Janssen-Ortho Inc. v. Apotex Inc.

Janssen-Ortho Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2008-06-17
Neutral citation
2008 FC 744
File numbers
T-1508-05
Decision Content
Date: 20080617
Docket: T-1508-05
Citation: 2008 FC 744
Ottawa, Ontario, June 17 2008
PRESENT: The Honourable Mr. Justice Shore
BETWEEN:
JANSSEN-ORTHO INC.
and DAIICHI SANKYO COMPANY, LIMITED
Applicants
and
APOTEX INC. and
THE MINISTER OF HEALTH
Respondents
REASONS FOR JUDGMENT AND JUDGMENT
TABLE OF CONTENTS
I. Overview.... 4
II. Introduction.. 5
III. Background.. 5
The patent at issue.. 5
Levofloxacin and Ofloxacin.. 6
The inventive story.. 11
(a) Research Activities. 11
(b) The Invention Date.. 12
Earlier litigation of this ‘080 patent.. 13
IV. Issues.. 14
V. Analysis.. 15
Burden of Proof. 15
A. Abuse of Process Consideration.. 16
The witnesses. 19
Janssen’s Witnesses. 19
Apotex’ Witnesses. 22
The ‘080 patent. 25
Laws of construction.. 25
Construction of claim 4 of the ‘080 patent. 27
Claim 4 of the ‘080 patent covers levofloxacin hemihydrate.. 29
B. Is Apotex’ allegation of infringement justified?. 31
Infringement of the ‘080 patent. 31
Legal principles. 31
Application to the facts. 31
The specification of the ‘080 patent is sufficient. 31
Conclusion.. 35
C. Are Apotex’ allegations of invalidity justified?. 35
i) Anticipation.. 36
Legal principles. 37
Application to the facts. 41
The ‘840 patent:. 41
Conclusion.. 43
ii) Obviousness. 44
Legal principles. 44
Application to the facts. 47
Prior Art. 48
(a) The Gerster Papers:. 48
(b) Ofloxacin References. 51
(c) Other References. 52
Climate in the relevant field and motivation at the time of the alleged invention.. 52
(a) Racemic fluoroquinolones were not resolved.. 52
(b) A skilled person would not expect chirality of methyl group to affect activity. 54
(c) Properties of flumequine not predictive of ofloxacin.. 55
(d) Other compounds teach away from importance of methyl group.. 57
Beneficial properties of levofloxacin are surprising and unexpected.. 59
(a) Levofloxacin's improved antimicrobial activity was unexpected.. 62
(b). Levofloxacin's lower toxicity was unexpected and not predictable.. 63
(c) Levofloxacin's increased solubility was unexpected.. 67
(d) Levofloxacin's Combination of the Three Beneficial Properties was Unexpected.. 70
Conclusion.. 70
Levofloxacin is inventive.. 70
iii) Claims broader than the invention made and lack of sound prediction.. 72
Legal principles. 72
Application to the facts. 74
Conclusion.. 75
D. Is the ‘080 patent void pursuant to paragraphs 40(1)(a) and (c) of the Patent Act? 75
The relevant legislation and its interpretation.. 76
(a) There was no breach of paragraph 40(1)(c) of the Patent Rules. 78
(b) There was no breach of paragraph 40(1)(a) of the Patent Rules. 80
(c) The Applicant and its agents acted in good faith.. 81
Conclusion.. 82
VI. Conclusion.. 83
VII. Abuse of Process Analysis and Conclusion.. 83
Legal Principles.. 83
Construction.. 85
Infringement.. 86
Anticipation.. 86
Sufficiency of Disclosure.. 88
Obviousness.. 89
(a) No attention was given to enantiomers in the quinolone field.. 89
(b) No better evidence that competitors were motivated to obtain levofloxacin.. 90
(c) The properties of levofloxacin were not expected.. 91
VIII. Costs.. 95
JUDGMENT.. 96
I. Overview [1] Claims, in regard to a patent, are neither to be construed too broadly nor too restrictively to ensure the patent’s potential viability. To prevent a viable patent from being relegated to a straitjacket, it requires breath in order to live out its exceptional privilege, the monopoly, it has been granted.
[2] “Slight alterations or improvements may produce important results…” and the “…patient searcher is as much entitled to the benefits of a monopoly as someone who hits upon an invention by some lucky chance or inspiration.”
(Farbwerke Hoechst Aktiengesellschaft vormals Meister Lucius & Bruning v. Halocarbon (Ontario) Limited, [1979] 2 S.C.R. 929, 104 D.L.R. (3d) 51 [Halocarbon]; Canadian General Electric Co., Ld. v. Fada Radio Ld., [1930] R.P.C. 69 at 88-89 (P.C.); American Cyanamid Company v. Berk Pharmaceuticals Limited, [1976] R.P.C. 231 at 257.)
[3] One cannot verify unexpected and unpredictable properties of new compounds. (Pfizer Canada v. Ratiopharm, 2006 FCA 214, [2007] 2 F.C.R. 137 at para. 24 [Pfizer v. Ratiopharm].)
[4] A person of ordinary skill in the art (POSITA) conducts the exercise as of the publication date of the patent. This exercise is conducted in a purposive and not overly literal manner that is fair and reasonable to the patentee and the public. Patent construction should be approached "with a judicial anxiety to support a really useful invention".
(Free World Trust v. Électro Santé, 2000 SCC 66, [2000] 2 S.C.R. 1024 at para. 54; Whirlpool Corp. v. Camco, 2000 SCC 67, [2000] 2 S.C.R. 1067 at 1089-1091; Consolboard v. MacMillan Bloedel (Sask.) Ltd., [1981] 1 S.C.R. 504, 122 D.L.R. (3d) 203 at 521 [Consolboard]; reference is also made to Pfizer Canada and Pharmacia Italia S.p.A. v. Mayne Pharmacy (Canada), 2005 FC 1725, 285 F.T.R. 1. [Pfizer v. Mayne].)
[5] On appeal, the Federal Court of Appeal expressly found the ‘080 patent to be valid. It concurred with Justice Hughes’ findings in the Federal Court that the patent was valid, that levofloxacin clearly demonstrated a special advantage and that Daiichi’s work was more than mere verification. It was ultimately found that the patent was not obvious and that the Applicants had established utility. (Novopharm Limited v. Janssen-Ortho, 2007 FCA 217, 366 N.R. 290 [Novopharm Apeal] and Janssen-Ortho v. Novopharm Limited, 2006 FC 1234, 301 F.T.R. 166 [Novopharm Trial].)
II. Introduction [6] This is a proceeding pursuant to subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 as amended (NOC Regulations). Janssen-Ortho Inc. (Janssen) and Daiichi Sankyo Company Limited (Daiichi) have applied to the Federal Court seeking an Order prohibiting the Minister of Health from issuing a Notice of Compliance (NOC) under C.08.004 of the Food and Drug Regulations, C.R.C., c. 870, to Apotex Inc. (Apotex) relating to an antimicrobial drug, known as levofloxacin, in the form of 250, 500 and 700 mg tablet strengths, until after expiry of Canadian Patent No. 1,304,080 (‘080 patent).
III. Background The patent at issue
[7] The patent at issue, Canadian Patent No. 1,304,080 (‘080 patent), was issued to the Applicant, Daiichi, on June 23, 1992,which discloses and claims the antibiotic levofloxacin, known in North America as LEVAQUIN. The Canadian filing date of the ‘080 patent is June 19, 1986, and unless held to be invalid, the ‘080 patent will expire on June 23, 2009. The patent claims priority from three separate patent applications filed in Japan; the first on June 20, 1985 [Application No. 134712/85]; the second on October 11, 1985 [Application No. 226499/85]; and the third on January 28, 1986 [Application No. 16496/86].
[8] Daiichi is also the owner of Canadian Patent 1,157,840 (‘840 patent), issued on May 22, 1984, which disclosed and claimed an antibiotic known as “ofloxacin”. Janssen was licensed by Daiichi to market ofloxacin in Canada, which it did under the brand name FLOXIN. The ‘840 ofloxacin patent expired on May 22, 2001.
[9] On July 18, 2005, the Respondent, Apotex, served on Janssen, a purported Notice of Allegation (NOA) concerning the ‘080 patent. The Respondent alleges that the ’080 patent is invalid as it does not meet the test for a selection patent. They argue that levofloxacin does not possess unexpected, special advantages over ofloxacin. Further, the selection of levofloxacin from the ofloxacin mixture did not require any inventive ingenuity. The Applicants submit that the issues in this application are substantially similar to the issues and evidence on obviousness and anticipation as previously submitted to this Court in earlier litigations (Court File Nos. T-214-03; T-2175-04 and A-500-06).
Levofloxacin and Ofloxacin [10] This case involves the related compounds ofloxacin and levofloxacin.
[11] Ofloxacin is an old substance. A skilled chemist would know its chemical structure and would be aware that it contains a feature known as a “chiral centre”. This feature is important to the present case as a molecule with a chiral centre can exist in one of two possible three-dimensional forms. The word “enantiomers” is used to describe the relationship between the two possible three-dimensional forms. Enantiomers are mirror images of each other and can be likened to the right and left hand version of the same compound. While enantiomers are similar in many respects, they have different chemical properties and often very different biological effects when administered as medicines.
[12] Chemists distinguish between the two enantiomers of a given compound by assigning labels to each one. One convention involves assigning the prefixes “R” or “S” to each enantiomer. A chemist can tell by looking at a chemical diagram whether a particular enantiomer is the R enantiomer or the S enantiomer. A different convention uses the prefixes (+) or (-) to distinguish between enantiomers. These prefixes are assigned depending on whether the enantiomer rotates plane-polarized light to the right (+) or to the left (-). One enantiomer will always be (+) while the other enantiomer will always be (-).
[13] In the case of ofloxacin, one enantiomer is referred to as (+)-ofloxacin (or alternatively as R-ofloxacin or R(+)-ofloxacin). The other enantiomer is referred to as (-)-ofloxacin (or alternatively as S-ofloxacin or S(-)-ofloxacin). For the purposes of this case, it is important to note that the S or (-) enantiomer of ofloxacin is called levofloxacin.
[14] The term “ofloxacin”, as it is used in the literature and described in the prior art, is generally used to refer to a specific type of mixture of that compound called a “racemic mixture” or a “racemate”. A racemic mixture is a mixture containing 50% of each enantiomer of a compound. Thus, a sample of ofloxacin racemate will contain equal amounts of S(-)-ofloxacin (levofloxacin) and R(+)-ofloxacin.
[15] The ‘840 patent discloses a process to make ofloxacin. A chemist following that process would obtain a racemic mixture of ofloxacin.
[16] Although racemic mixtures can be used for a variety of purposes including pharmaceuticals, it is often desirable to obtain a very pure sample of only one of the enantiomers. One means of obtaining a sample containing only one enantiomer is to start with a racemic mixture and separate it into its two constituent enantiomers. Generally, enantiomers cannot be separated mechanically and thus chemists must devise or apply chemical techniques to perform the separation. Different techniques may be used to perform the same separation; however, the purity of the products may differ, as may the cost or time involved in the separation.
[17] The two enantiomers of ofloxacin were disclosed in Japanese patent application No. 134712/85, published on June 20, 1985. This was the first disclosed isolation of the substantially pure enantiomers of levofloxacin achieved using a chemical technique called HPLC. The parties refer to this process as “Process A”. It is important to note that, although Daiichi had separated ofloxacin into two enantiomers, it did not yet know which enantiomer was “R” and which was “S”. In technical language, a chemist would say that Daiichi did not yet know “the absolute configuration” of each enantiomer.
[18] A second separation process, “Process B”, or the “enzymatic process” for separation, followed. A second Japanese patent application No. 226499/85 was filed, on October 11, 1985, disclosing a notable separation.
[19] Acute toxicity tests and X-ray diffraction analysis conducted on levofloxacin led to the final process, “Process C”, disclosed in the third Japanese patent application No. 016496/96. This application disclosed that the absolute configuration of levofloxacin was “S”, and also referred to its “higher… solubility and weaker toxicity”. (Applicant’s Application Record (AR), Hayakawa Affidavit at paras. 43-48, v. 4, Tab 6, pp. 720-721; Klibanov Affidavit, Exhibit I, v. 13, Tab 18, p. 3783.)
[20] The isolation of levofloxacin (that is, the (-)-or (S)- enantiomer of ofloxacin) is described within the ‘080 patent. The patent explicitly teaches that levofloxacin is twice as potent, less toxic, and ten times more soluble than ofloxacin, the racemic containing both levofloxacin and (+)-ofloxacin.
[21] The means by which the isolation of levofloxacin and the determination of not only the S configuration, but, more particularly, of the superior properties it exhibited, are disclosed in the ‘080 patent. At issue, in this application, is whether claim 4 includes within its scope both anhydrous levofloxacin and hemihydrate levofloxacin.
[22] The term anhydrous (or anhydrate) is used to describe a specific form of a compound that is completely free of water. A sample of anhydrous levofloxacin will not contain any water molecules.
[23] It is noted, however, that levofloxacin may also exist in a form where the individual levofloxacin molecules are very closely associated with water molecules. Different names are assigned to these forms depending on the number of water molecules that are associated with each individual molecule of levofloxacin. A hemihydrate will have two molecules of levofloxacin for each molecule of water.
The inventive story
(a) Research Activities
[24] Daiichi began trying to separate the enantiomers of ofloxacin, in April 1981. They had a series of failures until April 1984 when work began on what would eventually become known as processes A and B. (Hayakawa Affidavit at paras. 17-25, AR, v. 4, Tab 6, pp. 711-714.)
[25] Daiichi first isolated levofloxacin and the (+)-enantiomer of ofloxacin, in April 1985, using Process A. In April 1985, antimicrobial testing revealed that levofloxacin had about twice the activity of ofloxacin. In comparison the (+)-isomer had only between 1/8th to 1/100th the activity of levofloxacin.
[26] Daiichi completed Process B in September 1985, and on or about September 20, 1985, measured levofloxacin's solubility to be 22,500 µg/ml. (Hayakawa Affidavit at paras. 41-42, 55-56, AR, v. 4, Tab 6, pp. 719-720, 723.)
[27] In mid October, 1985, Dr. Kazuhisa Furuhama (a Daiichi toxicologist) conducted head to head acute toxicity tests and found that, for a group of five male mice intravenously injected at the 200mg/kg dose, for levofloxacin, there were no deaths, for ofloxacin, there were two, and for the (+)-enantiomer, there were three. At that time, Dr. Furuhama conducted further acute toxicity testing and determined the intravenous LD50 value for levofloxacin in male mice to be 243.8 mg/kg. This was higher than the established LD50 value for ofloxacin of 208 mg/kg, indicating levofloxacin to be less acutely toxic than ofloxacin. (Hayakawa Affidavit at paras. 59, 65-66, AR, v. 4, Tab 6, pp. 724-727; Kato Affidavit at paras. 15-17, AR, v. 10, Tab 14, pp. 2801-2802.)
[28] Later, on or about December of 1985, Daiichi determined the absolute configuration of the levofloxacin molecule to be "S". (Hayakawa Affidavit, Ex. BB, p. DAI-0024054, AR, v. 5, Tab 7, p. 1324; Novopharm Trial, above at para. 48.)
[29] Work on process C began in the fall of 1985. This application disclosed that the absolute configuration of levofloxacin was "S", and also referred to its "higher ... solubility and weaker toxicity". (Hayakawa Affidavit at paras. 43-48, AR, v. 4, Tab 6, pp. 720-721; Klibanov Affidavit Ex: I p. 2, AR, v. 13, Tab 18, p. 3783.)
(b) The Invention Date
[30] At the Novopharm Trial, Justice Roger Hughes, held that the date of invention was December 1985:
[50] It can be seen through this course of development that the final element of claim 4, determination of the S configuration, had been made by December 1985. I find therefore, that December 1985 is the relevant date of invention for consideration of issues as to inventive ingenuity and obviousness with respect to claim 4.
(Novopharm Trial, above at paras. 48-50.)
Earlier litigation of this ‘080 patent [31] The Court has previously considered the validity of the ‘080 patent in an application brought by Janssen-Ortho v. Novopharm Limited, 2004 FC 1631, 264 F.T.R. 202 [Novopharm]. Apotex was not a party to this litigation.
[32] In Novopharm, above, Justice Richard Mosley of the Federal Court considered the ‘080 patent in the context of an application for prohibition brought by Janssen in response to an NOA filed by Novopharm. Novopharm sought to market a generic levofloxacin drug product in Canada and alleged, in the NOA, that the ‘080 patent was invalid for lack of novelty, obviousness, ambiguity, overbreadth and lack of sufficiency.
[33] Justice Mosley dismissed this application. While he found that the previous patents did not provide all of the information a person of ordinary skill in the art would have required to come to the patent in question and that the patent was not ambiguous nor was the specification insufficient, he concluded that “beneficial properties discovered and set out in the ‘080 patent were not unknown.” Furthermore, he concluded that the “knowledge of the existence of and the possibility of separating the two enantiomers of ofloxacin was common to the ordinary chemist, and the determination of which enantiomer possessed a greater amount of the same benefits of the previously known racemic antibiotic was not surprising or inventive.” (Novopharm, above at para. 53.)
[34] In the Novopharm Trial, above, the Federal Court considered the proper construction of claim 4 of the ‘080 patent in the context of an action for patent infringement and validity.
[35] Justice Hughes found that claim 4 of the ‘080 patent was valid and infringed as the defendant had failed to establish that the said claim was invalid on the basis of obviousness or lack of inventive ingenuity. Despite the fact that the claim does not address medical properties or uses, Justice Hughes found, at paragraph 96, that, where the compound is new, it is sufficient that its utility be set out in the specification. He also found that the prior art did not contain any direction that the enantiomers of ofloxacin would be more active than the racemate nor did it instruct the skilled person as to how to separate or produce an enantiomer; therefore, claim 4 of the patent was not anticipated. Moreover, Justice Hughes determined that levofloxacin was of sufficient “inventive ingenuity” to merit valid patent protection as set out in claim 4. Recognizing that his finding was different than that of Justice Mosley, Justice Hughes explains that he benefited from extensive evidence that was not previously presented and determined that Novopharm failed to establish that claim 4 was invalid on the basis of obviousness or lack of inventive ingenuity. (Novopharm Trial, above at paras. 96, 104, 115 and 116.)
[36] The Federal Court of Appeal upheld Justice Hughes’ decision. (Novopharm Appeal, above.)
IV. Issues [37] This application raises the following issues:
A. Is this application an abuse of process?
B. Would Apotex’ marketing of its levofloxacin tablets for oral administration in a dosage strength of 250mg, 500mg and 750mg infringe claim 4 of Janssen’s ‘080 patent?
C. If infringement is the case, are any of Apotex’ allegations that the ‘080 patent is invalid, justified on the following bases:
i) Anticipation
ii) Obviousness;
iii) Claims broader than the invention made and lack of sound prediction.
D. Is Apotex’ allegation that the ‘080 patent is void pursuant to paragraphs 40(1)(a) and (c) of the Patent Act, justified?
V. Analysis Burden of Proof [38] In a proceeding under the Patented Medicines NOC Regulations, the first person has the burden of establishing that the allegations of infringement and invalidity contained in the NOA are not justified; however, because of the presumption of validity set out in subsection 43(2) of the Patent Act, R.S.C., 1985, c. P-4, the first person can meet the initial burden in respect of invalidity merely by proving the existence of the patent. (Pfizer Canada, Warner-Lambert Company and Parke Davis and Company v. Apotex, 2007 FCA 209, 366 N.R. 347 at para. 109, rev’g 2005 FC 1205, 279 F.T.R. 164 [Pfizer v. Apotex].)
[39] The burden is then on the second person to adduce evidence of invalidity and to put the allegations of invalidity contained in its NOA ‘in play’. To do so, the second person must adduce evidence which is not clearly incapable of establishing its allegations of invalidity. Hence, not only must the second person's NOA contain sufficient factual and legal basis for its allegations, but it must also adduce evidence of invalidity. Only once the second person has adduced sufficient evidence, on a balance of probabilities, does the first person have to establish on a balance of probabilities that allegations of invalidity are not justified. (Pfizer v. Apotex, above at paras. 109-110.)
A. Abuse of Process Consideration [40] A second person challenging a patent that has previously been upheld in a prohibition proceeding, under section 6 of the NOC Regulations, must establish that it has provided either “better evidence or a more appropriate legal argument” than existed in the previous case. (Sanofi-Aventis Canada v. Novopharm Ltd., 2007 FCA 163, [2008] 1 F.C.R. 174 at paras. 37-38, 50 [Sanofi-Aventis v. Novopharm].). As noted by Justice Hughes, in Eli Lilly Canada v. Novopharm Limited, 2007 FC 596, 58 C.P.R. (4th) 214 [Eli Lilly v. Novopharm], and Pfizer Canada and Parke, Davis and Company Ltd. v. Novopharm Limited, 2008 FC 11, [2008] F.C.J. No. 3 (QL) [Pfizer v. Novopharm], it is difficult for the Court to determine if there is better evidence or a more appropriate legal argument, based solely on the reasons for judgment in a prior proceeding.
[41] Better evidence: Apotex submits that the present case is distinguishable from the Novopharm Trial in that the evidence in the present proceeding is different than the evidentiary record before Justice Hughes; however, it is for the evidence itself to be recognized and acknowledged for its inherent validity. It must be shown to be so, not simply told that it is so.
[42] They submit that the evidentiary record at bar (unlike the evidentiary record in the Novopharm Trial and Novopharm cases) is that (1) Gerster’s method was not only used as a model by Dr. Hayakawa, but that the same technique was used, including the use of the same reagents; (2) Gerster’s method was not “inventive” as many other resolution techniques had been applied with success at the relevant time. For example, Justice Hughes recognized that Process A resulted in 100% optical purity, but this was a commercial chiral HPLC column bought from Sumitomo; (4) the ‘080 patent contemplated resolution and obvious equivalents; (5) no resolution method was claimed within the ‘080 patent; (6) Dr. Gerster provided evidence in this case that he only disclosed materials that were already considered routine and commonly known; (7) Daiichi was able to obtain levofloxacin at 83% optical purity, which may be considered to be in a “reasonably pure state” and capable of doing “its job for instance as an antimicrobial agent”; (8) the properties of increased activity, reduced toxicity and increased solubility were known and described in the prior art; (9) the Gerster 1985 disclosed the twofold increase in antimicrobial activity of the S(-)-compound over the racemate; (10) the activity / toxicity / solubility properties were expected and the “overall combination” of these properties does not exist for levofloxacin, because, with increased solubility, toxicity increases; (11) the Applicants assert that the invention relates only to antimicrobial activity; and (12) the Gerster 1982 is properly established as being prior art.
(Novopharm Trial, above at paras. 39, 43, 53, 95, 119 aff’d Novopharm Appeal, above at paras. 19-20; Eli Lilly v. Novopharm, above at para. 38; Gerster Affidavit at paras. 11-13, AR, v. 45, Tab 65, pp. 14458-14459; Partridge Cross Examination, AR, v. 23, Tab 33, q. 52, p. 7086.)
[43] In response, the Applicants argue that Apotex has not provided better evidence as they raise substantially similar issues and evidence on obviousness and anticipation while asserting the same prior art.
[44] More appropriate legal argument: Apotex submits that it has raised novel legal arguments that were not previously before the Court; however, the arguments may be based on different evidence but that does not necessarily make of “novel” arguments, better evidence, of itself. It contends that, contrary to the evidence that was previously before this Court (1) attention was given to enantiomers; (2) competitors were motivated to obtain levofloxacin; (3) properties of levofloxacin were expected; (4) there were many techniques to isolate or synthesize the enantiomers of ofloxacin; and (5) efforts of Daiichi were not extraordinary.
[45] In response, the Applicants argue that the Federal Court of Appeal has already made a determination that the ‘080 patent is a valid patent, and Apotex is simply attempting to recontest the validity of the patent as a selection patent by recasting its argument under different headings.
[46] Apotex argues that the Court has not previously considered the argument that levofloxacin itself is an anhydrate and, therefore, in producing a hemihydrate tablet, they will not infringe the ‘080 patent.
[47] On appeal, the Federal Court of Appeal expressly found the ‘080 patent to be valid. It concurred with Justice Hughes’ findings in the Federal Court that the patent was valid, that levofloxacin clearly demonstrated a special advantage and that Daiichi’s work was more than mere verification. It was ultimately found that the patent was not obvious and that the Applicants had established utility. (Novopharm Appeal, and Novopharm Trial, above.)
[48] The Applicants submit that many, if not all, of Apotex’ arguments have been considered by the Court in prior proceedings. In particular, it is apparent that the Court has previously considered whether the patent disclosure provides adequate information to support a finding that levofloxacin has an unexpected advantage over the prior art. Thus, it will be difficult for Apotex to assert that it has a “more appropriate legal argument”. It will also be difficult for Apotex to argue it has better evidence on this point.
The witnesses Janssen’s Witnesses [49] Janssen tendered the affidavit of seven expert witnesses, all of whom were cross-examined:
(a) Frank A. Bucci is an ophthalmologist specializing in ocular diseases including surgery of the eye. Dr. Bucci is the director of an eye surgery centre and has done thousands of surgical and other procedures related to the eye. Dr. Bucci has also lectured, given presentations and written extensively in the area of ophthalmology.
(b) Alexander M. Klibanov is a professor of Chemistry and Bioengineering at Massachusetts Institute of Technology. He has researched, lectured and written extensively in the area of synthesis and evaluation of optically active compounds using enzymes.
(c) Anne Langley is Associate Librarian and Adjunct Associate Professor of Chemistry at the Duke University Chemistry Library. She has extensive experience in researching information using a variety of resources and has written books, articles and reports on a range of library and information science topics including electronic resources from the scientific and engineering perspective.
(d) Dr. Allan S. Myerson is the Provost and Senior Vice President and Philip Danforth Armour Professor of Engineering at the Illinois Institute of Technology, Chicago. He specializes in the area of crystallization and solubility and has written and taught extensively on the subject.
(e) John J. Partridge has worked for the past 37 years in organic chemistry dealing with pharmaceuticals. He has extensive experience in drug discovery and development in the area of anti-infectives, including in the areas of antivirals, antibacterials such as cephalosporins and fluoroquinolones as well as antifungals.
(f) Dr. Joseph V. Rodricks is a consultant in toxicology with focus in safety and human health risk assessment and a visiting professor at Johns Hopkins University, Baltimore, where he teaches courses in toxicology and risk analysis. He has lectured and written extensively in the area of toxicology.
(g) Dr. Mark Philip Wentland is a Professor of chemistry and organic chemistry at Rensselaer Polytechnic Institution, Troy, N.Y. Dr. Wentland specializes in quinolones, a class of compounds that include those at issue. He was active in quinolones in the 1980’s, a period in which the subject matter of the ‘080 patent was developed. Dr. Wentland was actively working as a medicinal chemist in the quinolone area at the relevant time in the early 1980’s.
[50] Janssen also filed the evidence of six fact witnesses. Dr. Furuhama and Hiroyoshi Kinpara were the only two that were not cross-examined:
(a) Dr. Isao Hayakawa is one of the named inventors of the patent in suit. He joined Daiichi in 1969 and, in 1972, became involved in researching anti-infectives. In 1985, he became the Senior Researcher and the Pre-clinical Coordinator with respect to levofloxacin’s product development.
(b) Dr. Kazuhisa Furuhama is employed as a toxicologist at Daiichi Pharmaceutical Co. Dr. Furuhama was the scientist who conducted the toxicity screening tests for levofloxacin, which is the subject matter of Canadian Patent No. 1,304,080.
(c) Paul Herbert is a senior partner at the law firm of Riches, McKenzie & Herbert LLP where he practices intellectual property. A qualified barrister and solicitor and registered patent agent in Canada, he is responsible for prosecuting the Canadian Patent Application Serial No. 512,000, filed on June 19, 1986, which issued on June 23, 1992 as Canadian Patent No. 1,304,080.
(d) Dr. Michiyuki Kato is employed as a toxicological pathologist at Daiichi Sankyo Company, Limited. Dr. Kato worked in the Drug Safety Research Center of Daiichi Pharmaceutical Co. Ltd. at the time levofloxacin was developed, and is familiar with the toxicity screening tests for levofloxacin.
(e) Hiroyoshi Kinpara is Group Manager, Supervising and Operation Group, Intellectual Property Department of Daiichi Pharmaceutical Co., formerly Daiichi Seiyaku Co. Mr. Kinpara had previously been the Assistant Manager of Daïchi of Seiyaku Company’s legal department.
(f) Michael I. Stewart is a senior partner at Sim & McBurney, a partnership of patent and trade-mark agents engaged in the preparation, filing and prosecution of patent, trade-mark, industrial design, integrated circuit and copyright applications in Canada and the Unites States of America. He is also a registered patent agent in Canada and the United States where he has gained extensive experience in obtaining patents in a wide range of technologies.
[51] Janssen also provided the affidavits of Fumi Ishikawa and Phillip Schnell, Managers of TransPerfect Translation, mandated to review the translation of documents by linguists employed by TransPerfect Translation.
Apotex’ Witnesses [52] Apotex tendered the evidence of six expert witnesses, all of whom were cross-examined:
(a) Dr. Neal Castagnoli is the Peters Professor of Chemistry Emeritus at Virginia Polytechnic Institute and State University. A principal focus of his research during the past 30 years has been concerned with the analysis of the relationship between chemical structure and biological activity, including toxicity.
(b) Dr. Paul Erhardt is the Director of the Center for Drug Design and Development and Professor of Medicinal and Biological Chemistry at the University of Toledo. Dr. Erhardt’s research in medicinal chemistry focuses on small molecular therapeutics, drug and formulation design. Dr. Erhardt’s evidence addresses whether the ‘080 patent provides sufficient information to justify the selection of levofloxacin over ofloxacin on the basis of its unexpected properties.
(c) Dr. Richard Kellogg is the former Dean of Chemistry at the University of Groningen, and is currently the Director of Syncom BV, a company he co-founded in 1988 that specializes in all aspects of organic synthesis. Dr. Kellogg has published widely in the fields of chiral compounds, their synthesis and separation.
(d) Dr. Howard Leibowitz is the Sherwook J. and H. Lerene Tarlow Professor of Ophthamology at the Boston University School of Medicine. Dr. Leibowitz is a recognized expert in infectious disease of the eye and antimicrobial ocular medications. Dr. Leibowitz’ evidence addresses the use of ofloxacin and levofloxacin in ophthalmic treatments.
(e) Dr. Kurt Martin Mislow is the Hugh Stott Taylor Professor Emeritus Chemistry at Princeton University. Throughout his career, the dominant theme of his research has been the development of stereochemical theory with an emphasis on the study of molecular chirality in organic, inorganic and biochemical systems, including pharmaceutical agents.
(f) Mr. Gerald O.S. Oyen is a partner of the firm Oyen Wiggs Green & Mutala LLP and has practiced in the area of patent law and other areas of intellectual property since 1967. Mr. Oyen provides evidence on the issues relating to deemed abandonment and patent prosecution practice.
[53] Apotex also filed the affidavit of four fact witnesses. Dr. John F. Gerster was the only one to be cross-examined.
(a) Ines Ferreira is an employee for Apotex’ counsel’s law firm. Her affidavit introduces a copy of the following: Notice of Allegation from Apotex Inc; Canadian Letters Patent No. 1,304,080; schedules A, B and C of the Notice of Allegation, the Notice of Application in the Court File No. T-214-03 dated February 7, 2003; the Notice of Application filed in Court File No. T-214-03 dated February 11, 2005; the Notice of Application filed in the Court File No. T-1029-05 dated June 13, 2005; pages 91 and 93 of The Canadian Law and Practice Relating to Letters Patent for Invention; page 30 of King v. Uhlemann Optical Company, [1950] Ex. C.R. 142, 10 Fox Pat. C. 24; the Patent List for Levofloxacin obtained from Health Canada as well as a copy of Zbinden, G. et al. Significance of LD50 test for the toxicological evaluation of chemical substance.
(b) Dr. John F. Gerster is a retired corporate scientist with 3M Pharmaceuticals (Riker Laboratories). Dr. Gerster’s evidence relates to his poster presentation at the 1982 North American Medicinal Chemistry Symposium.
(c) Michele S. Katz is an Associate with Welsh & Katz Ltd. Her affidavit introduces documents from the United States District Court of New Jersey and West Virginia for Civil Action No. 3:02-cv-02794-GEB-JJH and Civil Action 1:02-cv-00032-IMK-JSK inclusively.
(d) Jordana Richmon is a law clerk at Apotex’ counsel’s law firm. Her affidavit introduces as exhibits the Civil Docket Report for case 1:02-cv-00032-IMK-JSK in the U.S. District Court, as well as a copy of Document No. 541 to the Civil Docket Report with attachment.
[54] Apotex also provided the affidavits of Huber, Iida, Liu, and Trippany.
(a) Marie-Luise Huber is an employee of Babel Translations. She holds a Bachelor of Science (Honours), and a Registered Australian and New Zealand Trade Mark Attorney. Her affidavit introduces an English translation of European Patent Application EP 0,078,362 A2 and German Patent Application DE 3,543,513 A1.
(b) Kazuhiko Iida is an employee of H. IIDA & Co., a chartered patent attorney’s office in Japan. Kazuhiko Iida was asked to provide English translations of the three Japanese Patent Applications.
(c) Xin Min Liu is an employee of Mornginside Translations and a former translator with the United Nations Chinese Translation Service and a contract translator of the US State Department. Xin Min Liu was asked to translate Synthesis and Structure Activities Relationship of Levofloxacin Analogues, Acta Pharmaceutica Sinica 34(3).
(d) Jennifer Trippany is a manager at LinguaLinx Inc, a full service translation agency where she is responsible for coordinating translation projects.
The ‘080 patent Laws of construction [55] A patent is construed from the perspective of the person skilled in the art to which the invention relates. The skilled person possesses the ordinary amount of knowledge incidental to that particular trade. (Consolboard, above at 523.)
[56] Person skilled in the art: The Applicants submit that the person skilled in the art of the ‘080 patent would be familiar with the principles and nomenclature of stereochemistry and would be aware that the ‘080 patent is directed toward the invention of a drug for use in humans to treat diseases.
[57] In the Novopharm Trial, Justice Hughes found that the person of ordinary skill would be “a person with at least a first level university education, and at least a few years of experience concerned with chemical compounds and deriving optically active compounds therefrom particularly in the area of compounds having medicinal uses.” (Novopharm Trial, above at para. 90.)
[58] Such a person would be familiar with the principles and nomenclature of stereochemistry and would be aware that the ‘080 patent is directed toward the invention of a drug for use in humans to treat diseases. The ‘080 patent specifically states that levofloxacin is “expected to be a very useful pharmaceutical agent as compared with the (±)-compound.” (Wentland Afidavit at para 45, AR, v. 31, Tab 45, p. 9866; Klibanov Affidavit at para. 24, AR, v. 12, Tab 17, pp. 3403-3404; ‘080 Patent p.2 In. 9-10; Hayakawa Affidavit Ex. A, AR, v. 4, Tab 6, p. 736.)
[59] Claim Construction: The Applicants assert only claim 4 of the ‘080 patent against Apotex in this proceeding. As such, the first task of the Court is to construe claim 4 of the ‘080 patent from the perspective of the skilled addressee.
[60] Claim construction precedes an assessment of infringement or validity. Claim construction is to be conducted purposively, in light of the patent as a whole, and not with excessive literalism. A patent is to be read through the eyes of a person of ordinary skill in the art, in an attempt to discern what the inventors of the patent intended. It must be read with a mind willing to understand, trying to achieve success and not looking for difficulties or seeking failure. (Whirlpool, above; Free World Trust, above at 1050.)
[61] A person of ordinary skill in the art (POSITA) conducts the exercise as of the publication date of the patent. This exercise is conducted in a purposive and not overly literal manner that is fair and reasonable to the patentee and the public. Patent construction should be approached "with a judicial anxiety to support a really useful invention". (Free World Trust, above at para 54; Whirlpool, above at 1089-1091; Consolboard, above at 521; reference is also made to Pfizer v. Mayne, above at 259-267.)
Construction of claim 4 of the ‘080 patent [62] Claim 4 of the ‘080 patent has already been construed by Justice Hughes, by Justice Mosley in a proceeding under the Patented Medicines NOC Regulations; and by Justice Irene M. Keeley in a United States action involving the U.S. 407 patent counterpart to the ‘080 patent (in which claim 2 corresponds to ‘080 claim 4). The Court, in each case, construed claim 4 (or its equivalent) to mean levofloxacin (or S(-) ofloxacin) in a way consistent with Justice Hughes' construction. (Novopharm, above at paras. 29-31; Ortho-McNeil Pharmaceutical v. Mylan Laboratories, 348 F. Supp. 2d 713 (N.D. W. Va. 2004) at 730.)
[63] Claim construction is a matter of law. In the recent case of Pfizer v. Novopharm, above, at paragraph 16, Justice Hughes reiterated that once a patent has been construed by the Court, it would require strong argument for a subsequent Court to come to a different result.