Fournier Pharma Inc. v. Canada (Health)

Fournier Pharma Inc. v. Canada (Health)
Court (s) Database
Federal Court Decisions
Date
2012-07-05
Neutral citation
2012 FC 740
File numbers
T-1184-10
Decision Content
Date: 20120705
Docket: T-1184-10
Citation: 2012 FC 740
Ottawa, Ontario, July 5, 2012
PRESENT: The Honourable Mr. Justice Zinn
BETWEEN:
FOURNIER PHARMA INC. and
FOURNIER LABORATORIES IRELAND LTD.
Applicants
and
THE MINISTER OF HEALTH,
ALKERMES PHARMA IRELAND LIMITED and SANDOZ CANADA INC.
Respondents
*PUBLIC REASONS FOR JUDGMENT AND JUDGMENT
(Confidential Reasons for Judgment and Judgment released June 15, 2012)
Notice of Compliance proceedings “should not be likened to actions for determining validity or infringement but are of the nature of proceedings in judicial review, to be held expeditiously, whose aim is to determine whether the Minister is free to issue the notice of compliance requested:” Apotex Inc v Canada (Minister of National Health and Welfare), [1997] FCJ No 1251 (FCA), at para 6.
I would add that because the scope of the proceeding is confined to administrative purposes only and not a final determination that may be made following a trial, it is reasonable for the Court to expect that the parties will focus their submissions, both written and oral, on the one or two or three serious, credible issues in dispute. These proceedings ought not to be seen as an occasion for parties to throw everything at the applications judge in order to see what might “stick.”
Reasons are issuing contemporaneously in two related applications: T-1184-10, Judgment 2012 FC 740, and T-991-10, Judgment 2012 FC 741. Both deal with the drug fenofibrate; however, each involves a different patent. Both were brought into play as a result of Sandoz Canada Inc. seeking permission to market its fenofibrate composition in Canada. The result in one application is not determinative of the other, although some substantive and procedural issues are common to both.
A Table of Contents follows.
TABLE OF CONTENTS
PARA.
OVERVIEW....................................................................................................................... 1
The Proceeding and Its Background.................................................................... 1
Burden of Proof.................................................................................................... 9
The Drug and the ‘054 Patent............................................................................ 10
The ‘054 Patent................................................................................................... 12
THE EVIDENCE.............................................................................................................. 13
Person of Ordinary Skill in the Art (POSITA)................................................... 15
Expert Evidence Filed By Fournier.................................................................... 17
Dr. Fernando Muzzio (On Infringement)............................................... 17
Dr. Fernando Muzzio (On Validity)....................................................... 23
Expert Evidence Filed by Sandoz...................................................................... 29
Dr. Grégoire Leclair................................................................................ 29
Dr. Abu Serajuddin................................................................................ 35
Dr. Isadore Kanfer.................................................................................. 41
Dr. Michael Mayersohn.......................................................................... 44
Additional Expert Evidence............................................................................... 48
Challenges to the Opinions of the Experts......................................................... 54
THE INTERPRETATION OF THE ‘054 PATENT........................................................ 68
Bioequivalence and Pharmacokinetic Profile..................................................... 70
At Least One Surface Stabilizer and Phospholipid-Free.................................... 82
Redisperses in a Biorelevant Media.................................................................... 84
Particle Size of the Fenofibrate in the Composition........................................... 88
Claim 20.............................................................................................................. 93
Conclusion on Construction of the ‘054 Patent................................................. 98
INFRINGEMENT.......................................................................................................... 102
ANTICIPATION............................................................................................................ 134
OBVIOUSNESS............................................................................................................. 140
CLAIMS BROADER / INUTILITY / SOUND PREDICTION................................... 148
INSUFFICIENCY OF DISCLOSURE......................................................................... 150
CONCLUSION.............................................................................................................. 152
OVERVIEW
The Proceeding and its Background
[1] Fournier Pharma Inc. markets LIPIDIL EZ in 48 mg and 145 mg tablets. The active pharmaceutical drug in LIPIDIL EZ is fenofibrate which reduces LDL (bad) cholesterol and increases HDL (good) cholesterol in patients.
[2] Sandoz Canada Inc. (Sandoz) has sought approval from the Minister of Health (Minister) to market Sandoz Fenofibrate E (the Sandoz Tablet), its generic version of LIPIDIL EZ. In its Abbreviated New Drug Submission (ANDS) filed with the Minister, Sandoz referenced LIPIDIL EZ “for the purpose of demonstrating bioequivalence or bioavailability characteristics” of the Sandoz Tablet. Three patents are listed on the register in respect of LIPIDIL EZ: Canadian Patent 2,219,475 (the ‘475 Patent), Canadian Patent 2,372,576 (the ‘576 Patent), and Canadian Patent 2,487,054 (the ‘054 Patent).
[3] The Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, as amended (PMNOC Regulations) provide that the person seeking a Notice of Compliance (NOC) (Sandoz in this case), referred to in the legislation as the “second person,” must serve a Notice of Allegation (NOA) on the person who filed the new drug submission that is referenced in its ANDS (Fournier Pharma Inc. in this case), referred to in the legislation as the “first person.”
[4] Sandoz served a separate NOA in respect of each of the above referenced patents. Fournier Pharma Inc. commenced three separate applications in this Court each seeking an order, pursuant to subsection 6(1) of the PMNOC Regulations, prohibiting the Minister from issuing a NOC to Sandoz in connection with its orally administered 48 mg and 145 mg tablets containing fenofibrate, until after the expiration of the relevant Canadian patents. Fournier Laboratories Ireland Ltd., a co-owner of the ‘054 Patent, joined with Fournier Pharma Inc. as applicants in this application (collectively Fournier). The three applications, and the patents at issue are as follows:
a. Court File T-991-10 filed June 24, 2010, in relation to the ‘576 Patent;
b. Court File T-1054-10 filed June 30, 2010, in relation to the ‘475 Patent; and
c. Court File T-1184-10 filed July 22, 2010, in relation to the ‘054 Patent.
[5] Court File T-1054-10 was discontinued by Fournier on January 25, 2012. The application in Court File T-1184-10 was heard the week commencing March 26, 2012, and Court File T-991-10 was heard the following week. Each application was heard separately; however, as noted below, an Order was issued prior to the hearings directing that some of the evidence filed in one proceeding could be referenced by the parties in the other proceeding.
[6] Unless Fournier is granted an order of prohibition, the Minister is prohibited from issuing a NOC to Sandoz until twenty-four (24) months after this proceeding commenced, i.e. until July 22, 2012, unless prior to that date the Court declares that the ‘054 Patent is invalid or if one of the other conditions in paragraph 7(2)(b) of the PMNOC Regulations apply.
[7] Sandoz alleges that the Sandoz Tablet does not infringe the ‘054 Patent because the size of the fenofibrate particles in the Sandoz Tablet do not fall within the fenofibrate particle size range set out in the claims of the ‘054 Patent. It further submits that to the extent of any infringement, the ‘054 Patent is invalid.
[8] The respondent Alkermes Pharma Ireland Limited (Alkermes), a co-owner of the ‘054 Patent, filed a record in this proceeding but no Memorandum of Fact and Law, and made no oral submissions. Its counsel attended the hearing.
Burden of Proof
[9] Subsection 43(2) of the Patent Act, RSC 1985, c P-4 provides that an issued patent is presumed to be valid “in the absence of any evidence to the contrary.” In a proceeding under the PMNOC Regulations if there is evidence in the record that, if accepted, is capable of establishing the invalidity of the patent, then the burden is on the applicant to establish on a balance of probabilities (the civil standard) that the allegations of invalidity are not justified: Abbott Laboratories v Canada (Minister of Health), 2007 FCA 153. Such evidence is in the record in this proceeding; accordingly, the issue for the Court is whether Fournier has proved on the balance of probabilities that all of the allegations raised by Sandoz are not justified.
The Drug and the ‘054 Patent
[10] Fenofibrate is known to reduce bad cholesterol in the blood and the risk of a heart attack; however fenofibrate comes with two central problems. First, it is almost insoluble in water. As a result, the patient must take large doses if an effective quantity of fenofibrate is to make its way into the blood stream. Second, the pharmacokinetics (the absorption and distribution) of fenofibrate vary on whether the patient takes it when in a fed or in a fasted state. It is better absorbed when taken in a fed state and particularly when taken with fatty foods. Dr. Mayersohn described as “diabolical” the fact that the patient is instructed to take fenofibrate with fatty food when the patient, on a low cholesterol diet, is otherwise instructed to avoid fatty food. The ‘054 Patent is directed to the problem of bioequivalence in the fed and fasted states.
[11] The disclosure of the ‘054 Patent, entitled “Nanoparticulate Fibrate Formulations” describes these challenges and asserts that “[t]he present invention satisfies these needs.” It explains that:
Because fibrates, including fenofibrate, are so insoluble in water, significant bioavailability can be problematic. In addition, conventional fibrate, including fenofibrate, formulations exhibit dramatically different effects depending upon the fed or fasted state of the patient. Finally, conventional fibrate, including fenofibrate, formulations require relatively large doses to achieve the desired therapeutic effects. There is a need in the art for nanoparticulate fibrate formulations which overcome these and other problems associated with prior conventional microcrystalline fibrate formulations. The present invention satisfies these needs.
The ‘054 Patent
[12] Fournier asserts that the Sandoz Tablet infringes two separate sets of claims: “(a) claims 10, 27- 28, and 38 as they depend on claims 1-3; and (b) claim 20 which it alleges specifically covers Sandoz’s 145 mg tablet.” The relevant claims from the ‘054 Patent are reproduced in Appendix A.
THE EVIDENCE
[13] The filing of evidence was partially reversed: Fournier and Alkermes filed their evidence on infringement and their factual evidence on invalidity first. Sandoz then filed all of its evidence on the application and Fournier and Alkermes then filed their responding expert evidence on invalidity.
[14] Fournier filed two affidavits, both sworn by its proposed expert, Dr. Fernando Muzzio: the first dealing with the issue of infringement and the second dealing with issues relating to invalidity. Alkermes filed two affidavits: the first sworn by Dr. Stephen B. Ruddy, one of the inventors named in the ‘054 Patent, and the other by Dr. Cory J. Berkland, who performed dissolution tests on the Sandoz Tablet. Sandoz filed affidavits sworn by its proposed four experts: Dr. Grégoire Leclair, Dr. Abu Serajuddin, Dr. Isadore Kanfer and Dr. Michael Mayersohn. It also filed an affidavit of Deborah Zak, a law clerk, attaching as exhibits the prior art referenced by Sandoz in its NOA and an affidavit of Christoph Heinemann, a law clerk, attesting that samples of the Sandoz Tablet were delivered to Fournier and Alkermes. As is discussed below, Sandoz urged the Court to draw an adverse inference from the fact that Fournier filed no test data on the Sandoz Tablets that had been provided to it.
Person of Ordinary Skill in the Art (POSITA)
[15] The identification of the POSITA identifies the person or group of persons to whom the patent is addressed. Because the patent is addressed to the POSITA, that person may assist the Court which is unlikely to have familiarity with the subject matter of the patent. However, that assistance is limited, as was observed by Justice Hughes in Merck & Co v Pharamscience Inc, 2010 FC 510, at para 70:
Experts may assist in two ways; first they may inform the Court as to the knowledge that a person skilled in the art would have had at the relevant time, so as to bring that knowledge to bear reading both the description and the claims; second, an expert may assist in explaining any technical terms not within the experience expected of a Court.
[16] Fournier’s expert, Dr. Fernando Muzzio, attests that the POSITA “would have a PhD in pharmaceutics along with 1-3 years of experience in the area of formulation of pharmaceutical products. Alternatively, the POSITA could have a Masters degree in pharmaceutics with 5-7 years of experience in the area of formulation of pharmaceutical products.” That description of the relevant POISTA does not vary significantly from that offered by Sandoz’s experts and I accept it as a statement of the qualifications of the POSITA. It is the same description accepted to be the POSITA in T-991-10.
Expert Evidence Filed By Fournier
Dr. Fernando Muzzio (On Infringement)
[17] Dr. Muzzio has a B.Sc. in Chemical Engineering from the University of Mar del Plata, Argentina, and a Ph.D. from the University of Massachusetts in Chemical Engineering. He is a Professor II of Chemical Engineering at Rutgers University and teaches a course called Pharmaceutical Unit Operations which includes lectures on size reduction of particles and milling. He directs a staff of approximately 130 persons at the National Science Foundation Engineering Research Center (NSFERC) where he oversees projects relating, in part, to nanoparticle stabilization of pharmaceutical products. As part of NSFERC’s industrial mentor program, he interacts and collaborates closely with an additional 120 representatives. He is also the Director of the National Science Engineering and Research training program in Nanopharmaceutical Engineering at Rutgers University. Additionally, he teaches courses for industry and regulatory agencies such as the U.S. Food and Drug Administration and he has authored approximately 200 peer-reviewed scientific papers and book chapters on subjects which include powder mixing fundamentals and mixing and segregation in tumbling blenders.
[18] In Dr. Muzzio’s affidavit on infringement, he says that Sandoz’s allegation that the Sandoz Tablet would not infringe any claims of the ‘054 Patent is incorrect. He provides his reading of the claims in the ‘054 Patent and notes that Sandoz’s only allegation of non-infringement with respect to claims 1-3 and 24-31 is:
The dispersion used to prepare the Sandoz tablets prior to formulation in the solid dosage form (the tablet) comprise particles which are not fenofibrate per se and/or which particles are not within the claimed particle size ranges. Furthermore, the Sandoz Tablets once formulated and in final dosage forms do not comprise particles of fenofibrate per se in the claimed particle size range.
[19] Dr. Muzzio reviews the manufacturing procedure of the Sandoz Tablet and refers to various figures and tables in Sandoz’s ANDS relating to the particle size of the fenofibrate and says that he has no doubt that the particle size of the fenofibrate in the Sandoz Tablet are within the ‘054 Patent’s claimed ranges. Finally, he notes that there are no manufacturing steps [ …] [ …]
[ …] such that the Sandoz Tablets, once formulated and in final dosage form, do not comprise particles of fenofibrate per se within the claimed particle size distribution range.
[20] Dr. Muzzio responds to Sandoz’s allegation that claims 13-16 are not infringed because the procedure to measure Tmax is not defined in the ‘054 Patent by pointing out that Tmax could be measured as part of a procedure well known as of May 2004.
[21] Dr. Muzzio responds to Sandoz’s allegation that claims 34-38 would not be infringed because the Sandoz Tablet does not have the dissolution required by providing a table illustrating the fenofibrate dissolution in the Sandoz Tablet and noting that it does fall within all of the ranges in claims 34-38.
[22] [ …]
[ …]
[ …]
[ …] .
Dr. Fernando Muzzio (On Validity)
[23] Dr. Muzzio opines that the inventive concept of the ‘054 Patent is that: (a) it has essentially the same bioavailability in the fed and fasted states; (b) the D50 particle size of fenofibrate is less than about 200 or 150 nm; (c) it has a rapid dissolution rate; (d) it redisperses to a particle size no larger than 2 μm; and (e) it permits reduced dosing.
[24] Dr. Muzzio says that none of the prior art referenced by Sandoz discloses or enables the POSITA to come to the inventive concept of the ‘054 Patent. Moreover, he says that the inventive concept of the ‘054 Patent would not have been obvious to the POSITA. In his opinion, the POSITA was unaware that it was possible to achieve essentially the same bioavailability in the fed and fasted state with fenofibrate compositions. The prior art included many attempts to reduce the food effect, but no one achieved what the ‘054 Patent claimed and achieved, the elimination of the food effect. He notes examples in the ‘054 Patent which, in his opinion, compel the conclusion that the 145 mg fenofibrate formulation of the invention would be bioequivalent to the prior art 200 mg formulation.
[25] Dr. Muzzio states that the different aspects of the inventive concept are what render the ‘054 Patent useful. He disagrees with Sandoz’s allegation that the ‘054 Patent lacks sound prediction. He says that the particle size was predicted through Examples 5 and 6 in the ‘054 Patent; guidance was given for the choice of surface stabilizers as the ‘054 Patent stated the preferred stabilizers and referenced the Handbook of Pharmaceutical Excipients; and the reduced dosage could be predicted through Example 8.
[26] Dr. Muzzio disagrees with the Sandoz experts who opined that the inventors of the ‘054 Patent were not entitled to claim any fenofibrate composition apart from the precise composition in Example 5 of the ‘054 Patent. Dr. Muzzio highlights and relies on one of the statements in the description which reads:
The following examples are given to illustrate the present invention. It should be understood, however, that the invention is not to be limited to the specific conditions or details described in these examples.
According to Dr. Muzzio, the POSITA would have understood that the claimed invention was not the formulation of Example 5, but rather that fenofibrate compositions with the claimed particle sizes can be made and will achieve bioequivalence in the fed and fasted states.
[27] Dr. Muzzio writes that the ‘054 Patent provided a sound line of reasoning to predict that other surface stabilizers not found in the stated example would likewise be effective. He notes that the dissolution profile was not overly broad and was demonstrated in Example 8. Similarly, he notes that the particle sizes were shown in Tables 1, 4, 5 and 7.
[28] Dr. Muzzio addresses and disagrees with Dr. Kanfer’s statement that the boundaries of the claims are undefined. In Dr. Muzzio’s opinion, the POSITA would have understood that the invention was limited to phospholipid-free compositions, for oral administration, with bioequivalence in fed and fasted states. No undue experimentation would be required to come to formulations covered by the invention described in the ‘054 Patent.
Expert Evidence Filed By Sandoz
Dr. Grégoire Leclair
[29] Dr. Leclair has a Ph.D. in Pharmaceutical Sciences from Université de Montréal, where he is currently employed as an Assistant Professor. His current research includes nanoparticulate compositions for active ingredients which have poor solubility in water.
[30] Dr. Leclair notes that the only examples in the ‘054 Patent which are shown to exhibit bioequivalence in the fed and fasted states are Examples 5 and 6 which relate to tablets containing 160 mg nanoparticulate fenofibrate. In his opinion, the POSITA would not understand any of the other ranges of particle size to be bioequivalent in the fed versus fasted states and therefore, in his view, the particle ranges claimed in the ‘054 Patent are too broad. Similarly, he says that the redispersion of the particle size is too broad because the claims do not contain a limitation. The claims in the ‘054 Patent merely state that redispersed particle sizes can be determined with reference to another U.S. patent.
[31] Dr. Leclair says that the lack of limitations relating to surface stabilizers in the claims of the ‘054 Patent also renders the claims of the ‘054 Patent too broad. He notes that all the preferred formulations set out in the ‘054 Patent use as surface stabilizers docusate sodium (DOSS) and hypromellose, and he says that the POSITA would know that the inventors could not predict which other stabilizers would provide compositions that are bioequivalent in the fed versus fasted states; because, as the ‘054 Patent indicates, not all stabilizers will work.
[32] Additionally, Dr. Leclair advances that there is no sound line of reasoning given as to why particle sizes under 2 μm would work, nor as to why other surface stabilizers could be effective. Dr. Leclair also notes that the ‘054 Patent does not describe how to measure the particle size in the composition.
[33] Finally, Dr. Leclair says that Dr. Muzzio’s assertion that the fenofibrate in the Sandoz Tablet has the same particle size as in the suspension used in the process to make the tablet is not correct. In his opinion, aggregation will inevitably occur [ …]
[ …] . Dr. Leclair describes a procedure he designed in order to determine the minimum particle size of the fenofibrate in the Sandoz Tablet and states that Dr. Muzzio has wrongly assumed that there is no agglomeration in the Sandoz Tablet. Dr. Leclair’s results show that the mean size of the fenofibrate in the Sandoz Tablet is greater than [ …] , with a D50 greater than [ …] and a D90 greater than [ …] . Moreover, [ …]
[ …]
[ …] .
[34] Lastly, Dr. Leclair disagrees with Dr. Muzzio that the inventors of the ‘054 Patent solved the food effect problem by making very small particles. Dr. Leclair states that the inventors did not demonstrate any comparison to other particle sizes. Also, he challenges Dr. Muzzio’s statement that: “The inventors report that the nanoparticlulate fenofibrate tablet of the invention was as effective at a dosage of 160 mg as the 200 mg dosage available in the prior art.” Dr. Leclair notes that the inventors state that:
Finally, as shown by the data in Table 16, below, administration of a 160 mg nanoparticulate fenofibrate tablet in a fasted state is not bioequivalent to administration of a 200 mg conventional microcrystalline fenofibrate capsule (TRICOR®) in a fed state. This is because CI 90% for the two treatments is outside 0.80 to 1.25 for AUC and Cmax [emphasis by Dr. Leclair].
Dr. Abu Serajuddin
[35] Dr. Serajuddin obtained his Bachelor in Pharmacy at Dhaka University in 1967, his Masters of Science in pharmaceutics from Colombia University in 1976 and his Ph.D. in Industrial Pharmacy from St. John’s University in 1982. His thesis related to solubility and dissolution of poorly soluble drugs. Since September 2008 he has been a Professor of Industrial Pharmacy at St. John’s University. Prior to joining St. John’s University, Dr. Serajuddin worked for more than 30 years in the pharmaceutical industry in a variety of positions relating to the development of drug formulations.
[36] Dr. Serajuddin explains the general knowledge of the POSITA at the relevant time and states that the advantages described in the ‘054 Patent as set out below “described the usefulness of the invention of the ‘054 Patent promised by the inventors:”
(1) smaller tablet or other solid dosage form size; (2) smaller doses of drug required to obtain the same pharmacological effect; (3) increased bioavailability; (4) substantially similar pharmacokinetic profiles of the nanoparticulate fibrate, preferably fenofibrate, compositions when administered in the fed versus fasted state; (5) improved pharmacokinetic profiles; (6) bioequivalence of the nanoparticulate fibrate, preferably fenofibrate, compositions when administered in the fed versus fasted state; (7) an increased rate of dissolution for the nanoparticulate fibrate, preferably fenofibrate, compositions; (8) bioadhesive fibrate, preferable fenofibrate, compositions; and (9) the nanoparticulate fibrate, preferably fenofibrate, compositions can be used in conjunction with other active agents useful in treating dyslipidemia, hyperlipidemia, hypercholesterolemia, cardiovascular disorders, or related conditions.
[37] Dr. Serajuddin reviews the claims of the ‘054 Patent and finds that they are broader than the invention itself. According to him, all the advantages “address what the composition of the invention does or is supposed to do but not what the composition is.” He also notes that notwithstanding the difficulty in selecting the surface stabilizer to be used, the inventors refer to a broad group of surface stabilizers that could be used in the compositions and then refer to thousands of possible surface stabilizers and combinations. According to him, the POSITA would know that there was nothing inventive in this or any of the other characteristics of the invention. Additionally, he states that the promised utilities cannot be predicted for the claimed compositions. In his opinion, the POSITA would not have been able to predict that the composition was physically stable and would be bioequivalent in the fed versus fasted states.
[38] Dr. Serajuddin also believes that the POSITA would require experimentation to practice what is found in the invention. In this regard, Dr. Serajuddin targets the very broad range of stabilizers. He says that to select those that would work as promised would require more than routine testing.
[39] Dr. Serajuddin reviews prior publications and states that from each of them the POSITA would have been able to prepare the compositions covered by the claims he identified in the ‘054 Patent.
[40] Dr. Serajuddin disagrees with the conclusion of Dr. Muzzio that the Sandoz Tablet would infringe the ‘054 Patent. Specifically, he disagrees with Dr. Muzzio’s statement that a tablet taken orally will redisperse in gastrointestinal fluids to the same size as the original particles used to prepare the formulation. Dr. Serajuddin refers to United States Patent 6,375,986 (US ‘986 Patent) which found redispersion to the particle size in the original suspension to be a problem. He states:
US ‘986 clearly shows that Dr. Muzzio’s statement is incorrect. In US ‘986, Elan states that it has discovered a combination of surfactants and surface stabilizers (for example DOSS, SLS and PVP) that resulted in an improvement in the particle size of the redispersed materials. However, the mean particle sizes of the redispersion was still more than 20 times larger than the mean particle size of the original suspension …
Dr. Isadore Kanfer
[41] Dr. Kanfer has a B.Sc. (Pharm) as well as a B.Sc. (Hons) and a Ph.D. (Pharm) from Rhodes University, South Africa. He is currently Professor and Dean Emeritus in the Faculty of Pharmacy of Rhodes University where he teaches undergraduate, Masters and Ph.D. courses relating to biopharmaceutical analysis, bioavailability, dissolution, bioequivalence, drug interaction, drug absorption and drug regulation.
[42] Dr. Kanfer reviews the ‘054 Patent and echoes Dr. Serajuddin in stating that the advantages listed in the description are the promises of the invention. Dr. Kanfer adds that the POSITA would also understand that the inventors were promising the nanoparticulate compositions to be stable. He provides graphs and tables to explain that none of the promises in the ‘054 Patent were demonstrated or soundly predictable.
[43] Dr. Kanfer says that the claims in the ‘054 Patent are too broad and cover formulations that would not work. He emphasizes that there is no direction as to which surface stabilizers would work and, as such, bioequivalence in the fed versus fasted states cannot be predicted; undue experimentation would be required.
Dr. Michael Mayersohn
[44] Dr. Mayersohn holds a B.Sc. in Pharmacy from Columbia University and was awarded a Ph.D. in Pharmaceutics/Pharmacokinetics from State University of New York in 1971. Since 1983 he has been a Full Professor of Pharmaceutical Sciences at the University of Arizona. He has conducted research projects which involved examination and characterization of oral bioavailability and pharmacokinetic properties of drugs and their metabolites in animals and humans.
[45] Dr. Mayersohn compares the ‘054 Patent to the prior art. In his view, Canadian Patent 2,423,335 (the ‘335 Patent) and WO Patent 02/24193 (the WO ‘193 Patent) describe and enable fenofibrate formulations having a particle size of most preferably 100 nm to 2 µm and although those prior patents prefer the use of phospholipid stabilizers, they also describe and enable the use of surface stabilizers that are not phospholipids. Additionally, he says that both can be administered without regard to food. Even if the ‘054 Patent was not anticipated, everything in the prior art rendered the inventive concept obvious.
[46] According to Dr. Mayersohn, the inventive concept of claims 1-3 are: (a) a stable nanoparticulate fenofibrate composition; (b) a particular particle size for the fenofibrate; (c) at least one surface stabilizer; (d) bioequivalence; and (e) redispersion in a biorelevant media. He says that the POSITA would not understand phospholipid-free to be part of the inventive concept since the ‘054 Patent lists useful stabilizers which include phospholipids. Alternatively, being phospholipid-free would have been obvious to the POSITA.
[47] Dr. Mayersohn reviews the prior art and states that the ‘335 Patent, WO ‘193 Patent, United States Patent 5,145,684 (US ‘684 Patent), United States Patent 5,510,118 (US ‘118 Patent), WO 01/21154 (WO ‘154 Patent), United States Patent 6,177,103 (US ‘103 Patent), and United States Patent 6,368,620 (US ‘620 Patent) all describe and enable the invention of the ‘054 Patent. Moreover, Dr. Mayersohn says, these prior patents render the inventive concept of the ‘054 Patent obvious.
Additional Expert Evidence
[48] One issue of significance in this application is the particle size of the fenofibrate particles in the Sandoz Tablet. It is also an issue of significance in T-991-10. A few days prior to the hearing of these applications, Fournier brought a motion seeking an order allowing the cross-referencing of certain affidavits and cross-examination transcripts as between Court Files T-1184-10 and T-991-10 on the basis that the evidence filed in these two applications by Sandoz, relating to the particle size of the fenofibrate in the Sandoz Tablet, was contradictory and that the interests of justice demanded that all of this evidence be before the applications judge in both matters.
[49] Sandoz resisted the motion, in part, on the basis that there is no conflict in the evidence, and in part of the basis that it would suffer prejudice because it has not had an opportunity to file expert evidence to assist the Court is assessing whether there truly is a conflict in the evidence.
[50] I granted the motion on the basis that:
[T]he interests of justice in having all of the relevant evidence before the Court and avoiding the possibility of conflicting findings of fact outweigh any prejudice of the sort Sandoz asserts it will suffer. Further, it is not clear that expert evidence of the type it says it would file is necessary or helpful to the Court in assessing what are statements of fact by the various expert witnesses.
[51] The issue as to whether there was any actual conflict in the evidence was to be determined as part of the decision on the merits of each application, if necessary.
[52] The portions of the Order relevant to this application are paragraphs 1 and 2 which read as follows:
1. The portions of the affidavit of Dr. Muzzio dated February 21, 2011, filed in T-991-10 on particle size, as well as the portions of his cross-examination transcript relating to particle size, are incorporated into the Applicants’ Record in T-1184-10.
2. The portions of the affidavits of Drs. Bogardus and Fairhurst in T-991-10 on particle size, as well as the portions of their cross-examination transcripts relating to particle size, are incorporated into the Applicants’ Record of T-1184-10.
[53] The evidence set out in these documents and the relevance, if any, in this application is discussed below.
Challenges to the Opinions of the Experts
[54] Both Fournier and Sandoz raised complaints about the expert(s) proposed by the other and made representations as to whether that evidence ought to be accepted and, if so, the weight it ought to be given.
[55] Fournier, at paragraph 12 of its Memorandum of Fact and Law, asked the Court to approach with caution the evidence of the experts put forward by Sandoz:
Sandoz put forward a 413 paragraph affidavit from Dr. Mayersohn (a pharmacist), a 384 paragraph affidavit from Dr. Serajuddin (a pharmacist), a 361 paragraph affidavit from Dr. Kanfer (a pharmacist), and a 241 paragraph affidavit from Dr. LeClair (a pharmacist). Sandoz’s experts were not always forthcoming in their cross-examinations, were difficult, refused to answer important questions, and accepted direction from Sandoz’s counsel to avoid answering questions. Not only were these witnesses advocates for Sandoz’s position, they clung to unreasonable positions with uncommon truculence, and in some cases gave evidence incapable of belief. Worse, Sandoz has put forward witnesses in this case who have given opinions directly opposite the position it has taken in the Notice of Allegation of T-991-10. If any of the issues in this application fall to be determined on the basis of any assessment of credibility, it is respectfully submitted that the evidence of Sandoz’s experts should be approached with caution, given the above [references omitted].
[56] Sandoz, for its part, at paragraphs 12 and 13 of its Memorandum of Fact and Law, challenged the evidence of Fournier’s expert, Dr. Muzzio:
Fournier’s only expert Dr. Muzzio admits that he does not have the credentials of the person to which the ‘054 Patent is addressed by his own definition.
Fournier has not challenged the qualifications of Sandoz’s experts or their expertise to provide the opinions in their affidavits and none of their opinions were shaken on cross-examination. Sandoz challenges the qualifications’ of Fournier’s expert Dr. Muzzio. Fournier did not permit Sandoz to complete his cross-examination [references omitted].
[57] Shortly before this application was heard, Sandoz brought a motion seeking to strike from the Application Record in this proceeding the affidavits of Dr. Muzzio on the ground that he was unresponsive and long winded, and because the respondent had been prevented from completing the cross-examination, despite being given additional time. I dismissed that motion and provided the following short endorsement setting out my reasons for so doing:
I accept that Dr. Muzzio’s responses to the questions asked were neither brief nor direct. He was, as was suggested by counsel, a difficult witness. However, Sandoz cross-examined this witness for four days and made no request at the end of that period for further cross-examination. It cannot now, a few days prior to the hearing on the merits, seek as a remedy the striking of that evidence when it failed to seek any additional time when it could have been provided.
It is also submitted that “Dr. Muzzio breached his signed Code of Conduct by relying on testing he had not done in his lab to support his opinion regarding sound prediction without referring to it in the Muzzio Validity Affidavit.” I am not satisfied on the balance of probabilities that the testing complained of was in the mind of the witness and formed a part of the basis for the opinion set out in the affidavit he provided. Rather, it appears more likely that this “testing” came to mind as he was being cross-examined and he mentioned it as a further basis to support his opinion. I find no breach of the Code of Conduct. Had I found a breach, given its nature, I would not have struck his evidence but rather would have determined that the violation would go to the weight to be given his evidence where there was conflicting evidence.
[58] It will be noted that the complaint raised by Fournier as to the challenges it faced in cross-examining the experts put forward by Sandoz mirror the complaint raised by Sandoz with respect to Fournier’s witness and which has been dealt with by the Court. For the reasons given in rejecting Sandoz’s motion to strike, I likewise give little weight to Fournier’s complaint. To paraphrase that endorsement, and with reference to Fournier’s complaint, I say this: Sandoz’s witnesses on some occasions were difficult; however, Fournier completed its cross-examination of them and made no request for further cross-examination or to have any objected questions answered.
[59] I find inappropriate and unfair the submission that the experts were advocates for Sandoz’s position. Each witness provided an affidavit as required by Rule 52.2 of the Federal Courts Rules, SOR/98-106, attesting that he or she had read and agreed to be bound by the Code of Conduct for Expert Witnesses. Paragraphs one and two of that Code provide as follows:
1. An expert witness named to provide a report for use as evidence, or to testify in a proceeding, has an overriding duty to assist the Court impartially on matters relevant to his or her area of expertise.
2. This duty overrides any duty to a party to the proceeding, including the person retaining the expert witness. An expert is to be independent and objective. An expert is not an advocate for a party [emphasis added].
[60] Fournier’s challenges to the impartiality of these witnesses are set out in footnotes 21 and 22 of its Memorandum of Fact and Law. These footnotes include the following two serious allegations: a witness’s “claim to have calculations – undisclosed contrary to the Code of Conduct – that yielded a 10% difference is reported to be 61%,” and similarities between the wording used in portions of the affidavits of Dr. Serajuddin and Dr. Mayersohn.
[61] I reject the submission that a Sandoz witness, contrary to the Code, failed to make a disclosure as has been suggested. Fournier cites as support for this allegation the cross-examination of Dr. Mayersohn taken October 28, 2011, Q 664-669 and 754-770. I see nothing