Eli Lilly Canada Inc. v. Mylan Pharmaceuticals ULC

Eli Lilly Canada Inc. v. Mylan Pharmaceuticals ULC
Court (s) Database
Federal Court Decisions
Date
2020-09-10
Neutral citation
2020 FC 816
File numbers
T-1627-16
Decision Content
Date: 20200910
Docket: T-1627-16
Citation: 2020 FC 816
Ottawa, Ontario, September 10, 2020
PRESENT: The Honourable Madam Justice St-Louis
BETWEEN:
ELI LILLY CANADA INC., ELI LILLY AND COMPANY, LILLY DEL
CARIBE, INC., LILLY, S.A. and ICOS CORPORATION INC.
Plaintiffs/Defendants by Counterclaim
and
MYLAN PHARMACEUTICALS ULC
Defendant/Plaintiff by Counterclaim
AND BETWEEN:
Court File No. T-1631-16 (T-1639-16)
ELI LILLY CANADA INC., ELI LILLY AND COMPANY, LILLY DEL CARIBE, INC., LILLY, S.A. and ICOS CORPORATION INC.
Plaintiffs/Defendants by Counterclaim
- and -
TEVA CANADA LIMITED
Defendant/Plaintiff by Counterclaim
AND BETWEEN:
Court File No. T-1623-16 (T-1624-16)
ELI LILLY CANADA INC., ELI LILLY AND COMPANY, LILLY DEL CARIBE, INC., LILLY, S.A. and ICOS CORPORATION INC.
Plaintiffs/Defendants by Counterclaim
- and -
PHARMASCIENCE INC. AND LABORATOIRE RIVA INC.
Defendants/Plaintiffs by Counterclaim
AND BETWEEN:
Court File No. T-1632-16
ELI LILLY CANADA INC., ELI LILLY AND COMPANY, LILLY DEL CARIBE, INC., LILLY, S.A. and ICOS CORPORATION INC.
Plaintiffs/Defendants by Counterclaim
- and -
APOTEX INC.
Defendant/Plaintiff by Counterclaim
PUBLIC JUDGMENT AND REASONS
(Confidential Judgment and Reasons issued August 6, 2020)
TABLE OF CONTENTS
I. Introduction 4
II. Procedural background 5
III. The pleadings and results 7
IV. Tadalafil 11
V. The statutory scheme under which the matter proceeds 13
VI. Decision on motion to update answers given on discovery 13
VII. Issue estoppel and judicial comity 14
A. Introduction 14
B. The 684 Patent NOC decision 15
C. Decision on issue estoppel and judicial comity 18
I. Burden of proof 20
II. Lilly’s fact witnesses 20
A. Dr. Karl Donn 20
B. Dr. Kenneth Ferguson 21
C. Dr. William Ernest Pullman 22
III. Expert witnesses 23
A. Defendants’ expert witnesses 23
(1) Dr. Sharon Baughman 23
(2) Dr. Peter Ellis 24
(3) Dr. Wayne Hellstrom 25
B. Lilly’s expert witnesses 26
(1) Dr. Hartmut Derendorf 26
(2) Dr. Gerald Brock 27
IV. The 684 Patent 31
A. Overview 31
B. The disclosure 31
C. The claims 38
V. Not a selection patent 38
VI. Claim construction 46
A. Relevant date for claim construction 46
B. Law of claim construction 46
(1) Introduction 46
(2) One construction for all purposes 47
(3) Purposive construction: essential and non essential elements 49
(4) Purposive construction: the patentee’s words 53
(5) Claim differentiation 56
C. Person skilled in the Art (PSA) 57
D. Prior art 58
(1) Sildenafil 59
(2) The 377 Patent 60
(3) The 784 Application 61
E. Common general knowledge 62
F. Claims needing construction 67
(1) Introduction 67
(2) Construction of Claim 10 (as it depends on Claim 9, as it in turn depends on Claims 3–6) 68
(3) Construction of Claims 13–16 72
VII. The Defendants’ counterclaims of invalidity 75
A. Introduction 75
B. Anticipation 76
(1) The anticipation allegations 76
(2) The anticipation framework 80
(a) Section 28.2 of the Patent Act and the Sanofi test 80
(b) The disclosure requirement 81
(c) The enablement requirement 85
(3) Conclusion on anticipation 87
C. Obviousness 87
(1) The obviousness allegations 87
(2) The obviousness framework 89
(a) Section 28.3 of the Patent Act 89
(b) The Sanofi test on obviousness 89
(c) First step: identify the notional PSA and the relevant common general knowledge of that person 91
(d) Second step: identify the inventive concept of the claim in question or if that cannot readily be done, construe it 91
(i) Issues 91
(ii) 1986: the Beloit framework 92
(iii) Section 28.3 of the Patent Act 93
(iv) Sanofi in 2008 94
(v) Post-Sanofi 95
(vi) The meaning of the term inventive concept 101
(vii) The subject-matter defined by a claim of the 684 Patent 103
(e) Third step: identify what, if any, differences exist between the matter cited as forming part of the “state of the art” and the inventive concept of the claim or the claim as construed 105
(f) Fourth step: Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention? 106
(3) Conclusion on obviousness 111
D. Conclusion on the counterclaims of invalidity 111
VIII. Lilly’s infringement claim 112
A. Principles 112
B. Conclusion on the infringement claim 113
IX. Election between damages and accounting of profits 114
X. Declaratory relief 115
XI. Sealing order 115
XII. Costs 115
I.
Introduction
[1] This decision relates to infringement actions of Canadian Patent No. 2,371,684 [the 684 Patent] by the Plaintiffs (hereinafter collectively referred to as “Lilly”) against each of four Defendants, Mylan Pharmaceuticals ULC, Apotex Inc., Teva Canada Limited, and Pharmascience Inc.-Laboratoire Riva Inc., and related counterclaims of invalidity by each of the Defendants.
[2] The reasons exposed in this case will be filed in each of the other three related cases. Additional reasons, pertaining to the litigation between Lilly and Apotex Inc. in regards to Canadian Patent No. 2,492,540 Patent [the 540 Patent] are exposed in Eli Lilly Canada Inc. and als. v Apotex Inc., 2020 FC 814. In the 540 Patent additional reasons, I repeat certain elements and sections of these reasons in order to allow their reading on a stand-alone basis.
II. Procedural background
[3] Lilly initially sued each of the four Defendants in independent actions for infringement of patents related to tadalafil. Each of the Defendants denied infringement and counterclaimed for a declaration of invalidity of the patents asserted against them. Over the course of these proceedings, Lilly has asserted four patents against the Defendants: (1) the 684 Patent, which expired on April 26, 2020, and relates to a dosage form of tadalafil; (2) the 2,379,948 Patent, which expired on April 26, 2020, and relates to a formulation comprising tadalafil; (3) the 540 Patent, which will expire on July 14, 2023, and relates to a manufacture process for making tadalafil; and (4) the 2,226,784 Patent [the 784 Patent] which expired on July 11, 2016, and relates to the use of tadalafil to treat erectile dysfunction [ED].
[4] On September 8, 2017, Prothonotary Tabib, at the request of the parties, bifurcated the actions as between liability and quantification phases. As per Prothonotary Tabib’s Order, the liability phase addresses the following issues: (i) whether the patents have been infringed by the Defendants; ii) whether the patents are valid; (iii) except for paragraphs 9, 28–36, 37–42 and 175 of Apotex’s Amended Statement of Defence and Counterclaim which shall be addressed in the quantification phase, whether Lilly are entitled to declaratory relief, injunctive relief, and delivery up; and (iv) Lilly’s entitlement, if any, to elect as between damages and an accounting of profits (except as it relates to paragraphs 28–36 of the Defence).
[5] On July 3, 2019, Prothonotary Tabib granted Lilly leave to amend their Statements of Claims, whereby only claims for infringement of the 684 Patent against all Defendants, and claims for infringement of the 540 Patent against Teva, which was subsequently withdrawn, and against Apotex, were maintained.
[6] Prothonotary Tabib also then granted Lilly leave to add, against all Defendants, claims for the infringement of the 784 Patent by reason of the manufacturing, importing and stockpiling of tadalafil for ED, prior to the expiration of the 784 Patent, and springboard damages flowing from that infringement. As a condition for granting leave to amend, all issues of validity, infringement and quantification relating to the 784 Patent were bifurcated and will be the subject of a separate trial after the determination of the liability issues for the 684 and 540 Patents.
[7] Although the actions have not been consolidated, they have been case managed together and proceeded together to trial for the liability phase, with hearings conducted from December 5, 2019 to February 7, 2020. Although the actions regarding the two patents at issue have not been bifurcated, the parties all agreed to the trial being divided in two separate components. The first component pertained to the liability phase of the 684 Patent, which involves all four Defendants, presenting a common case, and the second component pertained to the liability phase of the 540 Patent, which involves Apotex as the sole Defendant.
[8] The parties have not disputed that the law is the same in both components of the trial, although surprisingly, and as I will outline in the discussion regarding anticipation, Lilly presented different versions of the principle guiding the disclosure requirement of the anticipation analysis in each components.
III. The pleadings and results
[9] The Plaintiffs in this action are Eli Lilly Canada Inc. (Eli Lilly Canada), Eli Lilly and Company, Lilly Del Caribe, Inc., Lilly, S.A. and ICOS Corporation Inc.
[10] Eli Lilly Canada has a principal place of business in Toronto Ontario. Eli Lilly and Company has a principal place of business in Indianapolis, Indiana. Lilly Del Caribe, Inc. has a principal place of business in Caroline, Puerto Rico, and is incorporated in the Cayman Islands. Lilly, S.A. has a principal place of business in Madrid, Spain. ICOS Corporation Inc. has a principal place of business in Indianapolis, Indiana.
[11] Eli Lilly Canada markets 2.5mg, 5mg, 10mg and 20mg strengths of tadalafil tablets in Canada under the brand name CIALIS, for the treatment of (a) erectile dysfunction (ED) in men; (b) signs and symptoms of benign prostatic hyperplasia (BPH); and (c) treatment of ED and the signs and symptoms of BPH. Eli Lilly Canada also markets a 20mg strength of tadalafil tablet under the brand name ADCIRCA for the treatment of idiopathic pulmonary arterial hypertension (PAH) in the specified conditions.
[12] The Defendants are generic drug makers. Mylan Pharmaceuticals ULC has a principal place of business in Etobicoke, Ontario. Apotex Inc. has a principal place of business in Toronto, Ontario. Teva Canada Limited has a principal office or place of business in Toronto, Ontario. Actavis Pharma Company amalgamated into Teva Canada Limited, effective January 1, 2017, and Teva assumes all liabilities of Actavis prior to the amalgamation. Pharmascience Inc. is based in Montreal, Quebec, while Laboratoire Riva Inc. is based in Blainville, Quebec.
[13] In July 2016, each of the Defendants received a Notice of Compliance (NOC) for its version of tadalafil with CIALIS tadalafil as the Canadian Reference Product: Mylan-Tadalafil, Apo-Tadalafil, Teva-Tadalafil/Act-Tadalafil, and PMS-Tadalafil/Riva-Tadalafil. In 2016, after the 784 Patent expired, the Defendants entered the market by selling or by offering for sale their generic version of tadalafil in 2.5mg, 5mg, 10mg and 20mg tablets, except for Riva who has offered for sale and sold 5mg and 20mg tablets in Canada.
[14] In 2015, Apotex received a NOC for Apo-Tadalafil PAH 20mg tablets with ADCIRCA tadalafil as the Canadian Reference Product.
[15] Lilly assert that the Defendants have made, imported, used, sold or offered for sale tablets with the patented unit dosages and infringed or induced the infringement of Claim 10 (as it depends on Claim 9, as it in turn depends on Claims 3–6), and Claims 13–16 of the 684 Patent [the asserted Claims]. Lilly seek a declaration that the Defendants are infringing and inducing infringement, and have infringed or induced infringement of the asserted Claims of the 684 Patent, a declaration that the 684 Patent is valid and subsisting to expiry, a declaration that Lilly may elect as between damages and an accounting of profits, declaratory relief, injunctive relief and/or delivery up, and costs.
[16] The Defendants individually assert that they have not infringed any of the asserted Claims of the 684 Patent. They initially raised the Gillette defence (Free World Trust v Electro Santé Inc, 2000 SCC 66 [Free World Trust]), to submit they were simply doing what was taught by the expired 784 Patent, and also submit there can be no infringement because the patent is invalid. They counterclaimed, seeking a declaration that the 684 Patent or the asserted Claims are invalid, as well as costs.
[17] On November 26, 2019, the parties have jointly outlined the issues as follows:
a) Whether the parties are proper parties and have standing to bring this action;
b) Whether the Plaintiffs are estopped against re-litigating the findings in Eli Lilly Canada inc v Mylan Pharmaceuticals ULC 2015 FC 125 due to issue estoppel, collateral estoppel, comity and/or abuse of process;
c) Construction of Claim 10 as it depends on Claim 9, as it in turn depends on Claims 3–6, and Claims 13–16 of the 684 Patent;
d) Whether any of the asserted Claims are infringed;
e) Whether the Gillette defence applies;
f) Whether the asserted Claims are invalid by reason of
Overbreadth: are the asserted Claims broader than either the invention made by the named inventors of the 684 Patent or the invention disclosed in the specification of the 684 Patent?
Double patenting: are the asserted Claims invalid on the bases of same invention and/or obviousness-type double patenting in view of the subject-matter of Claims 1–28 of Canadian Patent No. 2,307,101?
Anticipation: does Canadian Patent Application No. 2,226,784 and/or PCT Application No. Wo 97/03675 anticipate the subject-matter of the asserted Claims?
Obviousness: would the subject-matter defined by the asserted Claims have been obvious on the claim date to a person skilled in the art?
Non-patentable subject-matter: does the subject-matter defined by the asserted Claims relate to non-patentable subject-matter (ie, a mere discovery and/or a method of medical treatment)?
Lack of sound prediction/no demonstration utility: have the requirements of either demonstration or sound prediction of utility as of the filing date of the 684 Patent been met?
Inutility/inoperability: does the subject-matter defined by the asserted Claims in fact possess utility?
Insufficiency: does the 684 Patent satisfy the requirements of subsection 27(3) of the Patent Act R.S.C., 1985, c. P-4 [the Patent Act]?
g) Whether the Plaintiffs are entitled to elect as between damages and an accounting of profits;
h) Whether the Plaintiffs are entitled to declaratory relief, injunctive relief and/or delivery up.
[18] At the start of the trial, the Defendants abandoned the issue of standing. Regarding infringement, only Lilly’s expert evidence has been adduced, and the Defendants have not asserted the Gillette defence in closing. It thus appears clear that, if the asserted Claims of the 684 Patent were valid, all the Defendants would have infringed.
[19] At opening, the Defendants indicated that their allegations of invalidity on the grounds of overbreadth, lack of sound prediction or demonstration and inutility/inoperability are asserted only in the event the asserted Claims are construed to include the side effect advantages (transcript of December 5, 2019 at page 20). Likewise, the Defendants indicated their allegation of non-patentable subject-matter is asserted only if the Court construes the asserted Claims in the 684 Patent as implicitly including a maximum daily dose (transcript of February 3, 2020 at pages 207–208).
[20] At closing, the Defendants did not address their allegations of invalidity on grounds of overbreadth, double patenting, lack of sound prediction/lack of demonstration, inutility/inoperability, and insufficiency.
[21] Lilly, in their Closing Memorandum, did counter the Defendants’ allegations of overbreadth and inutility/inoperability. Finally, at closing, Lilly no longer seek an injunctive relief, nor the delivery up of infringing drugs.
[22] In brief, and for the reasons exposed hereinafter, I find the 684 Patent is not a selection, and that the asserted Claims are anticipated and obvious, and are thus invalid.
[23] However, if I am wrong and the asserted Claims were valid, then all Defendants will have infringed or induced infringement of the asserted Claims of the 684 Patent.
IV. Tadalafil
[24] The drug substance at the heart of these proceedings is tadalafil. It is known as a phosphodiesterase (PDE) 5 inhibitor. The first approved PDE5 inhibiter was sildenafil, commercialised by Pfizer under the brand name Viagra, and approved in Canada on March 9, 1999. Tadalafil is the second in class PDE5 inhibiter drug product.
[25] In brief, tadalafil works to promote the relaxation of the penis’ smooth muscle, which, somewhat counterintuitively for a layperson, promotes penile erection. In brief, the penis’ smooth muscle, known as the corpora cavernosa, is in a contracted state when in normal resting state, and so restricts the arteries supplying blood to the penis. When an erection is triggered, the smooth muscle relaxes, no longer restricts the supply of arterial blood, which causes the penis to become tumescent. The smooth muscle relaxation results from a cascade of complex biochemical reactions within the body. Normally, sexual stimulation triggers the release of nitric oxide, which in turn leads to an increase in the production of a molecule called cyclic guanosine-3-5 monophosphate (cGMP). This cGMP molecule regulates the activity of other intracellular proteins and leads to the relaxation of the smooth muscle. Increasing cGMP promotes smooth muscle relaxation, which promotes penile erection. The intracellular breakdown of the cGMP is regulated by a class of enzymes known as cyclic nucleotide PDE, and in the penis, the most prevalent is the PDE5 family. Inhibiting PDE5 results in a slower breakdown of cGMP, which then accumulates, promotes the relaxation of the smooth muscle and, in turn, penile erection.
[26] Tadalafil was first claimed in the British patent GB no 9401090.7 (which Canadian equivalent is the 2,181,377 Patent (the 377 Patent)), filed on January 21, 1994 by Laboratoires Glaxo. A number of other patents were also granted in relation to tadalafil, now owned by Lilly as the results of successive commercial transactions.
[27] The 684 Patent relates to unit dosages of tadalafil and a few undisputed scientific indications are useful to understand these reasons.
· The drug development process includes mainly the preclinical studies and three stages of clinical trials before approval of the drug by the regulators. When a compound candidate is discovered, it is first tested in vitro and in vivo, on animals, for an initial assessment of possible effectiveness (animal pharmacology) and safety and tolerability (toxicology), and further assessments are later performed if the profile of the compound is suitable. If it is safe and tolerable on animal models with a suitable profile, it could be selected for phase I tests that are performed on healthy human subjects in increasing doses to assess safety and tolerability. In phase II, dose response efficacy studies are performed on patients to ascertain the dosage and the efficacy of the compound. Finally, phase III large scale studies are generally performed on patients, before a drug is put to the market. Throughout the preclinicals, and each of the phases, new data, including pharmacokinetic and pharmacodynamics data, are gathered about the drug.
· Pharmacokinetics (PK) are a set of parameters used to describe the concentration of a drug over a period of time in the body (also known as the effect of the body on the drug).
· Pharmacodynamics (PD) are a set of parameters used to describe the effect of the drug at the site of action following its administration (also known as the effect of the drug on the body).
· IC50 (potency measure) is the concentration required to inhibit 50% of the target compound.
· EC50 is the effective concentration of a drug required for a half-maximal response.
· The half-life of a drug in a human body is the time required for the body to eliminate half of that drug or to reduce by half the drug concentration.
V. The statutory scheme under which the matter proceeds
[28] The parties agree that the law of patents is wholly statutory. The Supreme Court of Canada (SCC) has confirmed it again in 2008, in one of the landmark decision I will discuss later, Apotex v Sanofi-Synthelabo Canada 2008 CSC 61[Sanofi]. The SCC cited Justice Judson’s words in Commissionner of Patents v Farbwerke Hoechest Aktiengesellschaft Vormals Meister Lucius & Bruning, [1964] SCR 49 at 57 that “There is no inherent common law right to a patent. An inventor gets his patent according to the terms of the Patent Act, no more and no less” (Sanofi para 12). The SCC also cited Lord Walker’s words in Synthon B.V. v SmithKline Beecham plc, [2005] UKHL 59 at paras 57–58:
57. The law of patents is wholly statutory, and has a surprisingly long history… In the interpretation and application of patent statutes judge-made doctrine has over the years done much to clarify the abstract generalities of the statutes and to secure uniformity in their application.
58. Nevertheless it is salutary to be reminded, from time to time, that the general concepts which are the common currency of patent lawyers are founded on a statutory text, and cannot have any other firm foundation (Sanofi at para12).
[29] As the patent in suit was filed after October 1, 1989, the current provisions of the Patent Act apply. The relevant sections of the Patent Act are reproduced in Annex II for ease of reading.
VI. Decision on motion to update answers given on discovery
[30] On the morning of December 10, 2019, Lilly filed a motion seeking leave to update four answers given on discovery, raising Rule 245 of the Federal Courts Rules, SOR/98-106: They relate to items 421 Q 1030, 433 Q 1052, 441 Q 1107, and 722A Q 2969.
[31] The motion was argued on December 13, 2019 and on December 16, 2019, I requested additional submissions on the prejudice the Defendants alleged they would suffer in the event that the motion to update answers given on discovery was granted (transcript of December 16, 2019 at page 1). I granted Lilly’s motion with short reasons to follow which I now give.
[32] I granted the motion on the basis that it would not be in the best interests of justice to deny the update because there was no compelling evidence suggesting that Lilly lacked diligence in answering discovery questions, and importantly, the Defendants had not established any prejudice (Apotex v Astrazeneca, 2012 FC 559 at paras 22–23, aff’d 2013 FCA 77). Despite having been granted the opportunity to do so, the Defendants did not state which witnesses they would need to re-examine for discovery, nor how their expert depositions would have been different, or how the trial would be impacted.
VII. Issue estoppel and judicial comity
A. Introduction
[33] As per the statement of issues, the Court must determine if Lilly are estopped against re litigating Justice de Montigny’s findings in Eli Lilly Canada Inc v Mylan Pharmaceuticals ULC, 2015 FC 125 [the 684 Patent NOC decision] due to issue estoppel, collateral estoppel, comity and/or abuse of process. In their Closing Memorandum, the Defendants argue there is no legal justification to depart from the conclusions of Justice de Montigny based on the legal principles of issue estoppel and judicial comity.
B. The 684 Patent NOC decision
[34] The 684 Patent NOC decision followed Eli Lilly Canada’s application for an order to prohibit the issuance of a NOC to Mylan for a generic version of tadalafil until the expiry of the 684 Patent (subsection 55.2(4) of the Patent Act and section 6 of the Patented Medicines (Notice of Compliance) Regulations, SOR 93-133).
[35] Mylan, the sole defendant, had then argued that if the 684 Patent were construed as a selection of the 784 Patent, the promised utility was neither demonstrated nor soundly predicted at the filing date, mainly because of the ongoing and serious problem of nitrate interaction. It added that, if the 684 Patent were not construed as a selection patent, it would fail for obviousness and anticipation, based on the 784 Patent, because the dose ranges of the 684 Patent fall entirely within those disclosed in the 784 Patent, and it would have been obvious to test lower doses.
[36] Justice de Montigny declined to issue the order sought by Eli Lilly Canada, and found the allegations of invalidity justified, in that the 684 Patent lacked utility, was anticipated by the 784 Patent and was obvious.
[37] In regards to the person skilled in the art (PSA), Justice de Montigny found the patent to be directed to a person or a drug development team having expertise in areas that are relevant to drug dosing, such as pharmacology and or pharmacokinetics, physiology, dose ranging and safety assessment of candidate therapeutics and with experience in the treatment of ED. This team could include physicians, clinicians, research scientists, pharmacologists, toxicologists and statisticians, with at least a couple of years of experience working in a drug development environment in academia or in the pharmaceutical industry.
[38] Justice de Montigny analysed the patent’s utility by reverting to the promise doctrine, since then abolished by the SCC in AstraZeneca Canada Inc v Apotex Inc, 2017 SCC 36 [AstraZeneca SCC]. He found the reduced side effect profile was not part of the claimed invention, but was merely a result of the invention (at para 148).
[39] Justice de Montigny acknowledged the fact that the only way for Eli Lilly Canada to avoid a finding of anticipation was to construe the 684 Patent as a selection, provided the improvement of tadalafil over sildenafil would be determined peculiar to the claimed dose range. He reviewed the three conditions set forth in In re Farbenindustrie AG’s Patents (1930), 47 RPC 289 (ChD), [IG Farbenindustrie] adopted by the SCC in Sanofi, and found that the third condition was not satisfied (at paras 104–105). Justice de Montigny concluded that the 684 Patent could not be a selection of the 784 Patent as “there is nothing in the specification (let alone the claims themselves) to the effect that the promised advantage is peculiar to this particular dosage to the exclusion of any other unit dose”, nor does it “assert that a larger number of unselected doses do not possess the same advantage”, which is an essential characteristic of a selection patent.
[40] On the co-administration of tadalafil and nitrates, Justice de Montigny concluded that Eli Lilly Canada had not demonstrated that doses of 1mg to 20mg of tadalafil had any improvement over sildenafil, that a sound prediction existed that a unit dose of 1mg to 20mg (at para 140) of tadalafil would provide an improvement in the nitrate interaction over sildenafil, nor that as of the time of the decision, there was such improvement.
[41] Justice de Montigny concluded that the 684 Patent was indeed anticipated by the 784 Patent. He cited section 28.2 of the Patent Act, and outlined that a patent is invalid if the essential elements of the claims were disclosed in such a manner that they became available to the public more than one year before the filing date, and were enabled to a skilled person (Eli Lilly Canada v Novopharm Limited, 2010 FCA 197 at paras 43–45 [Novopharm FCA]). Citing the SCC in Sanofi at paras 32 and 37 and Justice Hughes in Abbott Laboratoties v Canada (Minister of health), 2008 FC 1359 at para 75, Justice de Montigny ultimately concluded that all of the essential elements of the 684 Patent were disclosed by the 784 Patent, and that the 784 Patent provided the skilled person with enough information to perform the invention claimed in the 684 Patent without undue burden.
[42] Justice de Montigny determined that a maximum daily dose of 20mg was not an essential element of the claims of the 684 Patent. He based his finding both on the reading of the claims and disclosure, and on the Canadian prosecution history (file wrapper) of the 684 Patent where, following an objection on the basis of non patentable subject-matter, the applicant removed the reference to a maximum daily dose in order to have its patent approved.
[43] Regarding obviousness, Justice de Montigny framed the issue as whether it would have been obvious for the PSA that unit dosage form of tadalafil between 2 and 20mg, or more precisely between 2.5 and 5mg as asserted, would effectively treat ED. He found that it was more or less self evident that the lower and narrower doses of tadalafil in the 684 Patent would be effective in treating ED in humans and would result in a reduced side effect profile, and that the 684 Patent was obvious.
[44] Justice de Montigny also concluded that: (1) there is no question that sildenafil, as the only approved oral ED medication, would have guided the direction of research with regard to future ED medications acting through PDE5 inhibition; (2) it would be an overstatement to claim that there were an infinite number of predictable solutions, or that it was a long and arduous process involving the design and execution of complex clinical studies and the analysis of massive volumes of data resulting from those studies for a number of reasons he outlined; (3) a skilled person would likely have started the studies with doses of around 5mg and moved up to 50mg; and (4) the actual course of conduct did not establish otherwise.
C. Decision on issue estoppel and judicial comity
[45] The Defendants argue that issue estoppel applies to a number of discrete issues regarding which Lilly has failed to adduce “significant and important new evidence or argumentation” (Apotex v Pfizer Ireland, 2011 FCA 77 at para 25). They also argue that judicial comity applies to prevent this Court to decide the same legal issues, already decided by Justice de Montigny as there has been no demonstration that his legal determination were “manifestly wrong”.
[46] Lilly submit they are not estopped from re litigating the findings of the 684 Patent NOC decision due to issue estoppel, collateral estoppel, comity and-or abuse of process. According to Lilly, the Defendants’ argument must fail because PM (NOC) applications are summary proceedings, not actions, and only seek to prohibit the Minister of Health from issuing a NOC, as opposed to an in rem finding of infringement or validity. Lilly submit that the test for issue estoppel is not met here, that infringement actions are not abuses of process even though applications were decided on those patents under the old NOC Regulations, and that comity does not apply between NOC proceedings and a subsequent action for infringement and impeachment.
[47] I note that the evidence adduced before Justice de Montigny and the one adduced before this Court is different, and that he heard no viva voce testimony (Sanofi-Aventis Canada v Apotex Inc, 2009 FC 676, aff’d 2011 FCA 300). I also note that, before Justice de Montigny, the asserted claims were slightly different, and that Mylan argued that the 684 Patent was a selection while Eli Lilly Canada took no position in this regard. In this Court, Lilly now assert that the 684 Patent is a selection, while the Defendants now argue it is not. Finally, two legal principles have changed since Justice de Montigny’s decision, as the promise doctrine was abolished by the SCC and section 53.1 of the Patent Act was adopted.
[48] In regards to issue estoppel, I agree with Lilly’s position that the Defendants’ allegations of issue estoppel do not apply given the circumstances at hand. However, and in any event, I need not consider this issue further as I agree with Justice de Montigny’s conclusions on the issues that are common to our cases. Also, given my agreement on his analysis of the relevant common questions of law, I need not consider the deference I might have accorded his analysis (Biovail Corporation v Canada (Minister of National Health and Welfare), 2006 FC 784 at para 8).
I. Burden of proof
[49] Lilly bear the burden to prove, on a balance of probabilities, infringement of the asserted Claims of the 684 Patent, while the Defendants bear the burden to prove, on a balance of probabilities, their invalidity.
II. Lilly’s fact witnesses
A. Dr. Karl Donn
[50] Dr. Donn joined Glaxo in 1987. He is the former Product Development Leader, led a group that was responsible for development of all early human testing of compounds that came out of Glaxo US Discovery, and at the time of his retirement he was the Global Vice President of Project and Portfolio Management. He holds undergraduate degrees in chemistry and pharmacy and a Master and PhD in pharmacy.
[51] In 1991, Glaxo and ICOS signed a research agreement, and in 1995, Dr. Donn became involved in the tadalafil project until early 1997. The compound was known as GF 196960X at Glaxo, and as IC351 at ICOS. Dr. Donn led the team of cross-functional experts and was accountable to the committee that oversaw the development of all early stage compounds at Glaxo. His role was to integrate all the work that was being done on the project and to drive it forward as rapidly as possible.
[52] Dr. Donn testified essentially on the usual drug development process, the purpose for which the drug is being developed, the dosage, the preclinical studies and toxicity issues encountered, the healthy young and elderly male study, the termination of the Glaxo program, the guinea pigs test, and the knowledge the team had on sildenafil.
[53] Dr. Donn was overall a credible witness. However, there were slight discrepancies and gaps in his testimony, likely due to the passage of time.
[54] In particular, Dr. Donn failed to explain why, from early on in the tadalafil development process, the document GF 196960X Summary Exploratory Development Meeting of August 19, 1996 (Exhibit 22) indicated that “thus in man, 10mg, rather than 100mg, was found to exceed the estimated EC50 for 12h and 25 mg for 24h”, and that “25mg, therefore, seemed to be the most likely therapeutic dose in man, at least for cardiovascular indications where a 24-hour cover would be required”. This is a caveat in Lilly’s invention story.
B. Dr. Kenneth Ferguson
[55] Dr. Ferguson joined ICOS in 1990. When ICOS signed a research agreement with Glaxo, he was called upon to lead the product development team at ICOS and act as the principal correspondent with Glaxo. Dr. Ferguson became the product development team leader for what became known as tadalafil and led the work on a PDE5 inhibitor. He holds a BSc, and a PhD in pharmacology, and completed a postdoctoral fellowship.
[56] He testified essentially on his experience prior to the development of tadalafil, on the dosage choices, on the termination of the research agreement between ICOS and Glaxo as of January 1997, on the investigative brochure submitted to the US Food and Drug Administration (FDA), on US Patent 2003/0144296, where the DSD04 and DSD06 studies were cited, and on the low 2mg doses. Dr. Ferguson wrote in Exhibit 44 as author of a journal article that the low 2mg doses as in the DSD06 study had no effect. Dr. Ferguson recalled that it was a team that selected the dose for the DSD04 and DSD06, studies, without giving any specifics.
[57] Dr. Ferguson was a credible witness.
C. Dr. William Ernest Pullman
[58] Dr. Pullman is a named inventor of the 684 Patent. He is a medical doctor specialised in Internal Medicine Gastroenterology, has a BSc in Medical Science, and undertook PhD training at the Australian National University and the London Imperial Cancer Research Institute.
[59] In 1995, he joined Lilly as a Regional Medical Doctor. Sometime in 1998, he was called upon to work on the due-diligence team of the development of tadalafil in a joint venture between Lilly and ICOS in Indianapolis. He was the Director of medical affairs at Lilly ICOS until June 2001.
[60] Dr. Pullman testified essentially on his past experiences, on dosages, on nitrates interactions, on flushing, on his involvement with sildenafil, on the halting of clinical trials by the FDA, on his contribution to DSD06 and DSD04 and on female sexual dysfunction.
Although he was a credible witness, Dr. Pullman did not remember some of the details or did not have the details, especially on the dose selection of the DSD04 study. As a result, there still remained gaps in Lilly’s invention story, similar as found by Justice de Montigny in the 684 Patent NOC decision at para 171.
III. Expert witnesses
A. Defendants’ expert witnesses
(1) Dr. Sharon Baughman
[61] Dr. Baughman is an expert in the field of pre-clinical and clinical pharmacology including the pharmacokinetics and pharmacodynamics and metabolism of small molecule entities, the design, conduct, analysis and reporting of non-clinical and clinical studies and PK/PD modelling and dose selection. She received a PhD in Physical Organic Chemistry and BSc in Chemistry.
[62] Dr. Baughman was tendered as a expert witness in the field of preclinical and clinical pharmacology, including the pharmacokinetics, pharmacodynamics, and metabolism of protein and small molecule entities; the design, conduct, analysis, and reporting of nonclinical and clinical studies; and PK/PD modelling and dose selection. She submitted a report dated August 29, 2019 (Exhibit 69), in which she outlined how she would proceed onto the selection of doses with the tests and research results contained in Glaxo, ICOS, Lilly documents given by counsels.
[63] Lilly objected to the admissibility of her expert deposition on the basis that she had no experiences in small molecules drug development. I dismiss the objection as in any event, Dr. Baughman confirmed she did have experience working with pharmaceutical proteins, and later, pharmaceutical small molecules.
[64] I have considered Lilly’s comments that Dr. Baughman was not really blinded and I am satisfied she indicated accurately the circumstances of her opinion.
[65] I found Dr. Baughman to be direct, straightforward and engaging. She came across as independent, honest and thorough. I give her opinion much weight.
(2) Dr. Peter Ellis
[66] Dr. Ellis is a pharmacologist and expert with more than 35 years of drug development experience. He holds a BSc and a PhD in in pharmacology. He was part of the Pfizer Central Research team between 1981 and 2009 that discovered and developed the sildenafil molecule. Since 2009, he was Director of Pentropy Consulting Limited, providing drug development support to the pharmaceutical industry.
[67] Dr. Ellis was tendered as an expert witness in the fields of the discovery and development of drugs. This includes drugs used in the treatment of urological conditions, such as PDE5 inhibitors used to treat male erectile dysfunction (MED), preclinical and clinical pharmacology and dose selection for drugs, including the development, design, conduct, analysis, and reporting of preclinical and clinical pharmacology and dosing studies.
[68] He produced a main Expert Report, a Responding Report, and a Reply Report, dated respectively August 28, 2019, October 30, 2019, and November 25, 2019 (Exhibits 71–73).
[69] Lilly attack Dr. Ellis’ expert deposition on the basis that he was an argumentative witness on the stand, unable to answer simple questions without advocating for the Defendants. Lilly also argue that he placed the level of knowledge of the PSA at an excessively high level, and his evidence lacked credibility. As a whole, I found Dr. Ellis was a credible and nuanced witness.
(3) Dr. Wayne Hellstrom
[70] Dr. Hellstrom holds a BSc in physiology and has a doctor of medicine and master of surgery degree from McGill. He was a general surgery resident at the Montreal General Hospital and Royal Victoria Hospital before moving on to become a Resident and Chief Resident in Urology at the University of California San Francisco. He was also a fellow in andrology at the University of Calif