be relevant as testimony from an actual person of ordinary skill that would help to resolve conflicting expert evidence on obviousness (Windsurfing International Inc v Trilantic Corp (1985), 8 CPR (3d) 241 at 259-260, 35 ACWS (2d) 255 (FCA); Merck & Co Inc v Apotex Inc, 2005 FC 755 at para 73); and (iii) being relevant and material, should only be excluded if its prejudicial effect on the fairness and integrity of the proceeding outweighs its value (R v Collins (2001), 160 CCC (3d) 85, 2001 CanLII 24124 at para 19 (ONCA)).
[70] After considering both sides’ arguments, I dismissed the defendants’ motion to exclude Drs. Jansen and Janssen from testifying. I was not satisfied, based solely on the short descriptions of proposed testimony set out in will-say statements, that the evidence or parts of it would be inadmissible. I decided that admissibility was something I would need to determine after hearing the testimony or at least after hearing enough of it to make a ruling.
[71] I refused to direct, as the plaintiffs had requested, that Dr. Jansen’s and Dr. Janssen’s testimony be admitted as long as it was limited to facts within their personal knowledge as set out in the will-say statements. I held that admissibility was not simply a question of whether these witnesses stayed within the proposed testimony set out in their will-say statements. While the will-say statements were a constraint, I held that evidence falling squarely within the will-say statements might be inadmissible as opinion evidence or for other reasons.
[72] The result was that I declined to rule on admissibility before hearing the evidence and I reserved my determination on admissibility.
[73] As a practical way to minimize the disruption of objections during Dr. Jansen’s and Dr. Janssen’s testimony, it was agreed that the defendants would be permitted to register a general objection on the grounds set out in their motion and defendants’ counsel would only rise to object on a different ground (for example, a hearsay objection). I ruled on the additional objections from the bench.
[74] Turning to the general objection, I agree with the defendants that Dr. Jansen’s and Dr. Janssen’s testimony is inadmissible. Their testimony related to three general topics: (i) Jansen 1999; (ii) aspects of the state of the art; and (iii) whether these witnesses considered increasing the concentration of methotrexate solutions or creating a new methotrexate formulation.
[75] On the first topic, Drs. Jansen and Janssen testified about what they wrote in Jansen 1999. Sometimes the testimony strayed into an explanation of what they meant by certain statements in the article. Testimony repeating what was written in Jansen 1999 was unnecessary. Testimony elaborating on Jansen 1999 was irrelevant—I agree with the defendants that what is relevant to the issues in this action is how the skilled person reading Jansen 1999 would have understood the article at the relevant time, not what the authors intended. That said, Dr. Jansen’s and Dr. Janssen’s testimony about Jansen 1999 was not materially different from the plain meaning of the article and the expert witnesses’ opinions on what the skilled person would take from it. Therefore, practically speaking, nothing turns on whether these witnesses’ evidence about Jansen 1999 is admissible or not.
[76] On the second topic, Dr. Jansen and/or Dr. Janssen testified about the dosage forms and concentrations of methotrexate that were used as of July 2006. They also testified about whether they or their colleagues drew on information or products from the treatment of cancer to inform how to treat patients with autoimmune diseases, and whether patients with rheumatoid arthritis would experience injection pain with subcutaneously administered methotrexate. In my view, this evidence is inadmissible as improper expert opinion. In any event, and regardless of how the evidence is characterized, I do not agree with the plaintiffs that the evidence assists to resolve any contentious aspects of the experts’ evidence on the above points. Drs. Jansen and Janssen were not instructed on the proper framework, they did not approach these questions from the skilled person’s perspective in light of the applicable legal principles, their evidence did not clearly favour or contradict any experts’ opinion, and they did not provide sufficient explanation to assist the Court in resolving any contentious points about the state of the art or the common general knowledge.
[77] For similar reasons, I find Drs. Jansen’s and Janssen’s evidence in respect of the third topic to be inadmissible. They answered ‘no’ to a series of questions asking whether, as of July 21, 2006: (i) either of them had ever raised the concentration of methotrexate solutions above 25 mg/ml, had considered doing so, or had considered creating a new methotrexate formulation for subcutaneous administration to treat IADs; and (ii) anyone had suggested raising concentration above 25 mg/ml or whether they were aware of anyone else doing so. While the actions of an “actual” person of ordinary skill can be relevant to an obviousness analysis, the evidence of Drs. Jansen and Janssen is not relevant or helpful to the obviousness inquiry in this case. Their negative answers to the questions posed do not assist the Court to resolve any