Novo Nordisk Canada Inc. v. Cobalt Pharmaceuticals Inc.

Novo Nordisk Canada Inc. v. Cobalt Pharmaceuticals Inc.
Court (s) Database
Federal Court Decisions
Date
2010-08-03
Neutral citation
2010 FC 746
File numbers
T-1221-08
Decision Content
Federal Court
Cour fédérale
Date: 20100803
Docket: T-1221-08
Citation: 2010 FC 746
Ottawa, Ontario, August 3, 2010
PRESENT: The Honourable Madam Justice Mactavish
BETWEEN:
NOVO NORDISK CANADA INC. and
DR. KARL THOMAE GmbH
Applicants
and
COBALT PHARMACEUTICALS INC. and
THE MINISTER OF HEALTH
Respondents
PUBLIC REASONS FOR JUDGMENT AND JUDGMENT
(Confidential Reasons for Judgment and Judgment released July 15, 2010)
TABLE OF CONTENTS
PARA.
I. Introduction............................................................................................................... 1
II. Scientific Concepts.................................................................................................... 5
A. Stereochemistry................................................................................................... 6
B. Pharmacokinetics and Pharmacodynamics.......................................................... 15
III. Type 2 Diabetes...................................................................................................... 21
IV. The Development of Repaglinide.............................................................................. 32
A. The ’398 Patent................................................................................................. 40
B. The ’331 Patent Application.............................................................................. 47
C. Events Leading up to the ’851 Patent................................................................. 50
V. The Burden and Standard of Proof........................................................................... 67
VI. Construction............................................................................................................ 70
A. General Principles Governing the Construction of Patents.................................... 71
B. The Person of Ordinary Skill in the Art............................................................... 81
C. The Construction of the ’851 Patent................................................................... 89
VII. Validity.................................................................................................................. 135
A. Anticipation..................................................................................................... 144
i) The Test for Anticipation.............................................................................. 147
ii) Is Cobalt’s Allegation of Anticipation Justified?............................................ 156
B. Obviousness.................................................................................................... 176
i) The Test for Obviousness............................................................................ 178
ii) Is Cobalt’s Allegation of Obviousness Justified?........................................... 184
a) Rufer 1974............................................................................................ 189
b) Schentag............................................................................................... 196
c) Rufer 1979............................................................................................ 198
d) The ’398 Patent and the ’331 Patent Application................................... 204
e) Garrino.................................................................................................. 210
f) Verspohl................................................................................................ 218
g) Shinkai.................................................................................................. 223
h) Summary of Conclusions from the Prior Art............................................ 227
i) The Common General Knowledge Regarding Pharmacokinetics............. 233
j) Conclusion Regarding the Common General Knowledge of
Enantiomers and Pharmacokinetics........................................................ 273
k) The State of the Art Regarding Separation Techniques.......................... 274
l) The Application of the Sanofi Test........................................................ 305
C. Is the ’851 Patent Void pursuant to Section 53(1) of the Patent Act?............... 325
i) The Law Governing Section 53(1) of the Patent Act................................... 328
ii) Sufficiency of the NOA............................................................................... 337
iii) The Missing Legend.................................................................................... 343
iv) The Study Data........................................................................................... 351
v) Fairness Concerns..................................................................................... 365
VIII. Conclusion............................................................................................................ 369
IX. Costs.................................................................................................................... 370
I. Introduction
[1] Dr. Karl Thomae GmbH is the owner of Canadian Patent No. 2,111,851 (the “’851 patent”), which claims a compound known as repaglinide, its use for the treatment of Type 2 Diabetes, and processes to make it. Repaglinide is marketed in Canada by Novo Nordisk Canada Inc. under the brand name GlucoNorm®, in accordance with a Notice of Compliance received from the Minister of Health.
[2] Cobalt Pharmaceuticals Inc. seeks approval to sell a generic version of GlucoNorm® in Canada, to be called CO Repaglinide. In accordance with the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, as amended, Cobalt served a Notice of Allegation (NOA) dated June 23, 2008 on Novo Nordisk.
[3] Cobalt now admits that its repaglinide product will infringe the ’851 patent. However, Cobalt alleges, amongst other things, that the ’851 patent is not a valid selection patent, and that it is invalid on a number of bases, including anticipation, obviousness, double patenting, lack of utility, and insufficiency. Cobalt also asserts that the ’851 patent is void, as the inventors made material allegations about the utility of the patent which were untrue, and that they omitted information from the patent which ought to have been disclosed.
[4] By this proceeding, the applicants seek to prohibit the Minister of Health from issuing a Notice of Compliance to Cobalt until the expiration of the ’851 patent. For the reasons that follow, I have concluded that one of Cobalt’s allegations of invalidity is justified. Consequently, the application for an order of prohibition will be dismissed.
II. Scientific Concepts
[5] In order to put the invention claimed by the ’851 patent into context, it is first necessary to have an understanding of certain chemical structures and conventions. It is also necessary to have some understanding of both pharmacokinetics and pharmacodynamics.
A) Stereochemistry
[6] “Stereochemistry” is concerned with the three dimensional structure of compounds made up of atoms. Molecules having exactly the same chemical composition and the same sequence of covalent bonds may differ in their arrangement in three dimensions. Such compounds are referred to as “stereoisomers”.
[7] A carbon atom with four different functional groups attached to it is referred to as a “chiral centre”. A chiral centre may have two possible arrangements, such that one arrangement may not be superimposable on the other by rotating in space. In such cases, the carbon atom is referred to as stereogenic, and the compound is termed “chiral”.
[8] In order to describe the stereochemistry of molecules having chiral centres, chemists have devised a number of conventions. Where the direction from the highest to lowest priority atom or group attached to the chiral carbon, determined by atomic number, is clockwise, the chiral centre is described as being in the “R” position, whereas a counter-clockwise arrangement is referred to as being in the “S” position.
[9] Pairs of mirror image molecules that cannot be superimposed on each other are referred to as enantiomers. In this regard, an analogy is often drawn to left and right hands. Enantiomers have identical physical properties, including melting and boiling points, solubility, and reactivity, but may have very different biological properties from one another.
[10] Compounds comprising equal amounts of enantiomeric molecules in the “R” and “S” position are known as “racemic compounds” or “racemates”. The physical properties of a racemate can differ from those of its component enantiomers, and a racemate’s biological properties may also differ from either enantiomer.
[11] Because chiral centres exist in three dimensions, it is necessary to have a convention for indicating the atoms’ position in space when molecules are represented on paper. To distinguish isomers based on the arrangement of the atoms attached to the chiral centre in space, chemists show a bond that projects up from the plane of the paper, towards the viewer, with a solid wedge shape. A chemical bond that projects away from the viewer is indicated by a hatched wedge shape.
[12] Enantiomers may also be designated using the prefix “(+)” (also known as “dextro-rotatory”) or “(-)” (also known as “levo-rotatory”) before the formal chemical name. This represents the direction in which a solution of the enantiomer rotates polarized light. Knowing whether an enantiomer is (+) or (-) does not teach the absolute stereochemistry of an isomer, however, and without knowing whether the enantiomer is R or S, a person skilled in the art would not be able to draw its specific structure.
[13] While the R/S and +/- designations are different ways of describing enantiomers, there is no correlation between the two types of designation. Thus a compound could exist in the R(+) or R(-) form or in the S(+) or S(-) form. Repaglinide is an S(+) enantiomer.
[14] Racemates can be identified by the designation “(±)” or “RS” to indicate the presence of equal amounts of both enantiomers.
B) Pharmacokinetics and Pharmacodynamics
[15] Pharmacokinetics is the study of what the body does to a drug after it is administered, whereas pharmacodynamics explores what a drug does to the body.
[16] Amongst other things, pharmacokinetics can determine how long a drug remains in the body and the concentration of drug at various sites in the body. Once a drug is released into a body, there are four pharmacokinetic factors involved. These are absorption, distribution, metabolism and excretion.
[17] According to the applicants’ experts, pharmacokinetics are particularly important in the treatment of diabetes, and it is the applicants’ position that the most significant improvement of repaglinide over earlier diabetes treatments relates to its pharmacokinetic profile.
[18] It is common ground that one cannot know how an enantiomer will act in the body, that is, its pharmacokinetics, until it has actually been made and tested. Two enantiomers may behave very differently in the body when administered separately, although it can be expected that one enantiomer will likely show greater activity than the other, and that their pharmacokinetics may also differ.
[19] The experts agree that the relationship between enantiomers is very complex. By way of example, there are instances of one enantiomer converting to the other enantiomer once inside the body. Enantiomers can also have antagonistic effects or synergistic effects, or the racemate could be better than either enantiomer alone.
[20] With this understanding of some of the scientific concepts underlying this application, I turn now to consider the evidence regarding Type 2 Diabetes.
III. Type 2 Diabetes
[21] In order to understand the advantages claimed by the applicants’ repaglinide medication when used as a treatment for Type 2 Diabetes, it is first necessary to have some understanding of the nature of diabetes as an illness.
[22] The primary evidence with respect to diabetes and its clinical treatment was provided by Dr. Steven V. Edelman, a Professor of Medicine at the University of California at San Diego, where he works in the Division of Endocrinology, Diabetes & Metabolism. In addition to his involvement in an editorial capacity with a number of medical journals dealing with endocrinology and diabetes, Dr. Edelman has himself authored or co-authored nearly 200 publications and 60 abstracts relating to diabetes, and has also published books on the subject. I do not understand Cobalt to take issue with Dr. Edelman’s expertise or his evidence as it relates to the nature and treatment of diabetes, and I accept his evidence in this regard.
[23] According to Dr. Edelman, diabetes is a serious illness which affects more than 230 million people worldwide. While there are many different types of diabetes, the two most common types are known as Type 1 and Type 2 Diabetes.
[24] Type 1 Diabetes usually develops before the age of 20. It is believed to be an autoimmune condition, wherein antibodies are produced by the body that destroy the cells within the pancreas that produce insulin. Insulin is used by the body in using and storing glucose. The treatment for Type 1 Diabetes is insulin.
[25] Approximately 90% of individuals suffering from diabetes have Type 2 Diabetes, which is also known as diabetes mellitus. This form of the disease typically develops after the age of 35. Unlike Type 1 Diabetes, which is characterized by a lack of insulin in the body, Type 2 Diabetes is characterized by “insulin resistance”, which results in a lack of effectiveness in getting glucose into the body’s cells. Type 2 Diabetes is often initially treated with oral medication, but may require the administration of insulin as the disease progresses. This is because insulin resistance causes the pancreas to over-secrete insulin in an effort to compensate, which can in turn result in a condition known as “pancreatic exhaustion”.
[26] Although there is a strong genetic component to Type 2 Diabetes, other factors can contribute to its onset including obesity, age and a sedentary lifestyle. As a consequence, nutritional therapy and exercise are important parts of the treatment for this form of diabetes. However, when lifestyle modifications are insufficient to resolve the patient’s metabolic abnormalities, treatment with oral medication will be required.
[27] Until the mid-1990s, the only drugs available to treat Type 2 Diabetes were a class of drugs known as sulfonylureas (or “SFUs”). SFUs work by chronically stimulating the pancreas to produce insulin.
[28] SFUs are evidently very long-acting pharmaceuticals, and are often taken only once or twice a day. As a result, the patient’s pancreas is stimulated to produce insulin throughout the day. It is believed that it is this constant stimulation over a prolonged period that leads to pancreatic exhaustion. When a patient suffers from pancreatic exhaustion, the cells in the pancreas that produce insulin stop functioning properly, and are no longer able to deal with high levels of glucose in the blood. At this stage, patients with Type 2 Diabetes have to start taking insulin.
[29] Dr. Edelman states that prior to the availability of non-SFU anti-diabetic medication (of which repaglinide was the first example), approximately 35% of patients with Type 2 Diabetes would ultimately end up being treated with insulin.
[30] Hypoglycemia (or low blood sugar) is another problem that can arise with SFU treatment. Because of the long action of the SFUs, patients can become hypoglycemic if they skip a meal, or if they exercise too vigorously. Symptoms of hypoglycemia include sweating, dizziness, confusion, shakiness and difficulty speaking. According to Dr. Edelman, an episode of hypoglycemia is “an extremely unpleasant experience”. As a result, patients experiencing hypoglycemia often resist further treatment with SFU medications.
[31] Dr. Edelman asserts that patients with Type 2 Diabetes “needed a drug that was active long enough to stimulate insulin production during the postprandial state (the approximately 2 hour period of time after eating) but that would not continue to act throughout the day in order to avoid hypoglycemia”. He says that it is also important that such a medication take effect quickly, in order that it could be taken shortly before mealtime, so that the patient could avoid having to carefully time when he or she ate each meal.
IV. The Development of Repaglinide
[32] During the late 1960s and early 1970s, Dr. Karl Thomae GmbH (“Karl Thomae”) was working in the field of anti-diabetic treatments. By all accounts, this was, and remains, a highly competitive field.
[33] Karl Thomae had commercialized an SFU medication called gliquidone in the early 1970s. However, by the late 1970s, the focus of the company had changed, and it began looking for an alternative anti-diabetic medication that would address some of the concerns identified by Dr. Edelman.
[34] Other companies working in the field had begun working on a new class of anti-diabetics known as “benzoic acid derivatives”. Two benzoic acid derivative compounds with hypoglycemic activity had been reported in 1976, although neither was ever brought to market. The first of these was Hoecsht compound HB 699 (meglitinide), and the second was a Schering compound.
[35] Based upon these two external leads, Karl Thomae began an internal research project in 1976 which focused on benzoic acid derivatives. The aim of this project was to identify and develop one or more compounds with the same or better activity than the SFUs, but without the known associated risks such as hypoglycemia. Repaglinide ultimately became the world’s first commercial product from the meglitinide class.
[36] Karl Thomae had a research team working on this project. One of the members of this team was Dr. Wolfgang Grell, one of the seven named inventors of repaglinide. Dr. Grell is a synthetic organic chemist who worked as part of a team that included a clinician responsible for human studies, several biologists, including a cell biologist and a human biologist, and a lab specialist with experience in asymmetric hydrogenation.
[37] The benzoic acid derivatives that the Karl Thomae team was studying during this period had the following general structure:
[38] According to Dr. Grell, his team was using a “structure activity relationship” (or “SAR”) approach in their research. That is, they were changing the moieties attached to the general structure of the compound, specifically modifying the groups identified in the above structure as R1 through R4 and W, and then testing for activity.
[39] Between 1976 and 1983, some 900 compounds were synthesized and tested by Karl Thomae. As a result of these tests, it became apparent that even small changes to the above structure could result in significant and unpredictable changes to the biological properties of the compound in question.
A) The ’398 Patent
[40] Of the 900 compounds actually made and tested by the scientists at Karl Thomae by 1983, three showed sufficient activity to warrant further testing. These compounds were assigned the code names (rac)-AGDD-1446, (rac)-AZDF-265 and (rac)-AGEE-86. In December of 1983, Karl Thomae filed a patent application in Germany, which is the priority application for Canadian Patent No. 1,225,398 (both the priority application and the Canadian patent will be referred to in these reasons as the “’398 patent”). This application covered a class of benzoic acid derivatives of the general formula depicted above for use as anti-diabetics.
[41] There was intense competition in the field at this time, and as was explained by Dr. Grell, “[t]he strategy behind this initial patent filing was to allow Karl Thomae to gain protection for the benzoic acid derivatives [of a certain formula] as soon as possible ahead of any competitors”.
[42] It is common ground that the ’398 patent includes approximately one million compounds, one of which was the racemate of repaglinide. The ’398 patent discloses racemic and non-racemic compounds, and states that the enantiomers as well as the racemates are to be considered as within the scope of the invention. The patent also teaches a number of methods to make the compounds of the invention, including the enantiomers. It further identifies all of the claimed compounds as having blood sugar lowering activity. The ’398 Patent was filed in Canada on December 28, 1984, and included all of the compounds that had been synthesized by Karl Thomae to that date.
[43] The racemate of repaglinide was identified in the ’398 patent by the code name (rac)-AG EE 388 (the “388 compound”). Although the 388 compound is disclosed in the German patent application, it had yet to be synthesized or tested. However, within the one year period allowed between the initial filing in Germany and foreign country filings, many additional compounds, including the 388 compound, were synthesized and tested by the research team at Karl Thomae.
[44] Dr. Michael Mark is another of the inventors of repaglinide. Between 1985 and 1988, he was head of the laboratory for Metabolic Diseases in the Department of Biochemistry at Karl Thomae, where he was responsible for animal and in vitro studies in the field of diabetes mellitus, obesity and lipid metabolism.
[45] According to the evidence of Drs. Grell and Mark, between 1983 and 1986, a total of 150 additional benzoic acid derivatives were synthesized by the team at Karl Thomae. The 388 compound was first synthesized in October of 1984. Initial test data indicated that this compound showed good promise, with the result that the 388 compound was included as a separate compound claim at the end of the claims set out in foreign patent applications. It appears as the final two claims in the Canadian ’398 patent: in claim 42, which is a process claim, and claim 43, which is the claim for the compound itself.
[46] The 388 compound is the racemate of repaglinide and was referred to by Cobalt throughout this proceeding as “racemic repaglinide”. It can be depicted as:
B) The ’331 Patent Application
[47] On June 25, 1985, Karl Thomae filed the priority application for two new solid forms (or polymorphs or salts) of the 388 compound and their enantiomers (the “’331 patent application”). These compounds are said to have “valuable pharmacological features, namely effects on the intermediary metabolism, particularly a blood-sugar lowering effect”. The ’331 patent application is the European equivalent of Canadian Patent No. 1,292,000 (the “’000 patent”).
[48] According to the ’331 patent application, the novel compound could be produced using “methods generally known per se”.
[49] In addition to claiming the two new solid forms of the 388 compound, their enantiomers and their salts, the ’331 patent application claims, amongst other things, the use of the claimed compounds for the treatment of diabetes mellitus (or Type 2 Diabetes).
C) Events Leading up to the ’851 Patent
[50] Although both the ’398 patent and ’331 patent application claim the 388 compound and its enantiomers, the evidence of Drs. Mark and Grell is that their research group did not believe that there was any special advantage of enantiomers over racemates in the field of anti-diabetic drugs.
[51] Dr. Grell says that the team tried to synthesize the enantiomers of the racemic compounds that had been selected for development, although there was no suggestion from Karl Thomae management that they focus on these enantiomers. Dr. Mark agrees that as of mid-1985, the research and development activities of Karl Thomae did not involve focusing on the enantiomers of the 388 compound. Indeed, Dr. Grell says that up to the early- to mid-1990s, it was viewed as preferable to avoid enantiomers and chiral molecules altogether, as the chemistry involved in dealing with such compounds was more complicated and more costly.
[52] Cobalt takes issue with this evidence, particularly in light of the introduction in 1989 of Karl Thomae’s “Enantiomer Policy” (the Karl Thomae “Procedure for the Development Preparation of Chiral Active Substances”) and the increasingly rigorous requirements of regulatory agencies insofar as racemic compounds and their enantiomers were concerned. I will return to consider the significance of these matters in my consideration of Cobalt’s challenges to the validity of the ’851 patent, specifically in relation to the question of obviousness.
[53] In October of 1985, the first small amounts of the enantiomers of the 388 compound were obtained by the research team at Karl Thomae. According to Dr. Grell, the amounts obtained at this time were only sufficient for analytical testing and for exploratory activity tests in rats. Insufficient qualntities of the enantiomers were obtained to allow for the testing of their biological or pharmacokinetic properties.
[54] In a Research and Development meeting held at Karl Thomae that same month, the development of the 388 compound was initiated. According to Dr. Mark, the team proceeded with further development work on the 388 compound in 1986, with the intention of developing it into a commercial product by 1988. No consideration was being given at that time to looking to the enantiomers of the 388 compound for development.
[55] According to Dr. Mark, between 1986 and early 1988, 50 additional benzoic acid derivatives were synthesized by the research team. None of these compounds showed sufficient blood glucose-lowering activity as to justify their being pursued.
[56] Dr. Grell explains that earlier testing had revealed that (rac)-AGEE 86 (one of the other compounds of interest identified prior to the filing for the ’398 patent) and its enantiomers had proved to be teratogenic. That is, they could cause birth defects. As a consequence, when the team investigated the teratogenicity of the 388 compound, the decision was made to test its enantiomers for teratogenicity as well.
[57] In order to carry out these tests, it was necessary to synthesize larger quantities of the enantiomers of the 388 compound. Dr. Grell says that while the principal way to synthesize the enantiomers was already known because of the work that had been done on the (rac)-AGEE 86 enantiomers, additional work still needed to be done including the “optimization of the route and exploration of alternatives”.
[58] The steps followed by the research team in trying to isolate sufficient quantities of the enantiomers of the 388 compound are described at paragraphs 38 through 45 of Dr. Grell’s affidavit. According to Dr. Grell, an attempt in March of 1986 to resolve the 388 compound directly by means of L-arginine failed. In October and November of 1986, the group investigated another resolution method using eight different specified acids. The only “hit” that the team had was with N-acetyl-L-glutamic acid and one equivalent of the rac-amine. However, the samples obtained were at an unsuitably low purity level.
[59] Dr. Grell says that “partly by luck” and partly as a result of a “massive amount of work” that had been done in attempting to synthesize other enantiomers of benzoic acid derivatives, in January of 1987, a more suitable purity level was achieved using N-acetyl-L-glutamic acid. It was at this point, Dr. Grell asserts, that the group had its first procedure for resolving the enantiomers in sufficient quantity as to allow for pharmacokinetic and biological testing.
[60] Tests carried out in January and December of 1987 determined that the 388 compound and its enantiomers were non-teratogenic. Although Karl Thomae was now able to obtain sufficient quantity of the enantiomers of the 388 compound to allow for pharmacokinetic and biological testing, there was little interest at that time in exploring the enantiomers any further.
[61] Dr. Mark explains that it was known that, in vivo, one could ordinarily only hope to possibly achieve a two-fold increase in activity of an enantiomer over its racemate. In contrast, the SAR approach had the potential to result in a many-fold change in activity. Consequently, Dr. Mark and his colleagues did not believe that it was worth exploring the separation of racemates, and work continued on the development of the racemic 388 compound.
[62] Although Karl Thomae management decided to cancel its benzoic acid derivative anti-diabetic project in 1988, approval was obtained to continue with the development of the 388 compound. However, the focus of the work of the research team continued to be on the racemic compound, rather than its enantiomers.
[63] After the successful completion of toxicological studies in animals, in September of 1988 the first human trial of the 388 compound and its (S) enantiomer, repaglinide, was conducted with Dr. Grell as the sole test subject. Dr. Grell found that the (S) enantiomer had “very surprising plasma levels” and was more active than the 388 compound at lowering blood glucose. Dr. Mark says that, by itself, the observation of this improvement was not enough to cause Karl Thomae to pursue the (S) enantiomer over the racemic 388 compound.
[64] That changed, however, in late 1989 or early 1990. Karl Thomae was engaged in negotiations with Novo Nordisk regarding the potential licensing of the 388 compound. During the course of these negotiations, Novo Nordisk asked Karl Thomae for information regarding the enantiomers of the 388 compound. As a consequence, Karl Thomae undertook the study of the enantiomers for purposes of completing its due diligence work on the 388 compound.
[65] According to Dr. Mark, there was, at that time, no hope or expectation that either the (S) or (R) enantiomer would demonstrate superior pharmacokinetic properties over the racemic 388 compound. However, based on the results of studies of the (S) enantiomer (i.e. repaglinide), the company decided in April of 1990 to focus its efforts on the development of repaglinide, rather than the 388 compound.
[66] Through studies carried out between February of 1990 and April of 1991, repaglinide’s allegedly surprising biological and pharmacokinetic properties were discovered. A Patent Co-Operation Treaty application was filed on June 21, 1991, which subsequently led to the ’851 Patent. Novo Nordisk ultimately brought repaglinide to market.
V. The Burden and Standard of Proof
[67] Before turning to consider the issues raised by this application, it is first necessary to address the question of the burden and standard of proof in applications such as this. Although much has been written on these issues, I do not understand there to be any disagreement between these parties as to the burden and standard of proof in proceedings under subsection 6(1) of the PM (NOC) Regulations.
[68] Insofar as the validity of the ’851 patent is concerned, the patent will be presumed to be valid, in the absence of evidence to the contrary. If Cobalt fails to adduce any evidence on a ground of invalidity, that presumption is not rebutted.
[69] However, if Cobalt adduces some evidence which, if accepted, is capable of establishing the invalidity of the patent, thereby putting the allegations of invalidity “in play”, the burden will be on the applicants to establish on a balance of probabilities that all of the allegations of invalidity are not justified: see the Patent Act, R.S.C. 1985, c. P-4, s. 43(2); Abbott Laboratories v. Canada (Minister of Health), 2007 FCA 153, 59 C.P.R. (4th) 30 at paras. 9-10; Pfizer Canada Inc. v. Canada (Minister of Health) 2007 FCA 209, 60 C.P.R. (4th) 81 at para. 109.
VI. Construction
[70] The first task for the Court is to construe the ’851 patent. This must be done before consideration can be given to the issues raised by the parties in relation to the question of validity.
A) General Principles Governing the Construction of Patents
[71] The Court is to determine objectively, through the eyes of the person skilled in the art, what such a person would have understood the inventors to mean as of the relevant date: see Whirlpool Corp. v. Camco Inc., 2000 SCC 67, [2000] 2 S.C.R. 1067 at paras. 45, 53 [Whirlpool].
[72] The claims of a patent are to be construed purposively, having regard to the intentions of the inventors as derived from the patent and with reference to the entire specification. Where necessary, the whole of the patent should be interpreted, and not just the claims: Eli Lilly Canada Inc. v. Apotex Inc., 2008 FC 142, 63 C.P.R. (4th) 406 at para. 25; Eli Lilly Canada Inc. v. Novopharm Ltd., 2007 FC 596, 58 C.P.R. (4th) 214 at para. 103.
[73] A court should construe a patent with a judicial anxiety to support a useful invention: see Whirlpool at paras. 42-50; Free World Trust v. Électro Santé Inc., 2000 SCC 66, [2000] 2 S.C.R. 1024 [Free World Trust]; Consolboard Inc. v. MacMillan Bloedel Saskatchewan Ltd., [1981] 1 S.C.R. 504, 56 C.P.R. (2d) 145 at 157 [Consolboard].
[74] Construction of any given claim will depend on the common knowledge of a person skilled in the art of the patent with a mind willing to understand what is put to him or her and the knowledge of the art at the time the patent was published: Free World Trust at para. 31; Whirlpool at paras. 43, 45, and 49.
[75] Expert assistance may be provided with respect to the meaning of certain terms, as well as the knowledge that a person skilled in the art would have had as of the relevant date: see Janssen-Ortho Inc. v. Novopharm Ltd., 2007 FCA 217, 59 C.P.R. (4th) 116 at para. 4; Halford v. Seed Hawk Inc., 2006 FCA 275, 54 C.P.R. (4th) 130 at para. 11.
[76] In this case, expert evidence with respect to the construction of the ’851 patent was provided on behalf of the applicants by Dr. Hartmut Derendorf, who holds a Ph.D. in pharmacy, and is a Distinguished Professor and the Chairman of the Department of Pharmaceutics at the University of Florida. Dr. Dieter Enders also provided evidence for the applicants on this issue. Dr. Enders is a Professor within the Organic Chemistry Institute of RWTH at Aachen University, whose research focuses on synthetic chemistry.
[77] The applicants’ third expert on this issue of patent construction is Dr. Eugen Verspohl, who holds a Ph.D. in pharmacy from the University of Düsseldorf, and has been a Professor of Pharmacology and Toxicology, at the University of Münster since 1991.
[78] Cobalt’s expert evidence was provided by Dr. Ian Cunningham, Dr. Fakhreddin Jamali and Dr. Daniel Armstrong. Dr. Cunningham is an organic chemist with a Ph.D. from the University of Glasgow. He is currently an independent consultant to the pharmaceutical industry, after a 27-year career in the field.
[79] Dr. Jamali, has a Ph.D. in biopharmaceutics and pharmacokinetics from the University of British Columbia. In addition to being a Professor, and former Associate Dean of Research in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta, Dr. Jamali also works as a consultant to the pharmaceutical industry.
[80] Dr. Armstrong is a Professor of Chemistry and Biochemistry at the University of Texas at Arlington. He is an expert in the separation of enantiomers, and holds a Ph.D. in bio-organic chemistry from Texas A&M University
B) The Person of Ordinary Skill in the Art
[81] The “person skilled in the art” is an ordinary worker who is ordinarily skilled in the art to which the invention relates and who possesses the ordinary amount of knowledge incidental to that particular trade: Consolboard, above, at 523.
[82] Although the phrase often used in the jurisprudence is the “person of ordinary skill in the art”, in the case of patents of a highly technical and scientific nature, the “person of ordinary skill in the art” has been described as someone possessing a high degree of expert scientific knowledge and skill in the particular branch of the science to which the patent relates: Consolboard, above.
[83] The parties agree that because the ’851 patent addresses various areas of science, the notional person of ordinary skill in the art for the purposes of construing the patent would in fact be a composite person or drug development team made up of individuals with different areas of expertise.
[84] The applicants say that this notional person consists of “an amalgam of people with expertise in stereochemistry, medicinal chemistry, pharmacokinetics, and experience in the antidiabetic field.” This person would have a Bachelor’s degree in chemistry, and would have expertise in the principles of stereochemistry and medicinal chemistry. In addition, this person would have a degree in biology as well as familiarity with pharmacokinetic and pharmacodynamic principles.
[85] Cobalt agrees that the notional person skilled in the art should be a composite person or drug development team with experience in these different areas. However, relying on the evidence of Drs. Cunningham and Armstrong, Cobalt argues that this person should have the level of skill and knowledge of Master’s level education, which, it says, could be obtained through formal education or through practical experience. Moreover, Cobalt says that a member of this notional team should also have experience with the separation of enantiomers.
[86] The parties have not indicated where or how it would make a difference if the educational level of the notional composite person skilled in the art was at the Bachelor’s level as opposed to the Master’s level, nor did either side press this point of disagreement at the hearing. While I do not believe that anything turns on this question, I would find that the person skilled in the art would be the composite person or drug development team, made up of individuals with at least a Bachelor’s degree in the relevant fields, as well as work-related practical experience.
[87] I agree with the applicants that having regard to the subject matter of the patent, the person skilled in the art should have some familiarity with pharmacokinetic and pharmacodynamic principles. I also agree with Cobalt that because the patent relates to an enantiomer which has been separated from its parent racemate, it is only reasonable that a member of this notional drug development team possess knowledge and experience in enantiomeric separation.
[88] Keeping these principles in mind, I turn now to consider the ’851 patent.
C) Construction of the ’851 Patent
[89] The ’851 patent is entitled “(S)(+)-2-ethoxy-4-[N-[1-(2-piperidino-phenyl)-3-methyl-1-butyl]-aminocarbonylmethyl]-benzoic acid. The patent issued in Canada on February 26, 2002 from a PCT application filed on June 21, 1991, and will expire on June 21, 2011. In addressing this patent, the first issue for the Court is the proper construction of its claims.
[90] The parties agree that the relevant date for claims construction is January 7, 1993, that is, the date on which the ’851 patent was published.
[91] The applicants identify the invention claimed by the ’851 patent in their memorandum of fact and law as being repaglinide (also referred to as (S)(+)-2-ethoxy-4-[N-[1-(2-piperidino-phenyl)-3-methyl-1-butyl]-aminocarbonylmethyl]-benzoic acid), as well as methods to obtain it by separating it from its racemate, and its use in the treatment of Type 2 Diabetes.
[92] When the application was filed, repaglinide was referred to by the code AG-EE 623 ZW. Repaglinide is the (S) enantiomer of the racemic 388 compound (also referred to herein as “the racemate” or “racemic repaglinide”). The (R) enantiomer of the 388 compound was referred to in the ’851 patent as AG-EE 624 ZW.
[93] The claims of the ’851 patent that are at issue in this proceeding are claims 1-9 and 15-20. Claims 10-14 and 21 are process claims and are not at issue; nor are claims 22 to 24, which claim precursors and intermediates, an