Bayer Inc. v. Cobalt Pharmaceuticals Company

Bayer Inc. v. Cobalt Pharmaceuticals Company
Court (s) Database
Federal Court Decisions
Date
2013-10-22
Neutral citation
2013 FC 1061
File numbers
T-215-12
Decision Content
Date: October 22, 2013
Docket:
T-215-12
Citation: 2013 FC 1061
Toronto, Ontario, October 22, 2013
PRESENT: The Honourable Mr. Justice Hughes
BETWEEN:
BAYER INC. AND BAYER PHARMA AKTIENGESELLSCHAFT
Applicants
and
COBALT PHARMACEUTICALS COMPANY AND THE MINISTER OF HEALTH
Respondents
REASONS FOR JUDGMENT AND JUDGMENT
[1] This is an application brought 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 Cobalt Pharmaceuticals Company in respect of its proposed drospirenone + ethinylestradiol combination product until the expiry of each of Canadian Letters Patent No. 2,179,728 and 2,382,426.
[2] For the reasons that follow, I find that the application is allowed with respect to Canadian Patent No. 2,382,426 and dismissed with respect to Canadian Patent No. 2,179,728.
[3] The following is a table setting out the various topics dealt with in these Reasons by paragraph number:
THE PARTIES AND PRODUCT AT ISSUE
Paras 4 - 8
THE PATENTS AT ISSUE GENERALLY
Paras 9
THE '728 PATENT GENERALLY
Paras 10 - 12
THE '426 PATENT GENERALLY
Paras 13 - 15
THE EVIDENCE
Paras 16 - 19
FOREIGN DECISIONS
Paras 20 - 21
ISSUES
Paras 22 - 30
BURDEN
Para 31 - 33
GOING BEYOND THE NOTICE OF ALLEGATION
Paras 34 - 37
THE '426 PATENT
1. Person of Ordinary Skill in the Art
Para 38
2. Where the Shoe Pinches
Para 39
3. Description
Paras 40 - 48
4. The Claims - Construction
Paras 49 – 60
5. Non-Infringement
Paras 61 – 69
6. Validity - Obviousness
Paras 70 – 88
7. Utility and Sound Prediction
Paras 89 - 100
8. Overbreadth and Insufficiency
Paras 101 – 102
9. Ambiguity
Paras 103 - 106
10. Conclusion Respecting the '426 Patent
Para 107
THE '728 PATENT
1. Person of Ordinary Skill in the Art
Para 108
2. Where the Shoe Pinches – Dose Equivalent
Paras 109 – 110
3. The Description
Paras 111 – 123
4. The Claims - Construction
Paras 124 – 134
5. Non-Infringement
Para 135
6. Obviousness
Paras 136 – 139
7. Double Patenting
Paras 140 – 149
8. Utility and Sound Prediction
Paras 150 – 155
9. Method of Medical Treatment
Paras 156 – 162
10. Conclusions Respecting the '728 Patent
Para 163
COSTS
Para 164
THE PARTIES AND PRODUCT AT ISSUE
[4] The Applicant Bayer Inc. is a “first person” as described in the NOC Regulations. It has listed each of the two patents at issue with the Minister of Health in apparent accordance with those Regulations.
[5] The Applicant Bayer Pharma Aktiengesellschaft is the apparent owner of the two patents at issue. It is convenient simply to refer to the Applicants collectively as Bayer.
[6] 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.
[7] The Respondent Cobalt Pharmaceuticals Company is a “second person” as described in the NOC Regulations. On or about December 8, 2011, Cobalt served on Bayer a Notice of Allegation in apparent compliance with those Regulations, 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.
[8] 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.
THE PATENTS AT ISSUE GENERALLY
[9] There are two Canadian patents at issue; numbers 2,179,728 (the '728 patent) and 2,382,426 (the '426 patent). The application for each patent was filed with the Canadian Patent Office after October 1, 1989; therefore, the provisions of the “new” Patent Act, RSC 1985, c. P-4, applicable to patents applied for after that date, apply to both patents at issue here.
THE '728 PATENT GENERALLY
[10] The '728 patent is entitled “Composition for a Contraceptive Comprising an Estrogen and a Gestogen”. It names Jürgen Spona, Bernd Düsterberg, Frank Lüdicke, W. Feichtinger and Max Elstein as inventors. One of them, Bernd Düsterberg, gave evidence in these proceedings.
[11] The application for this patent was filed under the provisions of the Patent Co-Operation Treaty (PCT) with a filing date, effective in Canada, of December 22, 1994. The application was made available for public inspection (publication date) on June 29, 1995. The application claimed priority from a German application filed on December 22, 1993.
[12] The '728 patent was issued and granted in Canada on September 1, 2009. The term of the patent will expire December 22, 2014.
THE '426 PATENT GENERALLY
[13] The '426 patent is entitled “Pharmaceutical Combination of Ethinylestradiol and Diospirenone for Use as a Contraceptive”. It names Wolfgang Heil, Jurgen Hilman, Ralph Lipp and Renate Heithecker as inventors.
[14] 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.
[15] The '426 patent was issued and granted in Canada on February 28, 2006. The term of the patent will expire August 31, 2020.
THE EVIDENCE
[16] 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, although each party wished to comment upon what they perceived as shortcomings in their expertise. I am satisfied that all experts have given evidence that assists the Court in resolving the matters at issue and I am not prepared to find any of them lacking in credibility or lacking in sufficient expertise in the matters addressed in their evidence.
[17] Bayer filed the evidence of the following four fact witnesses, the first three of whom were cross-examined:
• Dr. Bernd Düsterberg of Oberkrämer, Germany. He is one of the named inventors of the '728 patent. He testified as to the developments leading up to the patent.
• Dr. Michael Korl Hümpel of Lübeck, Germany. He is a retired employee of Schering, now part of Bayer. He testified as to some of the developments leading up to the '426 patent.
• Dr. Johannes W. Tack of Berlin, Germany. He is a former employee of Schering. He testified as to some of the developments leading up to the '426 patent.
• Ms. Mira Rinnie of Mississauga, Ontario. She is a law clerk in the offices of Bayer’s Counsel. Her affidavit served to make of record certain documents. She was not cross-examined.
[18] Bayer filed affidavits of three expert witnesses, all of whom were cross-examined. In the circumstances of this case, each witness filed an affidavit directed to infringement issues; then, after Cobalt filed its affidavits on validity, these witnesses filed further affidavits directed to validity of one or other of the patents at issue. These witnesses are:
• Dr. Martyn Christopher Davies of Nottingham, United Kingdom. He is a Professor of Biomedical Surface Chemistry at the School of Pharmacy at the University of Nottingham. He testified as to validity and infringement of the '426 patent.
• Dr. Sari Kives of Toronto, Ontario. She is a staff physician at St. Michael’s Hospital, Toronto, in the department of obstetrics and gynecology. She testified as to how patients were advised, and prescribed in respect of Bayer’s YAZ product.
• Dr. Lee P. Shulman of Northbrook, Illinois. He is a practicing medical doctor and serves as Professor of Obstetrics and Gynecology, and Chief of the Division of Clinical Genetics at the Feinberg School of Medicine of Northwestern University. He testified as to validity and infringement of the '728 patent.
[19] Cobalt filed affidavits from two witnesses, both as experts. Both were cross-examined. They first filed affidavits as to validity then affidavits in reply as to infringement. They are:
• Dr. Bhagu Bhavnani of Waterdown, Ontario. He recently retired as a Professor of Obstetrics and Gynecology at the University of Toronto, and Director of Research at the Department of Obstetrics and Gynecology at St. Michael’s Hospital, Toronto. He testified as to infringement and validity of the '728 patent.
• Dr. Yashoda V. Pramar of New Orleans, Louisiana. She is a Professor of Pharmaceutics at the College of Pharmacy, Xavier University of Louisiana. She testified as to the validity and infringement of the '426 patent.
FOREIGN DECISIONS
[20] Counsel for each of the parties drew my attention to decisions in foreign Courts dealing with patents generally similar to one or other of the patents at issue here, and with issues similar to some issues in these proceedings. Some of the same witnesses whose evidence is before me gave evidence in those Courts, although at least in the United Kingdom and the United States, they appeared in person. Those decisions are:
• In the Court of the Commissioner of Patents for the Republic of South Africa, Case number: Patent 2004/4083, Bayer Pharma AG et al, Plaintiffs v Pharma Dynamics (Proprietary) Limited, Defendant.
In a decision dated 14 March 2013, Pretorius J held that a patent similar to the '426 patent was valid and infringed.
I am informed by Counsel that this decision is under appeal.
• In the United Kingdom, Floyd J of the Chancery Division, Patents Court, in a case cited as Gedeon Richter Plc v Bayer Schering Pharma AG, [2011] EWHC 583 (Pat), dealt with a patent similar to the '426 patent. He held certain claims, but not all claims, to be invalid for obviousness. The Court of Appeal (Justices Kitchin, Jacob and Mummery), in a decision cited as [2012] EWCA Civ 235, dismissed the appeal.
• The United States District Court District of Nevada, in Case No. 2:07-CV-01472-KJD-GWF and 2:08-CV-06995-KJD-GWF, between Bayer Schering Pharma AG et al v Watson Pharmaceuticals Inc, Judge Kent W. Dawson, granted Bayer’s motion for summary judgment of non-obviousness of certain claims of a patent similar to the '728 patent. The Court of Appeals for the Federal Circuit (Lourie, Schall and Prost) in case 2012-1424 reversed that decision on April 16, 2013 and held certain claims invalid for obviousness.
• The United States District Court for the District of New Jersey, Judge Sheridan, in Civil Action No. 05-CV-2308 (PGS) between Bayer Schering Pharma AG v Barr Laboratories, Inc., on March 3, 2008, found that certain claims of a patent similar to the '426 patent were invalid for obviousness. The Court of Appeal for the Federal Circuit, on a 2 to 1 split (Mayer and Friedman; Newman dissenting) in a decision dated August 5, 2009, affirmed that decision.
[21] None of these decisions is precedential in a Canadian Court. There may be many differences in the patents considered there, and here, that are critical. The evidence may have been different. There are differences in the law. I therefore note that different Courts and different judges can and do come to different results. These cases illustrate that. This is particularly so where the cases are vigorously contested and the decisions to be made could, in many cases, go either way; depending on the specifics of the patent, the evidence and the law with which each Court had to deal.
ISSUES
[22] The fundamental issue in a proceeding under the NOC Regulations is whether the allegations made by a second party, such as Cobalt, have been shown to be justified. Here, Cobalt has alleged that it will not infringe either of the '426 or '728 patents and that each of those patents, or each of the claims asserted by Bayer in respect of each, is invalid for a variety of reasons.
[23] In respect of the '426 patent, Bayer’s Counsel at the hearing advised that Bayer was not relying on any claims that extended to a “kit”; and where a claim extended to a “composition or kit”, it was only the composition that was relied upon. In argument, Bayer’s Counsel principally relied upon claim 31, although mention was made of claims 1 through 30, as well.
[24] In respect of the '728 patent, Bayer’s Counsel at the hearing advised that Bayer was relying only on claims 1, 2, 6, 7 and 8.
[25] Cobalt’s Counsel, by a letter to the Court dated October 1, 2013, advised that it was no longer pursuing the issue of improper listing. At the hearing, Cobalt’s Counsel advised that it was not pursuing, with respect to the '728 patent, the issue of non-infringement as set out in the latter part of paragraph 37 of its Notice of Allegation respecting exclusive use of females of a certain age. Counsel further advised that it would not be pursuing the Anticipation allegations as set out in paragraphs 38 through 42 of its Notice of Allegation; that it would not be pursuing the allegations of Insufficiency as set out in paragraphs 67 through 76 of that Notice; that it would not be pursuing the allegations of Overbreadth as set out in paragraphs 85 through 87 of that Notice; that Cobalt would not be relying on Canadian Patent No. 2,016,780 in respect of Double Patenting as set out in paragraph 112 of that Notice; and that it would not be relying on Invalid Selection Patent as set out in paragraphs 123 through 129 of that Notice. In respect of the '426 patent, Cobalt’s Counsel advised that it would not be relying upon allegations of Anticipation as set out in paragraphs 301 through 304 of that Notice.
[26] The Notice of Allegation also addresses another patent; Canadian Patent No. 2,261,137, but it is not at issue here.
[27] At the hearing itself, Cobalt’s Counsel, in argument, further restricted its arguments. In respect of the '426 patent, it argued non-infringement, obviousness, utility and sound prediction, overbreadth and insufficiency, and ambiguity. In respect of the '728 patent, Cobalt’s Counsel argued non-infringement, method of medical treatment, obviousness, double patenting, dose equivalent (a non-infringement argument) and utility and sound prediction.
[28] At a pre-trial conference with the parties, I urged each of them to give serious consideration to reduction of issues. I regret that this was only done at the hearing. I propose to consider only those issues that were raised and argued at the hearing.
[29] Therefore, I will address the following issues; namely, are Cobalt’s allegations, as they remain, justified in respect of:
1. The '426 patent, all claims other than the “kit” claims and, in particular, claims 1, 30 and 31:
1) non-infringement
2) validity in respect of:
i) obviousness
ii) utility and sound prediction
iii) overbreadth and insufficiency
iv) ambiguity
2. The '728 patent, claims 1, 2, 6, 7 and 8:
i) non-infringement
ii) obviousness
iii) double patenting
iv) dose equivalent
v) utility and sound prediction
[30] Before moving to those issues, I will briefly address the burden in these NOC matters. I will also address the question of going beyond the Notice of Allegation. With respect to each patent, I will first construe the claims at issue.
BURDEN
[31] 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.
[32] 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.);...).
[Emphasis added]
…
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.
[Emphasis added]
[33] Here Bayer complains that, despite a motion that it brought to compel Cobalt to produce samples, Cobalt refused to do so; and the Court would not compel it to do so. In the course of these proceedings, Cobalt 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 the “spray on” technique. The Court must then deal with Cobalt’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.
GOING BEYOND THE NOTICE OF ALLEGATION
[34] It has been firmly established by the Court of Appeal that the second person, a generic such as Cobalt, 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.
[35] 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.
[36] 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.
[37] 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.
THE '426 PATENT
1. Person of Ordinary Skill in the Art
[38] Bayer and Cobalt are in reasonable agreement as to the identity of the Person of Ordinary Skill in the Art (POSITA) to which the '426 patent is addressed. They agree that such a person is a pharmaceutical formulator with a degree in pharmaceutical sciences or a related field, with at least one or two years’ experience (Cobalt) or several years’ experience (Bayer). That is close enough.
2. Where the Shoe Pinches
[39] Cobalt argues that the '426 patent, including all the claims at issue, is directed to a contraceptive product in which the drospirenone component is “micronized”. Bayer argues that the patent is not restricted to “micronized” drospirenone, but to any form of drospirenone that achieves certain rapid dissolution characteristics.
3. The Description
[40] The Field of the 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.
[41] 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.
[42] 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.
[43] 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.
[44] The detailed disclosure goes on to describe carriers and excipients, particular dosages, other uses, dosage packaging, daily dosaging and rest period.
[45] At page 9, the patent addresses formulation in any manner known in the pharmaceutical art:
[46] 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.
[47] 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.
[48] The claims – 53 in all – follow.
4. The Claims - Construction
[49] Counsel for Bayer dealt principally with claim 31, but with claims 1 and 30, as well.
[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.
[60] Having construed claim 31, I will proceed to the other issues respecting the '426 patent.
5. Non-Infringement
[61] Cobalt’s Notice of Allegation, at paragraphs 294 to 300, states that neither the drospirenone nor the ethinylestradiol component of its oral contraceptive tablets will be in micronized form.
[62] From the Abbreviated New Drug Submission (ANDS) provided by Cobalt in evidence, it can be seen that the manufacturing process for the Cobalt product involves dissolving the drospirenone component and the ethinylestradiol component separately, spraying each onto an inert carrier, drying and blending the components.
[63] Dr. Davies, one of Bayer’s experts, says in respect of this process at paragraphs 71 to 73 of his infringement affidavit:
71. Cobalt manufactures its tablets by dissolving drospirenone into a solution and then spraying the solution onto lactose and cornstarch carrier particles. The other API, ethinylestradiol, is similarly dissolved into solution and sprayed onto the granules. After the solvent evaporates, the drugs remain scattered on the carrier surface.
72. The purpose of this deposition technique is to improve the dissolution rate of the drugs. When the inert carrier comes into contact with aqueous medium (for example the stomach) the drug particles will readily disperse and have a greater surface area available for dissolution and will rapidly dissolve. By keeping the drug particles apart, the carrier also acts to reduce the potential for aggregation (clumping together).
73. This method of improving the dissolution rate is specifically contemplated by the patent. Though in its Letter, Cobalt denies that it manufactures its tablets using in this matter, a review of its disclosure makes it clear that it is precisely using this method.
[64] Dr. Davies, at paragraph 77 of his Infringement Affidavit, states that this process “may” result in micronized particles:
77. Furthermore, the information provided by Cobalt regarding the particle size of the bulk drospirenone is meaningless because Cobalt’s method involves the dissolution of those particles in solution. When Cobalt dissolves the drospirenone, the particles break down and dissolve into the solution. The solution is then prayed onto the surface of the inert carriers, where drospirenone crystallizes as new particles. It is possible that the resulting particles have a particle size distribution and surface area that meet the definition of “micronized” as defined in the ‘426 Patent.This means that Cobalt’s manufacturing method may result in drospirinone in micronized form as defined in the ‘427 patent.
[65] At paragraph 79 of his Infringement Affidavit, Dr. Davies states that the only way for determining whether Cobalt uses drospirenone in micronized form is to examine actual tablets.
[66] Cobalt has refused to provide sample tablets.
[67] Cobalt has made no allegation in respect of non-infringement, other than its product will not be “micronized”. I have construed claim 31 of the '426 patent not to be restricted to a “micronized” tablet, but restricted only in respect of dissolution parameters. Cobalt has provided no information as to those dissolution parameters.
[68] Given that Cobalt is obliged in its Notice of Allegation to provide sufficient information so that Bayer can come to grips with the allegations made; and, given that Cobalt has supplied no sample tablets nor any evidence as to the dissolution parameters of its tablets, I must conclude that Cobalt’s allegations as to non-infringement of claim 31, and dependent claims, of the '426 patent are not justified.
6. Validity - Obviousness
[69] At paragraphs 305 through 339 of its Notice of Allegation, Cobalt has made allegations respecting the Common General Knowledge in The Art, and respecting Obviousness.
[70] In respect of this patent, which was filed effective August 31, 2000, and claiming priority from applications filed August 31, 1999, the Patent Act provides that obviousness is to be determined as of the “claim date” (section 28.3) which here is the priority date, August 31, 1999 (section 28.1). Cobalt’s Counsel at the hearing stated that Cobalt does not contest the applicability of August 31, 1999 as the claim date.
[71] The test for obviousness respecting a Canadian Patent as set out by the Supreme Court of Canada and subsequently considered by the Federal Court of Appeal was reviewed at length in my recent decision in Novartis Pharmaceuticals Canada Inc v Cobalt Pharmaceuticals Company, 2013 FC 985, at paragraphs 60 through 66. I will not repeat those paragraphs here, but I do have reference to the law as stated there.
[72] I have already discussed the person of ordinary skill in the art, to whom the patent is addressed.
[73] The relevant common general knowledge as of August 1999 has been discussed by the relevant experts for the parties; Dr. Davies for Bayer, and Dr. Pramar for Cobalt.
[74] Dr. Pramar’s evidence may be summarized in the following paragraphs of her Validity Affidavit:
I COMMON GENERAL KNOWLEDGE – 426 PATENT
Combined Oral Contraceptive Formulation of Drospirenone and Ethinylestradiol
88. As of August 31, 1999, the person skilled in the art would have known that drospirenone and ethinylestradiol could be combined or admixed using conventional methodologies in order to make an effective oral contraceptive. In the 426 Patent, the patentee lists several references that teach the use of drospirenone and ethinylestradiol for oral contraception.
89. Additionally, by August 31, 1999 a number of patents and other articles had been published that would have taught the person skilled in the art that drospirenone in combination with ethinylestradiol could be conventionally formulated to make an effective oral contraceptive.
. . .
Purpose of Micronization
94. Since the 1970s, drug formulators had developed many techniques to increase the bioavailability of orally administered drugs. By August 31, 1999, micronization was a well-established technique for increasing the bioavailability of such drugs.
. . .
Micronization of Spironolactone
96. As of August 31, 1999, the person skilled in the art would have known that drospirenone is a chemical analog of spironolactone.
97. As of August 31, 1999, the person skilled in the art would also have known that the absorption and bioavailability of spironolactone were improved by micronization. A number of prior art referenes taught this.
. . .
Micronization of Progesterone
101. As of August 31, 1999, the person skilled in the art would have known that drospirenone is a progestin (synthetic progestogen) that has progestinic effects similar to progesterone.
102. As of August 31, 1999, the person skilled in the art would also have known that the absorption and bioavailability of progesterone specifically was improved by micronization. A number of prior art references taught this.
. . .
Micronization of Spirorenone
105. As of August 31, 1999, the person skilled in the art would have known that drospirenone is a metabolite of spirorenone and that spirorenone is a steroid that has a similar structure to that of drospirenone.
. . .
106. As of August 31, 1999, the person skilled in the art would also have known that the absorption and bioavailability of spirorenone was improved by micronization. A number of prior art references taught this.
[75] Dr. Pramar reviewed papers known as Krause I, Krause II and Krause III; all published by Schering, a predecessor of Bayer. She concluded:
120. From reading the Krause papers, the person skilled in the art would have concluded that because spirorenone and drospirenone are related drugs (they are both steroids, they are both derivatives of spironolactone and both have the same chemical structure with the exception of one bond at one location), drospirenone would isomerize in vitro, but rapidly absorb in vivo. In particular, the person skilled in the art would have known that drospirenone would be absorbed faster than it is isomerized.
121. The person skilled in the art would also have realized that the in vitro acid instability of drospirenone would not be an issue in vivo and would have recognized that poor drug solubility would be the only significant challenge – one that could be largely overcome by micronization.
122. The person skilled in the art would have been cognizant of the limitations of in vitro testing as a surrogate for in vivo testing, and would have known that in vitro studies are unreliable unless they can be correlated with in vivo drug behaviour. (A point taught in the Aulton reference I mentioned at paragraph 99 above and another reference written by McGilveray and published in 1996 entitled “Overview of Workshop: In Vitro Dissolution of Immediate Release Dosage Forms: Development of In Vivo Relevance and Quality Control Issues” (a copy of which is attached as Exhibit “E-81” to my affidavit)).
[76] Dr. Pramar addressed spraying, “Deposition”, at paragraphs 123 and 124 of her affidavit:
Deposition Method
123. As of August 31, 1999, the person skilled in the art would have been familiar with the process of making a pharmaceutical composition via dissolving the active ingredient in a suitable solvent (such as methanol or ethyl acetate) and spraying this onto the surface of inert carrier particles followed by incorporation of those particles into the composition.
124. This formulation method, known as the deposition method, was taught in the art since at least the 1980’s.
[77] Dr. Davies disagrees with Dr. Pramar, essentially on the point that drospirenone, unlike other drugs such as spirorenone, was known to be acid labile; that is, it converts quickly to a somewhat different molecule (isomerizes) in the presence of acid – such as in t