Bayer Inc. v. Apotex Inc.

Bayer Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2014-05-07
Neutral citation
2014 FC 436
File numbers
T-1579-12
Decision Content
Date: 20140507
Docket: T-1579-12
Citation: 2014 FC 436
CONFIDENTIAL REASONS AND JUDGMENT RELEASED: May 7, 2014 PUBLIC REASONS FOR JUDGMENT RELEASED: June 4, 2014
BETWEEN:
BAYER INC. AND
BAYER PHARMA AKTIENGESELLSCHAFT
Applicants
and
APOTEX INC. AND
THE MINISTER OF HEALTH
Respondents
PUBLIC REASONS FOR JUDGMENT
HUGHES J.
[1] This is an application brought by the Applicants Bayer Inc. and Bayer Pharma Aktiengesellschaft, collectively Bayer, under the provisions of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 (NOC Regulations), to prohibit the Minister of Health from issuing a Notice of Compliance to the Respondent Apotex Inc. in respect of its proposed drospirenone and ethinylestradiol combination until the expiry of Canadian Letters Patent No. 2,382,426 (the ‘426 Patent).
[2] For the reasons that follow I find that Apotex’s allegations as to non-infringement are justified thus the application is dismissed.
I. INDEX [3] The following is a table setting out the various topics dealt with in these Reasons by page number:
I. INDEX.. 2
II. THE COBALT PROCEEDINGS. 2
III. THE PARTIES AND PRODUCT AT ISSUE.. 4
IV. THE ‘426 PATENT GENERALLY.. 5
V. THE EVIDENCE.. 5
VI. ISSUES. 9
VII. BURDEN.. 11
VIII. GOING BEYOND THE NOTICE OF ALLEGATION.. 14
IX. PERSON OF ORDINARY SKILL IN THE ART. 15
X. CLAIM CONSTRUCTION.. 20
XI. INFRINGEMENT. 26
XII. INELIGIBILITY OF THE ‘426 PATENT FOR LISTING.. 28
XIII. VALIDITY- ANTICIPATION.. 41
XIV. VALIDITY- AMBIGUITY/ INSUFFICIENCY.. 50
XV. VALIDITY- OTHER ALLEGATIONS. 51
XVI. CONCLUSION AND COSTS. 52
II. THE COBALT PROCEEDINGS [4] I have previously heard and disposed of an application brought by Bayer in respect of the ‘426 Patent under the NOC Regulations, as against a different Respondent, Cobalt Pharmaceuticals Company in proceeding Court Docket No. T-215-12. My decision dated October 22, 2013 is cited as 2013 FC 1061. This will be referred as the Cobalt Proceedings.
[5] In the Cobalt Proceeding I concluded that none of the allegations as to non-infringement or invalidity of the ‘426 Patent as raised by Cobalt in its Notice of Allegation and as restricted by Counsel in argument, were justified. Accordingly I gave Judgment prohibiting the Minister from issuing a Notice of Compliance to Cobalt until the expiry of the ‘426 Patent. That patent will expire on August 31, 2020.
[6] Cobalt has appealed to the Federal Court of Appeal from my decision (file no. A-376-13). The list of entries for that appeal indicates that a Record has been filed as have memoranda of argument by each party. No date for the hearing of that appeal has been set as of this time.
[7] At a pre-hearing conference which I held with Counsel for the parties I indicated that I had read the Record in the present proceedings and the memoranda of argument filed in these proceedings by each party. I indicated that I would be inclined to follow my decision in the Cobalt Proceedings unless a different issue has been raised in these proceedings or substantially different evidence was in the Record in these proceedings. On April 22, 2014 Counsel for Apotex, writing on behalf of both Apotex and the Applicants, filed a letter with the Court stating, inter alia:
The parties will not be making any submissions in Court File No. T-1579-12 in respect of Apotex’s allegation that Canadian Patent No. 2,382,426 is obvious, it being understood that, if the Court considers it necessary to dispose of this obviousness allegation, it will be found to be not justified for the reasons expressed in the Reasons for Judgment in the Cobalt Proceeding.
[8] With this in mind I have heard submissions from Counsel for each of the Applicants Bayer and the Respondent Apotex in the present proceedings. Some of the Reasons that follow are taken more or less directly from my Reasons in the Cobalt Proceedings 2013 FC 1061 in instances where the issues or evidence are not substantially different or the matters are not controversial.
III. THE PARTIES AND PRODUCT AT ISSUE [9] The Applicant Bayer Inc. is a “first person” as described in the NOC Regulations. It has listed the patent at issue with the Minister of Health in apparent accordance with those Regulations.
[10] The other Applicant Bayer Pharma Aktiengesellschaft is the owner of the patent at issue.
[11] Bayer distributes in Canada birth control tablets under the brand name YAZ. The tablets include as active ingredients 3 mg drospirenone + 20 mg ethinylestradiol in tablet form for oral administration.
[12] The Respondent Apotex Inc. is a “second person” as described in the NOC Regulations. On or about July 10, 2012, Apotex served on Bayer a Notice of Allegation stating that it has applied to the Minister of Health for a Notice of Compliance in order to distribute in Canada a generic version of Bayer’s YAZ tablets.
[13] The Respondent Minister of Health performs various duties as provided in the NOC Regulations; including, in appropriate circumstances, the issuance of a Notice of Compliance (NOC) to a second person, which would permit the sale of a generic version of a specified drug in Canada. The Minister took no active part in these proceedings.
IV. THE ‘426 PATENT GENERALLY [14] The '426 patent is entitled “Pharmaceutical Combination of Ethinylestradiol and Drospirenone for Use as a Contraceptive”. It names Wolfgang Heil, Jurgen Hilman, Ralph Lipp and Renate Heithecker as inventors.
[15] The application for this patent was filed under the provisions of the Patent Co-Operation Treaty with an effective filing date in Canada of August 31, 2000. The application was made available for public inspection March 8, 2001. The application claimed priority from both a United States and a European patent application, each filed August 31, 1999.
[16] The '426 patent was issued and granted in Canada on February 28, 2006. The term of the patent will expire August 31, 2020.
V. THE EVIDENCE [17] As is usual in proceedings of this kind, the evidence consisted of affidavits tendered by each of the parties, and transcripts of the cross-examinations conducted upon those affiants selected for cross-examination. The Court had no opportunity to observe any witness in person. Some witnesses were tendered as experts; no party objected to the fact that they were tendered as experts. I am satisfied that all experts have given evidence that assists the Court in resolving the matters at issue and I am not prepared, on the Record that I have, to find any of them lacking in credibility or lacking in sufficient expertise in the matters addressed in their evidence.
[18] Bayer filed the evidence of the following expert witness:
1. Dr. Martyn Davies of Nottingham, United Kingdom, a Professor in Biomedical Surface Chemistry, Laboratory of Biophysics and Surface Analysis at the School of Pharmacy at the University of Nottingham in the UK. He provided expert evidence as to the analysis of tablets of the kind Apotex wishes to sell in Canada and evidence as to several aspects of pharmaceutical chemistry matters at issue. At times his Affidavit strayed beyond the opinions of an expert into the areas of legal argument. I give those portions of his evidence little weight. Dr. Davies was cross-examined.
[19] Bayer also filed the evidence of the following fact witnesses
2. Dr. Wolfgang Heil of Seevetal, Germany. He presently works as a pharmacist. He was a member of the Pharmaceutical Development Group at Schering and is one of the named inventors of the ‘426 patent. He gave evidence as to the development of the product at issue. Schering was the predecessor of Bayer. He was cross-examined.
3. Dr. Michael Hümpel of Lübeck, Germany. He is now retired having worked at Schering (Bayer) from 1974 to 2006. He gave evidence as to the development of the product at issue. He was cross-examined.
4. Dr. Joachim Marr of Berlin, Germany. He is a Vice-President of Global Clinical Development in Women’s Health at Bayer. He gave evidence respecting the clinical studies of the product at issue. He was cross-examined.
5. Ms. Mira Rinnie of Aurora, Ontario. She is a law clerk in the offices of the solicitors for Bayer. Her affidavit served to make certain documents of record. She was not cross-examined.
6. Dr. Johannes W. Tack of Berlin, Germany. He presently works as COO of a pharmaceutical company unrelated to the parties to this proceeding, he did work for Schering between 1978 and 2001. He testified to the development of the product at issue. He was cross-examined.
[20] Apotex filed the evidence of the following fact witnesses:
1. Ms. Lisa Ebdon of Vaughan, Ontario. She is a law clerk in the offices of Apotex’s solicitors. Her affidavit served to make certain documents of record. She was not cross-examined.
2. Ms. Raquel Fernandez, of (….)She is an employee of (….)who supplies the tablets at issue to Apotex. She identified samples of certain (…) products and their dispatch to Apotex’s solicitors. She was cross-examined.
[21] Apotex filed the evidence of the following expert witnesses:
3. Dr. Michael Cima of Cambridge, Massachusetts. He is the David H. Koch Professor of Engineering and MIT Professor of Materials Science and Engineering at Massachusetts Institute of Technology (MIT). He gave evidence as to the testing of certain materials and as to pharmaceutical chemistry. He was cross-examined.
4. Dr. Paul J. Jarosz of Westminster, Colorado. He is a consultant in the pharmaceutical industry and has worked with a number of pharmaceutical companies in their research areas and has served as an adjunct professor. He gave evidence as to a number of pharmaceutical chemical matters. He was cross-examined.
5. Dr. Donald T. Jung of Cupertino, California. He is Director of Nonclinical and Clinical Pharmacology at Threshold Pharmaceuticals. He gave evidence directed to whether the claimed invention of the patent at issue was obvious. He was cross-examined. The issue of obviousness, hence his evidence, was not argued before me.
6. Mr. David Rosen of Cabin John, Maryland. He is a practicing United States attorney, a partner of Foley & Lardner LLP, FDA practice group leader and co-chair of its Life Sciences Interest Team. He gave evidence as to the legal effect of circumstances related to the United States clinical tests of the Bayer product. He was cross-examined.
7. Dr. James A. Simon of McLean, Virginia. He is a physician and currently Clinical Professor in the Division of Reproductive Endocrinology and Infertility at George Washington University School of Medicine. He gave evidence respecting clinical testing. He was cross-examined.
VI. ISSUES [22] Notwithstanding the disposition by this Court of issues of validity and infringement respecting the ‘426 patent in the Cobalt Proceedings, those issues are under appeal and thus are not yet finally determined in those proceedings.
[23] The parties have raised issues of validity and infringement in the present proceedings. As to infringement, the process used by Apotex to make the product at issue is arguably different from that used by Cobalt in the Cobalt Proceedings, and therefore requires fresh examination.
[24] In these proceedings Apotex has raised an issue as to whether the ‘426 patent was properly listed under the provisions of the NOC Regulations. That issue was not dealt with in the Cobalt Proceedings.
[25] As to validity of the ‘426 patent Apotex has raised several issues, some of which were dealt with in the Cobalt Proceedings. The issue of obviousness was dealt with in the Cobalt Proceedings and, as set out earlier in these Reasons, Apotex has, by the letter from its solicitors of April 22, 2014, agreed that, for the purposes of my decision, I may find that Apotex’s allegations as to obviousness are not justified. I so find.
[26] Further, by a letter from its solicitors dated April 28, 2014 Apotex advised that it did not intend to advance oral argument as to certain issues pertaining to construction, overbreadth and lack of utility and sound prediction but would rely on its written memorandum. In particular that letter advised the Court:
Apotex has decided to further streamline its oral argument and does not intend to advance oral arguments in respect of the following additional issues:
• Construction re: dissolution profile of claim 31 (Memorandum para. 30)
• Overbreadth re: claims to dissolution profile claim desired result (Memorandum paras. 92-93); and
• Lack of demonstrated utility and sound prediction (Memorandum paras. 97-103)
Apotex will instead rely only on the written arguments in its Memorandum of Fact and Law relating to these issues.
[27] At the hearing Bayer’s Counsel advised the Court that Bayer would be relying on the following claims of the ‘426 patent: claim 1 and dependent claims 2 to 8 and 12; claim 30; and claim 31 and dependent claims 36, 37, 39 to 42 and 47 to 50.
[28] I will first deal with some preliminary issues.
VII. BURDEN [29] The jurisprudence as to burden has not changed since I wrote my decision in the Cobalt Proceedings, therefore I will repeat that portion of my Reasons cited as 2013 FC 1060.
[30] I summarized the questions of burden in these matters where validity is at issue recently in Novartis Pharmaceuticals Canada Inc v Cobalt Pharmaceuticals Company, 2013 FC 985 at paragraph 23, which I adopt here:
[23] Who bears the burden when validity of a patent is at issue in NOC proceedings has been discussed many times in this Court. In brief: a patent is presumed to be valid in the absence of evidence to the contrary (Patent Act, s. 43(2)). The party alleging invalidity (here Cobalt) has the burden of putting forth evidence supporting its allegations. Once evidence is led the matter is determined by the Court on the civil burden of proof; namely, balance of probabilities. If the Court finds the matter to be evenly balanced, then it should find in favour of the person alleging invalidity since, under the NOC Regulations, subsection 6(2), the first person (here Novartis) bears the burden of demonstrating that the allegations of invalidity are not justified.
[31] Similarly, with respect to the second person’s [generic’s] allegations of non-infringement, the first person [innovator] bears the burden of proving that such allegations are not justified. This matter was recently reviewed by the Federal Court of Appeal in Pfizer Canada Inc v Minister of Health and Ratiopharm Inc, 2011 FCA 215, where Létourneau JA, writing for the Court, referred to earlier decisions of that Court in Fournier and Apotex to emphasize that these proceedings are administrative in nature, the purpose being to determine if the Minister is free to issue a Notice of Compliance; the proceedings are not to be confused with infringement or impeachment actions. He wrote at paragraphs 15 and 18:
15 The nature, purpose and scope of the NOC proceedings and their relationship with impeachment proceedings have been conveniently summarized by Layden-Stevenson J. (as she then was) in Fournier Pharma Inc. v. Canada (Minister of Health) (2004), 38 C.P.R. (4th) 297, 2004 FC 1718. At paragraphs 6, 8 and 9, she writes:
[6] As noted, this proceeding is brought under the Regulations. The history and scheme of the Regulations have been delineated in various decisions of the Federal Court of Appeal and need not be repeated here. See: Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1994), 55 C.P.R. (3d) 302 (F.C.A.);...). Basically, issues of non-infringement and validity between the patent holder (first person) and the person seeking a NOC from the Minister (second person) originate with a NOA, served on the first person by the second person, setting out the second person's allegations, including the legal and factual basis in support. The first person may disagree and apply to the court for an order prohibiting the Minister from issuing a NOC to the second person until after expiration of the patent.
...
[8] Section 6 proceedings are not to be likened to actions for determining validity or infringement. They are proceedings in judicial review, to be held expeditiously, whose aim is to determine whether the Minister is free to issue the requested NOC. Their scope is confined to administrative purposes: Apotex Inc. v. Canada (Minister of National Health and Welfare) (1997), 76 C.P.R. (3d) 1 (F.C.A.). The determination must turn on whether there are allegations by the second person sufficiently substantiated to support a conclusion for administrative purposes (the issuance of a NOC) that an applicant's patent would not be infringed if the second person's product is put on the market: Pharmacia Inc. v. Canada (Minister of National Health and Welfare) (1994), 58 C.P.R. (3d) 209 (F.C.A.).
[9] By merely commencing the proceeding, the applicant obtains what is tantamount to an interlocutory injunction without having satisfied any of the criteria a court would require before enjoining issuance of a NOC: Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1998), 80 C.P.R. (3d) 368 (S.C.C.);...). The Regulations allow a court to determine summarily, on the basis of the evidence adduced, whether the allegations are justified. Section 6 proceedings are not adjudicative and cannot be treated as res judicata. The patentee is in no way deprived of all the recourses normally available to enable it to enforce its rights. If a full trial of validity or infringement issues is required, this can be obtained in the usual way by commencing an action:
Pfizer Canada Inc. v. Apotex Inc. (2001), 11 C.P.R. (4th) 245 (F.C.A.);...).
…
18 The scope of application of section 8 and its interplay with impeachment proceedings were reviewed by our Court in Apotex Inc. v. Syntex Pharmaceuticals International Ltd., 2010 FCA 155. Writing for a unanimous court, Dawson J.A. held at paragraph 36:
[36] Under the 1993 version of the Regulations, when an innovator commenced a proceeding seeking a prohibition order it obtained the equivalent of an interlocutory injunction prohibiting the issuance of a notice of compliance for up to 30 months. The innovator need not have satisfied the criteria for obtaining injunctive relief and no undertaking for damages was required. In that circumstance, section 8 of the Regulations was intended to provide redress to the generic where the innovator failed to establish that the generic's allegations of invalidity or non-infringement were not justified. In my view, section 8 was not intended to provide redress where the innovator prevailed in the prohibition proceeding, even if the generic was later successful in patent litigation. It follows that I agree with the Judge that Apotex can not "reach back and apply the finding of invalidity in the action so as to argue that the '671 patent had 'expired' within the meaning of section 8" of the 1993 version of the Regulations.
[32] Here Bayer complains that in the course of these proceedings, Apotex has adduced only limited evidence as to its product, such as that it will contain 3 mg of drospirenone, and that the drospirenone will be formulated in accordance with a particular technique which it describes as molecular dispersion. The Court must then deal with Apotex’s allegations as to non-infringement and such evidence as there is in the record, so as to determine if those allegations are justified or not.
VIII. GOING BEYOND THE NOTICE OF ALLEGATION [33] It has been established by the Court of Appeal that the second person, a generic such as Apotex, has an obligation in its Notice of Allegation to raise all the facts and legal arguments upon which it relies in support of its allegations. It cannot craft new arguments, or raise new allegations or new facts or new prior art documents not set out in the Notice of Allegation. (AB Hassle v Canada (Minister of National Health and Welfare) (2000), 7 CPR (4th) 272, at paras 21-24; Proctor & Gamble Pharmaceuticals Canada, Inc v Canada (Minister of Health), 2002 FCA 290, at paras 21-26.
[34] While this may seem draconian since, undoubtedly, new matters may be raised as experts are consulted and evidence emerges, it is equally draconian for the first person who decides to institute proceedings to face shifting allegations and facts. The process is in need of change, but no interested person seems to be pressing for that change.
[35] As matters stand now, the Court must reject arguments based on facts or documents not set out in the Notice of Allegation nor can the Court address new allegations.
[36] I repeat the words of Stone JA in AB Hassle, supra where he wrote at paragraph 21 that the Notice of Allegation must set forth the legal and factual bases for the allegations in a sufficiently complete manner so as to enable the first person (here Bayer) to assess its course of action in response to the allegations.
IX. PERSON OF ORDINARY SKILL IN THE ART [37] The Field of Invention is set out at page 1 of the patent:
FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition comprising drospirenone and ethinylestradiol, a method of providing dissolution of drospirenone, methods of inhibiting ovulation by administration of drospirenone and the use of drospirenone and ethinylestradiol for inhibiting ovulation.
[38] The next section, Background of the Invention, acknowledges that oral contraceptive products made of a combination of a gestagen and an estrogen are prior art. It is acknowledged that one such gestagen, drospirenone, has been disclosed as useful in treating several disorders, and that a combination of drospirenone (drsp) and ethinylestradiol (ee) have been suggested as a possible, but not a preferred, combination for an oral contraceptive.
[39] The next section is Summary of the Invention, in which it is stated that a minimum dosage level, and a maximum dosage level, of drospirenone has been determined.
SUMMARY OF THE INVENTION
In the course of research leading to the present invention, it has surprisingly been found that a hitherto undisclosed minimum dosage level of drospirenone is required for reliable contraceptive activity. Similarly, a preferred maximum dosage has been identified at which unpleasant side effects, in particular excessive diuresis, may substantially be avoided.
[40] A “Detailed Disclosure of the Invention” begins at page 4. It is stated that, to ensure good bioavailability of drospirenone, it should be provided in a form that promotes rapid dissolution. The next paragraph addresses micronization, provides parameters of particle size and distribution, provides dissolution parameters, and indicates that it is possible to provide the product, invalid or micronized, by spraying onto an inert carrier. Without being limited to a particular theory, the patent says that the dissolution rate in vivo may result in higher bioavailability. The ethinylestradiol component may also be micronized or sprayed.
[41] The detailed disclosure goes on to describe carriers and excipients, particular dosages, other uses, dosage packaging, daily dosage and rest period.
[42] At page 9, the patent addresses formulation in any manner known in the pharmaceutical art:
[43] There follows a discussion that the tablets may be film-coated (not to be confused with enteric coated) and that the composition may be formulated in liquid form. Packaging, parenteral formulation, and transdermal formulation are discussed.
[44] Five examples follow. Example 1 deals with the preparation of tablets containing drospirenone and ethinylestradiol; both micronized. Example 2 deals with the dissolution rate of the drospirenone in such tablets. Example 3 with the dissolution rate of ethinylestradiol. Example 4 deals with the bioavailability of those components in the tablets. Example 5 deals with the contraceptive efficacy.
[45] The claims – 53 in all – follow.
X. CLAIM CONSTRUCTION [46] It is well established law in Canada that construction of the claims at issue must precede the inquiry as to infringement and validity. Construction is for the Court aided by expert evidence, if needed, as to the background state of the art and the meaning of specific terms. Construction is done in the context of the description contained in the patent, care being taken not simply to take this or that gloss from the description in interpreting the claim.
[47] Claim construction is not done in a vacuum, the Court must be cognizant as to the contentious issues raised by the parties. Sometimes this is referred to as “where the shoe pinches”. In the Cobalt proceedings the shoe pinched only in one place, whether all claims including claims 30 and 31 required that the drospirenone compound comprised only “micronized” particles of drospirenone or whether they including other forms such as particles onto which drosprirenone has been sprayed.
[48] In the present case the pinching of the shoe is broader, namely, do the claims include drospirenone found as a molecular dispersion(….). A further pinching here is whether the claims include ethinylestradiol in the form of a clathrate.
[49] In the present proceeding Bayer is asserting more claims than it did in the Cobalt Proceedings. In the Cobalt Proceedings, Bayer asserted, at the end of the day, only claims 30 and 31. In the present case Bayer asserts claim 1 and dependent claims 2 to 8 and 12; claim 30; and claim 31 and dependent claims 36,37, 39 to 42 and 47 to 50.
[50] I will start by repeating some of what I wrote at paragraphs 50 to 59 of my decision in the Cobalt Proceedings 2013 FC 1061.
[50] Claim 1 specifies micronized drospirenone, without stating the form in which ethinylestradiol is present:
[51] Claim 3 specifies that the ethinylestradiol may be micronized or sprayed:
[52] It is to be noted that no claim of the '426 patent specifically claims that the drospirenone component may be sprayed. This is unlike the circumstances in the United Kingdom Court of Appeal in Gedeon Richter, supra, where it can be seen from paragraph 30 of the Reasons of that Court that claim 2, and all claims dependent of claim 2, stipulate that the drospirenone may be “in micronized form or sprayed”. The patent laws of the United Kingdom permit claims to be amended by the Courts.
[53] Claim 30 defines the drospirenone component only by particle size (but not particle distribution, as also recited in the Description of the patent):
[54] Claim 31 defines the drospirenone component only by its dissolution rate:
[55] In considering claims 30 and 31, the parties are in contention. Cobalt argues that the particle size and dissolution rate parameters relate only to the micronized form of drospirenone. Bayer argues that at least the dissolution rate relates to drospirenone in any form, whether micronized or sprayed.
[56] Cobalt supports its argument by referring to page 4 of the Description of the patent where the particle size (and distribution) parameters, and the dissolution parameters, follow the discussion of the micronized drospirenone, and by referring to the claims in which explicit reference to spraying is made only in respect of the ethinylestradiol component.
[57] Bayer supports its position by saying that spraying the drospirenone component is mentioned at page 4 of the Description, and that at page 9 of the Description, it says that the composition may be formulated “in any manner known in the art: whether micronized or sprayed”. Bayer argues that the essential point of the patent is not micronized drospirenone; rather, it is rapid dissolution, as stated in the last sentence of the first paragraph at page 4, in the Detailed Disclosure:
To ensure good bioavailability of the compound, it is therefore advantageously provided in a form that promotes rapid dissolution thereof.
[58] This is followed up by the statement at the beginning of the last full paragraph at page 4:
Without wishing to be limited to any particular theory, it appears that the in vitro dissolution rate of drospirenone is connected to the dissolution rate in vivo resulting in rapid absorption of drospirenone in vivo on oral administration of the compound.
[59] While the matter is by no means free of doubt, I am of the opinion that Bayer’s interpretation is the correct one, and that claim 31, and its dependent claims, is not limited to drospirenone in its micronized form, but to any form in which the rapid dissolution rate stipulated by that claim can be achieved.
[51] Here, I must go further. In particular I must consider whether claim 31, including its dependent claims, include a circumstance where drospirenone appears in the form of a molecular dispersion (….). Also, I must consider whether the ethinylestradiol called for in any of the claims at issue include a clathrate of that compound.
[52] First I address claims 1 and its dependent claims, claims 2 to 8 and 12. I am satisfied that those claims are directed just to what they say they are directed, namely “micronized drospirenone particles” and not to any other form, for instance not to particles onto which drospirenone is sprayed and not to a composition wherein drospirenone appears as a molecular dispersion (….).
[53] In the Cobalt decision I did not particularly construe claim 30 as to the “drospirenone particles” but here I will so construe that term, as I did with claim 31, so as to include not only micronized drospirenone particles but also particles onto which drospirenone has been sprayed, so long as those particles meet the size parameters of claim 30.
[54] I did construe claim 31 and its dependent claims in the Cobalt decision so as not to be limited to drospirenone in its micronized form, but to any form in which the rapid dissolution by the claim can be achieved.
[55] The present issue for construction is whether claim 31 and its dependent claims, which requires “drospirenone particles” which “when provided the tablet form” has a particular dissolution profile can extend to forms other than particles of drospirinone or inert particles onto which drospirinone has been sprayed .
[56] The question can be put as whether “drospirenone particles” are particles of drospirenone, or can extend to particles onto which drospirenone has been sprayed as I have found in my Cobalt decision, or whether it can also extend to “particles of a solid matrix in which drospirenone has been dissolved.”
[57] I return to the description of the patent in particular at pages 4 and 9 which I set out earlier in these reasons but will repeat. At page 4:
DETAILED DISCLOSURE OF THE INVENTION
Drospirenone, which may be prepared substantially as described in, e.g., US 4,129,564 or WO 98/06738, is a sparingly soluble substance in water and aqueous buffers at various pH values. Furthermore, drospirenone is rearranged to an inactive isomer under acid conditions and hydrolysed under alkaline conditions. To ensure good bioavailability of the compound, it is therefore advantageously provided in a form that promotes rapid dissolution thereof.
It has surprisingly been found that when drospirenone is provided in micronized form (so that particles of the active substance have a surface area of more than 10,000 cm2/g, and the following particle size distribution as determined under the microscope: not more than 2 particles in a given batch with a diameter of more than 30um, and preferably <20 particles with a diameter of >10 um and <30 um) in a pharmaceutical composition, rapid dissolution of the active compound from the composition occurs in vitro (“rapid dissolution” is defined as the dissolution of at least 70% over about 30 minutes, in particular at least 80% over about 20 minutes, of drospirenone from a tablet preparation containing 3mg of drospirenone in micronized form, it is possible to dissolve it in a suitable solvent, e.g. methanol or ethyl acetate, and spray it onto the surface of inert carrier particles followed by incorporation of the particles containing drospirenone on their surface in the composition.
At page 9:
The composition of the invention may be formulated in any manner known in the pharmaceutical art. In particular, as indicated above, the composition may be formulated by a method comprising providing drospirenone and, if desired, ethinylestradiol in micrnoized form in said unit dosage form, or sprayed from a solution onto particles of an inert carrier in admixture with one or more pharmaceutically acceptable excipients that promote dissolution of the drospirenone and ethinylestradiol so as to promote rapid dissolution of drospirenone and preferably ethinylestradiol and oral administration.
[58] The patent describes, therefore, drospirenone that is provided in one of two forms, in micronized form, or drospirenone that has been dissolved in a solvent, sprayed in to an inert carrier particles, then dried. Reference is also made to formulation by “any manner known in the pharmaceutical art” The formulation of those particles (micronized or sprayed on) with other excipients can then proceed in any manner known in the pharmaceutical art.
[59] No mention is made of a process whereby drospirenone is dissolved into a matrix(….), then mixed in with the other ingredients. In such a process drospirenone is no longer a “particle” or even sprayed onto a “particle”, it is in solution.
[60] I therefore construe the term “drospirenone particles” as appearing in all of the claims at issue not to include a drospirenone solution nor particles of a matrix into which drospirenone has previously been dissolved.
[61] As to the other area in which the shoe pinches with respect to the ethinylestradiol I have discussed the evidence fully later in these reasons as to whether the ‘426 patent was eligible for listing. I conclude as I did in respect of that reasoning that the claims at issue include a clathrate of ethinylestradiol within the term ethinylestradiol.
XI. INFRINGEMENT [62] Having construed all of the claims at issue not to include a formulation in which the drospirenone is provided in form wherein it has been dissolved in a matrix I find that the Apotex product is prepared by a method in which the drospirenone has been provided in a form where it is first dissolved in a matrix. The process then proceeds (….) the material is compressed into tablets, and the tablets coated with a non-enteric material; all as more particularly explained at paragraphs 124 to 127 of Dr. Cima’s affidavit.
[63] The dissolution profile of the resulting tablet is almost identical to that of Bayer’s YAZ tablets and, to that extent, meets the parameters of claim 31 of the ‘426 patent.
[64] Each of Bayer’s and Apotex’s witnesses have provided evidence as to testing of certain samples by a technique known as Raman or, in the case of Dr. Cima, Raman and a scanning electron microscope. Dr. Davies’ evidence, presented on behalf of Bayer comments on tests conducted on samples of product produced by (….) for the South African market. Dr. Cima’s tests, presented on behalf of Apotex were performed on bulk drospirenone particles and representative Apotex tablets. As recited in my Order dated October 22, 2013 in these proceedings Apotex does not challenge that both Dr. Davies and Dr. Cima tested the same thing.
[65] The conclusions reached by Dr. Davies and Dr. Cima as to the results exhibited by their respective tests, are different. Dr. Davies argues, and I emphasize the word argue, at paragraphs 175 to 183 of his affidavit that Apotex has not proved that its product is a molecular dispersion of drospirenone. His opinion is largely based on an analysis of documents rather than scientific evidence; in so doing he stepped into the role of an advocate rather than providing expert scientific opinion. Dr. Cima, on the other hand, sticks to the role of a scientist. At paragraphs 129 and following of his affidavit he reviews the testing conducted under his direction and concludes, at paragraphs 153 to 159 that there are no particles of drospirenone or micronized drospirenone particles in the samples tested. I accept what Dr. Cima wrote at paragraphs 154 and 155 of his affidavit:
154. (….)
155. The results of the Raman spectroscopic analysis conducted in my laboratory on the tablet samples support the conclusion that the drospirenone is present in the granules as a solid solution (molecular dispersion). (….)
[66] I prefer Dr. Cima’s evidence, but, even if the evidence were equally balanced, Bayer has not overcome the burden that it bears of proving, on a balance of probabilities, that Apotex’s allegations of non-infringement are not justified.
[67] Given that the drospirenone is provided in a form which I have found is not within any claim at issue, and given that this is the basis upon which Apotex has alleged non-infringement, I find that Bayer has not established that Apotex’s allegation in this regard is not justified.
XII. INELIGIBILITY OF THE ‘426 PATENT FOR LISTING [68] Apotex has alleged that the ‘426 patent is ineligible for listing by Bayer under the provisions of the NOC Regulations as amended October 5, 2006. These allegations were raised in Apotex’s Notice of Allegation but no motion was brought, in this respect, under subsection 6 (5)(a) of those Regulations.
[69] The gist of Apotex’s allegation is that Bayer listed the ‘426 patent under the NOC Regulations in December 2008 as against its YAZ tablets. Those tablets contain, as the active ingredients, drospirenone and a molecular inclusion complex formed between ethinylestradiol (EE) and B-cyclodextrin (ie. EE-B-cyclodextrin complex). This is defined to by Apotex’s expert Jarosz as a clathrate. Apotex argues that this clathrate is not the ethinylestradiol as claimed in the ‘426 patent thus the patent is improperly listed in respect of the YAZ product.
[70] Bayer argues that Apotex cannot raise this issue at the hearing, it must do so by a motion brought before the hearing, which it did not do. In any event, Bayer argues that the ‘426 patent has been properly listed.
[71] First, as to whether this issue can be raised at the hearing or must be raised at an earlier motion, there have been several decisions of this Court which address the issue.
[72] In Pfizer Canada Inc. v Apotex Inc., 2005 FC 1421 Justice Mosley held that the issue could be raised at a hearing without a previous motion hearing been brought. He wrote at paragraphs 177 and 178:
[177] At any time prior to the hearing of this application, Apotex could have brought a motion under 6(5)(a). Apotex argues, however, that it would have been imprudent to do so and would have likely wasted time and resources because of the high standard required to strike out an application; that the listing was so plainly improper to be bereft of any chance of success : David Bull Laboratories (Canada) Inc. v. Pharmacia Inc. et al., [1995] 1 F.C. 588, 58 C.P.R. (3d) 209 (C.A.). If they can bring it at this stage, they also enjoy the tactical advantage that the burden to disprove the allegations rests with the applicants whereas Apotex would have carried the burden on a preliminary motion to dismiss.
[178] I accept that Apotex can make its allegation as part of these proceedings and is not required to bring a motion under subsection 6(5) in advance of the hearing of the 6(1) application. I am also satisfied that Pfizer has failed to establish on a balance of probabilities that the ‘071 patent was properly listed on the patent register as it was out of time when the NOC for the accelerated dosing regime for the 500 mg tablets was issued.
[73] In Abbott Laboratories v Canada (Minister of Health), 2007 FCA 187, the Court of Appeal determined that while the issue of eligibility is usually raised by way of a prior motion, the Trial Judge was not wrong in dealing with the matter at the hearing. Noel JA, for the Court on this panel, wrote at paragraphs 44 and 45:
[44] Finally, I note that Heneghan J. spoke