Lundbeck Canada Inc. v. Canada (Health)

Lundbeck Canada Inc. v. Canada (Health)
Court (s) Database
Federal Court Decisions
Date
2009-02-25
Neutral citation
2009 FC 146
File numbers
T-372-07
Decision Content
Date: 20090225
Dockets: T-372-07
T-991-07
T-1395-07
Citation: 2009 FC 146
Docket: T-372-07
BETWEEN:
LUNDBECK CANADA INC.
Applicant
and
THE MINISTER OF HEALTH AND
GENPHARM ULC
Respondents
and
H. LUNDBECK A/S
Respondent/Patentee
Docket: T-991-07
AND BETWEEN:
LUNDBECK CANADA INC.
Applicant
and
THE MINISTER OF HEALTH AND
APOTEX INC.
Respondents
and
H. LUNDBECK A/S
Respondent/Patentee
Docket: T-1395-07
AND BETWEEN:
LUNDBECK CANADA INC.
Applicant
and
THE MINISTER OF HEALTH AND
COBALT PHARMACEUTICALS INC.
Respondents
and
H. LUNDBECK A/S
Respondent/Patentee
PUBLIC VERSION OF REASONS FOR ORDERS
(Identical to Confidential Reasons for Orders issued 12 February 2009)
HARRINGTON J.
[1] These three applications deal with two words not in every day use; enantiomers and racemates. The patent in issue relates to (+) citalopram which is an enantiomer of citalopram. Citalopram, the subject of a patent which expired years ago, is a racemic compound containing unresolved (+) citalopram and (-) citalopram in equal amounts. It has been found useful as an antidepressant. Lundbeck claims that (+) citalopram, which has come to be known as escitalopram, is also useful as an antidepressant.
[2] The applications seek an order prohibiting the Minister from authorizing Genpharm, Apotex and Cobalt (hereinafter the respondents) from manufacturing and selling their generic versions of escitalopram until the patent expires in 2014, the whole pursuant to the Patented Medicine (Notice of Compliance) Regulations.
[3] Escitalopram is covered by Canadian patent 1,339,452 which was applied for in June 1989 based on a United Kingdom priority date of June 1988. It was granted in 1997 and expires in 2014. The Patent Act as it was immediately prior to 1 October 1989, applies. The patent is held by H. Lundbeck A/S of Denmark. Escitalopram is sold in Canada by its Canadian subsidiary, Lundbeck Canada Inc., in virtue of a Notice of Compliance obtained from Health Canada. Lundbeck Canada Inc. also succeeded in having the patent listed in the Register maintained by the Minister pursuant to the said PM (NOC) Regulations. Subsequent references to “Lundbeck” are either to the Danish or Canadian corporation as dictated by context.
[4] Unless the hurdles incorporated in the PM (NOC) Regulations are overcome, the Minister is disentitled from permitting the respondents from marketing their generic versions of escitalopram until the patent expires. These regulations have been intensely litigated and need not be analyzed in detail here. Reference is made to the decisions of the Supreme Court in Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare), [1998] 2 S.C.R. 193, 80 C.P.R. (3d) 368; Bristol-Myers Squibb Co. v. Canada (Attorney General), 2005 SCC 26, 39 C.P.R. (4th) 449 at paragraphs 5-24 (Biolyse) and Apotex Inc. v. Sanofi-Synthelabo Canada Inc., 2008 SCC 61, 69 C.P.R. (4th) 251 at paragraphs 7 and 12-17, as well as to the decision of Mr. Justice Hughes in Ferring Inc. v. Canada (Minister of Health), 2007 FC 300, 55 C.P.R. (4th) 271.
[5] Not content to await the expiry of the patent, each of the three respondents served Lundbeck with a “Notice of Allegation”, the upshot of each are submissions that patent ‘452 is invalid. Lundbeck responded by instituting these three applications for prohibition orders. The applications in effect serve as a statutory injunction for up to two years. As applicant, the overall burden of proof falls upon Lundbeck to persuade the Court that the factual and legal bases of the allegations are not justified. However since only invalidity is in issue, cognisance must be taken of the legally rebuttable presumption that the patent is valid. That presumption is a weak one, but it does behove the respondents to, at the very least, lead enough evidence to put validity in play. (Abbott Laboratories v. Canada (Minister of Health), 2007 FCA 153, 59 C.P.R. (4th) 30 and Pfizer Canada Inc. v. Apotex Inc., 2007 FC 971, 61 C.P.R. (4th) 305, per Mr. Justice Mosley at paragraphs 44-51)
ISSUES
[6] Ultimately, the only issue is whether or not the Minister should be prohibited from issuing a Notice of Compliance to one, some, or all of the respondents. The penultimate step in the process is to determine whether or not Lundbeck has persuaded the Court, on the balance of probabilities, that the allegations of invalidity are not justified. In some instances, but not the ones at hand, a determination that the allegations are not justified does not lead to a prohibition order. For instance, a party may be barred from obtaining such an order on the basis of abuse of process (Sanofi-Aventis Canada Inc. v. Novopharm Ltd., 2007 FCA 163, 59 C.P.R. (4th) 416 and Sanofi-Aventis Inc. v. Laboratoire Riva Inc., 2007 FC 532, 58 C.P.R. (4th) 109).
[7] All three respondents allege that the patent in issue is a selection patent chosen from a previous U.S. patent and is invalid because it falls short of the requisite criteria. Selection patents were dealt with very recently by the Supreme Court in Sanofi-Synthelabo, above. I shall refer to that decision as Plavix after the compound in issue so as to distinguish it from other cases cited herein in which either Sanofi or Apotex appears in the style of cause. Lundbeck asserts that escitalopram is not a selection patent; it is a per se patent for escitalopram itself. However, should it be found that it is a selection patent then it meets all the requirements thereof. I regard this issue as fundamental. If escitalopram is an invalid selection patent, it is not necessary to deal with the other allegations of invalidity.
[8] Although couched in somewhat different language, the three respondents further allege that, in any event, Lundbeck invented nothing deserving of a patent. One or more allege that escitalopram is not novel, was anticipated, was obvious, and lacks utility. Finally, more technical grounds of invalidity are asserted such as insufficiency of the specification and disclosure, overclaiming, or making irrelevant claims, lack of sound prediction, ambiguity and a lack of candour as well as wilful omissions contrary to section 53 of the Act.
DECISION
[9] Although they have not succeeded on every point, each of the respondents has, in my opinion, lead enough evidence to put validity into play. However, I have reached the conclusion that Lundbeck has established that the allegations are not justified in each of the three applications and so prohibition orders shall issue.
NATURE OF THE PROCEEDINGS
[10] It has been well-established that applications pursuant to the PM (NOC) Regulations are intended to be summary in nature and are not ultimately binding upon the parties as to validity or infringement. The parties are entitled to litigate those issues in a proper action, as well as other patent claims not covered by the Regulations such as product by process claims. Lundbeck only has to meet the allegations set out in the separate Notices of Allegation. Consequently, the result could differ from application to application. Non-infringement was not raised at all and so is not before me. These proceedings determine neither validity nor infringement.
[11] The advantages of an action over an application are well known. They include: a full discovery of documents based on affidavits in which all must be disclosed, not just the documents relied upon; viva voce examination for discovery; experts are qualified as such by the Court before testifying; a trial where witnesses are heard; and the judge is able to ask clarifying questions. In applications the evidence is heard outside court by way of affidavits and cross-examinations thereon. Transcripts, by their very nature, are sterile. By way of example, in Janssen-Ortho Inc. v. Novopharm Ltd., 2004 FC 1631, (2005), 35 C.P.R. (4th) 353 Mr. Justice Mosley held in the context of a PM (NOC) application that the patent was invalid for obviousness. Janssen-Ortho then took action for patent infringement and, following a full trial, succeeded before Mr. Justice Hughes (Janssen-Ortho Inc. v. Novopharm Ltd., 2006 FC 1234, 57 C.P.R. (4th) 6, aff’d 2007 FCA 217, 59 C.P.R. (4th) 116, leave to appeal to S.C.C. refused, [2007] S.C.C.A. No. 442.(QL)).
[12] I consider it important to emphasize the limited value of this decision because patents directed to escitalopram has been under attack in several jurisdictions.
[13] At trial in the U.K., it was found that claims 1 and 3 were invalid for insufficiency because they claimed the enantiomer made by any method but the specification only disclosed two ways of making it. (Generics (U.K.) Ltd. & Ors. v. H. Lundbeck A/S, [2007] EWHC 1040 (Pat), 2007 R.P.C. 32. However the Patents Court decision was reversed by the Court of Appeal in H. Lundbeck A/S v. Generics (U.K.) Ltd. & Ors., [2008] EWCA Civ 311, [2008] R.P.C. 19. I was informed during the course of argument that the case is proceeding to the House of Lords on the insufficiency point.
[14] In the United States, the American version of the patent was upheld both at trial and in appeal. I was informed that the appeal decision is final. (Forest Labs., Inc. v. Ivax Pharms., Inc. 438 F. Supp. 2d 479 (D. Del., 2006) aff’d 501 F.3d 1263 (Fed. Cir. 2007).
[15] The Australian patent was held to be valid at trial in Alphapharm Pty Ltd., v. H. Lundbeck A/S, [2008] FCA 559. That decision is said to be under appeal.
[16] However in Germany the Federal Patent Court ruled the patent was invalid on the grounds that the subject matter of the alleged invention was not novel and was not based on an inventive step. The nature of the proceedings was somewhat different from a common law trial. Witnesses were not heard and the judge was assisted by three others who had expertise in the field. That decision is also said to be under appeal.
[17] Of course, none of these decisions, either in findings of fact or in conclusions of law, is binding upon me. That is not to say that the rationale of those decisions may not be persuasive.
[18] In addition I was told that proceedings are pending in several other jurisdictions.
[19] These are three distinct applications which, although heard consecutively, were never joined. Lundbeck’s evidence is tailored somewhat to meet the different Notices of Allegation, but the affidavits of its factual and expert witnesses are essentially the same. However, these witnesses were cross-examined on three separate occasions. With the exception of Dr. Newton, called by both Genpharm and Cobalt, the respondents’ witnesses are different, although much of what they have had to say is the same.
[20] In each proceeding, Lundbeck obtained a protective order which had the effect of keeping much of the information in each of the applications confidential. They were kept absolutely separate and distinct until shortly before the hearings when, following a case management conference, it was agreed that counsel for the respondents could attend all three hearings without facing an in camera application. Memoranda of fact and law in all three applications were also exchanged.
[21] The application records, excluding copies of case law, total more than 29,000 pages. Argument on the validity of three claims of one patent lasted thirteen days. Given that the degree of commonality greatly surpasses the distinctiveness of each application, I have decided to render one set of reasons, identifying where necessary the points in issue which were not raised by all three respondents.
AN ORGANIC CHEMISTRY PRIMER
[22] As stated at the outset, citalopram is what is known as a racemate and escitalopram is one of the two enantiomers inherent therein. The parties assure me that every undergraduate student of organic chemistry, much less the skilled addressee of a patent, knows, and at all relevant times knew, that carbon-centered molecules have a three-dimensional structure. If that carbon atom is bonded to four different atoms or groups of atoms (as is the case here), the molecule is described as having an asymmetric centre. These compounds are identical save that they exist in two space-occupying forms called “enantiomers”. They are non-superimposable mirror images of one another. Such asymmetric molecules are called chiral, coming from the Greek word for hand, as a left hand and right hand are mirror images of each other and are not superimposable. When many drugs are created or synthesized, the result is an equal mixture of the two enantiomers. This mixture is called a racemic mixture or a racemate.
[23] Although the racemate and its enantiomers do not differ in their chemical or physical properties (and thus may be difficult to separate or resolve), they can, as noted by Professor Jenner, a witness called by Apotex, dock within the human body in different ways with biomolecules, such as proteins, which also have three-dimensional structure.. “…The best analogy to draw is a key and lock interaction… As a consequence they can have differing pharmacological properties...”
[24] Enantiomers are a subset of stereoisomers, which in turn are a subset of isomers. Isomers are molecules with the same chemical formula, but in which the atoms are arranged differently. Stereoisomers are isomers with the same atomic connectivity, but whose atomic arrangement in space is different. Enantiomers are stereoisomers that, as aforesaid, are mirror images of each other and not superimposable. They are molecules which have only one chiral centre and are to be distinguished from diasteromers which are stereoisomers that are not mirror images and may have more than one chiral centre. This distinction is important when it comes to separating or resolving a racemate.
[25] Enantiomers are the subject of two unrelated nomenclatures. An enantiomer is capable of directing the plane of polarization of polarized light in one direction or another. If the plane is turned clockwise, to the right, the enantiomer is called (+), d or dextro-rotary. If the plane is turned counter-clockwise it is called (-), l or levo-rotary.
[26] The second naming method is the Cahn-Ingold-Prelog convention which specifies absolute configuration. The substituents around the chiral centre are “sized” according to their atomic numbers. If the sequence from the largest to the smallest flows in a clockwise direction, the molecule is assigned the R or rectus designation. Otherwise it is assigned the S or sinister designation.
[27] There is no relationship between the plus and minus designations and the S and R designations. Escitalopram was first described as (+) or dextro, and only later as sinister.
[28] Although this information is drawn from the affidavits of Professor Stephen Davies, called by Lundbeck, and Dr. Frank Newton, called by both Genpharm and Cobalt, I have found no disagreement among the various experts as to the basic chemistry involved or that the racemate and each of its two enantiomers may work differently within the body.
PATENT CONSTRUCTION
[29] At the heart of any dispute regarding a patent is its meaning. The principles have been well-established and were clearly set forth by the Supreme Court in Free World Trust v. Électro Santé Inc., 2000 SCC 66, 9 C.P.R. (4th) 168 and Whirlpool Corp. v. Camco Inc., 2000 SCC 67, 9 C.P.R. (4th) 129. As applicable to these applications:
a. It is a statutory requirement that the patent contain a specification and end with a claim or claims “defining distinctly and in explicit terms the subject-matter of the invention for which an exclusive privilege or property is claimed”. The specification must be sufficiently full, clear, concise and exact “as to enable any person skilled in the art or science to which it pertains, or to which it is most closely connected, to make, construct, compound or use it”. (Patent Act, pre-1 October 1989, s. 34).
b. The patent is notionally addressed to a person skilled in the art or science of the subject-matter and is to be read as such a person would have read it when it first became public.
c. The claims are to be read in an informed and purposive way to permit fairness and predictability and to define the limits of the monopoly.
d. The claim portion of the patent specification takes precedence over the disclosure portion in the sense that the disclosure is read to understand what was meant by a word in the claims “…but not to enlarge or contract the scope of the claim as written and thus understood” (Whirlpool at para. 52).
e. To overclaim is to lose everything. If the inventor underclaims, the court will not broaden the monopoly in the interests of the “spirit” thereof
f. A patent is not an ordinary document. It meets the definition of a “regulation” in the Interpretation Act, and must be read to assure the attainment of its objects. “[C]laims construction is a matter of law for the judge, and he was quite entitled to adopt a construction of the claims that differed from that put forward by the parties.” (Whirlpool at para. 61.)
(See also Biovail Pharmaceuticals Inc. v. Canada (Minister of National Health and Welfare), 2005 FC 9, 37 C.P.R. (4th) 487, at para. 15).
[30] Pursuant to section 27 of the Patent Act, as it was prior to 1 October 1989, an inventor or legal representative thereof was entitled to obtain a patent for:
…an invention that was
(a) not known or used by any other person before he invented it,
(b) not described in any patent or in any publication printed in Canada or in any other country more than two years before presentation of the petition hereunder mentioned, and
(c) not in public use or on sale in Canada for more than two years prior to his application in Canada,.
…une invention qui
a) n'était pas connue ou utilisée par une autre personne avant que lui‑même l'ait faite,
b) n'était pas décrite dans quelque brevet ou dans quelque publication imprimée au Canada ou dans tout autre pays plus de deux ans avant la présentation de la pétition ci‑après mentionnée, et
c) n'était pas en usage public ou en vente au Canada plus de deux ans avant le dépôt de sa demande au Canada
[31] An invention was defined at section 2 as meaning:
[…] any new and useful art, process, machine, manufacture or composition of matter, or any new and useful improvement in any art, process, machine, manufacture or composition of matter
[…] Toute réalisation, tout procédé, toute machine, fabrication ou composition de matières, ainsi que tout perfectionnement de l'un d'eux, présentant le caractère de la nouveauté et de l'utilité.
SKILLED ADDRESSEE
[32] The qualities of the person to whom a patent addressed were dealt with in Whirlpool, above. Mr. Justice Binnie, at paragraph 70, quoted Mr. Justice Dickson in Consolboard Inc. v. MacMillan Bloedel (Saskatchewan) Ltd., [1981] 1 S.C.R. 504 at 523, 56 C.P.R. (2d) 145 quoting H.G. Fox, Canadian Law and Practice Relating to Letter Patent for Invention, 4th ed. (Toronto: Carswell, 1969) at page 204:
The persons to whom the specification is addressed are “ordinary workmen”, ordinarily skilled in the art to which the invention relates and possessing the ordinary amount of knowledge incidental to that particular trade. The true interpretation of the patent is to be arrived at by a consideration of what a competent workman reading the specification at its date would have understood it to have disclosed and claimed.
[33] Mr. Justice Binnie added at paragraph 71 that ““Ordinariness” will, of course, vary with the subject matter of the patent. Rocket science patents may only be comprehensible to rocket scientists.”
[34] Considerable detail was set out in the various affidavits as to the identity of this person, or group of persons, particularly as regards the common general knowledge prevalent at the time and the depth of the research required of such person into the prior art. This concern flows from the fact that at paragraph 70 of Whirlpool Mr. Justice Binnie also quoted from Beloit Technologies Inc. v. Valmet Paper Machinery Inc., [1997] EWCA Civ 993, [1997] R.P.C. 489 where Aldous L.J. said at page 494:
The notional skilled addressee is the ordinary man who may not have the advantages that some employees of large companies may have. The information in a patent specification is addressed to such a man and must contain sufficient details for him to understand and apply the invention. It will only lack an inventive step if it is obvious to such a man. [Emphasis added.]
[35] I very much doubt that, at the time, such an addressee had the analytical tools to find, and the inclination to read and digest, every single published document pertaining to racemates and enantiomers, as does today’s pharmaceutical company which, with the aid of more sophisticated computers and search engines, is driven to list an encyclopedia of prior art in its Notice of Allegation when it cannot market its product because it is on “patent hold”. Dr. Newton, for one, was armed with more prior art in these applications than he was in the U.K. trial. However, nothing turns thereon as I am persuaded that the resolution of citalopram by any method was not obvious even to an addressee who was perfect in every way.
[36] Suffice it to say that the patent is addressed to a team centred around a medicinal chemist who has access to and makes use of others with different skill sets such as analytical chemists and psychiatrists. It is not necessary to make a definitive finding as to the balance between the team’s formal education and laboratory experience, be it in a university or at a pharmaceutical company. Theoretical knowledge of, and practical experience in, the methods of resolving racemates is essential.
SELECTION PATENTS
[37] The term “selection patent” is to be found nowhere in the current or previous Patent Acts. It is a product of English jurisprudence. In E.I. Du Pont de Nemours & Co. (Witsiepe’s) Application, [1982] F.S.R. 303 (H.L.), Lord Wilberforce stated at page 309: “…[t]he difficulty arises when disclosure is made of a group or class of substances for which some advantage is claimed, and later it is found that one or more of this group or class possesses special advantages not belonging to the rest of the group or class and not previously identified. …”
[38] Following the decision of the Supreme Court in Plavix, above, there can be no doubt that in principle such patents are valid in Canada. Mr. Justice Rothstein drew upon English jurisprudence, more particularly the decision of Mr. Justice Maugham in the leading case of In re I.G. Farbenindustrie A.G.’s Patents (1930), 47 R.P.C. 289 (Ch.D), and stated at paragraph 9:
.… At p. 321, he explained that in the field of chemical patents (which would of course include pharmaceutical compounds), there are often two “sharply divided classes”. The first class of patents, which he called originating patents, are based on an originating invention, namely, the discovery of a new reaction or a new compound. The second class comprises patents based on a selection of compounds from those described in general terms and claimed in the originating patent. Maugham J. cautioned that the selected compounds cannot have been made before, or the selection patent “would fail for want of novelty”. But if the selected compound is “novel” and “possess[es] a special property of an unexpected character”, the required “inventive” step would be satisfied (p. 321). At p. 322, Maugham J. stated that a selection patent “does not in its nature differ from any other patent”.
Plavix was an enantiomer specifically claimed in the original or genus patent.
[39] The genus patent in Plavix only described the overall class of more than 250,000 compounds, racemates and enantiomers alike, in general terms. In order to discover Plavix’s special qualities, a racemate had to be resolved. This was the inventive step as found by Mr. Justice Shore in first instance (2005 FC 390, 39 C.P.R. (4th) 202), a finding which held sway throughout (2006 FCA 421, 59 C.P.R. (4th) 46).
[40] Although it may seem a little peculiar, and contrary to section 34(1)(b) of the Act, that if one claims a group of compounds, it may only be necessary to give a few examples as to how a few within the group may be made, it must be kept in mind that the genus patent may literally claim millions of different compounds. In May & Baker Limited and Others v. Boots Pure Drug Company Limited, [1950] UKHL 1, [1950] R.P.C. 23, not less than 97 million compounds had been claimed.
PATENT ‘452
[41] Patent ‘452 entitled “Enantiomers of Citalopram and Derivatives Thereof” states in the abstract of the disclosure that the invention relates to the two novel enantiomers of citalopram and to their use as antidepressant compounds. It is said to include pharmaceutically acceptable salts. After stating that previous attempts to resolve citalopram (which it noted had been previously disclosed in U.S. patent number 4,136,193, which was filed in January 1977) by crystallizing diastereomeric salts of citalopram had failed, it was discovered that a precursor of citalopram, a diol disclosed in U.S. patent number 4,650,884 filed in August 1985 entitled “Novel Intermediate and Method for Its Preparation” (which was also a racemic mixture) could be resolved into its enantiomers and in a stereoselective way converted to the corresponding citalopram enantiomers. Patent ‘452 described two reaction schemes by which the (+) enantiomer of citalopram could be obtained. Of the 11 claims only 1, 3 and 5, to the extent it is dependent on 3, are in issue. They claim:
- 1 -
A compound selected from substantially pure (+)-1-(3-Dimethylaminopropyl)-1-(4’-fluorophenyl)-1, 3-dihydroisoben-zofuran-5-carbonitrile and non-toxic acid addition salts thereof.
[…]
- 3 -
A pharmaceutical composition in unit dosage form useful as an antidepressant comprising a pharmaceutically-acceptable diluent or adjuvant and, as an active ingredient, an effective amount of a compound as defined in Claim 1.
[…]
- 5 -
A pharmaceutical composition in unit dosage form, useful as an antidepressant according to claim 3 or 4, wherein the active ingredient is present in an amount from 0.1 to 100 milligram per unit dose.
[42] U.S. patents ‘193 and ‘884, or at least ‘193, are said to be the patents from which Canadian patent ‘452 was selected. Patent ‘193 discloses a formula which might generate a few hundred different compounds. Citalopram was specifically claimed. Neither U.S. patent makes mention of stereochemistry in general, or the enantiomers of citalopram in particular, much less claims them.
Is escitalopram special?
[43] The most favourable reading that can be given to the ‘452 patent, a reading some of the respondents dispute, is that escitalopram is about 1.6 times more potent than citalopram. Since it was well within the realm of possibility that more, and indeed sometimes all, of the desired biological activity of a racemate might rest within one enantiomer rather than in the other, the discovery that escitalopram may be more beneficial than citalopram is not surprising. Indeed, if all of the desired activity resided in escitalopram, it would only be twice as potent as citalopram, which is not sufficiently unexpected to serve as the basis of a selection patent (GlaxoSmithKline v. Pharmascience Inc., 2008 FC 593). Surprises arise outside this range. There is no indication that escitalopram has other desirable or surprising traits such as less toxicity or an unexpected and substantial increase in solubility, stability, handling properties, processability or in its side effects profile. Consequently, if escitalopram is a selection patent, it is invalid.
[44] However, I am satisfied that escitalopram is not a selection patent. In Plavix, the Supreme Court clarified the circumstances in which a patent, selection or otherwise, may be invalided on the grounds of anticipation. In first instance, Mr. Justice Shore cited Free World, above, which approved the test for anticipation set out by Mr. Justice Hugessen in Beloit Canada Ltd. et al v. Valmet Oy (1986), 8 C.P.R. (3d) 289 (F.C.A.) at p. 297:
…. One must, in effect, be able to look at a prior, single publication and find in it all the information which for practical purposes, is needed to produce the claimed invention without the exercise of any inventive skill. The prior publication must contain so clear a direction that a skilled person reading and following it would in every case and without possibility of error be lead to the claimed invention. … [Emphasis added by Mr. Justice Shore.]
However, and drawing from the decision of Lord Hoffmann in Synthon B.V. v. SmithKline Beecham plc, [2005] UKHL 59, [2006] 1 All E.R. 685, [2006] R.P.C. 10, Mr. Justice Rothstein held that there are two components to anticipation: prior disclosure and enablement. “…[P]rior disclosure means that the prior patent must disclose subject matter, which, if performed, would necessarily result in infringement of that patent…” (para. 25).
[45] No trial and error experimentation is permitted at the disclosure stage, but such experimentation is permitted at the enablement stage (para. 27). The decision of Mr. Justice Hugessen has now been held to only be applicable to the disclosure stage.
[46] The evidence is clear that if the subject matter of either prior U.S. patent were worked, the result would be a racemate, not an enantiomer. Consequently it cannot be said that patent ‘452 formed part of either U.S. patent, and so the selection patent argument falls for lack of prior disclosure. (See Abbott Laboratories v. Canada (Minister of Health), 2008 FC 1359 at paragraph 75.)
[47] It was urged upon me that as a result of the Plavix decision, the disclosure and claim of a racemate in a prior patent is automatically a disclosure and claim of the enantiomers. That cannot be so. It is not enough to say that everyone knew there were two enantiomers within citalopram. That is no better than saying that any undergraduate student in organic chemistry could have read the formula and realized that citalopram contains a carbon atom bonded with four separate constituents. Nowhere do I see support in Plavix for the proposition that the claim of a racemate is ipso facto a claim for its two enantiomers. Considering that if one overclaims one gets nothing, and considering that one could not possibly know the exact qualities of the enantiomers, i.e. which, if either, would be useful in treating depression, I cannot construe the patent as invited by the respondents. In fact, at paragraph 19 Mr. Justice Rothstein said:
….Apotex implies that the current understanding of the law sets the bar for proving anticipation too high and that the acceptance of a system of genus and selection patents necessarily, or at least on the facts of this case, involves anticipation and therefore invalidity. I would reject the broader objection. …
[48] As shall be discussed later in these reasons, the utility of escitalopram could not be determined until citalopram was resolved in sufficient quantities to allow for suitable testing. Before the results were in, all that could be said was that escitalopram might be more beneficial than citalopram, or less beneficial, or toxic, or otherwise useless. It is common ground among the experts that some enantiomers are toxic or useless. If to claim a racemate useful in the treatment of depression is to claim the same usefulness for each of the two enantiomers then in such circumstances the inventor would have overclaimed and lost everything. U.S. Patent ‘193 is not one which contains layer upon layer of distinct claims such that, if the claim with respect to one enantiomer fell, the claim with respect to the other might survive. Although the R-enantiomer has some activity, no evidence was led that it is useful in the treatment of depression.
[49] We now turn to whether Lundbeck has established, on the balance of probabilities, that the other allegations are not justified, or that the respondents did not lead sufficient evidence to even put some of them in play.
ANTICIPATION
[50] The single document contemplated by section 27 of the Act and published not less than two years prior to the ‘452 application which might describe the subject matter claimed in a subsequent invention need not itself be a patent. Apart from the U.S. patents, the respondents rely on each of the two papers published by Dr. D.F. Smith in 1985 and 1986, which discuss depression and drugs that inhibit serotonin uptake. He also prepared a model and wrote “…Although effects of the individual enantiomers of citalopram have never been studied, the model predicts that the (R)-enantiomer…is far more potent than the (S)-enantiomer as 5-HT uptake inhibitor… Thus, the present model can be tested in determining whether these predictions are correct.” The prediction was incorrect as post the ‘452 patent it was determined that the (S) enantiomer was by far the more potent.
[51] This led, for example, Dr. McClelland, a chemist called by Apotex, to say “In these two papers Dr. Smith has clearly disclosed the two enantiomers of citalopram”. This cannot be correct. It was known to the addressee of the patent, and indeed to undergraduate organic chemistry students, that within citalopram were two enantiomers. Although it might not be a surprise that one might be more potent than the other, I agree with Professor Stephen Davies, called by Lundbeck, that one would not know the qualities of the two enantiomers without separating and testing them.
[52] As pointed out by Justice Lindgren of the Federal Court of Australia in Alphapharm, above, the Smith articles teach away from the invention covered by the ‘452 patent. The Smith articles do not disclose escitalopram as useful in the treatment of depression and are in no way enabling. Nor does the 1983 article by Waldmeier cited by Cobalt.
OBVIOUSNESS
[53] The Supreme Court’s decision in Plavix has also clarified the application of Beloit, above, to invalidity on the grounds of obviousness. Mr. Justice Hugessen had said at page 294:
The test for obviousness is not to ask what competent inventors did or would have done to solve the problem. Inventors are by definition inventive. The classical touchstone for obviousness is the technician skilled in the art but having no scintilla of inventiveness or imagination; a paragon of deduction and dexterity, wholly devoid of intuition; a triumph of the left hemisphere over the right. The question to be asked is whether this mythical creature (the man in the Clapham omnibus of patent law) would, in the light of the state of the art and of common general knowledge as at the claimed date of invention, have come directly and without difficulty to the solution taught by the patent. It is a very difficult test to satisfy.
[54] The skilled addressee is now allowed some imagination and intuition. After reviewing developments in the United States and the United Kingdom, Mr. Justice Rothstein held at paragraph 68 that there are circumstances which permit an element of “obvious to try”. He agreed with the current state of the law in the United Kingdom as summarized by Lord Hoffmann in the Court of Appeal on this same escitalopram invention (Generics (U.K.), above). Lord Hoffmann had in turn endorsed, at paragraph 24, the state of the law expressed at trial by Mr. Justice Kitchin:
…. The question of obviousness must be considered on the facts of each case. The court must consider the weight to be attached to any particular factor in the light of all the relevant circumstances. These may include such matters as the motive to find a solution to the problem the patent addresses, the number and extent of the possible avenues of research, the effort involved in pursuing them and the expectation of success.
[55] Mr. Justice Rothstein went on to apply the four-step approach outlined in the United Kingdom in Windsurfing International Inc. v. Tabur Marine (Great Britain) Ltd., [1985] R.P.C. 59 (C.A.) and in Pozzoli Spa v. BDMO SA, [2007] EWCA Civ 588. They are, as set out in Pozzoli by Jacob L.J.:
…In the result I would restate the Windsurfing questions thus:
(1) (a) Identify the notional “person skilled in the art”;
(b) Identify the relevant common general knowledge of that person;
(2) Identify the inventive concept of the claim in question or if that cannot readily be done, construe it;
(3) Identify what, if any, differences exist between the matter cited as forming part of the “state of the art” and the inventive concept of the claim or the claim as construed;
(4) Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention?
[56] Mr. Justice Rothstein noted that it is at this fourth step that the “obvious to try” issue will arise. At paragraphs 69 and 70 he set out four non-mandatory, non-exhaustive, factors to consider:
a) Is it more or less self-evident that what is being tried ought to work?
b) What is the extent, nature and amount of effort required?
c) Is there a motive provided in the prior art to find the solution?
d) The actual course of conduct which culminated in the making of the invention.
[57] This is not to say that other factors as listed by the Court of Appeal in Janssen-Ortho Inc. v. Novopharm Ltd., 2007 FCA 217, 59 C.P.R. (4th) 116, may not be relevant as well. Apart from motivation, at paragraph 25 the Court of Appeal referred to “[t]he climate in the relevant field at the time the alleged invention was made” and as secondary factors, commercial success and meritorious awards.
[58] Turning to Pozzoli, I have already identified the notional “person skilled in the art” as a team centered on a medicinal chemist, which team would also include analytical chemists.
[59] The construction of the claims does not present difficulty. Claim 1 is for substantially pure escitalopram and non-toxic acid additional salts thereof. Claim 3 is a chemical composition in unit dosage form useful as an antidepressant, and claim 5, insofar as it is dependant on claim 3, is for a unit dosage form wherein the active ingredient ranges from 0.1 to 100 milligrams per unit dose. The inventors do not claim that escitalopram is better than citalopram, notwithstanding some puffery to that effect in the disclosure.
[60] The difference between the prior art and the inventive concept of the invention is that, while the prior art disclosed the racemate citalopram useful as an antidepressant, it did not disclose or enable its enantiomers or even predict whether either of them would be useful as an antidepressant. The prior art did not allow the skilled addressee to “have come directly and without difficulty to the solution thought by the patent”, i.e. the resolution of the racemate in sufficient quantity to permit the testing disclosed in the patent. In my view, resolution was the inventive step. Once a sufficient quantity had been obtained, the testing to allow a prediction that escitalopram was useful as an antidepressant was mundane. It was the same test used for citalopram itself.
[61] The remaining question is whether viewed without knowledge of the escitalopram invention, would the differences between it and the prior art coupled with common general knowledge constitute steps obvious to the skilled addressee, or do they require a degree of invention.
[62] Obviousness is assessed at the date of invention. Lundbeck asserts that escitalopram was invented 21 April 1988. The fallback position is the U.K. patent application filed 14 June 1988. Among the respondents, Apotex originally took the position that the U.K. priority date was inappropriate because of differences in the text of the U.K. and Canadian patent applications. However, during oral argument it said i