Abbott Laboratories Limited. v. Canada (Ministry of National Health and Welfare)

Abbott Laboratories Limited. v. Canada (Ministry of National Health and Welfare)
Court (s) Database
Federal Court Decisions
Date
2006-11-21
Neutral citation
2006 FC 1411
File numbers
T-214-05
Decision Content
Date: 20061121
Docket: T-214-05
Citation: 2006 FC 1411
OTTAWA, ONTARIO, November 21, 2006
PRESENT: The Honourable Mr. Justice von Finckenstein
BETWEEN:
ABBOTT LABORATORIES LIMITED
TAP PHARMACEUTICALS INC.
Applicants
and
THE MINISTER OF HEALTH, NOVOPHARM LIMITED
and TAKEDA PHARMACEUTICAL COMPANY LIMITED
Respondents
REASONS FOR ORDER AND ORDER
[1] This is an application pursuant to s. 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 (“NOC Regulations”), for an Order prohibiting the Minister of Health from issuing a Notice of Compliance (“NOC”) under the Food and Drug Regulations, C.R.C. c. 870, to the Respondent, Novopharm Limited (“Novopharm”), with respect to Lansoprazole, 15 mg or 30 mg delayed-release capsules for oral administration until after the expiration of Canadian Patent 2,009,741 (the “741 Patent”).
[2] The Applicant, Abbot Laboratories Limited is a Canadian pharmaceutical company. TAP Pharmaceuticals Inc. (“TAP”), also an Applicant (collectively, “Abbott”), is a joint venture between Abbott and Takeda Pharmaceuticals Company Limited (“Takeda”). Takeda is the owner of the 741 Patent and TAP is a licensee of the patent. Abbott manufactures and markets a Lansoprazole composition under the trade name “PREVACID”.
[3] Lansoprazole itself is a known compound used to treat excess gastric acid secretions. The patent for the Lansoprazole compound, Canadian Patent 1,255,314, (the “314 Patent”), was also owned by Takeda but, expired on June 6, 2006. The use of Lansoprazole to treat excess gastric secretions is referred to as the “old use”.
[4] The 714 patent is a patent for the use of Lansoprazole as an antibacterial agent to treat and prevent infectious diseases caused by a bacterium now called Helicobacter pylori (also known as H. pylori) (formerly called Campylobacter pylori) which hereinafter is referred to as the “new use”. The NOC for the new use of Lansoprazole under the brand name PREVACID was issued to Abbott on April 7, 1998.
[5] Novopharm seeks the issuance of a NOC to allow it to produce a generic version of the 15 mg and 30 mg Lansoprazole. Novopharm intends to market the capsules under the name of “Novo-Lansoprazole”, a drug that is bioequivalent and therapeutically equivalent to PREVACID, but it will be marketed for the old uses only.
[6] To that end Novopharm in its Notice of Allegation (“NOA”), dated December 21, 2004, states:
The Novopharm Formulation will not infringe any of the claims of the ‘741 Patent because it will not be made, constructed, used or sold as an antibacterial composition or for the treatment or prevention of Helicobacter pylori infections. Novopharm is not seeking approval for the use of the Novopharm Formulation as an antibacterial composition or for the treatment or prevention of Helicobacter pylori infections and no such use will be included in our labeling and Product Monograph.
(Affidavit of Sonia Atwell, AR, Vol. 1, Exhibit “D”)
[7] Abbott in response started this application alleging, in essence, that infringement will occur as:
(a) Novopharm’s Product Monograph (“PM”) for Novo-Lansoprazole will encourage and promote the use of Novo-Lansoprazole for the treatment of ulcers caused by H. pylori;
(b) Novopharm’s labelling advocates a dosage regime that can only be used for the treatment of ulcers caused by H. pylori; and
(c) Novopharm’s sales and marketing strategy is designed to encourage and promote the use of Novo-Lansoprazole for the treatment of ulcers caused by H. pylori.
Issue
[8] There is no allegation of invalidity in this case, accordingly there is only one issue in this case, namely:
Is Novopharm’s allegation (that its proposed product Novo-Lansoprazole will not be “used or sold as an antibacterial composition or for the treatment or prevention of Helicobacter pylori infections”) justified?
Applicable Jurisprudence
[9] The jurisprudence regarding NOC’s is extensive. It is best set out by Justice Stone in Hoffman-La Roche Ltd. v. Canada (Minister of National Health & Welfare) (1996), 205 N.R. 331 at paragraph 8:
It seems to me that the core guidance of these decisions, insofar as it is applicable to the case at bar, may be summarized as follows:
1. Applications made pursuant to subsection 6(1) of the Regulations are governed by the procedural rules contained in Part V.1 of the Federal Court Rules, C.R.C. 1978, c. 663 -- "Applications for Judicial Review". Bayer AG, supra, per Mahoney J.A., at page 336;
2. The initiator of a section 6 proceeding, being the person having the carriage of the litigation, bears "the initial burden of proof" which is a difficult burden because "it must be to disprove some or all of the allegations in the notice of allegation which, if left unchallenged, would have allowed the Minister to issue a notice of compliance". Merck Frosst, supra, per Hugessen J.A., at page 319;
3. This burden, known in a civil case as either the "persuasive burden" or the "legal burden", is the burden of establishing a case to the civil standard of proof. By contrast, the "evidential burden" consists of the burden of putting an issue in play and means that a party has the responsibility to ensure that there is sufficient evidence of the existence or non-existence of a fact or an issue on the record to pass the threshold for that particular fact or issue. Nu-Pharm, supra, per Stone J.A., at page 33 [p. 16].
4. Where the notice of compliance of a second person alleges non-infringement, the court should start from the proposition that "the allegations of fact in the notice of allegation are true except to the extent that the contrary has been shown by the applicant". Merck Frosst, supra, per Hugessen J.A., at page 319;
5. In determining whether or not the allegations are "justified" "the court must then decide whether, on the basis of such facts as have been assumed or proven, the allegations would give rise in law to the conclusion that the patent would not be infringed by the respondent". Merck Frosst, supra, per Hugessen J.A., at page 319;
6. The Minister's decision of whether to issue a notice of compliance must turn on whether the allegations of the second person are "sufficiently substantiated to support a conclusion for administrative purposes ... that the applicant's patent would not be infringed if the generic's product is put on the market". Pharmacia, (Court File No. A-332-94) supra, per Strayer J.A., at page 216;
7. Where second persons fail to file notices of allegation or adequate notices of allegation they "must assume their own risk when it comes to attacks on the adequacy of such allegations once prohibition proceedings are commenced". Bayer AG, (Court File No. A-669-93) supra, per Strayer J.A., at page 134.
8. The requirement in paragraph 5(3)(a) of the Regulations that a second person provide a detailed statement "seems intended ... [to make] the patentee ... fully aware of the grounds on which the applicant seeks issuance of a NOC [that will not lead to infringement of the patent] before the patentee decides [page456] whether or not to apply to a court for a determination. Such disclosure would define the issues at a very early stage." Bayer AG, (Court File No. A-389-93) supra, per Mahoney J.A., at pages 337-338;
9. A bald statement of non-infringement in a detailed statement without any factual assertion in support thereof does not meet the requirements of subparagraph 5(1)(b)(iv) of the Regulations. Nu-Pharm, supra, per Stone J.A., at pages 41-42 [pp. 19-20];
10. A common law presumption that a second person's process would infringe the patent applies where: that person has asserted no facts to support his allegation of non-infringement; the evidence of non-infringement lay peculiarly within his knowledge; no evidence of non-infringement has been presented by that person; and the first person has no other available means of accessing such evidence. Nu-Pharm, supra, per Stone J.A., at page 45 [p. 20].
Findings Required
[10] As Novopharm made allegations of non-infringement in this case, it is inherent in a decision to grant a prohibition order that the Court form the view that Novopharm's allegations are not justified. Conversely, if the Court refuses to grant a prohibition order, it must have come to the conclusion that Novopharm’s activities would not infringe.
[11] Abbott’s allegation of infringement are based on subparagraph 5(1)(b)(iv) of the NOC Regulations which reads as follows:
5.(1) Where a person files or has filed a submission for a notice of compliance in respect of a drug and compares that drug with, or makes reference to, another drug for the purpose of demonstrating bioequivalence on the basis of pharmaceutical and, where applicable, bioavailability characteristics and that other drug has been marketed in Canada pursuant to a notice of compliance issued to a first person and in respect of which a patent list has been submitted, the person shall, in the submission, with respect to each patent on the register in respect of the other drug,
(a) state that the person accepts that the notice of compliance will not issue until the patent expires; or
(b) allege that
(i) the statement made by the first person pursuant to paragraph 4(2)(c) is false,
(ii) the patent has expired,
(iii)the patent is not valid, or
(iv) no claim for the medicine itself and no claim for the use of the medicine would be infringed by the making, constructing, using or selling by that person of the drug for which the submission for the notice of compliance is filed.
5.(1) Lorsqu'une personne dépose ou a déposé une demande d'avis de conformité pour une drogue et la compare, ou fait référence, à une autre drogue pour en démontrer la bioéquivalence d'après les caractéristiques pharmaceutiques et, le cas échéant, les caractéristiques en matière de biodisponibilité, cette autre drogue ayant été commercialisée au Canada aux termes d'un avis de conformité délivré à la première personne et à l'égard de laquelle une liste de brevets a été soumise, elle doit inclure dans la demande, à l'égard de chaque brevet inscrit au registre qui se rapporte à cette autre drogue :
(a) soit une déclaration portant qu'elle accepte que l'avis de conformité ne sera pas délivré avant l'expiration du brevet;
(b) soit une allégation portant que, selon le cas :
(i) la déclaration faite par la première personne aux termes de l'alinéa 4(2)c) est fausse,
(ii) le brevet est expiré,
(iii) le brevet n'est pas valide,
(iv) aucune revendication pour le médicament en soi ni aucune revendication pour l'utilisation du médicament ne seraient contrefaites advenant l'utilisation, la fabrication, la construction ou la vente par elle de la drogue faisant l'objet de la demande d'avis de conformité.
[12] There has been considerable jurisprudence about the meaning of subparagraph (iv) and whether infringement by third parties can be attributed to the generic producer (the second person) or whether it has to be induced, procured or otherwise be linked to the generic producer. The recent case of Pharmascience Inc v. Sanofi-Adventis Canada Inc., [2006] F.C.A. 229 puts an end to that debate when Madame Justice Sharlow stated:
54 The interpretive principle from Biolyse weighs against an interpretation of the NOC Regulations that assumes that they are intended to prevent all patent infringement. Biolyse is more consistent with an interpretation of the NOC Regulations that assumes that they are intended to prevent only infringement by (or infringement induced or procured by) generic drug producers who make abbreviated new drug submissions containing one of the stipulated comparisons to an existing drug product.
55 I turn now to the relevant words of subparagraph 5(1)(b)(iv) of the NOC Regulations, which sets out the required contents of a non-infringement allegation. It states that in a non-infringement allegation, the generic drug producer must allege that:
o ... no claim for the medicine itself and no claim for the use of the medicine would be infringed by the making, constructing, using or selling by that person of the drug for which the submission for the notice of compliance is filed.
* * *
o ... aucune revendication pour le médicament en soi ni aucune revendication pour l'utilisation du médicament ne seraient contrefaites advenant l'utilisation, la fabrication, la construction ou la vente par elle de la drogue faisant l'objet de la demande d'avis de conformité.
56 Pharmascience argues that the words "by that person" means that this provision refers only to acts of Pharmascience that would constitute infringement of the 457 patent (which I understand would include acts of Pharmascience that induce or procure infringement by others). Aventis argues that subparagraph 5(1)(b)(iv) is capable of being read more broadly, and should be read more broadly, so that it includes any infringement by anyone of the 457 patent that results in any way from the issuance of a notice of compliance to Pharmascience.
57 In my view, the interpretation proposed by Pharmascience is more consistent with the ordinary grammatical meaning of subparagraph 5(1)(b)(iv) of the NOC Regulations, and is also more consistent with the legislative scheme and purpose. Subsection 55.2(4) of the Patent Act and by extension the NOC Regulations are intended to prevent patent infringement by Pharmascience, not by patients.
58 The narrower interpretation proposed by Pharmascience is also more consistent with the general scheme of the Patent Act. The bargain represented by the 087 patent permits anyone to use the patented invention (that is, to make ramipril using one of the claimed processes) once the term of that patent expired in November of 2002. If Pharmascience is now prevented from obtaining a notice of compliance for its ramipril capsules for use in the treatment of hypertension only because the inevitable result is infringement of the 457 patent by patients who use the Pharmascience product for the treatment of cardiac insufficiency, the practical result will be an artificial extension of the monopoly represented by the now expired 087 patent. I do not believe that Parliament intended the NOC Regulations to permit such a result.
(Underlining added)
[13] From this I take it that in order for Abbott to succeed it has to prove on a balance of probabilities that infringement (by Novopharm or infringement by others induced or procured by Novopharm) will occur.
[14] In addition the NOC Regulations have been recently revised and came into force on October 5, 2006. The new subparagraph now reads:
(iv) no claim for the medicinal ingredient, no claim for the formulation, no claim for the dosage form and no claim for the use of the medicinal ingredient would be infringed by the second person making, constructing, using or selling the drug for which the submission is filed.
(iv) elle ne contreferait aucune revendication de l'ingrédient médicinal, revendication de la formulation, revendication de la forme posologique ni revendication de l'utilisation de l'ingrédient médicinal en fabriquant, construisant, utilisant ou vendant la drogue pour laquelle la présentation est déposée.
[15] With this jurisprudence in mind I will now address the facts of this case.
Construction of Patent
[16] The first step in a case dealing with alleged infringement is a construction of the patent in issue. The patent at issue is the 741 patent. The 741 Patent, entitled “Selective Antibacterial Agent”, contains 34 claims and concerns a new use of the Lansoprazole compound. It was issued on March 23, 1999, and will expire February 9, 2010. The parties agree that the only claims in issue here are claims 1 and 16.
[17] Claim 1 reads:
An antibacterial composition which contains an antibacterial effective amount of compound of the formula:
(wherein R1 stands for hydrogen, methoxy or trifluoromethyl; R2 and R3, being the same or different from each other, stand for hydrogen or methyl; and R4 stands for optionally substituted hydrocarbon residue and n denotes 0 or 1), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
Claim 16 reads:
A use for preventing or treating infectious diseases caused by the genus Campylobacter, of a compound of the formula:
(wherein R1 stands for hydrogen, methoxy or trifluoromethyl; R2 and R3, being the same or different from each other, stand for hydrogen or methyl; and R4 stands for optionally substituted hydrocarbon residue and n denotes 0 or 1), or a pharmaceutically acceptable salt thereof.
[18] The principles of patent claim construction have been stated by Justice Binnie in Free World Trust v. Électro-Santé Inc., [2000] 2 S.C.R. 1024 and Whirlpool Corp. v. Camco Inc., [2000] 2 S.C.R. 1067. These principles have been succinctly summarized by Harrington J. in Biovail Pharmaceuticals Inc. v. Canada (Minister of National Health and Welfare), 2005 FC 9 at paragraph 15, 267 F.T.R. 243:
1. A patent is construed as a bargain between the inventor and the public. In consideration of disclosing the invention, the inventor is given a temporary monopoly to exploit it.
2. It is a statutory requirement that the patent contain a specification and end with a claim or claims "defining distinctly and in explicit terms the subject-matter of the invention for which an exclusive privilege or property is claimed". The specification must be sufficiently full, clear, concise and exact "as to enable any person skilled in the art or science to which it pertains, or to which it is most closely connected, to make, construct, compound or use it". (Patent Act, R.S.C. 1985, c. P-4, as amended, s. 27)
3. The patent is notionally addressed to a person skilled in the art or science of the subject-matter and is to be read as such a person would have read it when it first became public. …
4. The claims are to be read in an informed and purposive way to permit fairness and predictability and to define the limits of the monopoly "[I]ngenuity of the patent lies not in the identification of the desired result but in teaching one particular means to achieve it. The claims cannot be stretched to allow the patentee to monopolize anything that achieves the desired result" (Free World Trust, paras. 31, 32).
5. The claim portion of the patent specification takes precedence over the disclosure portion in the sense that the disclosure is read to understand what was meant by a word in the claims "but not to enlarge or contract the scope of the claim as written and thus understood" (Whirlpool, para. 52).
6. It is only such novel features that the inventor claims to be essential that constitute the "pith and marrow" of the claim. "The key to purposive construction is therefore the identification by the Court with the assistance of the skilled reader, of the particular words or phrases in the claims that describe what the inventor considered to be the "essential" elements of his invention" (Whirlpool, para. 45).
7. Some elements of the claimed invention are essential and others are not, based either on common knowledge when the patent was published or according to the intent of the inventor, expressed or inferred from the claims. …
8. To overclaim is to lose everything. If the inventor underclaims, the court will not broaden the monopoly in the interests of the "spirit" thereof. This often, as in this case, results in layers of claims, each limitation serving as a potential safety net so that if the broadest claims fall, the monopoly may be saved in part by the more modest claims.
9. Yet a patent is not an ordinary writing. It meets the definition of a "regulation" in the Interpretation Act, and must be read to assure the attainment of its objects. "Claims construction is a matter of law for the judge, and he was quite entitled to adopt a construction of the claims that differed from that put forward by the parties." (Whirlpool, supra, paragraph 52 [61].)
[19] There is no dispute between the parties that the patent should be interpreted by reference to the state of the art as it existed in 1990. Further, the parties agree that the appropriate person skilled in the art would be a physician; someone who has an undergraduate level understanding of chemistry, has a medical degree and has completed an internship, with some exposure to clinical gastroenterology.
[20] As experts, the parties put forward the witnesses listed in Annex 1. None of the experts have been challenged as to their expertise and I see no reason to question their credentials. I accept their testimony except to the extent qualified in these Reasons.
[21] There is no dispute as to claim 1. It is simply a claim for a new use of the old Lansoprazole composition, namely as an effective antibacterial compound. This is different from the 314 patent which claimed the use of Lansoprazole as an inhibitor against excess acid secretions.
[22] However with respect to claim 16 Novopharm contends that it should be read:
(a) as a new use for Lansoprazole as an antibacterial agent against H. pylori; and
(b) as a claim for the use Lansoprazole alone. It should not be constructed to include a claim for the use of Lansoprazole in combination with other drugs.
Abbott on the other hand contends that it should be read as:
(a) a claim for the use of Lansoprazole against infectious diseases caused by H. pylori, and
(b) a claim for Lansoprazole alone or in conjunction with other drugs.
[23] Point a) is conclusively dealt with by the testimony of Abbott’s witness, Dr. Armstrong, who observed:
27. In 1990 there were no data, and there are none today, to support any suggestion that taking Lansoprazole can prevent a patient from acquiring an H. pylori infection. This is an important medical fact which given background to the meaning of “treating and preventing”. No person of ordinary skill in the art, reading the patent in 1990, would have concluded that Lansoprazole was being described for use in preventing an H. pylori infection. For this reason, among others, such a person would also understand, necessarily, that claim 16 cannot be directed at preventing or treating H. pylori infections (as Dr. Graham has it) but is clearly directed at preventing the diseases that such infections cause – ulcers.
28. A person with ordinary skill in the art reading the patent as a whole would understand that the invention relates to the antibacterial ability of Lansoprazole to prevent the diseases caused by H. pylori and that it is not limited to eradication of H. pylori or directed to the prevention of H. pylori infections from occurring.
(Reply Affidavit of Dr. David Armstrong, AR, Vol III at 527.)
[24] This interpretation is also supported by the plain meaning of the claim and gives significance to the words “diseases caused by” used in claim 16 while the interpretation put forward by Dr. Graham, Novopharm’s expert ignores them. Further support for this interpretation can also be found in Lilly ICOS LLC v. Pfizer Ltd. 59 BMLR 123 at paragraph 43. The Court will therefore adopt Dr. Armstrong’s interpretation. The significance of the reference to diseases will become obvious during the following discussion of the product monogram (“PM”) for Novo-Lansoprazole.
[25] As to point b) I see nothing in either claim that imports a limitation that Lansoprazole has to be used alone. We know from Whirlpool, supra as quoted in Biovail, supra that:
The claim portion of the patent specification takes precedence over the disclosure portion in the sense that the disclosure is read to understand what was meant by a word in the claims "but not to enlarge or contract the scope of the claim as written and thus understood" (Whirlpool, paragraph 52 [61]).
[26] Thus, even if there was a limitation implicit or explicit in the disclosure, it could not be imported into the claims. Drugs often are not administered in a pure state but mixed with an excipient or other drugs and the use of such drugs would be highly restricted if the mention of a use of a drug would be read as implying it has to be used alone. Unless the use claimed specifically employs such words as “alone” or “not in conjunction with other compounds” it would be improper to read such a limitation into the claim. Abbott’s expert, Dr. Fass stated:
55. The disclosure of the patent teaches the Lansoprazole exhibits antibacterial activity against H. pylori and can therefore be used to treat or prevent infectious diseases caused by H. pylori. This would be understood by a person skilled in the art (as defined below) to refer to the use of Lansoprazole either alone or in combination to treat or prevent the infectious diseases caused by H. pylori.
(Affidavit of Ronnie Fass, M.D., Applicant’s Record, Vol. III.)
[27] And more explicitly under cross-examination, Novopharm’s expert, Dr. Fred Saibil, stated:
Q. There is nothing in the patent claims that would exclude the use of Lansoprazole in patients who are taking other medications at the same time?
A. That’s correct.
(Cross-examination of Dr. Fred Saibil, Respondent’s Record, Vol. VI at 1136)
[28] Only Novopharm’s expert Dr. Graham suggested in paragraph 92 of his affidavit:
92. As at the Relevant Date, a person skilled in the art would understand the ‘741 Patent to be claiming the use of Lansoprazole, on its own, for the intentional eradication of H. pylori infectious diseases.
(Affidavit of Dr. David Y. Graham, Respondent’s Record, Vol. I.)
[29] Other than Dr. Graham, there was no evidence presented to contradict the contentions of Dr. Fass and Dr. Saibil. While Dr. Graham may be a great expert on H. pylori, the Court is not persuaded by his approach to patent construction. Accordingly, the Court will not read any limitation into claim 16. With this interpretation of claim 16, as suggested by Abbott, in mind let us then turn to the three contentions of Abbott.
Uncontested facts
[30] After reading the affidavits of both sides and the relevant cross-examinations the Court found that the experts of both sides basically agree on the following facts:
- Lansoprazole is a proton pump inhibitor (PPI) and is used for the prevention or treatment of patients with H. pylori infections among other indications. It is sometimes used either by itself (“monotherapy”) or with another medicine (“dual therapy”) or as a part of a combination therapy along with two antibiotics for eradicating H. pylori (“triple therapy”). Triple therapy is the gold standard in the treatment of infectious diseases caused by H. pylori. (See Affidavit of Dr Armstrong, AR, Vol III at paragraph 100, Affidavit of Dr Graham, RR, Vol. I at paragraph 69.)
- PREVACID, Abbott’s trade name for Lansoprazole, is used in Canada roughly in the following percentages:
(a) GERD – 52%
(b) Dyspepsia/Heartburn – 29%
(c) Peptic Ulcer – 4%
(d) NSAID – induced ulcer – 3%
(e) Other – 12%
(Affidavit of Dr. Armstrong, AR, Vol. III at paragraph 91.)
- There are three major causes of ulcers:
o H. pylori , causes approximately 90% of duodenal ulcers and approximately 80% of gastric ulcers ,
o Nosteroidal Anti-inflammatory Drugs ( NSAID); and
o Zollinger-Ellison Syndrome and other hypersecretroy states.
Other causes of ulcers, while extremely rare, exist.
(See Affidavit of Ronnie Fass, M.D., Affidavit of Dr. David Y. Graham, Affidavit of Dr. David Armstrong, Compendium of the Applicants; and the Transcript on Cross-examination of David Y. Graham dated June 2, 2006, Compendium of the Respondent, Novopharm Limited.)
Product Monograph
[31] Abbott contends there will be infringement of claim 16 as the PM of the proposed Novo-Lansoprazole will induce physicians to prescribe Novo-Lansoprazole for triple therapy.
[32] The product monograph (“PM”) for Novo-Lansoprazole provides:
SUMMARY PRODUCT INFORMATION
Route of
Administration
Dosage Form/
Strength
Clinically Relevant
Non-medicinal Ingredients
oral, delayed
Release
15 mg and 30 mg capsules
None
For a complete listing see Dosage Forms, Composition and Packaging section.
INDICATIONS AND CLINICAL USE
Adults
NOVO-LANSOPRAZOLE (Lansoprazole delayed-release capsules) is indicated in the treatment of the following conditions where a reduction of gastric acid secretion is required:
· Duodenal ulcer
· Gastric ulcer
· Reflux esophagitis including patients with Barrett’s esophagus, and patients poorly responsive to an adequate course of therapy with histamine H2-receptor antagonists.
· Healing of NSAID-Associated Gastric Ulcer, treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. (Controlled studies did not extend beyond 8 weeks).
· Reduction of Risk of NSAID-Associated Gastric Ulcers in patients with a history of gastric ulcers who require to continue taking a NSAID. (A controlled study did not extend beyond 12 weeks).
· Gastroesophageal reflux disease (GERD); treatment of heartburn and other symptoms associated with GERD.
· Pathological hypersecretory conditions including Zollinger-Ellison Syndrome.
(See DOSAGE AND ADMINISTRATION)
[33] While the record does not contain a PM of PREVACID, the Canadian Compendium of Pharmaceuticals Specialties 2006 (“CCPS”) provides the following reference for PREVACID:
SUMMARY PRODUCT INFORMATION
Route of
Administration
Dosage Form/
Strength
Clinically Relevant
Non-medicinal Ingredients
Oral
Capsules 15 mg, 30 mg
Cellulosic polymers, colloidal silicon dioxide, gelatin, magnesium carbonate, methacrylic acid, copolymer, starch, talc, sugar spheres, sucrose, polyethylene glycol, polysorbate 80, and titanium dioxide. Contains also the following dyes, D&C Red No.28, FD&C Blue No.1, FD&C Green No.3 (15 mg capsules only) and FD&C Red No.40.
Tablets 15 mg, 30 mg
Lactose monothydrate, microcrystalline cellutose, magnesium carbonate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, titanium dioxide, talc, mannilol, methacrylic acid, polyacrylate, polyethylene glycol, glyceryl monostearate, polysorbate 80, methyl citrate, ferric oxide, citric acid, crospovidone, aspartame, strawberry flavour and magnesium stearate. May also contain soya, lecithin
Intravenous
Lyophilized powder for reconstitution, 30 mg
Mannitol, meglumine, and sodium hydroxide. For a complete listing see Dosage Forms, Composition and Packaging.
Indications and Clinical Use: Note: When used in combination with antimicrobials for the eradication of H. pylori, the product monograph for those agents should be consulted.
Oral Administration: Adults: PREVACID (Lansoprazole delayed-release capsules), and PREVACID Fas Tab (Lansoprazole delayed-release tablets) are indicated in the treatment of conditions where a reduction of gastric acid secretion is required, such as:
1. Duodenal ulcer;
2. Gastric ulcer;
3. Reflux esophagitis including patients with Barrett’s esophagus, and patients poorly responsive to an adequate course of therapy with histamine H2 receptor antagonists;
4. Healing of NSAID-Associated Gastric Ulcer, treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. (Controlled studies did not extend beyond 8 weeks).
5. Reduction of Risk of NSAID-Associated Gastric Ulcers in patients with a history of gastric ulcers who require to continue taking a NSAID. (A controlled study did not extend beyond 12 weeks).
6. Symptomatic Gastroesophageal reflux disease (GERD); treatment of heartburn and other symptoms associated with GERD.
7. Pathological hypersecretory conditions including Zollinger-Ellison Syndrome. (See Dosage and Administration)
8. Eradication of H. pylori.
(AR Vol VIII p.1737)
The PM for Novo-Lansoprazole evidently mirrors the indication and clinical use of PREVACID’s as found in the CCPS, except for the addition of number 8 in PREVACID (“Eradication of H. pylori”).
[34] Novopharm argues that:
(a) there is no reference to H. pylori in its PM and therefore it does not induce or encourage infringement of the 741 patent;
(b) The Novopharm PM reflects the fact that Novopharm is only asking for an NOC regarding the old use of Lansoprazole; and
(c) The reference to H. pylori was deliberately left out. While H. pylori may cause 90% or duodenal ulcers and 80 % of gastric ulcers there are other causes of duodenal or gastric cancers and these are the ulcers the first two bullets refer to. They can’t be read to refer to H. pylori caused infections as these were specifically referred to in the last bullet of the CCPS reference for PREVACID, which was dropped from Novo-Lansoprazole’s PM.
[35] Abbott points out that Novopharm’s PM is, for all intents and purposes, identical to the reference for PREVACID in the CCPS. Like PREVACID’s reference, it refers to duodenal and gastric ulcers. Most duodenal or gastric ulcers are caused by H. pylori. The treatment for ulcers caused by H. pylori is triple therapy (a PPI (such as Lansoprazole) and 2 antibiotics). The Novopharm PM, given its prominent reference to duodenal and gastric ulcers will encourage or induce physicians to prescribe Novo-Lansoprazole for triple therapy. If Novopharm really intended to only target the old use market for Lansoprazole, i.e. gastric acid secretions, GERD and ulcers caused by Zollinger-Ellison Syndrome, NSAID’s or extremely rare other causes, it would have either left out the first two bullets or added after the first two bullets the words “other than ulcers caused by H. pylori”.
[36] The case law establishes that the PM ‘plays a key role …by providing the Court with an indication of the intentions of the generic company and the likelihood of infringement’ (see A.B Hassle v. Canada (Minister of Health and Welfare) (2002), 22 C.P.R. (4th) 1 at paragraph 55 per Sexton J.A).
[37] The experts from both sides agree that the ‘gold standard for treating ulcers caused by H. pylori would be triple therapy. Dr. Graham, the star witness for Novopharm, in his affidavit even went so far as to point out the dangers of monotherapy for H. pylori caused ulcers.
123. As at the Relevant Date, in context of the ‘741 Patent, the person skilled in the art knew that “preventing and treating” an H. pylori infection meant eradicating the H. pylori and that “an antibacterial effective amount” meant an amount that would eradicate the H. pylori.
124. Lansoprazole monotherapy does not eradicate H. pylori in vivo.
125. Due to the potential increased risk of gastric cancer, and the known lack of success, it would be foolish, dangerous and potentially negligent to prescribe Lansoprazole monotherapy to treat H. pylori.
(Affidavit of Dr. David Y. Graham, RR, Vol. I at 151.)
[38] Physicians prescribing medication for triple therapy can do so by either prescribing what is called an HpPAC (a separately identified package of drugs having its own Drug Identification Number and containing a PPI and two antibiotics) or prescribing the three compounds separately. The practice depends on the individual physician. The PM, which is addressed at physicians and pharmacists, has to be read through their eyes. The issues raised in this application only come into play when the three drugs are prescribed separately.
[39] Under cross-examination regarding the Novopharm PM and how a physician would interpret it in a situation where he had diagnosed an ulcer caused by H. pylori, Dr Graham observed the following:
Q. All right. If they look at the monograph which Novopharm wants to have approved by Health Canada, they would find that the Lansoprazole product is approved to treat a gastric ulcer. Correct?
A. They would find that.
Q. And the monograph says to the physician reading it that they can treat this ulcer with Lansoprazole monotherapy. Correct?
A. Well, that would hopefully not be what the physician would come away with.
Q. They would come away with some different conclusion?
A. Well, they have just diagnosed the presence of H. pylori infection –
Q. Okay.
A. – and an ulcer. They would make the presumptive diagnosis that that ulcer was caused by the H. pylori – may or may not be – and their next decision would be how to treat the H. pylori infection, so the ulcer would become less important or irrelevant, so they could chose any therapy for that. And then afterwards, because it’s a gastric ulcer, then they may decide to continue treatment until complete heal –
Q. All right.
A. – or may not.
Q. According to your view of the matter, they would be obliged, though having diagnosed the H. pylori, to treat it. Correct?
A. To treat the H. pylori.
Q. And the only acceptable treatment, in your view, would be eradication. Correct?
A. Well, that’s how you treat H. pylori.
Q. And so the person who looks at the Lansoprazole – Novo-Lansoprazole monograph wants to treat this ulcer, wants to treat this patient, would understand that in addition to the use of Lansoprazole, they would have to use probably two other antibiotics.
A. They would use some – Yeah. They would use probably –
Q. Gold standard.
A. – or four drugs, right.
Q. The first line treatment gold standard today would probably be two other antibiotic drugs. Correct?
A. That would be one of the options, yes.
Q. So a person reading that monograph, although they see the treatment of the ulcer as indicated for Novo-Lansoprazole, would understand that they have to actually use the Novo-Lansoprazole with two antibiotic drugs.
A. They would recognize that they would have to – They would use – If they’d chose that PPI –
Q. Right.
A. – for whatever reason –
Q. Assume that.
A. – that that would then be given with two other antibiotics.
(Cross-examination of Dr. David Y. Graham, AR, Vol. VI at 1030-32)
[40] Admittedly, Dr. Graham also points out that: a) physicians rarely look at a PM when making a prescription; and b) that a pharmacist might, when filling out the prescription, note that Novo-Lansoprazole has no indication for triple therapy use. This however, does not detract from the fact that the Novopharm PM is set up in such a way that, by his own admission, it can be seen to be a prescription of Novo-Lansoprazole for triple therapy which would be an encouragement to infringe claim 16 of the 741 patent.
[41] Given the expert testimony that ulcers caused by something other than H. pylori, NSAID’s or Zollinger-Ellison Syndrome are extremely rare, it is hard to understand why the reference to duodenal and gastric cancer is on the Novopharm PM and why it occupies the first two bullets.
[42] Accordingly, I find, based on the testimony of Novopharm’s most renowned witness, that on a balance of probabilities the Novopharm PM would induce a physician to prescribe Novo-Lansoprazole for a triple therapy to fight H. pylori-caused infections.
Label
[43] The proposed label for Novo-Lansoprazole has the following side panel:
Side Panel
[44] The Adult dosage displayed “15 mg to 30 mg once or twice daily, for one to eight weeks” includes the standard dosage for triple therapy against ulcers caused by H. pylori, namely “30 mg twice daily for one week”. (See Affidavit of Dr. Arni Sekar, RR, Vol. II at 420; Affidavit of Dr. Fred Saibil, RR, Vol. II at 305.)
[45] Dr. Sekar, Novopharm’s expert witness under cross-examination admitted the following:
Q. And you understand that the dosing in the HpPAC is 30 milligrams of Lansoprazole b.i.d.?
A. That is right.
Q. For one week?
A. Yes.
Q. And you know of no other use of Lansoprazole which is clinically indicated for a single week; correct?
A. Correct.
Q. You know of no other use of Lansoprazole, according to the statements in the monograph anyway, requiring 30-milligram dosing b.i.d.; right?
A. You are talking about the monograph…
Q. Yes.
A. …or my opinion?
Q. The monograph.
A. Yes. It is different with the investigation of NCCP, which we maybe should go into it right now, non-cardiac chest pain. It is well-established practice that if you are not too sure whether the pain is coming from the esophagus or not, you put them on a b.i.d. regime of the PPI for a w