Eli Lilly Canada Inc. v. Novopharm Limited

Eli Lilly Canada Inc. v. Novopharm Limited
Court (s) Database
Federal Court of Appeal Decisions
Date
2010-07-21
Neutral citation
2010 FCA 197
File numbers
A-454-09
Notes
Reported Decision
Decision Content
Federal Court of Appeal
Cour d'appel fédérale
Date: 20100721
Docket: A-454-09
Citation: 2010 FCA 197
CORAM: NADON J.A.
SHARLOW J.A.
LAYDEN-STEVENSON J.A.
BETWEEN:
ELI LILLY CANADA INC.,
ELI LILLY AND COMPANY,
ELI LILLY AND COMPANY LIMITED and
ELI LILLY SA
Appellants
and
NOVOPHARM LIMITED
Respondent
Heard at Ottawa, Ontario, on June 21 and 22, 2010.
Judgment delivered at Ottawa, Ontario, on July 21, 2010.
REASONS FOR JUDGMENT BY: LAYDEN-STEVENSON J.A.
CONCURRED IN BY: NADON J.A.
SHARLOW J.A.
Federal Court of Appeal
Cour d'appel fédérale
Date: 20100721
Docket: A-454-09
Citation: 2010 FCA 197
CORAM: NADON J.A.
SHARLOW J.A.
LAYDEN-STEVENSON J.A.
BETWEEN:
ELI LILLY CANADA INC.,
ELI LILLY AND COMPANY,
ELI LILLY AND COMPANY LIMITED and
ELI LILLY SA
Appellants
and
NOVOPHARM LIMITED
Respondent
REASONS FOR JUDGMENT
LAYDEN-STEVENSON J.A.
[1] The plaintiffs (Lilly) commenced an action for patent infringement against the defendant (Novopharm) with respect to Canadian Letters Patent No. 2,041,113 (the '113 Patent), a selection patent for the compound olanzapine (sold under the brand name Zyprexa), owned by Lilly. Olanzapine is used to treat schizophrenia.
[2] Years before, Lilly had obtained Canadian Letters Patent No. 1,075,687 (the '687 patent), a genus patent for approximately 15 trillion compounds predicted to be useful in the treatment of mild anxiety and certain kinds of psychotic conditions, such as schizophrenia and acute mania. The '687 Patent expired 15 years ago.
[3] Novopharm filed a statement of defence and counterclaim with respect to Lilly’s infringement action. Novopharm asserted that Lilly’s action could not succeed because the '113 Patent is invalid. Following a 44-day trial involving approximately 30 witnesses, a Federal Court judge (the trial judge) agreed with Novopharm and dismissed Lilly’s action. The claims of the '113 Patent were held to be invalid. The Federal Court decision (2009 FC 1018) is reported at 353 F.T.R. 35.
[4] Lilly appeals from the Federal Court judgment. Although various submissions and arguments were advanced on appeal, the core issue raises a single question: do the conditions for a valid selection patent constitute an independent basis upon which to attack the validity of a patent? I conclude that the answer to the question is no. The trial judge reached the opposite conclusion. In my view, he erred in doing so and, because he approached the matter on that basis, he failed to address adequately the issues of obviousness, double patenting, utility and sufficiency.
Background
[5] Chlorpromazine, the first commercially available antipsychotic medicine, became available in 1953. Although useful in treating schizophrenia, it induced extrapyramidal side effects (EPS) such as serious involuntary twitching of the face and tongue and painful body distortions. Haloperidol, introduced in the 1960s, also produced EPS. These drugs have been referred to as “typical” or first generation antipsychotics. Clozapine, an “atypical” or second generation antipsychotic, was introduced in 1968. Clozapine did not induce EPS, but was found to cause serious haematological side effects (dramatic reduction of white blood cells), known as agranulocytosis, in some patients. It was withdrawn from the market and although it later returned, recipients must undergo strict monitoring of their white blood cell counts.
[6] During the 1970s, scientists, including Lilly scientists, searched for a safe, clozapine-like compound that would not yield the side effects of EPS and agranulocytosis. Drs. Jiban Chakrabarti and David Tupper, Lilly chemists, conducted research into drugs having useful activity on the central nervous system. As a result of their research, the '687 Patent, listing Chakrabarti and Tupper as its inventors, was filed in 1975, issued on April 15, 1980 and expired in April, 1995.
[7] The '687 Patent covered a broad genus (or class) of approximately 15 trillion thienobenzodiazapine compounds. It listed specific examples and described the criteria for “preferred” and “most preferred” compounds. It encompassed, but did not disclose, olanzapine. The trial judge concluded that olanzapine fell within the “most preferred” compounds (reasons for judgment, para. 23). The '687 Patent specifically disclosed flumezapine, ethyl flumezapine and ethyl olanzapine (referred to as the '222 compound). It claimed flumezapine and ethyl flumezapine (claims 19 and 21).
[8] The '687 Patent stated that the thienobenzodiazapine compounds had displayed useful central nervous system activity in animal tests and had potent neuroleptic, sedative, relaxant and anti-emetic properties. They showed good CAR-CAT separation. CAR (conditioned avoidance response in rodents) test results suggest potential antipsychotic usefulness and CAT (liability to induce catalepsy in rodents) test results provide an indication regarding the occurrence of EPS. According to the patent, these properties rendered the compounds useful in the treatment of mild anxiety states and certain kinds of psychotic conditions, such as schizophrenia. The compounds boasted a high therapeutic index (wide margin between the effective dose and a gross toxic effect). The effective dosage range was very wide, from 0.1 to 20 mg per kg per day. The focus of the '687 Patent, as found by the trial judge, was on the compounds (their constituents, structure and the processes by which they could be made).
[9] Further research was conducted on some of the '687 Patent’s compounds. Dr. Chakrabarti published a paper in 1980 providing data on 76 of the compounds. Flumezapine and ethyl flumezapine initially appeared promising. However, ethyl flumezapine was abandoned in 1978 after dog studies revealed that the compound caused a reduction in white blood cells. Attention turned to flumezapine. This compound proceeded to clinical trials until reports of elevated liver enzymes and the muscle enzyme creatine phosphokinase (CPK) were reported in some patients in April, 1982. In consultation with the Food and Drug Agency (FDA), Lilly halted its trials. Although it could have continued its studies of flumezapine, Lilly management concluded otherwise and further work on flumezapine was discontinued.
[10] An additional seven compounds, one of which was olanzapine, were subsequently synthesized. The Lilly research team favoured olanzapine (a methyl rather than an ethyl compound) because of its overall performance on a series of animal and in vitro tests. By 1983, Lilly was satisfied that olanzapine showed potential as an antipsychotic. Studies continued and in 1986 olanzapine was given to healthy volunteers. In 1989, clinical trials began with patients. Lilly decided to file the '113 Patent, which characterizes olanzapine as a selection from the class of the '687 Patent. The patent for olanzapine was filed in Canada on April 24, 1991 and the '113 Patent issued July 14, 1998.
[11] The '113 Patent disclosed that Lilly “discovered a compound which possesses surprising and unexpected properties by comparison with flumezapine and other related compounds.” It also referred to other perceived advantages of olanzapine over prior-known antipsychotic agents not included in the genus patent. It declared that olanzapine is an effective antipsychotic for treatment of schizophrenia, exhibiting high activity “at surprising low dosage levels.” The preferred treatment for adults was said to be from 0.1 to 20 mg per day. The '113 Patent also claimed the drug’s pharmaceutical compositions.
The Trial Judgment
[12] As noted earlier, the trial of Lilly’s infringement action lasted 44 days and included the testimony of some 30 witnesses. Novopharm defended the infringement allegations against it and counterclaimed on the basis that the '113 Patent was invalid, specifically on grounds of anticipation, double patenting, wrong inventorship, obviousness, section 53 of the Patent Act, R.S.C. 1985, c. P-4 (the Act) and section 73 of the Act.
[13] In the reasons for judgment, the trial judge identified the '113 Patent’s stated advantages over both the '687 Patent and other antipsychotic drugs. He determined that the declared advantages over the '687 Patent compounds included: lower incidence of liver enzyme elevations compared to flumezapine; lower CPK levels than flumezapine; lower ESP liability than flumezapine; and no increase in cholesterol compared to ethyl olanzapine. Regarding the other antipsychotic drugs, the stated advantages were found to be: higher efficacy at low doses; lower elevation of prolactin; lower ESP liability; and no alteration of white blood cell count.
[14] The trial judge reasoned that if these advantages amounted to a substantial advantage secured by the drug (or a substantial disadvantage avoided in comparison with the genus patent), if they were known or predicted at the time of filing, and if they were adequately disclosed, the '113 Patent would be a valid selection patent.
[15] He concluded that there was insufficient evidence of the advantages identified by the '113 Patent. Specifically, the trial judge determined: the stated advantages were not substantial and peculiar; a person skilled in the art (POSITA) would not be able to appreciate any inventive difference between the '687 Patent and the '113 Patent; the test for sound prediction was not met; Lilly had very little idea about what olanzapine’s effect was likely to be; and the '113 Patent did not meet the requirements for adequate disclosure. His penultimate conclusion was that the '113 Patent did not meet the requirements for a valid selection patent. In brief reasons, the trial judge concluded that the '113 Patent was invalid for double patenting, anticipation and insufficiency of disclosure. He also summarily addressed the issue of obviousness.
Standard of Review
[16] The standard of review is articulated in Housen v. Nikolaison, [2002] 2 S.C.R. 235. There, the Supreme Court reiterated that an appeal is not a re-trial of a case. Questions of law are to be determined on a standard of review of correctness. This means that an appellate court is at liberty to replace the opinion of the trial judge with its own. The standard of review for findings of fact is palpable and overriding error, that is, the factual findings cannot be reversed in the absence of an error that is plainly seen.
Statutory Provisions
[17] The text of all statutory provisions referred to in these reasons is attached as
Schedule "A".
Issues
[18] As stated at the outset, the first and primary issue is whether the conditions for a valid selection patent constitute an independent basis upon which to attack the validity of a patent. This issue raises a question of law and is therefore reviewable on a standard of correctness. Issues regarding anticipation, obviousness, sufficiency and double patenting also arise. The applicable standards of review for these issues will be identified as each allegation of invalidity is addressed.
Selection Patents
[19] To properly situate the first issue, an appreciation of the nature of selection patents is required. The dearth of Canadian jurisprudence on the subject of selection patents was noted in Pfizer Canada Inc. v. Canada, [2007] 2 F.C.R. 137, 2006 FCA 214, leave to appeal dismissed, [2006] S.C.C.A. 335 (Pfizer). The topic has surfaced more frequently since that observation was made, most notably in Apotex Inc. v. Sanofi-Synthelabo Canada Inc., [2008] 3 S.C.R. 265, 2008 SCC 61 (Sanofi).
[20] Although not restricted to chemical patents, selection patents more commonly arise in that context. Simply stated, the originating (or genus) patent typically refers, in general terms, to a group of products or processes from all of which a particular result (or results) may be obtained or predicted. If a property, quality or use in relation to one or more members of the genus is subsequently discovered, that discovery may be an invention giving rise to a valid selection patent. As explained in Pfizer and Sanofi, selection patents exist to encourage researchers to further use their inventive skills so as to discover new advantages for compounds within the known class.
[21] A selection patent can be claimed for a selection from a class of thousands or for a selection of one out of two. In this case, as noted earlier, the '687 Patent covered a genus of approximately 15 trillion thienobenzodiazapine compounds. The '113 Patent is directed to a specific chemical compound, olanzapine, or an acid addition salt thereof.
[22] In Sanofi, a question was raised as to whether the fact that a patent had been issued for a genus of compounds necessarily means that a patent could not be issued for any compound falling within the genus. In other words, would it be impossible, as a matter of law, for any selection patent to be valid. Rothstein J., writing for the Court, referred to a line of authority stemming from I.G. Farbenindustrie A.G.’s Patents (1930), 47 R.P.C. 289 (Ch.D.) (I.G. Farbenindustrie) in support of the conclusion that a system of genus and selection patents is acceptable in principle. At paragraph 10 of his reasons, Rothstein J., relying on Maughan J. in I.G. Farbenindustrie, described the characteristics of a valid selection patent as follows:
1. There must be a substantial advantage to be secured or disadvantage to be avoided by the use of the selected members;
2. The whole of the selected members (subject to “a few exceptions here and there”) possess the advantage in question;
3. The selection must be in respect of a quality of a special character peculiar to the selected group. If further research revealed a small number of unselected compounds possessing the same advantage, that would not invalidate the selection patent. However, if research showed that a larger number of unselected compounds possessed the same advantage, the quality of the compound claimed in the selection patent would not be of a special character.
[23] While the I.G. Farbenindustrie conditions are clear enough, the question that arises in this case did not arise in that case, or in Sanofi. That question is: at what stage, or where, are the noted conditions for a valid selection patent to be addressed? That is the primary issue and it is an important one. As noted earlier, it is a question of law for which the standard of review is correctness.
Do the conditions for a valid selection patent constitute an independent basis upon which to attack the validity of a patent?
[24] Lilly asserted, in its written submissions, that the trial judge erred by creating an “illegitimate amalgam by merging the doctrine of sound prediction of utility with obviousness and sufficiency and in the process required Lilly to provide proof of the inventive step (i.e. the advantages) in the disclosure.” In Lilly’s view, the “selection” issue goes to the question of obviousness and is properly addressed as part of that inquiry.
[25] Novopharm criticized Lilly’s approach as being nothing other than a disguised and impermissible attack on the factual determinations of the trial judge. It maintained that Lilly prosecuted and pleaded the '113 Patent as a selection patent. Accordingly, Novopharm attacked it as such, arguing, among other things, that “Lilly had failed to demonstrate or soundly predict that olanzapine had the substantial or peculiar advantages promised for it in the '113 Patent.” It emphasized the trial judge’s findings that the alleged advantages “are not substantial and peculiar advantages for olanzapine over and above the '687 class (nor over prior known antipsychotics).” Novopharm summarized its position stating “there is no utility in the patent.”
[26] At the hearing of the appeal, the submissions in this respect were somewhat nuanced. Lilly clarified and focussed its position, arguing that there is no foundation in law for an independent validity attack based solely on the I.G. Farbenindustrie criteria. At the same time, it steadfastly maintained its assertion that the validity of a selection patent goes to obviousness. Novopharm, for its part, argued that the trial judge applied the proper approach “set out 80 years ago in I.G. Farbenindustrie… the foundation of selection patent law in Canada.” It referred to the definition of “invention” in section 2 of the Act and insisted that, in a selection patent, the advantages are part of the invention. If the advantages are not established, there is no invention. According to Novopharm, the trial judge construed the '687 and '113 Patents and then conducted a utility analysis.
[27] In my view, a challenge directed to a determination that the conditions for a selection patent have not been met does not constitute an independent basis upon which to attack the validity of a patent. Rather, the conditions for a valid selection patent serve to characterize the patent and accordingly inform the analysis for the grounds of validity set out in the Act – novelty, obviousness, sufficiency and utility. In short, a selection patent is vulnerable to attack on any of the grounds set out in the Act. I arrive at this conclusion for a variety of reasons.
[28] As noted in Sanofi, the conditions set out in I.G. Farbenindustrie describe selection patents (para. 9). In other words, the conditions are akin to a definition. Rothstein J. found I.G. Farbenindustrie to be a useful starting point for the analysis to be conducted (para. 11). It only stands to reason that in undertaking an analysis of novelty, obviousness, sufficiency and utility, one should know the nature of the beast with which one is dealing.
[29] The comments of Lord Walker in Synthon B.V. v. SmithKline Beecham plc, [2006] 1 All E.R. 685, [2005] U.K.H.L. 59 (Synthon) at paragraphs 57-58, reproduced below, were specifically cited with approval in Sanofi.
The law of patents is wholly statutory and has a surprisingly long history… In the interpretation and application of patent statutes, judge-made doctrine has over the years done much to clarify the abstract generalities of the statutes and to secure uniformity in their application.
Nevertheless, it is salutary to be reminded, from time to time, that the general concepts which are the common currency of patent lawyers are founded on a statutory text, and cannot have any other firm foundation.
Notably, the Act contains no reference to invalid selection.
[30] In I.G. Farbenindustrie, at page 322, Maugham J specifically stated as follows:
On consideration, I think it would be unwise to endeavour to state in definite language all the conditions on which a selection patent must depend; for after all a selection patent does not in its nature differ from any other patent and is open to attack on the usual grounds of want of subject-matter, want of utility, want of novelty and so forth.
Similarly, in Sanofi, at paragraph 9, Rothstein J. confirmed that a selection patent does not in its nature differ from any other patent. The same view is expressed in Harold G. Fox, Canadian Patent Law and Practice, 4th ed. (Toronto: Carswell, 1969) (Fox) at p. 91.
[31] Further, in Sanofi, Rothstein J. incorporated his inquiry regarding the alleged advantages of clorpidogrel bisulfate (Plavix) into his analyses of anticipation, obviousness and double patenting. He did not conduct an independent analysis with respect to the conditions of selection patents. It is no answer to say, as Novopharm did, that in Sanofi, advantages were not in issue. It is readily apparent from Novopharm’s memorandum of fact and law and its oral argument that, in the context of a selection patent, the alleged advantages are always in issue due to the patent’s very nature.
[32] Finally, the selection patent is discussed in relation to the requirement of sufficiency in Terrell on the Law of Patents, 16th ed. (London: Street& Maxwell, 2006) (Terrell) at pp. 279, 294. The selection patent is addressed specifically in relation to anticipation in Re E.I. du Pont de Nemours & Co. (Witsiepe’s) Application, [1981] F.S.R. 377 (C.A.), aff’d. [1982] F.S.R. 303 (H.L.) (E.I. Du Pont). Of course, as stated by Lilly, obviousness is relevant to the validity of a selection patent and, as Novopharm asserted, so is utility. The notion of selection permeates the entire analysis in relation to each of the grounds of alleged invalidity.
[33] Novopharm referred to no authority, and I have not found any, where the analysis of the conditions for a valid selection patent, without more, has rendered a patent invalid. It is safe to say that the paucity of authority, considered in combination with my comments above, indicates that no such freestanding ground of attack exists. To reiterate, a determination that the conditions for a selection patent have not been met does not constitute an independent basis upon which to attack the validity of a patent. To the extent that paragraph 27 of Pfizer or the dissenting reasons in Apotex Inc. v. Janssen-Ortho Inc., 2009 FCA 212, 392 N.R. 71, 75 C.P.R. (4th) 411 may be taken to imply otherwise, they should be disregarded. A selection patent is the same as any other patent. Its validity is vulnerable to attack on any of the grounds set out in the Act.
Application to this Case
[34] In this case, the trial judge, in identifying the issues, recognized that the main issue was the validity of the '113 Patent. He noted that Novopharm attacked the validity of the '113 Patent on numerous grounds. Then, at paragraph 10, he stated:
[…] but I am persuaded that the main one – that the '113 is not a valid selection patent – is supported by the preponderance of evidence and, therefore, I deal with the others briefly at the end of my reasons.
Novopharm’s other grounds were: anticipation, double patenting, wrong inventorship, obviousness, section 53 of the Act (misrepresentation) and section 73 of the Act (deemed abandonment). The grounds relating to wrong inventorship and those relating to sections 53 and 73 of the Act were not pursued on appeal and I will say nothing further about them.
[35] The trial judge examined the '113 Patent specifically in relation to the proclaimed advantageous qualities of olanzapine. He divided the advantages into two categories: the advantages of olanzapine over the other compounds of the '687 Patent and its superiority over other known antipsychotic drugs. He identified the claims in issue, then asked, “is the '113 Patent a valid selection patent?” He summarized the patent’s contents and then determined that the first step was to “decide whether one or more of the asserted advantages of olanzapine was known to exist, or was soundly predicted, at the time the '113 Patent was filed in 1991.” The second step, from the trial judge’s perspective, was to “decide whether at least one of them could be considered a substantial advantage over the '687 compounds and somewhat peculiar to olanzapine.” If so, the third step involved a determination of “whether the disclosure of that substantial and special advantage in the '113 Patent was adequate.” The trial judge concluded that if the answer to any one of the questions was negative, he was obliged to find the '113 Patent to be invalid.
[36] In his analysis, the trial judge answered the first identified question (whether the asserted advantages were known or soundly predicted at the time of filing) by referring briefly to selected expert evidence regarding the data and testing with respect to each of the alleged advantages in the '113 Patent. He concluded that the evidence showed no advantage for olanzapine over flumezapine or ethyl olanzapine ('687 Patent compounds) and no factual basis or line of reasoning for a prediction that olanzapine would have the asserted advantages over those compounds or a line of reasoning that would support a sound prediction. He also concluded that there was insufficient disclosure in the patent of any factual basis or line of reasoning. He reached the same conclusion with respect to any alleged advantage in comparison with other antipsychotic drugs.
[37] The trial judge answered the second question (whether the alleged advantages were substantial and peculiar) in the negative. He found, again on the expert evidence regarding the data and testing, that to the extent they existed at all, their magnitude was insignificant. He was particularly critical of the results of the study in dogs. Regarding the third question (adequate disclosure), he concluded that if the patent had set out the factual basis and line of reasoning on which the assertions of substantial and special advantages were based, then the disclosure requirements for a valid selection patent would have been satisfied. However, since he had already concluded, in answering the first question, that there were no advantages established and no factual basis or line of reasoning for a sound prediction, he found that the '113 Patent’s disclosure was insufficient.
[38] The trial judge ultimately concluded, on the basis just described, that the '113 Patent was not a valid selection patent. Except for obviousness, which I will come to later, he reasoned, largely on the same basis, that most of “the other grounds of attack on the '113 Patent [became] superfluous.”
[39] It is readily apparent that the trial judge regarded the I.G. Farbenindustrie conditions of a selection patent as an independent basis upon which to attack the validity of the '113 Patent. I have concluded earlier that a determination that the conditions for a selection patent have not been met does not constitute an independent basis upon which to attack a patent’s validity. A selection patent is the same as any other patent. Its validity is vulnerable to attack on any of the grounds set out in the Act. It necessarily follows that the trial judge erred in determining the validity of the '113 Patent on the basis that he did. That is not to say, however, that his analysis is not relevant to the issue of utility, or other grounds of validity.
Construction
[40] The relevant claims of the '113 Patent are claims 3, 6, 13, 14, 15 and 16. Those claims state:
Claim 3: 2-Methyl-10-(4-methyl-1-piperazinyl)-4H-thieno-[2,3-b][1,5] benzodiazepine.
Claim 6: The use of a compound according to claim 2 or 3 for the manufacture of a medicament for the treatment of schizophrenia.
Claim 13: A pharmaceutical composition comprising of the compound of claim 3 together with a pharmaceutically acceptable diluent or carrier therefore.
Claim 14: A pharmaceutical composition in a capsule or tablet form comprising 0.1 to 20 mg of the compound of claim 3.
Claim 15: A pharmaceutical composition in capsule or tablet form compromising 0.5 to 10 mg of the compound of claim 3.
Claim 16: A pharmaceutical composition in capsule or tablet form compromising from 2.5 to 5 mg of the compound of claim 3 together with a pharmaceutically acceptable diluent or carrier therefore.
[41] The trial judge, at paragraph 46 of his reasons, construed the claims as follows:
· Claim 3: Olanzapine;
· Claim 6: The use of olanzapine for the manufacture of a drug for the treatment of schizophrenia;
· Claim 13: A pharmaceutical composition comprising olanzapine and a pharmaceutically acceptable diluent or carrier;
· Claim 14: A pharmaceutical composition in capsule or tablet form containing 0.1 to 20 mg of olanzapine;
· Claim 15: A pharmaceutical composition in capsule or tablet form containing 0.5 to 10 mg of olanzapine;
· Claim 16: A pharmaceutical composition in capsule or tablet form containing 2.5 to 5 mg of olanzapine and a pharmaceutically acceptable diluent or carrier.
[42] No issue was taken by either Lilly or Novopharm with respect to the trial judge’s construction of the claims.
Anticipation
[43] Section 2 of the Act stipulates that an invention must be novel. When approaching an inquiry as to novelty, the invention must not have been anticipated. The reformulated approach to anticipation is articulated in Sanofi. To succeed in invalidating a patent on grounds of anticipation, an alleged infringer (here Novopharm), must satisfy the requirements of prior disclosure and enablement, considered separately.
[44] With respect to disclosure, section 28.2 of the Act is the governing section. Among other things, it requires that the invention was not disclosed “in such a manner that it became available to the public in Canada or elsewhere” more than one year before the patent was filed. Although Sanofi addressed disclosure in the context of the predecessor Act, the principles enunciated in Sanofi remain applicable. The POSITA reads the particular piece of prior art to understand whether it discloses the second invention. The evidence to be considered is comprised solely of the prior art, as the POSITA would understand it. No trial and error or experimentation is permitted.
[45] Where disclosure is found to exist, the second requirement (enablement) requires the POSITA to be able to perform the invention. Enablement is assessed having regard to the particular piece of prior art as a whole. The prior art must provide the POSITA, using his or her common general knowledge, with enough information to allow the subsequently claimed invention to be performed without undue burden. Where the invention arises in a field of technology where trials and experiments are generally carried out, routine trials are acceptable.
[46] In Sanofi, Rothstein J. is clear that in the case of a valid selection patent, the claimed compound is soundly predicted at the time of the genus patent, but it is not made and its special advantages are not known. After citing Lord Wilberforce’s observation in E.I. Du Pont that, “it is the absence of the discovery of the special advantages, as well as the fact of non-making, that makes it possible for such persons to make an invention related to a member of the class”, Rothstein J. concludes that “a patent should not be denied to the inventor who made and discovered the special advantages of the selection compound for the first time” (para. 31).
[47] The trial judge did not consider the elements of the Sanofi approach. He concluded that “by definition, the '113 Patent was anticipated by the '687 Patent.” Lilly argued that the trial judge erred in concluding as he did and ought to have applied what it characterized as the Sanofi anticipation test. Novopharm insisted that Lilly’s position ignored the factual findings that no substantial and peculiar advantages were possessed by olanzapine. Further, according to Novopharm, the Sanofi analysis breaks down when applied to a selection with no advantages. It was open to the trial judge to find that the '113 Patent was lacking in novelty.
[48] With respect, Sanofi is binding authority. A determination with respect to anticipation falls to be conducted in accordance with the elements of the approach set out in that authority and the trial judge’s failure to conduct an analysis in this respect is an error of law. Novopharm’s position and the trial judge’s statement, in my view, serve to illustrate the precariousness of addressing a selection patent differently than any other patent. Sanofi specifically cautions against such an approach. The trial judge’s view of anticipation was tainted by his determination that olanzapine was not the subject of a valid selection patent, which in turn was founded on his misguided view that the conditions for a valid selection patent constitute an independent basis upon which to assess a patent’s validity. That said, I think it is open to this Court, on the basis of the trial judge’s findings and the record, to determine whether the '113 Patent was anticipated.
[49] At paragraph 51 of his reasons, the trial judge defined the POSITA as one who would “possess a conglomeration of knowledge and experience in medicinal chemistry, toxicology, psychiatry, and pharmacology, as well as a capacity to interpret data from animal studies and appreciate their relevance to the treatment of human disease.” No issue has been taken regarding the identification or the qualifications of the POSITA.
[50] Lilly maintained that the expert evidence with respect to the two pieces of prior art (exclusive of the '687 Patent) relied upon by Novopharm was to the effect that there was no specific disclosure of olanzapine or its advantages in the prior art. Novopharm did not suggest otherwise. It merely relied upon the '687 Patent and the trial judge’s finding.
[51] In general terms, the '687 Patent discloses a process for synthesizing an immense number of compounds having a three ring structure in common. The trial judge concluded that the patent’s focus was on the compounds – their constituents, their structure and the processes by which they could be made. He said that the utility lay “in their potential use in the treatment of central nervous system disorders, including schizophrenia.”
[52] Turning to the disclosure requirement of anticipation, it bears repeating that, at this stage of the inquiry, it is the content of the prior art (the '687 Patent) that is relevant, not whether the content is true. Olanzapine was not one of the examples described in the '687 Patent. It was one of a large class of most preferred compounds described by reference to several criteria. It was not specifically disclosed in the '687 Patent. Nor had it been made before. Since its advantages (as alleged in the '113 Patent) could not have been ascertained until it was made, it was not disclosed, as defined in Sanofi, by the '687 Patent.
[53] Non-disclosure is sufficient to defeat Novopharm’s allegation of invalidity on the basis of anticipation. Since Novopharm must satisfy both requirements (disclosure and enablement) there is no need to address enablement because Novopharm fails on the disclosure prong of the test. The '113 Patent was not disclosed and therefore was not anticipated by the '687 Patent.
Obviousness
[54] Section 28.3 of the Act requires that an invention not be obvious. Sanofi endorsed the inquiry for obviousness set out in Windsurfing International Inc. v. Tabur Marine (Great Britain) Ltd., [1985] R.P.C. 59 (C.A.) (Windsurfing), restated in Pozzoli SPA v. BDMO SA, [2007] EWCA Civ 588 (Pozzoli), which requires the court to:
1. (a) Identify the notional “person skilled in the art”;
(b) Identify the relevant common 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.
[55] At the fourth stage of the Windsurfing approach, the issue of “obvious to try” arises. To find that an invention was “obvious to try”, and therefore invalid for obviousness, Sanofi teaches “there must be evidence to convince a judge on a balance of probabilities that it was more or less self-evident to try to obtain the invention. Mere possibility that something might turn up is not enough” (para. 66). The “obvious to try” inquiry will be appropriate in areas of endeavour where advances are often won by experimentation, such as in the pharmaceutical industry. A non-exhaustive list of factors to be taken into consideration is proposed at paragraph 69 of Sanofi.
1. Is it more or less self-evident that what is being tried ought to work?
Are there a finite number of identified predictable solutions known to persons skilled in the art?
2. What is the extent, nature and amount of effort required to achieve the invention? Are routine trials carried out or is the experimentation prolonged and arduous, such that trials would not be considered routine?
3. Is there a motive provided in the prior art to find the solution the patent addresses?
[56] The actual course of conduct that culminated in the making of the invention may be an important factor. In this inquiry, it is not enough that there is a possibility of finding the invention. The invention must be self-evident from the prior art and common general knowledge in order to satisfy the “obvious to try” test.
[57] In the context of a selection patent, the obviousness analysis considers the special properties of the compound, along with its alleged advantages, as described in the selection patent disclosure, for it is there that the inventiveness of the selection lies.
[58] The trial judge cited the Sanofi test for obviousness. Then, at paragraphs 145-149 of his reasons, he stated:
[145] It is clear that this test assumes an inventive step in arriving at the subject-matter of the patent in issue. As will be clear from the discussion above, I cannot find an inventive step in Lilly’s decision to develop olanzapine. In effect, Lilly was working on its own patent, the '687, trying to find a compound that could be safely administered to humans and achieve the purpose underlying the '687 Patent itself – good antipsychotic activity and low EPS.
[146] By the time the patent was filed in April 1991, Lilly had not found any unexpected,
substantial or special qualities for olanzapine that would justify a fresh monopoly. Lilly had
merely carried out routine testing of olanzapine’s properties. It had some early signals of safety and efficacy in a few small studies of healthy volunteers and patients. Lilly scientists showed persistence, diligence and sound science in getting olanzapine that far. New methods of synthesis had to be worked out (after an explosion in the lab during synthesis of flumezapine). But that is not enough for a patent. There must be an invention. And, in the context of a selection patent, the invention is the discovery of unexpected, substantial and special advantages.
[147] I would not conclude that the selection of olanzapine as a development compound was an
obvious choice. It made sense to try a non-ethyl, non-flourol compound given the problems
with earlier compounds. But olanzapine was not the only candidate under consideration, and did not even appear to be particularly active. It was not “more or less self-evident” that olanzapine would work.
[148] I think the best way to characterize olanzapine in 1991 is that it was an “almost invention” to use Justice Binnie’s term (Apotex Inc. v. Welcome Foundation Ltd., above at para. 84). It was neither obvious nor a genuine invention. It was a compound that showed promise and, later, some of the early positive indications were borne out. Lilly received some early signals of safety and efficacy, but nothing that would support an assertion of surprising and unexpected properties, and nothing that would set olanzapine apart from the other '687 compounds.
[149] I find that the development of olanzapine was neither obvious nor an invention. However, I must emphasize that I am using the term “invention” strictly in the legal sense, as the law applies to selection patents. Scientists, whether at Lilly or elsewhere, may well regard olanzapine as an invention, perhaps even a remarkable one. But that is not the question before me.
[59] Lilly accepted as correct the trial judge’s finding that the selection of olanzapine as a development compound was not an obvious choice and that it was not more or less self-evident that olanzapine would work. However, it asserted that the concurrent finding that olanzapine was not an invention was nonsensical. Lilly submitted that the finding of non-invention (related to whether there was enough data to support the advantages) should not have been relevant to the obviousness analysis. The patentee is not required to prove the advantages in order to have a selection patent.