2023 FC, 2023 FC 1686

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: A . Is the 691 Patent invalid due to obviousness? B . 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 toophthalmic drug deliver.

He is on the Editorial Board of numerous journals in the subjects of pharmaceutics and drug delivery and aSection 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 ophthalmicformulations and their ingredients, precorneal retention and clearance studies, ocular bioavailability and pharmacodynamicstudies, 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 animalstudies". [77] Allergan submits that Dr. Alany’s credibility was seriously undermined during cross-examination, in particular because hisdescription of the Common General Knowledge "(“CGK”") in this case materially differed from his expert evidence in the UnitedKingdom patent case involving LUMIGAN RC.

They argue that his evidence was selective, including his one-sided presentation of thebenefits of BAK as a preservative and penetration enhancer, while ignoring its cytotoxic effects and the ample literature suggesting thatits 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 positionin the litigation.

He did not mention that his evidence on the CGK of the Skilled Formulator as of March 2005 was so different in theUnited Kingdom case until this was pointed out to him in cross-examination. When challenged, he did not respond in a forthright mannerbut rather sought to dispute the point – despite the evidence that resoundingly confirmed it. His evidence about what formed CGK at therelevant time included many references that can only properly be considered as part of the state of the art.

Parts of his testimony werealso 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 theperspective of the POSITA: Sanofi at para 67.The POSITA is a hypothetical person possessing the ordinary skill and knowledge of theparticular art to which the invention relates and a mind willing to understand a specification that is addressed to them (Free World Trust vÉlectro 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; aparagon of deduction and dexterity, wholly devoid of intuition; a triumph of the left hemisphere over the right (Sanofi at para 52).

ThePOSITA may be conceived of as a team of people possessed of different skills (see Janssen Inc v Pharmascience Inc, 2022 FC 1218 atpara 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 anophthalmologist and a formulator. [83] The Skilled Ophthalmologist would have completed an MD degree as well as a residency program in ophthalmology, and wouldhave experience treating patients with glaucoma and ocular hypertension.

Indeed, the evidence indicates that most ophthalmologistsspend 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 pharmaceuticalformulations, as well as a few years of experience preparing formulations; in the alternative, the Skilled Formulator would have a PhD inone 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 ofthe invention and methods of its performance”" and "“to understand what was meant by the words in the claims”" (Tearlab Corporationv I-MED Pharma Inc, 2019 FCA 179 [Tearlab Corporation] at para 33, citing Consolboard Inc v MacMillan Bloedel (Sask) Ltd, (SCC), [1981] 1 SCR. 504 [Consolboard] at 520). As previously stated, claim construction is done from the perspective of thePOSITA. [86] There was no dispute between the parties on the question of claims construction.

Despite their agreement, claims constructionremains a question of law for me to determine (Whirlpool at para 76); Tearlab Corporation at para 28). In this case, the exercise is quitestraightforward.

A. Legal Principles [ 87 ] The general principles of claim construction are now well established, based on the three leading Supreme Court of Canada decisions: Whirlpool at paras 49-55 ; Free World Trust at paras 31-67 ; Consolboard at 520. [ 88 ] The Federal Court of Appeal summarized these principles in Tearlab Corporation : [32] " To identify these elements, the claim language must be read through the eyes of a [person of skill in the art (POSITA)], in light of the latter’s common general knowledge " ( Free World Trust at paras. 44-45 ; see also Frac Shack at para. 60; Whirlpool at para. 53 ).

As noted in Free World Trust : [51] … " The words chosen by the inventor will be read in the sense the inventor is presumed to have intended, and in a way that is sympathetic to accomplishment of the inventor’s purpose expressed or implicit in the text of the claims. However, if the inventor has misspoken or otherwise created an unnecessary or troublesome limitation in the claims, it is a self-inflicted wound. The public is entitled to rely on the words used provided the words used are interpreted fairly and knowledgeably.

" [Emphasis in the original.] [33] " Claim construction requires that the disclosure and the claims be looked at as a whole “to ascertain the nature of the invention and methods of its performance, … being neither benevolent nor harsh, but rather seeking a construction which is reasonable and fair to both patentee and public” " ( Consolboard at p. 520; see also Teva Canada Ltd. v. Pfizer Canada Inc. , 2012 SCC 60 , [2012] 3 S.C.R. 625 at para. 50 ). " Consideration can thus be given to the patent specifications to understand what was meant by the words in the claims.

One must be wary, however, not to use these so as “to enlarge or contract the scope of the claim as written and … understood” " ( Whirlpool at para. 52 ; see also Free World Trust at para. 32 ). " The Supreme Court recently emphasized that the focus of the validity analysis will be on the claims; specifications will be relevant where there is ambiguity in the claims " ( AstraZeneca Canada Inc. v.

Apotex Inc. , 2017 SCC 36 , [2017] 1 S.C.R. 943 at para. 31 ; see also Ciba at paras. 74-75 ). [34] " Finally, it is important to stress that claim construction must be the same for the purpose of validity and for the purpose of infringement " ( Whirlpool at para. 49 (b)). B. Asserted Claims [ 89 ] Although Allergan asserted in its Further Amended Statement of Claim that Juno would infringe at least one of Claims 1, 5, 16, 19 and 20 of the 691 Patent, prior to trial Allergan informed the Defendant and the Court that it was only asserting infringement of two Claims: (

a) Claim 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. (

b) Claim 19: Use of a composition according to any one of claims 1 to 16 for treating glaucoma or intraocular hypertension in a mammal. C. Parties’ Positions on Claims Construction [ 90 ] The parties both took the position that the claims mean what they say, and there is no particular question about the meaning of the key terms, as they would be understood by the POSITA. [ 91 ] In regard to Claim 16, it is a formulation containing a well-known active ingredient, bimatoprost, as well as BAK, which is the most commonly-used preservative used in eye drops.

The other excipients listed in Claim 16 are equally common, as is the adjustment of the pH of the composition to 7.3 (commonly done to correspond to the pH level of eye fluid). [ 92 ] On Claim 19, the parties submitted that the use of the eye drop formulated in accordance with Claim 16 is quite straightforward and did not require any specialized knowledge. D.

Analysis [ 93 ] The claims are quite straightforward, and a POSITA would understand them to mean what they say. [ 94 ] Claim 16 is a composition claim, and all of the elements that are referred to are well-known and commonly used substances found in other eye drops.

For the purposes of this case, the two key ingredients are 0.01% bimatoprost and 0.02% BAK by weight; a POSITA would interpret this as referring to 100 ppm bimatoprost and 200 ppm BAK. [ 95 ] Similarly, a POSITA would understand that the adjustment of the aqueous liquid formulated with the ingredients listed in Claim 16 would have a pH adjusted to 7.3 so that it corresponded to the pH found in the human eye.

Otherwise, the eye drop would irritate the eye. [ 96 ] Claim 19 is a use claim, and a POSITA would interpret it as meaning what it says: using the eye drop formulated in accordance with claims 1 to 16 for treating glaucoma or intraocular hypertension in a mammal. I will discuss below the pertinence of the reference in Claim 19 to the other claims listed in the 691 Patent, in particular Claim 1, but there is no question that the administration of an eye drop formulated in accordance with Claim 16 for treatment of these conditions would be a matter of routine for the Skilled Ophthalmologist.

[ 97 ] Nothing more needs to be said about claims construction in this case. The claims should be read in accordance with the plain meaning of their terms. As discussed below, the core of the dispute between the parties relates to the obviousness inquiry, in particular the nature of the inventive concept and whether the new formulation contained in Claim 16 was " “obvious to try.” " VII. Obviousness A. Legal Principles [ 98 ] The starting point on the law of obviousness is

section 28.3 of the Patent Act , RSC 1985, c P-4 [ Patent Act ]: " Invention must not be obvious " " 28.3 The subject-matter defined by a claim in an application for a patent in Canada must be subject-matter that would not have been obvious on the claim date to a person skilled in the art or science to which it pertains, having regard to " " Objet non évident " " 28.3 L’objet que définit la revendication d’une demande de brevet ne doit pas, à la date de la revendication, être évident pour une personne versée dans l’art ou la science dont relève l’objet, eu égard à toute communication : " " (

a) information disclosed before the one- year period immediately preceding the filing date or, if the claim date is before that period, before the claim date by the applicant, or by a person who obtained knowledge, directly or indirectly, from the applicant in such a manner that the information became available to the public in Canada or elsewhere; and " "

a) qui a été faite, soit plus d’un an avant la date de dépôt de la demande, soit, si la date de la revendication est antérieure au début de cet an, avant la date de la revendication, par le demandeur ou un tiers ayant obtenu de lui l’information à cet égard de façon directe ou autrement, de manière telle qu’elle est devenue accessible au public au Canada ou ailleurs; " " (

b) information disclosed before the claim date by a person not mentioned in paragraph (

a) in such a manner that the information became available to the public in Canada or elsewhere. " "

b) qui a été faite par toute autre personne avant la date de la revendication de manière telle qu’elle est devenue accessible au public au Canada ou ailleurs. " [ 99 ] Justice Rothstein of the Supreme Court sets out the following four-part test in Sanofi at paragraph 67 : In the result I would restate the Windsurfing questions thus: (1)(

a) Identify the notional “person skilled in the art”; (

b) Identify the relevant common general knowledge of that person;

(2) Identify the inventive concept of the claim in question or if that cannot readily be done, construe it;

(3) 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;

(4) 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? [Emphasis added.] It will be at the fourth step of the Windsurfing/Pozzoli approach to obviousness that the issue of “obvious to try” will arise. [ 100 ] In applying this test, the Court must be cautious not to employ hindsight bias in its obviousness analysis: Canada LP/Valeant Canada SEC v Generic Partners Canada Inc , 2019 FC 253 [ Valeant Canada ] at para 104 ; Meda AB v Canada (Minister of Health) , 2016 FC 1362 at para 138 ; Bridgeview Manufacturing Inc v 931409 Alberta Ltd (Central Alberta Hay Centre) , 2010 FCA 188 at para 50 .

On this point, I refer to the words of Justice James Hugessen in Beloit Canada Ltd c Valmet Oy, (1986) 8 CPR (3d) 289 at 295 (FCA) : Every invention is obvious after it has been made, and to no one more so than an expert in the field. Where the expert has been hired for the purpose of testifying, his infallible hindsight is even more suspect. It is so easy, once the teaching of a patent is known, to say, "I could have done that"; before the assertion can be given any weight, one must have a satisfactory answer to the question, "Why didn't you?" B.

Step 1 – The Skilled Person and their Common General Knowledge [ 101 ] As discussed above, there is no real debate about the notional POSITA. There was also broad agreement between the parties’ experts on many aspects of the relevant CGK, but they disagreed on certain core elements. In addition, Juno’s experts displayed some degree of confusion about what constitutes CGK as opposed to the " “state of the art” " . I found that Juno’s experts included many things in CGK that are more properly considered as part of the state of the relevant art. (1) The POSITA

[ 102 ] As outlined in

Part V above, " “The Skilled Person” " , 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. Both have some knowledge and experience relating to glaucoma and ocular hypertension. The Skilled Ophthalmologist has experience treating these conditions, and the Skilled Formulator has experience in the formulation of eye drops.

(2) The Common General Knowledge of the POSITA (

a) Legal Principles [ 103 ] The CGK consists of what the POSITA would generally know and accept at the relevant time: Sanofi at para 37 ; Mylan Pharmaceuticals ULC v Eli Lilly Canada Inc , 2016 FCA 119 at para 24 [ Mylan ]; Bell Helicopter Textron Canada Limitée v Eurocopter, 2013 FCA 219 [ Eurocopter ] at para 64-65 . CGK includes what the POSITA may reasonably be expected to know and to be able to find out; they are expected to be reasonably diligent in keeping up with advances in the field to which the patent relates: Whirlpool at para 74 . It is not a memory test.

The POSITA may be permitted to refer to standard texts and resources to " “look things up” " : Novopharm Limited v Janssen-Ortho Inc and Daiichi Pharmaceuticals Co, Ltd, 2007 FCA 27 at para 25 (2). [ 104 ] CGK does not include all the information in the public domain: Eurocopter at para 64 . The Federal Court of Appeal recently confirmed this point in Gemak Trust v Jempak Corporation , 2022 FCA 141 at 95-96: A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated.

Such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art”: Eli Lilly and Company v Apotex Inc, 2009 FC 991 at para 97 , quoting from General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd , [1972] RPC 457 at 482-483, itself quoting from British Acoustic Films (53 RPC 221 at 250). [ 105 ] CGK must be distinguished from the " “state of the art” " which is a broader category encompassing all previously disclosed information in the field.

The state of the art is the collection of learning in the field of the patent at issue and comprises all available teaching, however obscure or not generally accepted: Mylan at para 23 . The state of the art is used to assess whether an invention was anticipated, or is obvious.

CGK informs the way the claims and specifications are read by the POSITA: Mylan at para 25 . [ 106 ] Information only migrates from state of the art to CGK when a skilled person would become aware of it and accept it as " “a good basis for further action” " : Mylan at para 24 , quoting General Tire & Rubber Co v Firestone Tyre & Rubber Co, [1972] RPC 457 (CA) at 483. (

b) Common General Knowledge of the POSITA [ 107 ] The POSITA in this case is a team comprised of a skilled ophthalmologist and formulator, and some parts of the CGK are common to both. It will be convenient, however, to discuss the CGK of the Skilled Ophthalmologist and then set out the CGK for the Skilled Formulator. The relevant date for assessing CGK is March 16, 2005 (the claim date). (

i) The CGK of the Skilled Ophthalmologist [ 108 ] As of the relevant date, the CGK of the Skilled Ophthalmologist would include the following information, some of which is discussed above: The anatomy of the eye, including the protective corneal epithelial layer and its lipophilic quality, as well as the hydrophilic quality of the stroma; The causes of glaucoma and ocular hypertension, namely elevated IOP caused by an imbalance between the inflow and outflow of aqueous humour, which is associated with the degeneration of the trabecular mesh network; The risks associated with glaucoma and ocular hypertension, namely permanent vision loss due to damage to the ocular nerve caused by elevated IOP; The fact that to avoid vision loss, patients need to begin treatment to slow or halt the progression of these conditions before they become aware of any symptoms; and The importance of patient compliance, and the reasons some patients discontinue treatment or do not always follow their treatment regime (including disagreeable side-effects, the burden of taking several daily doses often involving a combination of drugs, and for some the physical difficulty of administering drops into their own eyes). [ 109 ] The Skilled Ophthalmologist would also have known that the two basic treatment approaches for these conditions involved surgery or drug treatment, with the latter being the preferred option. [ 110 ] In addition, the Skilled Ophthalmologist would have been aware of the categories of medication and the specific drugs that were commercially available at that time, as well as their main known benefits and side effects.

These included: Beta-blockers such as timolol (marketed as TIMOPTIC®) and betaxolol (marketed as BETOPTIC®). These were effective at lowering IOP by reducing the inflow of aqueous humour, and they transformed glaucoma care when they were first introduced. They were a common, first line treatment option. However, experience showed that their effectiveness declined after several years, after which combination therapies using multiple medications had to be administered.

In addition, they had systemic side effects that made them not suitable for persons with a variety of conditions, including certain cardiac diseases, asthma or severe chronic

pulmonary obstruction. They can also cause sleep disorders, depression, headache, nausea and dizziness, as well as ocular irritation and conjunctivitis. Some patients discontinued use because of these side effects; Prostaglandin Analogs (“PGA”) such as latanoprost (marketed as XALATAN®) and travoprost (marketed as TRAVATAN®). These classes of drugs lowered IOP by increasing the outflow of aqueous humour.

They became the preferred class of drugs for patients for whom beta-blockers were not suitable, and by March 2005 they were often the first line treatment because of their effectiveness in lowering IOP with relatively few side effects. A common side-effect was conjunctival hyperemia; Prostamides such as bimatoprost (which remains the only prostamide used in commercially available eye drops). Prostamides and PGAs are similar; they were described as " “sibling drugs” " .

Prostamides also reduce IOP by increasing the outflow of aqueous humour, and bimatoprost had the greatest average IOP reduction of all commercially available products. However, bimatoprost was also associated with the highest incidence of conjunctival hyperemia, and this became known to clinicians almost immediately after it entered the market. Bimatoprost had higher rates of hyperemia than PGAs.

Clinicians found that 20-25% of their patients would discontinue use of bimatoprost because of the unwanted side effects. [ 111 ] Reducing IOP was the only known treatment to prevent the progression of damage caused by glaucoma and IOH. It was known as of March 2005 that there are natural fluctuations in IOP, depending on an individual’s age, heartrate and the time of day. Studies had shown that it was important to seek to maintain IOP within target ranges throughout the day and to avoid wide fluctuations.

For most patients with elevated IOP, the target was to reduce it to the " “normal” " range of around 21 mmHg (millimeters of mercury). However, studies had shown that for patients with advanced damage, it was necessary to seek to reduce IOP even lower, towards the 10-12 mmHg level. [ 112 ] Finally, the Skilled Ophthalmologist would have known that as of 2005, eye drops were generally prescribed in multi-use bottles and therefore required a preservative to ensure that they remained safe for patients to use. BAK was (and remains) the most common preservative used in commercially available eye drops.

BAK is a very effective preservative, but the Skilled Ophthalmologist would have known that it disrupted the surface of the eye. [ 113 ] Despite the damage BAK caused to the eye, the Skilled Ophthalmologist knew that it was the most commonly used preservative, and was present in varying amounts in the different multi-use eye drops that were commercially available at that time.

The Skilled Ophthalmologist wanted as many different treatment options as possible to deal with glaucoma, and had to accept the risk-benefit trade- offs associated with the different medications, including the presence of BAK. [ 114 ] The Skilled Ophthalmologist knew that many patients required more than one drug to achieve an optimal IOP reduction towards the target level: approximately 30-40 % of patients are on more than one medication.

This increased the difficulty of patient compliance and added to the cumulative risks associated with the presence of BAK in each medication that patients were required to take daily. (ii) The CGK of the Skilled Formulator [ 115 ] The CGK of the Skilled Formulator in March 2005 included the anatomy of the eye, the need to reduce IOP in the treatment of glaucoma and IOH, and the importance of patient compliance with the prescribed treatment regime as discussed above. [ 116 ] Relating to the anatomy of the eye and the difficulty of formulating effective eye drops, the Skilled Formulator was aware of the ways in which the eye flushes foreign substances and the very limited amount of a drug that would actually penetrate the eye.

At the relevant time, the CGK of the Skilled Formulator included various techniques to deal with this challenge, including ways of keeping the drug on the surface of the eye for a longer period (e.g. ointments or gels) as well as techniques to increase the rate of penetration so that more of the active ingredient reached the target location inside the eye (e.g. by using penetration enhancers). [ 117 ] Associated with this, the Skilled Formulator’s CGK included the routes of administration of ocular pharmaceutical formulations (eye drops), with the corneal pathway being the primary route.

The Skilled Formulator was also aware of the two routes of absorption into the eye: transcellular (through the cell structure) and paracellular (using the gaps between cells). Related to this, the Skilled Formulator would have been aware of the barriers to penetration into the eye, including the lipophilic nature of the outer epithelial layer, which made it more difficult for water-based compounds to penetrate. A further barrier is the hydrophilic nature of the stroma, which is a layer deeper inside the eye.

This meant that oily, lipid compounds could more easily penetrate the outer layer, but would then have greater difficulty getting through the stroma. Water-based compounds faced the same barriers in reverse – being repelled by the outer layer, but easily penetrating the stroma. [ 118 ] In addition, the Skilled Formulator would have been aware of the basic functions of different excipients in pharmaceutical formulations.

For example, in addition to bimatoprost and BAK, Claim 16 of the 691 Patent lists a number of excipients and both expert formulators identified them as commonly-used and well-understood ingredients that served different functions in pharmaceutical formulations.

A large part of the training of formulators involves studying these excipients so that they can choose the right combination to achieve the desired effects while avoiding or minimizing undesirable side effects. [ 119 ] Claim 16 also refers to the composition being " “an aqueous liquid with a pH adjusted to 7.3.” " The Skilled Formulator would have known that it was important to adjust the pH level of eye drops to match the level of the eye because a more acidic formulation would cause a stinging sensation. C.

Step 2 – Inventive Concept [ 120 ] The second step of the Sanofi test is to " “[i]dentify the inventive concept of the claim in question or if that cannot readily be done, construe it” " (at para 67). This is a precursor to the third step, which involves identifying any differences between the state of the art and the inventive concept of the claim. [ 121 ] This is a key dispute between the parties in this case. Allergan argues that the inventive concept of Claim 16 must be understood

with reference to the specification in the 691 Patent, which makes clear that the inventive concept of the new formulation was to achieve IOP reduction that was comparable to that delivered by old LUMIGAN. Flowing from this, the inventive concept for Claim 19 was the use of the formulation set out in Claim 16 for the treatment of glaucoma or ocular hypertension. [ 122 ] Juno disputes this, arguing that the inventive concept of Claim 16 is simply the formulation set out there; since the words are clear, Juno submits that there is no need to refer to the specification.

Their argument also flows through to Claim 19, which they say simply involves using the formulation in Claim 16 to treat the listed conditions. [ 123 ] In the analysis below, I will set out the opinions of the various experts as well as the submissions of the parties, followed by a discussion of the legal principles that govern this analysis and my conclusions on the question. One additional feature of this case is that the inventive concept of the 691 Patent has been determined in previous litigation conducted under the prior PM(NOC) regime. The relevance of those prior decisions is discussed below.

(1) The Experts’ Opinions [ 124 ] Allergan’s experts advanced the view that Claim 16 is a formulation alone and that the language of the claim explained nothing about the utility of the formulation, why it is being claimed, what problem it purports to solve or what is inventive about it. Because of this, they assert that it is necessary to review the whole of the 691 Patent, not just the claims. [ 125 ] Dr. Noecker set out his understanding of the inventive concept in Claim 16 in his expert report: 115.

" Read in the context of the patent as a whole, a Skilled Ophthalmologist would understand that the inventive concept of Claim 16 to be an ophthalmic formulation that achieves comparable IOP lowering efficacy to LUMIGAN® (0.03% bimatoprost) but contains less bimatoprost (i.e. 0.01%), achieved by increasing the concentration of BAK in the formulation (i.e. from 50 ppm to 200 ppm). " [ 126 ] In Dr.

Noecker’s opinion, the POSITA would arrive at this understanding based on the following elements of the 691 Patent: The Patent’s title is " “Enhanced Bimatoprost Ophthalmic Solution” " – and since the POSITA would have been familiar with the existing commercial formulation for old LUMIGAN, as well as its shortcomings (in particular that it caused hyperemia), the POSITA would have understood that the new formulation was an " “enhancement” " over the existing product; The Examples in the Patent used old LUMIGAN as the " “control” " against which other formulations were compared; Example 2 demonstrated ex vivo that the aqueous humour concentration of bimatoprost increased by 57% with the addition of 200 ppm BAK, as compared to old LUMIGAN with 50ppm BAK; The results set out in Example 4 demonstrated that an ophthalmic solution containing 0.015% bimatoprost and 200 ppm BAK achieved significantly greater penetration of bimatoprost across the epithelial layer than did old LUMIGAN, while a solution with a concentration of 0.01% bimatoprost and 200 ppm BAK would achieve IOP lowering efficacy comparable to old LUMIGAN.

The results from this example would lead the Skilled Ophthalmologist to understand that a solution with less bimatoprost and more BAK than old LUMIGAN would achieve at least comparable efficacy; Example 5 stated that a formulation containing 0.015% bimatoprost and 125 ppm BAK achieved greater IOP reduction and less hyperemia than old LUMIGAN. From these results, the POSITA would expect that a formulation containing 0.01% bimatoprost and 200ppm BAK would provide comparable IOP lowering efficacy and less hyperemia than old LUMIGAN. [ 127 ] Dr.

Noecker’s opinion is that the inventive concept for Claim 19 is the use of the formulation in Claim 16 to treat glaucoma and IOH. [ 128 ] On both of these points, Dr. Berkland’s expert report sets out similar conclusions. He asserted that the Skilled Formulator would recognize that the Claims in the 691 Patent have a lower concentration of bimatoprost and a higher concentration of BAK than old LUMIGAN, but they would not know from reading the claims why these changes had been made.

Therefore, the Skilled Formulator would need to read the 691 Patent as a whole to understand why the new formulations were claimed and, more generally, to understand what is inventive about the claimed formulations. He also indicated that the inventive concept of Claim 19 is simply the use of the formulation set out in Claim 16 to treat glaucoma and IOH. [ 129 ] In contrast, Juno’s experts expressed the opinion that the inventive concept for the asserted claims is clear based on the wording of the claims themselves.

They say the inventive concept of these claims generally correspond to the claim construction they advanced, which involved a straightforward reading of the terms of the two claims. [ 130 ] Dr. Morgan stated that the overall inventive concept of the claims relates to the composition containing bimatoprost, BAK and other excipients as specified, where the compositions are in the form of aqueous liquid formulated for ophthalmic administration. Claim 16 also includes the pH of the composition as a component of the inventive concept.

In his opinion, the inventive concept of Claim 16 is not limited to any particular use or level of performance, except that it is formulated for ophthalmic administration. Claim 19 is for the use of the formulation to treat glaucoma and IOH in a mammal. [ 131 ] In support of his opinion about Claim 16, Dr. Morgan indicates that the wording of the claim is not ambiguous and the inventive concept is clear from its wording.

He also points out that if the POSITA reviewed the disclosure of the 691 Patent to understand whether comparable effectiveness to old LUMIGAN was part of the inventive concept, they would not find any statements by the inventors to support a claim that the composition in Claim 16 achieves a comparable effect. There are no studies of clinical effectiveness, and no statement that the new formulation achieves a comparable effect. The patent does not disclose a problem associated with old LUMIGAN. [ 132 ] Dr.

Morgan acknowledged that Example 5 indicates that administration of a formulation (labelled formulation " “J” " ) comprised of

0.015% bimatoprost, 125ppm BAK and 0.015% EDTA (ethylenediaminetetaacetic acid) resulted in greater IOP reduction and less hyperemia than old LUMIGAN. However, he pointed out that the inventors provided no information about how much of formulation J was to be applied, nor any test data to support this statement.

He also notes that the other Examples provide evidence of the concentration of bimatoprost achieved by other formulations as compared with old LUMIGAN, but none of these provide any indication that the new formulations had a " “comparable effect.” " Because of the absence of statements about comparable effect or any data to support such a claim, Dr. Morgan states that even if the POSITA reviewed the entire 691 Patent, they would not understand a comparable effect to be part of the inventive concept. [ 133 ] Dr. Alany’s opinion matches that of Dr. Morgan.

He adds that while the POSITA would recognize that the formulation in the claims contains less bimatoprost than old LUMIGAN, and that the composition in Claim 16 is formulated for ophthalmic administration, they would also not find any statement that the formulation was just as effective (or more effective) as the commercially available old LUMIGAN product. He notes there are no statements in the claims regarding a reduction in hyperemia. Furthermore, the description in the 691 Patent does not contain any data or discussion regarding any technical advantages of the excipients in the formulations.

Based on this, Dr. Alany’s opinion is that the inventive concepts of claims 16 and 19 are clear from the wording of the claims themselves. He states that even if the POSITA reviewed the description of the 691 Patent for help in understanding whether a comparable effect is part of the inventive concept, they would not see any assertion that the formulations of the claims achieve a comparable effect, including clinical efficacy, to that delivered by old LUMIGAN.

(2) The Submissions of the Parties [ 134 ] Allergan advances three main arguments on inventive concept. [ 135 ] First, Allegan argues that there is no reason to depart from the inventive concept of the 691 Patent set out in prior decisions of this Court and the Federal Court of Appeal.

In both Apotex FC and Cobalt FC , Justice O’Reilly of this Court found at paragraph 26 that " “… reading the ‘691 patent as a whole, the inventive concept of Claims 16 and 19 is a formulation with a reduced [bimatoprost] but with comparable efficacy to old LUMIGAN, achieved by increasing BAK.” " This was specifically affirmed by the Federal Court of Appeal ( Apotex FCA ) at paragraph 7(i). [ 136 ] Allergan argues that a finding on inventive concept is a question of law that is prima facie binding: Bayer Inc v Apotex Inc , 2016 FC 1013 [ Bayer ] at para 53 ; Apotex Inc v Pfizer Canada Inc , 2013 FC 493 at paras 11-12 . [ 137 ] Second, Allergan points out that the experts, including Dr.

Alany, accepted that the patent was about an " “enhanced” " bimatoprost ophthalmic solution, and reading the patent as a whole makes it clear that the inventors were describing formulations that were just as or more effective than the commercially available old LUMIGAN. Allergan also notes that Dr.

Morgan admitted that the data in Example 2 showed there is enhanced penetration of bimatoprost into the aqueous humour, and that increasing the amount of BAK would increase the permeability of bimatoprost and thereby increase the efficacy of the lower dose. [ 138 ] Allergan points to the consistent evidence of its experts that Claim 16 is merely a formulation (or recipe) and in order to understand its inventive concept it is necessary to examine the entirely of the 691 Patent.

Allergan submits that this approach is consistent with the binding case-law, citing the recent decision of the Federal Court of Appeal in Apotex Inc v Shire LLC , 2021 FCA 52 [ Shire ]. Allergan argues that in Shire , the Court of Appeal rejected the argument that patent claims ought to be considered without regard to any features or advantages not specifically included in the claims, and noted that while identifying the inventive concept is informed by claim construction, it remains a distinct exercise. Based on this, Allergan asserts that its

interpretation of the inventive concept of the claims – as a formulation with lower bimatoprost but comparable efficacy to old LUMIGAN, achieved by increasing BAK – should be adopted. [ 139 ] In response, Juno asserts that the prior decisions are not binding nor persuasive, given that they were based on the former PM(NOC) regime.

Juno submits that previous decisions under that regime had found that decisions made on applications to prohibit the issuance of an NOC were not binding in subsequent proceedings relating the validity of the same patent: Bayer ; Janssen Inc v Apotex Inc , 2021 FC 7 [ Janssen FC 2021] at paras 12 and 217 ; aff’d Janssen Inc v Apotex Inc, 2022 FCA 184 [ Janssen FCA ] at para 3 . [ 140 ] Juno submits that the identification of the inventive concept begins with the claims of the patent and only looks to the disclosure when necessary: Eli Lilly Canada Inc v Mylan Pharmaceuticals ULC , 2020 FC 816 at paras 291 , 293, 297-298 and 301; AstraZeneca Canada Inc v Apotex Inc , 2014 FC 638 at paras 267-269 .

Any particular result from the alleged inventive concept that is said to be a basis for distinguishing over the prior art must constitute an essential element of the claim: Hospira Healthcare Corporation v Kennedy Trust for Rheumatology Research , 2020 FCA 30 at para 71 . [ 141 ] In this case, according to Juno, there is no reason to look at the disclosure in the patent because the inventive concept is clear from the terms of the claims themselves.

The claims use well-known terms that can be understood without reference to the disclosure. [ 142 ] Juno rejects the attempt by Allergan to import a requirement of comparable efficacy into the claims because it unnecessarily imports ambiguous aspects of the disclosure. It points out that Dr. Berkland’s evidence was that a composition would be comparable if it fell within the error range of the control formulation in Example 4 of the 691 Patent, and that it would not mean " “exactly the same” " efficacy as old LUMIGAN but " “should be about the same.” " Juno also notes that Dr.

Berkland did not explain how he had followed his instructions to find a single inventive concept that flowed through the patent, but rather limited his evidence to only Claims 16 and 19. [ 143 ] As for Dr. Noecker, Juno argues that despite testifying that the invention was clear, he could not explain how a formulation containing 0.005% bimatoprost and 100 ppm BAK (in accordance with the range set out in Claim 1) could provide comparable efficacy to old LUMIGAN. In addition, Dr.

Noecker could not identify a single inventive concept that flows through the entire patent. [ 144 ] Instead, Juno argues that the inventive concept set out by Dr. Morgan and Dr. Alany should be preferred, noting their evidence that the wording of the claims was clear and there were no claims or evidence to support including comparable efficacy as part of the inventive concept.

(3) Analysis [ 145 ] Dealing first with Allergan’s argument regarding the prior decisions, I am not persuaded that I am bound by the prior determinations of the inventive concepts of Claims 16 and 19. In both Apotex FC and Cobalt FC, Justice O’Reilly stated at paragraph 26: " “In my view, reading the ‘691 patent as a whole, the inventive concept of Claims 16 and 19 is a formulation with reduced [bimatoprost] but with comparable efficacy to old LUMIGAN, achieved by increasing BAK.” " This was specifically confirmed by the Federal Court of Appeal in Apotex FCA at paragraph 7 (i).

In the ordinary course of things, a ruling by the Federal Court of Appeal dealing with the same claims in the same patent would be binding on me. [ 146 ] However, as counsel for Juno correctly points out, the prior determinations were made under the former PM(NOC) regime, which involved a different procedural framework and evidentiary process. Under the former regime, patent owners could bring an application to seek to prevent the Minister of Health from issuing an NOC, and these proceeded by way of affidavit evidence.

In some cases, subsequent actions for patent infringement were launched, involving the same parties and patent.

That two-step system has been replaced by the current PM(NOC) Regulations , which provide for a single action, with all of the usual discovery rights and where viva voce evidence can be heard. [ 147 ] Even under the old PM(NOC) regime, it was recognized that while claims construction and the determination of the inventive concept are questions of law, rulings on these questions made in the context of an application would only be prima facie binding on the judge hearing a subsequent patent infringement action.

As Justice Simon Fothergill explained in Bayer at paragraph 53 : " To the extent that this Court may have discretion to follow or depart from the previous construction adopted in the NOC proceedings, I consider the Federal Court of Appeal’s prior construction to be prima facie binding, but acknowledge that it may be revisited if warranted by the evidence. In other words, I will adhere to the construction given to the ‘426 patent by Justice Hughes and by the Federal Court of Appeal unless a party provides good reason not to.

The same holds true when defining the “inventive concept” of the patent and determining the “promise” of the patent, both of which are aspects of claim construction and are therefore questions of law… " [citations omitted] [ 148 ] That approach applies with even greater force, it seems to me, now that the underlying legal framework has been changed. For example, Justice Michael Phelan issued one of the last decisions under the old PM(NOC) regime, followed by one of the first decisions under the new one, dealing with the same parties and same patent and claims:

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