Allergan Inc. v. Juno Pharmaceuticals Corp.

Allergan Inc. v. Juno Pharmaceuticals Corp.
Court (s) Database
Federal Court Decisions
Date
2023-12-18
Neutral citation
2023 FC 1686
File numbers
T-1994-21
Decision Content
Date: 20231218
Docket: T-1994-21
Citation: 2023 FC 1686
Ottawa, Ontario, December 18, 2023
PRESENT: Mr. Justice Pentney
BETWEEN:
ALLERGAN, INC. AND ABBVIE CORPORATION
Plaintiffs
and
JUNO PHARMACEUTICALS CORP.
Defendant
PUBLIC JUDGMENT AND REASONS
(Confidential version issued on December 13 2023)
Table of Contents
I. Introduction 3
II. Background 5
A. The Parties 5
B. The 691 Patent 6
C. Previous Litigation Concerning the 691 Patent 8
(1) Litigation in Canada 8
(2) Litigation in Other Countries 10
D. Glaucoma, Intraocular Hypertension, & the Challenge of Creating Effective Eye Drops 11
(1) The Physiology of the Eye 12
(2) The Challenge of Human Behaviour 17
III. Issues 18
IV. Witnesses 19
A. Allergan’s Witnesses 19
(1) Dr. Noecker 19
(2) Dr. Berkland 21
(3) Dr. Chang (Inventor) 22
B. Juno’s Witnesses 23
(1) Dr. Morgan 23
(2) Dr. Alany 25
V. The Skilled Person 27
VI. Claim Construction 28
A. Legal Principles 29
B. Asserted Claims 30
C. Parties’ Positions on Claims Construction 30
D. Analysis 31
VII. Obviousness 32
A. Legal Principles 32
B. Step 1 – The Skilled Person and their Common General Knowledge 34
(1) The POSITA 35
(2) The Common General Knowledge of the POSITA 35
C. Step 2 – Inventive Concept 42
(1) The Experts’ Opinions 43
(2) The Submissions of the Parties 48
(3) Analysis 51
D. Step 3 – Differences between the State of the Art and the Inventive Concept 63
(1) Reducing the Amount of Bimatoprost 64
(2) Increasing the Amount of BAK 71
(3) Achieving Equal or Better IOP Reduction 85
(4) Conclusion on Sanofi Step 3 107
E. Step 4 – Obvious to Try 108
(1) The Evidence 110
(2) Submissions of the Parties 119
(3) Analysis 124
VIII. Sufficiency of Disclosure 128
IX. Conclusion 133
I. Introduction [1] This is a patent infringement action pursuant to s. 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [PM(NOC) Regulations].
[2] The patent at issue concerns a drug used to treat glaucoma and intra-ocular hypertension (“IOH”). Glaucoma is sometimes called the “silent thief of sight” because it slowly damages the eyes and can cause irreparable harm before there is any vision loss. Pressure inside of the eye, known as intra-ocular pressure (“IOP”), is a leading cause of glaucoma; it can damage the optic nerve at the back of the eye, and once that occurs the loss of sight is permanent. Ocular hypertension describes a condition in which a person’s IOP is above the normal range but they have not been diagnosed with glaucoma or have no detectable damage.
[3] Although there is no cure for glaucoma or ocular hypertension, there are some treatments that can slow or stop the condition. To be effective, such treatment must generally begin before the patient is aware of any loss of vision.
[4] The Plaintiffs own a patent for a product marketed as LUMIGAN RC that was launched in 2009 and is used to treat glaucoma and ocular hypertension by lowering the pressure inside the eye, referred to as intraocular pressure (“IOP”). LUMIGAN RC is an improvement over a previous formulation (LUMIGAN .03; hereafter “Old LUMIGAN”) that was successful in lowering IOP but had unwanted side effects.
[5] The Defendant seeks to obtain approval for a generic equivalent to the Plaintiffs’ LUMIGAN RC. The Defendant concedes that its product would infringe the LUMIGAN RC patent, but argue that the patent is invalid for obviousness and insufficient disclosure. The Plaintiffs seek to prevent the Defendants from entering the market with their generic drug formulation.
[6] Previous decisions of this Court and the Federal Court of Appeal under the prior regime found the Plaintiffs’ patent to be valid and prevented the entry into the market of generic equivalents. In addition, there has been litigation about the equivalent patent in both the United States and the United Kingdom. The question of whether those decisions are relevant to the current proceeding under the new Patented Medicines (Notice of Compliance) Regulation (“PM(NOC)”) regime is one of the issues raised in this case.
[7] At trial, only two claims of the patent remained in issue, and the parties focused most of their attention on the question of obviousness.
[8] For the reasons that follow I find in favour of the Plaintiffs. The Patent is not invalid for obviousness or lack of sufficient disclosure. The Plaintiffs are entitled to the declaration they seek.
II. Background
A. The Parties
[9] The Plaintiffs are Allergan Inc. (“Allergan”) and AbbVie Corporation. Allergan is an innovative pharmaceutical company incorporated under the laws of Canada.
[10] Allergan (Canada) filed submissions in Canada seeking Notices of Compliance (“NOC”) in respect of LUMIGAN RC (bimatoprost ophthalmic solution 0.01% w/v) for the treatment of elevated IOP in patients with open angle glaucoma or ocular hypertension. Subsequently, Allergan Canada amalgamated with the plaintiff AbbVie Corporation (“AbbVie”), and on September 9, 2022, the NOC for LUMIGAN RC was updated to reflect the amalgamation and now lists AbbVie as the NOC holder. Accordingly, under the PM(NOC) Regulations, AbbVie is a “first person.”
[11] Allergan (United States) is the owner of Canadian Patent No. 2,585,691 (“the 691 Patent”) which is in issue in this litigation. For ease of reference, AbbVie and Allergan (Canada and US) are referred to in these reasons as “Allergan”.
[12] Juno Pharmaceuticals Corp. (“Juno”) is a pharmaceutical company located in Ontario. It develops and sells generic drug products. Juno filed an Abbreviated New Drug Submission (ANDS) with Health Canada seeking approval of Juno’s 0.01% w/v bimatoprost solution for ophthalmic administration (the Juno Product) for the treatment of elevated IOP in patients with open angle glaucoma or ocular hypertension. For the purposes of its ANDS, Juno compared the Juno Product to LUMIGAN RC to demonstrate bioequivalence.
[13] As required by the PM(NOC) Regulations, Juno delivered a Notice of Allegation (NOA) relating to the 691 Patent to AbbVie on November 19, 2021. Juno is therefore a “second person” under the Regulations.
B. The 691 Patent
[14] The 691 Patent is titled “Enhanced Bimatoprost Ophthalmic Solution.” Its claim date is March 16, 2005. Its publication date is September 28, 2006. The patent expires on March 14, 2026.
[15] Allergan alleges that Juno will infringe claims 16 and 19 of the 691 Patent:
16. A composition comprising by weight 0.01% bimatoprost, 0.02% benzalkonium chloride, 0.268% sodium phosphate dibasic heptahydrate, 0.014% citric acid monohydrate, 0.81% sodium chloride, water, and wherein said composition is an aqueous liquid with a pH adjusted to 7.3.
19. Use of a composition according to any one of claims 1 to 16 for treating glaucoma or intraocular hypertension in a mammal.
[16] Claim 19 is a dependent claim that refers, inter alia, to Claim 1. Because this was raised by the Defendant as an issue in the trial, it is convenient to reproduce Claim 1 here:
1. A composition comprising from 0.005% to 0.02% bimatoprost by weight and from 0.01% to 0.025% by weight benzalkonium chloride, wherein said composition is an aqueous liquid which is formulated for ophthalmic administration.
[17] As noted earlier, LUMIGAN RC was developed because of issues regarding the old LUMIGAN product. Although old LUMIGAN was effective in lowering IOP, it caused a condition called conjunctive hyperemia, which is characterized by redness in the eye, itching and eye pain. The condition was serious enough that a significant number of patients stopped taking the medication. (Old LUMIGAN also caused some other side effects such as lengthening of the eyelashes which was a problem for people who wear glasses, but these are not relevant for this case). Allergan therefore sought to develop a formulation that was similarly effective in lowering IOP but did not cause the unwanted side effects.
[18] The new formulation discovered by Allergan involved two key changes from the formula for the old LUMIGAN product: a significant reduction in the amount of bimatoprost (the active ingredient) combined with a significant increase in the amount of benzalkonium chloride (“BAK”), the preservative used in both products. This is key to understanding the issues in this case, and the table set out below provides a useful summary:
Product
Bimatoprost
BAK
Old LUMIGAN
0.03% (300 ppm)
0.005% (50 ppm)
LUMIGAN RC
0.01% (100 ppm)
0.02 % (200 ppm)
Ppm = parts per million
C. Previous Litigation Concerning the 691 Patent
(1) Litigation in Canada [19] The 691 Patent has been the subject of litigation under the prior PM(NOC) regime in this Court and the Federal Court of Appeal: see Allergan Inc v Canada (Health), 2014 FC 567 [Apotex FC]; Apotex Inc v Allergan Inc, 2015 FCA 137 [Apotex FCA]; and see the companion case Allergan Inc v Canada (Health), 2014 FC 566 [Cobalt FC].
[20] Under the prior PM(NOC) regime, a patent holder would bring an application in this Court to prohibit the Minister of Health from issuing a NOC to a generic drug manufacturer to prevent the allegedly patent-infringing product from entering the market. The case was then dealt with under the Federal Courts Rules, SOR/98-106 that govern applications. This meant that evidence was tendered by affidavit, and the usual discovery process applicable to actions launched by statement of claim was not available.
[21] The two decisions of this Court, Apotex FC and Cobalt FC (by Justice James O’Reilly), are very similar, and so I will only summarize the Apotex FC decision, which involved an application for a NOC by Apotex, a generic pharmaceuticals company. In response to Allergan’s application, Apotex alleged that the 691 Patent was invalid on the grounds of obviousness, lack of utility and anticipation. Justice O’Reilly found in favour of Allergan and issued the prohibition order, thus preventing Apotex (and Cobalt Pharmaceuticals Company in the companion case) from entering the market. He accepted Allergan’s argument that the inventive concept of the 691 Patent included comparable efficacy to old LUMIGAN, and found that the new formulation involved inventive steps and was not obvious.
[22] After reviewing the evidence and arguments on the issues, Justice O’Reilly found that Apotex had not met its burden of showing that the 691 Patent was invalid, and so he issued the order of prohibition requested by Allergan.
[23] Apotex appealed, and the Federal Court of Appeal, in a short judgment, dismissed the appeal: Apotex FCA. For our purposes, two findings are relevant. The Court of Appeal found that there was no error in the construction of the 691 Patent or in the determination of the inventive concept adopted by Justice O’Reilly. Justice Eleanor Dawson for the Federal Court of Appeal found:
[7] Dealing with each asserted error, I am satisfied that:
i. The Federal Court did not err in its construction of the inventive concept of the 691 patent. The nub of Apotex’ argument is that the Federal Court inferred the inventive concept from data found in the 691 patent. In Sanofi, at paragraph 77, the Supreme Court found that the inventive concept of the claims there in issue was not readily discernible from the claims themselves. It was therefore acceptable to read the specification in the patent to construe the inventive concept. In the present case, the relevant claims related to a chemical composition and the use of the composition for treating glaucoma or intraocular hypertension in a mammal. The Federal Court found the composition claimed did not determine the claims’ inventive concept and so it construed the inventive concept by reading the patent as a whole. In doing so, the Federal Court considered the inventive concept in light of the disclosure of the patent from the viewpoint of the skilled reader. This was not an error of law and no palpable and overriding error has been shown in the Federal Court’s conclusion as to the inventive concept.
(Citing Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61, [2008] 3 SCR 265 [Sanofi].)
[24] The Federal Court of Appeal’s specific finding on inventive concept, and its relevance, if any, to the current proceeding is discussed below, and so I will not say more about it here.
(2) Litigation in Other Countries [25] In addition to the prior Canadian cases, Allergan holds an equivalent patent in other countries, which has been litigated in the United Kingdom and United States.
[26] In the case brought in the United Kingdom, the Court found that the patent was obvious, and therefore invalid: Allergan Inc v Aspire Pharma Ltd, [2019] EWHC 1085 (Pat); leave to appeal from this decision was denied.
[27] On the other hand, in the United States the challenge was dismissed because the court found the patent was not obvious: Allergan Inc v Sandoz Inc, No 6:11-cv-00441 (ED Tex Jan 1, 2014), and this decision was upheld on appeal by the Federal Circuit Court of Appeal: Allergan Inc v Sandoz Inc, No 14-1275 (Fed Cir 2015).
[28] In my view, nothing can be gained by a review of these decisions, because they are based on different facts assessed under different legal frameworks. Therefore no more need be said about them here.
D. Glaucoma, Intraocular Hypertension, & the Challenge of Creating Effective Eye Drops [29] Glaucoma is a chronic, progressive and incurable disease of the eye in which IOP is elevated. Left untreated, or if not treated effectively, glaucoma causes gradual, irreversible vision loss and can ultimately lead to total blindness. Almost 70 million people suffer from glaucoma, which is the second leading cause of blindness worldwide. It affects up to 2% of the total population, and up to 4% of people over age 75.
[30] As noted above, glaucoma is frequently called the “silent thief of sight” because patients with the condition do not experience any symptoms before significant vision loss occurs, and so they are not aware of what they are losing until it is gone. That presents a challenge because patients must begin daily treatment to stop the condition from advancing before they notice any problems with their vision, and for some the treatment can seem worse than the condition.
[31] Intraocular hypertension (IOH) and glaucoma are part of the same disease continuum. Patients diagnosed with glaucoma have suffered detectable damage to their optic nerves, nerve fiber layers and/or visual fields. Patients with IOH have elevated IOPs but no detectable damage to their optic nerves or nerve fiber layers, and no loss of their normal visual fields. Left uncontrolled, or inadequately controlled, ocular hypertension can cause damage to the optic nerve resulting in visual field loss, i.e. glaucoma.
[32] Higher than normal IOP causes damage to the optic nerve, which is the pressure-sensitive part of the eye. This nerve is the connection between the eye and the brain. High IOP causes damage to the nerve over time, so while the eye itself may be functioning, only some or none of the signals reach the brain. Glaucoma is diagnosed when the optic nerve is damaged, causing some loss of vision.
[33] The challenge of effective treatment involves confronting issues of physiology as well as the psychology of human behaviour. The first difficulty with treating ophthalmic conditions using eye drops comes down to a simple fact: effective treatment involves getting drugs into the eye, but the eye is very well designed to keep things out. A second challenge involves human nature: patients may stop using eye drops that cause discomfort or disagreeable side effects because they find the treatment can seem worse than the disease.
(1) The Physiology of the Eye [34] The human eyeball is a slightly asymmetrical sphere that is composed of several primary layers (see Figure 1 below).
[35] The anatomy of the eye includes:
(a)Cornea: The eye’s front surface (a clear dome over the iris), the cornea covers the iris, pupil, and anterior chamber. The cornea is responsible for approximately 70% of the total focusing ability of the eye;
(b)Iris: Located behind the cornea, is the colored part of the eye and contains the pupil. The iris adjusts the size of the pupil to control the amount of light entering the eye;
(c)Pupil: The black circle within the eye’s iris. The pupil’s size determines how much light enters the eye;
(d)Lens: Located behind the pupil, the lens focuses light on the retina;
(e)Sclera: The white of the eye;
(f)Conjunctiva: A thin clear mucous membrane that covers the outer surface of the sclera and lines the inner surfaces of the eyelids;
(g)Retina: Located at the back of the eye, receives images from the cornea and the lens and contains light-sensitive cells, called photoreceptors; and
(h)Optic Nerve: Transports visual signals from the retina in the back of the eye to the brain.
Figure 1
[36] The eyeball has three chambers of fluids. The anterior chamber is located in the front of the eye between the cornea and the iris. The areas in front of the lens on either side of the iris are filled with aqueous humour produced by the ciliary body, a ring of tissue that encircles the lens. The front portion of the eye does not have its own blood vessels and the aqueous humour provides nutrition, oxygen and antioxidants to that part of the eye. The posterior chamber is behind the iris but in front of the lens). The vitreous chamber is located in the centre of the eye behind the lens and in front of the retina.
[37] Glaucoma and ocular hypertension are characterized by elevated IOP, caused by an imbalance in the inflow and outflow of aqueous humour. In a healthy eye, the aqueous humour leaves the eye primarily by the trabecular meshwork and canal of Schlemm, from which it goes into systemic circulation. The conventional pathway accounts for much of the aqueous humour outflow. An alternative pathway is the uveoscleral route, in which the aqueous humour flows through the ciliary muscles and eventually into the choroid and sclera. Up to 30% of the outflow may follow this alternative route.
[38] The basic problem with glaucoma and ocular hypertension is that the eye’s drainage mechanisms do not allow aqueous humour fluid to flow out of the eye rapidly enough, which results in a rise in IOP. This is understood to be caused by degeneration of the trabecular meshwork. Because the inflow and outflow are not in balance, IOP increases which can cause damage to the optic nerve leading to disturbance of the visual field, and eventually total blindness.
[39] As with all medications, part of the effective treatment of a condition using eye drops involves getting the right amount of the active ingredient – the drug – to the right place and for the right amount of time. In the treatment of glaucoma and ocular hypertension, this involves getting the drug to penetrate the eyeball so that it can have the desired effect of lowing IOP.
[40] Very little of the active ingredient in an eye drop will be able to penetrate the eye. The experts testified that only 1% to 10% of a medication will get into the eye. As anyone who has ever had a speck of grit get into their eye will appreciate, the involuntary blinking and increased tear production reaction that if triggered can be a very effective way of flushing foreign substances or objects from the eye. The same thing can happen when administering an eye drop.
[41] The next barrier to getting the active ingredient inside the eyeball is the design of the eye itself. Topically applied ophthalmic drugs enter the eye through the cornea, the sclera and/or the conjunctiva. The cornea is the transparent ocular membrane that covers the front of the eyeball. The cornea is comprised of five layers. The outermost layer is the corneal epithelium, which is the eye’s primary barrier against the entry of foreign substances. This layer is comprised of many corneal epithelial cells packed tightly together in a unique arrangement called “tight junctions” (see Figure 2 below). This makes it difficult for foreign substances to penetrate the eye, unless they can penetrate the epithelial cells or are small enough to squeeze through the tight junctions.
Figure 2
[42] Behind the corneal epithelium are the Bowman’s layer, the stroma, the Descemet’s membrane, and the endothelium. To reach the interior of the eye via the cornea, a drug must pass through each of these layers. There are two ways in which a drug can do that. The first, called transcellular transport, involves the drug passing directly through the cells of each layer (i.e. enter a cell and exit out the other side, and then again through the next four layers of cells). The second, called paracellular transport, involves the drug squeezing between the small spaces in between the cells of each layer.
[43] The route that a drug takes to penetrate the eye depends on how the drug behaves in the presence of either water or lipids. Drugs that have an affinity for lipids are referred to as “lipophilic”; drugs that have an affinity for water are referred to as “hydrophilic”. It is more accurate to describe drugs as more or less lipophilic or hydrophilic, since these qualities are on a spectrum.
[44] The corneal epithelium is lipophilic, or oily, a bit like the outer layer of our skin. This serves to keep water from penetrating the eye, which would disturb our vision and cause an imbalance in the IOP. Lipophilic drugs can pass more easily through the epithelial cell layer, because lipids have an affinity for lipids. Drugs that have an affinity for watery (hydrophilic) environments will have a more difficult time penetrating the eye because water and lipids repel each other.
[45] Once a lipophilic drug has penetrated the cornea, it faces another hurdle because the stroma is more hydrophilic and will thus tend to repel the drug. Drugs with an affinity for water will pass through this layer more easily.
(2) The Challenge of Human Behaviour [46] The second major challenge associated with using eye drops to treat glaucoma or ocular hypertension is patient “compliance” (also referred to as “adherence”). No matter how well a medication may perform in the lab, it will not be an effective treatment if patients will not use it on a consistent basis. This is particularly important for glaucoma and ocular hypertension, for two reasons.
[47] First, as noted earlier, these conditions can progress and cause irreparable damage before the patient experiences any symptoms or otherwise becomes aware of the harm. Eye drops can slow or halt the progression of the condition by lowering IOP, but that requires the patient to start and continue the treatment even though they are not experiencing any problems. In that circumstance, one can understand why difficulties associated with taking the medication as prescribed – for example because it requires multiple daily doses, causes stinging or other discomfort when administered, or it results in unpleasant side effects – can lead patients to discontinue using it. As one expert testified at the trial, some patients may find the treatment worse than the disease, ignoring the longer-term consequences of their choice.
[48] Second, daily compliance with the treatment regime is especially important, because although fluctuations in IOP during the day occur naturally, studies have shown that wide variations in IOP can accelerate or increase the harm to the eyesight of patients with glaucoma or ocular hypertension. As one of the experts said, taking glaucoma medication is boring, because it requires a daily dose of one or more medications, often for the rest of a person’s life. And the patient will usually not notice any improvement in their vision, because the medication is actually only stopping further decline.
[49] With this background we turn to the issues and analysis of the matters in dispute.
III. Issues
[50] There are only two issues in this case:
Is the 691 Patent invalid due to obviousness?
Is the 691 Patent invalid for insufficient disclosure?
[51] Juno concedes that its generic drug will infringe the 691 Patent. The focus of the evidence and arguments was on Juno’s arguments about invalidity.
IV. Witnesses
[52] There was no real challenge to any of the experts’ qualifications, but the parties made submissions regarding the weight that should be accorded to their evidence. I set out an overview of the experts’ backgrounds and my overall credibility findings here; more detail is provided on specific points in the analysis of the issues in dispute in subsequent sections of the decision.
A. Allergan’s Witnesses
(1) Dr. Noecker [53] Dr. Robert Noecker is a practicing ophthalmologist and Assistant Clinical Professor of Ophthalmology at the Yale School of Medicine, as well as a Clinical Professor at the Frank Netter School of Medicine at Quinnipiac University. He also currently serves as Director of Glaucoma at Ophthalmic Consultants of Connecticut. He obtained his MD from the University of North Carolina’s School of Medicine in 1990 and completed his residency in ophthalmology in 1994. In total, he has over 30 years of experience studying and treating glaucoma and ocular hypertension.
[54] Dr. Noecker has expertise in the design and conduct of clinical trials and has participated in over 40 funded clinical trials, the majority related to glaucoma drugs, including LUMIGAN®, TRAVATAN®, and XALATAN®. He has also published over 100 peer-reviewed publications, with a particular focus on glaucoma, including on the efficacy and safety of bimatoprost and the use of the preservative BAK in ocular formulations. In 2005, on the priority date of the 691 Patent, Dr. Noecker was the Vice-Chair of the UPMC Eye Center at the University of Pittsburgh. He testified that he was treating about 200 glaucoma patients per week at that time.
[55] Dr. Noecker was qualified as an expert on the following terms:
Dr. Robert Noecker is an ophthalmologist with expertise in treating patients with glaucoma and ocular hypertension, including the efficacy and safety of bimatoprost and other compounds that lower intraocular eye pressure (“IOP lowering agents”). Dr. Noecker’s expertise also includes the design and conduct of clinical trials involving ophthalmic medicines, including IOP lowering agents. Dr. Noecker is an expert in the evaluation of preservatives used in ophthalmic solutions, including their safety and efficacy.
[56] Juno argued that Dr. Noecker’s evidence should be given less weight because he has “extensive and ongoing” ties to Allergan, having received research funding from the company since the 1990’s and because he has previously testified as an expert witness for Allergan. In addition, Juno submits that his evidence was marred by contradictory statements and an apparent lack of knowledge on certain key details. For example, they point out that Dr. Noecker’s description of the findings of a key research study was incorrect, and thus Juno contends that his evidence should not be relied upon.
[57] Overall, I found Dr. Noecker’s evidence to be clear and consistent, and he displayed an understanding of this role as an expert witness in the proceeding. In regard to Juno’s argument about his ties to Allergan, I was attentive to possible bias and did not perceive any.
[58] Juno’s challenge to Dr. Noecker’s evidence is discussed below, in particular the mistake he made in his expert report regarding a key piece of prior art. On this, Dr. Noecker readily acknowledged his error, and his expert report correctly referred to the document in another section. I do not find that this mistake diminishes his overall credibility.
[59] Dr. Noecker is clearly familiar with the various medications used for treating glaucoma and IOH at the relevant time based on his extensive clinical experience at that time, and he has written articles that directly address the key questions in dispute in this case. It should be noted that Juno’s experts cited Dr. Noecker’s research in their own reports. As discussed below, I give Dr. Noecker’s evidence substantial weight in analysing the key issues in dispute.
(2) Dr. Berkland [60] Dr. Cory Berkland is a pharmaceutical formulation scientist with expertise in ophthalmic pharmaceutical formulations. He received his PhD from the University of Illinois, Department of Chemical and Bimolecular Engineering. He currently holds the title of Solon E. Summerfield Distinguished Professor at the University of Kansas in the Department of Pharmaceutical Chemistry and the Department of Chemical Engineering. He has been teaching at the University of Kansas since 2005 and his teaching includes material on ocular drug delivery.
[61] Dr. Berkland also leads the Berkland Lab at the University of Kansas, which works on the interface of medicine and engineering in drug development. He is the CEO of a number of start-up companies developing ocular therapies and drugs. Dr. Berkland has published approximately 200 peer-reviewed papers, including on pharmaceutical formulation and ocular drug delivery systems. His expertise includes drug development, drug delivery, and the transport of drugs across biological membranes, including the corneal epithelium.
[62] Dr. Berkland was qualified as an expert on the following terms:
Dr. Cory Berkland is a pharmaceutical formulation scientist with expertise in ophthalmic drug delivery, including pharmaceutical formulations for ophthalmic application and their ingredients. His expertise includes drug development, drug delivery, and the transport of drugs across biological membranes, including the corneal epithelium. His expertise also includes design, development, and evaluation of ophthalmic drug delivery systems to administer drugs to the eye including in animal studies.
[63] Juno argued that Dr. Berkland revealed himself to be a witness lacking in independence, and they say he provided evasive testimony and refused to make concessions that other witnesses readily made. They point to inconsistent testimony on important matters, and argue that his review of the prior art was tainted by hindsight.
[64] Overall, I found Dr. Berkland to be a credible expert witness. His evidence was clear and consistent and he demonstrated a capacity to provide objective assistance to the Court, as required of an expert witness.
(3) Dr. Chang (Inventor) [65] Dr. Chin-Ming Chang is an inventor of the 691 Patent. Dr. Chang earned a PhD in Pharmaceutics from the University of Texas in 2005. He began his employment with Allergan in 1999 on the Formulation Development Team as a Senior Scientist. In 2003, he was promoted to Principal Scientist on this team. Dr. Chang was the lead formulator for Allergan’s Lumigan Enhancement Team (which eventually developed LUMIGAN RC) from 2003 until the completion of the project. He no longer works for Allergan.
[66] Juno argued that Dr. Chang’s evidence was incomplete, because he was not part of the Lumigan Enhancement Team from the beginning of the work. Therefore, he could not testify from personal experience about the earliest stages of the work that resulted in the development of LUMIGAN RC. Juno questioned why Allergan did not choose a fact witness who was part of the team during the entire period of work.
[67] Overall, I found Dr. Chang to be a credible witness, who acknowledged the limitations of his testimony. He testified in a forthright manner, and his evidence was not seriously challenged on cross-examination. I acknowledge the truth of Juno’s assertion that he did not have personal knowledge of the earlier phases of the team’s work. Given the documents that have been produced, and the unchallenged evidence that the first two years of effort did not produce a clinically viable alternative product, nothing turns on this issue.
B. Juno’s Witnesses
(1) Dr. Morgan [68] Dr. James Edward Morgan is a practicing ophthalmologist and clinical scientist at the University Hospital of Wales. He has also been Professor of Ophthalmology at Cardiff University since 1997. He has over 25 years of experience working in the field of ophthalmology with a specialized research interest in glaucoma. In 2005, Dr. Morgan was the consultant in charge of glaucoma services in Cardiff, working as a front-line clinician treating patients with glaucoma.
[69] Dr. Morgan has authored or co-authored over 109 peer-reviewed journal articles. He currently serves on the editorial board of The Journal of Glaucoma. He works in a clinical setting ten hours per week providing care to glaucoma patients and sees approximately 100 patients per month.
[70] Dr. Morgan was qualified as an expert on the following terms:
Dr. James Edwards Morgan is a medical doctor and specialist in ophthalmology with expertise in treating patients with glaucoma and conditions of elevated intraocular pressure (“IOP”), including the efficacy and safety of drugs used for the treatment of glaucoma and high IOP. Dr. Morgan is also a clinical scientist with a specialized research interest in glaucoma. He leads clinical glaucoma studies and provides direct patient care including glaucoma services. Dr. Morgan’s expertise includes the design and evaluation of ophthalmic therapies, as well as the detection, causes, prevention, and treatment of glaucoma and associated conditions, including in human and animal studies.
[71] Allergan argued that Dr. Morgan’s publications and research interests do not pertain to matters directly relevant to the case, and that his clinical experience is much more limited than that of Dr. Noecker. Allergan also asserts that Dr. Morgan’s answers were often evasive, and that his expert report was tainted by his failure to mention highly relevant prior art, as well as his omission of key facts.
[72] Overall, I found Dr. Morgan’s evidence to be of limited utility. Dr. Morgan described himself as a “clinician scientist”, but his limited clinical experience with glaucoma was evident from his lack of familiarity with some relevant glaucoma medications. He has also not studied or published on subjects directly relevant to the issues in this case. As regards his understanding of his duties as an expert witness, while I found Dr. Morgan to be genuine in his desire to be of assistance to the Court, I was troubled by certain of his answers for reasons set out in more detail below.
[73] As discussed below, while I give Dr. Morgan’s evidence some weight, I found his evidence to be of limited usefulness on the key points in contention.
(2) Dr. Alany [74] Dr. Raid Ghassan Alany is a pharmaceutical formulator who received his PhD in ocular drug delivery from the University of Otago, New Zealand, in 2001. He joined the faculty of the University of Auckland’s newly created Pharmaceutics program in 2001. In 2011, Dr. Alany joined the Kingston University, London, in the United Kingdom, as Professor of Pharmaceutics.
[75] Since 2017, Dr. Alany has been Professor of Pharmaceutical Formulation and Drug Delivery. His research relates mainly to ophthalmic drug deliver. He is on the Editorial Board of numerous journals in the subjects of pharmaceutics and drug delivery and a Section Editor for the journal Clinical and Experimental Ophthalmology on the subject of ocular pharmacotherapy.
[76] Dr. Alany was qualified as an expert on the following terms:
Dr. Raid Ghassan Alany is a pharmaceutical formulator with expertise in ophthalmic drug delivery, including ophthalmic formulations and their ingredients, precorneal retention and clearance studies, ocular bioavailability and pharmacodynamic studies, ocular irritation and tolerability and tear film stability studies. Dr. Alany’s expertise also extends to the preparation, design, development, manufacture, and evaluation of ophthalmic drug delivery systems, including in human and animal studies.
[77] Allergan submits that Dr. Alany’s credibility was seriously undermined during cross-examination, in particular because his description of the Common General Knowledge (“CGK”) in this case materially differed from his expert evidence in the United Kingdom patent case involving LUMIGAN RC. They argue that his evidence was selective, including his one-sided presentation of the benefits of BAK as a preservative and penetration enhancer, while ignoring its cytotoxic effects and the ample literature suggesting that its use should be avoided or minimized.
[78] Overall, I found Dr. Alany’s credibility as an expert witness to be significantly diminished because he did not provide forthright, careful and objective evidence in areas relating to his expertise. Instead, his evidence was heavily weighted in favour of Juno’s position in the litigation. He did not mention that his evidence on the CGK of the Skilled Formulator as of March 2005 was so different in the United Kingdom case until this was pointed out to him in cross-examination. When challenged, he did not respond in a forthright manner but rather sought to dispute the point – despite the evidence that resoundingly confirmed it. His evidence about what formed CGK at the relevant time included many references that can only properly be considered as part of the state of the art. Parts of his testimony were also confusing, and he often spoke to matters that fall within the expertise of a skilled ophthalmologist.
[79] As discussed below, I give Dr. Alany’s evidence little weight in the analysis of the key issues.
V. The Skilled Person
[80] Since patents and their claims are directed at “persons of skill in the art” (“POSITA”), the Court must construe a patent from the perspective of the POSITA: Sanofi at para 67.The POSITA is a hypothetical person possessing the ordinary skill and knowledge of the particular art to which the invention relates and a mind willing to understand a specification that is addressed to them (Free World Trust v Électro Santé Inc, 2000 SCC 66 [Free World Trust] at para 44, cited in Tetra Tech EBA Inc v Georgetown Rail Equipment Company, 2019 FCA 203 at para 25).
[81] The skilled person is understood to be a technician skilled in the art but having no scintilla of inventiveness or imagination; a paragon of deduction and dexterity, wholly devoid of intuition; a triumph of the left hemisphere over the right (Sanofi at para 52). The POSITA may be conceived of as a team of people possessed of different skills (see Janssen Inc v Pharmascience Inc, 2022 FC 1218 at para 112, citing Teva Canada Limited v Janssen Inc, 2018 FC 754 at paragraph 66, aff'd 2019 FCA 273).
[82] There was no real dispute between the parties that the POSITA, in regard to the 691 Patent, consists of a team comprised of an ophthalmologist and a formulator.
[83] The Skilled Ophthalmologist would have completed an MD degree as well as a residency program in ophthalmology, and would have experience treating patients with glaucoma and ocular hypertension. Indeed, the evidence indicates that most ophthalmologists spend a great deal of their professional lives helping patients with these conditions.
[84] The Skilled Formulator would have a Master’s degree in science or engineering relating to the preparation of pharmaceutical formulations, as well as a few years of experience preparing formulations; in the alternative, the Skilled Formulator would have a PhD in one of those same fields and would have acquired experience in preparing pharmaceutical formulations in the course of their training. The Skilled Formulator would have experience in preparing formulations for ophthalmic administration (i.e. eye drops).
VI. Claim Construction
[85] The first step in a patent suit, before assessing validity or infringement – is to construe the claims: Whirlpool Corp v Camco Inc, 2000 SCC 67, [2000] 2 SCR 1067 [Whirlpool] at para 43. This step requires the interpretation of the patent “to ascertain the nature of the invention and methods of its performance” and “to understand what was meant by the words in the claims” (Tearl