PATENTS
Application under Patented Medicines (Notice of Compliance) Regulations, enacted to thwart appropriation by generic drug companies of research, development of innovator companies—Generic, Apotex, wishing to manufacture, sell medicine ramipril, extremely effective angiotensin converting enzyme (ACE) inhibitor but needed notice of compliance (NOC)—Aventis, innovator, seeking to prohibit Minister from issuing NOC as sale by Apotex would infringe ′206 patent—Apotex suggesting patent invalid—Commencing this type of proceeding termed “draconian” by S.C.C. as innovator secures equivalent of interlocutory injunction without having to satisfy normal criteria for such relief—“Stereochemistry” explained—History of development of ACE inhibitors— Diagram depicting structure of enalapril—Review of work done on ACE inhibitors by Schering leading to application for ′206 patent—In 1981, Schering sought patent protection in Canada, claiming 1980, 1981 priority dates based on American patent application dates—′206 patent issued March 2001—Patent stated to cover compounds useful as ACE inhibitors and as anti-hypertensive agents—Patent of enormous value, has 13 years to run—Genus of compounds includes ramipril—Necessary to construe patent as matter of law—Case law on patent construction recently reviewed by Mosley J. in Merck & Co. v. Apotex Inc., 2005 FC 755—Key to purposive construction is identification by Court, with skilled reader’s assistance, of particular words, phrases in claim that describe what inventor considered “essential” elements of invention—Patent not addressed to ordinary member of public, but to worker skilled in art to which invention relates, one who will try to succeed, not one looking for difficulties or seeking failure—In case of highly technical, scientific patents, person would have to possess high degree of expert scientific knowledge, skill—Parties agreed Apotex’ case will turn on construction of Claim 12, directed to compound, and describing genus of eight stereoisomers, one of which is ramipril—Central issue: validity of ′206 patent —Major issue whether ′206 invalid for non-compliance with former Patent Act, s. 34 (“insufficiency”)—Aventis says notice of allegation (NOA) a nullity—Burden, standard of proof—Recent F.C.A. authority indicating this now well settled—Aventis had overall burden to establish none of Apotex’ allegations justified—But once Aventis proves patent’s existence, burden shifts to Apotex to establish, on balance of probabilities, invalidity—Major issue in case: whether Schering had sound basis for predicting compounds covered by claims in issue, especially Claim 12 of ‘206 patent, useful as ACE inhibitors and in treatment of hypertension— To be patentable, invention must be useful—If new compound, utility need not be stated in claims but must appear in disclosure—While utility may be shown by testing, under doctrine of sound prediction, inventor able to justify patent claims whose utility not actually demonstrated, but can be soundly predicted based on information, expertise available: Apotex Inc. v. Wellcome Foundation Ltd., [2002] 4 S.C.R. 153—Doctrine balances public interest in early disclosure of new, useful inventions with public interest in avoiding granting monopoly for speculation, lucky guesses—Soundness of prediction question of fact—In Wellcome, S.C.C. set forth three-part test for establishing sound prediction made: (1) factual basis for prediction; (2) inventor has articulable line of reasoning from which desired result can be inferred from factual basis; (3) must be proper disclosure, though need not advance theory why invention works—Not fatal that some compounds within area claimed may prove devoid of utility —Debate over date to be used in assessing prediction’s soundness—Determination whether 1980 priority date or 1981 Canadian filing date used important as going to having regard for work done at Schering between those dates in formulating, testing compounds—In Wellcome, relied on by all parties for positions on relevant date issue, S.C.C. explicitly stated, at para. 70, “inventor must have at the date of the patent application an articulable and ‘sound’ line of reasoning” and from this would appear Canadian filing date to be used in assessing soundness of prediction—This makes sense from policy perspective as is only then that inventor must commit to precise details of claims, specification to secure monopoly —But unnecessary to finally resolve issue, Court being satisfied that even as at later Canadian application date, Schering lacked sound basis for predicting compounds would be useful—Test in assessing adequacy of NOA restated by F.C.A. in Pfizer Canada Inc. v. Novopharm Ltd., 2005 FCA 270, at para. 4: “test . . . is whether the detailed statement was sufficient to make the patentee (Pfizer) fully aware of the grounds on which the generic (Novopharm) claimed that the relevant patent would not be infringed if an NOC was issued by the Minister”—Here, Apotex had put Aventis on notice it would argue Schering failed to establish by tests compounds covered by ′206 had requisite level of activity, pharmaco-logical, toxicological profiles—Aventis notified toxicity at issue—“Requisite pharmacological profile” would be understood as relating to bioavailability, selectivity—So Aventis was aware of basis for claim ′206 invalid as related to first two elements of sound prediction test—Turning to merits, necessary to consider, in detail, state of public knowledge of ACE inhibitors, nature, extent of work being done by Schering scientists at relevant time—By January 1980 it was known variety of structures could be used, each of which would interact with Angiotensin I to generate inhibiting effect— Having reviewed prior art, Court turned to work done at Schering—On August 5, 1980 Schering scientist made first compound within scope of ′206 patent and Schering says this was date of invention, work done from then until Canadian filing merely verification—Apotex submitted there was “disconnect” between what Schering did and what was claimed—Law clear that patentee not limited to specific compounds actually made, tested prior to filing for patent protection but may claim more broadly to cover class of compounds so long as claim based on sound prediction— “After-the-fact validation” was specifically rejected in Wellcome, so fact three compounds within patent later proved of commercial value of no help in determining soundness of prediction—While Court to approach issue with anxiety to support really useful invention, on balance of probabilities could not be concluded that, at relevant time, Schering’s prediction was sound—Moving to final element of test, whether proper disclosure, it is usually sufficient if specifica-tion furnishes full, clear, exact description of invention’s nature, manner in which can be practised—Relevant date was date of Canadian filing—Apotex says first step in Example 20A not operable to produce Claim 12 compounds—Court mindful that disclosure directed to one skilled in art, with mind willing to understand employing background knowledge, other public information, not desirous of misunderstanding —But necessary no additional inventive ingenuity required to make patent work, though sufficient if merely “ordinary workshop effort” remaining—Aventis, Schering say NOA inadequate in not asserting skilled person could not make Example 20A product having regard to whole of specification, common general knowledge—Clear from voluminous evidence adduced by Aventis, Schering regarding Example 20A, they fully appreciated nature of attack by Apotex—Court satisfied NOA sufficient on this issue—Evidence from American proceedings was hearsay, inadmissible unless within an exception to hearsay rule—No evidence three declarants unable to swear affidavits for this proceeding or were cross-examined in U.S.A. or Europe—As to operability of 20A, Court satisfied process described in mercuric acetate oxidation step in 20A operable in October, 1981—Court not persuaded by Apotex skilled person could not have created desired imine based on what generally known in field—Turning to sufficiency in relation to issues of separation, characterization of stereoisomers of ramipril, variety of techniques commonly known, available to “characterize” or determine structure, stereochemistry of compounds created, including: x-ray crystallography, chiroptic measurements, chemical degreda-tion, nuclear magnetic resonance spectroscopy and reactions conducted using single enantiomer of catalyst or reactant— ′206 patent discloses well-known separation techniques— While separation, characterization techniques may have been known by October 1981, without sufficient information as to physical characteristics of compounds, separation, characteri-zation could not be carried out—Disclosure of ′206 patent insufficient, as fails to teach how to separate, characterize stereoisomers—Evidence of witness who tried to carry out separation, characterization preferred to that of those speaking in theoretical terms—Since October 1981, ramipril has been separated, characterized but back then skilled person could not have done so without using inventive ingenuity so disclosure deficient in that regard—Schering not having satisfied any of elements of Wellcome sound prediction test regarding Claim 12 compounds—Prohibition application denied—In event Judge in error as to sound prediction, other issues raised by Apotex considered—Whether claims invalid for non-compliance with s. 34(1) of old Patent Act—Facts of case at bar unusual in that 20 years elapsed between filing, issuance of ′206 patent—During that time substantial advances in scientific knowledge—Situation could not now arise, due to introduction of “first to file” patent system—While use of issue date in assessing disclosure sufficiency allows Schering to have provided deficient consideration for monopoly grant and to benefit from advances in knowledge while application pending, F.C.A. held in AlliedSignal Inc. v. Du Pont Canada Inc. (1995), 61 C.P.R. (3d) 417, date of issue, not priority date, to be used in assessing sufficiency of disclosure—So patent not invalid under s. 34(1)—Next issue whether claims broader than invention or lack utility—Concept of “utility”, as used in patent context, explained—Utility not depending on marketability, that is, sufficiently useful to support commercialization (unless commercial utility promised)—Nor, for patent purposes, does it matter that compound may cause side effects—But patent invalid if claims substances devoid of utility: Monsanto Company v. Commissioner of Patents, [1979] 2 S.C.R. 1108—To be patentable, “invention” had to be “new and useful”: Patent Act, s. 2 definition of “invention”—Court must determine what ′206 patent promised—Patent promised utility as ACE inhibitors, anti-hypertensive agents—Expert evidence as to utility considered—Question not whether Schering scientists could have predicted compounds useful but whether in fact useful as ACE inhibitors, anti-hypertensive agents—Certain expert evidence ruled inadmissible as raised new facts, not merely supporting allegations in Apotex’ NOA especially as Aventis required to lead evidence first, relied on facts, definition of issues identified in NOA, lacked chance to respond: Mayne Pharma (Canada) Inc. v. Aventis Pharma Inc., 2005 FCA 50—At the end of day, burden on Apotex to show Claim 12 compounds lacked promised utility—Court not persuaded compounds lacked utility as ACE inhibitors—Apotex suggested all other side’s evidence went to ACE inhibition, relying on “Ergo” argument as to anti-hypertensive utility—Apotex submitted ACE inhibition not to be equated with anti-hypertensive effect—Argument rejected since, according to Apotex witness, anti-hypertensive effect of ACE inhibitor simple matter of bio-mechanics: inhibiting ACE, thereby reducing amount of Angiotensin II in body, automatically reduces blood pressure—Such issues as toxicity, potency go to commercial utility, do not detract from proposition ACE inhibition, of necessity, results in blood pressure reduction—Court not persuaded compounds within ′206 patent lack utility, as term used in patent law context— Remaining issues concerned overlap between ′206, other patents, were argued in summary fashion as not dispositive of case—Apotex argued ′206 invalid for anticipation but that issue does not arise in view of conclusion Schering lacked sound basis for prediction—In any event, invention claimed in ′206 patent not anticipated by that claimed in ′087—Free World Trust v. Électro Santé Inc., [2000] 2 S.C.R. 1024 stands for proposition test for anticipation is difficult to meet —Court not convinced ′087 claims class of compounds claimed in ′206—Apotex actually suggesting earlier invention was somehow anticipated by later one—For attack to succeed, Apotex had to establish both prior knowledge of use by Hoechst and missed patent applications conflict—As prior knowledge or use by Hoechst not established, unnecessary to determine whether missed conflict—As to submission patent invalid due to old Patent Act, s. 61(2), inapplicable as applies only if application filed after issuance of other patent relied on; ′206 patent application filed before issuance of ′087— Also, s. 61(2) merely provides procedure for prosecution phase, may not be relied on to invalidate issued patent: Beecham Canada Ltd. et al. v. Procter & Gamble Co. (1982), 61 C.P.R. (2d) 1 (F.C.A.)—Final issue whether claims in issue in ′206 invalid as “same invention-“, “obviousness-” type double patenting—Relationship between patents at issue in relation to double patenting addressed by Snider J. in Aventis Pharma Inc. v. Pharmascience Inc., [2005] 4 F.C.R. 301 (F.C.)—Judge held obviousness-type double patenting not limited to cases involving same inventor—Concluded ′087 patent added “something of a substantial character to existing knowledge”, found ′206 was genus patent, ′087 selection patent—Also held date of invention, not issuance, to be used for obviousness determination—Whether decision of Snider J. to be followed as matter of judicial comity—Must distinguish between legal conclusions, perhaps subject to comity principle, fact-findings, which depend on evidence adduced—Conclusion, as matter of first impression, double patenting not limited to same inventor not manifestly wrong, followed—Court agreeing with Snider J. invention claimed in ′206 not obvious in light of ′087, ′457 patents—Conclusion ′206 claims not identical to ′087, ′457 was patent construction question, matter of law, followed as matter of comity— Aventis’ application dismissed—Costs should follow event, include costs of second counsel, taxed at middle of column III—Patent Act, R.S.C. 1970, c. P-4, ss. 34, s. 61(2)—Patent Act, R.S.C., 1985, c. P-4, s. 2 “invention”.
Aventis Pharma Inc. v. Apotex Inc. (T-1742-03, 2005 FC 1283, Mactavish J., order dated 20/9/05, 109 pp.)