Ottawa, Ontario, April 26, 2007
PRESENT: The Honourable Madam Justice Mactavish
BETWEEN:
ABBOTT LABORATORIES LIMITED
Applicants
and
THE ATTORNEY GENERAL OF CANADA and
THE MINISTER OF HEALTH
Respondents
REASONS FOR JUDGMENT AND JUDGMENT
[1] By this application, Abbott Laboratories and Abbott Laboratories Limited (referred to collectively in this decision as “Abbott”) seek to judicially review a decision of the Minister of Health refusing to add Canadian Letters Patent No. 2,250,736 (the ’736 patent) to the Patent Register.
[2] Abbott says that in refusing to list ’736 patent on the Patent Register, the Minister erred by relying on irrelevant considerations, by making incorrect factual assumptions about how the food and drug approval system works, and by erroneously interpreting the Patented Medicines (Notice of Compliance) Regulations, SOR 93/133.
[3] For the reasons that follow, I am not persuaded that the Minister erred as alleged by Abbott. As a consequence, the application for judicial review will be dismissed.
Background
[4] On January 12, 1990, Abbott filed a New Drug Submission (“NDS”) for BIAXIN®. BIAXIN® is an antibiotic used in the treatment of mild to moderate infections caused by strains of designated micro-organisms. The primary active ingredient in BIAXIN® is clarithromycin.
[5] A Notice of Compliance was issued to Abbott on May 8, 1996, which identifies the product to which the NOC relates as “BIAXIN®”. The NOC further identifies the “Medicinal Ingredient(s)” as “Clarithromycin Film-Coated Tablets 250 mg”.
[6] Abbott subsequently filed a number of supplemental NDSs to allow it to market new dosage forms and strengths of clarithromycin under the BIAXIN® brand name, including BIAXIN® 125 mg/5 mL, BIAXIN® BID 500 mg and BIAXIN® XL500 mg, and obtained additional Notices of Compliance so as to permit it to do so.
[7] These subsequent NOCs all continue to identify the product name as “BIAXIN®”, and each identifies the Medicinal Ingredient(s) simply as “Clarithromycin”.
[8] On April 25, 2006, Abbott applied to have the ’736 patent listed on the Patent Register with respect to seven Supplementary New Drug Submissions (“SNDS”) relating to new dosage forms and strengths of clarithromycin sold under the BIAXIN® brand name.
[9] The ’736 patent claims compounds that are produced during the synthesis of clarithromycin, when certain solvents are used in that process. These compounds have chemical structures that are different from that of clarithromycin. One of these compounds is an oxime of erythromycin (the “Oxime”).
[10] According to Abbott, the Oxime is a “medicine”, in that it is an active pharmaceutical ingredient made in the process of synthesizing clarithromycin, which is contained in BIAXIN®.
[11] Abbott thus says that as Notices of Compliance have been issued for BIAXIN®, a drug containing the Oxime medicine, and given that the ’736 patent contains a claim to that medicine, it follows that the ’736 patent should be listed on the Patent Register in relation to BIAXIN®.
The Minister’s Provisional Decision
[12] By letter dated May 2, 2006, the Minister provisionally refused to list the ’736 patent in the Patent Register. In this regard, the relevant portion of the letter states:
The ’736 patent does not contain a claim to the medicine clarithromycin, or its use. Rather, the ’736 patent contains claims directed towards intermediate or derivative compounds which are not the medicine clarithromycin. Therefore, pursuant to the authority vested in the Minister of Health by subsection 3(1) of the Regulations, the ’736 patent will not be added to the Patent Register, subject to any written representations.
Abbott’s Further Submissions
[13] Representatives of Abbott met with the Associate Director of the Office of Patented Medicines and Liaison on July 21, 2006 to discuss this matter, and further written representations were provided by Abbott in a letter dated August 4, 2006.
[14] These representations included a summary of the opinion of Dr. Jerry Atwood, a Professor of Chemistry, who has experience in organic and pharmaceutical chemistry. It was Dr. Atwood’s view that the synthesis of clarithromycin will inevitably result in the production of clarithromycin, as well as the Oxime.
[15] Dr. Atwood was further of the view that the steps taken to purify the clarithromycin will not completely remove all of the Oxime, and that, as a result, some Oxime will inevitably be present in the final product.
[16] Finally, it was Dr. Atwood’s opinion that the Oxime had therapeutic value, and is thus a “medicine”.
The Minister’s Final Decision
[17] By letter to Abbott dated August 25, 2006, the Minister responded to Abbott’s written submissions, maintaining the position that the ’736 Patent was ineligible for listing on the Patent Register.
[18] In this regard, the Minister stated that the ’736 patent did not contain a claim for clarithromycin, or for the use of clarithromycin, as is required by paragraph 4(2)(b) of the PM(NOC) Regulations.
[19] In particular, the Minister disagreed with Abbott’s assertion that a “claim for a medicine itself” includes a single active ingredient or a combination of substances, and could include a product not identified in or approved by the NOC.
[20] In this regard, the Minister distinguished the decisions in Hoffmann-La Roche Ltd. v. Canada (Minister of National Health and Welfare) (1995), 67 C.P.R. (3d) 25 (F.C.A) and Eli Lilly Canada Inc. v. Canada (Minister of Health), 2003 FCA 24, [2003] 3 F.C. 140, 237 F.T.R. 160, which had been relied upon by Abbott. The Minister observed that in those cases, the medicine claimed corresponded with the medicine in the drug, which was not the case here.
[21] Moreover, the Minister was of the view that the only medicine that had been approved for use by the NOCs granted to Abbott with respect to its BIAXIN® products was clarithromycin, and not any derivatives, by-products or impurities which were not the medicine itself.
[22] The Minister observed that the medicine clarithromycin in the BIAXIN® product did not correspond with the medicine claimed in the ’736 patent, nor was it pharmaceutically equivalent to the medicine claimed in that patent. That is, a generic manufacturer with a drug containing the compounds claimed in the ’736 patent, would not be able to use BIAXIN® as the reference product.
[23] Ultimately, the Minister found that the Oxime derivative was not “the medicine”, and that only clarithromycin had been approved for use through the issuance of the NOC for BIAXIN®.
[24] The Minister concluded by saying that if Abbott chose to apply for a NOC for the ’736 Patent, it could be added to the Patent Register at that time, subject to the provisions of the PM(NOC) Regulations.
[25] As a consequence, the Minister refused to list the ’736 patent on the Patent Register. It is this decision that Abbott now seeks to judicially review.
Legislative Regime
[26] In order to put Abbott’s arguments into context, it is first necessary to have an understanding of the legislative regime governing the listing of patents on the Patent Register.
[27] The sale of pharmaceuticals in Canada is regulated by the Food and Drug Regulations, C.R.C. c. 870.
[28] An innovator company (or “first person”) may not manufacture and sell a new drug without the regulatory approval of the Minister of Health. If, after completing the review process contemplated by the regulatory process, the Minister is satisfied that a drug is safe, effective and otherwise complies with the Food and Drug Regulations, then a Notice of Compliance will be issued to the first person.
[29] The Patented Medicines (Notice of Compliance) Regulations in issue in this proceeding are those that were in place prior to the October, 2006 amendments (SOR/2006-242).
[30] Section 4 of the Regulations allows a first person to file patent lists with the Minister. Under the PM(NOC) Regulations, a patent owner may submit a patent list in respect of any drug containing a "medicine" for which a Notice of Compliance has been issued or is being sought.
[31] Section 2 of the PM(NOC) Regulations defines a “medicine” as:
[A] substance intended or capable of being used for the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or the symptoms thereof.
[32] The result of listing a patent is to allow the first person to use the PM(NOC) Regulations to shield the innovator company’s product against competition from generic manufacturers.
[33] Subsection 3(1) of the PM(NOC) Regulations empowers the Minister of Health to determine which patents are added to the Patent Register. The Minister is under a mandatory duty to maintain the register, and has the prima facie obligation to include patent lists submitted by patent holders on the register. However, the Minister may refuse to add a patent to the register if it is ineligible for inclusion.
[34] Also of relevance is subsection 3(3) of the PM(NOC) Regulations, which states that “No information submitted under section 4 shall be included on the register until after the issuance of the Notice of Compliance in respect of which the information was submitted.”
[35] The criteria to be used in determining whether or not a patent should be listed on the Patent Register are set out in section 4 of the PM(NOC) Regulations. The criterion in issue in this proceeding is that contained in paragraph 4(2)(b) of the Regulations, namely that in order to be eligible for listing on the Patent Register, the patent must contain a claim for the medicine, or for the use of the medicine, for which the particular Notice of Compliance was granted.
Issues
[36] The central issue in this application is whether the ’736 patent meets the requirements of paragraph 4(2)(b) of the Patented Medicines (Notice of Compliance) Regulations, and thus whether the Minister's interpretation of this statutory provision was correct.
[37] Abbott also asserts that the Minister erred by relying on an irrelevant and erroneous consideration in refusing to list the ’736 patent, namely the belief that in seeking to have the ’736 patent listed on the Patent Register, Abbott was trying to “evergreen” its other patents relating to BIAXIN®.
Standard of Review
[38] It appears to be settled law that the standard of review for a decision such as this is correctness (see Eli Lilly Canada Inc. v. Canada (Minister of Health), previously cited, and AstraZeneca Canada Inc. v. Canada (Minister of Health), 2006 SCC 49, [2006] 2 S.C.R. 560,
at ¶ 25.
Analysis
[39] The crux of this case is the extent to which the “medicine” referred to in the Notices of Compliance issued with respect to BIAXIN® must correspond to the innovation claimed in the patent sought to be listed, namely the ’736 patent.
[40] Abbott asserts that it has Notices of Compliance for BIAXIN®, and that BIAXIN® contains the Oxime. As attested to by Dr. Atwood in his affidavit filed in support of this application, the Oxime has therapeutic value and is thus a “medicine”, as defined in the PM(NOC) Regulations. Given that the ’736 patent relates to the Oxime, it therefore follows, Abbott says, that Abbott is entitled to list the ’736 patent on the Patent Register in relation to BIAXIN®.
[41] According to Abbott, it is fundamentally incorrect to suggest that by issuing Notices of Compliance for BIAXIN®, that Health Canada has approved the use of any particular medicine. In this regard, Abbott submits that the term “medicine” in the PM(NOC) Regulations is not defined by reference to ingredients “approved through the issuance of” a Notice of Compliance.
[42] Rather, Abbott says, the approval process for new drugs in Canada covers the drug as a whole in the final dosage form as it is used or sold, which drug may contain more than one substance capable of treating a disease.
[43] In this regard, Abbott relies on the evidence of Dr. Albert Liston, the former Assistant Deputy Minister of the Health Protection Branch of Health Canada. Dr. Liston has a doctorate in stereochemistry, and spent much of his career at Health Canada, in positions of increasing responsibility involving the drug approvals process.
[44] According to Dr. Liston, prior to issuing a Notice of Compliance for BIAXIN®, Health Canada would have evaluated BIAXIN® as a whole, in order to ensure that the drug is safe and effective. While conceding that the consideration of the active medicinal ingredient in a drug and its properties is a major part of the assessment, Dr. Liston nevertheless says that Health Canada’s evaluation would not have been limited to the primary medicinal ingredient in the drug, namely clarithromycin.
[45] That is, Dr. Liston says that the approval process would have covered the entire process of manufacture that results in the incorporation of the active pharmaceutical ingredient and any other compounds into the formulated drug product.
[46] I do not accept Abbott’s arguments.
[47] A review of the legislative scheme indicates that Notices of Compliance are issued in relation to drugs that contain specifically stated medicines.
[48] This is confirmed by the wording of subsection 4(1) of the PM(NOC) Regulations, which provides that:
4. (1) A person who files or has filed a submission for, or has been issued, a notice of compliance in respect of a drug that contains a medicine may submit to the Minister a patent list certified in accordance with subsection (7) in respect of the drug. [Emphasis added]
[49] Moreover, paragraph 4(2)(b) of the PM(NOC ) Regulations is quite clear that, to be eligible for listing on the Patent Register, the patent in question must contain a claim for “the medicine”, or for the use of “the medicine”, for which the particular Notice of Compliance was granted.
[50] In subsection 5(1) of the PM(NOC) Regulations, generic manufacturers must make allegations with respect to specific medicines. It would not be possible to do this, and considerable confusion would result, if the “medicines” in question were not specifically identified in New Drug Submissions and subsequently issued Notices of Compliance.
[51] As Justice Hughes observed in “Hughes and Woodley on Patents” (Second Edition) 1 LexisNexis Canada Inc. 215 at § 23:
A patent is placed on the list in respect of a particular drug, not a particular application. In order for a patent to be listed, it must claim a drug containing the same active ingredient – it may be of a different formulation or crystal structure – as the medicine for which a Notice of Compliance was given. The patent must pertain to the same active ingredient as that for which the Notice of Compliance pertains ….
[52] This very point was made in earlier litigation between these parties involving BIAXIN®. That is, in Abbott Laboratories v. Canada (Minister of Health), 2006 FC 120, [2006] 4 F.C. 41, rev’d on other grounds: 2007 FCA 73, Justice Harrington stated that:
… In any event, a patent may be listed on the register if it claims a drug containing the same medicine for which the notice of compliance was given, even though that medicine may be in a different form or crystal structure. [at ¶ 40, emphasis added]
[53] Finally, in Ferring Inc. v. Canada (Minister of Health), 2007 FC 300, Justice Hughes stated at that:
The criteria as to whether a patent is to be listed or not are set out in section 4 of the Regulations. There are a number of criteria, the most important of which for purposes of this discussion is that the patent contains a claim for the medicine or use of the medicine for which the particular NOC was granted, section 4(2)(b) of the pre-October 5, 2006 … regulations. [at ¶ 24, emphasis added]
[54] In this case, the Notices of Compliance issued in relation to BIAXIN® are clear, on their face, that the only medicinal ingredient covered by the Notices of Compliance is clarithromycin. While Notices of Compliance can clearly be issued in relation to drugs containing more than one medicinal ingredient, no other medicinal ingredient is identified in the NOCs issued in relation to BIAXIN®.
[55] I also do not accept Abbott’s contention that the fact that the Minister of Health issued Notices of Compliance for BIAXIN® means that the Minister would, of necessity, have considered and assessed the safety and efficacy of the Oxime as an active medicinal ingredient in that drug.
[56] In this regard, I would note that while arguing that the Minister of Health would have carefully examined the safety and efficacy of the Oxime as an active ingredient in BIAXIN® in the context of Abbott’s New Drug Submission for that drug, Abbott chose not to include a copy of its NDS in its application materials. Thus we have no way of knowing whether the Oxime was ever identified as an active medicinal ingredient by Abbott in its NDS, or whether the Oxime was ever assessed as such by the Minister of Health.
[57] We do know, however, that the only active medicinal ingredient identified by the Minister in the NOCs granted to Abbott for its BIAXIN® products is clarithromycin.
[58] Moreover, nowhere in the materials before me, apart from Dr. Atwood’s affidavit, is the Oxime identified as a medicine. In this regard, I note that a review of Abbott’s product monograph for BIAXIN® discloses that the only medicinal ingredient identified or discussed in the monograph is clarithromycin. Similarly, Abbott itself acknowledges that the Oxime is not mentioned in either the European or American Pharmacopeia.
[59] In these circumstances, I am prepared to draw an adverse inference against Abbott, and do not accept its submission that the NDS provided by Abbott to the Minister identified the Oxime as a medicine in BIAXIN®.
[60] This is not surprising. Even if I accept Dr. Atwood’s evidence that the Oxime has some therapeutic value, the fact is that the Oxime was not something that was specifically included in the drug formulation for BIAXIN® because of its therapeutic value.
[60]
[61] That is, as Dr. Atwood explained, the Oxime is a by-product of one of the manufacturing processes used to synthesize clarithromycin. It does not appear that it is a desirable by-product, as Dr. Atwood himself stated that the manufacturer would try to remove as much of the Oxime as possible from the formulation. Dr. Atwood then went on to state that the complete elimination of all of the Oxime from the finished clarithromycin product would not be possible, with the result that some Oxime would inevitably be present in the final product.
[62] Moreover, it is clear that the Oxime is not always created during the synthesis of clarithromycin, and its creation is dependent on the choice of solvent used during the synthetic process. According to Dr. Atwood, it is only when isopropyl acetate is used as a solvent that the Oxime will be produced. However, isopropyl acetate is only one of many chemical solvents that can be used in the synthesis of clarithromycin. Similarly, oximation is only one of the methods that can be used in the synthesis of clarithromycin.
[63] Given the foregoing, it is hardly surprising that the Oxime was not identified as a medicinal ingredient in BIAXIN®.
[64] As a consequence, I do not accept Abbott’s contention that the Oxime has previously been approved for use as a medicine through the Notices of Compliance issued in relation to BIAXIN®, or that it was ever even considered as such by Health Canada.
[65] Finally, I am not persuaded that the decision in Apotex v. Canada (2000), 181 D.L.R. (4th) 404, (F.C.A.) dictates that Abbott is entitled to have the ’736 patent added to the Patent Register, as it is an intermediate with therapeutic value, which is thus a “medicine”.
[66] Firstly, from the evidence of Dr. Atwood, it appears that the Oxime is not a true intermediate, in that it is not transient, but is rather the by-product of one of the synthetic routes that can be followed in the manufacture of clarithromycin.
[67] More importantly, a review of the Apotex decision discloses that while the Federal Court of Appeal stated that “it is certainly arguable that an intermediate with therapeutic value might be a medicine”, the Court was very careful to preface this comment by saying “For the purpose of this appeal, it is sufficient that there is no definitive finding that intermediates cannot, in any circumstances, meet the requirements of paragraph 4(2)(b).” Thus Apotex does not decide the issue one way or another.
[68] Moreover, in the more recent decision in Merck Frosst Canada & Co. v. Canada (Minister of Health) (2000), 7 C.P.R. (4th) 522 (F.C.T.D), aff’d 2001 FCA 136, the Federal Court of Appeal held that the Minister did not err in refusing to list patents on the Patent Register where those patents related to metabolites of a medicine identified in a Notice of Compliance, and made no claim to the medicine itself.
[69] It was in this context that Federal Court of Appeal observed that to disregard the terms of the Notice of Compliance by treating the drug in question as containing both the medicine specifically identified in the Notice of Compliance and its metabolites “could compromise the ability of the Minister to discharge the important statutory responsibilities for ensuring the effectiveness and safety of new drugs”. [at ¶ 9]
[70] While we are not dealing with a metabolite of the “medicine” in this case, but are dealing instead with a product of one of the synthetic routes than can be used to manufacture clarithromycin, the same point may nevertheless be made about the Oxime in issue in this case.
The Minister’s Reliance on an Irrelevant or Erroneous Consideration
[71] Finally, Abbott says that that the Minister erred by relying on an irrelevant consideration in relation to the ’736 patent, namely the erroneous assumption that in seeking to have the ’736 patent listed on the Patent Register, Abbott was seeking to “evergreen” Abbott’s other patents relating to BIAXIN®.
[72] While I accept Abbott’ submission that this is not a case of attempted evergreening on Abbott’s part, given that the ’736 patent will expire prior to the expiry of the other patents relating to BIAXIN®, I do not accept that the decision refusing to list the ’736 patent should be set aside on the basis that the Minister took irrelevant matters into consideration in concluding that the ’736 patent was not eligible for listing.
[73] Whether the Minister thought that this was a case of attempted evergreening or not, the fact of the matter is that the Minister’s interpretation of paragraph 4(2)(b) of the PM(NOC) Regulations was correct. The ’736 patent was not eligible for listing, and no other decision was possible in this case.
Conclusion
[74] For these reasons, this application for judicial review is dismissed.
Costs
[75] Both parties agree that the costs of this application should follow the event, and I so order.
JUDGMENT
THIS COURT ORDERS AND ADJUDGES that this application for judicial review is dismissed, with costs.
FEDERAL COURT
NAMES OF COUNSEL AND SOLICITORS OF RECORD
DOCKET: T-1711-06
STYLE OF CAUSE: ABBOTT LABORATORIES and
ABBOTT LABORATORIES LIMITED v.
THE ATTORNEY GENERAL OF CANADA
and THE MINISTER OF HEALTH
PLACE OF HEARING: Toronto, Ontario
DATE OF HEARING: March 5, 2007
APPEARANCES:
Caroline Zayid
Andrew J. Reddon FOR THE APPLICANTS
Eric Peterson
Natalie Henein FOR THE RESPONDENTS
SOLICITORS OF RECORD:
McCARTHY TÈTRAULT LLP
Toronto, Ontario FOR THE APPLICANTS
JOHN H. SIMS, Q.C.
Deputy Attorney General of Canada FOR THE RESPONDENTS