In Lundbeck Canada v. Minister of Health, 2009 FC 1102, the Federal Court of Canada (FC) dismissed Lundbeck's prohibition application against Ratiopharm in respect of two patents relating to memantine hydrochloride. Canadian patents 2,014,453 ('453 patent) and 2,426,492 ('492 patent) were listed by Lundbeck on the Patent Register under section 4 of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 (PMNOC Regulations). The patents relate to memantine, a drug used to treat individuals with Alzheimers. The '453 patent outlines the mechanism of action for memantine and the '492 patent suggests a method for combining memantine with other acetylcholine inhibitors (ACE inhibitors) to provide a synergistic effect. Ratiopharm served a Notice of Allegation on Lundbeck alleging that both the '453 and the '492 patents were invalid. The FC ruled that Ratiopharm's allegations of invalidity were justified with respect to both patents. In doing so, the FC employed the tests for anticipation, obviousness, utility and found a lack of good faith prosecution due to the failure to specifically identify adverse material in a disclosed prior art reference.

Anticipation

The FC first applied the test for anticipation as established by the Supreme Court's in Apotex Inc. v. Sanofi-Synthelabo Canada Inc., 2008 SCC 61 (Sanofi). The first element, "prior disclosure", is satisfied when a prior art reference discloses subject matter such that infringement of the patent would inevitably or necessarily result when the subject matter is performed. The second element, "enablement", is satisfied when a person skilled in the art is able to perform the invention without undue burden or an inventive step.

The FC found a Japenese patent reporting that a derivative of the chemical forumla claimed in the '453 patent was effective in treating a range of cerebrovascular disorders, including Alzheimer's. A German compendium of pharmaceuitcals also listed the derivative useful for treating, among other things, "organic brain syndrome", something that a skilled person would take to include Alzheimer's. A 1998 publication describing a study treating dementia patients observed that the array of symptoms treated with memantine include symptoms of Alzheimer's disease. As the practice of the cited prior disclosures would necessarily lead to infringement of the Lundbeck's '453 patent, it was found to be anticipated.

Obviousness

While not required to, the FC also addressed the issue of obviousness with respect to the '453 patent. The FC adopted the four step approach outlined in Sanofi. The first step requires an objective-subjective assessment of the person skilled in the art. The second step asks the FC to identify the inventive concept of the claim. The third step requires a comparison of any differences between the matter cited as forming part of the "state of the art" and the inventive claim. Lastly, the fourth step asks whether the differences outlined in step three constitute steps that would have been obvious to a person skilled in the art.

The Court found the question to be whether it was obvious that memantine could be useful in treating cerebral ischemia, as the term was defined in the '453 patent, including Alzheimer's disease. Ratiopharm pointed to the expansive claim construction of the patent by the applicant, intending it to cover all situations whereby an imbalance of neuronal stimulation mechanisms led to an excess inflow of calcium ions, and not just Alzheimer's disease. The FC founded that even if it was mistaken in its anticipation analysis, the prior art documents rendered the '543 patent obvious. The FC found that what was different after the '453 patent was the understanding of memantine's mechanism of action as a receptor antagonist. The FC noted, and the applicants conceded, that the mere explanation of the mechanism underlying a use already disclosed in the prior art cannot, without more, give rise to an invention. The FC held it was clear that chemical derivatives as claimed in the '453 patent were being previously being used to treat cerebral disorders, as that term is used in the '453 patent, including Alzheimer's disease. Applying this test, the FC ruled that previously disclosed publications relating to memantine and its positive effects had rendered the findings of the '453 patent obvious.

Utility

With respect to the '492 patent, the FC found that ratiopharm's assertion that the patent lacked utility was justified. Utility can either be demonstrated through testing or soundly predicted by facts and reasoning. As utility had not been demonstrated prior to the filing date, the FC focused their attention on the doctrine of sound prediction. The FC relied on the SC decision in Apotex Inc. v. Wellcome Foundation Ltd., 2002 SCC 77, which articulated a three part test for satisfying the doctrine of sound prediction. The first element is that there must be a factual basis for the prediction. In addition, the inventor must have a line of reasoning from which the desired result can be inferred. Lastly, there must be disclosure that reflects this line of reasoning. In the '492 patent, Lundbeck claims that the combination therapy of memantine and ACE inhibitors results in a synergistic effect. However, upon review of disclosure, there is no evidence to suggest that the combination therapy provides anything more than an additive effect. Therefore, the FC held that the '492 patent claims failed to satisfy the three part test of sound prediction.

Good Faith Prosecution

Although not necessary to do so, the FC also considered the issue of good faith prosecution imposed by paragraph 73(1)(a) of the Patent Act, R.S.C. 1985, c. P-4. This provision requires prior arts to be fully and fairly described by the applicants. It was alleged that Lundbeck failed to fully describe the importance of a prior art document, specifically that the applicants misrepresented that the prior art "taught away" from using a combination of memantine and an acetylcholinesterase inhibitor in the treatment of Alzheimer's disease. The patent examiner had required “an identification of any prior art cited in respect of the United States and European Patent Office applications”. The applicant's response identified two documents cited in the International Search Report, one of which was the prior art document. There is no discussion of the significance of Wenk in the patent agents' response, nor was a copy of the article provided to the patent examiner at that time. In reponse to am allegation of obviousness, Lundbeck replied "It is therefore of prime importance to note that, at that time, there were numerous articles in the prior art which warned against the combination of NMDA antagonists and AChE". The prior art document "taught that while some acetylcholinesterase inhibitors do lose their therapeutic effect when used in conjunction with memantine, others do not." Finding paragraph 73(1)(a) includes a duty to reply in good faith and accepting the reasoning in G.D. Searle v. Novopharm Ltd., 2007 FC 81, the FC found a duty of candour on the part of applicants in the prosecution of a patent application in Canada. The FC particularly noted the ex parte circumstances and the resulting "duty of ensuring that the Court is apprised of all of the relevant facts" when the ordinary checks and balances of the adversary system are not operative.The FC found that "the applicants' patent agents provided the patent examiner with four less relevant items of prior art which 'taught away' from pursuing the invention, yet failed to mention the one directly relevant study that came to the opposite conclusion."