Gilead Sciences, Inc. v. Canada (Health)

Gilead Sciences, Inc. v. Canada (Health)
Court (s) Database
Federal Court Decisions
Date
2016-08-23
Neutral citation
2016 FC 857
File numbers
T-1694-14
Decision Content
Date: 20160823
Docket: T-1694-14
Citation: 2016 FC 857
Ottawa, Ontario, August 23, 2016
PRESENT: The Honourable Mr. Justice Brown
BETWEEN:
GILEAD SCIENCES, INC. AND
GILEAD SCIENCES CANADA, INC.
Applicants
and
THE MINISTER OF HEALTH AND
APOTEX INC.
Respondents
PUBLIC JUDGMENT AND REASONS
(Confidential Judgment and Reasons released July 21, 2016)
I. Nature of the Matter [1] This was originally an application for an order pursuant to section 6 of the Patented Medicines (Notice of Compliance) Regulations, SOR/1993-133 as amended, SOR/1998-166, SOR/1999-379, SOR/2006-242 (PM(NOC) Regulations) prohibiting the Minister of Health from issuing a Notice of Compliance (NOC) in respect of a Notice of Allegation (NOA) sent by Apotex Inc. (Apotex or the Respondent) to Gilead Sciences Canada, Inc. (Gilead or the Applicant) dated June 19, 2014 in respect of two Canadian Patents, namely Nos. 2,261,619 (619 Patent) and 2,298,059 (059 Patent) and tablets for oral administration containing tenofovir disoproxil fumarate (300 mg) (TDF). The 619 Patent covers the drug VIREAD®.
[2] However Justice Barnes struck issues concerning the validity of the 059 Patent from Gilead’s Notice of Application by Order dated May 8, 2015 (Gilead Sciences, Inc v Canada (Health), 2015 FC 610). I will not refer further to the 059 Patent.
[3] Also by way of background, there is a companion case namely Court File No. T-1693-14, which I heard at the same sittings as the present file. This companion case, decided contemporaneously with the case at bar, concerns Canadian Patent No. 2,512,475 (475 Patent) and Gilead's product TRUVADA® which involves a combination drug comprised of VIREAD® which is covered by the 619 Patent, and another drug, namely emtricitabine or FTC, also known as Coviracil. In the companion case, Justice Heneghan determined that the 619 Patent was ineligible for listing on the Patent Register and therefore ineligible for inclusion in that proceeding: Gilead Sciences, Inc v Canada (Health), 2016 FC 231; the 619 Patent was therefore struck from the Patent Register for purposes of that court file. An appeal was dismissed by the Federal Court of Appeal on May 4, 2016: Gilead Sciences, Inc v Apotex Inc, 2016 FCA 140.
[4] The parties agree that my findings regarding the 619 Patent apply equally to the companion T-1693-14 application. The allegations and evidence regarding the 619 Patent are identical in both Court files.
[5] As noted, only the 619 Patent remains in this proceeding. The 619 Patent covers VIREAD®, a prodrug useful in the treatment and prophylaxis of HIV. In this case, a prodrug is a compound designed to allow another drug with known medical benefits (called the parent drug) to cross the intestinal wall after which the prodrug is transformed back into its parent drug in the body, where the parent drug may then do what it is designed to do. The purpose of a prodrug is to overcome a bioavailability barrier after oral delivery in circumstances where the parent drug itself is unable to cross the intestinal wall into the body, i.e., has little or poor bioavailability when delivered orally. VIREAD® is a prodrug, tenofovir disoproxil, in the fumarate salt form, together TDF, which allows the parent drug, tenofovir or PMPA, to cross the intestinal wall into a patient’s body where the parent drug can do what it is designed to do. The prodrug is also known as bis(POC)PMPA.
[6] The 619 Patent is examined on its merits in this Court file. The asserted claim in the 619 Patent is Claim 32, which describes the chemical compound tenofovir disoproxil (TD) and its salts, tautomers and solvates. Infringement is not in issue; Apotex admits its proposed new drug will infringe the 619 Patent if the Patent is valid. Instead, Apotex relies on invalidity, alleging Patent 619 is invalid because it is not new (anticipation), it is obvious, it is an invalid selection as a selection patent, and is not useful (lacks utility). In my view, after reviewing the law and evidence, I find on a balance of probabilities that the allegations in Apotex’s NOA are not justified. Therefore the Order of prohibition is issued.
II. Facts A. Notice of Allegation [7] The NOA dated June 19, 2014, alleges the 619 Patent (and the 059 Patent) are invalid on various grounds. Appended to the NOA are 199 documents. There is a Protective Order in place which is why these Reasons are issued in this Confidential version.
B. 619 Patent [8] The 619 Patent states in relevant parts:
BACKGROUND OF THE INVENTION [page 5]
The present invention relates to intermediates for phosphonomethoxy nucleotide analogs, in particular intermediates suitable for use in the efficient oral delivery of such analogs.
Such analogs per se and various technologies for oral delivery of these and other therapeutic compounds are known. See WO 91/19721, WO 94/03467, WO 94/03466, WO 92/13869, U.S. 5,208,221, 5,124,051, DE 41 38 584 Al, WO 94/10539, WO 94/10467, WO 96/18605, WO 95/07920, WO 95 79 /07919, WO 92/09611, WO 92/01698, WO 91/19721, WO 88/05438, EP 0 632 048, EP 0 481 214, EP 0 369 409, EP 0 269 947, U.S. Patent Nos. 3,524,846 and 5,386,030, Engel Chem. Rev. 77:349-367 1977, Farquhar et al., J. Pharm. Sci.72:324-325 1983, Starrett et al., Antiviral Res. 19:267-273 1992, Safadi et al., Pharmaceutical Research 10(9):1350-1355 1993, Sakamoto et al., Chem. Pharm. Bull. 32(6):2241-2248 1984, and Davidsen et al., J. Med. Chem. 37(26):4423-4429 1994.
Utilities: [page 35]
The compounds of this invention are useful in the treatment or prophylaxis of one or more viral infections in man or animals, including infections caused by DNA viruses, RNA viruses, herpesviruses (CMV, HSV 1, 5 HSV 2, VZV, and the like), retroviruses, hepadnaviruses, (e.g. HBV), papillomavirus, hantavirus, adenoviruses and HIV. Other infections to be treated with the compounds herein include MSV, RSV, SIV, FIV, MuLV, and other retroviral infections of rodents and other animals. The prior art describes the antiviral specificity of the nucleotide analogs, and the parental drug specificity is shared by the compounds of this invention.
Example 15 [page 56]
Oral Bioavailability of PMPA and PMPA Carbonates in Beagle Dogs
Example 16
Antiviral Activity of PMPA and PMPA Carbonates in Tissue Culture
Claims [page 70]
32. A compound having the structure:
and its salts, tautomers and solvates.
C. Witnesses (1) Experts (a) Gilead Dr. Franz Maag [9] Dr. Maag has been practicing for over 40 years in the area of organic chemistry with an emphasis on medicinal chemistry and experience with anti-viral agents, immunosuppressive agents and anti-HIV agents. He has authored articles on prodrugs and nucleoside chemistry, and contributed chapters to a textbook on prodrugs. Dr. Maag has been a consultant in the pharmaceutical and biotechnology field since 2010.
[10] By 1996 Dr. Maag had already accumulated fifteen years of experience as a researcher in various capacities for Hoffman-Laroche and Syntex Discovery. In October 1994, he was promoted to principal scientist in the institute of organic chemistry at Syntex Discovery Research in Palo Alto, California, where Dr. Maag led a medicinal chemistry group whose focus was on novel analgesic agents (i.e. painkillers). Dr. Maag also served as project team leader for the clinical development of a prodrug of the antiviral agent ganciclovir, in respect of which he is a named inventor of Canadian Patent No. 2,154,721. Syntex Discovery Research was later acquired and renamed as Roche Bioscience. In June 1996, Dr. Maag was promoted to senior research scientist at Roche Bioscience.
Dr. Ronald Borchardt [11] Dr. Borchardt has over 40 years of academic and research experience in drug and prodrug design and development. Dr. Borchardt has had an impressive academic career, publishing over 500 papers and 450 abstracts of presentations, chairing the Department of Pharmaceutical Science at the University of Kansas, receiving prizes and honorary degrees, and was more recently an editor of a 2-volume, 1,500-page book entitled “Pro-drugs: Challenges and Rewards”, to which Dr. Maag contributed two chapters.
[12] By 1996 Dr. Borchardt had already acquired over 25 years of experience in his field. He acquired a PhD degree in medicinal chemistry from the University of Kansas in 1970. During his tenure at The University of Kansas, Dr. Borchardt held academic appointments in the Departments of Pharmaceutical Chemistry (1983-present), Biochemistry (1971-1999) and Medicinal Chemistry (1981-1994). For 15 years, from 1983 to 1998, Dr. Borchardt was the Chairman of the Department of Pharmaceutical Chemistry at The University of Kansas. Since 2001, Dr. Borchardt has served as Editor-in-Chief of the Journal of Pharmaceutical Sciences. It was not contested, and I accept that this is the “official journal” of both the American Pharmacists Association and the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation. Dr. Borchardt has also served on the editorial advisory boards for many other journals in the pharmaceutical sciences, including: Journal of Drug Targeting (1992-2008), Pharmaceutical Research (1986-2005), Advanced Drug Delivery Reviews (1992-2004), Molecular Interventions (2000-2005), European Journal of Pharmaceutical Sciences (1998-2003), Journal of Peptide Research (1997-2001), AAPS (American Association of Pharmaceutical Scientists) Journal (1999-2001), Antiviral Research (1988-2000), and Journal of Medicinal Chemistry (1988-1993).
Dr. Richard Elion [13] Dr. Elion is a family medicine physician with experience in treating HIV. Dr. Elion started working with patients with HIV/AIDS in 1984, and was the medical director at Stuyvesant Polyclinic in 1985, when the clinic became the first community health center in New York City to offer HIV testing. Dr. Elion’s medical practice focused on HIV/AIDS. Dr. Elion also served as an advisor on various HIV/AIDS policy boards, and as an author and editor for publications with a focus on the treatment of HIV/AIDS. Dr. Elion is currently funded by Gilead in clinical research related to its integrase inhibitors, and has provided medical advisory services for Gilead in the past. Dr. Elion provided evidence on the treatment for HIV/AIDS at the relevant times, and clinical impact of VIREAD®.
(b) Apotex (i) Dr. Joseph Fortunak [14] Dr. Fortunak is a Professor of Chemistry at Howard University with a joint appointment in Pharmaceutical Sciences. Dr. Fortunak worked for SmithKline Beecham from 1983-1993, then for DuPont Pharmaceutical Company from 1993-2000, and then for Abbott Labs from 2000-2004. For example, Dr. Fortunak worked on the development of commercial manufacturing processes for Efavirenz (Sustiva, a non-nucleoside reverse transcriptase inhibitor) for the treatment of HIV during his term at DuPont Pharma (1993-2000), and emtricitabine (FTC or Coviracil), also for the treatment of HIV, while at Abbott Labs. Dr. Fortunak became a chemistry professor in 2004. Dr. Fortunak focused his academic career on initiatives implementing more effective API manufacturing processes to lead to greater accessibility to treatment globally and environmental sustainability.
(ii) Dr. Andrea Brancale [15] Dr. Brancale received his Master’s degree in 1996; his thesis was on the design and synthesis of novel heterocyclic compounds as anti-human immunodeficiency virus (HIV) agents. His master’s research work included making novel anti-HIV agents and conducting testing for these agents. He received his PhD in Medicinal Chemistry in 2001 with work which resulted in the invention of an oral prodrug for treatment for shingles and varicella (viruses). Dr. Brancale worked on a GlaxoSmithKline project designing novel prodrugs of nucleoside analogs for use as anti-HIV and anti-hepatitis B agents after his PhD. Dr. Brancale has been very active in the area of design and synthesis of novel nucleosides and nucleotide analogs.
Professor Andrew Owen [16] Professor Owen is a professor in the Department of Molecular and Clinical Pharmacology at the University of Liverpool. Prof. Owen obtained his M.Sc. degree in Pharmacology in 1998 and a PhD in Pharmacology in 2002. Prof. Owen has focused on HIV and AIDS basic and clinical pharmacology for almost 20 years. Prof. Owen is currently working on developing the first oral nanomedicine for treating HIV/AIDS and is extensively qualified in the field of pharmacology in HIV/AIDS treatment.
[17] Prof. Owen provides his opinion on the identity of the Skilled Person, the disclosure of the 619 Patent and whether it was anticipated by the EP 214 application, the state of the prior art at the relevant date, the promise of the Patent and whether the utility was demonstrated or soundly predicted at the relevant time.
(2) Fact Witnesses [18] Gilead presented affidavits from fact witnesses to provide context for the invention story of TD. The witnesses include: Dr. William A. Lee, current Senior Vice-President Research, and at the relevant time Vice-President for Pharmaceutical Product Development at Gilead; Dr. Reza Oliyai, currently Vice-President of Product Development and Clinical Supplies, and Research Scientist from 1994 to 2004 at Gilead; Dr. Valentino J. Stella, Professor at the University of Kansas with a research focus on prodrugs, drug stability, biopharmaceutics and pharmacokinetics, and the use of novel cyclodextrins, and co-inventor on the 619 Patent; and Dr. Michael Hitchcock, current Senior Advisor at Gilead and a member of the prodrug development team at Bristol Myers Squibb (BMS) before joining Gilead’s team in 1993.
[19] Dr. Hitchcock presents the work already accomplished at BMS on phosphononucleotide analogs (not PMPA), before 1991, in search of an orally bioavailable method of delivery for a medicine for HIV. Dr. Lee then provides a backdrop of the transition from BMS to Gilead for the prodrug development team, including John Martin who joined Gilead as head of R&D in 1990 and who was a co-inventor for bis(POM)PMEA.
[20] Dr. Stella and Dr. Oliyai explain their invention leading to the 619 Patent. Dr. Oliyai studied under Dr. Stella for his PhD in pharmaceutical chemistry, which he obtained in 1993. Dr. Stella’s laboratory was one of the few prodrug laboratories in existence at the relevant time. Dr. Oliyai was hired by Gilead in 1994, only one year after completing his PhD; he still works there today. Dr. Oliyai provided the invention story of TDF, leading to the 619 Patent, which is supported by Dr. Stella’s evidence.
a)Invention Story [21] In outlining the inventive story of TD as the oral prodrug for PMPA, I accept the evidence of Gilead’s witnesses who gave personally-witnessed first-hand evidence. The events outlined below took place almost 20 years ago. I appreciate they have an interest in the outcome of these proceedings, but the fact remains they were eye witnesses to and lived through the events in question. Their testimony in these material respects was not diminished in cross-examination and I find it credible and reliable.
[22] In the early 1980s, a deadly disease emerged as the Acquired Immune Deficiency Syndrome (AIDS) caused by a virus now known as Human Immunodeficiency Virus (HIV). HIV is a retrovirus. HIV has several steps in its development and replication. The steps in the HIV lifecycle offer potential points of attack to limit its spread including: proteases, integrases and reverse transcriptase (RT).
[23] In finding treatment for HIV, each potential point of attack may be considered. However, interrupting the activity of RT is very beneficial because it prevents viral replication and stops the HIV infection from spreading to healthy cells.
[24] In the mid-1980s, researchers from the Institute of Organic Chemistry and Biochemistry (IOCB) in Czechoslovakia and the Rega Institute for Medical Research (Rega) in Belgium invented a class of compounds known as acyclic phosphonomethoxy nucleotide analogs (PNAs) (also referred to as phosphonate nucleotides), that are active against viruses, particularly HIV, and could be used as nucleotide reverse transcriptase inhibitors (NRTIs).
[25] [………………………………Redacted.……………………………………………………………………………………………………………………………………………………………………………………..…..].
[26] [……………………………….Redacted……………………………………………….] Gilead’s fact witness, Dr. Hitchcock, collaborated with Drs. DeClercq and Balzarini of IOCB and Rega. Apotex's expert, Dr. Brancale, acknowledged they (as well as Dr. Stella, referred to below) were experienced, internationally renowned and distinguished from others because they are bright, inventive and innovative.
[27] While PMPA was among the licenced class, BMS did not select PMPA because no data showed any advantages over others in the class. [……………….Redacted…………………….] [……………………………………..….Redacted……………………………………………….] [……….Redacted……………….]. In addition, because of their two negative charges, PNAs could not be efficiently administered orally, and were instead limited to intravenous (IV) administration. An alternative would require the discovery of a suitable prodrug that would enable PNAs to be administered orally. Intravenous (IV) administration was costly in addition to being difficult to administer to the growing number of HIV infected persons. A prodrug was the answer.
[28] [……………………………….Redacted……………………………………………….] [………………………………..….Redacted……………………………………….]. According to a paper co-authored by Dr. Hitchcock only a handful of PMEA prodrugs (including bis(POM)PMEA) showed useful oral bioavailability. BMS [……………Redacted……………] [……………………….……………….Redacted……………………………………………….] [………………….Redacted…………………….] in 1991, and terminated its rights to the compounds. [……………………. Redacted…………………………………………………….] [……………………………….Redacted……………………………………….….].
[29] IOCB and Rega then approached other pharmaceutical companies with this class of compounds to find a new partner. One of these companies was Syntex, which, knowing about the nephrotoxicity and lack of bioavailability, declined to licence or proceed with the IOCB/Rega compounds.
[30] [……………………………….Redacted……………………………………………….] […Redacted…] Gilead, a small California-based start-up founded three years previously, took on these licences to conduct its own research into the PNA class of compounds and licenced the compounds with the goal of discovering a commercially viable oral antiviral drug.
[31] To advance somewhat in the inventive story and to place subsequent events in context, Gilead eventually formulated tenofovir disoproxil (TD) (also known as bis(POC)PMPA). TD is an oral prodrug of PMPA, and the allegedly new, useful and inventive compound at issue in this proceeding. TD alone (in its fumarate salt form, TDF), and in combination with other drugs, is an important medicine for treating HIV-1 infection, which requires an enzyme known as reverse transcriptase (RT) to successfully infect target cells and prevent their harmful replication. TD is a prodrug of a compound called tenofovir (or PMPA). The fumarate salt of TD is TDF; the fumarate salt is in the drug formulation to improve its stability.
[32] Without Gilead's claimed invention of TD as the orally administered, bioavailable prodrug for PMPA, PMPA only enters the body in sufficient quantities for therapeutic purposes when administered intravenously. The parties agree that PMPA's oral bioavailability was too low, that is, when consumed orally it did not pass through the intestinal wall into the body where PMPA is needed to do its work in the infected patient. As noted, intravenous or IV administration of PMPA was difficult for the growing number of HIV sufferers across North America and around the world. An orally administered product such as a pill would be better because it would be far easier to administer to far more patients. TDF is now a central part of antiviral therapy for HIV-infected patients, which the United States Department of Health and Human Services (HHS) has decreed as a preferred antiviral therapy. TD is a member of the PNA class of compounds.
[33] To return to the inventive narrative, […………………Redacted………………………] [………………………………….Redacted…………………………………………………….] [……………………….Redacted……………………………………………….] Dr. Hitchcock left BMS to join Gilead in part because of the phosphonate nucleotide analogs (PNAs) in respect of which Gilead had obtained the licences. Dr. Hitchcock hoped that at Gilead the issues observed at BMS might be mitigated, but knew it could fail.
[34] […………………………………..….Redacted……………………………………………….].
[35] PNAs possess a phosphonate group. Antiviral activity for these compounds, including PMPA, was first reported in the early 1990s. However, notwithstanding their antiviral activity, these PNA compounds exhibit nephrotoxicity in addition to poor oral bioavailability. Their negative charges inhibit absorption after oral administration such that they did not pass well through the intestinal wall into the lymphatic system.
[36] [……………………………….Redacted……………………………………………….] [……………………………….Redacted……………………………………………….] Gilead [………………………….Redacted……………………………………….]. While not part of the inventive story it is noteworthy that in 1999, the US Food and Drug Administration (FDA) declined Gilead's application for 60 and 120 mg oral doses of bis(POM)PMEA, because those doses, required for HIV treatment, caused kidney toxicity and carnitine depletion.
[37] In searching for a back-up to PMEA, Gilead found that structural differences among the compounds produced distinct properties. For example, a difference between PMEA and PMPA is the presence of the methyl group (CH3) in PMPA which creates a chiral carbon not present in PMEA. [……………………………….Redacted……………………………………………….] […………………….Redacted……………….].
[38] [……………………………….Redacted……………………………………………….] [……………….Redacted……………………………………….] The Gilead research team was instructed to find an alternative to PMEA in 1994. PMPA was selected. The team was later tasked with finding a suitable prodrug for PMPA. The first prodrug tested and used as a control was bis(POM)PMPA. The POM moiety was known to increase oral bioavailability, notwithstanding its toxicity due to pivalic acid. Pivalic acid leads to reduced levels of carnitine in the body, which can result in muscle weakness, heart disease and other undesirable consequences particularly for those suffering from HIV.
[39] [……………………………….Redacted……………………………………………….] [……………………………….Redacted……………………………………….].
[40] Gilead’s Drs. Lee and Oliyai described this work, including examples of PMPA prodrugs that Gilead attempted. They provided excerpts of lab notebooks, internal memos, research reports and summary charts of the synthesis and/or testing of the PMPA prodrugs. [..Redacted..] […………………………………..…….Redacted……………………………………………….] […………………………………..…….Redacted……………………………………………….] [………….Redacted…………………………….].
[41] Gilead scientists found, as the prior art taught, that the prodrug approach is unpredictable and requires empirical testing.
[42] According to the 619 Patent and to fact witnesses, more promising compounds were tested in vivo in dogs for oral bioavailability.
[43] [……………………………….Redacted……………………………………………….] [Redacted] Gilead’s management team was comprised of accomplished scientists, namely Dr. John Martin (an inventor of the bis(POM)PMEA while employed as a scientist at BMS, extensively involved in the BMS research program exploring PNAs licenced by IOCB/Rega, and at the relevant time Head of Gilead’s Research and Development), Dr. William Lee (an affiant in this case who obtained a Master of Science and PhD in Chemistry, did post-doctoral work in chemical physics at Ecole Polytechnique Fédérale in Lausanne, Switzerland, and a second post-doctorate in bioorganic chemistry at the University of California (Santa Barbara), and who was Vice-President of Pharmaceutical Product Development at the relevant time), and Dr. Norbert Bischofberger (responsible for Gilead’s discovery research group at the relevant time). […… ………………………………..….Redacted…………… ……………………………….….] [………………………………..….Redacted…………………………………………….….] [……………………………..…….Redacted………………………………………….…….] [……………………………..…….Redacted…………………………………………….….] [………………………………..….Redacted………….]
[44] Apotex criticizes this decision as one of “senior management” overriding scientists. I consider Apotex’s objections neither fair nor accurate. First, Gilead management was comprised of accomplished scientists. In addition, none of the literature disclosed or discussed carbonate prodrugs of phosphonate nucleotides analogs. Indeed, an article published in 1993 and authored by Drs. Oliyai and Stella (both inventors on the 619 Patent) demonstrated the instability of compounds containing both carbonates and phosphates. In my view, this decision was a reasonable management decision on the basis of the prior art available at the time.
[45] By late 1995 or early 1996, Gilead had not found a suitable PMPA prodrug over two years from obtaining the licence. [………………………………...Redacted…………………..] [.Redacted.].
[46] After exhausting the options it had identified, Gilead consulted with Prof. Stella of the University of Kansas, a pharmaceutical chemist and prodrug expert. Upon being briefed on Gilead's prodrug efforts, Dr. Stella was surprised by how many potential PMPA prodrugs Gilead had studied. [………………………………….Redacted……………………………………….] […………………………….………………….Redacted……………………………………….] [……………….Redacted…………………………….]
[47] In order to make and test new carbonate prodrugs, Gilead’s team was required to and did develop a new synthetic process. [……………………………….Redacted……………………..] [……………………….Redacted…………………………………………….] Drs. Arimilli and Dougherty synthesized other carbonate PMPA prodrugs, which were then analyzed.
[48] [……………………………….Redacted……………………………………………….] [..Redacted..]. TD showed adequate stability, which was not expected by the inventors. Based on its enhanced cellular permeability, solubility, efficacy, stability, low toxicity and improved oral bioavailability over PMPA, TD was selected for development and eventually patented in the 619 Patent.
III. Issues [49] In my view, the issues in this application are:
A. Whether Apotex discharged its relatively low burden in connection with its allegations of invalidity concerning the 619 Patent relating to Claim 32 on the grounds of:
i. Anticipation, if the 619 Patent is anticipated by European Patent Application 0,481,214 (“the EP 214 application”), or is an invalid selection patent from the genus of the EP 214 application, and if so, whether Gilead established on a balance of probabilities that such allegations are not justified;
ii. Obviousness, if Claim 32 is obvious, or obvious to try, as discussed in Sanofi;
iii. Lack of sound prediction or demonstrated utility as measured against the promise of the 619 Patent.
[50] The law is well-established that Apotex in order to succeed must first give an air of reality to each allegation in its NOA. If it does, the burden shifts to Gilead to establish on a balance of probabilities that Apotex’s allegations of invalidity are not justified.
[51] In my view, Gilead has established on a balance of probabilities that the allegations of anticipation, obviousness, and inutility are not justified.
IV. Analysis A. Preliminary Issues (1) Relevant Dates [52] The relevant dates for the assessment of the justifiability of the various allegations of invalidity are the following:
A. Patent Construction: Publication Date – February 5, 1998
B. Anticipation/Novelty: One year before Canadian Filing Date – July 26, 1996
C. Obviousness (State of the Art): Claim Date (Priority Date) – July 26, 1996
D. Utility: Canadian Filing Date – July 25, 1997
(2) Expert Blinding [53] The parties argued the issue of “blinding” of experts; Apotex asks me to assess the weight of each expert’s evidence with reference to the method by which the expert’s opinion was sought by counsel.
[54] I make the same comments in this case as I did in the companion case T-1693-14, but for convenience repeat my analysis here.
[55] The parties chose different methods of gathering information from their experts for their respective opinion affidavits. While counsel for Gilead provided the legal framework to its experts early, including legal tests for anticipation, obviousness, and utility, Apotex states it did not do so before the experts had drawn their own conclusions on issues such as the promise of the patent, claim construction, and the prior art.
[56] Apotex submits expert blinding has been recognized by this Court as a preferred method of gathering expert evidence and refers to: AstraZeneca Canada Inc v Apotex Inc, 2014 FC 638, per Rennie J, at para 321; Teva Canada Innovation v Apotex Inc, 2014 FC 1070, per Gleason J, at paras 94-96; Takeda v Apotex Inc, 2015 FC 570, per O’Reilly J, at paras 27, 29; Allergan Inc v Apotex Inc, 2016 FC 344, per Zinn J, at para 13. For this reason, it asks the Court to assess greater weight to the opinions of its experts when addressing these issues and conclusions by the expert witnesses. In my view the blinding of a witness is a factor, one of perhaps several, that goes to weight, but it is not a matter that goes to admissibility.
[57] Gilead, as a counter to Apotex’s allegations that Gilead’s expert evidence should be given less weight because experts were not blinded, argues that Apotex’s experts for the most part did not conduct their own research to determine the prior art, which indeed I find was substantially the case. Instead, the Apotex experts were provided with all or virtually all of the material relevant to their opinions on prior art and skilled person in the art by counsel for Apotex. Gilead submits this diminishes the weight I should give to Apotex’s expert evidence, essentially because Apotex witnesses are not stating what the state of the prior art or skilled person was, but were in effect simply opining on what Apotex’s counsel told them was the state of the prior art and knowledge of the skilled person.
[58] The Court has to weigh the evidence before it. On the blinding issue, I agree with Justice Gleason (as she then was) in Eli Lilly Canada Inc v Apotex Inc, 2015 FC 875 at para 166:
Insofar as concerns the allegation regarding lack of “blinding”, Apotex has tried to apply the decisions in Teva and AstraZeneca out of context. There, the experts whose credibility was found to be wanting based their construction of the patents in suit with a view to infringement and were able to come to their opinions based on the information in the generic company’s NOA. In Teva, this led to an especially tortured construction. In Teva and AstraZeneca, the approach taken was found to undercut the experts’ credibility as it led to an improper results-oriented opinion. Neither case can be read for the position that Apotex sought to advance here, namely, that in any case where one party blinds its experts but the other does not, the former’s evidence is to be preferred. Rather, these two decisions must be limited to the facts that arose in these cases.
And see to the same effect the approach taken by Justice Locke in his recent decision, Shire Canada Inc v Apotex Inc, 2016 FC 382 at paras 42-48.
[59] More generally the weighing of expert evidence is a question of fact. Having reviewed the law, and as counsel for Apotex candidly noted at the hearing, the blinding issue is a question of relevance, reliability and weight, and is not a doctrinal matter. I agree.
[60] For reasons set out, I prefer some experts’ evidence on certain issues, and other experts’ evidence on other matters, taking into account the arguments raised by both parties and assessing the appropriate weight to be given to the expert testimony.
a)Comity within the Court: determinations of Barnes J. [61] The parties disagreed on the extent to which the Court may rely on Justice Barnes’ prior decision in Gilead Science Inc v Canada (Health), 2013 FC 1270 (Teva). In Teva, Justice Barnes made determinations of fact with reference to the same patent as before me, on the issue of anticipation of TD by the EP 214 application.
[62] The question of whether findings on invalidity allegations in NOC proceedings are binding on subsequent NOC decisions has been considered before. The Federal Court of Appeal in Apotex Inc v Allergan Inc, 2012 FCA 308 found that only questions of law may be found binding as a matter of horizontal comity, and even in that context, findings on questions of law could be departed from if a subsequent court had reason to do so:
[49] It is apparent from the foregoing that it was not open to the Federal Court judge to issue a prohibition order for the purpose of having his concerns about the use of the doctrine of comity and the notion of abuse of process addressed by this Court on appeal. As noted earlier, the parties were entitled to have their dispute settled on the merits and the Federal Court judge by issuing a formal judgment that was contrary to the conclusions that he reached on the merits, failed in his task.
[50] Beyond this, the doctrine of comity has no application with respect to findings of fact. A finding that an invention is obvious because the solution proposed was plain to see is one of fact (671905 Alberta Inc. v. Q’max Solutions Inc., 2003 FCA 241 , para. 48; Laboratoires Servier v. Apotex Inc., 2009 FCA 222 , para. 67 (Servier); Apotex Inc. v. Wellcome Foundation Ltd., [2001] 1 F.C. 495, para. 61 (C.A.), aff’d 2002 SCC 77, [2002] 4 S.C.R. 153). In contrast, construing a patent in order to identify the inventive concept when it is not readily discernable for the claim itself requires looking at the whole of the patent (Sanofi, para. 77) and gives rise to a question of law (Western Electric Co. v. Baldwin International Radio of Canada Ltd., [1934] S.C.R. 570, pp. 572-573 (S.C.C.); Weatherford Canada Ltd. v. Corlac Inc., 2011 FCA 228, [2011] F.C.J. No. 1090, para. 24 – and the authorities referred to in these passages). It follows that unless the Federal Court judge could demonstrate that Crampton J.’s construction of the patent in order to determine the inventive concept was wrong or that distinct evidence adduced before him compelled him to reach a different conclusion, it would have been preferable for him to adhere to it.
[63] Based on this reasoning, I am not bound by Justice Barnes’ decision in Teva. Nor am I persuaded that I ought to apply comity except in the limited context of patent construction or on another question of law. That said, and for the record only, I note that Barnes J. in Teva, with different parties and differences in the evidence also ordered prohibition re the 619 Patent.
B. Claim Construction [64] Claim construction is an issue of law to be determined by the Court. The experts may provide guidance. The Claim is to be construed, based on the claim as it would be read by a Person of Ordinary Skill in the Art (Skilled Person), looking to the patent with a view to understand.
(1) Skilled Person [65] A patent is addressed to this notional Skilled Person, who is “unimaginative and uninventive, but at the same time is understood to have an ordinary level of competence and knowledge incidental to the field to which the patent relates and to be reasonably diligent in keeping up with advances”: AstraZeneca Canada Inc v Apotex Inc, 2014 FC 638 at para 51 (citing Merck & Co v Pharmascience Inc, 2010 FC 510 at paras 34-40), aff’d 2015 FCA 158. The “unimaginative and uninventive” language is found in Beloit Canada Ltd v Valmet OY (1986), 8 C.P.R. (3d) 289 (F.C.A.) [Beloit], where the Federal Court of Appeal refers to the “unimaginative skilled technician”, and Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61 at para 81, where the Supreme Court refers to inventiveness as foreign to the Skilled Person in the obviousness analysis. In my view, the Federal Court retained these concepts in its interpretation of the skilled technician in patent law: AstraZeneca Canada Inc v Apotex inc, 2014 FC 638 at para 51 (Rennie, J as he then was) (citing Merck & Co, Inc, v Pharmascience inc, 2010 FC 510 at paras 34-40 (Hughes, J)), aff’d 2015 FCA 158 (Dawson, J.A.).
[66] The parties agree the Skilled Person is a person or team of persons with an advanced degree (MSc or PhD) in medicinal, organic or pharmaceutical chemistry who has been engaged in the drug discovery process, and has a working knowledge of antiviral research activities, including the antiviral activity of phosphonomethoxy nucleotide analogs. However, Gilead’s experts Drs. Borchardt and Maag disagree with Apotex’s experts that the Skilled Person includes: (i) a person with expertise in prodrugs (although the Skilled Person would have been aware of prodrug efforts, and Dr. Borchardt said the inclusion of a team member with prodrug expertise would not affect his opinion in any event); and (ii) a clinician knowledgeable in treatment therapies of viral infections.
[67] In my view, the Skilled Person is a person or a team of persons with an advanced degree in pharmaceutical chemistry or a related field with knowledge of and experience in the antiviral research activities, including the antiviral activity of phosphonomethoxy nucleotide analogs, with some experience and knowledge of prodrugs. I agree with Gilead’s experts that the Skilled Person does not need to have experience in the clinical treatment of HIV specifically because the Patent would not be helpful to a treating physician, but only to the chemist manufacturing the prodrug. In this connection I note that the Patent refers to prodrugs and the Claim at issue (Claim 32) is a chemical formulation which does not comprise information including a prescribed dosage (posology) or other information which would be necessary for a treating physician. While Gilead’s experts noted that the Skilled Person at the time would not need expertise in prodrugs, in my view some experience and knowledge of prodrugs is part of the skill set of the Skilled Person. I make this finding because the patent specifically addresses prodrugs. The Patent is really only relevant to those who aim at inventing or making prodrugs in the treatment of the viral infections listed in the Patent.
[68] In this connection, I also prefer the evidence of Gilead’s witnesses because, by the time of the invention in 1996, its expert witnesses Dr. Borchardt and Dr. Maag had each been working as chemical scientists or researchers for at least fifteen years already. Dr. Maag had first-hand knowledge of the prior art and of what a Skilled Person would or would not know, including in the field of prodrugs. Conversely, the Apotex experts had less cumulative experience in chemistry research at the time. I have admitted the opinions of the Apotex witnesses in this regard; I do not agree that experts testifying on the state of the prior art and the knowledge of Skilled Person as it was some twenty years ago need to have been active in those fields at that time. But when measured against those who had long been active scientists, and had two decades of experience twenty years ago, I prefer Gilead’s evidence over Apotex’s.
(2) Claim Construction Conclusion [69] The only claim at issue in the 619 Patent is Claim 32, which states:
32. A compound having the structure:
and its salts, tautomers and solvates.
[70] The Skilled Person in my view, and the parties and their experts agree, would view the asserted claim as the disclosed compound tenofovir disoproxil and its salts, tautomers and solvates, as described in Claim 32; that is the proper construction of Claim 32.
C. Anticipation [71] The definition of “invention” in section 2 of the Patent Act requires that it be “new”, which engages the law of anticipation referred to in s. 28.2 of the Patent Act each of which are set out below:
2 In this Act, except as otherwise provided,
2 Sauf disposition contraire, les définitions qui s