Lundbeck Canada Inc. v. Ratiopharm Inc.

Lundbeck Canada Inc. v. Ratiopharm Inc.
Court (s) Database
Federal Court Decisions
Date
2009-11-23
Neutral citation
2009 FC 1102
File numbers
T-414-08
Decision Content
Date: 20091123
Docket: T-414-08
Citation: 2009 FC 1102
Ottawa, Ontario, November 23, 2009
PRESENT: The Honourable Madam Justice Mactavish
BETWEEN:
LUNDBECK CANADA INC.
H. LUNDBECK A/S and
MERZ PHARMA GmbH & Co. KGaA
Applicants
and
RATIOPHARM INC. and
THE MINISTER OF HEALTH
Respondents
PUBLIC REASONS FOR JUDGMENT AND JUDGMENT
(Confidential Reasons for Judgment and Judgment released October 28, 2009)
TABLE OF CONTENTS
PARA.
I. Introduction............................................................................................................... 1
II. Background............................................................................................................... 8
III. The Burden and Standard of Proof........................................................................... 22
IV. General Principles Governing the Construction of Patents.......................................... 26
V. The Person Skilled in the Art.................................................................................... 29
VI. The ’453 Patent....................................................................................................... 32
a) Construction...................................................................................................... 34
b) Validity.............................................................................................................. 67
i) Anticipation........................................................................................... 71
a)The Test for Anticipation..................................................................... 72
b) Which Prior Art can be Relied upon by ratiopharm?...................... 78
c)Is ratiopharm’s Allegation of Anticipation Justified?.............................. 96
Ishizu.......................................................................................... 101
The Rote Liste........................................................................... 112
Ambrozi..................................................................................... 121
Marcea...................................................................................... 132
d) Conclusion on the Issue of Anticipation....................................... 136
ii) Obviousness........................................................................................ 139
a) The Test for Obviousness........................................................... 140
b) Is ratiopharm’s Allegation of Obviousness Justified?.................... 146
Fleishhacker............................................................................... 154
Meldrum.................................................................................... 173
Greenamyre................................................................................ 180
c) Conclusion on the Issue of Obviousnes........................................ 189
iii) Utility 194
c) Infringement..................................................................................................... 216
d) Conclusions with Respect to the ’453 Patent.................................................... 217
VII. The ’492 Patent..................................................................................................... 218
a) Construction.................................................................................................... 223
b) Validity............................................................................................................ 231
i) Is ratiopharm’s Allegation of Anticipation Justified?............................... 233
Wenk.................................................................................................. 235
Jain..................................................................................................... 248
ii) Is ratiopharm’s Allegation of Obviousness Justified?............................. 250
iii) Is ratiopharm’s Allegation of Utility Justified?........................................ 254
iv) Has There been a Lack of Good Faith Prosecution?............................. 298
c) Infringement..................................................................................................... 353
VIII. Conclusion ........................................................................................................... 401
IX. Costs……………………………………………………………………………...403
I. Introduction
[1] Alzheimer’s disease is a particularly cruel illness. It slowly robs sufferers of their memories, their personalities, their autonomy and, ultimately, their lives. It also takes a terrible toll on the families, friends and caregivers of the afflicted.
[2] There is no cure for Alzheimer’s disease. For many years, the only treatment available in Canada slowed the progress of the disease in some patients with mild to moderate Alzheimer’s. Since 2004, a drug known as memantine hydrochloride (or “memantine”) has become available to treat individuals with moderate to advanced Alzheimer’s.
[3] There are two patents involving memantine listed by Lundbeck Canada Inc. on the Register maintained by Health Canada under section 4 of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, as amended (“PM(NOC) Regulations”), which are the patents at issue in this proceeding. Canadian patent 2,014,453 (the ’453 patent) is owned by two of the applicants, namely Merz Pharma GmbH & Co. KGaA and H. Lundbeck A/S. Patent 2,426,492 (the ’492 patent) is owned by H. Lundbeck A/S.
[4] Memantine is sold in Canada under the brand name “EBIXA” by the third applicant, Lundbeck Canada Inc. (“Lundbeck”), in accordance with a Notice of Compliance received from the Minister of Health.
[5] ratiopharm Inc. wishes to sell memantine in Canada, and is seeking to obtain a Notice of Compliance from the Minister of Health to allow it to do so. To this end, on December 21, 2007, ratiopharm filed an abbreviated new drug submission (or “ANDS”) with the respondent Minister of Health. ratiopharm compared its "ratio-MEMANTINE" drug to the EBIXA tablets manufactured by Lundbeck.
[6] In accordance with the PM(NOC) Regulations, on January 24, 2008, ratiopharm served a Notice of Allegation (NOA) on Lundbeck, alleging, amongst other things that both patents were invalid on a number of bases, including anticipation, obviousness, lack of utility, and, in the case of the ’492 patent, lack of good faith prosecution. ratiopharm further alleges that it would neither itself infringe, nor induce others to infringe either patent if it is allowed to manufacture and sell its ratio-MEMANTINE product in Canada for the ratiopharm Indication.
[7] By this proceeding, the applicants seek to prohibit the Minister from issuing a Notice of Compliance to ratiopharm until the expiration of the ’453 and ’492 patents. For the reasons that follow, I have concluded that certain of ratiopharm’s allegations of invalidity are justified as they relate to each of the patents in issue. I have also concluded that ratiopharm’s allegation of non-infringement is justified, as it relates to the ’492 patent. Consequently, the applicants’ application for an order of prohibition will be dismissed.
II. Background
[8] Alzheimer’s disease was first described by Alois Alzheimer, a German psychiatrist, in 1906. The disease is progressive and terminal, with patients going through mild, moderate and severe phases of the illness before finally succumbing to it.
[9] For decades, the only help available for Alzheimer’s patients was directed towards assisting patients and their caregivers with strategies to cope with the progression of the disease symptoms, and with care management. As of the late 1990s, the only drug therapy available for Alzheimer’s patients that appeared to have potential clinical benefits was a class of drugs known as acetylcholinesterase inhibitors.
[10] Acetylcholinesterase inhibitors act to inhibit the actions of the acetylcholinesterase enzyme in the brain. Acetylcholine is a neurotransmitter, or chemical messenger, that assists in the communication of signals between neurons in the brain. Acetylcholine is believed to be crucial in many brain functions including memory. By inhibiting the enzyme that breaks it down, acetylcholinesterase inhibitors allow more acetylcholine to act on the acetylcholine receptors in the brain.
[11] The mechanism of action of acetylcholinesterase inhibitors is based upon the “cholinergic hypothesis” of Alzheimer’s disease, under which it is hypothesized that Alzheimer’s disease is caused in part by the degeneration of brain cells (or neurons) that use acetylcholine as their primary neurotransmitter.
[12] There are three acetylcholinesterase inhibitors approved for use in Canada: donepezil, rivastigmine and galantamine. Until 2007, these drugs were approved and marketed in Canada only for the treatment of mild to moderate Alzheimer’s disease. In 2007, donepezil was also approved for use in the treatment of severe dementia of the Alzheimer’s type.
[13] In 2004, a new type of medication known as 1-amino-3,5-dimethyl admantane (or memantine) received conditional approval from Health Canada to be administered either on its own, or as an adjunctive therapy in combination with one of three approved acetylcholinesterase inhibitors.
[14] Memantine was the first drug approved for the treatment of moderate to severe Alzheimer’s disease. It is a N-methyl-D-asparate receptor antagonist, and is the only drug of this type used in the treatment of Alzheimer’s. As noted above, memantine is marketed in Canada by Lundbeck as EBIXA.
[15] Unlike acetylcholinesterase inhibitors, memantine’s mechanism of action is understood to relate to the “glutamate hypothesis” of Alzheimer’s disease. Under this hypothesis, it is theorized that Alzheimer’s disease is caused in part by the degeneration of brain cells, or neurons, that use glutamate as their primary neurotransmitter.
[16] Like acetylcholine, glutamate is a neurotransmitter that is known to play a role in brain functions, including memory. Memantine works on different brain receptors than do acetylcholinesterase inhibitors, namely the N-methyl-D-asparate (or “NMDA”) receptors, which are a type of glutamate receptor.
[17] It is necessary to activate the NMDA receptors in the brain for learning to occur and for memories to form. The glutamate hypothesis of Alzheimer’s disease theorizes that too much activity of the NMDA receptors leads to over stimulation of the neurons (known as excitotoxicity). Excitotoxicity, in turn, causes the destruction of neurons as a result of an excess inflow of calcium ions.
[18] As an NMDA receptor antagonist, memantine binds to the NMDA receptors without activating them. This prevents glutamate from itself binding to the receptors. It is believed that memantine thus prevents excitotoxicity and cell death in Alzheimer’s patients.
[19] Although its mechanism of action was not well-understood at the time, memantine was used in some countries, including Germany, as far back as the 1960s for the treatment of Parkinson’s disease. The brains of patients with Parkinson’s disease have reduced levels of the dopamine neurotransmitter. It was originally believed that memantine had “dopaminergic” properties. That is, it was thought that the drug either increased the levels of dopamine within the brain, or reduced the rate at which dopamine was removed from the brain.
[20] The applicants acknowledge that the discovery that memantine was not “dopaminergic”, and that it actually worked as an NMDA receptor antagonist was not, by itself, patentable: see Abbott Laboratories v. Canada (Minister of Health), 2008 FC 1359, 337 F.T.R. 17 at para. 71, aff’d 2009 FCA 94, 387 N.R. 347 (“Abbott”). However, the applicants say that this discovery was the “eureka moment” that led to the invention of using a whole new class of compounds for the treatment of Alzheimer’s disease.
[21] With this understanding of the basic operation of the medications currently available for the treatment of Alzheimer’s disease, and before turning to consider the two patents in issue in this case, I will first address the burden and standard of proof in proceedings such as this. I will then review the general principles governing the construction of patents, including the identification of the person skilled in the art, for the purposes of construing the patents in issue.
III. The Burden and Standard of Proof
[22] 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.
[23] With respect to the issue of infringement, where, as here, a generic manufacturer has alleged non-infringement in its NOA, the statements that it makes in this regard are presumed to be true. The onus is on the applicants to demonstrate, on a balance of probabilities, that the allegations of non-infringement are not justified. It will not be enough for an applicant to raise the possibility of infringement: see Novopharm Limited v. Pfizer Canada Inc. 2005 FCA 270, 42 C.P.R. (4th) 97, at paras. 19-20 and 24.
[24] Insofar as the validity of a patent is concerned, the patent will be presumed to be valid, in the absence of evidence to the contrary. If the generic fails to adduce any evidence on a ground of invalidity, the presumption is not rebutted.
[25] However, if the generic 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 applicant to establish on a balance of probabilities that all of the allegations of invalidity are not justified: see 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 v. Canada (Minister of Health) (2007 FCA 209, 60 C.P.R. (4th) 81, at para. 109 (F.C.A.).
IV. General Principles Governing the Construction of Patents
[26] Before examining the issues raised by the parties in relation to questions of validity and infringement, the Court must construe the patents in issue. The Court is to determine objectively, through the eyes of the person skilled in the art, what such a person would have understood the inventor or 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.
[27] 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. 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; Consolboard Inc. v. MacMillan Bloedel Saskatchewan Ltd., [1981] 1 S.C.R. 504, 56 C.P.R. (2d) 145 at 157.
[28] 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.
V. The Person Skilled in the Art
[29] The “person skilled 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: see Consolboard, above. I do not understand there to be any disagreement between the parties as to the identification of the appropriate person skilled in the art for the purposes of construing the two patents in issue in this proceeding.
[30] This hypothetical person may be described as “a medicinal chemist and a clinician, such as a psychiatrist, neurologist or geriatrician, practicing in the field of dementia and Alzheimer’s disease”.
[31] Keeping these principles in mind, I now turn to consider the first of the patents in issue.
VI. The ’453 Patent
[32] The inventors of the invention claimed in the ’453 patent are Joachim Borman, Markus R. Gold and Wolfgang Schatton. As was noted earlier, the ’453 patent is owned by Merz Pharma GmbH & Co. KGaA and H. Lundbeck A/S, and is entitled “Adamantane-derivatives in the Prevention and Treatment of Cerebral Ischemia”. The patent issued in Canada on March 28, 2000 from an application filed on April 11, 1990, which claimed priority from a European application filed April 14, 1989. The patent expires on April 11, 2010.
[33] In addressing this patent, the first issue for the Court is its proper construction.
a) Construction
[34] The parties agree that October 14, 1990, is the relevant date for the purposes of construing the patent.
[35] The claims at issue in this proceeding are claims 1, 2, 3, 6, 8, 10, 11 and 12, which state:
1. Use of an adamantine derivative of the general formula [Representative Drawing] wherein R1 and R2 are identical or different and represent hydrogen or a straight or branched alkyl group of 1 to 6 C atoms or, in conjunction with N, a heterocyclic group with 5 or 6 ring C atoms: wherein R3 and R4 are identical or different, being selected from hydrogen, a straight or branched alkyl group of 1 to 6 C atoms, a cycloalkyl group with 5 or 6 C atoms, and phenyl; wherein R5 is hydrogen or a straight or branched C1 - C6 alkyl group, or a pharmaceutically-acceptable salt thereof, for the prevention or treatment of cerebral ischemia.
2. Use according to Claim 1, wherein R1, R2 and R5 are hydrogen.
3. Use according to Claim 2, wherein R1, R2 and R5 are hydrogen, and R3 and R4 are methyl.
6. Use according to Claim 1, wherein R2 and R5 are hydrogen.
8. Use according to Claim 1, wherein R1 and R2 are hydrogen.
10. Use according to any of Claims 1-9 for the manufacture of a drug for the prevention or treatment of Alzheimer's disease.
11. Use according to Claim 1, wherein the adamantane derivative is used in an effective cerebral ischemia-alleviating or preventive amount.
12. Use according to Claim 11, wherein the adamantane derivative is used in an amount effective to prevent degeneration and loss of nerve cells after ischemia.
[36] Memantine is an adamantane derivative, as that term is defined in each of the above claims, and is specifically described in claim 3.
[37] The invention of the ’453 patent is described at pages 4 and 5 of the patent specification in the following terms:
The compounds according to formula (I) known from the above-cited patents have so far been used for the treatment of parkinsonian and parkinsonoid diseases. Their mode of action is attributed to a dopaminergic influence on the CNS [central nervous system], either by an increased release of the transmitter substance dopamine or by an inhibition of its uptake. This compensates the imbalance of dopamine / acetylcholine system.
In contrast to this type of disease, cerebral ischemia is characterized by a pathophysiological situation defined by an imbalance of neuronal stimulation mechanisms. In this context, the excessive inflow of calcium through NMDA receptor channels finally leads to the destruction of brain cells in specific brain areas. [citations omitted]
Therefore, in order to treat or eliminate this pathological situation, an antagonistic intervention is required with regard to the NMDA receptor channels. [citations omitted]
The present invention is aimed at preparing and employing compounds which can be chemically generated by simple methods, exhibiting an NMDA receptor channel-antagonistic and anticonvulsive action, for use in the prevention and treatment of cerebral ischemia.
This objective can be achieved according to the invention by using the 1-amino adamantanes of formula (I).
[38] The promise of the patent is described in the following terms:
It has been found unexpectedly that the use of these compounds prevents an impairment or further impairment, i.e., degeneration and loss of nerve cells, after ischemia. Therefore, the adamantane derivatives of formula (I) are especially suited for the prevention and treatment of cerebral ischemia after apoplexy, open-heart surgery, cardiac standstill, subarachnoidal h[e]morrhage, transient cerebro-ischemic attacks, perinatal asphyxia, anoxia, hypoglycemia, apnoea and Alzheimer’s disease.
[39] Each of the relevant claims of the ’453 patent claims an alleged new use of adamantane derivatives for the prevention or treatment of cerebral ischemia. The issue between the parties is the proper construction to be given to the term “cerebral ischemia”.
[40] The applicants say that “cerebral ischemia” is defined in the patent to refer to a “pathophysiological situation defined by an imbalance of neuronal stimulation mechanisms”. Inventors may define terms in the patent specification. Where this is done, the term should be considered by the Court as having the meaning so intended, regardless of whether it differs from the definition that would ordinarily be applied to the term by a skilled person.
[41] In contrast, ratiopharm contends that the plain and ordinary meaning of “cerebral ischemia” is the temporary loss of blood flow to the brain. Terms in a patent claim should be given their ordinary and plain meaning if they have one. Only exceptionally may terms bear a special or unusual meaning, either found in the specification or the technical knowledge possessed by persons skilled in the art.
[42] ratiopharm says that a patentee must clearly and explicitly state that it is giving a term a specific meaning in a patent, in order for the term to have a meaning different from its ordinary meaning. According to Dr. Joel Sadavoy, ratiopharm’s expert witness, that has not occurred in this case.
[43] The importance of the construction issue as it relates to the meaning of the term “cerebral ischemia” cannot be overstated, as it is conceded by ratiopharm that if the Court construes the patent in the manner suggested by Lundbeck, then the manufacture or sale of ratiopharm’s ratio-MEMANTINE product would necessarily infringe the ’453 patent.
[44] For the reasons that follow, I have concluded that properly construed, the term “cerebral ischemia” as it is used in the ’453 patent, refers to “an imbalance of neuronal stimulation mechanisms”.
[45] It is clear from the jurisprudence that although it is indeed the “golden rule” of patent construction that a term in a patent claim should be given its plain and ordinary meaning, that rule is not inviolate. A term may bear a special or unusual meaning “by reason either of a dictionary found elsewhere in the Specification or of technical knowledge possessed by persons skilled in the art”: see Ernest Scragg & Sons Ltd. v. Leesona Corp., [1964] Ex. C.R. 649, 45 C.P.R. 1 at para. 104.
[46] That is, if a patentee has put something in the specification that “plainly tells the reader that for the purpose of the specification he is using a particular word with a meaning which he sets out, then the reader knows that when he comes to the claims, he must read that word as having that meaning”: Minerals Separation North American Corp. v. Noranda Mines Ltd., [1952] J.C.J. No.2, 69 RPC 81, at para.17. The Privy Council went on to observe, however, that this is an awkward method of drafting, and should be avoided.
[47] In this case, Dr. Sadavoy, and at least one of the applicants’ experts, Dr. Nathan Herrmann, have agreed that as of October 1990, the term “cerebral ischemia” would have had an accepted, plain and unambiguous meaning to a person skilled in the art, namely, the interruption or loss of blood flow to the brain.[1]
[48] Dr. Sadavoy is a professor of psychiatry at the University of Toronto, the immediate past psychiatrist-in-chief and head of the geriatric and community psychiatry programs and director at the Cyril and Dorothy, Joel and Jill Reitman Centre for Alzheimer’s support and training. He holds the Sam and Judy Pencer and Family Chair in Applied General Psychiatry at Mount Sinai Hospital in Toronto. Dr. Sadavoy also holds numerous university and hospital appointments related to the field of psychiatry and geriatrics, and was the founding President of the Canadian Academy of Geriatric Psychiatry.
[49] Dr. Herrmann is also a professor of psychiatry at the University of Toronto and is a Staff Psychiatrist at the Sunnybrook Health Science Center, where he holds the position of Deputy Chief of the Department of Psychiatry, and head of the Division of Geriatric Psychiatry. He is also the Chair of the Pharmacy and Therapeutics Committee at the Sunnybrook Health Sciences Centre. His main research interest is the prevention and treatment of dementia and Alzheimer’s disease.
[50] In contrast, Dr. Wolfgang Schatton, one of the co-inventors of the invention claimed in the ’453 patent, states in his affidavit that the term was not well defined, at least in Germany, and was understood as having a number of different meanings as of October of 1990. Dr. Schatton is a pharmacist, with a doctorate in pharmaceutical chemistry from the University of Frankfurt. He was employed at Merz Pharma GmbH & Co. KGA from 1978 to 1991 as the head of the Pre-clinical Research Department, where he was involved in the development and study of memantine, including pre-clinical development and clinical studies.
[51] Even if the term “cerebral ischemia” was not clearly understood in Germany at the time in issue, I am satisfied, based upon the evidence of Drs. Sadavoy and Herrmann that as of October, 1990, the term “cerebral ischemia” would have had an accepted, plain and unambiguous meaning to a person skilled in the art in Canada, namely, the interruption or loss of blood flow to the brain.
[52] That is not, however, the end of the matter. The fact that a term may have an accepted and ordinary meaning is immaterial if it is made plain in the specification that the term is being used in a
particular sense: see Western Electric Co. v. Baldwin International Radio of Canada, [1934], S.C.R. 570 at 582.
[53] The question, then, is whether the patentees “acted as their own lexicographers” in this case, such that the term “cerebral ischemia” should be understood as having a meaning different from its ordinary meaning.
[54] A review of page 4 of the patent specification discusses the “old” use of memantine in the treatment of parkinsonian and parkinsonoid diseases, based upon a mode of action attributed to a dopaminergic influence on the central nervous system.
[55] The specification then goes on to state that:
In contrast to this type of disease, cerebral ischemia is characterized by a pathophysiological situation defined by an imbalance of neuronal stimulation mechanisms. In this context, the excessive inflow of calcium through NMDA receptor channels finally leads to the destruction of brain cells in specific brain areas…. [emphasis added]
[56] ratiopharm submits that the term “cerebral ischemia” was not defined in the patent. According to ratiopharm, for the statement cited above to amount to a definition, the words “is characterized by a pathophysiological situation” would have to be read out.
[57] I cannot accept this submission. In my view, with the statement at page 4 of the patent cited above, the patentee has clearly defined what is meant by the term “cerebral ischemia” for the purposes of the ’453 patent. Moreover, a review of other portions of the patent discloses that the term is not being used in its ordinary sense.
[58] By way of example, the specification goes on to state that:
Therefore, in order to treat or eliminate this pathological situation, an antagonistic intervention is required with regard to the NMDA receptor channels. [citations omitted]
The present invention is aimed at preparing and employing compounds which can be chemically generated by simple methods, exhibiting an NMDA receptor channel-antagonistic and anticonvulsive action, for use in the prevention and treatment of cerebral ischemia. [emphasis added]
It is clear from this that the invention contemplated by the ’453 patent relates to the central nervous system, rather than to blood flow.
[59] As was noted earlier, the promise of the patent is described in the following terms:
It has been found unexpectedly that the use of these compounds prevents an impairment or further impairment, i.e., degeneration and loss of nerve cells, after ischemia. Therefore, the adamantane derivatives of formula (I) are especially suited for the prevention and treatment of cerebral ischemia after apoplexy, open-heart surgery, cardiac standstill, subarachnoidal h[e]morrhage, transient cerebro-ischemic attacks, perinatal asphyxia, anoxia, hypoglycemia, apnoea and Alzheimer’s disease. [emphasis added]
[60] “Hypoglycemia” refers to the lack of glucose. “Asphyxia”, “anoxia”, and “apnoea” all relate to a lack of oxygen. Dr. Sadavoy acknowledged on cross-examination that all of these conditions could arise in circumstances unrelated to a lack of blood flow to the brain.
[61] Moreover, the test data presented in the ’453 patent seeks to demonstrate, amongst other things, that the compounds disclosed in the patent function as NMDA receptor antagonists, thereby preventing or treating “cerebral ischemia” as the term has been defined by the patentees. Dr. Sadavoy himself acknowledges in his affidavit that the tests do not pertain to the treatment of cerebral ischemia in its ordinary sense.
[62] I am therefore satisfied that applying the teachings of the disclosure, the term “cerebral ischemia” is being used by the patentees throughout the patent (including the claims), to describe the pathophysiological situation defined by an imbalance of neuronal stimulation mechanisms that can occur in a variety of situations and in association with a variety of conditions, including Alzheimer’s disease.
[63] In the context in which it is used in the ’453 patent, the term “cerebral ischemia” should be construed to mean “an imbalance of neuronal stimulation mechanisms”. Accordingly, the relevant claims of the patent should be construed as follows:
CLAIM 1
Use of an adamantane derivative of [chemical formula which includes memantine], or a pharmaceutically-acceptable salt thereof, for the prevention or treatment of an imbalance of neuronal stimulation mechanisms as described at page 4 of the patent.
CLAIMS 2, 3, 6, 8
Use according to Claim 1, wherein [chemical formula which includes memantine].
CLAIM 10
Use of an adamantane derivative of the kind disclosed in any of Claims 1-9, or a pharmaceutically-acceptable salt thereof, for the prevention or treatment of an imbalance of neuronal stimulation mechanisms for the prevention or treatment of Alzheimer’s disease.
CLAIM 11
Use according to Claim 1, wherein the adamantane derivative is used in an effective [neuronal stimulation imbalance] alleviating or preventive amount.
CLAIM 12
Use according to Claim 11, wherein the adamantane derivative is used in an amount effective to prevent degeneration and loss of nerve cells after an imbalance of neuronal stimulation mechanisms.
[64] Before leaving the issue of construction I would note that similar patents have been the subject of litigation in Germany and the United States. In a December 2007 decision, the German Federal Patent Court construed the term "cerebral ischemia" as it is used in the corresponding European Patent (No. 0 392 059) in the manner urged by ratiopharm. That is, the German Court construed the term “cerebral ischemia” to mean “inadequate circulation in the brain”, resulting in consequences that could lead to cell death: neuraxpharm Arzneimittel GmbH U. Co. KG v. Merz Pharma GmbH & Co. KGaA, File Reference 3Ni 59/05 (EU) leading in conjunction with 3 Ni 20/07 (EU) 3 Ni 34/07 and 3 Ni 54/07 (German Federal Patent Court), at para. 1.2.1.
[65] However, it is not clear from the German Court’s reasons whether the term “cerebral ischemia” was specifically defined in the patent as is the case here. Nor is it clear what legal principles are applied by German Courts in construing patents in cases such as this.
[66] In contrast, in a recent “Markman” proceeding, a United States Magistrate Judge was called upon to construe a similar patent. In that case, the Magistrate Judge recommended that the term “cerebral ischemia” (a term specifically defined in the American patent in terms essentially identical to those in issue here) should be construed to mean “an imbalance of neuronal stimulation mechanisms”: Forest Laboratories Inc. v. Cobalt Laboratories Inc., 2009 WL 1916935 (D.DEL.). ratiopharm concedes that the interpretive principles applied by the American Court are very similar to those governing this case.
b) Validity
[67] Although numerous allegations of invalidity were advanced in ratiopharm’s NOA in relation to the ’453 patent, only three were pursued at the hearing of this matter. ratiopharm submits that the patent is invalid for both anticipation and obviousness. ratiopharm also contends that utility was neither demonstrated nor disclosed in the patent, and that Lundbeck has not satisfied the test for sound prediction.
[68] As the Supreme Court of Canada recently observed in Apotex Inc. v. Sanofi-Synthelabo Canada Inc., 2008 SCC 61, [2008] 3 S.C.R. 265 (“Sanofi”), anticipation and obviousness are related concepts. However, although both require an examination of the prior art, that prior art must be treated differently depending on whether the issue is anticipation or obviousness.
[69] In examining an allegation of anticipation (or lack of novelty), the Court must determine whether the claimed invention has already been disclosed to the public in a single disclosure in such a way as to enable it to be put into practice: see Synthon BV v. Smithkline Beecham plc, [2005] UKHL 59, [2006] 1 All ER 685, at para. 25, and Eli Lilly Canada Inc. v. Novopharm Ltd., 2009 FC 301, at para. 58.
[70] In contrast, where obviousness (or lack of invention) is alleged, the Court may consider a number of prior disclosures that would have been known or found by a person skilled in the art, in order to determine whether an inventive step has been taken: Eli Lilly Canada Inc., at para. 58.
i) Anticipation
[71] The parties agree that in accordance with section 28.2(1)(a) of the Patent Act, the date to be used in assessing whether the invention claimed in the ’453 patent was anticipated is April 14, 1989, that is, one year prior to the date on which the application for the ’453 patent was filed in Canada.
a) The Test for Anticipation
[72] Insofar as the test for anticipation is concerned, the Supreme Court recently reviewed the law on this point in Sanofi, at paras. 23-37. The Court held that two separate requirements must be established in order for there to be anticipation. These are prior disclosure and enablement.
[73] “Prior disclosure” means that the prior art must disclose subject matter which, if performed, would inevitably or necessarily result in infringement of the patent. The person skilled in the art looking at the disclosure must be “taken to be trying to understand what the author [of the prior patent or other disclosure] meant. At this stage, there is no room for trial and error or experimentation by the skilled person. He is simply reading the prior [art] for the purposes of understanding it”: see Sanofi, at para. 25, citing Synthon.
[74] “Enablement” means that the person skilled in the art “would have been able to perform the invention” without undue burden. The person skilled in the art is assumed to be willing to make trial and error experiments to get it to work: Sanofi, at paras. 26-27.
[75] As to how much trial and error or experimentation will be permitted before a prior disclosure will be found not to constitute an enabling disclosure, the Court held that if an inventive step is required to get the invention to work, the earlier publication will not have provided enabling disclosure. Even if no inventive step is necessary, the person skilled in the art must still be able to perform or make the invention work without undue burden: Sanofi, at para. 33.
[76] The Court then went on at paragraph 37 of Sanofi to provide a non-exhaustive list of factors that may be applied in considering the question of enablement. It noted, amongst other things, that “routine trials are acceptable and would not be considered undue burden. But experiments or trials and errors are not to be prolonged even in fields of technology in which trials and experiments are generally carried out. No time limits on exercises of energy can be laid down; however, prolonged or arduous trial and error would not be considered routine”.
[77] In considering the issue of novelty or anticipation, the Court must look at the invention as claimed: see ratiopharm Inc. v. Pfizer Ltd., 2009 FC 711, at para. 157.
b) Which Prior Art can be Relied upon by ratiopharm?
[78] The next question for determination is which prior art can be relied upon by ratiopharm in relation to the issues of disclosure and enablement, as there is a dispute between the parties in this regard.
[79] ratiopharm cited four publications in its NOA which, it says, anticipate the ’453 patent. These are:
1. L. Ambrozi and W. Danielczyk, “Treatment of Impaired Cerebral Function in Psychogeriatric Patients with Memantine – Results of a Phase II Double Blind Study”, Pharmacopsychiat. 21, (1988) 144-146. (“Ambrozi”)
2. Ishizu Application (Japanese Patent Publication No. JP 58-4718, published January 1, 1983). (“Ishizu”)
3. The 1986 German “Rote Liste”, at p. 63 009.
4. Marcea et al, “Effect of Memantine versus dh-Ergotoxin on Cerebro-organic Psycho-syndrome”, Therapiewoche, (1988) 38: 3097-3100 (“Marcea”)
[80] In its memorandum of fact and law and again at the hearing, ratiopharm argued that an article by W.W. Fleischhacker and others entitled “Memantine in the Treatment of Senile Dementia of the Alzheimer Type”, (1986) 10:1 Prog. Neuropsychopharmacol. Biol. Psychiatry 87 (“Fleischhacker”) also anticipated the invention claimed by the ’453 patent.
[81] The applicants object to arguments based on the Fleischhacker article being advanced by ratiopharm in relation to the issue of anticipation. The applicants point out that although the article was referenced by ratiopharm in its NOA with respect to the issue of obviousness, nowhere is the article mentioned in the NOA in relation to the question of anticipation.
[82] The applicants submit that they were entitled to be fully apprised of the allegations against them before commencing this proceeding, so as to allow them to make a meaningful and informed decision as to whether to expose themselves to the risk of damages under section 8 of the PM (NOC) Regulations.
[83] Furthermore, had they been aware that Fleischhacker was being cited in support of ratiopharm’s anticipation argument, the applicants submit that different evidence may have been adduced, and different or additional questions could have been asked in cross-examination. I note, however, that the applicants did not adduce any evidence as to the insufficiency of the NOA in this regard, nor did they identify any specific evidence that would have been adduced or any particular questions that would have been asked on cross-examination, but were not.
[84] ratiopharm argues that it drew the Fleischhacker article to Lundbeck’s attention in its NOA, albeit in relation to the issue of obviousness. Moreover, ratiopharm was ordered to deliver its evidence in relation to the issue of anticipation first. As a consequence, ratiopharm says that Lundbeck and the other applicants were made fully aware of the case that they had to meet in relation to the issue of anticipation at that time, and had a fair opportuni