Date: 20041202
Docket: A-607-03
Citation: 2004 FCA 413
CORAM: ROTHSTEIN J.A.
NOËL J.A.
MALONE J.A.
BETWEEN:
GENPHARM INC.
Appellant
and
AB HASSLE
ASTRAZENECA AB
ASTRAZENECA CANADA INC.
TAKEDA CHEMICAL INDUSTRIES, LTD., and
THE MINISTER OF HEALTH
Respondents
Heard at Toronto, Ontario, December 1 and 2, 2004.
Judgment delivered from the Bench at Toronto, Ontario, December 2, 2004.
REASONS FOR JUDGMENT OF THE COURT BY: ROTHSTEIN J.A.
[1] This is an appeal from a December 11, 2003, order of Layden-Stevenson J. of the Federal Court, made under the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, as amended by SOR/98-166 (the "Regulations"). By her order, Layden-Stevenson J. prohibited the Minister of Health (the "Minister") from issuing a Notice of Compliance to Genpharm regarding omeprazole capsules until expiration of Canadian Patents 1,292,693 ('693), 1,338,377 ('377), 2,025,668 ('668) and 2,133,762 ('762). AB Hassle is the owner of the '693 and '668 Patents and AstraZeneca AB is the owner of the '762 Patent. These respondents, including AstraZeneca Canada Inc., will be referred to as Astra. The '377 Patent is owned by the respondent Takeda Chemical Industries, Ltd.
The Justified and Obviousness Tests
[2] Genpharm argues that Layden-Stevenson J. erred in using the wrong standard of proof in respect of the "justified" test in subsection 6(2) of the Regulations and in using the wrong legal test in respect of Genpharm's obviousness allegations relative to the '693 and '377 Patents.
[3] This Court rejected Genpharm's "justified" and obviousness test arguments in its decision in Genpharm v. Procter & Gamble, 2004 FCA 393, issued on November 22, 2004. We understand that Genpharm does not resile from these arguments, but in this Court the state of the law on those issues is as set forth in the Genpharm v. Procter & Gamble decision.
Are the '693 and '377 Patents Obvious or Anticipated?
[4] Nonetheless, Genpharm argues that even on the test for obviousness that the Court confirmed in Genpharm v. Procter & Gamble, the claims in the '693 and '377 Patents are obvious. It also argues that the claims in the '693 Patent are anticipated by a pre-existing European Patent 124,495 (the '495 Patent).
[5] At paragraph 42 of her reasons, Layden-Stevenson J. quoted from this Court's decision in AB Hassle et al. v. Apotex Inc. et al. (2003), 312 N.R. 288 to outline the circumstances of the claims of the '693 Patent. At paragraphs 4, 5 and 6 of AB Hassle, the Court stated:
[4] ...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.
[5] 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 content with the passage of time. This problem of storage stability can be addressed by including alkaline reacting constituents in the omeprazole core. However, when a tablet containing an alkaline core which is in direct contact with the enteric coating is ingested, some of the gastric juice in the stomach diffuses through the enteric coating into the omeprazole core during the time the tablet resides in the stomach before it is emptied into the small intestine. The gastric juice causes parts of the omeprazole core to dissolve which, in turn, interfere with and eventually dissolve the enteric coating.
[6] The object of the invention disclosed in the relevant patents is to provide an enteric coated tablet of omeprazole which is resistant to dissolution in the stomach. This is obtained by having an inert subcoating between the omeprazole core and the enteric outer coating.
[6] Claim 1 of the '693 Patent provides that an inert subcoating is to lie between the omeprazole core region and the outer enteric coating. Genpharm says that gelatin capsules were referred to in the prior '495 Patent; that the '693 Patent disclosure states that in the case of gelatin capsules, the gelatin capsule itself serves as a separating layer; that this must mean that a gelatin capsule constitutes an inert subcoating; and since gelatin capsules were referred to in the prior '495 Patent, the use of the gelatin capsule as the inert subcoating in the '693 Patent was anticipated.
[7] This argument reads the gelatin capsule reference in the '693 disclosure out of context. It is apparent from the context that, where a gelatin capsule is used, it must be of the inert type. Nothing in the '495 Patent refers to a layer over the core as being inert or that gelatin capsules must be inert. This was the finding of Layden-Stevenson J. at paragraphs 86 and 87 of her reasons. There is no basis for this Court to interfere with that finding.
[8] Alternatively, Genpharm argues that a technician skilled in the art would have no difficulty in selecting the appropriate gelatin - that is, an inert gelatin. Layden-Stevenson J. dealt with this evidence at paragraphs 70 and 71 of her reasons. She concluded that Genpharm's evidence of obviousness was based on its witnesses having the benefit of hindsight. She was not satisfied on a balance of probabilities that a person skilled in the art would directly and without difficulty arrive at the '693 invention. Genpharm has not demonstrated any palpable and overriding error in this conclusion.
[9] With respect to the '377 Patent, the argument is again one of obviousness. Genpharm says that the '377 Patent addresses the stability of omeprazole by the use of mechanically added salt to the omeprazole. Genpharm says this means of achieving stability was obvious from prior art. It says there were four routes for arriving at this result and a formulator would arrive at the '377 result in the ordinary course of his work.
[10] The context in which Genpharm makes its argument was described by Layden-Stevenson J. at paragraph 111 of her reasons:
It must be recalled that the uncontradicted evidence is that it is not known from the prior art that instability existed in enteric coated solid dosage forms, let alone that pH was a causative factor of instability. Nor was the use of an alkaline compound to stabilize omeprazole in the solid state previously disclosed. It is within this context that Genpharm makes its argument.
[11] She found that Genpharm's position regarding obviousness respecting the '377 Patent resembled the English "worth a try" test. Before this Court, Genpharm agreed that the English "worth a try" test is not applicable in Canada. At paragraph 113, Layden-Stevenson J. concluded that the solution of the '377 Patent would, absent the "worth a try" approach, not be arrived at directly and without difficulty. There was evidence to support that conclusion. Genpharm has not demonstrated any palpable and overriding error in Layden-Stevenson J.'s conclusion on this point.
Infringement
[12] With respect to the '668 and '762 Patents, Genpharm's argument is that its omeprazole will not infringe these patents. The '668 and '762 Patents are for new uses of omeprazole. The '668 Patent claims are directed to the use of omeprazole in the treatment of Campylobacter infections (Campylobacter is now known as H. pylori.)
[13] The '762 Patent is directed at combining the use of omeprazole and antibiotics to treat gastritis and peptic ulcers caused by H. pylori bacteria. The '762 Patent disclosure states that the combination of both active ingredients, i.e. omeprazole and antibiotics, can be in one tablet or capsule containing the omeprazole and antibiotics or in separate tablets or capsules, one of omeprazole and the other or others of the antibiotics.
[14] Having regard to Genpharm's product monograph, Layden-Stevenson J. concluded at paragraphs 156 and 192 of her reasons that if a Notice of Compliance for its omeprazole were issued to Genpharm and Genpharm were to sell its omeprazole, patients would infringe the '668 and '762 Patents.
[15] While she made a number of findings with respect to the product monograph, it is necessary to refer to only one for purposes of these reasons. At paragraph 155(m) of her reasons she states:
(m) The fourth passage dealing with the results of studies conducted on H. pylori positive and negative patients constitutes a blatant attempt, in my view, to leave the reader with the impression that Genpharm's omeprazole is to be used for treating H. pylori.
[16] The studies referred to by Layden-Stevenson J. are represented in tables in the product monograph entitled:
Multiple-Dose Study Summary Table of the Comparative Data Omeprazole Capsules and Tablets (1 x 20 mg) in H. pylori Negative Patients
and
Multiple-Dose Study Summary Table of the Comparative Data Omeprazole Capsules and Tablets (1 x 20 mg) in H. pylori Positive Patients
The "fourth" passage from the product monograph referred to by Layden-Stevenson J. follows immediately after the tables and states:
The data supports the conclusion that GEN-OMEPRAZOLE delayed-release capsules and Losec_ delayed-release tablets have an equivalent pharmacodynamic effect, and can therefore be used equally effective in the treatment of conditions where eradication of gastric acid secretion is required.
[17] It is this passage that she says constitutes the blatant attempt to leave the reader with the impression that Genpharm's omeprazole may be used for treating patients with H. pylori. We infer that her reference to "blatant attempt" is tantamount to a finding that Genpharm would be attempting to induce others to infringe Astra's patents.
[18] Genpharm argues that the product monograph passage relied upon by Layden-Stevenson J. only refers to the use of omeprazole for one of its old uses, eradication of gastric acid secretion. But there is no explanation as to why Genpharm would include in its product monograph a study relative to H. pylori positive patients, if it was not intending to imply that Genpharm's omeprazole could be used to eradicate gastric acid secretions in the treatment of H. pylori infections, the new use of omeprazole protected by the '668 Patent.
[19] The same is true in respect of the '762 Patent. The '762 Patent protects the new use of omeprazole together with antibiotics for the treatment of gastritis and peptic ulcers caused by the H. pylori bacteria. The product monograph says that Genpharm's omeprazole is equivalent to Astra's omeprazole and can be used effectively "in the treatment of conditions where eradication of gastric acid secretion is required." Conditions where eradication of gastric acid secretion is required include gastritis and peptic ulcers caused by the H. pylori bacteria. Genpharm's representation immediately following the tables referring to H. pylori positive patients implies that gastritis or peptic ulcers caused by the H. pylori bacteria can be treated by Genpharm's omeprazole together with antibiotics, the invention of the '762 Patent.
[20] Genpharm strongly objects to Layden-Stevenson J.'s finding in respect of the product monograph. It says there was no evidence led by Astra to demonstrate that the product monograph would induce infringement of the '668 or '762 Patents. However, the product monograph was itself in evidence and it was open to Layden-Stevenson J. to draw an adverse inference from it.
[21] That was especially the case in view of other evidence that was filed by Genpharm. In an affidavit filed by Genpharm's deponent, Richard Pike, it was stated that Genpharm's product monograph "... would make no mention whatsoever of Campylobacter [H. pylori] infections..."
[22] The tables referring to the H. pylori studies were not included in Genpharm's original product monograph. The H. pylori studies were only included in a revised product monograph that was prepared after Genpharm submitted its affidavit evidence in the prohibition proceedings. Genpharm says the revised product monograph was requested by Astra and was put into evidence by Astra. Genpharm says it had no opportunity to explain why it included the H. pylori studies as its time for filing affidavits had expired when Astra introduced the revised product monograph into evidence.
[23] Astra says that it was open to Genpharm to seek leave to file a supplementary affidavit explaining the inclusion of the H. pylori studies when the Pike affidavit had previously said there would be no mention of H. pylori infections in its product monograph. Genpharm does not respond to Astra's argument. Rather, Genpharm argues that the word "infection" does not appear in the H. pylori study tables and therefore Dr. Pike's evidence remains accurate. We cannot accept that argument. The reference to H. pylori positive patients on the table means patients infected with H. pylori bacteria.
[24] Genpharm takes issue with Layden-Stevenson J.'s conclusion that it failed to address some of the '762 Patent claims in its detailed statement of the legal and factual basis for its allegation of non-infringement. At paragraph 190 of her reasons, she concluded:
Similarly, here, Genpharm has failed to address some of the claims of the '762 patent (claims 68 and 69 do not form part of this analysis). It has not provided the facts, in its detailed statement, that address the claims where omeprazole is taken with antibiotic, but not in a single dosage form. In so doing, it has not advanced the facts to support its allegation of non-infringement of those claims. As a result, its NOA cannot be found to be justified.
[25] In its detailed statement, Genpharm states:
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.
[26] Genpharm says that its statement means that it will not label and market its omeprazole in combination with an antibiotic either in the same tablet or in separate omeprazole and antibiotic tablets. Genpharm's detailed statement says that its omeprazole capsules will not contain an antibiotic. We can only read that to mean that Genpharm will not label or market omeprazole capsules containing both omeprazole and an antibiotic. Nothing in the detailed statement says Genpharm will not label and market its omeprazole tablets or capsules together with antibiotics in separate tablets or capsules for the treatment of gastritis or peptic ulcers caused by the H. pylori bacteria.
[27] In Procter & Gamble at paragraph 24, this Court stated:
I do not say that it is necessary for the generic producer to address each and every dependent patent claim if the basic claim or claims that describe the invention are addressed in the detailed statement. However, it is not open to the generic producer to ignore patent claims that describe the basic invention. If it does so, it will not be providing facts demonstrating that "no claim for the use of the medicine would be infringed", and its notice of allegation will be defective and not in compliance with s. 5.
Genpharm's statement does not, as it must, address the use of omeprazole and antibiotics in separate tablets or capsules and as such, it is defective and not in compliance with section 5 of the Regulations.
Conclusion
[28] For all these reasons, we have concluded that Layden-Stevenson J. did not err in law and made no palpable and overriding error in fact that would justify this Court interfering with her order prohibiting the Minister of Health from issuing a Notice of Compliance to Genpharm for its omeprazole product prior to expiry of the '693, '377, '668 and '762 Patents.
Form of Order
[29] Finally, Genpharm takes issue with the form of the order made by Layden-Stevenson J. It reads:
Pursuant to subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, as amended, the Minister of Health is prohibited from issuing a notice of compliance to Genpharm Inc. in respect of 10 mg and 20 mg omeprazole capsules until after expiration of Canadian patents 1,292,693 ('693), 1,338,377 ('377), 2,025,668 ('668) and 2,133,762 ('762).
[30] Genpharm is concerned that in the absence of an express reference to the Notice of Allegation which gave rise to the prohibition order, it may be barred forever from applying again for a Notice of Compliance in respect of omeprazole until expiry of the four patents at issue here.
[31] The order need not be varied. Except in unusual circumstances not applicable here, the order of Layden-Stevenson J., even though it does not expressly refer to the Notice of Allegation, operates only with respect to the Notice of Allegation that was before her (See Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1997), 72 C.P.R. (3d) 468 at 476-478 (F.C.T.D.)).
[32] The appeal will be dismissed with one set of costs to AB Hassle, AstraZeneca AB and AstraZeneca Canada Inc. and one set of costs to Takeda Chemical Industries, Ltd., each calculated at the upper end of Column III of the Tariff.
"Marshall Rothstein"
J.A.
"M.N."
"JBDM"
FEDERAL COURT OF APPEAL
Names of Counsel and Solicitors of Record
DOCKET: A-607-03
STYLE OF CAUSE: GENPHARM INC. Appellant
- and -
AB HASSLE, ASTRAZENECA AB, ASTRAZENECA CANADA INC., TAKEDA CHEMICAL INDUSTRIES, LTD., and THE MINISTER OF HEALTH
Respondents
PLACE OF HEARING: TORONTO, ONTARIO
DATE OF HEARING: December 1 & 2, 2004
REASONS FOR JUDGMENT
OF THE COURT: (Rothstein, Noël & Malone, JJ.A.)
RENDERED FROM THE
BENCH BY: ROTHSTEIN J.A.
APPEARANCES BY:
Mr. Roger Hughes For the Appellant
Mr. Gunars Gaikus
Ms. Yoon Kang For the Respondents (AB Hassle / AstraZeneca)
Mr. Gary O'Neill
Ms. Martha Savoy For the Respondent (Takeda)
SOLICITORS OF RECORD:
Sim, Hughes, Ashton, McKay
Toronto, ON For the Appellant
Smart & Biggar
Toronto, ON For the Respondents (AB Hassle / AstraZeneca)
Gowling Lafleur Henderson LLP
Ottawa, ON For the Respondent (Takeda)
Morris Rosenberg
Deputy Attorney General
of Canada
Ottawa, ON For the Respondent (Minister)
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