Pfizer Canada Inc. v. Canada (Health)

Pfizer Canada Inc. v. Canada (Health)
Court (s) Database
Federal Court Decisions
Date
2007-01-25
Neutral citation
2007 FC 91
File numbers
T-507-05
Decision Content
Date: 20070125
Docket: T-507-05
Citation: 2007 FC 91
OTTAWA, ONTARIO, January 25, 2007
PRESENT: The Honourable Mr. Justice von Finckenstein
BETWEEN:
PFIZER CANADA INC. and
WARNER-LAMBERT COMPANY, LLC
Applicants
and
THE MINISTER OF HEALTH and
RANBAXY LABORATORIES LIMITED
Respondents
REASONS FOR ORDER AND ORDER
[1] This is a proceeding pursuant to s. 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 as amended (“NOC Regulations”), for an Order prohibiting the Minister of Health (the “Minister”) from issuing a Notice of Compliance (“NOC”) under the Food and Drug Regulations, C.R.C. c. 870, to the Respondent, Ranbaxy Laboratories Limited (“Ranbaxy”), with respect to atorvastatin calcium, 10 mg, 20 mg, 40 mg, or 80 mg strength tablets until after the expiration of Canadian Patent No. 1,268,768 (the “768 Patent”) and Canadian Patent No. 2,021,546 (the “546 Patent”).
Procedural Background
[2] The Applicants, Pfizer Canada Inc. and Warner-Lambert Company, LLC (collectively, “Pfizer”) are “first parties” as defined by the NOC Regulations. Warner-Lambert Company, LLC owns the 768 Patent and the 546 Patent, and is a party to this application by reason of section 6(4) of the NOC Regulations. These two patents are listed with respect to atorvastatin calcium 10 mg, 20 mg, 40 mg, and 80 mg strength tablets and marketed under the trade name Lipitor.
[3] The 768 Patent was filed on May 7, 1987 and issued on May 8, 1990. It is based on the priority filing of U.S. Patent No. 868,867, which was filed on May 30, 1986. As such, the 768 Patent falls under the “old” provisions of the Patent Act, R.S.C. 1985, c. P.4 as they pertain to patents granted in respect of applications filed in Canada before October 1, 1989. This patent is concerned with a large class of compounds and pharmaceutical compositions, which all share a common generic structure and are used to inhibit the biosynthesis of cholesterol. It contains 9 claims. At issue here is claim 1. Claims 2 to 8 are derivatives of claim 1, and claim 9 is a process claim.
[4] The 546 Patent was filed with the Canadian Patent Office on July 19, 1990, and published on January 22, 1991. It is based on a priority filing of U.S. Patent No. 384,187, which was filed on July 21, 1989, but which has since been abandoned and is now continued under U.S. Patent No. 5,273,995. Accordingly, the patent is governed by the “new” provisions of the Patent Act and the relevant date upon which the patent will be interpreted is the date of publication, i.e., January 22, 1991 (Whirlpool Inc. v. Camco Inc., [2000] 2 S.C.R. 1067 at para. 56). The 546 Patent was issued to Warner-Lambert Company, a predecessor of the Applicant Warner-Lambert Company, LLC on April 29, 1997. It expires on July 19, 2010. This patent, similar to the 768 Patent, also pertains to compounds used to inhibit the biosynthesis of cholesterol. However, it provides for the “surprising” inhibition of the biosynthesis of cholesterol. It contains 12 claims, which are directed to atorvastatin acid or atorvastatin lactone and the pharmaceutical acceptable salts thereof. It also contains a use claim for people suffering from hypercholesterolemia. The only claim in dispute is Claim 6, which claims the hemicalcium salt of atorvastatin.
[5] Ranbaxy, the “second parties” as defined by the NOC Regulations, filed with the Minister of Health an abbreviated new drug submission (“ANDS”) with respect to 10 mg, 20 mg, 40 mg, and 80 mg strength tablets of atorvastatin calcium (“Ran-Atorvastatin”). In its ANDS, Ranbaxy compares Ran-Atorvastatin to Lipitor and references the 768 Patent and the 546 Patent.
[6] Ranbaxy sent a Notice of Allegation (“NOA”) to Pfizer in a letter dated January 31, 2005, pursuant to paragraphs 5(1)(b)(iii) and 5(1)(b)(iv) of the NOC Regulations. Ranbaxy’s letter of allegation contains allegations of invalidity and non-infringement made with respect to the 768 Patent and the 546 Patent. The NOA alleges that the 768 Patent is not infringed because the 768 Patent is directly solely to the racemic mixtures of the compounds claimed. This issue is in essence a matter of construction of the 768 Patent. The NOA also alleges that the 546 Patent is invalid for four reasons: obviousness, anticipation, insufficiency, and double patenting.
[7] In response to Ranbaxy’s NOA, Pfizer filed its Notice of Application on March 17, 2005. Pfizer seeks to prohibit the Minister of Health from issuing a NOC to Ranbaxy prior to the expiration of the 768 Patent and the 546 Patent. Pfizer disputes Ranbaxy’s allegations and argues that they are not justified.
Chemical Background - Underlying Concepts
[8] In order to provide a context to the discussion that follows, I will briefly describe the underlying concepts and what the invention involves.
[9] First, cholesterol is synthesized in most body tissues and is necessary for normal body functions. Cholesterol is carried throughout the body on two types of particles: low density lipoproteins (LDL) and high density lipoproteins (HDL).
[10] Cholesterol biosynthesis is the process of producing cholesterol in the body. Cholesterol is synthesized through a biochemical pathway made up of a number of steps (between 20-40).
[11] Many different enzymes (proteins that control biochemical reactions) are involved in cholesterol biosynthesis. One of the early steps in the cholesterol biosynthesis pathway involves an enzyme called HMG-CoA reductase. This step is often called the “rate limiting step” in the pathway.
[12] Drugs that prevent HMG-CoA reductase from performing its functions in the cholesterol biosynthesis pathway are called HMG-CoA reductase inhibitors. By inhibiting cholesterol biosynthesis, these drugs decrease the production of cholesterol.
[13] Statins are drugs which function as HMG-CoA reductase inhibitors. There are two kinds of statins: those derived from natural products (i.e., natural statins) and those produced synthetically (i.e., synthetic statins). Natural statins are derived from fungal fermentation. Synthetic compounds are produced by medicinal chemists. Lipitor is a member of a class of synthetic statins.
[14] In this case we are concerned with the field of stereochemistry. Stereochemistry involves the study of relative spatial arrangements of atoms within molecules. “Isomers” are compounds that have the same molecular formula, but are not identical. One main class of isomers is “stereoisomers”. In stereoisomers, the atoms are connected sequentially in the same way, but the isomers differ in the way the atoms are arranged in space. These structural differences mean that the physical and/or chemical properties of isomers are often different.
[15] A diagram of molecules and its constituent atoms and bonds is commonly referred to as a structural formula. A structural formula often appears as a series of letters (representing atoms), numbers, and lines (representing chemical bonds). However, these structural formulas may also be depicted by structural diagrams which show their stereochemistry. In general plain lines depict bonds approximately in the plane of the drawing; bonds to atoms above the plane are shown with a bold wedge (starting from an atom in the plane of the drawing at the narrow end of the wedge); and bonds to atoms below the plane are shown with short parallel lines.
[16] When a carbon atom is attached to four different atoms or groups of atoms, it is called an “asymmetric carbon atom or a “chiral centre”. This configuration means that the stereochemistry around an asymmetric carbon creates two molecules which are chemically identical but which are mirror images of one another. In other words, they differ in the three-dimensional arrangements of their constituent atoms. Molecules having this relationship to each other are known as enantiomers.
[17] “Enantiomers” are a pair of isomers that are non-superimposable mirror images of one another. The most common analogy for enantiomers is a pair of hands. Enantiomers have identical physical, chemical and spectral properties (unlike other stereoisomers), but their biological properties are often different. A process wherein enantiomers are separated is called a “resolution”.
[18] “Racemate”, also known as a “racemic mixture”, is a 50/50 mixture of enantiomers. A racemate is a different form of matter from individual enantiomers. The properties of a molecule will depend not only on the molecule itself, but on the molecules that surround it. The individual molecules of a racemate will be surrounded by molecules with different chiralities. Therefore, the physical properties of a racemate will be different than individual enantiomers.
[19] A number of conventions are used to name enantiomers. One such convention is based on the fact that enantiomers rotate plane-polarized light in equal but opposite directions. Enantiomers are designated left handed (levo or “-”) or right handed (dextro or “+”) configurations to indicate the direction in which the light is rotated. Specifically, the enantiomer that rotates light in a clockwise direction is designated “+”. The enantiomer that rotates light in a counter-clockwise direction is designated “-”. To be designated either + or -, an enantiomer must be tested.
[20] Unlike single enantiomers, a racemate has no effect on plane-polarized light. A racemic mixture has equal amounts of the + and – enantiomers. In other words, half of the molecules will rotate light one way and the other half will rotate it the other way because it has equal amounts of both enantiomers. This is often shown using the symbol “±”.
[21] Another convention is to name enantiomers according to the configuration of their asymmetric carbon atoms, using the symbols “R” and “S”. R and S indicate how the four atoms surrounding an asymmetric carbon atom are oriented in space. There is no relationship between the R/S convention and the convention that uses + and -. An R-enantiomer could be + or -.
[22] When the precise stereochemistry around an asymmetric carbon is not known and when there is more than one asymmetric carbon in a molecule, chemists use another convention to show “relative configuration” (meaning the configuration at any asymmetric carbon with respect to that of any other asymmetric carbon in the same molecule). The convention identifies the asymmetric carbons as having configurations that are the same or different. If the configurations of two asymmetric carbons atoms are the same (that is, both R or both S), they are labelled R*,R* or S*,S*. If the configurations are different (that is, one R and one S), the asymmetric carbons are labelled R*,S*.
Nomenclature
[23] This might be a good point to say a few words about the nomenclature of this case to clear up any possible confusion. Lipitor contains the calcium salt of atorvastatin. Atorvastatin is an enantiomer; is the name given to the R-trans enantiomer of the atorvastatin racemate. The compound from which the enantiomers are resolved has no name of its own. It is called the atorvastatin racemate or atorvastatin racemic mixture. The S-trans enantiomer also has no name of its own and is always referred to as the S-trans enantiomer.
Applicable Jurisprudence
[24] The jurisprudence regarding NOCs is extensive. It is best set out by Stone J.A. in Hoffman-La Roche Ltd. v. Canada (Minister of National Health & Welfare) (1996), 205 N.R. 331 at para. 8, 70 C.P.R. (3d) 206 (F.C.A.):
It seems to me that the core guidance of these decisions, insofar as it is applicable to the case at bar, may be summarized as follows:
1. Applications made pursuant to subsection 6(1) of the Regulations are governed by the procedural rules contained in Part V.1 of the Federal Court Rules, [C.R.C. 1978, c. 663] - "Applications for Judicial Review". Bayer AG, supra, per Mahoney J.A., at page 336 [C.P.R.];
2. The initiator of a section 6 proceeding, being the person having the carriage of the litigation, bears "the initial burden of proof" which is a difficult burden because "it must be to disprove some or all of the allegations in the notice of allegation which, if left unchallenged, would have allowed the Minister to issue a notice of compliance". Merck Frosst, supra, per Hugessen J.A., at page 319 [C.P.R.];
3. This burden, known in a civil case as either the "persuasive burden" or the "legal burden", is the burden of establishing a case to the civil standard of proof. By contrast, the "evidential burden" consists of the burden of putting an issue in play and means that a party has the responsibility to ensure that there is sufficient evidence of the existence or non-existence of a fact or an issue on the record to pass the threshold for that particular fact or issue. Nu-Pharm, supra, per Stone J.A., at page 197 [N.R.];
4. Where the notice of compliance of a second person alleges non-infringement, the court should start from the proposition that "the allegations of fact in the notice of allegation are true except to the extent that the contrary has been shown by the applicant". Merck Frosst, supra, per Hugessen J.A., at page 319 [C.P.R.];
5. In determining whether or not the allegations are "justified" "the court must then decide whether, on the basis of such facts as have been assumed or proven, the allegations would give rise in law to the conclusion that the patent would not be infringed by the respondent". Merck Frosst, supra, per Hugessen J.A., at page 319 [C.P.R.];
6. The Minister's decision of whether to issue a notice of compliance must turn on whether the allegations of the second person are "sufficiently substantiated to support a conclusion for administrative purposes ... that the applicant's patent would not be infringed if the generic's product is put on the market". Pharmacia, (A-332-94) supra, per Strayer J.A., at page 216 [C.P.R.];
7. Where second persons fail to file notices of allegation or adequate notices of allegation they "must assume their own risk when it comes to attacks on the adequacy of such allegations once prohibition proceedings are commenced". Bayer AG, (A-669-93) supra, per Strayer J.A., at page 134 [C.P.R.];
8. The requirement in s. 5(3)(a) of the Regulations that a second person provide a detailed statement "seems intended ... [to make] the patentee ... fully aware of the grounds on which the applicant seeks issuance of a NOC [that will not lead to infringement of the patent] before the patentee decides whether or not to apply to a court for a determination. Such disclosure would define the issues at a very early stage." Bayer AG, (A-389-93) supra, per Mahoney J.A., at pages 337-338 [C.P.R.];
9. A bald statement of non-infringement in a detailed statement without any factual assertion in support thereof does not meet the requirements of s. 5(1)(b)(iv) of the Regulations. Nu-Pharm, supra, per Stone J.A., at page 199 [N.R.]; and
10. A common law presumption that a second person's process would infringe the patent applies where: that person has asserted no facts to support his allegation of non-infringement; the evidence of non-infringement lay peculiarly within his knowledge; no evidence of non-infringement has been presented by that person; and the first person has no other available means of accessing such evidence. Nu-Pharm, supra, per Stone J.A., at page 200 [N.R.].
Burden of Proof
[25] Much has been stated with respect to the burden of proof. Section 6(2) of the NOC Regulations provide that the court can make an order prohibiting the Minister from issuing an NOC until after the expiration of the patent at issue if it finds that none of the allegations by the second party are justified. The overall burden of proof in these proceedings is on the first person (the applicant, Pfizer) to establish on a balance of probabilities that the allegations set forth in the NOA are not justified. However, the evidentiary burden is on the second person (Ranbaxy) to put each of the issues “in play”. If the second person is successful in doing so, then the first person is entitled to rely on the presumption of validity of the patent established by subsection 43(2) of the Patent Act. Once these issues are “in play” the persuasive burden lies with the first party to disprove the allegations raised in the NOA.
[26] Where the NOA has made allegations of non-infringement, the court must start from the proposition that the allegations of fact in the NOA are true, unless it has been proven otherwise. Thus, in order for the first person to establish that the allegations in the NOA are not justified, the first person must demonstrate either that the statements which are assumed to be correct, do not result in a finding of non-infringement or that all or most of the facts relied on by the second person to justify its allegations of non-infringement are wrong. The first party must demonstrate that the evidence as to infringement is not mere speculation, but that there are substantial grounds (AstraZeneca v. AB v. Apotex Inc., 2004 FC 44, 245 F.T.R. 196, 33 C.P.R. (4th) 125 at paras. 79-86).
Findings Required
[27] In order to grant a prohibition order, the court must find that the allegations are not justified, i.e., that the patents are valid and that it will be infringed. However, to refuse a prohibition order only requires the court to find that either the patent is invalid or that it will not be infringed, but not both.
Patent Construction
[28] Any case involving patents starts with construction of the patent. It is to be done by the Court before issues of infringement or invalidity is considered. In Biovail Pharmaceuticals Inc. v. Canada (Minister of National Health and Welfare), 2005 FC 9, (2005), 37 C.P.R. (4th) 487, 267 F.T.R. 243, Justice Harrington succinctly summarized the jurisprudence on the rules for patent construction at paragraph 15, which I intend to follow:
It is a pre-requisite to considerations of both patent validity and infringement that the language of what is claimed in the patent be properly considered. The Court can do no better than to take the same approach in an NOC proceeding, keeping in mind the restricted purpose of the proceeding. The Supreme Court has done much to codify and clarify patent claim construction in two recent cases handed down the same day: Free World Trust v. Electro-Sante Inc., [2000] 2 S.C.R. 1024, 9 C.P.R. (4th) 168 and Whirlpool Corp. v. Camco Inc., [2000] 2 S.C.R. 1067, 9 C.P.R. (4th) 129. The reasons in both were given by Mr. Justice Binnie. I take the following principles as having particular relevance to this case:
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).
7. Some elements of the claimed invention are essential and others are not, based either on common knowledge when the patent was published or according to the intent of the inventor, expressed or inferred from the claims. This lies at the heart of Biovail’s position that Novopharm's allegation that it will not infringe the ‘320 patent is not justified. Put another way, was it obvious at the time the patent was published that the substitution of a variant would make a difference?
8. To overclaim is to lose everything. If the inventor underclaims, the court will not broaden the monopoly in the interests of the “spirit” thereof. This often, as in this case, results in layers of claims, each limitation serving as a potential safety net so that if the broadest claims fall, the monopoly may be saved in part by the more modest claims.
9. Yet a patent is not an ordinary writing. It meets the definition of a “regulation” in the Interpretation Act, and must be read to assure the attainment of its objects. “Claims construction is a matter of law for the judge, and he was quite entitled to adopt a construction of the claims that differed from that put forward by the parties” (Whirlpool, para. 61).
Applicable Patent Act
[29] The 768 Patent is governed by the “old” Patent Act, and as such the construction of the patent is to be done at the date of issue, May 8, 1990. The 546 Patent is governed by the “new” Patent Act, and the relevant date for claims construction is the date of publication, January 22, 1991.
Person Skilled in the Art
[30] The Court interprets patents with the aid of persons skilled in the arts; after all, the patents are addressed to such persons. However, it is worth recalling that although the evidence of the experts are helpful in understanding the knowledge that a person skilled in the art is expected to possess as of the relevant date, construction of the patents is ultimately a task for the Court to decide.
[31] Dr. Roush for Pfizer states that the person skilled in the art of the 768 Patent and the 546 Patent is the following:
59. The person of ordinary skill in the art would have at least a Bachelor of Science degree in organic chemistry, medicinal chemistry or related chemistry, coupled with several years of relevant experience in medicinal chemistry.
60. The person of ordinary skill in the art would have a general knowledge concerning the class of drugs called stains, although this knowledge could come from a review of published literature (including patents). This person would know that the literature was not limited to naturally occurring statins, such as mevinolin and compactin, but also included information relating to synthetic stains.
61. The person of ordinary skill in the art would have knowledge of stereochemistry. They would have some general knowledge concerning biochemistry, and possibly enzymology. However, this knowledge would be at a substantially lower level than the person’s knowledge of chemistry or medicinal chemistry.
62. In the case of the 546 Patent, the person of ordinary skill would be aware of the statins that were commercially available on July 21, 1989. The person would also have at least a general knowledge of methods for resolving racemic mixtures into their component enantiomers on a laboratory scale; for example, by using chromatographic or selective precipitation techniques. However, a person of ordinary skill would not necessarily be able to resolve racemic mixtures on a commercially viable scale, or develop a practical, commercially viable enantioselective synthesis for molecules that are as complex as statins.
(A.R. Vol. 3 at 743-44.)
[32] Dr. Clive for Ranbaxy states:
9. From reading the 768 Patent, it seems clear to me that the person skilled in the art would be someone interested in synthesizing pharmaceutical active compounds, especially statins that are useful hypocholesterolemic and hypolipidemic agents.
10. The person skilled in the art would need to be skilled in organic synthesis, have a detailed understanding of stereochemistry and knowledge about the statin field. As a result of my own experience at the time, I regard a Ph.D. in organic chemistry with an emphasis on synthesis and probably some post-doctoral experience as an appropriate level of training for the skilled person of the 768 Patent. In my view, the person skilled in the art could be a team of people, at least one of whom would have Ph.D. training and probably some post-doctoral experience.
(A.R. Vol. 16 at 4841.)
[33] For the 546 Patent, Dr. Cunningham states:
68. In my opinion, the skilled addressee of the 546 Patent would be an R&D project team concerned with agents for the inhibition of cholesterol biosynthesis. Such a project team would include as key members medicinal and process chemists and formulators. I shall refer to this team in this affidavit as the “skilled addressee.”
(A.R. Vol. 18 at 5600.)
[34] The Court finds that the addressee is a person skilled in the art who is an organic or medicinal chemist – a person with at least a Bachelor of Science degree and with experience conceiving, creating, synthesizing and testing compounds to be used as medicines. It would also be a person familiar with the agents used for the inhibition of cholesterol biosynthesis.
Experts
[35] Both Pfizer and Ranbaxy have submitted the evidence of numerous expert witnesses with respect to the construction of the 768 Patent, the 546 Patent, the nature of atorvastatin, and the expectations of a person skilled in the art. The professional qualifications of these experts have been summarized in Annex 1.
[36] Pfizer challenged Ranbaxy’s expert witnesses, Dr. Moss and Dr. Clive as being unqualified to speak on the on the matter of how a person skilled in the art would read the Patents. In particular, Pfizer argues [emphasis in original]:
122. Ranbaxy’s witnesses are not sufficiently informed or familiar with the art of the 768 Patent to speak persuasively to how a person would read or understand the 768 Patent. Dr. Moss was not instructed on how patent claims are construed by courts in Canada and as a result applied the wrong test. Dr. Clive agreed to assist Ranbaxy with this case before reading the Notice of Allegation. The inference to be drawn from this is that Dr. Clive did not approach his task with a mind willing to understand. He had made up his mind before seeing any of the evidence in this case.
123. Dr. Clive does not have sufficient knowledge in the field to which the 768 Patent relates to opine as to what the ordinary skilled person would have known and understood about it. The “art” of the 768 Patent is that of medicinal chemistry, an important branch of organic chemistry that deals with the development of new drugs. A medicinal chemist is best placed to review the prior art and take from it the clues which a person or ordinary skill in the art would use to develop strategies to find more active compounds. Dr. Clive is not a medicinal chemist. He has never worked in the pharmaceutical industry, nor participated in a drug discovery program.
[37] In addition, Pfizer argues that Dr. Scallen “willingly demonstrated his lack of objectivity. Allegedly assuming the mantle of an advocate, Dr. Scallen refused to answer questions unless they were distorted into questions that he wished had been asked.” As for Dr. Cunningham, Pfizer argues that with respect to the 546 Patent, he employed hindsight analysis and only selectively reviewed the prior art.
[38] I find these allegations against Dr. Moss, Dr. Clive and Dr. Scallen unwarranted. The differences in the opinions of the experts were principally a matter of degree and I find them all respectively qualified. In addition, Justice Hughes in Janssen-Ortho v. Novopharm Limited, 2006 FC 1234 at para. 90 stated with respect to an ordinary person skilled in the art:
Further, with respect to evidence as to the understanding of such person, the Federal Court of Appeal has said that a witness on the subject need not be that very person, so long as they are in a position to provide appropriate evidence as to what such a person would have known and understood at the relevant time (Halford v. Seed Hawk Inc., [2006] F.C.J. No. 1205, 2006 FCA 275 at para. 17).
[39] Accordingly, I find all of the experts qualified for the testimonies that they proffered and I will treat the expert evidence in the same way as Justice Campbell in AB Hassle v. Apotex Inc., 2003 FCT 771, (2003), 27 C.P.R. (4th) 465 at para. 16 (F.C.):
16 Each of the expert witnesses to the present case have sworn that the evidence they have provided is true. On this basis, an evaluator of the evidence must start from the proposition that the witnesses are credible unless good cause is shown, and can be articulated, to the contrary (for an example of this general principle see: Maldonado v. Canada (Minister of Employment and Immigration), [1980] 2 F.C. 302 (C.A.). That is, while they might hold differing views on a given topic, it must be assumed that they are not just saying things to bestow a benefit on the party who is relying on their evidence. In my opinion, it is unfair to the witnesses and, accordingly, to each of the parties, to make negative credibility findings in the guise of findings of weight without seeing and hearing each witness testify.
Issues
[40] First: are Ranbaxy’s allegations regarding the 768 Patent (that claims 1 to 8 of the 768 Patent are limited to racemic mixtures) unjustified?
[41] Second: are Ranbaxy’s allegations regarding claim 6 of the 546 patent (invalidity on the basis of anticipation, obviousness, insufficient support, and double patenting) unjustified?
Analysis re Issue 1
[42] Ranbaxy alleges that claims 1 to 8 of the 768 patent will not be infringed as these claims are limited to racemates. Given that claims 2 to 8 are derivatives of claim 1, the Court will restrict its analysis to claim 1.
Construction of Claim 1 of the 768 Patent
[43] The claims of a patent are to be read in a way that would fulfill the inventor’s express purpose or that is implicit in the text of the claims. This is to be done by taking into consideration the knowledge that a person skilled in the art is expected to possess. The Supreme Court of Canada in Free World Trust v. Électro Santé Inc., 2000 SCC 66, [2000] 2 S.C.R. 1024, at para. 51, 194 D.L.R. (4th) 232 stated:
The involvement in claims construction of the skilled addressee holds out to the patentee the comfort that the claims will be read in light of the knowledge provided to the court by expert evidence on the technical meaning of the terms and concepts used in the claims. The words chosen by the inventor will be read in the sense the inventor is presumed to have intended, and in a way that is sympathetic to accomplishment of the inventor's purpose expressed or implicit in the text of the claims. However, if the inventor has misspoken or otherwise created an unnecessary or troublesome limitation in the claims, it is a self-inflicted wound. The public is entitled to rely on the words used provided the words used are interpreted fairly and knowledgeably.
[44] The only claim of relevance here is Claim 1. It reads as follows.
Claim 1: A compound of structural formula I
wherein X is -CH2-, -CH2CH2-, -CH2CH2CH2- or
-CH2CH(CH3)-;
R1 is 1-naphthyl; 2-naphthyl; cyclohexyl; norbornenyl; 2-, 3-, or 4-pyridinyl; phenyl, phenyl substituted with fluorine, chlorine, bromine, hydroxyl; trifluoromethyl; alkyl of from one to four carbon atoms, alkoxy of from one to four carbon atoms, or alkanoyloxy of from two to eight carbon atoms;
either of R2 or R3 is -CONR5R6
R5 and R6 are independently hydrogen; alkyl of from one to six carbon atoms; 2-, 3-, or 4-pyridinyl; phenyl; phenyl substituted with fluorine, chlorine, bromine, cyano, trifluoromethyl, or carboalkoxy of from three to eight carbon atoms;
and the other of R2 or R3 is hydrogen; alkyl of from one to six carbon atoms; cyclopropyl; cyclobutyl; cyclopentyl; cyclohexyl; phenyl; or phenyl substituted with fluorine, chlorine, bromine, hydroxyl; trifluoromethyl; alkyl of from one to four carbon atoms, alkoxy of from one to four carbon atoms, or alkanoyloxy of from two to eight carbon atoms;
R4 is alkyl of from one to six carbon atoms; cyclopropyl; cyclobutyl; cyclopentyl; cyclohexyl; or trifluoromethyl;
or a hydroxy acid or pharmaceutically acceptable salts thereof, derived from the opening of the lactone ring of the compounds of structural formula I above.
[45] The background to the 768 Patent is described in the disclosure as:
The present invention is related to compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents. More particularly, this invention concerns certain trans-6-[2-(3- or 4- carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-ones and the corresponding ring-opened acids derived therefrom which are potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase), pharmaceutical compositions containing such compounds, and a method of inhibiting the biosynthesis of cholesterol employing such pharmaceutical compositions.
[46] The disclosure of the 768 Patent also sets out two reactions sequences to create the compounds, describes the uses of the compounds, indicates on a table the activity of several compounds when compared to a prior art compound, Compactin, and provides four examples of the particular methods for preparing compounds of the present invention.
[47] The experts for both sides agree that:
a. Claim 1 of the 768 Patent covers a class of compounds of structural formula I wherein each of the positions: X, R1, R2, R3 and R4 are selected from a list of identified possibilities;
b. Reaction sequences I and II only produce racemates;
c. No mention of resolution into enantiomers is made anywhere in the patent;
d. The three compounds within Table I are racemates;
e. Example 1 describes the production of racemic atorvastatin lactone; and
f. Formula I of claim I has to be read in context.
[48] The expert witnesses for Pfizer, Drs. Doyle and Roush, argue that the context of the 768 Patent demonstrates the following:
a) There is nothing within the 768 Patent to suggest that the inventor intended to limit the 768 Patent to only the racemate;
b) The 768 Patent states that the patent relates to the “trans-form”, which includes the R-trans, the S-trans enantiomers, as well as mixtures of these two;
c) Claim 5 specifies the ± which means that the inventor knew to limit it to the racemate;
d) Although the reaction sequences only produce racemates, a person of ordinary skill knew how to resolve; and
e) The language of the Canadian Patent No. 1,330,441 Patent (a process patent that discloses how to produce certain chemical compounds among them atorvastatin) supports the interpretation that the 768 Patent is not limited to racemates because it indicates that there are 4 possible isomers.
[49] In contrast, the expert witnesses for Ranbaxy, Drs. Clive and Moss argue that the context shows that the 768 Patent refers only to racemate for the following reasons:
a) The passage in the 768 Patent regarding the “trans-form” in association with Example 1 means that the trans term is limited solely to the trans-racemic mixture;
b) The reaction sequences only produce racemate;
c) The 768 Patent does not speak about resolving racemates;
d) In May 1990, the person skilled in the art would have known that a racemate could be resolved into the individual enantiomers. The inventor intentionally omitted resolution from the 768 Patent. Thus, it is directed towards racemates only.
e) Since synthesis of a single enantiomer is difficult and time consuming, its omission means that it was not performed;
f) Claim 6 and 7 are racemic compounds and it did not have the ± attached, unlike with claim 5; and
g) Table 1 does not explicitly indicate that the individual enantiomers had been isolated and tested for activity. This is required because enantiomers have very different properties.
[50] Clearly there is a clash of expert opinions here. After considering all the facts and expert advice in my view, the 768 Patent is not limited to racemates for the following reasons.
[51] First, the 768 Patent does not explicitly limit the 768 Patent to the racemate. It clearly states that it contemplates the trans-form, which includes both enantiomers. In particular, as stated earlier, it states:
The compounds of structural formula I above possess two asymmetric carbon centers, one at the 4-hydroxy position of the pyran-2-one ring, and the other at the 6-position of the pyran-2-one ring where the alkylpyrrole group is attached. This asymmetry gives rise to four possible isomers, two of which are the R-cis- and S-cis-isomers and the other two of which are the R-trans- and S-trans- isomers. This invention contemplates only the trans- form of the compounds of formula I above.
[52] Second, although the examples in the 768 Patent describing particular methods for the preparation of compounds contemplated by the invention produces only racemic mixtures, the patent specifically stated that the examples are merely illustrative and did not limit the scope of the invention. The 768 Patent states on page 17:
These examples are illustrative and are not to be read as limiting the scope of the invention as it is defined by the appended claims.
[53] Third, claim 5 undisputedly covers only racemates by the use of the ± symbol. The use of the stereo-descriptor by the inventor demonstrates that he knew when to limit the claims to racemates. By implication, when the inventor does not use ± , he means to cover both racemates and enantiomers.
[54] Fourth, the Stokker article entitled, “3-Hydroxy-3-methylglutaryl coenzyme A Reductase Inhibitors. 1. Structural Modification of 5-Substituted 3,5-Dihydroxypentanoic Acids and Their Lactone Derivatives” (1985) 28 J. Med. Chem. 347-358, was a document that a person skilled in the art would likely become aware of given that it predates the patent by one year. It was a study on statins and it reported that the activity resided principally in the R-trans- isomer and not the S-trans- isomer.
[55] Fifth, it was common general knowledge, undisputed by the experts of both parties, that a person of ordinary skill would know how to resolve the racemic mixture into its individual enantiomers using known chemical techniques.
[56] Sixth, a skilled person knew that compactin and mevinolin, two naturally occurring statins, were potent inhibitors of HMG-CoA reductase and were single 4(R)-trans- isomer enantiomers.
[57] Lastly, in the U.K. decision of Ranbaxy UK Ltd v. Warner-Lambert Co., [2006] F.S.R. 14 (Patents Ct.), aff’d [2007] R.P.C. 4 (C.A.), Justice Pumfrey of the Chancery Division (Patents Court) dealt with European (UK) patent 0247633 (the UK equivalent of the 768 Patent) on this very issue. Justice Pumfrey held at paragraph 41:
In the '633 patent, it is absolutely clear from context throughout that formula (I) is being used to denote a racemate. In my judgment, every time the skilled person sees formula I or formula X he will see it with eyes that tell him that in that race