Sanofi-Synthelabo Canada Inc. v. Apotex Inc., 2005 FC 390

Date: 20050321

Docket: T-668-03

Citation: 2005 FC 390

Ottawa, Ontario, the 21^st 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:

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 I_d exhibits a platelet aggregation inhibiting activity, the levo-rotatory enantiomer I_i being inactive. Moreover, the inactive levo-rotatory enantiomer I_i 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:

[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 will not have been anticipated, although it may fail on the ground of obviousness. To anticipate the patentee's claim, the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented. (Emphasis added.)

The Court notes that the Supreme Court of Canada quoted with approval from General Tire on the issue of anticipation in Free World^[24]:

A signpost, however clear, upon the road to the patentee's invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee.

In Xerox of Canada Ltd. v. IBM Canada Ltd.^[25], Justice Collier cited The King v. Uhlemann Optical Co.^[26]:

...The whole invention must be shown to have been published with all the directions necessary to instruct the public how to put it into practice.

As was decided by this Court in Pfizer Canada Inc. v. Apotex Inc.^[27], a claim to a specific chemical compound cannot be anticipated by a prior art reference which only teaches a broad class or genus of compounds into which the compound falls because the prior art reference does not give directions which inevitably result in the specific compound.

[56]            With respect to the identification of specific beneficial properties in a particular compound selected from a more general class of compounds, Fox in Canadian Law and Practice (4^th edition) at pages 89-90 states the following:

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. (Citations omitted and emphasis added.)

In Re E.I. Du Pont Nemours & Co. Application^[28], the House of Lords, in regard to newly identified beneficial properties, held:

The law regarding selection patents has been developed to deal with this problem... The present position was compendiously stated by Lord Diplock:

... The inventive step in a selection patent lies in the discovery that one or more members of a previously known class of products possess some special advantage for a particular purpose, which could not be predicted before the discovery was made... The quid pro quo for the monopoly granted to the inventor is the public disclosure by him in his specification of the special advantages that the selected members of the class possess. (Beecham Group v. Bristol Laboratories International S.A. [1978] R.P.C. 521 at 579). (Emphasis added.)

In Pfizer^[29], this Court stated the following:

The ICI Patent [the prior art] is an originating patent while the Pfizer Patent is a selection Patent. The former claims the genus; the second claims the species. ICI's '263 Patent is directed generally to fungicidal triazoles and imidazoles. Fluconazole is not specifically described and neither were its superior and previously unknown efficacy described or known. The ICI Patent did not include the fluconazole compound. ICI was not the first inventor of this compound and never made it.

It is not disputed that fluconazole is encompassed within the broad generic scope of the claims of the ICI Patent and likewise with respect to the processes, but is not specifically identified therein. (Emphasis added.)

Application to the facts

[57]            Based on the law, the question before the Court is whether a person skilled in the art was given such a clear direction that, by reading and following the '875 patent (or its U.S. or French equivalents) would in every case and without possibility of error make a compound or pharmaceutical composition within the claims of the '777 patent (e.g. the bisulfate salt of clopidogrel).

[58]            Further to the Court's analysis as to whether the dextro-rotatory isomer of the racemate and its bisulfate salt were specifically disclosed in the prior art, it considered whether the prior art gave clear instructions by which to obtain in every case a separated dextro-rotatory isomer of the racemate; the Court then completed its analysis as to whether the prior art disclosed the beneficial properties of the dextro-rotatory isomer of the racemate and of its bisulcate salt.

[59]            Turning first to the issue of specific disclosure of the dextro-rotatory isomer of the racemate, the most that can be said about the '875 patent is that it discloses the existence of optical isomers as part of a large class of compounds, as can be seen from some extracts taken from the '875 patent:

"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) (Emphasis added.)

But nowhere in the '875 patent is there a disclosure of any specific optical isomer, which means there is certainly no specific disclosure of the dextro-rotatory isomer of the racemate nor of the bisulcate salt of the dextro-rotatory isomer. The Pfizer decision is a good example of this principle. In that case, the prior art taught and claimed a genus. The prior art patent was not found to be an anticipation of the specific compound called fluconazole as one could follow the prior art and yet, not be able to make fluconazole; had the right selection been made, one would have been able to make this compound. The Court is of the view, contrary to Apotex, that the principle set out in the Pfizer decision, was not invalidated by the Federal Court of Appeal in SmithKline Beecham Pharma Inc. v. Apotex Inc. (C.A.)^[30]. At paragraphs 18 and 19, the Federal Court of Appeal stated:

...SmithKline refers to Pfizer, supra, Farbwerke Hoechst v. Halocarbon (Ontario) Ltd., [1979] 2 S.C.R. 929">[1979] 2 S.C.R. 929, at page 942; and General Tire & Rubber Co. v. Firestone Tyre & Rubber Co., [1972] R.P.C. 457 (C.A.). SmithKline argues that those cases stand for the proposition that a prior art does not anticipate a later invention if the instructions provided by the prior art could bring about a product that is outside the claims of the later invention...

... The cases referred to by SmithKline are distinguishable from the situation before this Court. In each of the cases cited by SmithKline, the instructions of the prior art set out a general class of compounds or reactions from which one could arrive at the later invention. The later inventions were not anticipated in those cases because the particular compounds in the claimed invention were not identified in the prior art and, therefore, the identification of the particular compounds used in the claimed invention was novel and inventive. (Emphasis added.)

The Federal Court of Appeal merely stated that the facts in the SmithKline case were distinguishable from those in the Pfizer, Farbwerke Hoechst AG Vormals Meister Lucius & Bruning v. Halocarbon (Ontario) Ltd.^[31] and General Tire decisions. The Court reaffirmed the principle that a prior art patent, that does not identify a specific compound of a broad generic class of compounds, is not anticipated.

[60]            With respect to whether the prior art gave clear instructions to obtain, in every case and without possibility of error, a separated dextro-rotatory isomer of the racemate, the Court notes a key finding from the evidence: the experts of both parties agree that the '875 patent contains no teaching on how to separate the disclosed racemates into their optical isomers and that following the teachings of the examples in the '875 patent, one would only obtain a racemate, never an optical isomer.^[32] This fact, in itself, is sufficient to conclude that the '777 patent was not anticipated by the '875 patent.

[61]            According to Apotex, the mention in claim 1 of the '875 patent that "if desired, its enantiomers are separated" is sufficient to instruct the skilled person in the art to separate the racemate into its isomers, any work needed to make the separation was purely routine - the separation techniques being well-known to skilled persons at the relevant time - and a skilled person could, with experimentation, eventually obtain the isomers. Apotex' legal premise, based on the Federal Court of Appeal's decision in SmithKline is that the skilled person's ability to exercise his or her mechanical skill under the anticipation test, includes the ability to perform tests.

[62]            Apotex also argues that Sanofi's assertion, that the prior art does not teach how to make the claimed isomers, implies that the prior art patents were insufficient and claimed more broadly than they disclosed, which would not be an argument open to Sanofi.

[63]            Finally, Apotex adds that, even if Sanofi's process for separating the isomers of the racemate was inventive and therefore anticipated, claims relating to this process are not at issue herein. The impugned claims of the '777 patent do not relate to processes for the separation of isomers. As such, the absence of such information from the '875 patent is irrelevant. The Court does not agree.

[64]            First, it is a well-established principle that a patent must contain all the directions necessary to instruct the public on how to put every part of the invention claimed into practice (Xerox^[33], Farbwerke Hoechst^[34]).

[65]            Second, the Court reads the Beloit anticipation test "in every case and without possibility of error" as meaning that experimentation is not permitted. In other words, the skilled reader following the prior art must be able to arrive at the invention claimed in the impugned patent the first time he or she tries and every time thereafter. The Court does not believe that the SmithKline decision modifies the legal test for anticipation. At paragraph 20 of the decision, the Federal Court of Appeal used a phraseology reminiscent of the test as defined above:   

...The Applications Judge determined that it is not at all surprising that any person skilled in the art who was confronted by the "pink hue problem" would invariably turn to the alternative formulation methods disclosed by the '060 patent to arrive at a solution without any inventive step. (Emphasis added.)

[66]            Third, the Court is aware of the fact that the prior art mentions the existence of isomers without giving instructions on how to obtain the separated isomers. Whether this means that the prior art claimed too broadly than it disclosed is not the issue before this Court. The issue at bar is the validity of the '777 patent, not that of the '875 patent.

[67]            Fourth, as to the process claims in the '777 patent, not at stake, this reality does not change the fact, that an earlier patent, claimed to be anticipatory, needs to describe at least a method - even if, not the one described in the latter patent - that enables the skilled reader to arrive at the claimed invention.

[68]            The evidence, on the record, reveals that a person skilled in the art, who would presumably have followed the prior art had it been sufficient, indeed, did not obtain the separated isomers the very first time he tried. The experts also agree that a person skilled in the art could not predict which of the conventional separation methods would work, before trying them out, with the particular racemate at issue. This involves an element of incertitude, fatal to the anticipation test.

[69]            The very fact that Mr. Badorc, the inventor of the '777 patent, could not separate the isomers the first time he tried, shows that the prior art's teachings were clearly insufficient to meet the anticipation test of "in every case". As attested in Mr. Badorc's affidavit^[35], the separation of the isomers from the racemate took him six months and involved trying several different methods, with failures along the way. Apotex replies that Mr. Badorc, though the inventor, was not, at the relevant time, an individual who possessed the necessary expertise to qualify as a person skilled in the art; and his difficulties, in obtaining the dextro-rotatory isomer from the racemate, are therefore not indicative of the sufficiency of the disclosure of the prior art. In light of Mr. Badorc's specialized experience and background described earlier, the Court is satisfied that Mr. Badorc possessed the characteristics of a person skilled in the art as previously discussed in the specified jurisprudence.

[70]            Dr. Klibanov also confirmed that, while there were various separation techniques known at the relevant time, their successful application to a specific compound was impossible to predict^[36]. As for Apotex' experts, although they stated that the person skilled in the art would eventually have found the right technique derived from the well-known separation techniques at the time^[37], they did not say that the separation of the racemate into its isomers would certainly have been achieved upon the first attempt.

[71]            As a result, the Court then considered the analysis as to whether the prior art disclosed the beneficial properties of the dextro-rotatory isomer of the racemate and of its bisulcate salt. Having read the prior art carefully, the Court is satisfied that there is no disclosure in it of the beneficial properties associated, specifically, with the dextro-rotatory isomer. Nor is there a disclosure of any advantages which flow from using the bisulcate salt in combination with the dextro-rotatory isomer. As discussed earlier, the dextro-rotatory isomer of the racemate is not even, specifically, disclosed in the prior art. In light of this, the beneficial properties of a compound undisclosed in the prior art could obviously not have been, specifically, described in such prior art. The earlier patents, according to Apotex, disclose that both isomers are active and non-toxic; there is no "discovery" in finding the levo-rotatory isomer to be inactive and less well tolerated; rather, it is a recognition of an error in Sanofi's previous patents. In any event, the impugned claims of the '777 patent are not directed to the use of one isomer over another, but simply to the isomer itself. The preference of the dextro-rotatory isomer over the levo-rotatory isomer is then not part of the claims and thus not relevant to the anticipation analysis. Finally, Apotex argued that, as conceded by Dr. Klibanov, a skilled person could ascertain the activity of the two isomers using well-known methods.

[72]            The Court is of the view that the prior art discloses that the racemate - not both isomers - is active and non-toxic. The Court is satisfied that there is a discovery, the discovery that it is more specifically the dextro-rotatory isomer that is active and non toxic in the overall racemate, which renders the impugned patent unanticipated. The Court also notes that, although Dr. Klibanov agreed with Apotex' experts that a skilled person could have ascertained the activity and characteristics of two isomers and of different salts using well-known methods at the time^[38], they did not say that the beneficial properties of these isomers and of their salts - let alone of the dextro-rotatory isomer and of its bisulcate salt - would be known with certitude before conducting the tests designed to identify the respective properties of the isomers and of the salt. As discussed earlier, the last part of the previous sentence refers to the test for anticipation and it is not met in light of the evidence on the record. Someone had to do the work required to discover a successful separation technique and had to test the separated dextro-rotatory isomer and its bisulcate salt to identify their specific properties, and it is Mr. Badorc, in the employ of Sanofi, in fact, who did so.

Conclusion

[73]            Therefore, the evidence is to the effect that the '777 patent is not anticipated.

b) Obviousness

Legal principles

[74]            The question of obviousness must be addressed as of the date of the invention, which is deemed to be February, 17 1987 (priority date).

[75]            Under the Old Act, there is no relevant section for the purposes of considering whether a patent is obvious. Rather, the issue of obviousness is a judicial test which flows from the jurisprudence. A claim of a patent is invalid for obviousness if a person skilled in the art would have come directly and without difficulty to the solution taught by the patent, given the information disclosed in the cited art and the common general knowledge as of the date of invention. The test for obviousness was set out in Beloit^[39]:

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.)

[76]            Hindsight or ex post facto analysis must not be used in the assessment of whether an invention is obvious. Justice Hugessen gave the following warning in Beloit^[40]:

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?" (Emphasis added.)

[77]            Recognizing the point specific fact pattern in the case at bar, the Court adopts the following line of reasoning with respect to obviousness.

[78]            A patent is only obvious if the solution to the problem is very plain. Suggestions or signposts in the prior art are not sufficient to render a patent invalid for obviousness. The person skilled in the art must be able to say that he or she would know that the invention would work and would have the benefits associated with the invention in light of the publicly available information. The person skilled in the art must know that the solution or the benefits would be present without testing (excluding, of course, simple verification of already known information). The test for obviousness is not whether it was "worth a try". These principles were enunciated in Farbwerke Hoechst, in Bayer Aktiengesellschaft v. Apotex Inc.^[41] (decision upheld by the Ontario Court of Appeal^[42])and in AB Hassle v. Genpharm Inc.^[43]. In Farbwerke Hoechst^[44], the Supreme Court of Canada wrote:

On this point the Federal Court of Appeal reached a different conclusion, Jackett C.J. saying (at p. 471):

The learned Trial Judge appears to have proceeded upon the assumption that the requirement of "inventive ingenuity", is satisfied unless the "state of the art" at the time of the alleged invention was such that it would have been obvious to any skilled chemist "that he would successfully produce isohalothane (assuming the monomer used here and hydrogen bromide) in the 'liquid phase'." (The italics are mine.) I do not think that the learned Trial Judge's assumption is correct as a universal rule. I would not hazard a definition of what is involved in the requirement of "inventive ingenuity" but, as it seems to me, the requirement of "inventive ingenuity", is not met in the circumstances of the claim in question where the "state of the art" points to a process and all that the alleged inventor has done is ascertain whether or not the process will work successfully.

In my view this statement of the requirement of inventive ingenuity puts it much too high. Very few inventions are unexpected discoveries. Practically all research work is done by looking in directions where the "state of the art" points. On that basis and with hindsight, it could be said in most cases that there was no inventive ingenuity in the new development because everyone would then see how the previous accomplishments pointed the way. The discovery of penicillin was, of course, a major development, a great invention. After that, a number of workers went looking for other antibiotics methodically testing whole families of various microorganisms other than penicillium notatum. This research work was rewarded by the discovery of a number of antibiotics such as chloromycetin obtained from streptomyces venezuelae as mentioned in Laboratoire Pentagone v. Parke, Davis & Co., [1968] R.C.S. 307, tetracycline as mentioned in American Cyanamid Co. v. Berk Pharmaceuticals Ltd., [1976] R.P.C. 231 where Whitford J. said (at p. 257): "A patient searcher is as much entitled to the benefits of a monopoly as someone who hits upon an invention by some lucky chance or an inspiration". I cannot imagine patents obtained for antibiotics and for various processes for their production being successfully challenged on the basis that the discovery of penicillin pointed the way and there was no inventive ingenuity in the search for other antibiotics and in the testing and the development of processes. In my view, the true doctrine was clearly stated by the Privy Council in Pope Appliance Corporation v. Spanish River Pulp and Paper Mills, [1929] A.C. 269, where Viscount Dunedin said (at pp. 280-1):

... After all, what is invention? It is finding out something which has not been found out by other people. This Pope in the present patent did. He found out that the paper would so stick, and the practical problem was solved. The learned judges below say that all this might have been done by any one who experimented with "doctors" and air blasts already known. That is that some one else might have hit upon the invention. There are many instances in various branches of science of independent investigators making the same discovery. That does not prevent the one who first applies and gets a patent from having a good patent,.... (Emphasis added.)

In Bayer Aktiengesellschaft ^[45],the Ontario Court (General Division) stated:

...although it may have been logical to an actual skilled person at the time, based on the state of the art, to conduct certain testing, that is not open to the mythical skilled technician. The mythical researcher cannot have an inquiring or thinking mind which ultimately would lead him or her to the answer but rather he or she is expected to instantly and spontaneously exclaim, without more, "I already know the answer and it is obvious". Nor is it appropriate to say that there were significant telltales which pointed the way for the mythical expert or that there were sufficient clues which made the invention "worth a try". (Emphasis added.)

Still in Bayer Aktiengesellschaft ^[46], the Ontario Court (General Division) stated:

There appears, however, to be a significant difference in the abilities of the English hypothetical skilled technician and the Canadian one. Indeed, making inquiries or testing, seems to be something outside the ken of the notional Canadian skilled technician. In Cabot Corp. v. 318602 Ontario Ltd. (1988), 20 C.P.R. (3d) 132 at p. 146, 19 C.I.P.R. 204, 9 A.C.W.S. (3d) 317 (F.C.T.D.), Rouleau J. quoted H.G. Fox in Canadian Law and Practice Relating to Letters Patent for Inventions at pp. 70-1, as stating in part:

"In order that a thing shall be 'obvious', it must be something that would directly occur to someone who was searching for something novel, a new manufacture, or whatever it might be, without the necessity of his having to do any experimenting or serious thought, or research, whether the research be in the laboratory or amongst literature." (Emphasis added.)

In AB Hassle v. Genpharm^[47], the Federal Court of Appeal confirmed that the English "worth a try" approach was not applicable in Canada:

With respect to the '377 Patent, the argument is again one of obviousness. Genpharm says that the '377 Patent addresses the stability of omeprazole by the use of mechanically added salt to the omeprazole. Genpharm says this means of achieving stability was obvious from prior art. It says there were four routes for arriving at this result and a formulator would arrive at the '377 result in the ordinary course of his work.

The context in which Genpharm makes its argument was described by Layden-Stevenson J. at paragraph 111 of her reasons:

It must be recalled that the uncontradicted evidence is that it is not known from the prior art that instability existed in enteric coated solid dosage forms, let alone that pH was a causative factor of instability. Nor was the use of an alkaline compound to stabilize omeprazole in the solid state previously disclosed. It is within this context that Genpharm makes its argument.

She found that Genpharm's position regarding obviousness respecting the '377 Patent resembled the English "worth a try" test. Before this Court, Genpharm agreed that the English "worth a try" test is not applicable in Canada. At paragraph 113, Layden-Stevenson J. concluded that the solution of the '377 Patent would, absent the "worth a try" approach, not be arrived at directly and without difficulty. There was evidence to support that conclusion. Genpharm has not demonstrated any palpable and overriding error in Layden-Stevenson J.'s conclusion on this point. (Emphasis added.)

[79]            Therefore, this position concerning obviousness was adopted rather than any other.

Application to the facts

[80]            It is important to remember that the process claims (claims 6 to 9) in the '777 patent, which explain a method to separate the racemate into its isomers, are not contested in these proceedings. But even though process claims are not at stake, a necessary additional step after following the teachings of the prior art (e.g. the '875 patent) in order to obtain the compounds disclosed in claim 1 (dextro-rotatory isomer of the racemate) and in claim 3 (bisulcate salt of the dextro-rotatory isomer of the racemate) is to separate the racemate into its isomers (using a successful method, even if it is not the one disclosed in the '777 patent), in order to obtain the dextro-rotatory isomer of the racemate. Experts from both parties listed five well-known separation techniques at the time the '777 patent was invented: forming the diastereomeric salts of the racemate and performing a fractional crystallization; directly resolving the enantiomers using chiral chromatography; synthesis from optically active reagents; immunoassay techniques; and direct chromatographic resolution^[48]. There was no evidence presented to this Court that knowledge at the relevant time was such that a person skilled in the art would know before trying the different separation techniques which one would work with the racemate at issue in this case. The only evidence before this Court is that the person skilled in the art would eventually find the right technique out of the well-known separation techniques^[49]. Through this evidence, what the experts are really saying from a legal perspective is that separating the racemate was worth a try. Having to try different methods, though they be well-known, in order to discover which one will yield the desired result cannot mean that the desired result, in this case, the compounds in claims 1 and 3 and their pharmaceutical compositions, was obvious.

[81]            Second, not only did the compounds in claims 1 and 3 of the '777 patent require first the separation of their racemate, which was not obvious, but these compounds needed to be tested in order for their respective beneficial properties to be discovered. The Court first turns to the dextro-rotatory isomer of the racemate (claim 1). Though methods to discover the properties of separated isomers were well known^[50], there is no evidence that knowledge was such at the relevant time that a person skilled in the art would know before separating the racemate into its isomers and then testing the separated dextro-rotatory isomer what the dextro-rotatory isomer's properties would be. The only evidence before this Court is that using standard techniques, a skilled person in the art would be able to discover the properties of each separated isomer^[51]. Here again, having to try different separation techniques with uncertainty as to whether each or some specific techniques would actually result in a successful separation and then having to perform tests to discover what the properties of the dextro-rotatory isomer of the racemate were, cannot mean that this compound and its beneficial properties were obvious. The properties that were discovered in the case of the dextro-rotatory isomer were its high activity and its low toxicity, as compared to the levo-rotatory isomer^[52].

[82]            The Court then gave its attention to the bisulcate salt of the dextro-rotatory isomer of the racemate (claim 3). Though different pharmaceutically-acceptable salts could have been tried in combination with the dextro-rotatory isomer of the racemate (some of these salts being, indeed, present in the examples of the '875 patent), there was no evidence that a person skilled in the art would know before trying the different salts in combination with the dextro-rotatory isomer what the bisulcate salt's beneficial properties would be. The only evidence before this Court is that in using known techniques, a person skilled in the art would have been able to discover the properties of a salt used in combination with an isomer^[53]. Again, having to try different separation techniques with uncertainty as to whether each or some specific techniques would actually result in a successful separation and then having to perform tests to discover what the properties of the bisulcate salt used in combination with the dextro-rotatory isomer of the racemate would be, cannot mean that this compound and its beneficial properties were obvious. The properties that were discovered in the case of the bisulcate salt of the dextro-rotatory isomer were its easy crystallization, its non-hygroscopic characteristic and its good water solubility, as compared to other salts^[54].

[83]            It flows from the finding that claims 1 and 3 were not obvious and that claims 10 and 11, being composition claims, were not obvious either.    

Conclusion

[84]            The invention of the impugned claims of the '777 patent was the work of a patient researcher who tried technique after technique, combination of reactants after combination of reactants, pharmaceutically-acceptable salts after pharmaceutically-acceptable salts before finding a product that would be beneficial^[55] for society; this work, as tedious as it was, therefore reaped its reward in its outcome. Due to the a priori unknown beneficial properties of the dextro-rotatory isomer of the racemate and of its bisulcate salt, which first required the racemate separation into its isomers using a technique that could not be guaranteed to succeed before trying it, a person skilled in the art would not in light of the prior art have been led directly and without difficulty to the dextro-rotatory isomer of the racemate, its bisulcate salt and their pharmaceutical compositions. Consequently, claims 1, 3, 10 and 11 of the '777 patent are not obvious.

3. Double patenting

[85]            Apotex alleges that the '777 patent is invalid on the basis of same invention double patenting or obvious-type double patenting (Whirlpool^[56]). In order for there to be same invention double patenting, the claims must be identical or coterminous. The '875 patent claims a large class of compounds and the racemate, while the '777 patent claims the separated dextro-rotatory enantiomer. Thus, two different and distinct compounds are claimed in these patents. Therefore, the claims of the '777 patent and the '875 patent are not identical or coterminous.

[86]            With respect to obviousness-type double patenting, the claims must exhibit novelty or ingenuity in order for the second patent to be valid. For the reasons discussed above, according to Apotex, the '777 patent does exhibit novelty and ingenuity and thus is not invalid on the basis of obviousness-type double patenting.

[87]            In any event, Apotex' argument of double patenting adds nothing more to its argument based on anticipation or obviousness. In this case, all of the relevant art that is being relied on for double patenting is the same art that is being relied upon for anticipation and obviousness. Double patenting is only employed to achieve the benefit of relying on internal work that is not public to prevent the issuance of two patents for essentially the same invention.

CONCLUSION

[88]            Someone following the teachings of the prior art would only be able to make the racemate and not the dextro-rotatory isomer. Therefore, claim 1 of the '777 patent was not anticipated by the prior art.

[89]            Since a chemist would not be able to determine which isomer possessed the beneficial properties without first making the optical isomer and then testing it, claim 1 of the '777 patent is not obvious in light of the prior art.

[90]            Again, since the prior art does not explain how to obtain a separated dextro-rotatory isomer of the racemate and does not specifically teach the bisulcate salt of the dextro-rotatory isomer, this compound could not have been obtained following the prior art and therefore claim 3 of the '777 patent is not anticipated.

[91]            There is also sufficient inventive ingenuity in the invention of the bisulcate salt of the dextro-rotatory isomer due to its unexpected properties, including, its not being hygroscopic when most of the other salts are, to make claim 3 unobvious.

[92]            In light of the above, claims 10 and 11 with respect to pharmaceutical compositions of the dextro-rotatory isomer of the racemate are neither anticipated nor obvious.

[93]            Accordingly, the application for an order of prohibition is granted with costs.

[94]            As the Minister did not participate, there shall be no order as to costs in his regard.

"Michel M.J. Shore"

                                                                                                   Judge                         

APPENDIX 1 - GLOSSARY

STEREOCHEMISTRY

A specialized branch of organic chemistry which deals with the spatial orientation of the atoms in organic molecules.

ISOMER

Different compounds with the same molecular formula.

STEREOISOMERS

Compounds that are identical except for the way in which their atoms are oriented in space.

ENANTIOMERS

Stereoisomers that are non-superimposable mirror images of each other.

OPTICAL ISOMERS

Enantiomers are often referred to as "optical isomers" because they are optically active.

OPTICALLY ACTIVE

A substance that rotates the plane of polarized light.

CHIRAL CENTER

A carbon atom that is bonded to four different atoms or groups of atoms.

RACEMATE

A substance containing equal amounts of two optical isomers. Commonly represented with a ("), (RS) or (dl) symbol.

DEXTRO-ROTATORY (DEXTRO, + or d)

Optically active compounds that rotate the plane of polarized light to the right or in a clockwise direction.

LEVO-ROTATORY (LEVO, - or l)

Optically active compounds that rotate the plane of polarized light to the left or in a counterclockwise direction.

                                     FEDERAL COURT

    NAMES OF COUNSEL AND SOLICITORS OF RECORD

DOCKET:                   T-668-03

STYLE OF CAUSE: SANOFI-SYNTHELABO CANADA INC.

and SANOFI-SYNTHELABO

v.

APOTEX INC. and THE MINISTER OF HEALTH

PLACE OF HEARING:                                 Ottawa, Ontario

DATE OF HEARING:           February 21-25, 2005

REASONS FOR       

ORDER AND ORDER:        The Honourable Mr. Justice Shore

DATE OF REASONS FOR

ORDER AND ORDER:        March 21, 2005

APPEARANCES:

Mr. Anthony G. Creber                                    

Ms. Cristin A. Wagner

Mr. Jay Zakaib

Mr. Donald M. Cameron                                   FOR THE APPLICANTS

Mr. Harry Radomski                

Mr. Andrew A. Brodkin                                   

Mr. Rick Tuzi                            FOR THE RESPONDENTS

SOLICITORS OF RECORD:

Gowling Lafleur Henderson LLP                                   

Ottawa, Ontario                        FOR THE APPLICANTS

Goodmans LLP                         FOR THE RESPONDENT,

Toronto, Ontario                       APOTEX INC.

Mr. John H. Sims                      FOR THE RESPONDENT,

Deputy Attorney General of Canada                              THE MINSITER OF HEALTH