Janssen-Ortho Inc. v. Novopharm Ltd.

Janssen-Ortho Inc. v. Novopharm Ltd.
Court (s) Database
Federal Court Decisions
Date
2004-11-19
Neutral citation
2004 FC 1631
File numbers
T-214-03
Notes
Digest
Decision Content
Date: 20041119
Docket: T-214-03
Citation: 2004 FC 1631
Ottawa, Ontario, this 19th day of November, 2004
Present: The Honourable Mr. Justice Mosley
BETWEEN:
JANSSEN-ORTHO INC. and
DAIICHI PHARMACEUTICAL CO., LTD.
Applicants
and
NOVOPHARM LIMITED and
THE MINISTER OF HEALTH
Respondents
REASONS FOR ORDER AND ORDER
[1] Janssen-Ortho Inc., and Daiichi Pharmaceutical Co. Ltd., seek an order to prohibit the Minister of Health from issuing a Notice of Compliance to Novopharm Limited, regarding the marketing of tablets of an antimicrobial drug known generically as "levofloxacin" until after the expiry of Daiichi's levofloxacin patent. Janssen-Ortho is licensed by Daiichi to sell the drug in Canada under the brand name LEVAQUIN. Novopharm alleges that the patent is invalid for lack of novelty, obviousness, ambiguity, overbreadth and insufficiency of specification. Novopharm further asserts that its version of levofloxacin would not in any event infringe any of the patent's claims. The substantive issue in these proceedings is whether Novopharm's allegations of non-infringement and invalidity of the patent are justified.
BACKGROUND
The Parties
[2] Janssen-Ortho is the "first person" referred to in section 2 and subsection 4(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, (the "NOC Regulations"). Pursuant to subsection 6(4) of the NOC Regulations, Daiichi Pharmaceutical, as the owner of the patent, was made a party to this proceeding, however, as per subsection 6(1) of the NOC Regulations, the "first person", that is Janssen-Ortho, initiates and seeks relief in this prohibition proceeding. Janssen-Ortho has listed the patent at issue on the Patent Register in relation to its NOCs for LEVAQUIN. It markets the drug in 250 mg and 500 mg tablet form.
[3] The respondent, Novopharm, is the "second person" cited in section 2 and subsection 5(1) of the NOC Regulations. By letter dated December 20, 2002, Novopharm sent to Janssen-Ortho a Notice of Allegation ("NOA"), including a detailed statement of the legal and factual basis for its allegation, pursuant to paragraph 5(3)(c) of the NOC Regulations. It seeks a NOC to market 250 mg and 500 mg tablets of levofloxacin hemihydrate.
[4] The respondent, the Minister of Health (the "Minister"), is responsible for the review of applications by drug companies for the issuance of NOCs under the Food and Drug Regulations, C.R.C. 1985, c. 870. The Minister did not file materials in this application.
The Patent at Issue
[5] To understand the invention claimed in the patent at issue, certain chemistry terms and relationships must be understood. I have had the benefit of counsel's assistance and the expert affidavits filed by both sides. Janssen-Ortho's primary expert, Dr. Klibanov, is a Professor of Chemistry and Bioengineering at the Massachusetts Institute of Technology. Novopharm's expert, Dr. Caldwell, is the Dean of the Faculty of Medicine at the University of Liverpool. Both experts have extensive credentials and background in pharmacology and organic chemistry. For convenience, definitions of the terms employed in these reasons, based on my understanding of the evidence, are set out in Annex "A" .
[6] The patent at issue, Canadian Patent 1, 304, 080 (the " '080 patent") was granted to Daiichi Pharmaceutical on June 23, 1992. The filing date of the '080 patent is June 19, 1986 and it will expire on June 23, 2009.
[7] Daiichi is also the owner of Canadian Patent 1, 157, 840 (the " '840 patent"), issued on May 22, 1984, which disclosed and claimed an antibiotic known as "ofloxacin". Janssen-Ortho was also 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.
Levofloxacin and Ofloxacin
[8] Levofloxacin, the subject of the '080 patent and these proceedings, and ofloxacin, disclosed in the expired '840 patent, can both be described as broad-spectrum, synthetic antibacterial agents useful in the treatment of infections caused by certain strains of microorganisms, such as certain types of pneumonia, influenza, skin infections and urinary tract infections. Ofloxacin and levofloxacin formulas have also been marketed for eye infections under different brand names.
[9] Ofloxacin is a racemic compound, that is a substance containing equal amounts of two optical isomers. An isomer is one of a number of molecules that have the same constituent atoms; however, the bonds between the atoms are oriented differently in space. Their optical quality refers to their ability to rotate the plane of polarized light, that is, light focussed to shine only in one direction. Optical isomers that rotate polarized light to the right, in a clockwise direction, are "dextrorotatory" and use the symbols (+) or (d) for "dextro". Optical isomers that rotate polarized right to the left, in a counter-clockwise direction, are "levorotatory" and use the symbols (-) or (l) for "levo". The drug at issue here is the S(-) optical isomer of ofloxacin, hence "levofloxacin".
[10] Another term for describing optical isomers is "enantiomer" . An enantiomer is one of a pair of non-superimposable mirror images; by analogy, one's hands. Compounds that exhibit this quality are called "chiral". They possess a chiral centre and in carbon compounds, such as ofloxacin, the chiral centre is a carbon atom that is bound to four different atoms or groups of atoms, where all four groups are different. Chirality confers a specific three-dimensional shape on a molecule.
[11] When produced, levofloxacin was discovered to possess beneficial properties over both racemic ofloxacin and the R(+) optical isomer. The specification of the '080 patent, under the heading "Background of the Invention" at pages 1-2, discloses the beneficial properties of the S(-) enantiomer of ofloxacin (levofloxacin) in contrast to the racemic ofloxacin and the R(+) compound, as follows:
... The present inventors obtained optically active compounds of the racemic Ofloxacin and found that the S(-)-compound possesses an antimicrobial activity of about 2 times higher than that of the (")-compound and acute toxicity LD50 weaker than that of the (")-compound as determined in mice by intravenous administration. On the other hand, the present inventors found that the R(+)-compound exhibits an antimicrobial activity of only about 1/10 to 1/100 times that of the (")-compound, whereas it possess an acute toxicity substantially equal to that of the (")-compound. That is, the S(-)-form of Ofloxacin has been found to have very desirable properties, i.e., increased antimicrobial activity and reduced toxicity, and is expected to be a very useful pharmaceutical agents [sic] as compared with the (")-compound. Further, both the R(+)- and S(-)-compounds of Ofloxacin in the free form have markedly high water-solubility as compared with the (")-compound and as compared with free compounds of this type, and can be used as injectable preparations. These advantages will be apparent from the experimental data shown hereinafter.
ISSUES
[12] 1. Burden of proof with respect to patent validity.
2. How should the '080 patent be construed?
3. Is Novopharm's allegation that the '080 patent is invalid justified because of
a) Obviousness;
b) Anticipation; or
c) Other allegations of invalidity?
4. Is Novopharm's allegation that the '080 patent will not be infringed by its product justified?
ANALYSIS
Burden of Proof with Respect to Patent Validity
[13] It is well-established that the legal burden of proving that the second person's allegations are not justified is on the person seeking the prohibition order, namely Janssen-Ortho. Janssen-Ortho must establish, on a balance of probabilities, that Novopharm's allegations are not justified. While Janssen-Ortho bears the overall legal burden, Novopharm has the evidential burden to put "in play" the allegations set out in its NOA and its detailed statement: see Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1994), 55 C.P.R. (3d) 302 (F.C.A.), Pharmacia Inc. v. Canada (Minister of National Health & Welfare) (1995), 60 C.P.R. (3d) 328 (F.C.T.D.), aff'd (1995) 64 C.P.R. (3d) 450 (F.C.A.), and Bayer Inc. et a. v. Minister of National Health and Welfare et al. (2000), 6 C.P.R. (4th) 285 (F.C.A.). The facts contained in the NOA and detailed statement are presumed to be true, at least with respect to allegations of non-infringement, except to the extent that the contrary has been shown by the applicant: see Merck Frosst, supra, at 319.
[14] Janssen-Ortho accepts that with respect to infringement, the legal burden is clearly its own. However, with respect to validity, the applicant submits that the burden of proof in a NOC proceeding shifts to the respondent due to the presumption that the patent is valid pursuant to section 45 of the pre-1989 Patent Act. The parties agree that as the application for the '080 patent was made in 1986, the Patent Act, R.S.C. 1985, c. P-4 applies.
[15] The applicant relies on Merck Frosst, supra in support of this contention, referring to the following words of Hugessen J.A. at page 319:
As I understand the scheme of the regulations, it is the party moving under s. 6, in this case Merck, which, as the initiator of the proceedings, has the carriage of the litigation and bears the initial burden of proof. That burden, as it seems to me, is a difficult one since it must be to disprove some or all of the allegations in the notice of allegation which, if left unchallenged, would allow the Minister to issue a notice of compliance. There may, of course, be some presumptions (such as for example the statutory presumption of validity of a patent) (Patent Act, s. 43) which may help the moving party and have the effect of displacing the burden of proof. ...
[16] The applicant also relies on the Supreme Court of Canada decisions of Monsanto Canada Inc. v. Schmeiser, 2004 SCC 34, (2004) 320 N.R. 201 and Apotex Inc. v. Wellcome Foundation Ltd., [2002] 4 S.C.R. 153, arguing that they indicate that the burden of demonstrating invalidity is on the person attacking the patent, that is the second person, or respondent, in a NOC proceeding. The applicant also says that the language used by the Supreme Court in these decisions indicates that the determination of invalidity can only be made after the Court is satisfied that the Commissioner of Patents was "clearly wrong", or made an unreasonable decision in granting the patent in the first place. The applicant submits that the reasoning of the Supreme Court in these patent actions applies equally to NOC proceedings.
[17] The respondent Novopharm refers to the 2000 Federal Court of Appeal decision in Bayer, supra, where Sharlow J.A. commented on the statutory presumption of validity and how this affected the burden of proof in a NOC proceeding. Novopharm submits that the presumption of validity is spent when the respondent puts forward evidence to the contrary and if, in the end, the evidence on both sides is a "draw", then the applicant cannot be granted a prohibition order, as the overall legal burden, on a balance of probabilities, was its to carry. At paragraph 6 of Bayer, Sharlow J.A. stated as follows:
In seeking to discharge its burden of proving the allegation to be unjustified, Bayer relied on the statutory presumption of the validity of its patent. Because that presumption exists, it may be said that Apotex, as the party responding to the application for a prohibition order, has a burden of proof in this sense: if Apotex had adduced no evidence that was capable of establishing the invalidity of the patent, Bayer could have succeeded on the basis of the statutory presumption alone. As the Motions Judge correctly said at paragraph 15:
A statutory presumption, for example, may assist Bayer and "have the effect of displacing the burden of proof".
[emphasis added]
[18] Justice Sharlow noted that the second person in that case had adduced evidence in the form of an affidavit. She then observed, at paragraph 9, that rebutting the statutory presumption of validity will depend on the strength of the evidence going to invalidity:
The operation of the statutory presumption in the face of evidence of invalidity depends upon the strength of the evidence. If the evidence proves on a balance of probabilities that the patent is invalid, the presumption is rebutted and is no longer relevant: Diversified Products Corp. v. Tye-Sil Corp. (1991), 35 C.P.R. (3d) 350 (F.C.A.) at p. 359.
[19] The applicant replies that Bayer is not authority for the proposition that as soon as the respondent files a "speck of evidence", the burden shifts to the applicant on the issue of validity in a NOC proceeding. Janssen contends that the evidence of the second person must demonstrate that the patent is invalid on a balance of probabilities before the statutory presumption is rebutted and no longer relevant.
[20] I read the Bayer decision as indicating that a second person's evidence must not be clearly incapable of sustaining its allegations, and if it meets that threshold, then the statutory presumption will be spent and cannot aid the applicant for the purpose of a NOC summary proceeding. This interpretation is supported by the language of section 45 of the pre-1989 Patent Act, that the presumption is to apply "in the absence of any evidence to the contrary". I note, however, that simply succeeding in rebutting the presumption does not mean that a second person will be successful in a prohibition application, as it must still put sufficient evidence "in play" to challenge the validity of the patent as well as the applicant's expert evidence, while the overall legal burden remains with the applicant.
[21] The applicant's reliance on the Supreme Court's reasoning in the Schmeiser and Wellcome decisions, with regard to the burden of proof, is not helpful in my view, as both were patent actions for declarations of invalidity and infringement. I do not agree that such reasoning is directly applicable in a NOC proceeding, which has been held to be akin to a summary proceeding by way of an application, involving its own unique set of principles and regulations, and where any finding regarding infringement or validity is not determinative of that matter in any subsequent patent action. As held in Merck Frosst, supra, at 319, a NOC proceeding is not an action and its object is "solely to prohibit the issuance of a notice of compliance under the Food and Drug Regulations."
Construction of the '080 patent
[22] At the heart of the dispute between the parties as to the construction of the '080 patent is whether it claims the levorotatory optical isomer, as found or already disclosed within racemic ofloxacin (Novopharm's position) or claims such enantiomer as a separate, inventive compound (Janssen's position). Related to that question is the issue of whether "S(-)" as used to describe the levo-enantiomer of ofloxacin can be construed to mean the S(-) isomer in a substantially pure form.
[23] As held by the Supreme Court of Canada in Whirlpool Corp. v. Camco Inc., [2000] 2 S.C.R. 1067 and Free World Trust v. Électro Santé Inc., [2000] 2 S.C.R. 1024, a patent claim is to be construed in a "purposive" way, which involves a realistic construction of the language of the claims through the eyes, and with the learning, of a person skilled in the art (para. 44 Whirlpool, supra). Moreover, the Court may look at the entire specification of the patent in order to understand the words as stated in any disputed claim, provided this does not enlarge or contract the scope of the actual patent claims.
[24] Claim construction remains, in the end, a question of law for the Court to decide: Whirlpool, supra, and Beecham Canada Ltd. v. Procter & Gamble Co. (1982), 61 C.P.R. (2d) 1 (F.C.A.). The key to purposive construction, as articulated by Justice Binnie in Whirlpool, supra, is for the Court to identify the particular words or phrases in the patent claims that describe what the inventor considered to be the "essential elements of his invention" (para. 45).
[25] There are 19 claims of the '080 patent. Claims 1, 3, 5, 10 and 11 claim various processes to make levofloxacin and related compounds. The parties agree that the process claims are not at issue in these proceedings. Claims 2, 4, 6, 12-17 and 19 claim, among other substances, levofloxacin and/or its salts and hydrates. Claims 7, 8, 9 and 18 relate to pharmaceutical formulations which contain levofloxacin, including its salts and hydrates.
[26] Janssen argues that a purposive construction of the relevant claims, including a reading of the specifications, discloses that the invention here is the recognition of the unexpected and beneficial properties that are present in the S (-) enantiomer and where the claim can be properly read as covering that enantiomer, the court should support its validity.
[27] Novopharm contends that all of the claims of the patent to a S (-) compound - without the limitation that it be pure, partially purified or isolated, or unaccompanied by the R (+) compound - cover the racemate, ofloxacin. The drafter of the claims erred, it argues, in not incorporating any purity limitation. Accordingly, Novopharm contends that the claims as written read on the racemate and there is nothing novel in the compounds claimed and the claims cannot be saved by the patent disclosure.
[28] In my view, the claims of the '080 patent would be read by a person skilled in the art as referring to the levorotatory isomer of ofloxacin and not to racemic ofloxacin. In claims 1, 2 and 10 of the '080 patent the phrase "S(-)... compound" is employed, as are solid-coloured wedges in the graphical depictions of the formulas for the compounds in the claims. The use of the "S" and "(-)" symbols and the solid-coloured wedges designates, from what the expert affidavit evidence has revealed in this proceeding, an optically active isomer with an "S" configuration rotating the plane of polarized light in a counter-clockwise direction. Racemic ofloxacin would not be described using the S(-) prefix. Moreover, the specification of the '080 patent confirms this construction of the claims. The disclosure refers to "optically active compounds of Ofloxacin" or the "racemic Ofloxacin" in contrast to the description of the S(-) enantiomer.
[29] Having reviewed the claims with the aid of the expert evidence in this proceeding, I am satisfied that the patent disclosure must form part of the construction to give the Court an understanding of the meaning behind the chemical formulae in the claims. This disclosure indicates that the antimicrobial activity of the optical (-) and (+) isomers of ofloxacin against various microorganisms was compared to that of the ofloxacin racemate. This demonstrates, in my view, that discovery of the beneficial properties in the S(-) optical isomer was the object and usefulness of this patent.
[30] With respect to the question of whether "S(-)" - as used to describe the levo-enantiomer of ofloxacin in the '080 patent - can be construed to mean S(-) in a substantially pure form, I accept that proposition. A chemist skilled in the art when reading "S(-)-pyridobenzoxazine compound" as described in a particular formula would, in my opinion, accept that such compound is principally made up of the S(-) enantiomer of a racemic compound, wherein the optical activity of the S(-) enantiomer is not only detectable, but dominant. The lack of numeric quantification of the purity level of the S(-) enantiomer is not fatal to distinguishing this compound from either the racemic compound or the R(+) enantiomer.
[31] This construction of the '080 patent is similar to that employed by Judge Keeley of the U.S. Northern District Court of West Virginia in Ortho-McNeil Pharmaceutical Inc., et. al. v. Mylan Laboratories, Inc. et al., 267 F. Supp. 2d 533 (N.D. W. Virg. 2003), where the U.S. patent[1] to levofloxacin was challenged. While this Court is in no way bound by the Mylan decision as a precedent and is conscious of the differences between Canadian and U.S. patent law, the reasoning was of general use to this Court in construing the '080 patent.
[32] The existence of such enantiomers of racemic ofloxacin seems undoubtedly accepted prior to 1984 and it was the development of a process for producing the S(-) enantiomer and the discovery of the beneficial properties of this enantiomer over racemic ofloxacin or the R isomer that are claimed in the '080 patent. Whether the invention claimed was obvious or anticipated, or was improperly set out in the patent claims and is vulnerable on other grounds of invalidity, are the issues dealt with in my analysis below.
Invalidity
[33] As noted above, the parties agree that the Patent Act, R.S.C. 1985, c. P-4 governs this Court's analysis. This version of the Patent Act is commonly referred to as the "pre-October 1, 1989" Patent Act. Subsections 27(1) and 61(1) of that Act are relevant and provide:
27. (1) Subject to this section, any inventor or any legal representative of an inventor of an invention that was
(a) not known or used by any other person before he invented it,
(b) not described in any patent or in any publication printed in Canada or in any other country more than two years before presentation of the petition hereunder mentioned, and
(c) not in public use or on sale in Canada for more than two years prior to his application in Canada,
may, on presentation to the Commissioner of a petition setting out the facts, in this Act termed the filing of the application, and on compliance with all other requirements of this Act, obtain a patent granting to him an exclusive property in the invention.
61. (1) No patent or claim in a patent shall be declared invalid or void on the ground that, before the invention therein defined was made by the inventor by whom the patent was applied for, it had already been known or used by some other person, unless it is established that
(a) that other person had, before the date of the application for the patent, disclosed or used the invention in such manner that it had become available to the public;
(b) that other person had, before the issue of the patent, made an application for patent in Canada on which conflict proceedings should have been directed; or
(c) that other person had at any time made an application in Canada which, by virtue of section 28, had the same force and effect as if it had been filed in Canada before the issue of the patent and on which conflict proceedings should properly have been directed had it been so filed.
27. (1) Sous réserve des autres dispositions du présent article, l'auteur de toute invention ou le représentant légal de l'auteur d'une invention peut, sur présentation au commissaire d'une pétition exposant les faits, appelée dans la présente loi le "dépôt de la demande", et en se conformant à toutes les autres prescriptions de la présente loi, obtenir un brevet qui lui accorde l'exclusive propriété d'une invention qui n'était pas :
a) connue ou utilisée par une autre personne avant que lui-même l'ait faite;
b) décrite dans un brevet ou dans une publication imprimée au Canada ou dans tout autre pays plus de deux ans avant la présentation de la pétition ci-après mentionnée;
c) en usage public ou en vente au Canada plus de deux ans avant le dépôt de sa demande au Canada.
61. (1) Aucun brevet ou aucune revendication dans un brevet ne peut être déclaré invalide ou nul pour la raison que l'invention qui y est décrite était déjà connue ou exploitée par une autre personne avant d'être faite par l'inventeur qui en a demandé le brevet, à moins qu'il ne soit établi que, selon le cas :
a) cette autre personne avait, avant la date de la demande du brevet, divulgué ou exploité l'invention de telle manière qu'elle était devenue accessible au public;
b) cette autre personne avait, avant la délivrance du brevet, fait une demande pour obtenir au Canada un brevet qui aurait du donner lieu à des procédures en cas de conflit;
c) cette autre personne avait à quelque époque fait au Canada une demande ayant, en vertu de l'article 28, la même force et le même effet que si elle avait été enregistrée au Canada avant la délivrance du brevet et pour laquelle des procédures en cas de conflit auraient dû être régulièrement prises si elle avait été ainsi enregistrée.
Obviousness
[34] Turning first to obviousness, the Federal Court of Appeal in Diversified Products Corp. v. Tye-Sil Corp. et al. (1991), 35 C.P.R. (3d) 350 (F.C.A.) described the requirement that an invention not be obvious at page 365:
There is no specific section in the Patent Act relating to the requirement for inventiveness or inventive ingenuity, but it has been held and is no longer questioned that by use of the words "invention" and "inventor" throughout the Act, inventiveness or inventive ingenuity is required to obtain a valid patent. ...
[35] The commonly accepted test for obviousness was set out in Beloit Canada Ltd. v. Valmet Oy, (1986),8 C.P.R. (3d) 289 (F.C.A.) by Hugessen, J.A. as follows at page 294:
The test for obviousness is not to ask what competent inventors did or would have done to solve the problem. Inventors are by definition inventive. The classical touchstone for obviousness is the technician skilled in the art but having no scintilla of inventiveness or imagination; a paragon of deduction and dexterity, wholly devoid of intuition; a triumph of the left hemisphere over the right. The question to be asked is whether this mythical creature (the man in the Clapham omnibus of patent law) would, in the light of the state of the art and of common general knowledge as at the claimed date of invention, have come directly and without difficulty to the solution taught by the patent. It is a very difficult test to satisfy.
[Emphasis added]
[36] In determining whether a patent claim is obvious, the Court must avoid using the benefit of hindsight. The question to ask is whether the solution taught by the patent would be "plain as day" to the skilled technician who was searching for something novel, without having to do experimentation or research. Suggestions or signposts in the prior art are not sufficient to make a patent invalid for obviousness: Apotex Inc. v. Wellcome Foundation Ltd. (1998), 79 C.P.R. (3d) 193 (F.C.T.D.), varied but not on the issue of obviousness, [2001] 1 F.C. 495 (C.A.), aff'd [2002] 4 S.C.R. 153, Bayer Aktiengesellschaft v. Apotex Inc. (1995), 60 C.P.R. (3d) 58 (Ont. Gen. Div.), varied on other grounds (1998), 82 C.P.R. (3d) 526 (O.C.A.), leave to appeal to the Supreme Court of Canada denied [1998] S.C.C.A. No. 563(QL) and Fabwerke Hoechst v. Halocarbon (Ont) Ltd., [1979] 2 S.C.R. 929. To refer to another oft-quoted passage from Beloit, supra, at page 295:
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?"
[37] With obviousness, the invention need not be disclosed in one single patent or piece of prior art, as is the case for anticipation. The Court is entitled to look at all the patents and other publications that a skilled technician would discover in a "reasonable and diligent search" to determine whether the resulting "mosaic" leads directly to the invention: Illinois Toolworks Inc. v. Cobra Fixations Cie. (2002), 221 F.T.R. 161, aff'd on this point, varied only with respect to costs: (2003), 312 N.R. 184 (F.C.A.).
[38] The critical date for assessing obviousness is the claimed date of the invention. The '080 patent claims priority from three Japanese patent applications. The respondent submits that the applicant has not led evidence to establish the date of invention; therefore, the relevant date for evaluating obviousness must be taken as being no earlier than the earliest possible priority date, one year prior to the Canadian patent application, June 20, 1985. The applicant conceded this at the hearing and I accept that this is the correct date in light of sections 28 and 29 of the Patent Act as it read prior to October 1, 1989.
[39] Further, in evaluating the prior art on the question of obviousness, such art must have been in the public domain. The applicant contends that only art that could be located in a "reasonably diligent search by a skilled workman" should be considered.
[40] The respondents Notice of Allegation dated December 20, 2002, cites 26 alleged prior art references with respect to obviousness including the '840 ofloxacin patent described above, the corresponding U.S. ofloxacin patent[2], U.S. and Japanese patents relating to other racemic compounds with antimicrobial properties and several academic articles and presentations, notably:
Repta et al., "Utilization of an Enantiomer as a Solution to a Pharmaceutical Problem:Application to Solobilization of a 1,2-Di(4-piperazine-2.6-dione) propane", J.Pharm.Sciences, Vol. 65(2), 238 (1976).
Gerster et al., "Proceedings of the North American Medicinal Chemistry Symposium", Toronto (Canada), 153 (1982.
Gerster et al., Poster Presentation to the North American Medicinal Chemistry Symposium, Toronto, Canada June, 1982.
[41] Counsel for Janssen takes issue with the fact that Novopharm has not established how the cited references were located or how any of the references would have been reasonably located without the benefit of hindsight. In particular, Janssen refers to the two 1982 Gerster references which one of its affiants, Dr. Hans Schroeder, could not locate in any Canadian library, despite about two days of searching. Since Novopharm has not put forward any evidence suggesting how these references could be or were obtained, the applicant argues that they are not valid prior art references.
[42] Novopharm maintains that the Gerster references were publicly available in 1982. Both relate to a paper Gerster presented at a 1982 Toronto four-day symposium sponsored by three major professional societies. One of these references was subsequently cited in the list of references in a 1985 article in the Journal of Antimicrobial Chemotherapy and also in the list of references of U.S. Patent No. 5,053,407.
[43] With respect to the remainder of the references cited by Novopharm, Janssen maintains that they do not disclose the beneficial properties of the S(-) optical isomer, since these were only ascertainable through separating the isomer from the racemate and performing multiple experiments with the S(-) and R(+) enantiomers and racemic ofloxacin. The applicant submits that it was only after the S(-) optical isomer was "made" and then experimentation performed, that the invention, that is levofloxacin as a separate compound having certain benefits, was discovered. This discovery has enough inventive ingenuity to demonstrate that the patent claims are not obvious.
[44] The applicant refers to an article written by Novopharm's expert, Dr. Caldwell, entitled "Putting Chirality to Work: The Strategy of Chiral Switches", wherein he recognized that in pairs of enantiomers in racemic mixtures it is uncertain which enantiomer is the "antagonist" or "active" one. Janssen stresses, relying on Bayer Aktiengesellschaft, supra that the test for obviousness does not involve testing or experimentation, but rather the mythical, skilled technician is expected to "instantly and spontaneously" know the answer which the patent teaches from the state of knowledge in the art at the date of invention.
[45] The respondent, also relying on Bayer Aktiengesellschaft, supra, submits that the applicants' interpretation of the test for obviousness is incorrect since the case law establishes that the notional person skilled in the art is entitled to carry out routine investigations including chemical analyses directed to merely determining characteristics of a known compound. Novopharm describes the tests done to determine the relative pharmacological characteristics of known enantiomers of racemic compounds as in the nature of "mere verification" of inherent, already known attributes of the compound, rather than in the nature of "searching for something novel". This "searching for something novel" must form part of the inventive process, as per Bayer Aktiengesellschaft, supra, and such inventiveness is lacking in the '080 patent.
[46] Novopharm refers to the Federal Court of Appeal decision of SmithKline Beecham Pharma Inc. v. Apotex Inc. (2002), 21 C.P.R. (4th) 129 (F.C.A.) where the prior art disclosed that the drug could be formulated by conventional methods, and that "mechanical skill" rather than inventive genius was required in order to arrive at the claims in the impugned patent; the "improvements" noted in the patent's disclosure merely verified the properties of a known substance formulated using common techniques.
[47] The '080 patent can be described as a "selection patent" in that levofloxacin was selected out of its class of substances - the racemate and the two enantiomers - because of its beneficial properties. The following passage from H.G. Fox in The Canadian Law and Practice Relating to Letters Patent for Inventions, 4th Ed., (Toronto: Carswell Company Ltd., 1969), pp.89-90, describes inventiveness in the context of selection patents:
Invention may be exercised by selecting one out of a number of substances for a particular purpose even though others of that class have been used before for the same purpose, provided there is a special advantage to be derived from the use of the selected substance and its selection constitutes a definite advance upon existing knowledge. While one who merely picks out a number of items from an already disclosed group or series has not invented anything, yet it may be otherwise if his researches have led him to the discovery that certain items in the group or series possess qualities or characteristics peculiar to themselves and hitherto unknown.
[Emphasis added]
[48] Novopharm relies on the following passage from Fox, supra at page 90:
Selection patents are more usually met with in the chemical, than in the other arts. If for practical purposes it is not obvious to skilled chemists in the state of chemical knowledge existing at the date of a selection patent that the selected components possess a special property, there is then, or at least there may be, a sufficient inventive step to support the patent. But mere verification is not invention. Where the method of manufacture is laid down in the originating patent, the selection patent must not be an exact reproduction of the same process coupled with a statement of the properties possessed by the selected bodies. No man can have a patent merely for ascertaining the properties of a known substance.
[Emphasis added]
[49] Novopharm submits that the '080 patent does not meet the requirements for a selection patent. Adopting Professor Fox's words, it argues that mere verification is not invention and that a selection patent must not reproduce the same process with a statement of the properties possessed by the selected bodies. Unlike the patent at issue in the case of Re E.I. DuPont Nemours & Co. Application, [1982] F.S.R. 303 (H.L.), the respondent asserts that the '080 patent does not make a discovery of a selected entity that has different valuable properties in a different field.
[50] Janssen's position is that section 32 of the Patent Act permits a patent based on improvements to any patented invention and there was such an inventive step in ascertaining that levofloxacin possesses special properties in comparison to the racemate, ofloxacin.
[51] What Fox and the jurisprudence suggest, in my view, when dealing with selection patents, is that in order to demonstrate sufficient inventive ingenuity, there must be discovered some special advantage or quality, previously unknown, or an advantage discovered for a new use, which constitutes a definite advance upon the knowledge already existing with regard to the original group or series. In Pfizer Canada Inc. v. Apotex Inc. (1997), 77 C.P.R. (3d) 547 (F.C.T.D.), Richard J. (as he then was), found a selection patent valid that claimed the pharmaceutical preparation of fluconazole, the originating patent having claimed "an enormous class of compounds".
[52] In that case, the compound described in the subsequent patent was not described in the original patent, and neither were "its superior and previously unknown efficacy" previously known. The Court there relied upon expert evidence that described the surprising features of fluconazole, and the discovery that it was soluble in water as compared to the earlier disclosed compound that was virtually insoluble. Justice Richard concluded that since fluconazole had "unexpected and valuable properties which are not possessed by the structurally closest compounds disclosed" in the original, prior patent, it was not invalid on the grounds of either obviousness or anticipation.
[53] In my view, in the case at hand, such reasoning is applicable, but to bring about the opposite result. The beneficial properties discovered and set out in the '080 patent were not unknown. They were the same beneficial properties found in ofloxacin, only to a greater degree of effectiveness. Further, I find that 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. This determination was made from one of three possibilities, not a great number of possibilities; that is, either the S (-) enantiomer, R (+) enantiomer or the racemate would exhibit better qualities, in comparison to each other, relating to the properties of antimicrobial activity, toxicity or solubility.
[54] With regard to Janssen's contention that if experimentation or testing is required in order to determine the invention, the resulting invention cannot be said to be obvious, I am persuaded by Novopharm's submission that the test for obviousness does not exclude routine testing to determine characteristics of known compounds, not undertaken for the purpose of "searching for something novel", but rather for the purpose of verifying the actual attributes of already known compounds, where the results indicate no new uses or surprising results, or properties that are clearly superior to the already known parent compound. Concerning the issue of determining whether there has been an inventive step or "undue experimentation" in the obviousness inquiry, see the reasoning of Justice Dawson of this Court in Pfizer Canada Inc. v. Apotex Inc. (2002), 22 C.P.R. (4th) 466 (F.C.T.D.) at paras 103-114.
[55] As noted above, the respondent relied upon several U.S. patents filed well prior to 1985 among the 26 references cited as prior art.
[56] U.S. Patent 3,917,609 disclosed tricylic fluorquinolone, an antibacterial compound, and indicated that one of the optically active isomers was much more active as an antibacterial agent. U.S. Patent 3,976,651 disclosed another tricylic fluorquinolone that had found one isomer to have more antimicrobial activity than the other. According to Dr. Caldwell, these are racemic compounds similar in structure to ofloxacin.
[57] Dr. Caldwell, at paragraphs 72-73 of his affidavit, refers to U.S. Patent 4,314,081, which states that with respect to the racemic compound in qu