Sanofi-Synthelabo Canada Inc. v. Apotex Inc.

Sanofi-Synthelabo Canada Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2005-03-21
Neutral citation
2005 FC 390
File numbers
T-668-03
Decision Content
Date: 20050321
Docket: T-668-03
Citation: 2005 FC 390
Ottawa, Ontario, the 21st day of March 2005
Present: THE HONOURABLE MR. JUSTICE SHORE
BETWEEN:
SANOFI-SYNTHELABO CANADA INC.
and SANOFI-SYNTHELABO
Applicants
and
APOTEX INC. and
THE MINISTER OF HEALTH
Respondents
REASONS FOR ORDER AND ORDER
INTRODUCTION
A window to the science
"We must all pledge ourselves to recovering accessible science as an honourable intellectual tradition. The rules are simple: no compromise with conceptual richness; no bypassing of ambiguity or ignorance; removal of jargon, of course, but no dumbing down of ideas."[1]
A window to the law
...obviousness is an attack on a patent based on its lack of inventiveness. The attacker, says, in effect, "Any fool could have done that." Anticipation, or lack of novelty, on the other hand, in effect assumes that there has been an invention but asserts that it has been disclosed to the public prior to the application for the patent. The charge is: "Your invention, though clever, was already known."
...
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?" [2] (Emphasis added.)
"...scientific findings are morally neutral; their use is not."[3]
A door to the science and the law
Striving for justice in each and every case, thus recognizing each with its respective separate multitude of variables, or that which is called clinical jurisprudence,[4] demands that a point-specific fact pattern be respected as it is different in its constituent parts from other fact patterns, in other cases. Thereby, analysis and assessment by a Court takes place to decide which law and which jurisprudence applies, and, furthermore, how it applies to a point-specific fact pattern. A smorgasbord of jurisprudence cannot, holus-bolus, be considered applicable to a point-specific fact pattern, other than simply for the legal tests involved, and no more, as the fact pattern distinctions of certain cases are so specific unto themselves, that they would obliterate the possibility of understanding a different point-specific fact pattern that has to be considered on its own distinct merits when applying the legal tests.
INDEX
INTRODUCTION
OVERVIEW
BACKGROUND
Nature of the proceedings
ISSUES
ANALYSIS
Burden of proof
The '777 patent
Laws of construction
Person skilled in the art
Construction of the '777 patent
The '875 patent
The witnesses
1. Infringement of the '777 patent
Legal principles
Application to the facts
Gillette defence
Conclusion
2. Invalidity of the '777 patent
a) Anticipation
Legal principles
Application to the facts
Conclusion
b) Obviousness
Legal principles
Application to the facts
Conclusion
3. Double patenting
CONCLUSION
OVERVIEW
[1] This application was brought under section 6 of the Patented Medicines (Notice of Compliance) Regulations[5](Regulations) in response to a Notice of Allegation (NOA) sent by Respondent, Apotex Inc. (Apotex). The Notice of Allegation was sent as part of Apotex' attempt to market a generic version of the Applicants, Sanofi-Synthelabo Canada Inc. and Sanofi-Synthelabo (Sanofi), clopidogrel bisulfate tablets, which are commercially referred to as PLAVIX. In these proceedings, Sanofi seeks an order prohibiting the Minister of Health (Minister) from issuing a Notice of Compliance (NOC) with section C.08.004 of the Food and Drug Regulations[6] to Apotex for its 75 mg clopidogrel bisulfate tablets until the expiry of Sanofi's Canadian Letters Patent No. 1,336,777 ('777 patent) in 2012. A NOC entitles an entity to put its product on the market.
[2] The '777 patent, one of whose inventors is Alain Badorc, discloses and claims compositions of matter, namely the compound clopidogrel, certain salts of clopidogrel (including specifically clopidogrel bisulfate) and pharmaceutical preparations containing clopidogrel and its salts. When formulated in a pharmaceutical composition, clopidogrel is an inhibitor of blood platelet aggregation.
[3] The issues in this case are whether Apotex' allegations of non-infringement of the
'777 patent and invalidity of claims 1, 3, 10 and 11 of the '777 patent on the basis of anticipation, obviousness and double patenting are justified. Apotex' invalidity argument is based on its affirmation that the compositions of clopidogrel contained in Sanofi's '777 patent were already disclosed and claimed as inventions in the prior art, namely Sanofi's Canadian Letters Patent No. 1,194,875 ('875 patent), its American and French equivalents (United States Patent No. 4,529,596 and French Patent No. 82 12599) and a number of other prior art references.
BACKGROUND
Nature of the proceedings
[4] Apotex served Sanofi a NOA, which determines the scope of the issues to be decided in this case. Sanofi, as the Applicant, must prove that Apotex' allegations to the effect that the latter will not infringe a valid patent are not justified. The proceedings under the Regulations neither serve to determine validity nor infringement. The aim is to determine whether the Minister is free to issue the requested NOC.
[5] Subsections 6(1) and 6(2) of the Regulations provide:
6. (1) A first person may, within 45 days after being served with a notice of an allegation pursuant to paragraph 5(3)(b) or (c), apply to a court for an order prohibiting the Minister from issuing a notice of compliance until after the expiration of a patent that is the subject of the allegation.
(2) The court shall make an order pursuant to subsection (1) in respect of a patent that is the subject of one or more allegations if it finds that none of those allegations is justified. (Emphasis added.)
6. (1) La première personne peut, dans les 45 jours après avoir reçu signification d'un avis d'allégation aux termes des alinéas 5(3)b) ou c), demander au tribunal de rendre une ordonnance interdisant au ministre de délivrer un avis de
conformité avant l'expiration du brevet visé par
l'allégation.
(2) Le tribunal rend une ordonnance en vertu du paragraphe (1) à l'égard du brevet visé par une ou plusieurs allégations si elle conclut qu'aucune des allégations n'est fondée. (La Cour souligne.)
ISSUES
[6] The ultimate question for the Court to determine is whether it should grant an order prohibiting the Minister from issuing Apotex a NOC until after the expiration of Sanofi's '777 patent.
[7] For the above determination to be made, the following questions must be answered.
1. Would Apotex' marketing of its 75 mg clopidogrel bisulfate tablets infringe claims 1, 3, 10 or 11 of Sanofi's '777 patent?
2. If infringement is the case, are the infringed claim(s) invalid
(a) by reason of anticipation by the prior art?
(b) by reason of obviousness in light of the prior art?
3. Is the '777 patent invalid because of double patenting?
[8] Justice Harrington's comments in Biovail Pharmaceuticals Inc. v. Canada (Minister of National Health and Welfare)[7] describe potential consequences dependent on the findings:
... it is inherent in a decision to grant a prohibition order that the Court form the view that Novopharm's [Apotex] allegations are not justified, i.e. the Court must form the view that the patents are valid and that Novopharm [Apotex] would infringe them. There must be a finding on both points. However, if the Court refuses to grant a prohibition order, it must have formed the view that Novopharm [Apotex] would not infringe or that the patents are invalid. It is not necessary to find on both points.
ANALYSIS
Burden of proof
[9] In order to address the issues, it is necessary for the Court to envisage the burden of proof. The Applicant must demonstrate, on a balance of probabilities, that the Respondent's allegations of non-infringement and invalidity of the '777 patent are not justified. The Applicant has the overall legal burden of proof. Nevertheless, the Respondent, as the entity which had made its allegations in the NOA, has the obligation to put these "in play", i.e. to ensure that there is sufficient evidence of these allegations by which to present issues for examination (Eli Lilly & Co. v. Nu-Pharm Inc. (C.A.)[8] ).
[10] With respect to the allegation of non-infringement, a presumption exists that the facts relating to non-infringement in the NOA are true except to the extent that the contrary is shown by the Applicant (Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare)[9]).
[11] There has been some debate relating to the burden of proof with regard to the allegation of patent invalidity. A line of thought now establishes that, while the overall burden is on the Applicant to prove that the allegation is not justified and taking into consideration that the latter is entitled to rely upon the statutory presumption of patent validity[10], the evidentiary burden rests with the Respondent to provide evidence strong enough to prove that the patent is invalid (Bayer Inc. v. Canada (Minister of National Health and Welfare)[11], Hoffmann-La Roche Ltd. v. Canada (Minister of National Health and Welfare)[12], Bayer AG v. Apotex Inc.[13], AB Hassle v. Apotex Inc.[14], Procter & Gamble Pharmaceuticals Canada Inc. v. Canada (Minister of Health)[15]). Sanofi argues that, in addition to rebutting the statutory presumption of validity, the Respondent must also show that the Commissioner of Patents erred in allowing the '777 patent. The Court finds this argument not to be directly pertinent as these proceedings are not in the form of an action wherein the Commissioner of Patents's decision is under attack; rather, the Court has to decide whether an order prohibiting the Minister of Health from issuing a NOC should be granted. In other words, the Court could be said to be reviewing a proposed Minister's decision to issue a NOC.
The '777 patent
Laws of construction
[12] The determination of infringement and validity is a two-step process. First, the claims of the '777 patent must be construed. Second, Apotex' allegations of non-infringement and invalidity must be considered.
[13] The principles of patent construction, as summarized by Justice Harrington in Biovail, at para. 15, from the Supreme Court of Canada's decisions in Free World Trust v. Électro-Santé Inc.[16] and Whirlpool Corp. v. Camco Inc.[17] serve as guide posts:
1. A patent is construed as a bargain between the inventor and the public. In consideration of disclosing the invention, the inventor is given a temporary monopoly to exploit it.
2. It is a statutory requirement that the patent contain a specification and end with a claim or claims "defining distinctly and in explicit terms the subject-matter of the invention for which an exclusive privilege or property is claimed". The specification must be sufficiently full, clear, concise and exact "as to enable any person skilled in the art or science to which it pertains, or to which it is most closely connected, to make, construct, compound or use it". (Patent Act, R.S.C. 1985, c. P-4, as amended, s. 27)
3. The patent is notionally addressed to a person skilled in the art or science of the subject-matter and is to be read as such a person would have read it when it first became public. (More will be said about this skilled reader.)
4. The claims are to be read in an informed and purposive way to permit fairness and predictability and to define the limits of the monopoly "[I]ngenuity of the patent lies not in the identification of the desired result but in teaching one particular means to achieve it. The claims cannot be stretched to allow the patentee to monopolize anything that achieves the desired result" (Free World Trust, paras. 31, 32).
5. The claim portion of the patent specification takes precedence over the disclosure portion in the sense that the disclosure is read to understand what was meant by a word in the claims "but not to enlarge or contract the scope of the claim as written and thus understood" (Whirlpool, para. 52).
6. It is only such novel features that the inventor claims to be essential that constitute the "pith and marrow" of the claim. "The key to purposive construction is therefore the identification by the Court with the assistance of the skilled reader, of the particular words or phrases in the claims that describe what the inventor considered to be the "essential" elements of his invention" (Whirlpool, para. 45). (Emphasis added.)
Person skilled in the art
[14] The Court will reproduce Justice Harrington's description in Biovail[18] of the person skilled in the art:
He or she is an ordinary workman, skilled in the subject matter taught by the invention. Although not a dullard, but lacking in imagination, he nevertheless keeps up with the literature and is skilled in reading a patent, not only within the context of its subject matter, but also as a legal document. He reads patents in this and other jurisdictions as if he read them the day they were first made public, casting aside all he has learned since then.
[15] The Supreme Court of Canada described the person skilled in the art as follows in Free World[19]:
The patent is not addressed to an ordinary member of the public, but to a worker skilled in the art described by Dr. Fox as
a hypothetical person possessing the ordinary skill and knowledge of the particular art to which the invention relates, and a mind willing to understand a specification that is addressed to him...
[16] In Whirlpool[20], the Supreme Court of Canada added:
The patent claims were not addressed by Whirlpool's research engineers to their colleagues in Whirlpool's product development group. The patent claims were necessarily addressed to the wider world of individuals with ordinary skills in the technology of clothes washing machines. As Aldous L.J. observed in Beloit Technologies Inc. v. Valmet Paper Machinery Inc., [1997] R.P.C. 489 (Eng. C.A.), at p. 494:
The notional skilled addressee is the ordinary man who may not have the advantages that some employees of large companies may have. The information in a patent specification is addressed to such a man and must contain sufficient details for him to understand and apply the invention. It will only lack an inventive step if it is obvious to such a man.
Dickson J. placed the same emphasis on "ordinariness" in Consolboard, supra, at p. 523:
The persons to whom the specification is addressed are "ordinary workmen", ordinarily skilled in the art to which the invention relates and possessing the ordinary amount of knowledge incidental to that particular trade. The true interpretation of the patent is to be arrived at by a consideration of what a competent workman reading the specification at its date would have understood it to have disclosed and claimed.
"Ordinariness" will, of course, vary with the subject matter of the patent.
(Emphasis added.)
[17] The Court is of the view that an ordinary person, as defined in Whirlpool, can make an extraordinary discovery.
[18] According to Apotex, the skilled person to whom the '777 patent is addressed is a notional individual who has a master's degree in organic chemistry, is experienced in separating enantiomers from racemates, is experienced in the selection of salt forms of active ingredients for use in pharmaceutical products, is familiar with the manufacture of dosage formulations and is familiar with pharmacological and toxicological issues as would arise in selecting an active ingredient for inclusion in a drug formulation. The skilled person already possessed very detailed and extensive knowledge about the subject of the '777 patent.
[19] According to Sanofi, the person skilled in the art in this case is a technician who can hold a degree in chemistry, pharmacy or some related field and who possesses experience in synthesizing, preparing and investigating pharmaceutically active compounds. This person is also aware of common and conventional methods known in the art of chemistry at a given time and is competent in carrying out such methods.
[20] It is important to recognize that the above-quoted decisions of the Supreme Court of Canada do not allow for descriptions of a person skilled in the art to fit one party's needs over that of another.
Construction of the '777 patent
[21] The '777 patent relates to the invention of the dextro-rotatory isomer of the racemate. A "racemate" is a substance containing equal amounts of two "optical isomers" (also referred to as "enantiomers" and used interchangeably in these reasons). The term "racemate" in these reasons refers specifically to the methyl alpha-5 (4, 5, 6 , 7-tetrahydro (3, 2-c) thieno pyridyl) (2-chlorophenyl)-acetate compound. "Stereoisomers" are compounds that have the same molecular formula but whose atoms are oriented differently in space. Their optical activity refers to their ability to rotate the plane of polarized light. The "dextro-rotatory isomer" rotates the plane of polarized light to the right or in a clockwise direction and is represented by (+), d or "dextro". The dextro-rotatory isomer of the racemate in this case is commonly referred to as "clopidogrel"; both terms are therefore used interchangeably in these reasons. The "levo-rotatory isomer" rotates the plane of polarized light to the left or in a counter-clockwise direction and is represented by (-) , l or "levo". A description that does not include the stereochemistry of a compound, i.e. which does not indicate a (+) or a (-), informs a chemist that it is a racemate and not one of its optical isomers. For the reader's convenience, a glossary is attached as Appendix 1 to these reasons.
[22] The dextro-rotatory isomer of the racemate has beneficial properties over both the racemate and the levo-rotatory isomer. Specifically, the advantages described at page 1 of the '777 patent include that the dextro-rotatory isomer contains the platelet aggregation inhibiting activity and is better tolerated (i.e. less toxic):
In an unexpected manner only the dextro-rotatory enantiomer Id exhibits a platelet aggregation inhibiting activity, the levo-rotatory enantiomer Ii being inactive. Moreover, the inactive levo-rotatory enantiomer Ii is the less well tolerated of the two enantiomers.
[23] The '777 patent also relates to the invention of the bisulfate salt of the dextro-rotatory isomer. "Bisulfate salt" is sometimes called "hydrogen sulfate". The dextro-rotatory isomer in a free base form (i.e. not as a salt) exists as an oil. The '777 patent reveals the following information. Oily products are usually difficult to purify and it is preferable to use products which can be purified by crystallization for the preparation of pharmaceutical compositions. Many of the salts of the dextro-rotatory isomer precipitated in an amorphous form and/or were hygroscopic, a property which makes them difficult to handle on an industrial scale. Many of the salts classically used in pharmacy proved to be difficult to purify. The '777 patent states that, of the many salts its inventors tried, only the bisulfate, hydrobromide and taurocholate salts crystallized easily, were not hygroscopic and were sufficiently water soluble to make their use as active medicinal principles particularly advantageous. The bisulfate salt was perfectly stable and useable in a pharmaceutical formulation.
[24] The '777 patent contains eleven claims. Apotex' NOA alleged that claims 6, 7, 8 and 9 of the '777 patent, being process claims, are not relevant to these proceedings. These latter claims describe how to separate the racemate into its isomers, using a technique which consists in forming the diastereomeric salts of the racemate and performing a fractional crystallization. Apotex also alleged that claims 2, 4 and 5 of the '777 patent are not at stake in these proceedings as they claim salts of clopidogrel that Apotex does not intend to use.
[25] The construction of the impugned claims, i.e. claims 1, 3, 10 and 11, is not contentious. They read as follows:
1. Dextro-rotatory isomer of methyl alpha-5 (4, 5, 6 , 7-tetrahydro (3, 2-c) thieno pyridyl) (2-chlorophenyl)-acetate and its pharmaceutically acceptable salts.
3. Hydrogen sulfate of the dextro-rotatory isomer of methyl alpha-5 (4, 5, 6, 7-tetrahydro (3, 2-c) thieno pyridyl) (2-chlorophenyl)-acetate.
10. A pharmaceutical composition comprising an effective amount of a compound according to claim 1, as active ingredient, in admixture with a pharmaceutically acceptable carrier.
11. Composition according to claim 10, comprising unit doses containing from 0.001 g to 0.100 g of active ingredient.
[26] Claim 1, therefore, claims the free base of clopidogrel (dextro-rotatory isomer of the racemate) as well as its pharmaceutically acceptable salts. Claim 3, on the other hand, only claims the bisulfate salt of clopidogrel. It follows that claim 10 claims a pharmaceutical composition which contains the free base of clopidogrel or a pharmaceutically acceptable salt and claim 11 claims a composition where the amount of the active ingredient is in a range of 0.001 g to 0.100 g.
The '875 patent
[27] The '875 patent and its American and French equivalents are the principal prior art references relied upon by Apotex in its NOA for anticipation, obviousness and double patenting. The '875 patent expired in 2002. For simplicity purposes, reference will only be made to the latter patent.
[28] The general teaching of the '875 patent discloses that a class of compounds are useful in providing platelet aggregation inhibiting activity. The '875 patent discloses a number of possible alternatives which, when added up, totals more than 250,000 possible different compounds but only 21 individual compounds are specifically identified (i.e. Derivatives 1-21). These 21 compounds are set out in the examples to the '875 patent. Example 1 at page 3 deals with Derivative No. 1:
Methyl %-[4,5,6,7-tetrahydro-thieno[3,2-c]-5-pyridyl]-o.chlorophenylacetate (R=-CH3; X=2-Cl) derivative No. 1
This is the racemate from which the separated isomers were obtained in the '777 patent.
[29] The '875 patent recognizes that the compounds have a chiral center (i.e. a carbon atom that is bound to four different atoms or groups of atoms) and therefore can exist as racemates or isomers. The passages of the '875 patent stating the existence of isomers directly or by reference to other claims are the following:
"These compounds include an asymmetrical carbon which may exist in the form of 2 enantiomers. The invention also concerns each of the enantiomers and their mixture [racemate]." (page 1)
"The invention concerns a process for the preparation of derivatives of general formula (I): ... as well as the 2 enantiomers or their mixture [racemate]." (page 18)
Claim 1 "A process for the preparation of derivatives of general formula (I): ... as well as the 2 enantiomers or their mixture [racemate] of these compounds of formula (I); wherein: ... if desired, its enantiomers are separated and/or it is salified by mineral or organic acid action; ..." (page 14)
Claim 8 "Process according to claim 1 for the preparation of methyl %-[4,5,6,7-tetrahydro-thieno[3,2-c]-5-pyridyl]-o.chlorophenylacetate, wherein the 4,5,6,7-tetrahydro thieno[3,2-c]pyridine is condensed over the methyl 2-chloro-o.chlorophenylacetate, and the derivative sought, which is isolated, is obtained." (page 15)
Claim 14 "Derivatives of general formula (I): ... as well as the 2 enantiomers or their mixture of these compounds of formula (I)...
Claim 15 "Methyl %-[4,5,6,7-tetrahydro-thieno[3,2-c]-5-pyridyl]-o.chlorophenylacetate, each time it is obtained by the process of claim 8 or its manifest chemical equivalents." (page 16) (Emphasis added.)
Nevertheless, there is no teaching in the '875 patent on how to separate the racemates into their isomers. Following the teachings of the examples in the '875 patent, one would only obtain racemates, never their isomers.
[30] There is also no teaching on any separated isomer, i.e. no mention or suggestion that there are any pharmaceutical or toxicological differences between the isomers of the disclosed racemates with respect to activity or tolerability. The '875 patent only discloses that the racemate has inhibiting properties on platelet aggregation and possesses low toxicity.
[31] Derivative No. 1 is the hydrochloride salt of the racemate. Following Derivative No. 1 would only result in a racemate and not an isolated isomer and would only yield the hydrochloride salt of the racemate not its bisulfate salt. The bisulfate salt is indeed used in four of the twenty-one examples given in the '875 patent, but in neither of these four examples is it used in combination with the racemate, let alone with its dextro-rotatory isomer.
The witnesses
[32] As the qualifications of the experts and their expertise in the subject matter are not contested, a brief description of both parties' experts is provided. A summary of the experts' opinion evidence in respect of specific issues follows in chronological order:
[33] The Sanofi witnesses consisted of a fact witness, Alain Badorc, and an outside expert, Dr. Alexander Klibanov.
[34] Mr. Badorc is one of the inventors of the '777 patent. He has been employed by Sanofi since 1972. He obtained a "Diplôme Universitaire de Technologie" (DUT) in chemistry in 1972 from the Université de Rennes in France. From 1982 to 1992, he spent approximately half of his time working on the class of compounds known as thienopyridines, the class of compounds at stake here. His testimony provided the background as to how the invention of the '777 patent came about. He explained the different separation techniques he had tried before finding a successful technique to obtain the separated dextro-rotatory isomer. He also provided a timeline of his endeavours.
[35] Professor Klibanov is a Professor from the Massachusetts Institute of Technology. His evidence explained that the bisulfate clopidogrel tablets that Apotex proposes to market are encompassed in the '777 patent. He stated that the '875 patent only shows how to obtain racemates and does not teach how to separate them into their isomers. According to him, the separation of isomers had always been a straightforward procedure, especially in the mid-1980s. Even if the separation could eventually be arrived at using conventional separation techniques, it was impossible to predict whether a specific technique would result in the successful separation of the racemate into its isomers without first trying the different separation techniques. There is also no suggestion in the '875 patent that any separated isomer, let alone the dextro-rotatory isomer of the racemate, has greater activity and/or lower toxicity than the other isomer. According to Dr. Klibanov, it was only through experimentation that the properties of a separated isomer could have been determined. The benefits of using the bisulfate salt (as opposed to other salts) in combination with the dextro-rotatory isomer could only have been discovered after the salt was synthesized, isolated and tested to determine its properties.
[36] Apotex put forward six witnesses: Mr. Samuel Tekie, who put into evidence the prior art references, as well as five outside experts, Dr. Robert S. Brown, Dr. Peter J. Stang, Dr. Robert Allan McClelland, Dr. Gilbert Stephen Banker and Dr. Robert Samuel Langer.
[37] Dr. Brown is a Professor of Chemistry at Queen's University. Dr. Stang is a Professor of Chemistry at the University of Utah. They commented on methods of racemate separation. Essentially, their evidence was that, while there were a number of standard techniques that could be used to separate a racemate into its isomers, one would not know which technique would, in fact, be successful before trying these different standard techniques.
[38] Dr. McClelland, one of Apotex' lead experts, is a Professor of Chemistry at the University of Toronto. His evidence was that the '875 patent provides clear directions on how to obtain isomers given that the patent states that "the derivative sought is obtained, which is isolated, and if desired, its enantiomers are separated" and that, at the relevant time, the person skilled in the art knew how to separate a racemate into its isomers using conventional methods. According to Dr. McClelland, the '875 patent also contains clear directions to the bisulfate salt of the dextro-rotatory isomer as the bisulfate salt is one of the preferred salts in that patent - of the eight examples of esters of formula (I) (the racemate being an ester), four of the examples use the bisulfate salt. Dr. McClelland also indicated that, at the relevant time, it was commonly known in the art that when a racemate displayed biological activity, that activity often resided more in one isomer than in the other. It was also commonly known in the art that the less active or inactive isomer could have greater toxicity. The person skilled in the art, as part of his or her common practice, would have tested the isomers, using routine conventional methods to evaluate their respective properties. He confirmed that the advantages associated with a particular isomer are unpredictable and can only be ascertained by carrying out suitable experiments, which require first to separate the racemate into its isomers and then to compare their respective properties with those of the racemate.
[39] Dr. Banker is Dean Emeritus and Distinguished Professor Emeritus at the College of Pharmacy, University of Iowa. Dr. Langer is a Professor of Chemical and Biomedical Engineering at the Massachusetts Institute of Technology. They approached the issue of obviousness from the view that one could carry out routine experiments. Their evidence was that the separation of the racemate into its isomers, the testing of the isomers to discover their properties and the testing of salts to find the most advantageous one, would eventually be arrived at using well-known separation and testing methods.
1. Infringement of the '777 patent
Legal principles
[40] If the impugned device takes all of the essential elements of the invention, that constitutes infringement (Free World). If an essential element is different or omitted, that does not then constitute infringement (Free World).
Application to the facts
[41] Apotex' product would clearly infringe the '777 patent. To demonstrate such infringement, it is only necessary to review claim 3 of the '777 patent. It reads:
3. Hydrogen sulfate of the dextro-rotatory isomer of methyl alpha-5 (4, 5, 6, 7-tetrahydro (3, 2-c) thieno pyridyl) (2-chlorophenyl)-acetate.
Claim 3 of the '777 patent specifically claims the hygrogen sulfate (which is also called bisulfate salt) of the dextro-rotatory isomer. Apotex stated in its NOA that it proposes to sell the bisulfate salt of the dextro-rotatory isomer. At page 1 of its NOA, Apotex states:
Apotex has filed a Submission for a Notice of Compliance with the Minister of Health for a tablet for oral administration comprising clopidogrel bisulphate in a dosage amount of 75 mg for inhibiting Platelet Aggregation.
Therefore, Apotex would clearly infringe claim 3.
[42] In addition, claim 1 claims the dextro-rotatory isomer and its pharmaceutically acceptable salts, which necessarily include the bisulfate salt. Thus, Apotex would also infringe claim 1 of the '777 patent. In his affidavit, Dr. Klibanov confirms that Apotex would indeed infringe claim 1.
[43] Claims 10 and 11 of the '777 patent claim inter alia pharmaceutical compositions contain salts of the dextro-rotatory isomer as the active ingredient with a pharmaceutically acceptable carrier in a dose of strength of 1 to 100 milligrams (0.001 to 0.100 grams). Apotex stated in its NOA that it would be selling tablets containing 75 milligrams of the active ingredient (the bisulfate salt of the dextro-rotatory isomer). Apotex tablets would necessarily contain a pharmaceutically acceptable carrier and, therefore, Apotex would also infringe claims 10 and 11 of the '777 patent.
[44] At paragraphs 29 and 30 of his affidavit, Dr. Klibanov confirmed that claims 1, 3, 10 and 11 of the '777 patent would indeed be infringed for the above-mentioned reasons.
Gillette defence
[45] Apotex argues that claims 1, 3, 10 and 11 of the '777 patent would not be infringed by marketing its 75 mg clopidogrel bisulfate by virtue of the "Gillette defence". It is recalled that claims 6, 7, 8 and 9 of the '777 patent, being process claims, are not relevant to these proceedings, and that claims 2, 4 and 5 of the '777 patent are not at stake, as they claim salts of clopidogrel that Apotex does not intend to use.
[46] In Almecon Industries Ltd. v. Nutron Manufacturing Ltd.[21], Justice Wetston described the Gillette defence as follows:
... if the product which is allegedly infringing cannot be distinguished from prior art, and it falls within the claims of the patent in suit, then the patent is invalid for anticipation or obviousness. On the other hand, if the patent does not include the alleged infringing product, there is no patent infringement: Gillette Safety Razor Company v. Anglo Trading Company Ltd., [1913] 30 R.P.C. 465, at page 480. Thus, the defendant contends that it must succeed on either invalidity or non-infringement.
[47] A common law defence created by the House of Lords in 1913, the Gillette defence allows a defendant to deny both the infringement and the validity of the patent and thus "spare himself the trouble of demonstrating on which horn of the well known dilemma the plaintiff has impaled himself, invalidity or infringement" (Gillette Safety Razor Company v. Anglo-American Trading Company Ld.[22]).
[48] The Court notes that, in its NOA, which is the all-important document in this regard, Apotex does not allege that it will not infringe claims 1, 3, 10 and 11 of the '777 patent. Rather, Apotex alleges that these claims are invalid if they are asserted to be infringed. Pages 4 and 5 of Apotex' NOA state the following:
Non-Infringement
Apotex' manufacture, use and sale of the bisulfate salt (also known as the hydrogen sulfate salt) of the d-Enantiomer will not infringe claims 2, 4, and 5 of the '777 Patent since these claims are restricted to the hydrochloride, hydrobromide and taurocholate salts of the d-Enantiomer respectively.
Gillette Defence
Further, if you assert that any of the claims of the '777 Patent are infringed by our manufacture and use of our formulation containing the bisulphate salt of the d-rotatory enantiomer of methyl %-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate used by Apotex, then we allege that the claims asserted to be infringed must be invalid in accordance with the principles set out in the decision of the House of Lords in Gillette Safety Razor Company v. Anglo-American Trading Company Ltd., (1913) R.P.C. 465, and the decision of J.K. Smit & Sons, Inc. v. Richard S. McClintock [1940], SCR 279.
Apotex's 75mg tablet is in accordance with the prior art as disclosed by the teachings of Canadian Patent No. 1,194,875, published on its issue date of October 8, 1985. Further, the use of such a product to inhibit action on blood platelet aggregation and for use in anti-thrombotic activity is also in accordance with the teachings disclosed within Canadian Patent No. 1,194,875. (Emphasis added.)
[49] The Gillette defence arises only where there is a defence of non-infringement coupled with an allegation of invalidity. As there is no allegation of non-infringement, the Gillette defence cannot be invoked and need not be analyzed. In essence, the defence raised by Apotex is simply another way of making its allegation of invalidity.
Conclusion
[50] The Court concludes that Apotex' 75 mg clopidogrel bisulfate tablets would infringe Sanofi's '777 patent, i.e. that Apotex' product is the same product as that protected by the '777 patent.
2. Invalidity of the '777 patent
[51] The basis for Apotex' assertion that the '777 patent is invalid, is based on that which is claimed in the '777 patent: that it was not new and/or obvious in light of the disclosure in the '875 patent (and other similar patents).
[52] In considering the validity of a patent, the statute in force at the date of application must be taken into account. The '777 patent was filed prior to the amendments to the Patent Act, R.S.C. 1985, c. P-4 in 1989 and is, therefore, considered as an "Old Act" patent. Consequently, determinations concerning validity are governed by the Patent Act, R.S.C. 1985, c. P-4 (Old Act).
a) Anticipation
Legal principles
[53] Under the Old Act, an anticipatory prior art reference must have described the subject matter of a particular claim of the '777 patent as of February 8, 1986, this date being two years prior to the filing date of the '777 patent in Canada on February 8, 1988.
[54] Subsection 27(1) of the Old Act reads:
27 (1) Subject to this section, any inventor or 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 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.
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.
[55] Anticipation means that the exact invention had already been made and publicly disclosed. The test for anticipation was described in Beloit and adopted by the Supreme Court of Canada in Free World:
One must, in effect, be able to look at a prior, single publication and find in it all the information which, for practical purposes, is needed to produce the claimed invention without the exercise of any inventive skill. The prior publication must contain so clear a direction that a skilled person reading and following it would in every case and without possibility of error be led to the claimed invention. (Emphasis added.)
The choice of the phrase "in every case and without possibility of error" is an important choice of words. The mere possibility that one could be within the claim is not, in and of itself, sufficient for anticipation. The UK Court of Appeal stated this as follows in General Tire & Rubber Co. v. Firestone Tyre & Rubber Co.[23]:
If, on the other hand, the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee' s claim, but would be at least as likely to be carried out in a way which would not do so, the patentee's claim wil