Date: 20031112
Docket: T-135-02
Citation: 2003 FC 1334
OTTAWA, (ONTARIO), THIS 12TH DAY OF NOVEMBER 2003
Present: THE HONOURABLE MR. JUSTICE MARTINEAU
BETWEEN:
H. LUNDBECK A/S and LUNDBECK CANADA INC.
Applicants
- and -
THE MINISTER OF HEALTH and APOTEX INC.
Respondents
REASONS FOR ORDER AND ORDER
[1] The applicants H. Lundbeck A/S and Lundbeck Canada Inc. (collectively Lundbeck) are seeking an order under section 6 of the Patented Medicines (Notice of Compliance) Regulations, SOR/1993-133 (Regulations) prohibiting the Minister of Health (the Minister) from issuing a Notice of compliance (NOC) to the respondent Apotex Inc. (Apotex) in respect of 20 mg and 40 mg tablets of citalopram hydrobromide (citalopram) until after the expiration of Canadian Patent No. 2,049,368 ('368 Patent).
[2] Before any new drug is marketed and sold in Canada it must receive the approval of the Minister. It must meet certain safety and other standards pursuant to the Food and Drugs Act, R.S.C. 1985, c. F-27 and its regulations. A NOC is only issued once those standards are met (Food and Drug Regulations, C.R.C. c. 870, Division 8, Part C (1978)). In conjunction with and as part of its new drug submission, each manufacturer must submit a proposed product monograph which sets out the proposed uses to which the product may be put once approved by the Minister. The Minister will not approve a product for a particular use unless the submitting drug manufacturer has sought approval for that use. Once approved, a final product monograph is issued by the Minister as part of the NOC documents.
[3] A drug manufacturer who holds a patent on a drug, and who has been issued a NOC for the drug, can file a patent list with the Minister in respect of that drug. This patent list appears on a register maintained by the Minister (the Register). There are no connections between the use specified in the NOC and the use appearing on the patent list. When a manufacturer applies for a NOC with respect to a drug that is either compared or referenced to a patented drug (which appears on the Register) it must support its application with an allegation that the listed drug will not be infringed. The Notice of allegation (NOA) must be served on the patent holder. The latter then has 45 days to challenge the NOA and apply for an order from the Federal Court prohibiting the Minister from issuing the NOC (Regulations, sections 3 to 5). By commencing a prohibition application in response to a NOA, the applicant obtains a remedy which is tantamount to a presumptive interlocutory injunction not available to any other class of patentees (Apotex Inc. v. Canada (Attorney General) (2000), 6 C.P.R. (4th) 165 at 178 (F.C.A.); Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1998), 80 C.P.R. (3d) 368 at para. 33 (S.C.C.); Merck Frosst Canada Inc. v. Apotex Inc. (1977), 72 C.P.R. (3d) 170 at pp. 175-77 (F.C.A.); and Bayer AG v. Canada (Minister of National Health and Welfare) (1993), 51 C.P.R. (3d) 329 at 337 (F.C.A.)).
[4] Under paragraph 6(1) of the Regulations, the burden of proof lies on the applicant. This burden is a difficult one since the latter must disprove some or all of the allegations made which, if left unchallenged, would allow the Minister to issue an NOC. Therefore, the Court should start from the proposition that the allegations of fact in the NOA are true except to the extent that the contrary has been shown by the applicant. The respondent is under no obligation to file any evidence. Therefore, the applicant cannot expect to make its case "out of the mouth of the respondent" (Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1994), 55 C.P.R. (3d) 302 at 320 (F.C.A.)). Moreover, the applicant is limited to the grounds it has asserted in its Notice of application for discharging its burden of establishing, on a balance of probabilities, that the respondent's allegation of non-infringement is not justified. (Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare), supra, at 319 (F.C.A), aff'd (1994), 75 F.T.R. 97 (T.D.); Hoffman-La Roche Ltd. v. Canada Minister of National Health and Welfare (1996) 70 C.P.R. (3d) 206 (F.C.A.); SmithKline Beecham Inc. v. Apotex Inc. (1999), 1 C.P.R. (4th) 99 at 111 (F.C.T.D.), aff'd. [2001] F.C.J. No. 3 (F.C.A.) (QL); Abbott Laboratories, Ltd. v. Nu-Pharm Inc. (1998), 83 C.P.R. (3d) 441 at 445 (F.C.A.); and Pharmacia Inc. v. Canada (Minister of National Health and Welfare) (1995), 60 C.P.R. (3d) 328 at pp. 339-343 (F.C.T.D.), aff'd 64 C.P.R. (3d) 450 (F.C.A.)).
[5] Furthermore, the proceedings contemplated by the Regulations are not designed to address or consider speculative suggestions about what might happen in the future. The process envisions a summary proceeding whereby a patent owner may deal with a specific assertion that the respondent will not presently infringe its patent by making, using, and selling the drug in question (Zeneca Pharma Inc. v. Canada (Minister of National Health and Welfare) (1996), 69 C.P.R. (3d) 451 at 453 (F.C.A.); Pharmacia Inc. v. Canada (1994) 58 C.P.R. (3d) 209 at 217 (F.C.A.); and Merck Frosst Canada Inc. v. Canada (1994), 55 C.P.R. (3d) 302 at 320 (F.C.A.).
[6] At issue in this case is H. Lundbeck A/S '368 Patent relating to citalopram.
[7] H. Lundbeck A/S is a pharmaceutical company that focusses solely on the treatment of central nervous system problems. Lundbeck Canada Inc. is the Canadian subsidiary of H. Lundbeck A/S of Denmark. Apotex is a Canadian generic pharmaceutical manufacturer seeking the issuance of a NOC from the Minister for the manufacturing and selling of citalopram tablets, for use in the treatment of depression, a prior art use.
[8] On August 16, 1991, H. Lundbeck A/S filed an application for the '368 Patent entitled Treatment of Cerebro-Vascular Disorders. The patent was granted on October 23, 2001, and will expire on August 16, 2011. It was listed on the Register on November 29, 2001. The '368 Patent covers the use of citalopram for the manufacture of a medicament for the treatment of cognitive disorders or amnesia associated with dementia and cerebro-vascular disorders (CVD). The '368 Patent also covers a pharmaceutical composition for the treatment of dementia or CVD comprising citalopram (the claimed uses).
[9] Claims 1 and 8 are relevant for this proceeding and read as follows:
1. Use of [citalopram] or a pharmaceutically-acceptable acid addition salt thereof, for the manufacture of a medicament for the treatment of cognitive disorders or amnesia associated with dementia and of cerebrovascular disorders.
8. A pharmaceutical composition or medicament for the treatment of dementia and cerebrovascular disorders comprising an amount of [citalopram] or a pharmaceutically-acceptable acid addition salt thereof, which is effective for such purpose, and a pharmaceutically-acceptable diluent or carrier.
[10] On December 17, 2001, Lundbeck received a NOA from Apotex whereby the latter claims no infringement to the '368 Patent. As for the legal and factual basis for the said allegation, Apotex asserts that its product is not intended for any of the claimed uses. More particularly, Apotex will not seek approval for its product for any such uses that would be included in the citalopram product monograph. Apotex further asserts that the only use that will be included in Apotex' product monograph will be use for the treatment of depression, a use well known and documented in the prior art (the unclaimed use).
[11] On January 28, 2002, alleging that claims 1 and 8 will be infringed, Lundbeck applied for an order in accordance with paragraph 6(1) of the Regulations prohibiting the Minister from issuing a NOC to Apotex in respect of 20 mg and 40 mg tablets of citalopram until after the expiration of the '368 Patent. Lundbeck has subsequently filed three affidavits, namely, the affidavits of Jeff MacLean, President and General Manager of Lundbeck Canada Inc., Dr. Kiran Rabheru, a geriatric psychiatrist, and Dr. Serge Gauthier, a neurologist. By their training, attested to by their resumes, and considering that their qualifications as experts were not challenged, Dr. Serge Gauthier and Dr. Kiran Rabheru qualify as expert witnesses.
[12] The facts are relatively simple. The '368 Patent contains a specific description of the drug, and a list of 21 claims. The novelty element in '368 Patent is the use of citalopram to treat dementia and CVD (the claimed uses). Citalopram is already known as an anti-depressant, as the patent itself states. In this case, it is undisputed that Apotex intends to manufacture and sell a drug containing citalopram.
[13] Citalopram is part of a class of pharmaceutical drugs called "selective serotonin reuptake inhibitors" (SSRI), a type of drug which has shown itself very useful in the treatment of depression and depressive illness. SSRI acts on the serotonic system, generally linked to mood, feelings of well-being, anxiety, and such. At the present time, Lundbeck is the only manufacturer of citalopram in Canada allowed to sell the product, which is marketed under the registered brand name Celexa®. Lundeck obtained a NOC for its product in tablets of 10 mg, 20 mg and 40 mg in February 1999. The NOC issued by the Department of Health specifies that Celexa® is to be used for the symptomatic relief of depressive illness. However, the NOC does not cover the uses of Celexa® claimed in the '368 Patent (i.e., treatment of senile dementia, CVD or any other disorder named in the patent claims).
[14] According to the specifications of the '368 Patent, senile dementia may be "senile dementia of any genesis such as neurodegenerative, traumatic, cerebrovascular, anoxic, etc., i.e. dementia of Alzheimer's type, multi-infarct dementia, or vascular dementia, etc.", while CVD are "brain damages caused by cerebral infraction, cerebral hemorrhage, cerebral arteriosclerosis, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or the like, e.g. ischemia, and the psychological and neurological sequel of such damages".
[15] In their affidavits, both Dr. Rabheru and Dr. Gauthier state that there are patients affected by both depressive illness and cognitive impairment due to dementia or CVD. According to Dr. Rabheru:
The relationship between depression and cognitive impairment is complex (1,2). A major depressive episode may precede the clinical manifestations of an irreversible dementia (3). Conversely depressive syndrome is common during the early stages of an established dementia (4). In Alzheimer's patients having dementia, major depression may occur in 15% of patients and less severe syndromes in 30%-40% of the demented population (5). Depression has been found to occur in approximately 25 % of patients with cerebrovascular disease (6) and 30-60% of stroke patients experience depression within 24 months of having a stroke (7). Thus, there is a clear overlap of patients being afflicted with both depressive illness and cognitive impairment due to dementia and/or cerebrovascular disorders.
(My emphasis)
[16] Dr. Gauthier agrees:
There is a wide range of prevalence figures in the published literature, but there is consensus that depression is more common in demented patients than the general population (Table 1) below.
[17] He also concludes:
There are sufficient data and biological plausibility to support a broader action of citalopram as an antidementia drug, above and beyond its original use as antidepressant.
(My emphasis)
[18] In view of the above evidence, Lundbeck argues that Apotex will directly infringe claims 1 and 8 of '368 Patent. In this regard, Lundbeck submits that whether or not Apotex intends to manufacture and sell its tablets for the patented uses is irrelevant. Accordingly, Lundbeck submits that infringement does not depend upon what Apotex intends to do but upon what it actually does. Since citalopram treats both depression and dementia or CVD, and since there is an overlap of patients affected with both depression and dementia or CVD, there will be direct infringement if a NOC were issued to Apotex. (AB Hassle v. Canada (Minister of National Health and Welfare) (2000), 9 C.P.R. (4th) 79 (F.C.T.D.) at 87; AB Hassle v. RhoxalPharma Inc., [2002] F.C.J. No. 1083 (T.D.) (QL); Zeneca Pharma Inc. v. Apotex Inc. (1995), 61 C.P.R. (3d) 190 (F.C.T.D.), rev'd on other grounds (1996), 69 C.P.R. (3d) 451 (F.C.A.); Computalog Ltd. v. Comtech Logging Ltd. (1992), 44 C.P.R. (3d) 77 at 88 (F.C.A.)).
[19] Apotex reiterates that it is not seeking approval for any use specific in the patent nor will it be included in their product monograph. The only use that will be included in their product monograph will be the treatment of depression, which was a prior art use. Adopting the position that Lundbeck's evidence does not support a conclusion of direct infringement, Apotex has chosen not to produce any evidence nor to cross-examine the affiants of Lundbeck. Since the allegations of fact in the NOA are to be considered true, except to the extent that the contrary has been shown by the applicants, Apotex invites the Court to dismiss the prohibition application on the basis that Lundbeck has not established, on a balance of probabilities, that issuing the NOC would result in an infringement of the '368 Patent.
[20] I have come to the conclusion that the present application must fail for the following reasons.
[21] First, I note that claim 1 of the '368 Patent claims the manufacture of a drug product containing citalopram for the claimed uses. Accordingly, if Apotex does not manufacture citalopram tablets for the claimed uses, but rather, manufacturers citalopram tablets solely for the unclaimed use, there can be no direct infringement of claim 1. Claim 8 is for the use of citalopram for the treatment of dementia or CVD, where citalopram is "effective" for such uses. Therefore, for Apotex's tablets to infringe claim 8, it must be established that both the "purpose" of the tablet is to be used for the treatment of dementia or CVD, and that the tablet is "effective" for such uses. Neither of the foregoing has been alleged, much less proven by Lundbeck in this proceeding. I conclude that there can be no direct infringement of claims 1 and 8 either by Apotex or by independent third parties, namely, patients.
[22] Second, there is no conclusive evidence to sustain Lundbeck's allegation of direct infringement:
• The statements made by Drs. Rabheru and Gauthier in their respective affidavits provide a rather academic perspective regarding the occurrence of dementia in depressed patients and the beneficial effects of citalopram, based on their review of some scientific literature concerning a wide variety of disorders, including depression, anxiety, psychotic symptoms, cognitive impairment, cerebrovascular dementia, behavioural and psychological symptoms of dementia (BPSD) and dementia of the Alzheimer's type.
• Both experts admit that the relationship between depression and cognitive disorder is "complex" and "poorly understood", and also admit that there is a "wide range" of figures regarding the prevalence of both ailments in patients in the published literature. In this regard, the figures advanced to support the "approximate incidence" of dementia and/or CVD among depressed patient populations in the affidavits do not state whether the depression and the dementia and/or CVD occurred simultaneously in patients or whether these were two ailments suffered by the patients over a prolonged period of time (for example, depression merely "preceded" or was merely a "prodrome" to the dementia or, perhaps, was completely unrelated to the dementia).
• Neither experts challenge the fact that citalopram will only be legally approved and indicated for the treatment of depression (the unclaimed use). Indeed, neither experts make any mention as to whether they, or any other physicians, would prescribe citalopram to patients suffering from both depression and dementia or CVD.
• Finally, Lundbeck has not produced surveys or other similar evidence to demonstrate the prescription habits of physicians, the frequency, if any, of physicians in failing to diagnose dementia or CVD in depressed patients, and the dispensation practices of pharmacists. This prove to be a fatal flaw in the Lundbeck's evidence.
[23] Third, the case law does not support Lundbeck's assertion of direct infringement. The decisions relied upon by Lundbeck are distinguishable on the basis that citalopram has already been used to treat depressive illness (the unclaimed use). Moreover, the overlap of patients affected with both depression and dementia or CVD does not suffice per se to establish direct infringement.
[24] In this respect, the present application is virtually the same as the one brought forward by Lundbeck against Genpharm Inc., which was dismissed by this Court on October 3, 2003 (H. Lundbeck A/S v. Canada (Minister of Health) 2003 FC 1145). In H. Lundbeck A/S, supra, Lundbeck produced the same evidence and made the same fundamental arguments as in the present application. Blais J. found Lundbeck's evidence inconclusive. Further, Blais J. dismissed Lundbeck's assertion of infringement on the basis that it was unfounded in law. In the present case, Lundbeck has not convinced me that this decision (which is presently appealed) is manifestly wrong nor that the Court failed to consider binding authorities which would have produced a different result (Glaxo Group Ltd. v. Canada (Minister of National Health and Welfare) (1995), 64 C.P.R. (3d) 65 at pp. 67-68 (F.C.T.D.); Apotex Inc. v. Merck & Co., [2002] F.C.J. No. 236 at para.12 (T.D.) (QL)).
[25] This Court and the Federal Court of Appeal decisions in AB Hassle v. Canada (Minister of National Health and Welfare) (2001), 213 F.T.R. 161 (T.D.), (2002), 22 C.P.R. (4th) 1 (F.C.A.) are relevant for this proceeding. Curiously, the applicant has chosen to rely on another decision, AB Hassle v. RhoxalPharma Inc. 2002 FCT 780 (Gibson J.), which dealt with the same issue but came to a different conclusion.
[26] In AB Hassle v. Canada (Minister of National Health and Welfare), supra, the applicants had alleged both direct and induced infringement. The patent at issue claimed a new use of a known compound, omeprazole. The claims of the patent were respectively directed to the use of omeprazole for the treatment of campylobacter infections, the manufacture of a medicament for such purpose, and a pharmaceutical preparation for the same use wherein the active ingredient was omeprazole. The generic manufacturer alleged that no claim for the medicine or the use of the medicine would be infringed, since its product would not be made, used or sold for the treatment of campylobacter infections. At trial, O'Keefe J. refused to issue the prohibition order because he was not satisfied that infringement, direct or indirect, had been established. He specifically held that, absent surveys of physicians' practices or other similar evidence, there was no evidence that physicians would prescribe Apotex' drug product for any of the unapproved patented use. Justice O'Keefe's decision was affirmed by the Federal Court of Appeal: (2002), 22 C.P.R. (4th) 1 (F.C.A.).
[27] That being said, I fully endorse the comments made by Blais J. in H. Lundbeck A/S, supra, with respect to the contrary decision rendered by Gibson in AB Hassle v. RhoxalPharma Inc., supra,which was rendered a few months before the Federal Court of Appeal decision in AB Hassle v. Canada (Minister of National Health and Welfare), supra.
[28] The present case is clearly distinguishable from the facts in Genpharm Inc. v. Procter & Gamble Inc., [2002] 20 C.P.R. (4th) 1 (F.C.A.); (2003) 26 C.P.R. (4th) 180 (T.D.). In any event, as stated by the Federal Court of Appeal in AB Hassle v. Canada (Minister of
National Health and Welfare), supra, at paragraph 56, Genpharm is not authority for the proposition advanced today by Lundbeck that "mere sale by a generic [manufacturer], without more, of a medicine subject to a use patent is sufficient to constitute infringement for the purpose of subpara. 5(1)(b)(iv) [of the Regulations]."
[29] In Genpharm Inc., supra, Proctor and Gamble (P & G) owned a patent for a new way of using an existing drug (a polyphosphonate, specifically, etidronate or etidronate disodium) in intermittent cycles in the treatment of osteoporosis. The use of plyphosphanates to inhibit bone loss was well known, but was not considered very useful in a chronic condition, such as osteoporosis because it also tendered inhibit bone formation. Genpharm proposed to sell its product both in 200 and 400 mg tablets, although P & G didronel, the equivalent in the market of Pajet's disease and hypercalcenia of malignancy, was only available in a 200 mg size. Contrary to the present proceeding, P & G had adduced abundant evidence in respect of Genpharm's intent, the product monograph, and the marketplace, including possible interchangeability with the referenced brand name drug product. Furthermore, in the present case, this Court is not aware in what dosages citalopram tablets would be prescribed for the claimed uses and the unclaimed use (depression).
[30] I further note that in Genpharm Inc., supra, the intermittent use of 400 mg tablets was approved, patented and protected. A NOC had been issued for that specific use. Issuing a NOC to Genpharm for similar tablets was likely to give rise to infringement. Hence, the Federal Court of Appeal had no difficulty to conclude that the evidence "overwhelmingly demonstrated that the actions and intentions of Genpharm would inevitably lead to an infringement" (AB Hassle v. Canada (Minister of National Health and Welfare), supra, at para. 18 (F.C.A.)). This is not the case here. In fact, Lundbeck has not even challenged Apotex' intentions nor its activities in respect of the approval and marketing of its drug. At the hearing, counsel for Lundbeck has suggested that the contraindications in Apotex' product monograph should have mentioned that its product was contraindicated in patients with Alzheimer's disease or CVD. Unfortunately, I cannot pronounce myself on the merit of this new argument who comes before this Court too late. It should not be entertained any further as this Court received no evidence with respect to any existing practice to mention patent restrictions as contraindications in a product monograph.
[31] Finally, Lundbeck's assertion that '368 Patent will be directly infringed is inconsistent with the purposes of the Regulations and also raises serious policy issues. If Lundbeck's proposed interpretation of the Regulations were correct, Lundbeck would be able to artificially extend its monopoly over the use and selling of the product simply because there is always the possibility that someone somewhere will use the drug for the prohibited, patented purpose. In doing so, generic manufacturers would effectively be barred from entering the market. Surely, this is not what is intended by the Regulations. Absent evidence of future infringement, and based solely on a mere theoretical future possibility of infringement, a generic manufacturer should not be kept off the market (AB Hassle v. Canada (Minister of National Health and Welfare), supra, at para. 57 (F.C.A.); Zeneca Pharma Inc. v. Canada (Minister of National Health and Welfare), supra, at pp. 453-54 (F.C.A.); SmithKline Beecham Inc. v. Apotex Inc., supra, at para. 40 (F.C.T.D.); and by analogy: Warner-Lambert Co. v. Apotex Corp., Apotex Inc., and Torpharm Inc., 2003 U.S. App. Lexis 594 (U.S. Ct. App. Fed. Cir.)). Therefore, properly construed, there can be no direct infringement to claims 1 and 8 to the aforesaid patent. With respect to indirect or "induced" infringement, Lundbeck has not raised this ground and is now barred from raising it at this late stage. In any event, Lundbeck has failed here to allege and prove the requisite elements of the test for induced infringement (AB Hassle v. Canada (Minister of National Health and Welfare), supra, at para. 68 (T.D.)).
[32] In conclusion, I reiterate that the '368 Patent makes no claim as to depression. Since that use was well established, it could not have been patented. Apotex has currently alleged that it will sell its citalopram tablets to pharmacists and wholesalers, not to patients, in accordance, and for, their approved use, namely, for the treatment of depression. There has been no suggestions that Apotex's NOA was inadequate or that it failed to address relevant patent claims. The allegations of fact in the NOA are true except to the extent that the contrary has been shown. In the case at bar, Lundbeck's allegations of infringement are purely speculative and are not supported by the evidence. Manifestly, Lundbeck has not proved, on a balance of probabilities that, if a NOC were issued to Apotex and it were to manufacture, market, or sell the aforesaid tablets, claims 1 and 8 of the '368 Patent would be infringed.
ORDER
THIS COURT ORDERS that the application requesting an Order in accordance with paragraph 6(1) of the Regulations, prohibiting the Minister from issuing a NOC to Apotex, be dismissed with costs in favour of Apotex. There will be no order as to costs, in favour of or against, the Minister.
__________________________________
Judge
FEDERAL COURT
NAMES OF COUNSEL AND SOLICITORS OF RECORD
DOCKET: T-135-02
STYLE OF CAUSE: H. LUNDBECK A/S and LUNDBECK CANADA INC. v. THE MINISTER OF HEALTH and APOTEX INC.
PLACE OF HEARING: MONTREAL
DATE OF HEARING: OCTOBER 21, 2003
REASONS FOR ORDER
AND ORDER: THE HONOURABLE MR. JUSTICE MARTINEAU
APPEARANCES:
Ms. Marie Lafleur FOR APPLICANTS
Mr. Martin Sheehan
Mr. Harry Radomski FOR RESPONDENT
Mr. Andrew Brodkin Apotex Inc.
SOLICITORS OF RECORD:
FASKEN MARTINEAU DuMOULIN LLP FOR APPLICANTS
Montreal, Quebec
GOODMANS LLP FOR RESPONDENT
Toronto, Ontario Apotex Inc.