Aventis Pharma Inc. v. Apotex Inc.

Aventis Pharma Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2005-09-20
Neutral citation
2005 FC 1283
File numbers
T-1742-03
Notes
Digest
Decision Content
Date: 20050920
Docket: T-1742-03
Citation: 2005 FC 1283
OTTAWA, ONTARIO, SEPTEMBER 20, 2005
PRESENT: THE HONOURABLE MADAM JUSTICE MACTAVISH
BETWEEN:
AVENTIS PHARMA INC.
Applicant
and
APOTEX INC. AND THE MINISTER OF HEALTH
Respondents
and
SCHERING CORPORATION
Respondent/Patentee
REASONS FOR ORDER AND ORDER
TABLE OF CONTENTS
PARA.
I. Introduction........................................................................................................................... 1
II. Nature of the Proceedings..................................................................................................11
III. Stereochemistry..................................................................................................................25
IV. Background........................................................................................................................35
V. Schering's Work on ACE Inhibitors..................................................................................43
VI. The '206 Patent..................................................................................................................53
VII. The Construction of Claim 12...........................................................................................61
VIII. Issues..................................................................................................................................73
IX. The Burden and Standard of Proof....................................................................................75
X. Sound Prediction...............................................................................................................81
i) The Proper Date for Assessing the Soundness of Schering's
Prediction..............................................................................................................88
ii) Was There a Factual Basis for the Prediction? and
Did the Inventors Have an Articulable Line of Reasoning from Which the Desired Result Could Be Inferred from the Factual
Basis?....................................................................................................................98
iii) Conclusion on the First Two Elements of the Wellcome Test.............................156
iv) Was There Proper Disclosure?............................................................................159
a) Operability of Example 20A....................................................................167
b) Sufficiency of the NOA...........................................................................174
c) Does Example 20AWork?.......................................................................178
d) Should the Barton, Teetz and Taylor Declarations be
Admitted as Evidence?............................................................................194
e) Analysis With Respect to the Operability of Example 20.......................207
f) Were There Other, Non-Inventive Ways to Do It?..................................217
g) Sufficiency in Relation to the Issues of Separation and
Characterization.......................................................................................223
h) Analysis...................................................................................................243
v) Conclusion with Respect to the Third Element of the
Wellcome Test......................................................................................................253
vi) Conclusion with Respect to Sound Prediction.....................................................255
XI. Are the Claims in Issue in the '206 Patent Invalid for Failure to
Comply with the Requirements of Subsection 34(1) of the Old
Patent Act?.......................................................................................................................259
XII. Are the Claims in Issue Broader than the Invention or
Do They Lack Utility?.....................................................................................................269
i) The Law Relating to Utility.................................................................................270
ii) What did the '206 Patent Promise by Way of Utility?........................................276
iii) The Evidence Relating to Utility.........................................................................282
iv) Analysis................................................................................................................294
v) Conclusion in Relation to the Issue of Utility......................................................322
XIII. Overlap Issues..................................................................................................................323
XIV. Are the Claims in Issue Invalid By Reason of Anticipation?..........................................332
XV. Are the Claims in Issue in the '206 Patent Invalid by
Reason of Section 61(2) of the Old Patent Act?..............................................................350
XVI. Are the Claims in Issue in the '206 Patent Invalid
by Reason of Double Patenting?.....................................................................................355
XVII. Conclusion.......................................................................................................................369
XVIII. Costs.................................................................................................................................370
XIX. Order................................................................................................................................372
I. INTRODUCTON
[1] Angiotensin I is a peptide occurring naturally in the human body. As a result of the action of an enzyme known as angiotensin converting enzyme or "ACE", angiotensin I is converted by the body into a second peptide known as Angiotensin II. Angiotensin II is a vasoconstrictor or pressor. That is, it causes the muscles surrounding blood vessels to contract, thereby narrowing the blood vessels, causing blood pressure to rise.
[2] It has long been posited that if one could affect the synthesis of angiotensin II through the inhibition of ACE, blood pressure in humans could be lowered. By the late 1970's, a number of pharmaceutical companies were actively involved in research in this area.
[3] On October 20, 1981, Schering Corporation filed an application for a Canadian patent for a group of compounds which were said to be useful as ACE inhibitors and anti-hypertensive agents. As a result of protracted conflict proceedings, patent 1,341,206 (the '206 patent) did not issue until March 20, 2001.
[4] Under a licence granted by Schering, Aventis Pharma Inc. manufactures a drug containing a medicine called ramipril, which is one of the compounds covered by the '206 patent. It is common ground that ramipril is an extremely effective ACE inhibitor.
[5] In accordance with Section 5 of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, on June 20, 2003, Apotex Inc. served a Notice of Allegation on Aventis in relation to ramipril. In its Notice, Apotex asserts that the '206 patent is invalid on a number of bases. Apotex contends that Schering did not have a valid basis for soundly predicting that the compounds in the'206 patent, and, in particular, in Claim 12 of the patent, would, if made, be useful for their stated purpose. Apotex further says that the '206 patent is invalid as the claims are broader than the invention and lack utility. Apotex also challenges the validity of the '206 patent on the grounds of insufficiency, anticipation and double patenting.
[6] In addition, Apotex relies on section 61(2) of the pre-1989 Patent Act, R.S.C. 1970, c. P-4 (the "old Patent Act") to say that the '206 patent should not have issued in light of the fact that other patents had been granted to Aventis' predecessor, Hoechst Aktiengesellschaft (patent No. 1,187,087 or the "'087 patent" and patent No. 1,246,457 or the "'457 patent". The '087 patent covers some of the compounds within the '206 patent, including ramipril, whereas the '457 patent covers the use of compounds, including ramipril, for the treatment of cardiac insufficiency.
[7] Finally, Apotex asserts that a conflict should have been declared between the '206 patent and the '087 patent.
[8] In this application, Aventis seeks an order declaring that the Notice of Allegation is not a valid Notice of Allegation as contemplated by the PM(NOC) Regulations. In the alternative, Aventis seeks an order prohibiting the Minister of Health from issuing a Notice of Compliance to Apotex for ramipril until after the expiration of the '206 patent. Because of its interest in these proceedings, as owner of the '206 patent, Schering has been named as a respondent in this case, although it is allied in interest with Aventis.
[9] The Minister of Health did not participate in the hearing of this matter.
[10] For the reasons that follow, I am dismissing Aventis' application.
II. NATURE OF THE PROCEEDINGS
[11] Aventis' application is brought under the PM(NOC) Regulations. The legislative history and purpose of these Regulations has been described in detail in a number of decisions, and need not be repeated here. (See, for example, Bristol-Myers Squibb Co. v. Canada (Attorney General), [2005] S.C.C. No. 26; Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare), [1994] F.C.J. No. 662, 55 C.P.R. (3d) 302 (F.C.A.); AB Hassle v. Canada (Minister of National Health and Welfare), [2000] F.C.J. No. 855, 7 C.P.R. (4th) 272 ; and Novartis AG et al. v. Abbott Laboratories Ltd. et al., [2000] F.C.J. No. 941, 7 C.P.R. (4th) 264 (F.C.A.)).
[12] For the purpose of this proceeding, it is, however, helpful to have some understanding of the regulatory scheme as it relates to disputes of this nature.
[13] The Supreme Court of Canada has accepted the view that the PM(NOC) Regulations were enacted to thwart the possible appropriation by generic drug companies of the research and development initiatives of innovator companies: Bristol-Myers Squibb Co., supra, at para. 45.
[14] Under the terms of the licence between Aventis and Schering, Aventis is entitled to manufacture and sell ramipril in Canada. In accordance with the Regulations, Aventishas listed the '206 patent on the Patent Register maintained by the Minister of Health, in relation to ramipril oral capsules in a variety of strengths.
[15] Apotex would like to be able to manufacture and sell ramipril in Canada, but cannot do so without first being issued a Notice of Compliance (NOC) by the Minister.
[16] In this proceeding, Aventis seeks to prohibit the Minister from issuing a NOC to Apotex, on the basis that the manufacture and sale of ramipril by Apotex would infringe the '206 patent. As noted earlier, Apotex asserts that, for a number of different reasons, the '206 patent is not valid. There is no issue of infringement in this case.
[17] The issues of patent validity between Aventis and Schering, on the one hand, and Apotex on the other, originate with the service of Apotex's Notice of Allegation (NOA) on Aventis. Pursuant to sub-section 5(3) of the PM(NOC) Regulations, Apotex is required to include a detailed statement of the legal and factual basis for its allegations in its NOA.
[18] In accordance with section 6 of the Regulations, Aventis has applied for an order prohibiting the Minister of Health from issuing a Notice of Compliance to Apotex until after the '206 patent has expired.
[19] Proceedings under section 6 of the PM(NOC) Regulations are not to be equated with actions for the determination of patent validity or infringement. Rather, they are judicial review proceedings, whose aim is to determine whether the Minister is free to issue the requested NOC to Apotex.
[20] The scope of such proceedings is limited to administrative purposes - that is, whether or not a NOC should issue to Apotex: Apotex Inc. v. Canada (Minister of National Health and Welfare), [1997] F.C.J. No. 1251, 76 C.P.R. (3d) 1 (F.C.A.). My decision must turn on whether the allegations made by Apotex are justified so as to support the conclusion, for administrative purposes, that the '206 patent would not be infringed if Apotex's product were put on the market: Pharmacia Inc. v. Canada (Minister of National Health and Welfare), [1995] 1 F.C. 588, 58 C.P.R. (3d) 209 (F.C.A.).
[21] Under the regulatory scheme, by commencing this proceeding, Aventis obtains what is tantamount to an interlocutory injunction, without having first satisfied any of the usual criteria for the obtaining of such relief: Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare), [1998] 2 S.C.R. 193. As the Supreme Court of Canada noted in the Bristol-Myers Squibb Co. decision previously cited, in such circumstances, applications for NOC's such as that filed by Apotex simply go into the 'deep freeze' until the statutory procedures play themselves out (assuming that this occurs within the 24 month period provided for in the Regulations).
[22] It is the existence of this statutory freeze that has caused the Supreme Court of Canada to describe this process as 'draconian': Merck Frosst, supra.
[23] The PM(NOC) Regulationsallow the Court to determine summarily, on the basis of the evidence adduced, whether Apotex's allegations are justified. Section 6 proceedings cannot be treated as res judicata: AB Hassle v. Genpharm Inc., [2003] F.C.J. No. 1910, 2003 FC 1443,
_ 11.
[24] These proceedings do not serve to deprive either Aventis or Scheringof any rights that they might otherwise have with respect to the '206 patent. If a full trial of the validity issues is required, this can be obtained in the usual way by commencing an action: Pfizer Canada Inc. v. Apotex Inc. (2001), 11 C.P.R. (4th) 245 (F.C.A.), _ 25; Novartis A.G. v. Apotex Inc. (2002), 298 N.R. 348 (F.C.A.), 2002 FCA 440, _ 9.
III. STEREOCHEMISTRY
[25] Before turning to the facts of this case, it is first necessary to have an understanding of certain chemical structures and conventions, in order to understand the nature of the invention claimed in the '206 patent.
[26] "Stereochemistry" is concerned with the three dimensional spatial orientation of compounds made up of atoms. Molecules having exactly the same chemical composition and the same sequence of covalent bonds may differ in their arrangement in three dimensions. Such compounds are referred to as "stereoisomers".
[27] The term "chiral centres", as it appears in stereochemistry, is used in connection with carbon atoms. A carbon atom with four different functional groups attached to it is referred to as a "chiral centre". A chiral centre may have two possible arrangements, such that one arrangement may not be superimposable on the other by rotating in space. In such cases, the carbon atom is referred to as stereogenic, and the compound is termed 'chiral'.
[28] In order to describe the stereochemistry of molecules having chiral centres, chemists have devised a number of conventions. Where the direction from the highest to lowest priority atom or group attached to the chiral carbon, determined by atomic number, is clockwise, the chiral centre is described as being in the "R" position, whereas a counter-clockwise arrangement is referred to as "S".
[29] Because chiral centres exist in three dimensions, it is necessary to have a convention for indicating the atoms' position in space, when molecules are represented on paper. To distinguish isomers based on the arrangement of the atoms attached to the chiral centre in space, chemists show a bond that projects up from the plane of the paper, towards the viewer, with a solid wedge shape. A chemical bond that projects away from the viewer is indicated by a hatched wedge shape.
[30] Where two groups are attached to separate carbon atoms, chemists use the term "cis" to describe situations where both groups are on the same side of the plane. The term "trans" is used where the two groups are on opposite sides of the plane.
[31] Pairs of mirror image molecules that cannot be superimposed on each other are referred to as enantiomers. In this regard, an analogy is often drawn to left and right hands. Diasteromers are stereoisomers that are different in stereochemistry and which are not mirror images. Enantiomers have identical physical properties, whereas diasteromers differ in their physical properties. That is, diasteromers will have different melting and boiling points, solubility, reactivity, affinity towards adsorbents and partition coefficients. These differences are important, as they can be used by a person skilled in the art to separate diasteromers.
[32] Stereochemistry played a very important role in the development of ACE inhibitors, as ACE is a chiral molecule. To be effective as an ACE inhibitor, the compound in question must be able to interact with the chiral ACE. ACE will exhibit a preference for certain chiral configurations - just as a left hand will prefer a left glove. The closer the fit of the chiral ACE molecule to the ACE inhibitor - the more effective will be the inhibitory effect.
[33] The development of ACE inhibitors in the late 1970's and early 1980's was complicated by the fact that the precise configuration of ACE was not known, and, indeed, has only recently been understood.
[34] With this understanding of some of the basic concepts of stereochemistry, I turn now to review the events leading up to the development of Schering's ACE inhibitors.
IV. BACKGROUND
[35] The development of ACE inhibitors originated with the discovery that a series of peptides isolated from the venom of the Brazilian Pit Viper could be effective in inhibiting ACE, in vitro. A compound known as teprotide was subsequently synthesized, which proved to be an effective anti-hypertensive agent in humans. However, teprotide was only effective through intravenous administration.
[36] The transformation of an intravenously active peptide into an orally effective ACE inhibitor occurred as a result of work done by a group working for Squibb, headed by Dr. Miguel Ondetti. Although the precise structure of ACE was not known at the time, the Squibb scientists were able to construct a model for ACE, relying upon what was known about another enzyme known as carboxypeptidase A.
[37] Based upon this analogy, in 1977, the Squibb group developed a compound known as captopril. Captopril was the first small molecule, orally effective ACE inhibitor. The molecular structure of captopril is:
[38] It should be noted that there are two chiral centres in captopril, both of which are in the "S" configuration. The five-membered ring structure on the right side of the molecule is a naturally occurring amino acid known as proline.
[39] Although captopril functioned as an ACEinhibitor, it did produce a number of side-effects, such as loss of taste, the excretion of protein in urine and skin rashes. Nevertheless, its success prompted a number of other pharmaceutical companies to try to develop new and patentable analogs.
[40] In particular, Merck, Sharp and Dohme focussed on removing the thiol group (the structure on the left side of the captopril molecule), replacing it with a carboxmethyl function. On June 18, 1980, at a medicinal chemistry conference in Troy, New York, Merck disclosed that it had developed a compound known as enalapril, which had demonstrated activity as an ACEinhibitor.
[41] The structure of enalapril is:
[42] As can be seen from this diagram, enalapril has three chiral centres, all in the "S" configuration. It can also be observed that while enalapril lacks the sulphur moiety present in captopril, what remained consistent from captopril to enalapril was the presence of the proline unit or five-membered ring structure on the right side of the compound.
V. SCHERING'S WORK ON ACEINHIBITORS
[43] Although more will be said further on in this decision about the development work done by Schering during the late 1970's and early 1980's, it is helpful at this point to have an overview of the nature of the research work that was being done by Schering leading up to the application for what would become the '206 patent.
[44] Prior to the Merck announcement at the Troy conference in June of 1980, scientists at Schering, including Dr. Elizabeth Smith, were trying to develop an anti-hypertensive compound that would be more effective than captopril. While Merck's work involved the removal of the thiol group, Schering's work focussed on a different aspect of the captopril molecule - that is the proline unit.
[45] By late 1979 or early 1980, Dr. Smith and her colleagues had found that the replacement of the proline in captopril with certain fused ring or spirocyclic moieties resulted in efficacious compounds.
[46] As a result of the Merck disclosure at the Troy conference, the Schering scientists decided to try to create compounds based, in part, upon the Merck work on the thiol end of the molecule, but also using the fused ring moieties that Schering had already been working on in relation to the proline end of the molecule. That is, Schering's scientists decided to try using various bicyclic ring structures in place of the proline on an enalapril-typemolecule.
[47] This proposed work was documented in an invention disclosure report dated June 20, 1980. According to Dr. Smith, this report shows the conception of the generalized structure of the compounds in what ultimately became the '206 patent.
[48] On August 5, 1980, Dr. Smith made the first compound within the scope of the '206 patent, which became known as SCH 31335. Over the next few months, Dr. Smith and the other scientists at Schering made several of these compounds using different bicyclic ring structures. Initial testing of these compounds indicated that they demonstrated ACE inhibition activity.
[49] On October 23, 1980, Scheringapplied for a patent in the United States in relation to this work. A second American patent was applied for on April 28, 1981.
[50] Throughout this time, Dr. Smith and her colleagues continued to create and test additional compounds using the bicyclic ring structure coupled with Merck's enalapril-type "backbone". One of the compounds created during this period was SCH 31925, which contained molecules having a 5,5 ring structure at the proline end. Preliminary pharmacological testing revealed that SCH 31925 was a potent ACE inhibitor.
[51] Dr. Smith says that SCH 31925 is within the scope of Claim 12 of the '206 patent, which, the parties are agreed, is the primary claim in issue in this case.
[52] On Oct. 20, 1981, Schering applied for patent protection in Canada for its work in this area. Schering's application claimed priority dates of October 23, 1980, and April 28, 1981, based upon the American patent application dates. The Canadian application ultimately resulted in the issuance of the '206 patent in March of 2001.
VI. THE '206 PATENT
[53] The '206 patent is entitled "Carboxyalkyl Dipeptides, Processes for Their Production and Pharmaceutical Compositions Containing Them". The patent states at page one that it relates to compounds (carboxyalkyldipeptides) which are useful as inhibitors of angiotensin-converting enzyme and as anti-hypertensive agents.
[54] The '206 patent covers within its claims three currently commercial compounds - ramipril, spirapril and trandolapril. This makes it an extremely valuable patent. Its value is enhanced by the fact that the patent only issued in 2001, and thus has some 13 years left to run.
[55] The claims of the '206 patent are broad and cover a genus of compounds that include ramipril. It should be noted, however, that nowhere in the '206 patent is there specific disclosure of either ramipril or ramiprilat, nor any claim or claims directed to those compounds alone. Ramiprilat is the metabolite formed in the body of those who take ramipril.
[56] The breadth of the scope of the '206 patent is confirmed by the evidence of Dr. Garland Marshall, whose affidavit was filed by Apotex. Dr. Marshall is a Professor of Biochemistry and Molecular Biophysics and of Biomedical Computing at the Washington University School of Medicine at Washington University.
[57] Claim 1 of the '206 patent claims a genus of carboxyalkyldipeptides of a general formula consisting of three main units: (a) bicyclic rings in a variety of configurations; (b) a central alanyl unit; and (c) the end chain unit, and is not limited to a specific stereochemistry. Dr. Marshall estimates that there are in excess of 24,000,000 compounds included within Claim 1.
[58] Claim 2 also covers compounds with a specified general formula and is not limited to specific stereoisomers. Dr. Marshall estimates that the number of compounds encompassed by this claim to be in excess of 200,000,000.
[59] The claims in issue in this case are Claims 1, 2, 3, 6, 12 and 13. Dr. Marshall estimates the number of compounds encompassed by Claims 3, 6, 12 and 13 to range from 150,000, in the case of Claim 3, to 8 in the case of each of Claims 12 and 13.
[60] Ramipril is one of the compounds that comes within Claims 1, 2, 3, 6, and 12 of the '206 patent. Claim 13 covers a number of compounds, including ramiprilat.
VII. THE CONSTRUCTION OF CLAIM 12
[61] Before addressing the issues relating to the validity of the '206 patent, it is necessary to construe the patent. The construction of a patent is a matter of law: Canamould Extrusions Ltd. v. Driangle Inc., [2004] F.C.J. No. 226, 30 C.P.R. (4th) 129 _ 3 (F.C.A.).
[62] The jurisprudence relating to the construction of patents was recently succinctly summarized by Justice Mosley in Merck & Co. v. Apotex Inc., [2005] F.C.J. No. 937, 2005 FC 755, _ 26, where he stated:
A 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. Claims are to be read in an informed and purposive way to permit fairness and predictability and to define the limits of the monopoly. 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, supra at paragraph 45).
[63] The patent is not addressed to an ordinary member of the public, but to a worker skilled in the art described by Dr. Harold 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. This hypothetical person has sometimes been equated with
the "reasonable man" used as a standard in negligence cases. He is assumed to be a
man who is going to try to achieve success and not one who is looking for difficulties
or seeking failure."
(H.G. Fox, in The Canadian Law and Practice Relating to Letters Patent for Inventions, 4th Ed. (Toronto: Carswell Co. Ltd., 1969) at p. 184, cited in Free World Trust v. Électro Santé Inc., [2000] 2 S.C.R. 1024, 2000 SCC 66, _ 44).
[64] In the case of patents of a highly technical and scientific nature, the person skilled in the art would be someone "possessing a high degree of expert scientific knowledge and skill in the particular branch of the science to which the patent related": Consolboard Inc. v. MacMillan Bloedel (Saskatchewan) Ltd., [1981] 1 S.C.R. 504.
[65] There is no question that a patent filed under the old Patent Act is to be construed as of the date of issue: Free World Trust, supra, _ 54. The '206 patent was issued on March 20, 2001.
[66] The parties agree that Claim 12 is the narrowest claim in the '206 patent, and that Apotex's case will stand or fall on whether it succeeds in relation to this claim. It is therefore unnecessary to construe any of the other claims.
[67] Claim 12 reads:
The compound 1-[N-(1-carboethoxy-3-phenylpropyl-(S)-
alanyl]octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid and
its pharmaceutically acceptable salts thereof.
The parties also agree that Claim 12 can properly be depicted as:
[68] The proper construction of Claim 12is not in dispute in this case. The parties are in agreement that properly construed, Claim 12 is directed to a compound, and describes a genus of eight stereoisomers, one of which is ramipril.
[69] The general structure of Claim 12 depicted above describes a group of molecules with a 5,5 bicyclic ring structure in lieu of the proline ring in the class of compounds disclosed and claimed by Merck in the enalapril patent.
[70] The molecular structure of Claim 12 has five chiral centres, each of which is indicated with an asterisk in the above diagram. The claim restricts the stereochemistry of two of the chiral centres to the "S" position. The two chiral centres contain the carbons to which the carboxylic acid (-COOH) and the methyl (-COOC2H5) are attached. The stereochemistry of the three remaining chiral centres is not specified, meaning that they can have either an "R" or an "S" configuration.
[71] Given that the three unspecified chiral centres can be in either the "R" or "S"configuration, the formula of Claim 12describes 2x2x2 (23 or 8) stereoisomers.
[72] In the case of ramipril, all five chiral centres are in the "S" position.
VIII. ISSUES
[73] The central issue to be determined in this case is the validity of the '206 patent in light of Apotex's allegations. Apotex's Notice of Allegation raises the following issues in relation to the validity of the '206 patent:
1. Did Schering have a sound basis for predicting that the compounds covered by the claims in issue would be useful as ACE inhibitors and in the treatment of hypertension in humans?
2. Are the claims in issue in the '206 patent invalid for failure to comply with the requirements of section 34 of the old Patent Act("insufficiency")?
3. Are the claims in issue broader than the invention or do they lack utility?
4. Are the claims in issue invalid by reason of anticipation?
5. Are the claims in issue in the '206 patent invalid by reason of section 61(2) of the old Patent Act? and
6. Are the claims in issue in the '206 patent invalid by reason of double patenting?
[74] In its Notice of Application for Judicial Review, Aventis asserts that Apotex's NOA is a nullity. At the hearing of this application, both Aventis and Schering identified several areas in which they say that Apotex either failed to provide a sufficient factual and legal basis to support its arguments, or was trying to rely on evidence or arguments that were not identified in the NOA. Each of the arguments as to the alleged deficiencies in Apotex's NOA will be addressed in the context in which they arise in the course of this decision.
IX. THE BURDEN AND STANDARD OF PROOF
[75] Before turning to consider each of the attacks on the validity of the '206 patent mounted by Apotex, threshold questions arise as to the burden and standard of proof in proceedings such as this. Each of the parties made extensive submissions at the hearing as to their respective perspectives on these questions.
[76] It is not necessary to review the various authorities cited by each of the parties to support their arguments on these issues, as it appears from the recent jurisprudence emanating from the Federal Court of Appeal that the matter is now well settled: see Proctor and Gamble Pharmaceuticals Canada Inc. v. Canada (Minister of Health), [2004] F.C.J. No. 1973, 2004 FCA 393, _ 12-24.
[77] As the Applicant in these proceedings, Aventis has the overall burden of establishing that none of Apotex's allegations are justified. In this case, all of the issues raised by Apotex in its NOA relate to the validity of the '206 patent. In the absence of evidence to the contrary, there is a statutory presumption that a patent is valid: section 45 of the old Patent Act, subsection 43(2) of the post-1989 Patent Act, R.S.C. 1985, c.P-4.
[78] Relying upon the presumption of validity, Aventis can thus meet its initial burden merely by proving the existence of the patent.
[79] Once this is done, the burden shifts to Apotex to establish that the patent is invalid. The standard of proof that Apotex is required to satisfy is that of a balance of probabilities: Bayer v. Canada (Minister of National Health and Welfare), [2000] F.C.J. No. 464, 6 C.P.R. (4th) 285 (F.C.A.), _ 9.
[80] With this understanding of the burden and standard of proof, I turn now to consider the various grounds of attack on the validity of the '206 patent raised by Apotex in its Notice of Application.
X. SOUND PREDICTION
[81] Much of the time in this hearing was devoted to the question of whether Scheringhad a sound basis for predicting that the compounds covered by the claims in issue, and, in particular, by Claim 12 of the '206 patent, would be useful as ACEinhibitors, and in the treatment of hypertension in humans.
[82] To be patentable, an invention must be useful. Where the compound is a new one, its utility need not be stated in the claims, but utility must be set out in the disclosure.
[83] In the case of a pharmaceutical invention, utility may be demonstrated through testing. It is not, however, essential that complete testing have been carried out: the doctrine of sound prediction can be relied upon by an inventor to justify patent claims whose utility has not been actually demonstrated, but can be soundly predicted based upon the information and expertise available: Apotex Inc. v. Wellcome Foundation Ltd., [2002] 4 S.C.R. 153, 2002 SCC 77.
[84] In Wellcome, the Supreme Court of Canada noted that the doctrine of sound prediction balances the public interest in the early disclosure of new and useful inventions - even before their utility has been fully verified by tests - with the public interest in avoiding the granting of monopoly rights in exchange for speculation, misinformation or lucky guesses: supra, _ 66 and 69.
[85] The soundness or otherwise of the prediction is a question of fact.
[86] In the Wellcome case, the Supreme Court of Canada articulated a three-part test that must be satisfied in order to establish that a sound prediction has been made by the purported inventor. The three elements of the test are:
1. There must be a factual basis for the prediction;
2. The inventor must have an articulable line of reasoning from which the desired result can be inferred from the factual basis; and
3. There must be proper disclosure, although it is not necessary to provide a theory as to why the invention works.
[87] To be sound, a prediction does not need to amount to a certainty, as it does not exclude the risk that some compounds within the area claimed may prove to be devoid of utility.
i) The Proper Date for Assessing the Soundness of Schering's Prediction
[88] There was much debate between the parties at the hearing as to the proper date to be used to assess the soundness of the prediction made by the '206 patent. Apotex says the soundness of Schering's prediction should be determined as of the earliest of the priority dates claimed in the Canadian patent application - that is, October 23, 1980, whereas Aventis and Schering both submit that the date that should be used is the Canadian filing date of October 20, 1981.
[89] This issue is important, as the soundness of a prediction is to be assessed based upon the information and expertise available at the relevant time. The determination of whether the October 23, 1980 priority date is to be used versus the October 20, 1981 Canadian filing date affects whether, in assessing the soundness of the prediction, regard may be had to the work that Dr. Smith and her colleagues at Schering did between October of 1980 and October of 1981 in formulating and testing compounds within the '206 patent.
[90] The parties all rely on the Supreme Court's decision in the Wellcome case to support their respective positions regarding the relevant date.
[91] A review of the Wellcome decision discloses that there was no debate between the parties as to the appropriate date for assessing the soundness of the prediction in issue, and, perhaps as a result of this, the phrases "application date" and "priority date" are used virtually interchangeably in the decision. By way of example, at paragraphs 3, 56, 71 and 72, Justice Binnie refers to the priority date as being the date to be used in evaluating the soundness of the inventor's prediction, whereas in paragraphs 46, 55 and 97 reference is made to the date of the Canadian application as being the relevant date.
[92] However, it is in paragraph 70 of the decision that the Court sets out the tripartite test for sound prediction, explicitly stating that "[T]he inventor must have at the date of the patent application an articulable and 'sound' line of reasoning from which the desired result can be inferred from the factual basis".
[93] Thus, while the issue is not free from doubt, it appears that the Wellcome test contemplates that the Canadian filing date be used for the purposes of assessing the soundness of the prediction.
[94] This makes a certain amount of sense, from a policy perspective, as it is only when the application for patent protection is filed in Canada that the inventor is required to commit him- or herself to the precise details of the patent claims and specification for the purposes of obtaining a monopoly in Canada.
[95] The date of filing for patent protection in another country may be of some assistance in ascertaining the date of the invention for patents governed by the old Patent Act (the new Patent Act contemplates a 'first to file' priority system as opposed to the 'first to invent' regime under the former legislation). Nevertheless, as happened here, inventors are free to continue to carry out additional research and testing, and to add additional information to the patent claims and specification, prior to filing for a patent in Canada.
[96] As a consequence, I intend to assess the soundness of Schering's prediction based upon the information and expertise available as at October 20, 1981. However, for the reasons that follow, it is not necessary to finally resolve this issue in this case, as I am satisfied that even using the later Canadian application date, as submitted by Aventis and Schering, Schering did not have a sound basis for predicting that the compounds coming within the '206 patent would be useful as ACEinhibitors and anti-hypertensive agents.
[97] In applying the three-part Wellcome test, the parties generally dealt with the first two issues together, and I intend to do so here.
ii) Was There a Factual Basis for the Prediction? and
Did the Inventors Have an Articulable Line of Reasoning from Which the Desired Result Could Be Inferred from the Factual Basis?
[98] The first issue that has to be addressed is the sufficiency of Apotex's NOA as it relates to the first two parts of the Wellcome test.
[99] In its NOA, Apotex asserts that:
We also allege that each of the Claims in Issue of the '206 Patent is invalid on the basis that the claims are broader than the invention (if any) made. By the relevant date, which we allege in every case to be the earliest priority filing date of the '206 Patent (October 23, 1980), the purported inventors of the '206 Patent did not make, isolate, characterize or test all of the compounds covered by the Claims in Issue. [at page 5]
[100] Apotex then goes on to identify, at some length, the compounds that were not made, isolated, characterized or tested prior to the earliest of the priority dates.
[101] Further on in the NOA, Apotex goes on to say, specifically in relation to t