Abbott Laboratories v. Canada (Health)

Abbott Laboratories v. Canada (Health)
Court (s) Database
Federal Court Decisions
Date
2009-07-07
Neutral citation
2009 FC 648
File numbers
T-1129-07
Decision Content
Federal Court
Cour fédérale
Date: 20090707
Docket: T-1129-07
Citation: 2009 FC 648
Toronto, Ontario, July 7, 2009
PRESENT: The Honourable Madam Justice Heneghan
BETWEEN:
ABBOTT LABORATORIES and
ABBOTT LABORATORIES LIMITED
Applicants
and
THE MINISTER OF HEALTH
and SANDOZ CANADA INC.
Respondents
REASONS FOR JUDGMENT
(Confidential Reasons for Judgment issued on June 19, 2009)
I. Introduction
[1] Abbott Laboratories and Abbott Laboratories Limited (the “Applicants” or “Abbott”) apply pursuant to the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 (the “NOC Regulations”) for an order prohibiting the Minister of Health from issuing a Notice of Compliance (“NOC”) to Sandoz Canada Inc. (the “Respondent” or “Sandoz”), pursuant to section C.08.004 of the Food and Drug Regulations, C.R.C. c. 870 until the expiry of the Canadian letters patent 2,285,266 (the “ ‘266 Patent”), 2,358,395 (the “ ‘395 Patent”) 2,325,541 (the “ ‘541 Patent”) and 2,209,714 (the “ ‘714 Patent”).
[2] This application was commenced in response to a Notice of Allegation (“NOA”) dated May 7, 2007 and served by the Respondent on that day. The Respondent alleged that the Abbott patents are invalid on several grounds including obviousness, lack of actual utility, lack of sound prediction utility and double patenting.
[3] On June 19, 2007, the Applicants filed their application, pursuant to the NOC Regulations, claiming that the allegations are not justified and requesting the issuance of a Prohibition Order.
A. The Parties
[4] The Applicant Abbott Laboratories is a Canadian company that distributes and sells pharmaceutical products.
[5] The Applicant Abbott Laboratories Limited, a company incorporated under the laws of the United States of America, is the parent of Abbott Laboratories and is the owner of the patents at issue in this proceeding. The Applicants are engaged in the development and manufacture of innovative pharmaceutical products.
[6] Sandoz is the Canadian subsidiary of a multinational generic pharmaceutical manufacturer. It has applied for an NOC to permit it to market its version of clarithromycin extended-release 500 mg tablets.
[7] The Minister of Health (the “Minister”), although a party to this proceeding, is not actively participating in it.
B. The Drug
[8] Clarithromycin, or 6-0-methoxy erythromycin is an erythromycin derivative and an antibiotic. It is administered to humans in a composition or formulation. Abbott sells this product in an extended release (“ER”) 1000 mg formulation under the trade name BIAXIN®XL (“BIAXIN”).
[9] Clarithromycin is the active pharmaceutical ingredient (“API”) in Abbott’s BIAXIN tablets. BIAXIN is administered for the treatment of mild to moderate bacterial infections.
[10] In order to work, the clarithromycin is released from the formulation, dissolved, absorbed through the bloodstream, distributed to various tissues, metabolized, and ultimately eliminated from the body. The path that the drug takes from the formulation through the body depends on the biological characteristics of the drug in the body, specifically its absorption, distribution, metabolism and excretion (“ADME”).
[11] Prior to the ‘266 Patent, these clarithromycin tablets were sold only in an immediate release (“IR”) formulation. This required a patient to take multiple daily doses of the tablets. Multiple daily doses can lead to poor patient compliance and affect the efficiency of treatment. A second problem with the IR composition was the phenomenon of taste perversion, an adverse effect which can lead to non-compliance by a patient with the treatment regime.
[12] Abbott tried to resolve the issues related to multiple dosing by creating an extended release (“ER”) formulation. This allows patients to take only one 1000 mg tablet daily, rather than taking a 500 mg tablet twice a day, that is in the morning and at night.
[13] An important aspect of the ER formulation is that it maintains adequate drug levels in the blood over the extended period of time. This advantage is known as the demonstration of favourable pharmacokinetics (“p-kinetics”), that is the study of the movement of drugs, especially the rates of absorption and excretion of drugs.
[14] In terms of p-kinetics, the area under the plasma concentration time curve (“AUC”) describes the measure or quantity of the total amount of a drug that is delivered in 24 hours. The C-maximum (“C-max”) is the maximum drug concentration in the blood that is attained over the period. The C-minimum (“C-min”) is the minimum drug concentration in the blood reached over the period. The T-maximum (“T-max”) is the time at which the C-max is reached. Bioavailability is the measurement of the amount of the drug available in the blood upon reaching the body’s systemic circulation. The Degree of Fluctuation (“DFL”) is the measure of the difference between the C-max and the C-min. In particular, it measures the variation in the drug levels between the lowest and highest levels during the steady state, the steady state being the point at which the rate of drug supply to the body equals the rate of drug removal from the body.
[15] Abbott first attempted to address the issue of multiple dosing with a once-daily formulation by combining clarithromycin with alginate in a matrix (the “Alginate Formulation”) and obtained a patent in respect of this product, that is the 2,209,714 (the “‘714 Patent”). The Alginate Formulation is sold in the United Kingdom under the name KLARICID® . However, the ‘714 Patent does not address the phenomenon of taste perversion. Abbott wanted to meet the need for a composition that would allow once-daily dosing and which would also address the issue of taste perversion, as compared with the IR formulation.
C. The Patents
[16] Although the NOA referred to four patents, only two patents are the subject of this proceeding, that is the ‘266 Patent and the ‘395 Patent.
i) The 266 Patent
[17] The ‘266 Patent is entitled “Extended Release Formulations of Erythromycin Derivatives”. The invention in the patent relates to “pharmaceutical compositions of erythromycin derivatives with an extended release of an active compound in the gastrointestinal environment.” The invention relates to a pharmaceutical composition that is taken daily as a single dose.
[18] The ‘266 Patent contains 12 claims. Only Claims 11 and 12 are in issue.
[19] The ‘266 Patent was filed in the Canadian Patent Office on March 6, 1998 and claimed priority from U.S. Patent 08/838,900. The priority date is April 11, 1997. Pursuant to sections 28.1 and 28.2 of the Patent Act, R.S.C., 1985, c. P-4 (the “Patent Act”) the claim date is the earliest of the date the application was regularly filed with the Canadian patent office; the date a previous application was regularly filed with the Canadian Patent Office that reveals the subject matter defined by the claim in the new application; or the convention priority date, if applicable. In the present case, the earliest of the three dates is the convention priority date. The claims will therefore be assessed as of April 11, 1997.
[20] The ‘266 Patent contains an ER composition that is comprised of a pharmaceutically active compound and a pharmaceutically acceptable polymer. The pharmaceutically active compound is an erythromycin derivative, in particular, clarithromycin, which varies from about 45 – 60 percent by weight of the composition with the preferred amount being 50 percent.
[21] The pharmaceutically acceptable polymer may be a water soluble hydrophilic polymer, most preferably being a low viscosity hydroxypropyl methylcellulose (“HPMC”), with viscosity ranging from about 50 centipoise (“cps”) to 200 cps, the most specific amount being 100 cps, and commercially available under the trade-mark METHOCEL K 100 LV from the Dow Chemical Company. The amount of the polymer can range from 5 to 50 percent, the most specific variance being from 10 – 30 percent by weight of this composition.
[22] The remainder of the composition is made up of pharmaceutically acceptable excipients and/or fillers such as lactose, starches, glucose and the like. The amount of lubricant within the composition will generally vary from about 0.5 to about 10 percent by weight of the composition.
[23] The ‘266 Patent provides p-kinetics that are suitable for once-daily dosing but that are superior to those of the Alginate Composition of the ‘714 Patent.
[24] The ‘266 Patent describes the ER composition by comparing its p-kinetics to those of the IR composition. These are measured in a comparative p-kinetic study between the two compositions.
[25] It was discovered that the C-max of clarithromycin in the ER formulation is statistically significantly lower than that in the IR composition when the IR composition is given twice daily, while the AUC and C-min levels were maintained throughout the 24 hour period. The ER composition is advantageous because the patient is exposed to a lower spike of the drug concentration at the peak of the cycle, while maintaining whatever minimum concentration that is necessary for good effect and still maintaining the overall delivery as measured by the AUC.
[26] As stated, the claims of the ‘266 Patent relevant to this proceeding are Claims 11 and 12. Claim 11 relates to an ER composition made according to Claims 1 through 10, where the erythromycin derivative is clarithromycin. Claim 12 relates to the composition in Claim 11, where clarithromycin comprises 50 percent of the weight of that composition.
ii) The ‘395 Patent
[27] As previously noted, the ‘714 Patent does not address the issue of taste perversion. Originally Abbott had filed one patent application for its invention of the formulation, their favourable p-kinetics and the improved taste profile. However, during the prosecution of the ‘266 Patent, the Commissioner of Patents required Abbott to divide out any claim relating to improved taste profile into a separate application. This led to the ‘541 application from which the ‘395 Patent ultimately issued. In light of this background, the make-up of the ER clarithromycin composition in the ‘395 Patent is the same as that described relative to the ‘266 Patent.
[28] The ‘395 Patent also is entitled “Extended Release Formulations of Erythromycin Derivatives”. It was filed on March 6, 1998 and claims priority from U.S. Patent 08/838,900. The priority date is April 11, 1997. For the reasons referred to above, this claim will be assessed as of April 11, 1997.
[29] The invention described in the ‘395 Patent shows that when the active compound and the polymer are combined, they yield an improved taste profile and a reduction in adverse effects related to the digestive system.
[30] Abbott is relying on and asserting Claim 22 of the ‘395 Patent. This claim relates to an ER composition described in Claims 12 through 21, where the composition formed has an improved taste profile as compared to the IR composition.
iii) The ‘541 Patent
[31] The ‘541 Patent likewise is entitled “Extended Release Formulations of Erythromycin Derivatives”. The ‘541 Patent is in issue in this proceeding only insofar as Sandoz alleges that the ‘395 Patent is invalid for double patenting over it. The ‘541 Patent was dedicated to the public by a Notice of Dedication dated January 20, 2009 which Notice was filed with the Canadian Patent Office on January 20, 2009.
[32] The ‘541 Patent was filed in the Canadian Patent Office on March 6, 1998 and claims priority to U.S. Patent 08/838,900. The priority date is April 11, 1997.
D. The NOA
[33] By letter dated May 7, 2007 Sandoz served its NOA upon the Applicants, pursuant to subsection 5(3) of the NOC Regulations, respecting the Abbreviated New Drug Submission (“ANDS”). The ANDS was filed in respect of Sandoz’s version of clarithromycin extended-release 500 mg tablets for oral administration for the treatment of mild to moderate infections caused by susceptible strains of the designated microorganism of specified diseases of the upper respiratory tract and of the lower respiratory tract.
[34] The NOA was lengthy and raised allegations of non-infringement, improper listing on the Patent Register and invalidity in respect of four patents, that is the ‘714 Patent, the ‘266 Patent, the ‘541 Patent and the ‘395 Patent. Not all of these issues were addressed in the parties’ written Memoranda of Law.
E. The Evidence
[35] Both parties filed affidavits from factual and expert witnesses. The qualifications of the experts is not challenged although each party challenged the credibility and reliability of some of the opinion evidence that was submitted.
i) The Applicants’ Witnesses
[36] Abbott filed the affidavits of Ms. Sonia Atwell, Ms. Claire Nachbauer, Dr. Cynthia Holas, Dr. Daniel Weiner and Dr. Gilbert Banker.
[37] Ms. Atwell is a law clerk with the law firm of McCarthy Tétrault LLP, solicitors for the Applicants. In her affidavit, she referenced a letter dated March 28, 2000 from the Canadian Intellectual Property Office requesting the amendment of the ‘266 Patent.
[38] Ms. Nachbauer is a Senior Paralegal in the Intellectual Property Litigation Department at Abbott Laboratories. She was asked to obtain copies of the study reports on adverse effects data for Abbott Studies M96-454, M97-667, M97-756, M97-734 and M02-472. In her affidavit, she deposed that Studies M95-454, M97-667, M97-756 and M97-734 were catalogued and entered into Abbott’s Global Pharmaceutical Regulatory Affairs Department’s Research Information Center (“RIC”) RIC/Webcat database as of November 17, 1997, March 30, 1999, April 2, 1999 and April 21, 1999, respectively. This means that the study reports and adverse effect data for each of these studies was available to the inventors of Abbott’s patents before October 2001.
[39] Dr. Holas is the Assistant Director of Trial Specialty in Clinical Operations at Abbott Laboratories. She had formerly been a Clinical Project Manager with the Anti-Infective Clinical Project Team at Abbott Laboratories from July 2002 to December 2005. In that capacity, she managed Abbott’s internal databases. The Clarithromycin Master Inventory List (“CMIL”), which is found on the database, is a complete listing of every study involving clarithromycin that was sponsored or managed by Abbott. Dr. Holas deposed that the M02-472 study was the last Abbott study that was undertaken since 2002.
[40] Dr. Weiner is a statistician at Pharsight Corporation. He holds a Ph.D. in statistics from the University of Kentucky and has worked for more than 25 years in the pharmaceutical industry. He was asked to provide an opinion on the issue of whether certain ER clarithromycin formulations exhibit an improved taste profile and a statistically significant reduction in the severity of adverse effects to the digestive system when compared against IR formulations.
[41] Dr. Weiner dealt with the ‘395 Patent and in that regard, he conducted a meta-analysis of all relevant Abbott studies to determine whether the ER formulation of the ‘395 Patent showed an improved taste profile. A meta-analysis involves the pooling of all relevant data, including that from multiple studies, in order to assess the differences in safety results to determine statistical significance. He referred to the CMIL which contains all of Abbott’s studies on clarithromycin and selected those studies, for the purpose of his meta-analysis, which showed the following criteria:
(a) The ER formulations had to be 10-30 percent by weight of HPMC;
(b) The studies had to have been head-to-head, in that the ER formulation must have been administered in the same study as the IR formulation to control against variability arising from test differences;
(c) The ER formulations must have been administered in dosages of 1,000 mg once-daily, while the IR formulations had to have been administered in 500 mg twice-daily doses; and
(d) The AUC for the ER clarithromycin formulation had to be bioequivalent to that of the IR formulation, because a requirement under the ‘395 Patent is that the ER formulation must deliver an equivalent amount of total drug as the IR formulation, although over a longer period.
[42] Applying these parameters, Dr. Weiner concluded that the only relevant studies for use in his meta-analysis were M96-454, M97-667, M97-756, M97-734 and M02-472. Using the Cochran-Mantel-Haenszel (“CMH”) method to analyze the pooled data, which compares the ER and IR groups against each other, Dr. Weiner found that the incidence of taste perversion for the ER formulation in the ‘395 Patent were statistically significantly lower than those under the IR formulation and that there was less than a one in twenty chance that this difference in the incidence of taste perversion between the formulations could have been due to chance alone.
[43] Dr. Banker is Dean Emeritus and the John L. Lach Distinguished Professor of Drug Delivery Emeritus at the University of Iowa College of Pharmacy. He obtained his Ph.D. in 1957 from Purdue University. He was asked to provide an opinion on the allegation of non-infringement and invalidity set out in the NOA.
[44] Dr. Banker addressed a number of issues, beginning with a definition of the person skilled in the art. In his opinion, this person would have experience in the art of pharmaceutical formulation and an understanding of p-kinetics. He would hold a Bachelor of Sciences degree in Chemistry, Pharmacy or something similar, with at least two years experience in the pharmaceutical industry and experience in designing and evaluating formulations.
[45] Dr. Banker commented on the allegations of obviousness and said that a person skilled in the art and reading the six prior art references cited by Sandoz in its NOA would have believed that an attempt to create an ER formulation with clarithromycin and an HPMC polymer would likely result in reduced bioavailability, which is the least desirable outcome for a drug like clarithromycin.
[46] He offered the opinion that even if by experimentation a person skilled in the art reached a bioavailable ER composition using HPMC, it still would not have been obvious how to do so in a way that provides the comparator p-kinetic advantages of the ‘266 and ‘395 Patents, or in a way that achieves an improved taste profile. He said that in the absence of intensive experimentation, a person skilled in the art would not be able to obtain the claimed compositions and accordingly, the subject matter of these patents is not obvious.
[47] Dr. Banker also commented on the actual utility of the ‘395 Patent. He said that the data contained in Table VI of the ‘395 Patent demonstrates that there was indeed an observed improvement in taste profile for the claimed ER composition as compared to the IR composition. Further, while Sandoz alleges that the M97-667 and M97-756 studies show that the claimed compositions do not have an improved taste profile, Dr. Banker disagreed with that allegation. He said that these studies show an observed decrease in the incidence of taste perversion in the formulation claimed by the ‘395 Patent.
[48] Dr. Banker also said that Sandoz’s reference to taste panels and super tasters demonstrates its misconception of the nature of “taste profile”. Taste panels and super tasters relate to the assessment of the taste of a compound on the tongue or in the mouth. This is different from taste perversion as discussed in the ‘395 Patent. There it is defined as an adverse event and occurs after ingestion. According to Dr. Banker, it is inappropriate to use taste panels or super tasters to evaluate taste perversion.
[49] Dr. Banker also addressed the issue of double patenting in relation to the ‘266, ‘541 and ‘395 Patents. He said that there are three specific inventions identified in these three patents and that none of the inventions are invalid for double patenting. He said that the ‘266 Patent claims clarithromycin and HPMC compositions for ER release and as having certain p-kinetics. The ‘541 Patent claims compositions with the added limitation that these compositions have an improved taste profile. Dr. Banker said that there is no double patenting over the ‘266 Patent, since the improved taste profile in the ‘541 Patent is not the same invention as that claimed in the ‘266 Patent, and because improved p-kinetics and taste profile do not necessarily co-exist with the claims under the ‘266 Patent.
[50] Further, Dr. Banker observed that there is no double patenting over the ‘541 Patent by the ‘395 Patent, since the ‘395 Patent has the additional limitation of a statistically significant reduction in the severity of adverse effects to the digestive system which does not arise from the ‘541 Patent formulations. He noted that a reduction in the severity of effects on the digestive system do not go hand in hand with improved p-kinetics or with an improved taste profile. Accordingly, in Dr. Banker’s opinion, the reduction in the severity of the effects on the digestive system is not obvious from the claims of the ‘266 or ‘541 Patents.
ii) The Respondent’s Witnesses
[51] The Respondent filed the affidavits of Ms. Pamela Christoforakis, Dr. Metin Celik, Dr. Walter G. Chambliss, Dr. Thomas R. Einarson and Dr. Jake J. Thiessen.
[52] Ms. Christoforakis is a law clerk with Hazzard & Hore LLP, solicitors for Sandoz. She attached a copy of the NOA as an exhibit to her affidavit, as well as the 147 prior art references upon which Sandoz relies.
[53] Dr. Celik is a Research Professor of Pharmaceutical Processing at the Department of Industrial and Systems Engineering, Rutgers, The State University of New Jersey and President of Pharmaceutical Technologies International Inc. He obtained a Ph.D. in Pharmaceutical Technology from De Montfort University in 1984. He was retained to opine on the allegations relating to non-infringement, obviousness, anticipation and double patenting.
[54] With respect to the issue of obviousness relative to the ‘266 Patent, he said that it was known that formulations like those disclosed in the ‘266 Patent would generally reveal the same p-kinetics as those disclosed in the ‘266 patent. As well, he said that the WO 95/30422 patent (the “‘422 patent”) sets out the necessary parameters required of the ‘266 Patent, but uses azithromycin.
[55] Dr. Celik noted that azithromycin, erythromycin and clarithromycin were all known to be similar in their make-up and that if the skilled person would have formulated one of these in a certain way, he would have formulated the others in the same way. In his opinion, it would have been obvious for the skilled person to substitute clarithromycin to arrive at the claimed composition.
[56] Dr. Celik also said that the ‘395 Patent is obvious, since it was known by the 1990’s that macrolide antibiotics like clarithromycin exhibited concentration-dependent side effects and that these side effects could be reduced by limiting the concentration of the dose.
[57] Dr. Chambliss is a Professor of Pharmaceutics at the University of Mississippi and a Research Professor in the National Center for Natural Products Research in the Research Institute of Pharmaceutical Sciences at the University of Mississippi. He obtained his Ph.D. in Pharmaceutics in 1982 from the University of Mississippi. He was asked to give an opinion on Sandoz’s allegations of invalidity in respect of the ‘266 and ‘395 Patents.
[58] Dr. Chambliss also addressed the notion of the person skilled in the art, on behalf of Sandoz, and said that such person would be one with a Ph.D. in pharmaceutical science or a similar field, with at least two years experience in either pharmaceutical formulations or in an equivalent field. He offered an alternative definition, that is a person holding a Bachelor’s or Master’s degree in the said field but with significantly more experience in formulating pharmaceutical products.
[59] Dr. Chambliss addressed the allegation of obviousness in relation to the ‘266 and ‘395 Patents. He tendered the opinion that these patents are obvious in light of the prior art, as of the claim date of April 11, 1997. He said that it was well known at this date that hydrophilic polymers like HPMC could be used to make the ER formulation claimed.
[60] Dr. Chambliss also said that as of the relevant date, the prior art showed how to make ER formulations using HPMC, teaching in particular that low viscosity grades were appropriate for poorly water soluble drugs like clarithromycin.
[61] Dr. Chambliss also said that clarithromycin could easily be substituted for known formulations consisting of a similar drug called azithromycin such that a skilled person would have been led easily to the claimed patents. He also said that the p-kinetics claimed in the ‘266 Patent were well-known and previously disclosed.
[62] Dr. Chambliss addressed the allegation of lack of sound prediction utility in relation to the ‘395 Patent. He used a broader interpretation of taste perversion than was used by Dr. Banker and said that a skilled person would understand the term as referring to both the initial taste of the drug in the mouth of a patient and any undesirable taste resulting from the systemic effects of ingestion. He said that the prior art reveals a broader definition of taste perversion than that offered by Dr. Banker.
[63] Dr. Chambliss also said that the Abbott studies that allegedly show an improved taste profile used an inadequate number of subjects such that the results cannot be considered statistically significant. He said that it was not known if the comparative IR tablets had an aqueous coating. This coating has been previously found to enhance taste profile. If the ER tablets were coated and the IR tablets were not, this might explain any noted improvement in taste profile, as between the ER and IR compositions.
[64] Finally, Dr. Chambliss commented on the allegation of invalidity on the basis of double patenting, in reference to the ‘266, ‘541 and ‘395 Patents. He expressed the opinion that these three patents each disclose and claim the same formulation. The claims of the ‘266 Patent cover p-kinetics, the claims of the ‘541 Patent cover improved taste profile and the claims of the ‘395 Patent cover p-kinetics and improved taste profile. In Dr. Chambliss’ opinion, the claims overlap and so the ‘395 Patent is invalid for double patenting.
[65] Dr. Einarson is an Associate Professor of Pharmacy Administration at the Leslie Dan Faculty of Pharmacy at the University of Toronto and an Associate Professor of Health Policy, Management and Evaluation at the Faculty of Medicine, also at the University of Toronto. He obtained his Ph.D. in Pharmacy in 1987 from the University of Arizona. He was asked to provide an opinion on the meta-analysis that was conducted by Dr. Weiner.
[66] Dr. Einarson addressed the issue of lack of actual utility of the ‘395 Patent. He reviewed the meta-analysis that was conducted by Dr. Weiner and concluded that it was flawed. He said that the five studies that Dr. Weiner considered differ in design and patient population and that Dr. Weiner used a method of analysis, that is the fixed effects model that is customarily used only when study protocols are the same. Dr. Einarson said that the proper method was the random effects model, which accounts for differences in the study protocols.
[67] Dr. Einarson also criticized Dr. Weiner for having failed to conduct a proper literature search. He said that he himself had conducted a search and had located thirty-five studies regarding adverse effects of clarithromycin between ER and IR formulations. After combining these studies with those chosen by Dr. Weiner, he concluded that there was not a statistically significant difference in taste profile between the ER and IR compositions.
[68] Dr. Thiessen is the Hallman Director of the School of Pharmacy and the Director of the Health Sciences Campus at the University of Waterloo. He was asked to give an opinion on the issues of the lack of actual utility and the lack of sound prediction utility.
[69] He reviewed the product monographs for Abbott’s various forms of clarithromycin and found that there was no difference in taste profile between the IR and ER compositions. He also concluded that two articles, one by John Murray et al. and the other by Jay Adler et al., each of which was co-authored by an employee of Abbott, did not show any difference in taste profile between the two compositions. He concluded that the ER composition lacked utility.
[70] Dr. Thiessen considered the M96-454 study done by Abbott. He expressed the opinion that this study, which is the only one available as of the Canadian filing date of March 6, 1998, provides a sample group that is too small to give any meaningful result relative to the issue of taste profile. He said that the conclusions in this study concerning the incidences of taste perversion were also inconclusive because the amount of lactose used in the ER versus the IR formulation could have impacted on the taste results. He concluded that the improved taste profile of the ER composition was not soundly predicted.
II. Issues
[71] The following issues arise from this application:
1. Should the Court permit the admission of new evidence from Sandoz relative to the ‘395 Patent?
2. How should Claims 11 and 12 of the ‘266 Patent and Claim 22 of the ‘395 Patent be construed?
3. Are Sandoz’s allegations of invalidity respecting the ‘266 and ‘395 Patents valid in relation to:
(a) Obviousness of the ‘266 and ‘395 Patents;
(b) Actual utility of the ‘395 Patent;
(c) Sound prediction utility of the ‘395 Patent; and
(d) Double Patenting in relation to the ‘395 Patent over the ‘266 and ‘541 Patents.
III. Discussion and Disposition
[72] The parties filed a considerable amount of evidence in relation to this proceeding. I will not refer to all of the evidence contained within the record but instead will base my conclusions upon that evidence which I found to be most relevant, credible and reliable. I have not ignored evidence to which I do not explicitly refer.
A. Nature of This Proceeding
[73] This application seeks to prohibit the issuance of a NOC to the Respondent for its product which contains clarithromycin. The Applicants challenge the Respondent’s NOA on the grounds that the allegations of invalidity of the ‘266, and ‘395 Patents are not justified.
[74] A NOC grants marketing approval for drugs in Canada. It is issued by the Federal Government, indicating that all requirements have been met pursuant to the Food and Drug Regulations for the protection of public health and safety. The NOC Regulations authorize owners of existing patents for pharmaceutical products to file a “patent list” relative to those products for which they hold a NOC. The NOC Regulations refer to the person filing such a list as the “first person”. In this case, the Applicants are the “first person”.
[75] The framework of the NOC Regulations allows generic drug manufacturers to rely on prior approval of related pharmaceutical products in applying for marketing approval of their generic form of the products. Manufacturers who produce the same drug may file an application for a NOC that refers to and relies on the fact that prior approval has been granted for the brand-name version of the drug. Such a manufacturer is known as the “second person” and that is the Respondent’s status.
[76] The NOC Regulations prohibit the Minister of Health from issuing a NOC until all relevant product and use patents in the earlier approved medicine, as described in the patent list, have expired. Consequently, a second person must either wait until patent expiry before receiving a NOC or it may submit a NOA to the Minister with its new drug submission.
[77] The NOC Regulations require service of the NOA upon the first person. Section 5 sets out the grounds upon which a NOA is to be based. Briefly, the NOA must assert either that the first person is not the patentee, that the patent is expired or invalid, or that it would not be infringed if a NOC were issued.
[78] Following service of the NOA, the Minister may issue a NOC to the second person, unless the first person avails of its right, pursuant to section 6(1) of the NOC Regulations, to seek an order from the Federal Court prohibiting the Minister from issuing the NOC. Any such step must be taken by the first person within 45 days after receipt of the NOA and once such a proceeding is commenced, the issuance of a NOC to the second person is stayed for a maximum period of twenty-four months.
B. Burden of Proof
[79] Before addressing the specific aspects of this case, I will briefly address the jurisprudence applicable to the burden of proof and the question that must be answered in a NOC proceeding. It is well-established that the burden of proving that the second person’s, that is, Sandoz’s, allegations are not justified is on the person seeking the Prohibition Order, Abbott. Abbott must establish, on a balance of probabilities, that Sandoz’s allegations are not justified. Sandoz must put its allegations “in play” through its NOA. However, once that has been done, Abbott bears the burden of proving that such allegations are not justified, on a balance of probabilities: see Eli Lilly Co. v. Nu-Pharm Inc. (1996), 69 C.P.R. (3d) 1 (F.C.A.), Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1994), 55 C.P.R. (3d) 302 (F.C.A.) and SmithKline Beecham Pharma Inc. v. Apotex Inc., [2001] 4 F.C. 518 (T.D.), aff’d (2002), 291 N.R. 168 (F.C.A.).
[80] Second, the Court must determine whether Sandoz’s allegations of invalidity are justified or not. In Pharmacia Inc. v. Canada (Minister of National Health and Welfare) (1994), 58 C.P.R. (3d) 209 (F.C.A.) (“Pharmacia”) the Federal Court of Appeal commented upon the standard to be applied to this type of proceeding, at page 216:
...these proceedings are not actions for determining validity or infringement: rather they are proceedings to determine whether the Minister may issue a notice of compliance. That decision must turn on whether there are allegations by the generic company sufficiently substantiated to support a conclusion for administrative purposes (the issue of a notice of compliance) that the applicant’s patent would not be infringed if the generic’s product is put on the market…
[81] In Smith Kline, Justice Gibson considered the evidentiary burden in proceedings under the NOC Regulations where invalidity of a patent is alleged. At pages 533 to 534 he wrote the following:
Against the foregoing, I conclude that while an evidential burden lies on Apotex to put each of the issues raised in its Notice of Allegation in play, if it is successful in doing so, the persuasive burden or legal burden then lies with SmithKline. Assuming Apotex to be successful in putting the issue of validity of the ‘637 Patent in play, SmithKline is entitled to rely on the presumption of validity of the patent created by subsection 43(2) of the Act.
The persuasive burden or legal burden that lies with SmithKline in the circumstances described in the preceding paragraph is, however, impacted by the nature of the proceeding here before the Court. In Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare), [(1994), 55 C.P.R. (3d) 302 (F.C.A.)] Mr. Justice Hugessen, for the Court, wrote at pages 319-20:
As I understand the scheme of the regulations, it is the party moving under s. 6, in this case Merck, which, as the initiator of the proceedings, has the carriage of the litigation and bears the initial burden of proof. That burden, as it seems to me, is a difficult one since it must be to disprove some or all of the allegations in the notice of allegation which, if left unchallenged, would allow the Minister to issue a notice of compliance.
…
In this connection, it may be noted that, while s. 7(2)(b) [of the Regulations] seems to envisage the court making a declaration of invalidity or non-infringement, it is clear to me that such declaration could not be given in the course of the s. 6 proceedings themselves. Those proceedings, after all, are instituted by the patentee and seek a prohibition against the Minister; since they take the form of a summary application for judicial review, it is impossible to conceive of them giving rise to a counterclaim by the respondent seeking such a declaration. Patent invalidity, like patent infringement, cannot be litigated in this kind of proceeding.
Thus, the burden on SmithKline is only to disprove the allegations in the notice of allegation, not to justify declaration of validity and infringement or conversely to negative claims for declarations of invalidity and non-infringement.
[82] The burden lies on Abbott, as the Applicants, to refute the allegations set forth by Sandoz in its NOA dated May 7, 2007. Therefore, like any plaintiff or applicant, Abbott has the overall legal burden of proof. Sandoz, as the Respondent, has an obligation to put the allegations set out in its NOA in play.
[83] The present proceeding is a summary proceeding pursuant to the NOC Regulations and the Federal Court Rules, 1998, SOR/98-106 (the “Rules”) governing applications for judicial review. A finding of invalidity or infringement in the context of this type of proceeding is not determinative of that issue in any subsequent action: Pharmacia at page 216.
Issue 1: Admission of Sandoz’s Additional Evidence
[84] Prior to the hearing, Abbott brought a motion seeking to strike paragraphs 88 to 93 and 96 of Dr. Thiessen’s affidavit on the basis that these paragraphs address matters that exceed the scope of the NOA. The Respondent defended the inclusion of these paragraphs on the grounds that the evidence was proper reply to the evidence submitted by the Applicants. Prothonotary Aalto ruled that the Applications Judge would be better placed to deal with the status of the challenged paragraphs.
[85] Paragraphs 88 to 93 and paragraph 96 address the contents of Abbott’s product monographs for BIAXIN, BIAXIN BID and BIAXIN XL contained within the 2006 Compendium of Pharmaceuticals and Specialties, and relates to Sandoz’s allegations of the apparent lack of improvement in taste profile in Abbott’s ER tablet as compared to the IR equivalent. The evidence of Dr. Thiessen is directed at undermining the conclusions of the Applicants’ evidence. In this regard, I am satisfied that Dr. Thiessen’s evidence is admissible as reply evidence.
[86] The exhibits attached to Dr. Thiessen’s affidavit in relation to the challenged paragraphs consist of product monographs and labels, and are also admissible as they serve as the basis for his evidence in reply. Further, the documents were produced by Abbott in the course of its business and were known to the Applicants. While the Applicants argue that the documents should not be admitted into evidence because it has been shown, during the cross examination of Dr. Thiessen, that the Respondent failed to disclose certain materials to Dr. Thiessen before he gave his opinion, that is a matter that goes to the weight to be given to the evidence in question and not to its admissibility.
[87] In any event, in the course of oral argument, the Respondent did not actively pursue any submissions on the issue of the product labels.
Issue 2: Claims Construction
[88] The first step in determining whether Sandoz’s allegations of invalidity are justified is to construe the disputed claims of the ‘266 and ‘395 Patents. As held by the Supreme Court of Canada in Whirlpool Corp. v. Camco Inc., [2000] 2 S.C.R. 1067 (“Whirlpool’) and Free World Trust v. Électro Santé Inc. (2000), 9 C.P.R. (4th) 168 (“Free World Trust”) the patent claim is to be construed in a “purposive” way and the Court must lo