Teva Canada Limited v. Janssen Inc.

Teva Canada Limited v. Janssen Inc.
Court (s) Database
Federal Court Decisions
Date
2018-07-18
Neutral citation
2018 FC 754
File numbers
T-944-15
Notes
A correction was made on September 26, 2018.
Decision Content
Date: 20180718
Docket: T-944-15
Citation: 2018 FC 754
Ottawa, Ontario, July 18, 2018
PRESENT: The Honourable Mr. Justice Locke
BETWEEN:
TEVA CANADA LIMITED
Plaintiff
and
JANSSEN INC. and MILLENNIUM PHARMACEUTICALS, INC.
Defendants
AND BETWEEN:
MILLENNIUM PHARMACEUTICALS INC., JANSSEN INC., CILAG GMBH INTERNATIONAL, CILAG AG and JANSSEN PHARMACEUTICA NV
Plaintiffs by Counterclaim
and
THE UNITED STATES OF AMERICA REPRESENTED BY THE DEPARTMENT OF HEALTH AND HUMAN SERVICES
Patentee added pursuant to s. 55(3) of the Patent Act
and
TEVA CANADA LIMITED
Defendant by Counterclaim
PUBLIC JUDGMENT AND REASONS
(Confidential Judgment and Reasons issued July 18, 2018)
I. Overview 3
II. Background to the Patented Technologies 5
III. Overview of the Patents in Suit 12
A. The 936 Patent 12
B. The 146 Patent 16
C. The 706 Patent 19
IV. Legal Principles 21
A. Claim Construction 21
B. Obviousness 27
(1) Selection Patents 31
(2) Commercial Success/Meritorious Awards 32
C. Infringement 33
V. Witnesses 34
A. Millennium’s Fact Witnesses 35
(1) Dixie-Lee Esseltine 35
(2) James Brodie 35
(3) Julian Adams 36
(4) Louis Plamondon 37
(5) Ross Stein 38
(6) Valentino Stella 39
(7) John Bishop 39
B. Millennium’s Expert Witnesses 40
(1) Alexander Vinitsky 40
(2) Roger Snow 42
(3) Bradley Anderson 43
(4) Anthony Barrett 45
C. Teva’s Expert Witnesses 46
(1) Raj Suryanarayanan 46
(2) Sherwin Wilk 47
(3) William Bachovchin 47
(4) George Kabalka 49
VI. Analysis 49
A. 936 Patent: Obviousness 50
(1) Person Skilled in the Art 52
(2) Common General Knowledge 52
(a) The 904 Application 53
(3) Inventive Concept 58
(4) Differences between the State of the Art and the Inventive Concept 59
(5) Obviousness 59
(a) Boronic Acid Warhead 59
(b) Dipeptide 61
(c) Leu Side Chain at P1 62
(d) Phe at P2 63
(e) Pyrazine Carbonyl as the N-Terminal Blocking Group 64
(f) Conclusion on Obviousness 65
B. 146 Patent: Obviousness 69
(1) Person Skilled in the Art 71
(2) Common General Knowledge 74
(3) Inventive Concept 77
(4) Differences between the State of the Art and the Inventive Concept 78
(5) Obviousness/Obviousness to Try 79
(a) Is it more or less self-evident that what is being tried ought to work? Are there a finite number of identified predictable solutions known to persons skilled in the art? 80
(b) What is the extent, nature and amount of effort required to achieve the invention? Are routine trials carried out or is the experimentation prolonged and arduous, such that the trials would not be considered routine? 81
(c) Is there a motive provided in the prior art to find the solution the patent addresses? 85
(d) Conclusion on Obviousness 86
C. 706 Patent: Claim Construction 88
(1) Person Skilled in the Art 89
(2) Large-scale 90
(3) Step (aa) 92
(4) Step (bb) 94
(5) Step (cc) 95
(6) Step (dd) 96
(7) Claim 2 96
(8) Claim 3 97
(9) Claim 4 97
(10) Claim 5 98
D. 706 Patent: Infringement by Teva-bortezomib 98
E. 706 Patent: Infringement by Act-bortezomib 99
F. 706 Patent: Obviousness 100
VII. Conclusion 100
JUDGMENT in T-944-15 102
ANNEX 103
I.
Overview
[1] This action began as a claim by the plaintiff, Teva Canada Limited (Teva), against Janssen Inc. (Janssen) and Millennium Pharmaceuticals, Inc. (Millennium) for compensation under s. 8 of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [the Regulations] for losses suffered during the time that Teva was kept off the market for its version of a drug for treating cancer that is marketed in Canada by Janssen under the name Velcade. The active pharmaceutical ingredient is bortezomib. Teva’s product is called Teva-bortezomib. Because of Teva’s recent amalgamation with Actavis Pharma Company (Actavis), it is also relevant to consider Actavis’s product called Act-bortezomib.
[2] Janssen had rights in Canada to Canadian Patent Nos. 2,203,936 (the 936 Patent) and 2,435,146 (the 146 Patent). In 2012, it commenced two applications under the Regulations against Teva seeking orders prohibiting the issuance of a notice of compliance (NOC) to Teva until expiration of the 936 and 146 Patents, respectively. Millennium was named as a party in the applications, as owner of the 936 Patent and as licensee and sub-licensor of the 146 Patent.
[3] Both applications were dismissed by decisions of Justice Robert L. Barnes concluding that the claims in issue of each of the 936 and 146 Patents were invalid for obviousness. These decisions are cited as Janssen Inc v Teva Canada Limited, 2015 FC 247 and Janssen Inc v Teva Canada Limited, 2015 FC 184, respectively. Teva subsequently obtained its NOC and commenced the present action.
[4] Janssen and Millennium defended the present action on a number of grounds, including that Teva is not entitled to compensation because any sales it was prevented from making due to the delay in the issuance of its NOC would have been of products that infringed the 936 and 146 Patents, as well as Canadian Patent No. 2,738,706 (the 706 Patent). In addition, Janssen and Millennium, as well as Cilag GmbH International, Cilag AG and Janssen Pharmaceutica NV, counterclaimed against Teva seeking various remedies (including damages) for the alleged infringement of the 936, 146 and 706 Patents since Teva obtained its NOC.
[5] In its reply in the main action and in defence against the counterclaim, Teva denied infringement of the 936, 146 and 706 Patents and alleged, among other things, that all of the claims in issue are invalid.
[6] The parties have managed to reach agreement on a number of issues, including the quantum of any compensation or damages that may be payable. The parties have indicated that only the following issues remain in dispute:
With regard to the 936 Patent,
With regard to the 146 Patent,
With regard to the 706 Patent,
Whether claims 37 and 69 are obvious;
What is the inventive concept, and
Whether the asserted claims are obvious;
How the claims should be construed,
Whether Teva‑bortezomib infringes,
Whether Act-bortezomib infringes, and
Whether the asserted claims are obvious.
II. Background to the Patented Technologies
[7] As indicated, this case concerns three patents related to a treatment for certain blood cancers (multiple myeloma and mantle cell lymphoma) in respect of which the active molecule is bortezomib. Cancers are the result of an uncontrolled reproduction (proliferation) of mutated cells. Bortezomib, like many other cancer treatments, acts to limit this uncontrolled reproduction. The following paragraphs provide a general description of bortezomib and how it works to treat cancer.
[8] Bortezomib is a boronic acid analog of a dipeptide. A peptide is a string of amino acids; a dipeptide comprises two amino acids. By comparison, a tripeptide comprises three amino acids and a tetrapeptide comprises four. An amino acid is composed of an amino group, a carboxyl group and a side chain, all bonded together. It is the side chain that gives each amino acid its distinctive characteristics. There are 20 natural amino acids, and many more unnatural amino acids. The amino acids in a peptide are often identified sequentially as P1, P2, P3 (if present), and so on. The P1 amino acid has a free carboxyl group and is referred to as the C‑terminus. The last amino acid in the peptide has a free amino group and is referred to as the N‑terminus.
[9] It is known to replace the carboxyl group of the P1 amino acid with something else. This produces what is called an amino acid analog. In the case of bortezomib, the carboxyl group is replaced by a boronic acid.
[10] There is no limit to the number of amino acids that can be strung together in a peptide. Longer peptides are called proteins. These can have hundreds and even thousands of amino acids.
[11] Reproduction of cells, whether cancer cells or normal cells, requires the breaking (or cleaving) of proteins. This is done using enzymes called proteases as catalysts. Each protease has a different chemical profile which favours it to react chemically with certain positions on certain proteins to achieve the cleaving. The cancer treatment of relevance in this case involves inhibiting the function of one particular protease called the proteasome.
[12] The proteasome is a particularly complex protease that was discovered only in the late 1970s, and whose function remains somewhat mysterious because it does not behave consistently like any of the known classes of proteases. For a time, the proteasome was known as the multicatalytic protease because it has several different areas of activity.
[13] For many years, the proteasome was considered an atypical serine protease based largely on the knowledge that certain (but not all) classes of compounds known to inhibit proteases having a serine amino acid residue at the active site (serine proteases) were also effective at inhibiting the proteasome. However, Seemüller et al, “Proteasome from Thermoplasma acidophilum: a threonine protease” (1995) 268:5210 Science 579-582 revealed that the proteasome has a threonine amino acid residue at the active site, making it a threonine protease.
[14] One of the challenges in protease inhibition as a cancer treatment is to target cancer cells with maximum effect while minimizing the effect on healthy cells. There is little point in killing cancer cells in a patient if the patient’s healthy cells are equally affected. The measure of the effect of a protease inhibitor is called potency. The characteristic of good potency against target cells while having minimal effect on non-target cells is called selectivity or specificity.
[15] Testing of potency in vitro is reported as Ki (the inhibitory constant). This reports the affinity of a molecule to the enzyme to be inhibited. The lower the Ki value, the greater the potency. Even where a compound is shown to be potent in vitro, its ability to penetrate a target cell in order to reach the protease therein to be inhibited is not certain. This ability can be tested and the result is reported as IC50 (the half-maximal inhibitory concentration). Again, the lower the IC50 value, the greater the potency. Finally, even where a compound is shown to be potent and capable of penetrating a cell, it must be tested in vivo.
[16] The center of the function of a protease inhibitor is its “warhead”. This is the location that is intended to bond chemically with the target protease and impede its protein-cleaving function. A cell that is unable to cleave proteins cannot clear the clutter of unwanted proteins. This can lead to the death of the cell. A cancer-treating peptide analog like bortezomib has a warhead accompanied by a particular sequence of amino acids chosen to facilitate chemical binding of the analog with the target protease.
[17] A last portion of a protease-inhibiting peptide analog is a protecting group, also known as a blocking group or capping group. It is located at the N-terminus and its function is to prevent the amino group of the last amino acid in the peptide string from inadvertently reacting with surrounding compounds and thereby changing its chemical make-up.
[18] I turn now to a description of the bortezomib molecule. Its chemical name is N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid, and it is shown in Figure 1 below.
Figure 1
[19] Figure 2 below highlights P1 and the fact that the carboxyl group thereof is replaced with a boronic acid, which is identified with two OH groups bonded to a boron atom (shown as a small B within the molecule). The boronic acid is the warhead.
Figure 2
[20] The side chain of P1 is based on leucine (sometimes abbreviated as Leu). It is shown as the three-armed star attached to the dashed line. Therefore, Figure 2 highlights a boroleucine amino acid analog.
[21] The dashed line shows the stereochemistry of the amino acid analog. Most amino acids are chiral, meaning that they can exist in one of two forms that contain the same atoms but are mirror images of each other (enantiomers). These two forms are sometimes referred to as the D and L isomers. A dashed line indicates that the side chain is oriented going into the page. On the other hand, a wedge (as highlighted in Figure 3 below, for example) indicates a side chain that is coming out of the page.
[22] The foregoing explanation of Figure 2 accounts for the “L-leucine boronic acid” portion of the chemical name of bortezomib.
[23] The amino acid highlighted below in Figure 3 is at the P2 position. It is the L enantiomer of phenylalanine (sometimes abbreviated as Phe).
Figure 3
[24] The remainder of the molecule, which is highlighted in Figure 4 below, is pyrazine carbonyl, acting as the N-terminal protecting group.
Figure 4
[25] This highlighted portion accounts for the “N-(2-pyrazine)carbonyl” portion of bortezomib’s chemical name. The “2” in “2-pyrazine” indicates the position of the nitrogen atoms (shown as N in the molecule) in the pyrazine ring.
[26] There are two different but related uses for an N-terminal protecting group. It may be used during synthesis of a peptide to prevent the N-terminus from reacting in an unwanted way. This type of protecting group is often selected for easy removal in a subsequent step in peptide synthesis when something is to be added at the N-terminus. The second type of N-terminal protecting group is not intended to be removed. It is used when synthesis is complete to stabilize the peptide and assist with binding to the protease. This type is often called a blocking group. In this decision, the terms “protecting group” and “blocking group” are used interchangeably.
[27] There are five characteristic components of the bortezomib molecule that are important to bear in mind:
It is a dipeptide;
It has a boronic acid warhead;
It has a Leu side chain at P1;
It has Phe at P2; and
It has pyrazine carbonyl as its N-terminal protecting group.
[28] Tripeptides generally offer greater potency than dipeptides, but they are generally more difficult to synthesize, less soluble and less metabolically stable. Tripeptides, being larger molecules than dipeptides, are also more inclined to experience difficulty in penetrating a target cell in order to reach the proteasome. Without cell penetration, even the most potent compound will not be able to inhibit the proteasome in vivo. Peptides are synthesized piece by piece. Accordingly, a tripeptide is made from a dipeptide.
III. Overview of the Patents in Suit
[29] Before launching into an analysis of the issues in dispute, it will be useful to provide an overview of each of the patents in suit.
A. The 936 Patent
[30] The 936 Patent is entitled “Boronic Ester and Acid Compounds, Synthesis and Uses”. It issued to Millennium on April 12, 2005, based on an application that was filed on October 27, 1995 and published on May 9, 1996. The 936 Patent claims priority from US applications that were filed on October 28, 1994 and May 16, 1995, though Millennium does not rely on the first priority application. Accordingly, the parties agree that the claim date of the 936 Patent (explained below) is May 16, 1995. The 936 Patent expired on October 27, 2015, the 20th anniversary of its filing date.
[31] The 936 Patent names six inventors, of whom three testified at trial: Julian Adams, Ross Stein and Louis Plamondon.
[32] The 936 Patent was developed within a small biotech start-up company then known as MyoGenics. MyoGenics was later renamed ProScript. In 1999, ProScript was purchased by Leukocyte. Later that same year, Leukocyte was acquired by Millennium.
[33] Ross Stein was hired at MyoGenics upon its founding in late 1993 as its first scientist. His goal was to find proteasome inhibitors for use in treating muscle wasting associated with cancer. Upon his arrival at MyoGenics, Dr. Stein was aware of the commercial availability of peptide analogs with an aldehyde warhead as proteasome inhibitors. These known aldehyde peptide analogs had potency against the proteasome, but were not sufficiently selective – they had too much potency against non-target proteases. Within a week of his arrival, Dr. Stein decided to explore other warheads using backbones known for aldehydes. These other warheads included boronic acids and various ketones. Dr. Plamondon indicated in his testimony that using known backbones as a starting point is very common in discovery chemistry.
[34] Until the arrival of Julian Adams around March 1994, MyoGenics did not have the expertise to synthesize boronic acid peptide analogs. Even with his arrival, MyoGenics did not have the necessary equipment, and was obliged to go outside to obtain such analogs.
[35] Though results of tests involving ketones were disappointing, the first test with a boronic acid warhead yielded potency 100-times better than the corresponding aldehyde warhead, and with much improved selectivity. This result was particularly encouraging because the comparator aldehyde compound was one of the best then known. This first test with a boronic acid warhead was with a tripeptide analog. However, the potency was so good that it was decided there was potency to spare and that dipeptide boronic acid analogs should be tested. Results on these further tests were also very encouraging.
[36] Over the following months, Dr. Adams and his colleagues (Dr. Plamondon joined in October 1994) conducted in vitro tests on 150 to 200 compounds. About 100 of these tests are reported in the 936 Patent. Table II therein reports Ki values against the proteasome for 93 boronate compounds (boronic acids and esters), seven of which are esters and 86 of which are boronic acids. Of the 93 compounds listed in Table II, five are tripeptides and 88 are dipeptides. All but four of the compounds listed in Table II had L-Leu side chains at P1, like bortezomib. Other side chains tested at P1 were D-Leu and L-Phe. A variety of amino acids were tested at P2. A variety of N-terminal blocking groups were also tested. All of the compounds listed in Table II showed some level of potency.
[37] Tables IV and V in the 936 Patent report on the selectivity of certain of the tested compounds for the proteasome over other proteases. These other proteases are Cathepsin B in Table IV, and Human Leukocyte Elastase, Cathepsin G and Human Pancreatic Chymotrypsin in Table V. All of the boronate compounds listed, five in Table IV and five in Table V, showed selectivity.
[38] Table VI in the 936 Patent reports the results of proteasome inhibition testing inside target cells (IC50) by certain of the compounds listed in Table II. Of the 47 compounds listed in Table VI, one is an ester and 46 are boronic acids. Also, four are tripeptides and 43 are dipeptides. All of the compounds listed in Table VI showed some level of potency in cells.
[39] Finally, Table VII reports results of testing in vivo, in mice. Three compounds were tested in this way, all dipeptide boronic acids. All showed inhibition.
[40] The 936 Patent recognizes that peptidyl boronic acids and esters were known, and had been shown to be inhibitors of certain proteolytic enzymes (proteases) and to inhibit the growth of cancer cells. In this context, the 936 Patent cites the following prior art references: (i) US Patent No. 4,499,082 (the 082 Patent), (ii) US Patent No. 4,537,773, (iii) PCT Application Publication No. WO 91/13904 (the 904 Application), (iv) Kettner et al, “Inhibition of the Serine Proteases Leukocyte Elastase, Pancreatic Elastase, Cathepsin G, and Chymotrypsin by Peptide Boronic Acids” (1984) 259:24 J Biol Chem 15106-15114, and (v) US Patent No. 5,106,948 (the 948 Patent).
[41] Though the 936 Patent describes a broad range of boronic ester and acid compounds, many of which are encompassed within some of the claims thereof, the only claims in issue are 37 and 69. Claim 69 is limited to bortezomib. Claim 37 encompasses bortezomib and five other dipeptidyl boronic acid compounds, all having a Leu side chain at P1.
[42] Generally speaking, the 936 Patent can also be considered the “compound patent”.
B. The 146 Patent
[43] The 146 Patent is entitled “Formulation of Boronic Acid Compounds”. It issued to the United States of America (as assignee) on March 29, 2011, based on an application that was filed on January 25, 2002 and published on August 1, 2002. Millennium is a licensee of the 146 Patent. The 146 Patent claims priority from a US provisional application that was filed on January 25, 2001. This is therefore the claim date of the 146 Patent. The 146 Patent is set to expire on January 25, 2022, the 20th anniversary of its filing date.
[44] The 146 Patent names a single inventor, Shanker Gupta. However, two co-inventors were added in 2013 by Order of this Court: Valentino J. Stella and Wanda Waugh (Janssen Inc v Teva Canada Limited (22 May 2013), Ottawa T-2195-12 (FC)). Dr. Stella testified at the trial before me.
[45] With reference to several prior art references, including US Patent No. 5,780,454 (the 454 Patent) which corresponds to the 936 Patent, the 146 Patent notes that peptide boronic ester and acid compounds are useful as proteasome inhibitors. However, the 146 Patent also notes that certain boronic acid compounds are unstable under certain conditions, thus complicating the characterization of their pharmaceutical agents and limiting their shelf life. The 146 Patent therefore recognizes a need for improved formulations of boronic acid compounds.
[46] Dr. Stella testified that in early 1997 he received from Dr. Gupta the assignment to study bortezomib and create a stable formulation for its administration. He was given the structure of the bortezomib molecule in February 1997 and he received the compound itself in March 1997. In addition to the known instability of bortezomib, Dr. Stella learned quickly that it is difficult to dissolve. After determining that the solubility of bortezomib was well short of target, Dr. Stella tried various techniques to try to improve the results. None of these efforts was successful in improving solubility without causing other problems.
[47] For reasons that were not clear, Dr. Stella failed to have any literature search conducted concerning bortezomib at the beginning of his research. A literature search was conducted only in August 1997. It is also notable that this initial search failed to reveal the 936 Patent, even though it had been published by then. As a result, Dr. Stella and his team were unaware, during his formulation work, of any of the prior art cited in the 146 Patent. Dr. Stella and his team were also unaware that bortezomib has a tendency to form boroxines, compounds comprising three bortezomib molecules.
[48] Relatively early in his work (in July 1997), Dr. Stella thought to try lyophilisation (freeze-drying) which was known to assist with instability issues generally. Dr. Gupta was opposed to this approach. Dr. Stella had insufficient supplies of bortezomib to test lyophilisation at the same time as other avenues that had Dr. Gupta’s support. It was only in October 1997, after other efforts had proved fruitless, that Dr. Gupta reluctantly agreed to tests involving lyophilisation.
[49] As part of their study of bortezomib, Dr. Stella and his team conducted a detailed study of its degradation pathways. This study was published as Wu, Waugh & Stella, “Degradation Pathways of a Peptide Boronic Acid Derivative, 2-Pyz-(CO)-Phe-Leu-B(OH)2” (2000) 89:6 J Pharm Sci at 798-765 (Wu 2000). Wu 2000 disclosed that bortezomib presented erratic stability behaviour. Wu 2000 stated that the degradation of bortezomib is quite complicated, but concluded that the major degradation pathway is oxidative in nature. Wu 2000 was published early enough to qualify as prior art to the 146 Patent.
[50] The solution offered by the 146 Patent is esters of boronic acids. The claims of the 146 Patent define ester compounds of dipeptide, tripeptide and tetrapeptide boronic acids (claims 1-15, 54, 56), such ester compounds lyophilized (claims 16-32, 55 and 57), methods for preparing such lyophilized compounds (claims 33-53, 58), methods for reconstituting such lyophilized compounds (claims 59-80), and compositions and lyophilized cakes comprising the claimed compounds (claims 81-84).
[51] The claims in issue are claims 30, 45, 46 and 81-84. Claim 30 is simply lyophilized mannitol ester of bortezomib. Claims 45 and 46 both relate to a method of preparing lyophilized mannitol ester of bortezomib as defined in claim 33. Claim 81 is a composition comprising (i) any of the compounds, lyophilized or not, defined in claims 1-32 and 54-57 and (ii) a pharmaceutically-acceptable carrier. Claim 82 is a composition comprising (i) a lyophilized compound prepared in accordance with the method of any one of claims 33-53 and (ii) a pharmaceutically-acceptable carrier. Claim 83 is a lyophilized cake comprising any of the compounds defined in claims 1-32 and 54-57. Claim 84 is a lyophilized cake comprising the compound of formula (1) prepared in accordance with the method of any one of claims 33-53.
[52] Though all of the claims in issue concern lyophilized compounds, many of the compounds contemplated in other claims of the 146 Patent are not defined as being lyophilized.
[53] Just as the 936 Patent can be considered the “compound patent”, the 146 Patent can be considered the “formulation patent”.
C. The 706 Patent
[54] The 706 Patent is entitled “Synthesis of Boronic Ester and Acid Compounds”. It issued to Millennium on October 14, 2014, based on an application that is deemed to have been filed on March 24, 2005 and published on October 20, 2005. The 706 Patent is a divisional of Canadian Patent Application No. 2,560,886. The 706 Patent claims priority from a US application that was filed on March 30, 2004. This is therefore the claim date of the 706 Patent. The 706 Patent is set to expire on March 24, 2025, the 20th anniversary of its deemed filing date.
[55] The 706 Patent names seven inventors. One of them, John Bishop, testified at trial.
[56] The 706 Patent concerns the synthesis of boronic ester and acid compounds on a large scale. As in the 146 Patent, the 706 Patent makes reference to several prior art references, including the 454 Patent (which corresponds to the 936 Patent) to state that peptide boronic ester and acid compounds are useful as proteasome inhibitors. The 706 Patent also notes prior art that recognizes bortezomib as one such peptide boronic acid proteasome inhibitor that has shown significant antitumor activity. The 706 Patent indicates that known methods of synthesizing boronic ester and acid compounds were difficult to perform successfully on a production scale.
[57] Dr. Bishop testified that he was hired by Millennium in July 2000 to lead process development for Velcade. Because Phase I tests were showing remarkably good results, there was pressure to accelerate the development of a process for large-scale manufacture of Velcade. Millennium wanted to achieve in 18 to 24 months what usually takes four to eight years. Simultaneously, Millennium needed product to continue clinical trials. Millennium directed significant resources to Dr. Bishop’s group in order to meet these goals.
[58] One early challenge for Dr. Bishop and his team surrounded the fact that bortezomib is very potent and hence highly toxic in production quantities. Special manufacturing facilities were required to address the dangers associated with bortezomib production at large scale. However, peptide synthesis is specialized. Only a limited number of manufacturers were capable of meeting stringent targets for product purity. The usual peptide manufacturers to which Millennium might turn did not have the required special manufacturing facilities to handle bortezomib in large quantities.
[59] Dr. Bishop solved this early challenge by splitting the work. He retained Ash Stevens (who had manufactured early batches for clinical testing) to produce more batches in the short term to permit continued clinical testing. In parallel, he worked with Boehringer Ingelheim (BI) to develop a large-scale production process.
[60] The principal goals of the production process development work were to realize a reliable and commercially feasible large-scale process that would offer purity greater than 99%.
[61] The 706 Patent describes and claims a four-step process for the large-scale manufacture of bortezomib or a boronic acid anhydride thereof, in which each step comprises several sub-steps. These steps and sub-steps are discussed in greater detail in the analysis below of claim construction for the 706 Patent. The 706 Patent comprises five claims, of which claim 1 is the only independent claim. All five claims are in issue.
[62] The 706 Patent can also be considered the “process patent”.
IV. Legal Principles
A. Claim Construction
[63] Claims construction is antecedent to consideration of both validity and infringement issues: Whirlpool Corp v Camco Inc, 2000 SCC 67 at para 43 [Whirlpool]. The same claim construction applies for all issues, including infringement and validity issues: Whirlpool at para 49(b).
[64] A patent is not addressed to an ordinary member of the public, but to a worker skilled in the art described as:
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 him. This hypothetical person has sometimes been equated with the “reasonable man” used as a standard in negligence cases. He is assumed to be a man who is going to try to achieve success and not one who is looking for difficulties or seeking failure.
(See Free World Trust v Électro Santé Inc, 2000 SCC 66 at para 44 [Free World Trust], quoting from Harold G. Fox, The Canadian Law and Practice Relating to Letters Patent for Inventions, 4th ed (Toronto: Carswell, 1969) at 184 [Fox].)
[65] The skilled person to whom the patent is addressed is deemed to be unimaginative and uninventive, but at the same time is understood to have an ordinary level of competence and knowledge incidental to the field to which the patent relates and to be reasonably diligent in keeping up with advances: AstraZeneca Canada Inc v Apotex Inc, 2014 FC 638 at para 51, aff’d 2015 FCA 158, rev’d on other grounds 2017 SCC 36.
[66] The person skilled in the art may also be a team of people: Pfizer Canada Inc v Pharmascience Inc, 2013 FC 120 at para 28; General Tire & Rubber Company v Firestone Tyre and Rubber Company Limited, [1972] RPC 457 at 482 (UKCA).
[67] As stated in Catnic Components Ltd v Hill & Smith Ltd, [1982] RPC 183 at 242-243 (UKHL), and quoted in Whirlpool at para 44:
A patent specification should be given a purposive construction rather than a purely literal one derived from applying to it the kind of meticulous verbal analysis in which lawyers are too often tempted by their training to indulge. The question in each case is: whether persons with practical knowledge and experience of the kind of work in which the invention was intended to be used, would understand that strict compliance with a particular descriptive word or phrase appearing in a claim was intended by the patentee to be an essential requirement of the invention so that any variant would fall outside the monopoly claimed, even though it could have no material effect upon the way the invention worked.
[Emphasis in original.]
[68] In construing the claims purposively, it is important to bear in mind that the language of the claims is prime: Free World Trust at para 40.
[69] The claims language will, on a purposive construction, show that some elements of the claimed invention are essential while others are non-essential. Identification of elements as essential or non-essential is made:
(i) on the basis of the common knowledge of the worker skilled in the art to which the patent relates;
(ii) as of the date the patent is published;
(iii) having regard to whether or not it was obvious to the skilled reader at the time the patent was published that a variant of a particular element would not make a difference to the way in which the invention works; or
(iv) according to the intent of the inventor, expressed or inferred from the claims, that a particular element is essential irrespective of its practical effect;
(v) without, however, resort to extrinsic evidence of the inventor's intention.
[Emphasis in original.]
(See Free World Trust at para 31.)
[70] Claim elements are presumed to be essential, and a party alleging otherwise bears the onus of establishing non-essentiality. The Supreme Court of Canada (SCC) in Free World Trust at para 55 stated:
…For an element to be considered non-essential and thus substitutable, it must be shown either (i) that on a purposive construction of the words of the claim it was clearly not intended to be essential, or (ii) that at the date of publication of the patent, the skilled addressees would have appreciated that a particular element could be substituted without affecting the working of the invention, i.e., had the skilled worker at that time been told of both the element specified in the claim and the variant and “asked whether the variant would obviously work in the same way”, the answer would be yes: Improver Corp. v. Remington, [[1990] F.S.R. 181], at p. 192. In this context, I think “work in the same way” should be taken for our purposes as meaning that the variant (or component) would perform substantially the same function in substantially the same way to obtain substantially the same result. In Improver Corp. v. Remington, Hoffmann J. attempted to reduce the essence of the Catnic analysis to a series of concise questions, at p. 182:
(i) Does the variant have a material effect upon the way the invention works? If yes, the variant is outside the claim. If no: –
(ii) Would this (i.e.: that the variant had no material effect) have been obvious at the date of publication of the patent to a reader skilled in the art? If no, the variant is outside the claim. If yes: –
(iii) Would the reader skilled in the art nevertheless have understood from the language of the claim that the patentee intended that strict compliance with the primary meaning was an essential requirement of the invention? If yes, the variant is outside the claim.
[Emphasis in original.]
[71] The foregoing questions are sometimes referred to as the Improver questions. It is understood that a party seeking to establish that a claim element is not essential (i.e., that the variant falls within the scope of the claim) must be successful on all three questions. Even though the SCC’s own phrasing of two questions at the beginning of the passage quoted in the previous paragraph appears to be disjunctive, it seems clear that both questions must be answered in favour of the patentee: Shire Canada Inc v Apotex Inc, 2016 FC 382 at paras 137‑138.
[72] In construing the claims of a patent, recourse to the disclosure portion of the specification is (i) permissible to assist in understanding the terms used in the claims, (ii) unnecessary where the words are plain and unambiguous, and (iii) improper to vary the scope or ambit of the claims: Mylan Pharmaceuticals ULC v Eli Lilly Canada Inc, 2016 FCA 119 at para 39 [Mylan]; Procter & Gamble Co v Beecham Canada Ltd (1982), 61 CPR (2d) 1 at 11, [1982] FCJ No 10 (QL) (FCA).
[73] Terms used in the claims must be read in the context of the patent as a whole, and it is therefore unsafe in many instances to conclude that a term is plain and unambiguous without a careful review of the specification: Whirlpool at para 52, quoting from William L. Hayhurst, “The Art of Claiming and Reading a Claim” in Gordon F. Henderson, ed, Patent Law of Canada (Toronto: Carswell, 1994) 190.
[74] Because there is potential for tension between the guidance provided in the preceding two paragraphs, I reproduce here the discussion of Justice Russell Zinn in Janssen-Ortho Inc v Canada (Health), 2010 FC 42 at paras 115-116, 119, on this point, with which I agree:
[115] In my view, the whole of the specification (including the disclosure and the claims) may be examined to ascertain the nature of the invention. Where the words of the claims are plain and unambiguous and capable of only one interpretation by a person skilled in the art, recourse to the disclosure is unnecessary. This is not to say that the interpreter should not examine the disclosure. In my view, one should do so, but with caution. Recourse may be had to the disclosure for the purpose of confirming the interpretation arrived at from examining the claims alone or to disclose an ambiguity in the language of the claims that was not otherwise evident. However, the patentee cannot expand the monopoly specifically expressed in the claims by borrowing phrases from the disclosure and placing them into the language of the claims.
[116] I agree with Novopharm that when one looks beyond the language of the claims at issue one ought first look at the dependent claims as an aid to interpreting the independent claims, before one resorts to the disclosure.
[…]
[119] I do not take the Supreme Court of Canada to be saying that in every case one must examine the disclosure prior to construing the claims of the patent; rather, I take the Court in Whirlpool and Free World Trust to be raising a caution that one should not reach a firm conclusion as to the meaning of the words in the claims being construed without having tested one’s initial interpretation against the words of the disclosure. When that is done, if the disclosure suggests another interpretation of the terms used in the claims, then resort to the meanings given in the disclosure is proper, subject to the proviso that the invention that is protected is what is expressed in the claims which cannot be added to by anything mentioned in the disclosure that has not found its way into the claims as drafted. As was noted by Justice Taschereau in Metalliflex Ltd. v. Rodi & Wienenberger Aktiengesellschaft, [1961] S.C.R. 117, at p. 122:
The claims, of course, must be construed with reference to the entire specifications, and the latter may therefore be considered in order to assist in apprehending and construing a claim, but the patentee may not be allowed to expand his monopoly specifically expressed in the claims “by borrowing this or that gloss from other parts of the specifications”.
[All emphasis by Zinn J.]
[75] As stated in Consolboard Inc v MacMillan Bloedel (Sask) Ltd, [1981] 1 SCR 504 at 520:
We must look to the whole of the disclosure and the claims to ascertain the nature of the invention and methods of its performance, (Noranda Mines Limited v. Minerals Separation North American Corporation [[1950] S.C.R. 36]), being neither benevolent nor harsh, but rather seeking a construction which is reasonable and fair to both patentee and public. There is no occasion for being too astute or technical in the matter of objections to either title or specification for, as Duff C.J.C. said, giving the judgment of the Court in Western Electric Company, Incorporated, and Northern Electric Company v. Baldwin International Radio of Canada [[1934] S.C.R. 570], at p. 574, “where the language of the specification, upon a reasonable view of it, can be so read as to afford the inventor protection for that which he has actually in good faith invented, the court, as a rule, will endeavour to give effect to that construction”. Sir George Jessel spoke to like effect at a much earlier date in Hinks & Son v. Safety Lighting Company [(1876), 4 Ch. D. 607]. He said the patent should be approached “with a judicial anxiety to support a really useful invention”.
[76] If a patentee has put something in the patent specification that plainly tells the reader that, for the purpose of the specification, s/he is using a parti