Pfizer Canada Inc. v. Canada (Minister of Health)

Pfizer Canada Inc. v. Canada (Minister of Health)
Court (s) Database
Federal Court Decisions
Date
2006-12-07
Neutral citation
2006 FC 1471
File numbers
T-560-05
Decision Content
Date: 20061207
Docket: T-560-05
Citation: 2006 FC 1471
OTTAWA, ONTARIO, December 7, 2006
PRESENT: The Honourable Mr. Justice von Finckenstein
BETWEEN:
PFIZER CANADA INC.
and WARNER-LAMBERT COMPANY, LLC
Applicants
and
THE MINISTER OF HEALTH
and NOVOPHARM LIMITED
Respondents
REASONS FOR ORDER AND ORDER
[1] This is an application pursuant to s. 6(1) of the Patented Medicines (Notice of Compliance) Regulations, 1993, SOR/93-133 (“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, Novopharm Limited (“Novopharm”), with respect to atorvastatin calcium, 10 mg, 20 mg, 40 mg, or 80 mg strength tablets until after the expiration of Canadian Patent 2,021,546 (the “546 Patent”).
Procedural Background
[2] The Applicants, Pfizer Canada Inc. and Warner-Lambert Company, LLC (collectively, “Pfizer”), manufacture and sell an anti-cholesterol drug under the trade name LIPITOR, which is contained in the 546 Patent. The active ingredient of LIPITOR is the atorvastatin calcium, a salt.
[3] 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 384,187 filed on July 21, 1989, but which has since been abandoned and is now continued under U.S. Patent 5,273,995. Accordingly, the patent is governed by the Patent Act, R.S.C. 1985, c. P-4 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).
[4] The 546 Patent was issued to Warner-Lambert Company, a predecessor of the Applicant Warner-Lambert Company, LLC on April 29, 1997, and it expires on July 19, 2010. The only claim in dispute is claim 6.
[5] Novopharm is seeking an NOC to allow it to produce a generic version of atorvastatin calcium. In making its application, Novopharm sent a Notice of Allegation (“NOA”) in a letter dated February 3, 2005, to Pfizer comparing its drug to LIPITOR and referencing the 546 Patent. The NOA alleges that the 546 Patent is invalid for three reasons: anticipation, obviousness, and double patenting. The relevant portions of the NOA are attached hereto as Annex 1.
[6] Pfizer disputes these allegations and brought this application seeking an order prohibiting the Minister from issuing an NOC to Novopharm prior to the expiration of the 546 Patent.
Chemical Background - Underlying Concepts
[7] In order to provide a context to the discussion that follows, I will briefly describe the underlying concepts and what the invention involves.
[8] 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).
[9] 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).
[10] 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.
[11] Drugs that prevent HMG-CoA reductase from performing its functions in the cholesterol biosynthesis pathway are called HMG-Co-A reductase inhibitors. By inhibiting cholesterol biosynthesis, these drugs decrease the production of cholesterol.
[12] 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.
[13] Pfizer made the following statements regarding LIPITOR:
LIPITOR® is a blockbuster, but not in the traditional sense: it was not the first drug in its class. Rather, it was the fifth in the commercial statin marketplace. However, it is one of a kind and the first of its kind: it is a novel compound; it is the first statin to be formulated as a calcium salt (all previous statins were formulated as sodium salts); it is the first synthetic statin to be marketed in a form other than as a racemate.
LIPITOR® has become a commercial success because of the advantageous properties of atorvastatin calcium. It has dominated the market: it has become the first drug ever to reach over a billion dollars in sales in its first year, is currently the largest selling drug in every country in which it is sold, and is the largest selling drug of all time.
Not surprisingly, Novopharm wants to take as large a share of the valuable LIPITOR® market as it can by selling its own atorvastatin calcium, a generic copy. To do so, it must invalidate the single patent claim, claim 6, to the most successful salt in pharmaceutical history.
(A.R. Vol. 29 at 9940.)
Prior Patents
[14] The 546 Patent is based on the prior art of U.S. Patent 4,681,893 (“893 Patent”). The 893 Patent was filed with the U.S. Patent Office on May 30, 1986, and issued on July 21, 1987. It describes a class of statins, including natural statins which were commercialized as lactones and compounds. The 893 Patent includes individual enantiomers and mixtures, including racemic mixtures.
[15] “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. “Racemate”, also known as a “racemic mixture”, is a 50/50 mixture of enantiomers.
[16] The invention of the 893 Patent provided for compounds with the structural formula:
Wherein X is –CH2—, --CH2CH2—, --CH2CH2CH2— or –CH2CH(CH3)—
[17] It also provides a list of substituents for R1 to R4, including substituents making up the atorvastatin racemate.
[18] Thus, the 893 Patent describes a broad class of compounds including the 4-hydroxypyran-2-ones and the corresponding ring-opened acids, and the pharmaceutically acceptable salts thereof.
[19] These compounds are in practice used in its salt form. The salt most commonly used was the sodium salt, although any number of salts may be used. In describing what “pharmaceutically acceptable metal salt” meant, the 893 Patent includes the following salts: sodium, potassium, calcium, magnesium, aluminium, iron, and zinc ions, but it did not draw special attention to the calcium salt specifically.
[20] The 893 Patent gave a detailed description of the racemic mixture by stating [emphasis added]:
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.
[21] “Cis” and “Trans” are terms which imply relative stereochemistry. Cis means that two chemical groups in a molecule are on the same side of a plane, but it does not tell you which side of the plane the groups are on. Trans means that two chemical groups in a molecule are on opposite sides of a plane.
[22] This might be a good point to say a few words about the nomenclature of this case to clear up any possible confusion. 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 R- trans enantiomer of the atorvastatin racemate is called the atorvastatin. The S- trans enantiomer has no name of its own and is always referred to as the S-trans enantiomer. LIPITOR contains the calcium salt of atorvastatin (the R-trans enantiomer).
[23] The 893 Patent corresponds to the Canadian Patent 1,268,768 (“768 Patent”). The 768 Patent was filed on May 7, 1987, and issued on May 8, 1990.
[24] Approximately three years after the 893 Patent was filed, the Applicants filed another patent, this time a process patent with the Canadian Patent Office on February 7, 1989. This was the Canadian Patent 1,330,441 (“441 Patent”).
[25] The 441 Patent discloses and claims chemical processes that can be used to make chemical compounds. This includes processes used in the production of atorvastatin.
Issue
[26] Are Novopharm’s allegations (that the 546 patent is invalid on the basis of anticipation, obviousness and double patenting) justified?
Applicable Jurisprudence
[27] 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.];
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
[28] Pfizer in its factum states at para. 122:
Facts that are set out in the Notice of Allegation in relation to allegations of invalidity are not presumed to be true. A presumption that facts in a Notice of Allegation are true arises only with respect to allegations of non-infringement. The only allegations in this case are allegations of invalidity. As a result, no facts set out in Novopharm’s Notice of Allegation are presumed to be true.
(A.R. Vol. 29 at 9972.)
[29] This is not a correct reflection of the law on this point. The issue of the interaction of s. 43(2) of the Patent Act and the NOC Regulations has been dealt with on numerous occasions by this Court (see Pfizer Canada Inc. v. Apotex Inc., 2002 FCT 1138, (2002), 22 C.P.R. (4th) 466 at paras. 82-83, 225 F.T.R. 1, Dawson J.; Abbott Laboratories v. Canada (Minister of Health), 2004 FC 1349, (2004), 36 C.P.R. (4th) 437 at paras. 103-106, 260 F.T.R. 276, Gibson J.; aff'd 2005 FCA 250, (2005), 339 N.R. 277; GlaxoSmithKline Inc. v. Genpharm Inc., 2003 FC 1248, (2003), 30 C.P.R. (4th) 360 at para. 45, 241 F.T.R. 42, Heneghan J.; Janssen-Ortho Inc. v. Novopharm Ltd. 2004 FC 1631, (2004), 35 C.P.R. (4th) 353, at paras. 13-21, 264 F.T.R. 202, Mosley J.; Sanofi-Synthelabo Canada Inc. v. Apotex Inc., 2005 FC 390, (2005), 39 C.P.R. (4th) 202 at 209, 271 F.T.R. 159, Shore J.).
[30] All these cases stand for the proposition that the applicant must demonstrate on a balance of probabilities, that the respondent's allegations of non-infringement or invalidity of the patent are not justified. As Shore J. stated in Sanofi-Synthelabo, supra at para. 9:
The applicant has the overall legal burden of proof. Nevertheless, the Respondent, as the entity which has made its allegations in the NOA, has the obligation to put these allegations "in play", i.e. to ensure there is sufficient evidence of these allegations by which to present issues for examination (Eli Lilly & Co. v. Nu-Pharm Inc. (1996), 69 C.P.R. (3d) 1, [1996] F.C.J. No. 904 (F.C.A.) (QL)).
[31] It is thus the duty of the Court to consider each of the allegations of invalidity, and in view of the evidence submitted by the Respondent, determine whether the evidence submitted was sufficient to rebut the statutory presumption of validity. If the evidence was sufficient, the Court then considers the evidence as a whole to determine whether the Applicant had satisfied its burden of disproving the Respondent's allegation of invalidity.
Findings Required
[32] Given the nature and structure of NOC proceedings, in order to grant the requested prohibition order, the Court must come to the conclusion that Novopharm’s allegations are not justified. Conversely, in order to not grant a prohibition order, the Court must make a determination that the patent is invalid.
Experts
[33] Both parties called a host of experts. Attached as Annex 2 is a list of the experts called by each side. The experts differed in their testimony. Particularly, their evidence differs on what a person skilled in the art would have known or assumed. Their evidence will be extremely helpful in dealing with the issues of anticipation and obviousness. These issues however, are ultimately questions for the Court to decide in light of the expert testimonies received. Accordingly, I will treat the expert evidence in the same way as Campbell J. in AB Hassle v. Apotex Inc., 2003 FCT 771, (2003), 27 C.P.R. (4th) 465 at para. 16:
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.
Patent Construction
[34] Any case involving patents starts with construction of the patent. 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, Harrington J. 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.)
Patent Construction in This Case
[35] The relevant claims in the 546 Patent, claims 1, 2, and 6 read as follows:
Claim 1:
[R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-((1-
methylethyl)-3-phenyl-4-[(phenylamino)-carbonyl]-1H-pyrrole-1-heptanoic acid or (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl-N,4-diphenyl-1-[2-
(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide; and pharmaceutically acceptable salts thereof.
Claim 2:
A compound of Claim 1 which is [R-(R*R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-((1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid.
Claim 6:
The hemicalcium salt of the compound of Claim 2.
Fortunately, these complex formulae have been given simpler names such that Claims 1, 2, and 6 can be read more easily as follows:
Claim 1: Atorvastatin acid or atorvastatin lactone; and pharmaceutically acceptable salts thereof.
Claim 2: Atorvastatin acid.
Claim 6: The hemicalcium salt of the compound of Claim 2.
[36] The only claim in issue in these proceedings is Claim 6. It claims the hemicalcium salt of atorvastatin.
[37] Dr. Roush for Pfizer made the following remarks regarding a person skilled in the art:
57. I understand that the person of ordinary skill in the art is one who would share the expected common knowledge of competent ordinary workers within the field of the 546 Patent as of July 21, 1989. The “art” in this case is that of medicinal chemist, an important branch of organic chemistry that deals with the development of new drugs, typically by generating SAR data sets based on hard work and long hours in the laboratory.
58. 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 recent experience in synthesizing organic molecules.
(A.R. Vol. 3 at 441.)
[38] Dr. Heathcock for Novopharm stated with respect to a person skilled in the art:
22. It is my opinion that one of the people to whom the ‘546 patent is directed is an organic chemist who is involved in the development and synthesis of complex organic molecules, including pharmaceutical active ingredients.
23. This person would have at least a Bachelor of Science degree, and more likely a post-graduate degree, in organic chemistry or medicinal chemistry along with several years of experience in synthesizing organic compounds.
(A.R. Vol. 14 at 4661.)
[39] In other words, both parties generally agree that a person skilled in the art would be 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.
[40] Expert witnesses called as persons skilled in the art who attempted to interpret the patent were Dr. Roush, Dr. Spargo and Dr. Heathcock.
[41] Dr. Roush for Pfizer states the following:
63. The 546 Patent specifically discloses and claims atorvastatin calcium. The 546 Patent specifically discloses that atorvastatin has unexpected and surprising activity to inhibit cholesterol biosynthesis. In particular, the 546 Patent specifically discloses that atorvastatin has ten times the inhibitory activity (of the biosynthesis of cholesterol) as compared to a racemic mixture of atorvastatin and its corresponding S-trans enantiomer.
64. This increase in activity of atorvastatin over the racemic mixture is unexpected and surprising. A person of ordinary skill in the art would expect, at most, a two-fold increase in activity upon separation of the enantiomers from the racemic mixture. This two-fold activity increase assumes, however, that all of the activity of the racemic mixture resides in one of the enantiomers, the other one being totally inactive. In the case of atorvastatin, the S-trans enantiomer is not inactive. The data on page 8 of the 546 Patent shows that the S-trans enantiomer has activity. As such, the actual expected activity increase that a person of ordinary skill would anticipate for the more active enantiomer over the racemic mixture containing it would be less than two-fold. In this context, the ten-fold increase in activity is surprising and more certainly unexpected.
65. The 546 Patent identifies atorvastatin calcium as the most preferred embodiment of the invention at page 4 lines 21 to 24 wherein it states: “The most preferred embodiment of the present invention is [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)-carbonyl]-1H-pyrrole-1-heptanoic acid, hemicalcium salt”.
(A.R. Vol. 3 at 442.)
[42] Dr. Heathcock for Novopharm essentially concurs:
94. The ‘546 patent suggests that the 3R,5R isomer (also referred to as the 3-(R)-trans isomer when in the lactone form) is 10-fold more effective in inhibiting HMGR than atorvastatin racemate. It further states that this “surprising inhibition” is “unexpected,” and states that “an ordinarily skilled artisan may not predict the unexpected and surprising inhibition of cholesterol biosynthesis of the present invention.” In support of these assertions, the ‘546 patent provides on page 8 the following table of biological data:
Compound
IC50, μM/liter
[R-(R*R*)] isomer (3R,5R)
0.0044
[S-(R*R*)] isomer (3R,5R)
0.44
Racemate
0.045
95. As expected, the assay shows that the 3R,5R enantiomer is the active enantiomer. On the basis of this data, the bioactivity of the 3R,5R enantiomer would appear to be 10-fold greater than that of the racemate. A person of ordinary skill in the art would typically only expect an improvement of up to 2-fold when comparing the active enantiomer to the corresponding racemate (that is, if all of the biological activity resides in the 3R,5R enantiomer and none in the 3R,5R).
(A.R. Vol. 14 at 4284.)
[43] In addition Dr. Spargo on behalf of Pfizer asserts:
30. The 546 Patent states (on page 3) that the invention provides for compounds consisting of atorvastatin, its lactone form, and pharmaceutically acceptable salts of atorvastatin. It is stated at page 4 of the 546 Patent that “the most preferred embodiment of the present invention is [atorvastatin] hemicalcium salt.”
31. This would teach a person skilled in the art reading the 546 Patent that the hemicalcium salt of atorvastatin is preferred over all other salts. The 546 Patent therefore teaches persons skilled in the art to preferably use atorvastatin calcium.
32. The 546 Patent states that the atorvastatin enantiomer has approximately ten times the inhibitory activity of a racemic mixture. Any salts of atorvastatin would be expected to have the higher inhibitory activity than salts of the racemic mixture. Thus, when the patent states that the calcium salt is preferred, a person skilled in the art would understand that the preference necessarily refers to that salt’s superior physical properties over the other salts of atorvastatin.
(A.R. Vol. 8 at 2393.)
[44] Upon reading the patent, and taking into account the expert advice so as to read it through the eyes of a person skilled in the art, the Court reads the disclosure as explaining the following:
- atorvastatin in its lactone form, its corresponding ring-opened acid form, and the pharmaceutically acceptable salts thereof is useful for lowering cholesterol levels in mammals, including humans.
- atorvastatin in its lactone form, its corresponding ring-opened acid form, and its pharmaceutically acceptable salts thereof provides an unexpected and surprising inhibition of cholesterol biosynthesis; unexpected in that it is ten-fold increase over the inhibition provided by the racemic mixture. The data for this ten-fold increase comes from a CSI screen disclosed in the 893 Patent. All compounds for the CSI screen were prepared as described in the 893 Patent.
- the most preferred embodiment of the invention described in the 546 Patent is the hemicalcium salt of the atorvastatin acid.
- the compounds of the lactone form, the corresponding ring-opened acid form, and the pharmaceutically acceptable salts thereof all have generally equivalent utility.
Selection Patent
[45] Pfizer claims that the 546 Patent is a selection patent. Specifically, Pfizer asserts in its factum:
2. The claim at issue in this proceeding is a claim to a selection invention. The claim to atorvastatin calcium (also called the hemicalcium salt of atorvastatin) is a selection of a compound having advantageous improvements from a broad class of thousands of compounds and salts described in a prior Pfizer patent (Canadian Patent 1,268,768 (the “768 Patent”)). The invention is the selection of one specific compound, atorvastatin calcium, from that broad class of compounds and the recognition of its preferred physical properties and unexpected and surprising activity of atorvastatin calcium.
21. A person of ordinary skill would read and understand the 546 Patent as disclosing atorvastatin calcium as the particular salt form that exhibits the unexpected and surprising inhibition of cholesterol biosynthesis and having the most preferred physical properties. In terms of formulation, “most preferred properties” would be understood by persons of ordinary skill to represent the salt form with the best combination of physical properties -- including solubility, hygroscopicity, stability and processability.
37. … Thus, atorvastatin calcium not only has surprising and unexpected biological activity, it also has the best set of physical properties, which was also surprising and unexpected. In fact, it was the selection of the calcium salt which made atorvastatin a commercially feasible product for the first time.
(A.R. Vol. 29 at 9940, 9945, 9950 [underlining added].)
[46] According to Pfizer, the 546 Patent reveals two special advantages of the hemicalcium salt of the atorvastatin acid over the rest of the group (in this case the racemic mixture of the atorvastatin and the S-trans enantiomer of the atorvastatin), namely:
a. an unexpected ten-fold increase in activity when a person skilled in the art would have only expected a two-fold one, and
b. the best combination of physical properties of this salt -- including solubility, hygroscopicity, stability and processability, over all the other salts mentioned in the 893 Patent.
[47] Novopharm disputes both of these claims. It alleges that the data regarding the ten-fold advantage is unreliable (more about that later) and that no special advantage regarding the hemicalcium salt of atorvastatin is provided within the 546 Patent.
[48] The rules for selection patents are well known and have their origin in I.G. Farbenindustrie A.G.’s Patents (1930), 47 R.P.C. 289 at 322 (High. Ct. Ch.) where Maugham J. observed:
Three general propositions may, however, I think, be asserted as true: - First, a selection patent to be valid must be based on some substantial advantage to be secured by the use of the selected members. (The phrase will be understood to include the case of a substantial disadvantage to be thereby avoided.) Secondly, the whole of the selected members must possess the advantage question. Thirdly, the selection must be in respect of a quality of a special character which can fairly be said to be peculiar to the selected group.
[49] The rationale for such policy can be found in Lord Glaisdale’s observation in E.I. du Pont de Nemours & Co. (Witsiepe’s) Application, [1982] F.S.R. 303 at 313 (H.L.) [underlining added]:
The type of invention which the law of selection patents was designed to foster appears from the speech of my noble and learned friend, Lord Diplock, in Beecham Group Ltd. v. Bristol Laboratories International S.A. [1978] R.P.C. 521, 579:
“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 (In re I.G. Farbenindustrie A.G.’s Patents (1930) 47 R.P.C. 283 per Maugham J. at pp. 322/3.) The quid prop 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.”
[50] I propose to deal with these propositions in the reverse order. In light of the above jurisprudence, I have some trouble agreeing with the second proposition that the 546 Patent selects the hemicalcium salt of the atorvastatin acid from all the other pharmaceutically acceptable salts. Admittedly, the disclosure of the 546 Patent states at page 4, lines 21-24:
The most preferred embodiment of the present invention is [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)-carbonyl]-1H-pyrrole-1-heptanoic acid, hemicalcium salt.
[51] Dr. Spargo points out that a person skilled in the art would know that this refers to “that salt’s superior physical properties over the other salts of atorvastatin” (A.R. Vol. 8 at 2394).
[52] Even Dr. Adelstein, Novopharm’s witness conceded this point under cross examination.
Q. This is teaching you that, of all the aspects of the invention that are disclosed in the ‘546 patent, the most preferred embodiment is the atorvastatin hemicalcium salt. Right?
A. Yes.
Q. You would agree then that, reading the ‘546 patent, the person of ordinary skill in the art would know that atorvastatin calcium is the most preferred embodiment of this invention?
A. Yes.
(A.R. Vol. 16 at 5066.)
[53] From the various experts, it seems clear that typically, the preferred properties of a salt are low hydroscopicity, good dissolution and good compaction. However, the 546 Patent does not tell the world in what way the properties of the hemicalcium salt are unexpectedly superior over other pharmaceutically acceptable salts. In other words, the patent does not disclose the special advantage peculiar to the hemicalcium salt that was hitherto unknown and that is revealed in the 546 Patent.
[54] I have no reason to reject Dr. Spargo’s and Dr. Adelstein’s explanation (that a person skilled in the art knows that ‘preferred embodiment’ refers to that salt’s superior physical properties over the other salts of atorvastatin). However, this is not enough for a selection patent; it is an insufficient disclosure as the special characteristics of hemicalcium are neither identified nor quantified. The mere assertion that the hemicalcium salt of atorvastatin is the preferred embodiment of the invention does not meet the requirements of a selection patent. As Maughan J. specifically stipulated in I. G. Farbenindustrie, supra at 323 [underlining added]:
I must add a word on the subject of the drafting of the specification of such a patent. It should be obvious, after what I have said as to the essence of the inventive step, that it is necessary for the patentee to define in clear terms the nature of the characteristic which he alleges to be possessed by the selection for which he claims a monopoly. He has in truth disclosed no invention whatever if he merely says that the selected group possesses advantages. Apart altogether from the question of what is called sufficiency, he must disclose an invention; he fails to do this in the case of a selection for special characteristics, if he does not adequately define them. The cautions repeatedly expressed in the House of Lords as regards ambiguity have, I think, special weight in relation to selection patents. (Natural Colour etc. Ld. v. Bioschemes Ld., (1915) 39 R.P.C. 256, at p. 266; and see British Ore etc. Ld. v. Minerals Separation Ld., (1910) 27 R.P.C. 33, at p. 47.)
[55] As the foregoing analysis has shown, the 546 Patent does not meet the requirements of a valid selection patent claim in terms of a salt selection.
Significance of Selection Patent
[56] The entire case stands or falls on the issue of selection patent and specifically the ten-fold increase in activity of one of the enantiomers over the racemate. If the 546 Patent is a valid selection patent, this is a complete answer to the allegations of anticipation, obviousness and double patenting. None of Novopharm’s witness have asserted either:
a. that a ten-fold activity was anticipated on the basis of the 893 Patent;
b. that it was obvious to a person skilled in the art that resolving the racemate of atorvastatin would result in a ten-fold increase of activity by the enantiomer; quite the contrary they allege that a two-fold increase was to be expected; or
c. that the 441 Patent or the 768 Patent discloses or claims an enantiomer of atorvastatin that displays a ten-fold increase of activity of the enantiomer over the racemate.
[57] Pfizer in its first proposition asserts that the 546 Patent is a selection patent that selects atorvastatin in its lactone form, its corresponding ring-opened acid form, and the pharmaceutically acceptable salts thereof from the range of compounds described in the 893 Patent. According to Pfizer, the 546 Patent discloses an unexpected advantage hitherto unknown: the ten-fold increase in activity in lieu of the expected two-fold increase. Thus, the key issue becomes whether Novopharm can effectively challenge the 546 Patent as a selection patent; i.e., challenge the claim to the ten-fold increase in activity. In my view, it cannot for the following reasons.
I. Insufficiency of the NOA
[58] Novopharm in its NOA makes allegations of invalidity based on anticipation, obviousness and double patenting. The NOA makes absolutely no reference to selection patents or inutility. Nor is there any mention that the data used to support the selection patent is questionable, unreliable or unsupported.
[59] Novopharm takes the position that the NOA is not deficient. It argues that implicit in the allegations of anticipation, obviousness and double patenting is the allegation that the 546 Patent is not a selection patent. This selection patent is based on an alleged ten-fold advantage. That advantage depends on the CSI 118 data displayed in the disclosure of the patent. Therefore, although neither selection patent nor defective data are mentioned in the NOA, Novopharm maintains that they are implicitly ‘in play’ through the allegation of anticipation, obviousness and double patenting.
[60] Novopharm further asserts that it did not know that the issue of selection patents would be raised or that the support for the data was based on such fragile grounds until it received the affidavits from Pfizer and cross-examined on them.
[61] Finally, Novopharm argues that P