Novopharm Limited v. Janssen-Ortho Inc.

Novopharm Limited v. Janssen-Ortho Inc. Court (s) Database Federal Court of Appeal Decisions Date 2007-06-07 Neutral citation 2007 FCA 217 File numbers A-500-06 Decision Content Date: 20070607 Docket: A-500-06 Citation: 2007 FCA 217 CORAM: NADON J.A. SHARLOW J.A. MALONE J.A. BETWEEN: NOVOPHARM LIMITED Appellant and JANSSEN-ORTHO INC. and DAIICHI PHARMACEUTICAL CO., LTD. Respondents Heard at Toronto, Ontario, on March 13 & 14, 2007. Judgment delivered at Ottawa, Ontario, on June 7, 2007. REASONS FOR JUDGMENT BY: SHARLOW J.A. CONCURRED IN BY: NADON J.A. MALONE J.A. Date: 20070607 Docket: A-500-06 Citation: 2007 FCA 217 CORAM: NADON J.A. SHARLOW J.A. MALONE J.A. BETWEEN: NOVOPHARM LIMITED Appellant and JANSSEN-ORTHO INC. and DAIICHI PHARMACEUTICAL CO., LTD. Respondents REASONS FOR JUDGMENT SHARLOW J.A. [1] This is an appeal by Novopharm Limited from a judgment of Justice Hughes of the Federal Court (2006 FC 1234) declaring claim 4 of Canadian Letters Patent No. 1,304,080 (the “080 patent”) to be valid. Novopharm admitted that if claim 4 was valid, it was infringed. The 080 patent [2] The 080 patent is governed by the provisions of the Patent Act, R.S.C. 1985, c. P-4, pertaining to patents applied for prior to October 1, 1989. The application for this patent was filed in Canada on June 19, 1986 and claims priority from patent applications filed in Japan on June 20, 1985, October 11, 1985 and January 28, 1986. [3] The 080 patent was granted to the respondent Daiichi Pharmaceutical Co., Ltd. on June 23, 1992, which stills owns the 080 patent and has licensed it to the other respondent, Janssen-Ortho Inc. The 080 patent will expire on June 23, 2009 unless it is held to be invalid. Construction of Claim 4 [4] In any case in which the validity or infringement of a patent claim is in issue, it is necessary to construe the claim: Whirlpool Corp. v. Camco Inc., [2000] 2 S.C.R. 1067 at paragraph 43. The relevant date for the construction of the 080 patent is the date of its issuance, June 23, 1992. The patent must be understood as being addressed to a person skilled in the art, taking into consideration the knowledge that such a person is expected to possess on that date. The construction of a patent claim is a task for the Court and must be based on the whole of the disclosure and the claim, assisted by expert evidence as to the meaning of certain terms and the knowledge that a person skilled in the art is expected to possess on the relevant date. [5] Novopharm does not list an error of patent construction as one of its grounds of appeal. However, one of its arguments relating to obviousness includes, as one step in the analysis, the assertion that the construction of claim 4 adopted by Justice Hughes improperly reads in a purity claim where none is expressed or implied. Janssen and Daiichi responded to that point as a challenge to the correctness of the construction of claim 4 adopted by Justice Hughes. [6] Claim 4 of the 080 patent reads as follows: 4. S(-)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3- de][1,4]benzoxazine-6-carboxylic acid. That is the chemical name of the compound that may be called either levofloxacin or S(-) ofloxacin. (For the purposes of this appeal, those two terms are treated as synonymous.) [7] Justice Hughes, after reviewing and analysing the relevant portions of the disclosure and the claims of the patent, concluded (at paragraph 95 of his reasons) that claim 4 should be construed as follows: S(-) ofloxacin, different from that contained in the racemate, obtained in a reasonably pure state. [8] Before embarking on a consideration of the issues raised in this appeal in relation to the construction of claim 4, it is necessary to understand what levofloxacin is. [9] Levofloxacin is one of the two enantiomers of ofloxacin. The invention of ofloxacin was disclosed in Canadian Letters Patent No. 1,167,840 issued on May 22, 1984. [10] It is undisputed that persons skilled in the art would have known well before 1992 that ofloxacin is a racemate with a single chiral centre. The chiral centre of a racemate may be envisioned as a junction in the molecule at which a joined element may be oriented in one of two opposite directions. The two variations, called enantiomers, are mirror images of each other. [11] An enantiomer is said to be “optically active” if it rotates a plane of polarized light. By convention, if the rotation is clockwise, the enantiomer is a “right” enantiomer and is represented in a chemical formula by a “+” symbol. If the rotation is counter clockwise, the enantiomer is a “left” enantiomer and is represented in a chemical formula by a “-” symbol. Within a given quantity a racemate, there will be equal amounts of left and right enantiomers. A racemate will not rotate a plane of polarized light because the rotations caused by the left and right enantiomers cancel each other out. [12] Extracting one enantiomer of a racemate is called “resolving” the racemate. Each of the two enantiomers of a racemate is a different compound than the racemate, and may have different properties, including different medicinal properties. A sample produced by the separation process will have an excess of one enantiomer over the other. That is referred to as the enantiomeric excess and is a measure of the purity of the sample. Referring to the example given by Justice Hughes in paragraph 36 of his reasons, if a sample contains 95% of the left enantiomer and 5% of the right enantiomer, the enantiomeric excess (the difference) is 90%. In certain cases, the repetition of a particular technique for resolving a racemate may produce samples of greater purity after each repetition, but the evidence does not establish that continuous repetitions of a particular technique will necessarily achieve a desired level of purity. [13] If claim 4 is construed simply as “levofloxacin”, it could be argued that the claim must be obvious because the existence of levofloxacin is disclosed in the ofloxacin patent and is necessarily present in ofloxacin. Novopharm does not propose that interpretation. I conclude that Novopharm would agree with Justice Hughes that claim 4 includes a claim for levofloxacin different from that contained in ofloxacin. [14] Novopharm takes issue with the qualifying phrase “in a reasonably pure state”, arguing that no standard of purity is expressed or implied in the patent specification or in the patent claim. Novopharm’s argument is supported by the evidence of their expert Professor John Caldwell. His written expert statement (Appeal Book, Volume 34, page 9549) says that a person skilled in the art would not read into the claims of the 080 patent any limitation as to purity. He cited, by way of contrast, a number of patents in which a “substantially pure” limitation was expressed in a patent claim for an enantiomer. [15] Claim 4 does not expressly refer to a degree of purity. However, the specification in the patent indicates that levofloxacin obtained by the method described in example 6 (page 27 of the patent) results in levofloxacin with a 90% enantiomeric excess. [16] In support of the construction of claim 4 adopted by Justice Hughes, Janssen and Daiichi cite the evidence of Professor Alexander Klibanov. He says in his written expert report (Appeal Book, Volume 14, pages 3487-8), that a person skilled in the art would have understood claim 4 of the 080 patent to claim an “optically pure” form of the S(-) ofloxacin, that “practically all” of the molecules would be S(-) ofloxacin, and that the compound would be “substantially free” of the opposite enantiomer. He did not attempt in his initial report to quantify any of these expressions. Rather, he seemed to be responding to statements in Novopharm’s pleadings that he interpreted as an assertion that the language of claim 4 (the chemical name of levofloxacin or S(-) ofloxacin) would include a compound with any amount of levofloxacin. That construction of claim 4 would include the ofloxacin (which contains 50% left and 50% right enantiomers) and would also include a compound containing only a slight excess of the left enantiomer over the right enantiomer. Professor Klibanov rejected that asserted and stated that a person skilled in the art would understand that a purity limitation is implicit in claim 4. [17] Professor Klibanov’s reply expert report (Appeal Book, Volume 15, at pages 4046-8) discusses the degree of purity that he suggests is implicit in the 080 patent. Although he does not express an opinion on a precise number, he points out that examples 7, 11 and 16 in the 080 patent use different methods of obtaining levofloxacin, each yielding a similar high [α]D value, which he describes as a measure of “optical purity” which reflects enantiomeric excess. He also cites the method in example 6 of the patent specification, which indicates that levofloxacin obtained by that method results in levofloxacin with a 90% enantiomeric excess. Some support for Professor Klibanov’s understanding of the language of claim 4 is provided in the oral testimony of Professor Caldwell (Appeal Book, Volume 3, page 781). [18] The conclusion of Justice Hughes as to the construction of claim 4 is supported by the preponderance of the relevant expert evidence, and the record does not compel a different construction. For the purposes of this appeal, I accept the construction of claim 4 determined by Justice Hughes. [19] I would add only that it is not clear whether Justice Hughes, in construing claim 4 to include the qualifying phrase “in a reasonably pure state”, was paraphrasing the various expressions used by Professor Klibanov or was choosing a less exacting purity standard. It may be necessary in another case to clarify the meaning of the phrase “in a reasonably pure state” as used by Justice Hughes, but it is not necessary to do so in this appeal. Is Claim 4 ambiguous? [20] Novopharm argues that if claim 4 is properly construed to include the qualifying phrase “in a reasonably pure state”, then the claim is ambiguous because there is no way of knowing whether a given sample would fall inside or outside the claim: Hoffmann-La Roche Ltd. v. Apotex Inc. (1989), 24 C.P.R. (3d) 289 (F.C.A.) at page 299. Justice Hughes rejected this argument on the basis that a person skilled in the art would understand the qualifying phrase “in a reasonably pure state” to refer to the degree of purity required for the substance “to [do] its job for instance as an antimicrobial agent” (paragraph 119 of his reasons). [21] There is a conflict in the evidence as to what degree of purity is required to meet this functional test, a conflict that Justice Hughes did not consider it necessary to resolve. Novopharm cannot succeed on this point in the absence of evidence establishing that a resolution of the conflict is not reasonably possible. In my view, the evidence falls considerably short of that. [22] I conclude that Justice Hughes did not err when he concluded that claim 4, as he construed it, is not ambiguous. Obviousness [23] The accepted legal test for obviousness is stated as follows in the leading case of Beloit Canada Ltd. et al. v. Valmet OY (1986), 8 C.P.R. (3d) 289 (F.C.A.) at page 294, per Hugessen J.A.: 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. [24] The inquiry mandated by the Beloit test is factual and functional, and must be guided by expert evidence about the relevant skills of the hypothetical person of ordinary skill in the art, and the state of the art at the relevant time. The expert evidence must be carefully assessed as to its credibility and reliability. The classic warning from Beloit about hindsight must always be borne in mind (at page 295, per Hugessen J.A.): Every invention is obvious after it has been made, and to no one more so than an expert in the field. Where the expert has been hired for the purpose of testifying, his infallible hindsight is even more suspect. It is so easy, once the teaching of a patent is known, to say, "I could have done that"; before the assertion can be given any weight, one must have a satisfactory answer to the question, "Why didn't you?" [25] There is no single factual question or a set of questions that will determine every case, or any particular case. Justice Hughes, at paragraph 113 of his reasons, proposes a list of factors to be considered when the validity of patent is challenged on the basis of obviousness. The list is apparently derived from a survey of numerous cases from Canada, the United States and the United Kingdom. In my view, despite the continual debate as to whether the legal test for obviousness is the same in all of those countries, the list of factors proposed by Justice Hughes is helpful to guide the required factual inquiry, and as a framework for the factual analysis that must be undertaken. What follows is an edited version of his list: Principal factors 1. The invention What is in issue is the patent claim as construed by the Court. 2. The hypothetical skilled person referred to in the Beloit quotation It is necessary to identify the skills possessed by the hypothetical person of ordinary skill in the art. 3. The body of knowledge of the person of ordinary skill in the art The common knowledge of the hypothetical person of ordinary skill in the art includes what the person may reasonably be expected to know and to be able to find out. The hypothetical skilled person is assumed to be reasonably diligent in keeping up with advances in the field to which the patent relates (Whirlpool at paragraph 74). The presumed knowledge of the hypothetical skilled person undergoes continuous evolution and growth. Not all knowledge is found in print form. On the other hand, not all knowledge that has been written down becomes part of the knowledge that a person of ordinary skill in the art is expected to know or find. 4. The climate in the relevant field at the time the alleged invention was made The general state of the art includes not only knowledge and information but also attitudes, trends, prejudices and expectations. 5. The motivation in existence at the time the alleged invention to solve a recognized problem “Motivation” in this context may mean the reason why the claimed inventor made the claimed invention, or it may mean the reason why one might reasonably expect the hypothetical person of ordinary skill in the art to combine elements of the prior art to come up with the claimed invention. If within the relevant field there is a specific problem that everyone in the field is trying to solve (a general motivation), it may be more likely that the solution, once found, required inventive ingenuity. On the other hand, if there is a problem that only the claimed inventor is trying to solve (a unique or personal motivation), and no one else has a reason to address that problem, it may be more likely that the solution required inventive ingenuity. However, if commonplace thought and techniques can come up with a solution, there may be a reduced possibility that the solution required inventive ingenuity. 6. The time and effort involved in the invention The length of time and expense involved in the invention may be indicators of inventive ingenuity, but they are not determinative because an invention may be the result of a lucky hit, or the uninventive application of routine techniques, however time consuming and expensive they may be. If the decisions made in arriving at the solution are few and commonplace, that may indicate that no inventive ingenuity was required to arrive at the solution. If the points for decision were many and choices abundant, there may be inventiveness in making the proper decisions and choices. Secondary factors These factors may be relevant but generally bear less weight because they relate to facts arising after the date of the alleged invention. 7. Commercial success Was the subject of the invention quickly and anxiously received by relevant consumers? This may reflect a fact that many persons were motivated to fill the commercial market, which may suggest inventive ingenuity. However, it may also reflect things other than inventive ingenuity such as marketing skills, market power and features other than the invention. 8. Meritorious awards Awards directed to the alleged invention may be recognition that the appropriate community of persons skilled in the art believed that activity to be something of merit. That may or may not say anything about inventive ingenuity. [26] Justice Hughes included as a secondary factor “subsequently recognized advantages”, referring to the advantages of the claimed invention that are perceived only after the date of the invention. Justice Hughes said that this factor is of limited usefulness in considering inventive ingenuity, and should be given little weight. I find it difficult to envisage a situation where a subsequently recognized advantage to a claimed invention would be of any assistance in determining whether inventive ingenuity was required to make it. I can imagine a situation where the commercial success of an invention is attributable to a subsequently recognized advantage, but that would not assist the inquiry as to inventive ingenuity. I recognize that it is impossible to imagine every possible situation, but given the current state of the jurisprudence I would be inclined to give this factor no weight except in the most extraordinary case. [27] I emphasize that this list is a useful tool, but no more. It is not a list of legal rules to be slavishly followed; nor is it an exhaustive list of the relevant factors. The task of the trial judge in each case is to determine, on the basis of the evidence, sound judgment and reason, the weight (if any) to be given to the listed factors and any additional factors that may be presented. [28] I would also repeat the caution of Justice Hughes that catchphrases derived from this list or from the jurisprudence are not to be treated as though they are rules of law. I agree with the following comment of Justice Hughes from paragraph 113 of his reasons: In this regard phrases such as "worth a try" and "directly and without difficulty" and "routine testing" have been used by the courts. It is not useful to use such phrases as they tend to work their way into expressions of law or statements of expert witnesses. Sachs L.J. deprecated the coining of such phrases in General Tire & Rubber Company v. Firestone Tyre & Rubber Company Limited, [1972] R.P.C. 195 at pages 211-12. [29] I turn now to the specific grounds of appeal raised by Novopharm in relation to obviousness. Were conventional prior art methods used to produce the claimed invention in 1982? [30] Novopharm argues that Justice Hughes erred in ignoring uncontroverted evidence that conventional prior art methods had been used to produce the claimed invention in 1982. This argument refers to evidence that Daiichi, the employer of the claimed inventor Dr. Hayakawa, used known techniques to successfully resolve the (+) and (-) enantiomers of ofloxacin in 1981 and 1982. However, that evidence does not establish that the levofloxacin produced at that time met an acceptable level of purity. Justice Hughes found as a fact that the first isolation of substantially pure levofloxacin did not occur until 1985. That conclusion was open to him on the evidence. Purity and quantities [31] Novopharm argues that Justice Hughes (a) improperly grafted onto the test for obviousness a “minimum quantity” and “minimum purity” requirement, (b) made a palpable and overriding error in finding as a fact that known techniques could produce only minute quantities of material, and (c) made a palpable and overriding error in finding as a fact that known techniques could produce only impure material. [32] These grounds of appeal refer to a statement made by Justice Hughes at paragraph 115 of his reasons that, prior to 1985, known techniques for the separation of a racemate into its enantiomers produced, when applied to ofloxacin, “only minute quantities of impure material, scarcely enough to interest anyone in activity”. This is a factual conclusion that was open to Justice Hughes on the evidence. It is relevant to the question of whether the invention is obvious, and Justice Hughes made no error in taking it into account as a fact that weakens Novopharm’s argument that claim 4 is invalid for obviousness. The Gerster posters [33] Novopharm argues that Justice Hughes misapplied the test for obviousness (a) by failing to find claim 4 invalid because the “Process C” described in the patent specification as being the preferred method of obtaining levofloxacin was copied from and was a straightforward application of a process disclosed in the 1985 Gerster poster, (b) by disregarding the 1985 Gerster poster as relevant prior art because it was not mainstream or commonplace, (c) by applying a novelty standard that has no relevance to the determination of obviousness, and (d) by failing to find the 1982 Gerster poster was relevant prior art. [34] The evidence is that in the early 1980s Dr. Hayakawa, the inventor named in the 080 patent, tried without success to obtain levofloxacin of an acceptable level of purity. It is undisputed that in the fall of 1985, Dr. Hayakawa attended a conference at which Professor John Gerster made a presentation relating to flumequine, an antimicrobial compound that is structurally similar to ofloxacin. His presentation included a poster illustrating a method obtaining S(-) flumequine from a racemic intermediate compound. Dr. Hayakawa made notes of the poster, tried the technique, and employed the same method to produce levofloxacin with an acceptable level of purity. That method is substantially the same as Process C as described in the patent specification. [35] Dr. Hayakawa is not only a person skilled in the art, but a person who is an acknowledged inventor. Therefore, the manner in which Dr. Hayakawa used the knowledge obtained from the 1985 Gerster poster cannot, by itself, establish that an uninventive person of ordinary skill in the art could be expected to have used the same knowledge to the same effect. [36] The evidence is that at the relevant time, chirality was a relatively new field, but Daiichi was doing considerable work in that area. Only Dr. Hayakawa was trying to obtain levofloxacin from ofloxacin, and his efforts in the early 1980s had not met with sufficient success to satisfy his objectives. Justice Hughes characterized the technique described in the 1985 Gerster poster as not mainstream or commonplace. As I read that comment, he did not intend to exclude the 1985 Gerster poster from consideration as prior art. He was merely recognizing that, considered against the general state of the art, the 1985 poster had special significance to Dr. Hayakawa because of his specialized work and the particular problem that was occupying him. The evidence discloses no sound basis for concluding that a person of ordinary skill in the art with knowledge of the 1985 Gerster poster would have made the same connections as Dr. Hayakawa. [37] The evidence cited by Novopharm on this point is the evidence of Professor Michael Chong, whose evidence dealt with a poster prepared by Professor Gerster in 1982. Although that poster is similar to the 1985 Gerster poster, it is directed to flumequine itself whereas the 1985 paper is directed to a flumequine derivative. Justice Hughes found as a fact that at the relevant time, the 1982 poster was not in the public domain and was not accessible through diligent research. There is no basis for disturbing that finding of fact. [38] The suggestion that Justice Hughes applied a “novelty” standard appears to be based on a misinterpretation of his statement (at paragraph 114 of his reasons) that there is no evidence that Professor Gerster or anyone else had applied the technique in the 1985 Gerster poster to ofloxacin. That was a factual statement that correctly reflects evidence in the record. It may be an observation of only marginal relevance, but that does not mean that Justice Hughes was wrong to say it. I do not read this statement as an attempt to change or embellish the legal test of obviousness. Motivation [39] Novopharm argues that Justice Hughes erred in the weight he gave to “motivation” in the test for obviousness. As I read the reasons of Justice Hughes, he gave significant weight to that factor in dismissing Novopharm’s challenge to the validity of claim 4 on the basis of obviousness. [40] The motivation of Daiichi to obtain the enantiomers of ofloxacin explains the activities of Dr. Hayakawa during the relevant period. The business objective of Daiichi was to produce patentable substances with useful medicinal properties. Daiichi owned the patent for ofloxacin. Because it was thought that the enantiomer of an antimicrobial racemate such as ofloxacin may prove to have antimicrobial properties superior to that of the racemate, Daiichi was motivated to isolate the enantiomers of ofloxacin. That motivation would have been reinforced by the fact that American drug regulators and clinicians were pressing Daiichi for information about the enantiomers of ofloxacin. The interests and focus of other researchers in the field during the same period were not on ofloxacin at all, indicating that others skilled in the art were not motivated to work on the same problem that was occupying Dr. Hayakawa. Justice Hughes found as a fact that, during the relevant period, Daiichi was motivated to obtain levofloxacin from ofloxacin, and no one else was. That was a factual conclusion that was reasonably open to him on the record. [41] Novopharm does not and could not reasonably suggest that motivation is irrelevant in this case, but argues that Justice Hughes gave motivation undue weight. That is an allegation of a factual error. A factual conclusion must stand absent palpable and overriding error. I can find no basis in the record for concluding that such an error was made in this case. Predictability [42] Novopharm argues that Justice Hughes erred in applying a requirement for “predictability with certainty” to the determination of obviousness. [43] As I read the decision of Justice Hughes, he found that a person of ordinary skill in the art would have known that ofloxacin is a racemate and that each enantiomer would possess properties different from the racemate, but would not know the degree of difference, and in particular would not be able to predict the degree to which a particular enantiomer would have different properties of antimicrobial activity. These are factual conclusions that were open to Justice Hughes on the record. As factual statements, they are not to be considered in isolation, but rather as one part of the entire factual picture that is relevant to the question of obviousness in the particular circumstances of this case. Read in context, these statements do not and are not intended to change the legal test for obviousness or to make it more onerous. The cross appeal [44] The respondents filed a notice of cross-appeal, but the cross-appeal was abandoned. Conclusion [45] For the reasons stated above, I would dismiss this appeal with costs. “K. Sharlow” J.A. “I agree M. Nadon J.A.” “I agree B. Malone J.A.” FEDERAL COURT OF APPEAL NAMES OF COUNSEL AND SOLICITORS OF RECORD DOCKET: A-500-06 (APPEAL FROM A JUDGMENT OF MR. JUSTICE HUGHES OF THE FEDERAL COURT DATED OCTOBER 17, 2006, No. T-2175-04) STYLE OF CAUSE: NOVOPHARM LIMITED -and- JANSSEN-ORTHO INC. and DAIICHI PHARMACEUTICAL CO. LTD. PLACE OF HEARING: Toronto, Ontario DATE OF HEARING: March 13 & 14, 2007 REASONS FOR JUDGMENT BY: Sharlow J.A. CONCURRED IN BY: Nadon J.A. Malone J.A. DATED: June 7, 2007 APPEARANCES: David W. Aitken Marcus Klee FOR THE APPELLANT Neil Belmore Lindsay Neidrauer Michael Charles Andrew I. McIntosh FOR THE RESPONDENT JANSSEN-ORTHO FOR THE RESPONDENT DAIICHI PHARMACEUTICAL CO., LTD. SOLICITORS OF RECORD: Osler, Hoskin & Harcourt LLP Ottawa, Ontario FOR THE APPELLANT Gowling Lafleur Henderson LLP Toronto, Ontario Bereskin & Parr Toronto, Ontario FOR THE RESPONDENT JANSSEN-ORTHO FOR THE RESPONDENT, DAIICHI PHARMACEUTICAL CO. LTD.