AB Hassle v. Genpharm Inc.

AB Hassle v. Genpharm Inc.
Court (s) Database
Federal Court Decisions
Date
2003-12-22
Neutral citation
2003 FC 1443
File numbers
T-2005-01
Notes
Digest
Decision Content
Date: 20031222
Docket: T-2005-01
Citation: 2003 FC 1443
BETWEEN:
AB HASSLE, ASTRAZENECA AB and
ASTRAZENECA CANADA INC.,
Applicants,
- and -
GENPHARM INC., TAKEDA CHEMICAL INDUSTRIES, LTD.
and THE MINISTER OF HEALTH,
Respondents.
REASONS FOR ORDER
[Confidential Reasons for Order issued on December 11, 2003]
LAYDEN-STEVENSON J.
[1] Omeprazole is a member of the benzimidazol family of compounds. It is a potent inhibitor of gastric acid secretion but is inherently unstable, particularly in acidic conditions. Genpharm Inc. takes issue with certain patents relating to omeprazole (marketed under the trade name LOSEC). It alleges invalidity regarding some patents and alleges that its generic product will not infringe others.
THE APPLICATION AND THE PARTIES
[2] AB Hassle is the owner of Canadian patents 1,292,693 ('693) and 2,025,668 ('668). AstraZeneca AB (the successor to AstraAB) is the owner of Canadian patent 2,133,762 ('762) and Takeda Chemical Industries, Ltd. (Takeda) is the owner of Canadian patent 1,338,377 ('377 or Takeda patent). AstraZeneca Canada Inc., with the consent of the owners, included these patents on its patent list for its omeprazole and omeprazole magnesium products.
[3] On November 9, 2001, the applicants AB Hassle, AstraZeneca AB and AstraZeneca Canada Inc. (collectively Astra) filed a notice of application naming Genpharm Inc. (Genpharm), Takeda, and the Minister of Health (the Minister) as respondents. The notice of application, brought pursuant to the Patented Medicine (Notice of Compliance) Regulations, SOR/93-133, as amended SOR/98-166, SOR/99-279 (the Regulations), seeks declaratory relief with respect to Genpharm's notice of allegation (NOA) dated September 27, 2001, and alternatively, an order prohibiting the Minister from issuing a notice of compliance (NOC) to Genpharm in respect of nine Canadian patents. Takeda, as owner of the Takeda patent, is not an applicant in this matter, but it adopts and relies on the submissions of Astra and makes additional submissions regarding its patent. The Minister administers the Regulations. The Minister did not file submissions and was not represented at the hearing. Over time, Genpharm withdrew a number of its allegations and Astra, in turn, withdrew the relief sought regarding those allegations. At the hearing, four patents remained in controversy.
BACKGROUND
[4] Genpharm's NOA is dated September 27, 2001, and specifies that Genpharm's submission relates to omeprazole capsules in strength concentrations of 10 mg and 20 mg. It alleges invalidity with respect to patents '693 and '377 and non-infringement with respect to patents '668 and '762. Patents '693 and '377 are formulation patents. The '693 patent relates to a formulation that consists of an alkaline reacting compound added to an omeprazole core, an enteric coating and an inert water soluble or rapidly disintegrating subcoating layer between the two. The invention claimed by the '377 patent is with respect to the addition of basic inorganic salts to omeprazole for stabilization purposes. The '688 patent claims a new use for omeprazole as an antimicrobial agent and the '762 patent relates to a combination of a substance that inhibits gastric acid secretion and an acid-degradable antibacterial compound.
[5] Three proceedings, involving these parties and relating to omeprazole, precede this one. All three were eventually withdrawn. On March 26, 1999, Genpharm sent its first NOA in relation to omeprazole. It alleged (relevant to this proceeding) non-infringement with respect to the '377 and '668 patents, and non-infringement and invalidity on the basis of anticipation and obviousness regarding the '693 patent. An application for prohibition was commenced on May 7, 1999 (T-809-99). Genpharm withdrew its allegations regarding invalidity on July 11, 2000.
[6] On September 13, 1999, a second NOA was forwarded alleging invalidity of the '377 patent on the basis of anticipation, obviousness and double-patenting. A notice of application to prohibit issuance of a NOC was filed on October 28, 1999 (T-1884-99). The third NOA was dated July 11, 2000, and alleged invalidity of the '693 patent. A third application for prohibition was commenced August 25, 2000 (T-1603-00).
[7] All three proceedings, as stated earlier, were discontinued. The first discontinuance followed the decision of the Federal Court of Appeal in AB Hassle v. Canada (Minister of National Health and Welfare) (2000) 7 C.P.R. (4th) 272 where the court determined that a second person could not rely on further evidence not contained in its NOA. The remaining proceedings were discontinued when the Minister advised Genpharm that its submission for approval of its omeprazole product was considered to be withdrawn. The proceedings scheduled for hearing in this court on January 8, 2001, were discontinued, without prejudice, on consent of the parties. When Genpharm's appeal, within the Minister's department regarding the Minister's decision, was successful, Genpharm delivered a new NOA. By order of the Prothonotary dated November 31, 2001, certain evidence, transcripts of cross-examinations and court documents from the prior proceedings (T-809-99, T-188-99 and T-1603-00) form part of the record in this proceeding. The parties were also permitted to file additional evidence.
THE NATURE OF THE PROCEEDING
[8] As earlier stated, 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.); AB Hassle v. Canada (Minister of National Health and Welfare), supra; Novartis AG et al. v. Abbott Laboratories Ltd. et al. (2000), 7 C.P.R. (4th) 264 (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.
[9] Genpharm is a generic drug producer (the second person) and wishes to distribute in Canada an omeprazole drug by comparing the drug that it wishes to market with that of Astra (the first person), already approved by the Minister. Under section 5 of the Regulations, Genpharm provided a NOA to Astra in respect of certain patents that Astra has listed under the provisions of section 4 of the Regulations. Astra's application under section 6 of the Regulations is in response to Genpharm's NOA.
[10] 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 issue 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.)
[11] 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] 2 S.C.R. 193; Bristol-Myers Squibb Canada Inc. v. Canada (Attorney General) (2001), 11 C.P.R. (4th) 539 (F.C.A.). 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 ususal way by commencing an action: Pfizer Canada Inc. v. Apotex Inc. (2001), 11 C.P.R. (4th) 245 (F.C.A.); SmithKline Beecham Pharma Inc. v. Apotex Inc. (2001), 14 C.P.R. (4th) 76 (F.C.T.D.) aff'd.. (2002), 291 N.R. 168 (F.C.A.); Novartis A.G. v. Apotex Inc. (2002) 298 N.R. 348 (F.C.A.).
THE NOA
[12] A copy of Genpharm's complete NOA is attached to these reasons as Schedule "A". The portions relevant to this proceeding are reproduced here.
Patent 1,292,693
... [the] claims of this patent ... are invalid.
This patent is directed to and claims an oral enteric coated formulation containing a core material of an active substance coated with one or more subcoating layers and one or more enteric coating layers. The active substance is omeprazole or a salt of omeprazole [...]
You are fully aware of the factual and legal basis for these allegations by reason of the Affidavits of Richard K. Pike sworn September 13, 1999; Dr. James Steven Rowe sworn September 9, 1999; Dr. James Steven Rowe sworn March 22, 2000; the exhibits to said affidavits and cross-examinations thereon and exhibits filed and identified therein in proceedings before the Federal Court of Canada T-809-00 in which you and Genpharm among others were parties. All of said affidavits save the last of Dr. Rowe have been filed therein, the last Dr. Rowe affidavit was not filed but you did receive a copy. To the references referred to by Dr. Rowe as rendering this patent obvious there is added and relied upon, Deschesne et al. "Research on Conditions for Application of Enterosoluble Gastric-Resistance Coating with Eudragit L 30D" J. Pharm Belg., 1982, 37, 4, pp. 273-282.
Further details as to the factual and legal bases for the above allegations is provided in the attached reports.
Patent 1,338,377
This patent is not valid. You are fully aware of the factual and legal basis for the allegation by reason of the affidavits of Dr. James Steven Rowe and exhibits thereto, sworn December 14, 1999 and April 26, 2000 filed, in respect of the first affidavit, and attempted to be filed in the case of the second affidavit, in Federal Court of Canada Trial Division proceedings T-1884-99 in which you and Genpharm, among others, were parties.
Patent 2,025,668
This patent is directed to and claims the use of omeprazole or a pharmaceutically acceptable salt thereof in the treatment of infectious diseases, especially such caused by Campylobacter pylori. Genpharm's product will not indicate any of the uses listed in this patent. Genpharm's omeprazole capsules will be labelled and marketed for inhibiting gastric acid secretions. Genpharm's omeprazole capsules will not be labelled or marketed for the treatment of infectious diseases, such as those caused by Campylobacter pylori. Therefore, Genpharm's proposed drug product has not infringed, does not infringe, and would not if marketed infringe any claims of this patent.
Patent 2,133,762
This patent is directed to and claims a pharmaceutical composition for the treatment of gastritis and peptic ulcer comprising, in combination a histamine - H2 blocker or proton pump inhibitor, which inhibitor may be omeprazole, and an acid degradable antibacterial component.
Genpharm's omeprazole capsules will not contain either a histamine - H2 blocker or an acid degradable antibacterial component, nor will they be labelled or marketed for the claimed composition. Thus, the Genpharm capsules will not infringe upon this patent.
ISSUES
[13] The parties agree that the issues to be determined are those delineated by the applicant at paragraph 173 of its Memorandum of Fact and Law (Genpharm Memorandum of Fact and Law at paragraph 212 and Takeda Memorandum of Fact and Law at paragraph 35). They are:
(a) whether the NOA is an abuse of process
(b) whether Genpharm has provided a detailed statement of the legal and factual basis
for its allegation as required by the Regulations; and
(c) whether Genpharm's allegations are justified, namely:
(i) whether Genpharm's allegation of invalidity of the '693 patent is justified;
(ii) whether Genpharm's allegation of invalidity of the '377 patent is justified;
(iii) whether Genpharm's allegation of non-infringement of the '668 parent is justified;
(iv) whether Genpharm's allegation of non-infringement of the '762 patent is justified.
At the hearing, Astra did not argue issue (b) and Takeda made only passing reference and stated that it was not "pushing it". I do not intend to deal further with this issue. I will address the remaining issues, for the most part, in the order in which they were argued.
THE '693 PATENT
[14] The application that resulted in the '693 patent was filed on April 29, 1987, and claims priority from a UK application filed on April 30, 1986 (priority date). The '693 patent issued on December 3, 1991. It is a formulation patent that consists of an alkaline reacting compound added to an omeprazole core, an enteric coating, with an inert water soluble or rapidly disintegrating subcoating layer in between. The '693 patent contains 19 claims. The Claims of the '693 patent are attached to these reasons as Schedule "B". For ease of reference, Claim 1 is reproduced here.
1. An oral pharmaceutical preparation comprising: (a) a core region comprising an effective amount of a material selected from the group consisting of omeprazole plus an alkaline reacting compound, an alkaline omeprazole salt plus an alkaline reacting compound and an alkaline omeprazole salt alone; (b) an inert subcoating which is soluble or rapidly disintegrating in water disposed on said core region, said subcoating comprising one or more layers of materials selected from among tablet excipients and polymeric film-forming compounds; and (c) an outer layer disposed on said subcoating comprising an enteric coating.
[15] Claims 2 to 16 depend, either directly or indirectly, from Claim 1. Claim 17 restates claim 1 in process form. Claim 18 comprises a commercial package containing a preparation of any one of claims 1 to 16 together with instructions for use for the treatment of gastrointestinal diseases. Claim 19 claims use of the preparation according to any one of claims 1 to 16 for the treatment of gastrointestinal diseases.
[16] Genpharm's allegation is that the claimed invention of the '693 patent was obvious and is therefore not inventive. It says that the skilled person, as of the priority date (April 30, 1986), would have been led directly and without difficulty to it in light of the common general knowledge and the prior art available at the time. It argues that claims 5, 13 and 19 are insufficient and ambiguous. Genpharm also alleges invalidity on the basis of anticipation with respect to claims 1, 7, 8, 11 and 17 and says that each lacks novelty.
THE EVIDENCE
[17] Both Astra and Genpharm submitted affidavits from formulation experts. Astra also relied on the affidavit of its employee. All affiants were cross-examined. There was no challenge, from either side, regarding the qualifications and expertise of the proposed expert witnesses.
[18] Astra relied on the evidence of three witnesses.
(1) Dr. John Rees, who swore affidavits on July 26, 1999, January 31, 2000, September 25, 2000, and April 2, 2002, is a consultant to the pharmaceutical industry. In relation to the allegations regarding the '693 patent in this proceeding, Astra relies on the January 31, 2000 (Rees 1) and the April 2, 2002 (Rees 2) affidavits. Dr. Rees received his Ph.D. from the school of pharmacy, University of London in 1967. He worked in the pharmaceutical industry for eighteen years following which, until 1997, he was a professor in the school of pharmacy and pharmacology and head of pharmacology practice at the University of Bath. He has published extensively on various aspects of pharmaceutical formulation, including articles on film forming.
(2) Dr. Gordon L. Amidon, who swore an affidavit on April 1, 2002, is the Charles R. Walgreen, Jr. professor of pharmacology at the College of Pharmacy, University of Michigan and has held that position since 1994. He received his Ph.D. in pharmaceutical chemistry from the University of Michigan in 1971. He worked in the pharmaceutical industry for ten years, held academic appointments when he was not employed in the industry, and now offers research and consulting services to the industry. He is the recipient of various research awards and has published extensively in the fields of pharmaceutics, physical pharmacy and pharmaceutical chemistry.
(3) Brigitta Rook swore an affidavit on January 27, 2000, and is vice president, Global Regulatory Affairs, Gastrointestinal, AstraZeneca. She has been employed by the AstraZeneca group of companies since her graduation as a pharmacist in 1968, originally in marketing and later in the stability section of the pharmaceutical laboratory. In 1970, she was appointed to a position in research administration of regulatory affairs and became the group manager in 1985. Her duties as a group manager included the preparation of regulatory submissions related to the conduct of clinical trials involving omeprazole and the preparation of applications for governmental approval for sale of omeprazole.
[19] Genpharm also relied on the evidence of three witnesses.
(1) Dr. James Steven Rowe swore affidavits on September 9, 1999 (Rowe 1), March 22, 2000 (Rowe 2), December 14, 1999 (Rowe 3), April 26, 2000 (Rowe 4), October 24, 2000 (Rowe 5) and February 6, 2002 (Rowe 6). In relation to the '693 patent, Genpharm relies on Rowe 1, 2, 5 and 6. Dr. Rowe is the scientific director of a consulting company that offers services covering all aspects of product development from initial concept through to product launch. He was employed in the pharmaceutical industry for nearly ten years after graduating with a Bachelor of Pharmacy degree in 1966. From December, 1976, until April, 1983, he was a research fellow and lecturer at the school of pharmacy, University of London. He completed his Ph.D. in pharmaceutics in 1980 during his tenure at the University of London. In 1983, he returned to consulting work in the pharmaceutical industry. He has published, although not as extensively as Drs. Rees and Amidon.
(2) Dr. Michael John Story swore an affidavit on May 7, 2002, and is a consultant to the pharmaceutical industry. He obtained his Ph.D. in chemical engineering from the University of Cambridge, England, in 1967. Thereafter, he was employed by various pharmaceutical entities. He was responsible for development of the formulation of capsules containing enteric coated pellets of erythromycin. He has had extensive experience in almost all aspects of drug formulation development.
(3) Dr. Philip Andrew Marshall swore an affidavit on February 8, 2002, and is an independent consultant in the area of pharmaceutical chemistry, regulatory affairs and manufacturing practices in the industry. Dr. Marshall received his Ph.D. in 1979 from the University of Adelaide in Australia. He has more than twenty years of commercial experience in the industry in all aspects of product development. His publications, spanning a period of over twenty-five years, include papers in scientific and non-scientific journals, conference abstracts and presentations. Dr. Marshall is the author of six reports, prepared at the request of Australian solicitors in relation to patent proceedings in the Australian Federal Court. The reports are exhibited to his affidavit along with the correspondence from the solicitors regarding the reports.
THE POSITIONS OF THE PARTIES
Astra
[20] Astra argues that the '693 patent claims a novel oral formulation of omeprazole. It acknowledges that an enteric coated formulation of omeprazole was known in the prior art. It says that omeprazole is acid labile (degrades due to acid) and needs to be protected from the acidic gastric juice of the stomach. Resistant to highly acidic conditions, enteric coating protects acid labile compounds in their passage through the stomach (gastric resistance). Astra maintains that there was no suggestion in the prior art that an enteric coated omeprazole formulation should be modified by adding an alkaline compound or a subcoating. The expectation was that an enteric coating would be compatible with omeprazole.
[21] Astra submits that the inventors of the '693 patent determined instability of omeprazole on direct or indirect contact with an enteric coating. To enhance stability of an enteric coated dosage form, an omeprazole core must also contain an alkaline reacting compound. Such an alkaline core dissolves the enteric coating upon permeation of water of gastric juice and compromises the enteric coat. A water soluble subcoating is required to ensure both storage stability and gastric resistance.
[22] It is said that it was unexpected, in view of the prior art, that omeprazole or an alkaline core would interact with an enteric coating and that a water soluble subcoating would be effective to prevent gastric resistance failure caused by permeation of water of gastric juice.
[23] Astra's witness Dr. Rees considers the difficulties a skilled person would have encountered in formulating omeprazole and acknowledges that such a person would consider enteric coating. However, given the stability characteristics of omeprazole, the person would encounter discolouration while preparing the core. This situation would necessitate a significant research program. The skilled person may eventually consider the addition of an alkaline compound to the core to be worth trying, but would then observe further discolouration. The skilled person may eventually increase alkalinity, but that would result in gastric resistance failure. The person would have expected that properly applied enteric coating would perform as intended and would likely focus on trying to address the gastric resistance problem. The skilled person would not have been led to the claimed invention.
[24] Instead, the person would be in the difficult position of either worsening the discolouration problem by lowering the alkalinity to increase the gastric resistance or exacerbating the gastric resistance problem in increasing the alkalinity to cure discolouration. The skilled person would have been faced with no apparent solution to the dilemmas because an interaction in the solid state between an enteric coat and a core would not have been expected. Even assuming that a skilled person was able to identify the cause of the failure in gastric resistance, he or she still would not have been led to the claims invention since the patent discloses that gastric resistance failure resulted from permeation of water of gastric juice. A subcoating material that is water soluble or rapidly disintegrating in water is the very last thing that a skilled person would have expected to solve the gastric resistance problem.
[25] Dr. Amidon says that a skilled person would have had to undertake significant experimentation in order to try to determine the causes of the conflicting storage stability and gastric resistance problem. Even assuming the person would have arrived at the claimed preparation, the path would not have been direct or without difficulty.
[26] Ms. Rook explains that Astra decided to change the formulation for Phase III clinical studies because the formulation used for Phase II clinical studies (which did not have a subcoating) was found not to have adequate stability. The Phase III formulation included an alkaline reacting compound and a subcoat. The change in the formulation, which delayed the regulatory submission process, confirms that the claimed invention was not obvious.
Genpharm
[27] Genpharm submits that the '693 patent deals with how the drug omeprazole is formulated into capsules or other oral preparations. The patent acknowledges that it was known that omeprazole could be formulated into pellets that were coated with an enteric coat and placed into a capsule for oral administration. The patent also acknowledges that it was known that omeprazole was unstable in acidic conditions but that, at least for the purpose of clinical trials, it was sufficiently stable when coated with an enteric acidic coating. The patent says that the problem encountered was that over the long-term in storage, the enteric coated drug proved unstable and, to address this problem, the "invention" was to place a soluble or rapidly disintegrating subcoat between the omeprazole and the enteric coat. Genpharm contends that, before the application for the patent was filed, omeprazole was a known drug, useful for inhibiting gastric secretions, known to be acid sensitive, and had been formulated, among other things, in a solid dose taking the form of enteric coated pellets in a capsule.
[28] Genpharm's witness, Dr. Rowe, explains the steps that he would have taken to formulate omeprazole as a formulator skilled in the art as of 1986. He would have reviewed the available literature, conducted pre-formulation studies, coated omeprazole using commercial techniques and conducted stability studies. In so doing, he would have arrived at the same starting point as in the '693 patent at page 2, lines 30-35, i.e. while the storage life of the enteric coated product was acceptable for clinical studies, it was insufficient for long-term storage. He maintains that a skilled person would have considered adding an alkaline compound to stabilize a core containing a drug that is unstable in acid. A skilled person would have been aware of the use of either acidic or basic material to enhance the stability of a drug depending on its pH stability profile. Determining the optimal environment for the stability of a drug was a "simple routine test which a technician could have carried out". Although he would not initially have suspected the interaction between omeprazole in the core and the acidic groups in the enteric coat to be a likely cause of the problem, he would certainly have been aware of the possibility of this occurring as it was generally accepted that this type of reaction did occur. He states that as a "matter of ordinary formulation practice" it would have been obvious to him and other formulators to apply a subcoat as part of the routine development of the formulation of this product. The use of a subcoat as a solution to separate the alkaline core from the enteric coat was obvious and was not novel.
[29] Dr. Story, relying on prior art and a review of the '693 patent, says that it is known that omeprazole can be stabilized by the use of alkaline substances and this leads the skilled person to formulate omeprazole in the presence of alkali. He regards the use of a subcoat as obvious.
[30] Dr. Marshall describes the task he completed and refers to his reports. He was asked to do a hypothetical exercise based on instructions and information that was provided in stages. He did not complete any testing or experiments. On completion of his sixth report, his ultimate result was to provide a "leaky" subcoat containing a mixture of hydroxpropylcellulose or hydroxpropylmethycellulore (HPMC) between the omeprazole core and the enteric coat. He did not have the patent before him when he completed his exercise.
THE PRIOR ART
[31] The complete listing of prior art relied upon by Dr. Rowe is attached to these reasons as Schedule C. The primary references discussed by Drs. Rowe and Story are summarized here.
[32] EP Patent 0 124 495 (the '495 patent) entitled "Omeprazole Salts", published November 7, 1984 - describes salts of omeprazole and discloses processes for their preparation, pharmaceutical compositions containing such salts, and their use medicine. The patent makes reference to enteric coated tablets, enteric coated soft gelatin capsules and hard gelatin capsules containing enteric coated granules of the active compound. It discloses the instability of omeprazole in suspension and states that, upon storage without any precautions being taken, it "degraded at a rate which is higher than desired".
[33] Pilbrant and Cederberg (Pilbrant) - an article published in 1985 by Drs. A. Pilbrant and C. Cederberg entitled "Development of an oral formulation of omeprazole". The article reports on studies conducted with respect to a solid dosage form of omeprazole in the form of enteric coated pellets. It states, among other things, that it is very slightly soluble in water, very soluble in alkaline solution, and degrades very rapidly in water solutions of low pH values. Preformulation studies revealed that moisture, solvents and acidic substances have a deleterious effect on the stability of omeprazole and should be avoided in pharmaceutical formulation. It additionally states that two principal options exist for the formulation of an oral solid dosage from - a "conventional oral dosage form from which omeprazole is released and absorbed rapidly enough to avoid degradation in the stomach" and an enteric dosage form. The former was ruled out on the basis of the bioavailability results from the study that showed more than half of the omeprazole in that form degraded in the stomach. The authors considered the enteric coated dosage form "offers the best possibilities" although it must be "perfectly coated and acid resistant since, if the active ingredient leaks out of the dosage form in the stomach, it is almost immediately degraded. The same situation arises if an acidic medium can diffuse into the dosage form through pin-holes or damage in the enteric coating".
[34] Shin-Estu H-17 - a technical information sheet of the Shin-Estu Chemical Company dated March, 1975, and entitled "Enteric Coating on Tablets Containing Alkaline Matter". It states a problem and proposes a solution for stability loss in relation to enteric coated tablets containing alkaline matter such as ammonium chloride, lithium carbonate or sodium-salicylate when stored at high temperatures. The difficulty was found to be improved by "putting stearic acid in the intermediate film which is considered to work as some buffer to imaginable ion-exchange reaction between alkaline and enteric material". A report of the testing of two formulations for absorption rate in gastric fluid and disintegration time and intestinal fluid are provided. The testing involved enteric coated tablets with both an intermediate and an undercoat of Pharmacoat 606 (a Shin-Estu brand of hydroxypropylmethycellulose (HPMC), a water soluble coating that becomes substantially insoluble in water when stearic acid is added).
[35] Shin-Estu P-30 - another technical information sheet dated April, 1980, and entitled "Stability of Methyl-dopa Tablet Coated with Pharmacoat 606". It deals with a problem caused by a reaction between a drug that was unstable under alkaline conditions and Pharmacoat 606. The proposed solution was the addition of acidic material to the core tablet or to the coat.
[36] British Patent 760,403 (Abbott) - a 1953 patent relating to improvements in enteric coats, specifically the use of certain mineral solids in the enteric coats. The specification contemplates the use of portions of the enteric coating with other known enteric coatings. One of the examples in the patent is a formulation of erythromycin, an acid labile compound. The patent states that a medicament which has a highly alkaline pH may conceivably attack and weaken or destroy the film forming substance, but coating is still viable for such incompatible drugs by, for example, subcoating with a compatible material and then applying an outer coating of the desired enteric coating.
[37] Rohm Pharma GMBH, Lehman et al., January 1983 "Practical Course in Lacquer Coating" - a publication produced with respect to a course given by Rhom Pharma, the producer of Eudragit film-forming polymer preparation. It is concerned with enteric coating for tablets and teaches the reader how to produce such tablets. The document describes the features of Eudragit L, confirms that it would be suitable for use as an enteric coating and could be used on cores that contain a highly moisture sensitive drug in order to reduce the rate of moisture ingress into the core.
[38] Astra's position regarding the prior art, succinctly stated, is that there is no motivation to modify the prior art omeprazole formulation (only two prior art documents relate to omeprazole); there is no prior art reference that discloses addition of an alkaline compound to stabilize an acid labile core; the subcoating documents teach away from the claimed subcoating to address gastric resistance failure; the textbook references relied upon do not address the problem of enteric coating reacting with a core, and some of those references post date the priority date of the '693 patent.
ANALYSIS
[39] The burden of proof in section 6 proceedings was articulated by Mr. Justice Gibson in SmithKline Beecham, supra, at paragraphs 14 and 15 as follows:
Against the foregoing, I conclude that while an "evidential burden" lies on Apotex to put each of the issues raised in its Notice of Allegation "in play", if it is successful in doing so, the "persuasive burden" or "legal burden" then lies with SmithKline. Assuming Apotex to be successful in putting the issue of validity of the '637 Patent "in play", SmithKline is entitled to rely on the presumption of validity of the patent created by subsection 43(2) of the Act.
The "persuasive burden" or "legal burden" that lies with SmithKline in the circumstances described in the preceding paragraph is, however, impacted by the nature of the proceeding here before the Court. In Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare), [(1994), 55 C.P.R. (3d) 302 (F.C.A.)] Mr. Justice Hugessen, for the Court, wrote at pages 319-20:
As I understand the scheme of the regulations, it is the party moving under s. 6, in this case Merck, which, as the initiator of the proceedings, has the carriage of the litigation and bears the initial burden of proof. That burden, as it seems to me, is a difficult one since it must be to disprove some or all of the allegations in the notice of allegation which, if left unchallenged, would allow the Minister to issue a notice of compliance. [...] In this connection, it may be noted that, while s. 7(2)(b) [of the Regulations] seems to envisage the court making a declaration of invalidity or non-infringement, it is clear to me that such declaration could not be given in the course of the s. 6 proceedings themselves. Those proceedings, after all, are instituted by the patentee and seek a prohibition against the Minister; since they take the form of a summary application for judicial review, it is impossible to conceive of them giving rise to a counterclaim by the respondent seeking such a declaration. Patent invalidity, like patent infringement, cannot be litigated in this kind of proceeding.
Thus, the burden on SmithKline is only to disprove the allegations in the notice of allegation, not to justify declarations of validity and infringement or conversely to negative claims for declarations of invalidity and non-infringement.
See also: Pfizer Canada Inc. v. Apotex Inc. (2002), 22 C.P.R. (4th) 466 (F.C.) at paragraphs 82, 83 and GlaxoSmithKline Inc. v. Genpharm Inc. 2003 FC 1248, [2003] F.C.J. No. 1582 at paragraph 34.
[40] The first step in the analysis is to construe the claims of the patent. As stated earlier, all claims in the '693 patent relate back to claim 1. In Canamould Extrusions Ltd. et al. v. Driangle Inc. (2003), 25 C.P.R. (4th) 343 (F.C.T.D.), at paragraphs 31 and 32, I discussed some of the principles emanating from the companion decisions Free World Trust v. Électro Santé Inc. (2000), 9 C.P.R. (4th) 168 (S.C.C.) and Whirlpool Corporation v. Camco Inc. (2000), 9 C.P.R. (4th) 129 (S.C.C.). My comments are apposite for purposes of this matter.
Patent construction is antecedent to issues of validity and infringement. The patent is to be construed as of the date of its publication. The Patent Act, R.S.C. 1985, c. P-4 (the Act) and purposive construction promote adherence to the claims and this in turn promotes fairness and predictability. The claims perform a public notice function by setting out the scope of the monopoly so that the public may know where it may go with impunity. The claim language must be read in an informed and purposive way. Claim interpretation is neither literal nor based on vague notions such as the "spirit of the invention". The more scope for searching for the "spirit of the invention" and the "pith and substance" of the invention, the less the claims can perform their public function. A patent falls within the definition of "regulation' in the Interpretation Act, R.S.C. 1985, c. I-21 and as such merits a construction that best assures attainment of its objects. The inventor's intention is manifested in the patent claims as interpreted by a person skilled in the art. The average person skilled in the particular art of the patent is not a grammarian or etymologist and does not indulge in a meticulous and verbal analysis.
The content of a patent specification is regulated by section 27 of the Act. The disclosure is the quid provided by the inventor in exchange for the quo of the monopoly. An inventor is not obliged to claim a monopoly on everything new, ingenious and useful disclosed in the specification. The usual rule is that what is not claimed is considered disclaimed. Regard may be had to the specification to understand what is meant by a word in a claim, but not to enlarge or contract the scope of the claim as written and thus understood. The claims and the disclosure are construed with a mind willing to understand. The words chosen by the inventor will be read in the sense that the inventor intended and in a way that is sympathetic to the accomplishment of the inventor's purpose, expressed or implicit, in the text of the claims. If the inventor, however, has misspoken or otherwise created an unnecessary or troublesome limitation in the claims, it is a self-inflicted wound. The public is entitled to rely on the words used provided the words used are interpreted fairly and knowledgeably.
[41] The hearing of this application concluded on October 31, 2003, after 5 days of argument. On November 3, 2003, the Federal Court of Appeal released its reasons for judgment in Apotex Inc. v. AB Hassle, AstraZeneca AB and AstraZeneca Canada Inc. and The Minister of Health 2003 FCA 409, [2003] F.C.J. No. 1601, a matter involving the '693 patent.
[42] Mr. Justice Rothstein referred to the disclosure of the '693 patent to ascertain the circumstances of the invention. He stated as follows:
To be effective, the omeprazole must be released in the small intestine and not in the stomach. In order to prevent the omeprazole from being degraded by acidic gastric juices in the stomach, an enteric coating covering the omeprazole core is required. The enteric coating dissolves in the neutral to alkaline environment found in the small intestine after allowing the omeprazole to pass through the stomach unaltered.
However, if a conventional enteric coating is applied directly to the omeprazole core, the omeprazole rapidly decomposes, with the result that the pharmaceutical preparation (or, in everyday language for purposes of this case, a tablet) becomes badly discoloured and loses omeprazole