AB Hassle v. Apotex Inc.

AB Hassle v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2003-06-20
Neutral citation
2003 FCT 771
File numbers
T-1914-01
Decision Content
Date: 20030620
Docket: T-1914-01
Citation: 2003 FCT 771
PRESENT: The Honourable Mr. Justice Campbell
BETWEEN:
AB HASSLE and ASTRAZENECA CANADA INC.
Applicants
- and -
APOTEX INC. and THE MINISTER OF HEALTH
Respondents
REASONS FOR ORDER AND ORDER
CAMPBELL J.
[1] Since 1990, the Applicants ("Astra") have held the Canadian Patent 1,264,751 ("the Patent" or "the 751 Patent") to a form of omeprazole, namely certain base addition salts of omeprazole which are compounds effective in treating gastric acid disorders. Now, some three years from the expiry of the Patent, the Respondent, Apotex Inc. ("Apotex") attacks the Patent's validity pursuant to the provisions of the Patented Medicines (Notice of Compliance) Regulations ("NOC " and "the Regulations").
[2] Of particular importance in the present case is the magnesium base addition salt of omeprazole, which is claim 4 of the 751 Patent, and in respect of which, Apotex wishes to obtain a NOC from the Minister of Health in order to sell and advertise the drug. In order to accomplish this, pursuant to the Regulations, a determination is required in the present summary proceeding that the Patent is invalid.
[3] The legal considerations with respect to the NOC process are well established (see: Hoffmann-LaRoche Ltd. v. Canada (Minister of National Health and Welfare), 70 C.P.R. (3d) 206 at pp.210-212) and are not in contest in the present application, with the important exception of the evidentiary and persuasive burden of proof in an application such as the one in the present case where patent validity is the only issue for determination.
[4] In its Notice of Allegation ("the NOA"), Apotex alleges that the Patent is invalid on the ground of anticipation; Apotex argues that the 751 Patent is invalid because Astra's European Patent Application 5129 published in 1979 ("the 5129 Application") teaches an uninventive person skilled in the art how to produce Astra's salt form of omeprazole.
[5] The filing date of the 5129 Application is important because, by s.27(1)(b) of the Patent Act, for Astra to obtain the 751 Patent, the invention it claims must not have been described in any publication printed more than two years before the date of filing the application for the Patent, which was March 2, 1984.
[6] Apotex also alleges that the Patent is invalid on the ground of obviousness; the primary allegation is that the prior art to the Patent, including the 5129 Application, shows that Astra's salt form of omeprazole was known by persons skilled in the art and would have been produced accordingly.
[7] The Canadian equivalent to the 5129 Patent Application resulted in the now expired Patent 1127158 ("the 158 Patent"). The only importance of the 158 Patent in the present case is with respect to the allegation of double patenting which is addressed below in Section F.
[8] It is common ground that the science underlying the 751 Patent was no mystery when the Patent was granted. Omeprazole is but one of thousands of compounds claimed in the 5129 Patent Application and patented in Canada by the 158 Patent. There is no disagreement that, from looking at its formula, a person skilled in the art would know that "salts", being either "base addition salts" or "acid addition salts" of the compound omeprazole, could be formed without difficulty. An introduction to the science is needed to understand the difference between the two. The following is a helpful precis:
Acids, Bases and Salts
Once a chemical entity such as omeprazole is synthesized, it is common for salts of the parent chemical entity to be prepared in order to alter certain physical and chemical properties of the compound for the purposes of drug development, for example, solubility, storage stability, etc.
Salts can be viewed generally as the product of a reaction between an "acid" and a "base". An acid is a chemical entity whose molecules tend to lose a hydrogen (H), i.e. hydrogen donor, and a "base" is a chemical entity whose molecules tend to receive a hydrogen, i.e. hydrogen acceptor. A base addition salt is formed when a chemical entity reacts with a base and loses a hydrogen. An acid addition salt is formed when a chemical entity reacts with an acid and gains a hydrogen.
Some chemical entities have a number of functional groups within them, some of which are hydrogen acceptors and some of which are hydrogen donors, thus permitting them to become either base addition salts or acid addition salts. Omeprazole is such a chemical entity.
A base addition salt of omeprazole may be obtained by removing the hydrogen attached at the N1 nitrogen position of the benzimidazole. For example, a base addition salt of omeprazole would be obtained by reacting omeprazole with the base sodium hydroxide (NaOH) resulting in sodium omeprazole (the Na displacing the hydrogen at the N1 nitrogen position of the benzimidazole). The hydrogen would join the OH to become H2O, water.
Omeprazole may also be reacted to form an acid addition salt. Omeprazole has, in principle, two potential sites that could act as the proton acceptor necessary to create the acid addition salt, namely, the N3 nitrogen position of the benzimidazole and the N1 nitrogen position of the pyridine. An acid addition salt of omeprazole could be created by reacting omeprazole with hydrochloric acid (HCl) to create omeprazole hydrogen chloride in which the donated hydrogen would bind at either the N3 position of the benzimidazole or the N1 position of the pyridine, together with the addition of the chlorine to the molecule.
The strength or weakness of an acid or of a base is the measure of its strength in donating a hydrogen in the case of an acid and its strength in accepting a hydrogen in the case of a base. The stronger the acid, the greater the propensity to donate a hydrogen and hence the more readily it will react with a base to form a base addition salt.
The strength of an acid or of a base is measured by, among other things, a value known as the pK value, pKa in the case of acids and pKb in the case of bases. The stronger the acid or base is, the lower the pKa or pKb value will be.
When an acid and base react to form a salt, whether the resultant solution formed is neutral, acidic or basic will depend upon the strength of the acid and base used in the reaction. Hence, reacting equal parts of a strong acid and a strong base or a weak acid and a weak base will result in a solution that is essentially neutral as evidenced by the resulting pH (the measure of basicity/acidicity) of that solution being essentially 7. In contrast, the reaction of equal parts of a strong acid and a weak base would result in a solution that is acidic, meaning that the pH of the solution would be less than 7 whereas the reaction of equal parts of a weak acid and strong base would result in a solution that would be basic, meaning that the pH of that solution would be greater than 7.
(Respondent's Record (RR), pp. 4-6, excluding footnotes)
[9] The 751 Patent claims rights to certain "base addition salts" of omeprazole. If there could be no difficulty in understanding how to produce the base addition salt of omeprazole, the important question naturally arises: How is Astra entitled to patent protection? Astra argues that, while the science was well understood that a person skilled in the art could produce base addition salts of omeprazole, that same skilled person operating in a therapeutic environment would not because it would not have been expected that a base addition salt of omeprazole would have therapeutic value.
[10] As it turns out, base addition salts of omeprazole certainly do have therapeutic value, and Astra argues that the creative spark of its invention is this discovery.
[11] Thus, the present case revolves around the difference between "could" and "would". That is, while an uninventive person skilled in the art could have come to the 751 Patent from the teachings of the 5129 Patent Application, would he or she?
[12] A word is required concerning the credibility of the expert witnesses on both sides of the present application who swore affidavits and who went through cross-examination thereupon.
[13] On behalf of Astra, the following experts gave evidence by way of affidavit:
1. Dr. Peder Berntsson, PhD in Organic Chemistry, was employed as the Senior Scientific Advisor, Scientific Patent Support, at Astra until 2001.
2. Dr. James D. Wuest, PhD in Organic Chemistry, is a Professor of Chemistry at the University of Montreal.
3. Dr. Gordon Amidon, PhD in Pharmaceutical Chemistry, is a Professor of Pharmacy at the University of Michigan.
4. Dr. Christopher T. Rhodes, PhD in Pharmaceutics, is a Professor of Applied Pharmaceutical Sciences at the University of Rhode Island and President of PharmaCon Inc., a pharmaceutical consulting firm.
[14] On behalf of Apotex, the following experts gave evidence by way of affidavit:
1. Dr. Zak T. Chowhan, PhD in Pharmaceutical Chemistry, is an independent consultant in the field of Pharmaceutical Development.
2. Dr. Eli Shefter, PhD in Pharmaceutics, is an independent consultant.
3. Dr. Hendricksson, PhD in Organic Chemistry, is a Professor of Chemistry at Brandeis University in Massachusetts.
4. Dr. Edward Lee-Ruff, PhD in Organic Chemistry, is a Professor of Chemistry at York University in Toronto.
5. Dr. Robert McClelland, PhD in Chemistry, is a Professor of Chemistry at the University of Toronto.
6. Dr. Robert S. Brown, PhD in Chemistry, is a Professor of Chemistry at Queens University.
7. Dr. Michael V. Sefton, ScD in Chemical Engineering, is a Professor in and Director of the Institute of Biomaterials and Biomedical Engineering at the University of Toronto and a Professor in the Department of Chemical Engineering and Applied Chemistry at the University of Toronto.
[15] Each side to the present case cast aspersions of partisanship on the experts of the other in an attempt to impact negatively upon their credibility. As will be seen below, I have assigned weight to the evidence provided by the experts, but this is done according to what each says in the full context of the evidence on the record, and not according to who they are and whatever possible connection they have with the party for whom they are testifying.
[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.
[17] I have absolutely no reason to question the credibility of each of the experts in the present case.
A. The preliminary objection
[18] In 1998, Apotex made its first attempt to attack the validity of the 751 Patent under the Regulations. This attempt was aborted after its expert witnesses were cross examined on their affidavits. It appears that two of the experts held opinions that were contrary to Apotex's interests as alleged in the NOA; it appears that Apotex concluded that it just did not have the evidence it required to succeed in proving its allegations. The 1998 attempt was discontinued by Court order on an agreement between Apotex and Astra.
[19] Thus, the NOA in the present case is Apotex's second attempt. It is important to note that counsel for Astra in the present case confirmed during the course of oral argument that the discontinuance of the 1998 NOA did not result in any cost or inconvenience to Astra. However, as a preliminary objection in the present case, Astra makes the argument that this second attempt by Apotex constitutes an abuse of the Court's process. When pressed for the exact reason for taking this position, counsel for Astra confirmed that it has to do with the evidence of the two witnesses who supplied evidence against the allegations in the 1998 NOA. Indeed, in the present application, without any notice provided in the written submission, during the course of oral argument Astra attempted to get the evidence of these witnesses into the record of the present case on an argument that this could be done through hearsay evidence contained in the affidavit of a lawyer and patent agent who is a member of Astra's legal team. Understandably, counsel for Apotex objected. As a result, on the basis of lack of notice, I disallowed Astra's evidentiary attempt.
[20] Apotex's first NOA attempt ended by an agreement without apparent detriment to Astra before the Court was involved directly in the NOC process. I see no basis for an abuse of process argument simply because Apotex has made a second attempt.
[21] During the course of the hearing, counsel for Astra admitted that the abuse of process argument really centres on the fact that Astra would like to have used the evidence of Apotex's two unhelpful witnesses in the present case, but could not. In answer to the question "why not?", counsel for Astra responded that it could be assumed that they would not be available simply because they had given evidence on behalf of Apotex.
[22] There is no evidence that Apotex has acted unfairly in using the NOC process allowed under the Regulations, and, specifically, there is no evidence that Apotex has done anything to inhibit Astra's ability to produce the evidence it believes would be helpful in the present application. As a result, in my opinion, there is no conduct by Apotex that gives rise to an abuse of process concern. Thus, during the course of oral argument, I rejected Astra's abuse argument.
B. The burden of proof with respect to patent validity
[23] Apotex argues that, in part, the purpose of the Regulations is to permit a patent owner to proceed summarily to protect its patent rights where the generic's allegations of non-infringement or invalidity have "no merit". I find that, certainly with respect to an attack of invalidity, Apotex's argument does not reflect the present state of the law.
[24] Justice Stone at 210 to 211 of Hoffman-La Roche, supra, provides the following analysis specifically with respect the NOC process with respect to allegation of infringement:
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".
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.
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".
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".
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". [footnotes omitted] [Emphasis added]
[25] However, specifically with respect to allegations of patent invalidity, in Bayer Inc. v. Canada (Minister of National Health and Welfare) [2000] F.C.J. No. 464, the Appeal Division of this Court has clarified the evidential burden on Apotex in the present case. At paragraph 5, Justice Sharlow says as follows:
An application for a prohibition order under the Patent Medicines (Notice of Compliance) Regulations is like any other application for judicial review in the sense that the applicant has the burden of establishing its entitlement to the order sought. Bayer, in other words, had the burden of proving that the allegation of invalidity made by Apotex was not justified. The Motions Judge said as much in paragraph 15 of his reasons:
The substantive issue in this application is whether Bayer has discharged its burden in establishing that the Apotex allegation of invalidity is not justified.
In seeking to discharge its burden of proving the allegation to be unjustified, Bayer relied on the statutory presumption of the validity of its patent. Because that presumption exists, it may be said that Apotex, as the party responding to the application for a prohibition order, has a burden of proof in this sense: if Apotex had adduced no evidence that was capable of establishing the invalidity of the patent, Bayer could have succeeded on the basis of the statutory presumption alone. As the Motions Judge correctly said at paragraph 15:
A statutory presumption, for example, may assist Bayer and "have the effect of displacing the burden of proof".
The quotation is from Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1994), 55 C.P.R. (3d) 302 (F.C.A.), where Hugessen J.A. said at 319:
As I understand the scheme of the [Patent Medicines (Notice of Compliance) Regulations], it is the party moving under s. 6, in this case Merck, which, as the initiator of the proceedings, has the carriage of the litigation and bears the initial burden of proof. That burden, as it seems to me, is a difficult one since it must be to disprove some or all of the allegations in the notice of allegation which, if left unchallenged, would allow the Minister to issue a notice of compliance. There may, of course, be some presumptions (such as for example the statutory presumption of validity of a patent ) [...] which may help the moving party and have the effect of displacing the burden of proof.
However, in this case Apotex did adduce evidence, in the form of an affidavit, that the Motions Judge correctly accepted as going to the question of validity.
The operation of the statutory presumption in the face of evidence of invalidity depends upon the strength of the evidence. If the evidence proves on a balance of probabilities that the patent is invalid, the presumption is rebutted and is no longer relevant: Diversified Products Corp. v. Tye-Sil Corp. (1991), 35 C.P.R. (3d) 350 (F.C.A.) at 359. [Emphasis added]
[26] Bayer, supra was cited with approval by Justice MacDonald in Hoffmann-La Roche v. Canada (Minister of National Health and Welfare) [2000] F.C.J. No. 1356, where he said:
Nu-Pharm challenges the motions judge's approach to the presumption of validity under the Patent Act. In Bayer v. Canada (Minister of National Health and Welfare) [2000] F.C.J. No. 464 (QL) at para. 9, Sharlow J.A. stated:
The operation of the statutory presumption in the face of evidence of invalidity depends upon the strength of the evidence. If the evidence proves on a balance of probabilities that the patent is invalid, the presumption is rebutted and is no longer relevant: Diversified Products Corp. v. Tye-Sil Corp. (1991), 35 C.P.R. (3d) 350 (F.C.A.) at 359.
Muldoon J.'s finding that Nu-Pharm's evidence was insufficient to displace the statutory presumption is a finding that, on a balance of probabilities, Nu-Pharm did not prove that the patent was invalid. We see no legal error in the approach of the learned judge.
[27] Therefore, the question is not whether Apotex's invalidity allegations have "no merit"; the question to be answered in the present case is: Has Apotex proved, on a balance of probabilities by the evidence supporting its allegations in the NOA, that the 751 Patent is invalid?
C. Features of the 751 Patent
[28] The opening passages of the 751 Patent, as abridged, are as follows:
Novel compounds
Field of the invention
The invention relates to novel salts of the known compound omeprazole
Background of the invention
The compound known under the generic name omeprazole ... which is described i.a. in European patent specification [the 5129 Application] is being extensively investigated clinically as a gastric acid secretion inhibiting agent.
Omeprazole is useful for inhibiting gastric acid secretion as well as for providing gastrointestinal cytoprotective effects in mammals and man. In a more general sense, omeprazole may be used for prevention and treatment of gastrointestinal inflammatory diseases in mammals and man, including e.g. gastritis, gastric ulcer, and duodenal ulcer. Furthermore, omeprazole may be used for prevention and treatment of other gastrointestinal disorders where cytoprotective and/or gastric antisecretory effect is desirable, e.g. in patients with gastrinomas, in patients with acute upper gastrointestinal bleeding, and in patients with a history of chronic and excessive alcohol consumption
The term "omeprazole" as used in this specification designates the neutral form of the compound of the formula (I), that is the form as given in the formula (I) without salt forming components present.
A problem with omeprazole is its stability characteristics. Upon storage without any special precautions being taken, it is degraded at a rate which is higher than desired. At storage during accelerated conditions, that is a +37oC and at a relative humidity of 80% for a period of 6 months, about 6% of the substance is converted to degradation products. While the rate of decomposition of omeprazole at normal storage conditions is lower, it is nevertheless desirable to obtain physical forms of omeprazole which exhibit improved stability. This need for more stable forms of omeprazole is apparent when considering the often considerable time periods involved from synthesis of the active substance through its incorporation in pharmaceutical preparations, distribution of the finished product to pharmacies etc. up to the consumption of the preparation by the patient. The present invention provides such forms of omeprazole which exhibit improved storage stability.
The invention
It has been found that the novel alkaline salts of omeprazole ... are more stable during storage than the corresponding neutral form of omeprazole. The salts...are also easier to handle than the neutral form in the manufacture of pharmaceutical dosage units. ...The Mg 2+ salt is particularly preferred. (Applicant's Record (AR), pp.47-50)
[29] The relevant claims of the 751 Patent, wherein formula I represents specific base addition salts of omeprazole, are as follows:
1. A compound of the formula I
(I)
wherein n is 1, 2, or 4; and An+ is Li+, Na+, K+, Mg2+, Ca2+, Ti4+, N+(R1)4 or H2N-C+NH2-NH2
wherein R1 is an alkyl group containing 1-4 carbon atoms.
...
4. A compound according to claim 1 wherein An+ is Mg2+
...
8. A pharmaceutical composition comprising as active ingredient an effective amount of a compound according to claim 1, 2 or 3 in admixture with pharmaceutically acceptable diluent or carrier.
9. A pharmaceutical composition comprising as active ingredient an effective amount of a compound according to claim 4 in admixture with pharmaceutically acceptable diluent or carrier.
(AR, p.62, p.64)
[30] Claim 4 protects the magnesium base addition salt of omeprazole which is of particular practical interest to Apotex.
[31] The key feature of the Patent is that a base addition salt of omeprazole is a solid. As will be discussed below, Astra's NOA alleges that, from the prior art, solution studies of omeprazole would inevitably lead to the formation of the base addition salt in solution. With respect to its allegation, Apotex tenders evidence that, in the course of doing the solution studies as part of standard pre-formulation procedure in the study of omeprazole, the stability of the base addition salt of omeprazole would be determined and this quality would be appreciated; consequently, Apotex argues, Astra cannot claim an invention.
[32] With respect to the relevance of the solution studies, it is important to make a finding with respect to Apotex's "salt in solution" argument. There is no dispute that the compound of base addition salt of omeprazole is a solid. The dispute is with respect to whether the compound exists when in solution.
[33] I find that the determination of the question is a matter of chemistry theory. Astra has produced cogent evidence to prove that, in aqueous solution, the base addition salt of omeprazole is no longer present. Under cross-examination, Apotex's experts have agreed that this is a correct statement in theory.
[34] In order to support its argument, Astra relies on the affidavit of Dr. Amidon, which states as follows:
A "salt" is a solid substance consisting of distinct ions with opposite charges. In the context of an omeprazole salt, each omeprazole anion (negatively charged omeprazole ion) is associated with cations (positively charged species). Once such a salt is dissolved, the salt itself is no longer present. Rather, one has a solution containing the omeprazole anions and salt cations plus any other additives to the solution. While a salt might be isolated from the solution, the solution containing ions is not the salt per se.
My conclusion in this regard is reinforced by the disclosure to the '751 patent. In each of examples 1 to 9 the end product of the preparation is a solid material described as a salt. At page 4, the inventors describe the synthetic process, including the fact that the "salt is thereafter isolated". (AR, pp. 177-178)
[35] Dr. Wuest also referred to the solid state of salts, as follows:
A salt is a substance that consists of distinct ions of opposite charges. Salts are normally understood to be solid substances. In general, salts result from the reactions of acids and bases. The most common example of a salt is sodium chloride (NaCl), which is comprised of a sodium cation (Na+) and a chloride anion (Cl-). It is formed under appropriate conditions when the base NaOH reacts with the acid Hcl. (AR, p. 1716)
[36] Astra also supports its argument that salt compounds are solids by relying on the testimony of many of Apotex's witnesses, obtained through cross-examination. Dr. Sefton answered as follows:
Q. Do you understand the word "compound" to be referring to- and let's go back to my hypothetical with the sodium chloride dissolved in the aqueous solution. When we had the sodium chloride, the solid substance, in our hand, that could be referred to as a compound?
A. Yes.
Q. Then, when it was completely dissociated and solvated in dilute aqueous solution, could we still say we have a compound, sodium chloride, in solution?
A. No, I would be hard-pressed to call that a compound now.
Q. That is because the sodium chloride, when it is completely dissociated in the manner I described, would not be understood by people in your field to be a compound because you don't have the molecules per se anymore.
A. Yes. I would be inclined to think of it- I would not be using the word "compound" in that solution of sodium chloride so easily.
Q. But you are comfortable that the solid material sodium chloride can be described as a compound?
A. Yes. (AR, pp. 5045-5046)
[37] In addition, Astra questioned Dr. Lee-Ruff as follows:
Q. I want to ask you next about the word "compound". Are you familiar with that word as a word that is a term of art in chemistry?
A. Yes.
Q. If I read out something to you, can you tell me whether you agree or disagree with this being a definition acceptable to you for "compound":
"A substance composed of atoms or ions of two or more elements in chemical combination. The constituents are united by bonds or valent forces. A compound is a homogenous entity where the elements have definite proportions by weight and are represented by a chemical formula".
A. I would agree.
....
Q. In accordance with this definition I have read out, does that definition include a situation where in aqueous solution you have anions and cations which are each completely solvated? For example, if you took sodium chloride and put it into a dilute aqueous solution and you had water molecules surrounding the anions and the cations, would the definition of "compound" that I read out include anions that were solvated in the way that I have described?
A. It would include both the anions and the cations which are solvated. What you have is a solution of the compound.
Q. Would you include in the compound the water which is solvating the anions and the cations?
A. I would not simply because the solvation forces are a lot weaker than the forces that are associated with the binding of the anion and cation in the compound itself.
Q. What do you mean by "the compound itself" in that context that you have just been describing?
A. In the sense that the compound is the sodium chloride and the fact the water is associated would not be part of the compound simply because these interactions are relatively weak compared to the interactions between the anions and cations, sodium chloride.
...
Q. That attraction force in the solid state is overcome in the aqueous solution by the combined or total forces exerted by the water in respect of the cation and the anion.
A. That is correct.
Q. Given that and, in particular, given that there is a greater attraction in the aqueous solution between the individual cations and anions and the water molecules as compared to the attraction between the sodium and the chlorine in the solid state, when we go back to this definition of "compound" that I read out to you and, in particular, the part that talks about the constituents being united by bonds or valence forces, would you not have to describe what we have in solution in a way that would include the water molecules since they are now the constituents that are involved in the greatest attraction forces with the anions and cations?
A. The solvation shell interaction of the anions and cations with the water molecules is not co-valent bonds, they are not ionic bonds. They are weaker electrostatic interactions. I would refer to the aqueous solution of sodium chloride as a solution of the original salt.
Q. The original salt being what you had in the solid-
A. The solid sodium chloride.
Q. In this definition that we looked at it talks about constituents united by bonds or valence forces. On the right-hand side of the diagram you are looking at [AR, p.4439] there are no bonds, are there?
A. No, those are weak electrostatic interactions between water molecules and the anions and cations. I would not call this a formal bond in the sense of an ionic bond or a co-valent bond.
...
Q. According to the definition, you would not have a compound. If we go back to my example of sodium chloride being what is illustrated in the diagram before you, you would not have in solution the compound sodium chloride. It does not exist, per se, in the solution.
A. According to the definition, you are correct.
Q. Is it your view that the compound, sodium chloride, does exist in solution, that the compound, per se, exists in solution if it is totally dissolved and completely dissociated?
A. Yes, it exists as a solution of sodium chloride, just like any solid when dissolved exists as a solution of that particular solid.
Q. That term denotes what you started with in the solid state. Correct?
A. Yes. (AR, pp. 4453-4458)
[38] Finally, during his cross-examination, Dr. Chowhan said the following:
Q. Just focussing on the word "compound", do you understand the word "compound" in the context of pharmaceuticals or chemicals generally to signify a solid material?
A. Not necessarily.
Q. Let me give you a further example. If I take sodium chloride, table salt, if I have it in my hand, it is a white crystalline material. Do you agree?
A. Yes.
Q. If I put it into my glass of water and mix around the water, it will disappear. Correct?
A. Right.
Q. It disappears because the sodium chloride dissolves in the water.
A. Yes.
Q. As part of the dissolution process, the sodium part of the sodium chloride and the chloride part of the sodium chloride move apart. Yes?
A. Yes.
Q. And they are solvated by the water molecules. Right?
A. Right.
Q. When I had the sodium chloride in my hand, the crystalline material, and it was a solid, I could refer to that as a compound, could I not?
A. Of course.
Q. And you would understand what I am referring to?
A. If you had it in your hand, yes.
Q. After I have dissolved it in the water, in your view, do I have the compound?
A. You have the compound in solution.
Q. What does that mean?
A. That means it is a solution. It is dissolved.
Q. It has been dissolved.
A. Yes.
Q. But the solid material no longer exists.
A. Yes. (AR, pp. 3846-3848)
[39] On the basis of the evidence quoted, I find that the compound of base addition salt of omeprazole does not exist in solution.
[40] The question now is whether the Patent can withstand Apotex's attacks of invalidity. I accept Astra's argument that Apotex is bound by the legal and factual basis for the allegations set out in the NOA, and that the issues set out in the NOA may not be expanded or amended by Apotex during the proceeding(AB Hassle v. Canada (Minister of National Health and Welfare (2000) 7, C.P.R. (4th) 272 at 288, 289 (C.A.).
[41] In the analysis which follows, I have adopted the written argument strategy put forward by Astra which is to first cite directly from the NOA as it is framed by Apotex under various topic headings, and then to decide with respect to the content of each.
D. The attack of anticipation
[42] Section 27(1) of the Patent Act stipulates that a patent will only be valid where it describes a novel invention that has not previously been anticipated by a prior invention. An invention is said to be anticipated if its essential features are disclosed in a single piece of prior art as stated by Justice Hugessen in Beloit Canada Ltd. et al. v. Valmet ((1986), 8 C.P.R. (3d) 289 (F.C.A.)) at 297 as follows:
One must, in effect, be able to look at a prior single publication and find in it all the information which, for practical purposes, is needed to produce the claimed invention without the exercise of any inventive skill. The prior publication must contain so clear a direction that a skilled person reading and following it would in every case without possibility of error be led to the claimed invention. Where, as here, the invention consists of a combination of several known elements, any publication which does not teach the combination of all the elements claimed cannot possibly be anticipatory.
[43] The test for anticipation was also clearly set out by Wetston J. in Almecon Industries Ltd. v. Nutron Manufacturing Ltd. (1996) 65 C.P.R. (3d) 417 at 428-429, affirmed (1997) 72 C.P.R. (3d) 397 (F.C.A.), leave to appeal denied [1997] S.C.C. No. 374) as follows:
In Proctor & Gamble Co. v. Kimberly-Clark of Canada Ltd. (1991), 40 C.P.R. (3d) 1 (F.C.T.D.), Teitelbaum J. noted than an analysis of anticipation involves a two-fold test. Firstly, the court must consider whether the prior disclosure gives clear and unmistakable directions which would, in every case and without possibility of error, lead a skilled person to arrive at what is covered by the claims of the patent-in-suit. In other words, in light of the prior patent, was it inevitable that a skilled person would be led to discover the patent-in-suit?
If the first question is answered in the affirmative, the court must then ask if the prior patent conveys enough information which, for practical purposes, would be sufficient for the skilled person to know how to make the claimed invention without the exercise of any inventive skill. This is the enabling disclosure test. Thus, in order to satisfy the tests of anticipation, one has to show that the prior patent has enough description to enable the skilled person to construct the invention and put it to its proper use.
[44] Anticipation also precludes the grant of a patent where the invention claimed has been in prior use.
1. Is the 5129 Application a prior single publication?
[45] The 5129 Application makes claim to many compounds, and, with respect to each, the "therapeutically acceptable salt thereof". Claim 23 of the 5129 Application refers precisely to omeprazole.
[46] Apotex argues that the 751 Patent is invalid primarily because the 5129 Application is a "prior single publication" which meets the test for anticipation as quoted. Elements of this document important to the argument are as follows:
AB HÄSSLE
Mölndal/SWEDEN
Inventors: U`Junggren and S E Sjöstrand
KM 575-1
79-03-07
UI/LB/EMH
Gastric acid secretion agents
The present invention relates to new compounds having valuable properties in affecting gastric acid secretion in mammals, including man, as well as the process for their preparation, method of affecting gastric acid secretion and pharmaceutical preparations containing said novel compounds.
The object of the present invention is to obtain compounds which affect gastric acid secretion, and which inhibit exogenously or endogenously stimulated gastric acid secretion. These compounds can be used in the treatment of peptic ulcer disease.
It is previously known that compounds of the formula I and II wherein R1 and R2 are each selected from the group consisting of hydrogen, alkyl, halogen, cyano, carboxy, caboxyalkyl, carboalkoxy, carboalkoxyalkyl, carbemoyl, carbemoyloxy, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl and acyl in any position, R3 is selected from the group consisting of hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl, and alkylsulphonyl, and R4 is selected from the group consisting of straight and branched alkylene groups having 1 to 4 carbon atoms, whereby at most one methylene group is present between S and the pyridyl group, and whereby the pyridyl group may be further substituted with alkyl or halogen, possess inhibiting effect of gastric acid secretion.
It has now, however, surprisingly been found that the compounds defined below possess a still greater inhibiting effect than those given above.
Compounds of the invention are those of the general formula III in which R1 and R2 are the same or different and are selected from the group consisting of hydrogen, alkyl, halogen, carbomethoxy, carbethoxy, alkoxy and alkanoyl in any position, R6 is selected from the group consisting of hydrogen, methyl, and ethyl, R3, R4 and R5 re the same or different and are each selected from the group consisting of hydrogen, methyl, methoxy, ethoxy, methoxyethoxy, and ethoxyethoxy, with the proviso that R3, R4 and R5 are not all hydrogen, and the further proviso that when two of R3, R4 and R5 are hydrogen, the third of R3, R4 and R5 is not methyl.
The invention also extends to therapeutically acceptable salts of compounds of formula III [as claimed in Claims 1 to 6].
...
Depending on the process conditions and the starting materials, the end product is obtained either as the f