Date: 19980220
Docket: T-1712-95
BETWEEN:
AB HASSLE and ASTRA PHARMA INC.
Applicants
- and -
THE MINISTER OF NATIONAL HEALTH AND WELFARE
and APOTEX INC.
Respondents
REASONS FOR ORDER
NOËL J.:
[1] This is an application by AB Hassle and Astra Pharma Inc. (the "applicants") pursuant to section 6(1) of the Patented Medicines (Notice of Compliance) Regulations ,1 (the "Regulations"), for an order prohibiting the Minister of National Health and Welfare (the "Minister") from issuing a notice of compliance ("NOC") to the respondent Apotex Inc. (the "respondent") in respect of the medicine omeprazole, including the medicine omeprazole capsules 20 mg and 40 mg, until after the expiration of each of the Canadian Patents Nos. 1,127,158 ("158) and 1,129,417 ("417).2 These patents will expire in July of 1999.
[2] This application is the second s. 6(1) proceeding between these parties in respect of the medicine omeprazole. The first was commenced by the applicants further to an initial notice of allegation dated April 27, 1993.3 In advancing it, the respondent stated that it was relying on its contractual right to obtain pharmaceutical supplies from Novopharm Limited, a company entitled to manufacture omeprazole by virtue of a compulsory licence issued with respect to the applicants" patents.
[3] By order dated June 29, 1993, Dubé J. ordered that the respondent"s allegation of non-infringement be limited to the one asserted in its notice of allegation dated April 27, 1993 as described above.4
[4] The first proceeding was concluded on May 3, 1996 by the order of Richard J. Its effect was to prohibit the Minister from issuing an NOC to the respondent until after the expiration of applicants" patents "158 and "417. This order was issued on consent but without prejudice to the parties" rights on appeal.5
[5] Following the commencement of the first proceeding but before its disposition before Richard J., the respondent delivered to the applicants a further notice raising a fresh allegation in respect of omeprazole. This new allegation was predicated on the respondent"s contention that it had available to it a process for the manufacture of omeprazole that did not infringe the applicants" patents.
[6] On August 10, 1995, in response to the respondent"s second notice of allegation, the applicants filed the Originating Notice of Motion which is the subject matter of the present proceeding. Since then, a number of interim disputes have arisen. Of significance is a motion which was brought by the applicants for an order declaring the second notice of allegation null and void on the basis that the issue of infringement with respect to omeprazole had been finally decided by the order of
Richard J.
[7] On January 8, 1997, MacKay J. dismissed the applicants" motion on the ground that it raised issues which could not be properly decided in the context of interlocutory proceedings. Specifically, MacKay J. concluded that "the time for considering the weight to be given to any evidence is when the evidence as a whole is considered, at the hearing of the originating notice of motion ... ".6
[8] A protective order was issued by Gibson J. on September 11, 1995 with respect to the present proceeding. Both parties consented to its withdrawal during the course of the hearing with the result that I can now address the issue of infringement without reservation. Before doing so, certain procedural issues must be addressed.
PROCEDURAL ISSUES
[9] As a result of the decision of the Court of Appeal in Eli Lilly and Company et al. v. Apotex et al.,7 the applicants can no longer argue that the matter underlying the present proceeding is res judicata having regard to the prior order of Richard J. This issue was not pursued.
[10] With respect to the legal and factual basis relied upon by the respondent, the applicants state that it ought to be restricted to the grounds set forth in the notice of allegation dated June 23, 1995 and the three initial affidavits filed upon the protective order being issued in this matter. They argue that the additional grounds advanced in the subsequent affidavit sworn to by Dr. Slemon are distinct and novel grounds which ought not to be treated as properly forming part of the legal and factual basis upon which the notice of allegation was given.
[11] The issue as to what properly forms part of the factual basis advanced by a second person in support of a notice of allegation is a significant one as it is now established that facts advanced in conformity with section 5(3) are presumed to be true. However, the affidavit of Dr. Slemon was introduced with leave of the Court8 and in my view any objection to its introduction should have been dealt with at that time. The applicants have since responded to these additional grounds and it is too late now to argue that they ought to be disregarded.
[12] The applicants also argue that the respondent by issuing a second notice of allegation with respect to omeprazole has openly flaunted the order of Dubé J. which explicitly prohibited the respondent from relying on any further notice of allegation with respect to the medicine omeprazole. The respondent has allowed its appeal against that order to remain pending for almost five years. The applicants argue that this behaviour amounts to an abuse of process and should be sanctioned accordingly.
[13] It seems clear that the respondent by issuing a fresh notice of allegation against the explicit terms of the order of Dubé J. while not prosecuting its appeal against that order has acted in a manner which tends to undermine the authority of the Court. However, the appropriate sanction if there should be one is unclear to me and having noted the matter I prefer to allow it to pass without more.9
[14] I now turn to the facts as they pertain to the issue of infringement.
THE FACTS
[15] The process which the respondent claims to be non-infringing was developed by Torcan Chemical Ltd. ("Torcan"). Prior to developing this process Torcan held a compulsory license in respect of omeprazole.
[16] Torcan had first obtained this compulsory license on February 26, 1987. It was surrendered in October of 1991. Subsequently, the government abolished compulsory licenses granted after December 20, 1991.
[17] In a letter dated August 22, 1992 to the Commissioner of Patents, the President of Torcan, Dr. Jan Oudenes, complained bitterly about the "disastrous consequences" which the abolition of compulsory licenses would have on Torcan"s business plans with respect to omeprazole. Specifically, Dr. Oudenes made the point that if Torcan had not surrendered its compulsory license in good faith, it would have continued to hold a valid license for omeprazole despite the abolition of compulsory licensing.
[18] The letter was to no avail, and Torcan adopted another approach to preserve its entitlement to make omeprazole. It commissioned its senior chemist, Dr. Clarke Slemon, the task of developing a process for making omeprazole which would avoid the claims of patent "158.
[19] Dr. Slemon began by reviewing information gathered by Torcan scientists who had previously made quantities of omeprazole according to the teachings of the "158 patent for the purpose of experimenting with the method. Significant deficiencies were said to have been identified and Dr. Slemon eventually and unexpectedly came up with a discovery which, according to the respondent, overcomes these deficiencies. This process is the subject of U.S. Patent No. 5,374,730 ("730) which was issued to Torcan on December 20, 1994.10 That is the process (the "Torcan process") which the respondent says is available to it and which forms the basis of the allegation of non-infringement.
[20] A great deal of affidavit evidence has been advanced by the parties with respect to the Torcan process. Following the filing of the originating notice of motion and upon the issuance of the confidentiality order by Gibson J., the respondent filed the affidavits of Dr. Robert McClelland, a professor in the Department of Chemistry at the University of Toronto, Dr. James Hendrickson, a professor in the Department of Chemistry at Brandeis University, and Dr. Jan Oudenes.
[21] In response, the applicants filed the affidavits of Dr. James Wuest, science professor at the University of Montreal, and Dr. Peder Berntsson, Senior Director and head of the Patents Department at Astra Hassle AB.
[22] The respondent then obtained leave to file the affidavit of Dr. Slemon to which the applicants responded with the affidavit of Dr. Tony Durst, Vice-Dean, Faculty of Science at the University of Ottawa, and the further affidavits of Drs. Wuest and Berntsson.
[23] The respondent has advanced several arguments in support of its allegation. The first argument attacks the soundness of the "158 patent. The respondent contends that the key steps in the processes described in claims 1 and 8 of the "158 patent either do not work or yield unstable and impure intermediate compounds which render the ultimate synthesis of omeprazole impractical. The respondent maintains that the "158 process is prone to degradation, decomposition and purification problems. In order to offset these failings, the respondent submits that the "158 process must take place under conditions which reduce the efficacy of the reaction and undermine the viability of large scale production of omeprazole.
[24] The respondent maintains that the applicants are aware of the "158 process deficiencies. In the respondent's view, it was these deficiencies that motivated the applicants to develop and patent an improved process. This new process, which is the subject matter of U.S. Patent No. 5,386,032 ("032), is said to reduce the acidity of the environment in which omeprazole is synthesized.
[25] The respondent's second argument is that its process eliminates the flaws of the "158 patent. The respondent claims that the Torcan process employs special intermediate compounds, a sulfide-amide, compound D, and a sulfoxide-amide, compound E, which are not taught by the "158 patent. Compound E is produced through the oxidation of compound D. According to the respondent, both compounds D and E are a crystalline solids whereas the parallel intermediates in the "158 patent are oils. It is alleged that these compounds allow for the synthesis of omeprazole under conditions which preclude decomposition and facilitate purification.
[26] The respondent's third and final argument highlights the inventiveness of its process, with particular emphasis on the novelty of compound E. The respondent contends that the scientific literature of the day expressly discouraged the use of this type of intermediate because of its susceptibility to the Pummerer rearrangement. The respondent suggests that the Torcan process is inventive in the sense that Dr. Slemon was able to elaborate a combination of compounds that allow for the use of this type of intermediate without any of the side effects encountered in the literature. The respondent therefore asserts that the Torcan process uses compounds that are not obvious chemical equivalents to those in patent "158 and in a manner not within the contemplation of that patent. As further evidence of this assertion the respondent refers to patent "730 granted by the U.S. Patent Office.
[27] The applicants stress that the manner in which omeprazole may be synthesized under patent "158 is not limited. This means that the processes set out in the patent may take place under a variety of reaction conditions. The reaction conditions which are subject to vary include the physical state of the intermediate compounds as well as the acidity and temperature under which omeprazole may be synthesized. In the applicants" view, given the breadth of the "158 patent in terms of reaction conditions, the physical state of the intermediate and the level of compound purity are simply not relevant in determining whether its process and the Torcan process are distinct.
[28] In any event, the applicants take the position that the distinctions identified by the respondent with respect to the physical state of the intermediates and the level of compound purity are not supported by the evidence. The applicants note that both their process and the Torcan process require the oxidation of a sulfide to form a sulfoxide. The sulfide used in the applicants" process is called compound IV. According to the applicants the only tangible difference between their process and the Torcan process is the introduction of a carboxamide group to compound D, the sulfide employed by Torcan. The applicants claim that the addition of the carboxamide group results in a very minor and insignificant variant of compound IV and would have no material effect on the way their own process functions. Furthermore, although the applicants maintain that the actual physical state of the sulfide intermediate is inconsequential given that in both processes oxidation takes place in solution, they insist that both compounds D and IV are crystalline solids.
[29] With respect to purification, the applicants maintain that under their process omeprazole is readily purified through recrystallization. The applicants note an absence of any evidence adduced by the respondent which would indicate otherwise. Moreover, according to the applicants, the documentary evidence reveals that the Torcan process obtains a significantly lower yield of omeprazole than that obtained using the "158 process. In the applicants" view, a lower yield suggests that it is in fact the Torcan process that is prone to purification problems.
[30] The applicants also take issue with the respondent"s evidence regarding the Pummerer rearrangement. The applicants note that the respondent"s initial position is reflected by the affidavits Drs. Hendrickson and McClelland which featured evidence relating only to the physical state of the intermediates and to the purification of omeprazole. It was only after the applicants had responded to these issues that the respondent, through the affidavit of Dr. Slemon, asserted the Pummerer arrangement as being relevant in this proceeding.
[31] The applicants assert that the respondent"s "belated reliance" on the Pummerer rearrangement is untenable. According to the applicants, the scientific articles relied upon by Dr. Slemon for the proposition that compound E was considered unworkable given its susceptibility to the Pummerer rearrangement, also demonstrate that the Pummerer rearrangement takes place very slowly and can be easily avoided under minimal acidity and cooler temperatures. The applicants claim that a person skilled in the art would appreciate that the Torcan sulphide D could be oxidized to the sulfoxide E under the same conditions contemplated by the "158 patent. The applicants therefore conclude that the Torcan process constitutes an obvious chemical equivalent.
ANALYSIS AND DECISION
[32] The Court must, on a balance of probabilities, determine whether the applicants have succeeded in countering the allegation made by the respondent. As this allegation is based on a non-infringing process, this requires the Court to determine whether the applicants have established that the respondent"s process infringes the relevant claims of patent "158.
[33] Only claims 1 and 8 are said to be relevant. As their wording is plain and unambiguous, I need not go beyond those claims in construing their ambit.11
[34] In considering the issue of infringement, courts have adopted a purposive approach:
| My Lord, a patent specification is a unilateral statement by the patentee, in words of his own choosing, addressed to those likely to have a practical interest in the subject matter of his invention (i.e. "skilled in the art"), by which he informs them what he claims to be the essential features of the new product or process for which the letters patent grant him a monopoly. It is those novel features only that he claims to be essential that constitute the so-called "pith and marrow" of the claim. A patent specification should be given a purposive construction rather than a purely literal one derived from applying to it the kind of meticulous verbal analysis in which lawyers are too often tempted by their training to indulge. The question in each case is: whether persons with practical knowledge and experience of the kind of work in which the invention was intended to be used, would understand that strict compliance with a particular descriptive word or phrase appearing in a claim was intended by the patentee to be an essential requirement of the invention so that any variant would fall outside the monopoly claimed, even though it could have no material effect upon the way the invention worked.12 |
[35] It is common ground that but for the presence of the carboxamide group in the Torcan process, it would fall literally within claim 1 of the "158 patent. Having regard to its presence, the applicants take the position that only claim 8 is literally infringed on the basis that it claims omeprazole when prepared by a process according to claim 1 or "an obvious chemical equivalent".
[36] In ascertaining whether the process developed by Torcan is "an obvious chemical equivalent", I must determine whether the Torcan process was in effect already embodied in claim 1 so as to strip it of any inventiveness. More precisely:
| The question to be answered is whether at the date of the invention ... an unimaginative skilled technician, in light of his general knowledge and the literature and information on the subject available to him on that date, would have been led directly and without difficulty to the ... invention.13 |
or as Hugessen J.A. put the matter in Beloit Canada:14
| The classical touchstone for obviousness is the technician skilled in the art but having no scintilla of inventiveness or imagination; a paragon of deduction and dexterity, wholly devoid of intuition; a triumph of the left hemisphere over the right. The question to be asked is whether this mythical creature (the man in the Clapham omnibus of patent law) would, in the light of the state of the art and of common general knowledge as at the claimed date of invention, have come directly and without difficulty to the solution taught by the patent. |
Keeping these principles in mind, I now turn to the evidence.
[37] Patent "158 embodies 89 claims related to the synthesis of omeprazole, a medicine which inhibits gastric acid secretion. As noted, the applicants have asserted claims 1 and 8 as being relevant for the purposes of this proceeding.15 Claim 1 covers four processes for the preparation of omeprazole or certain of its chemical antecedents. The applicants assert that there are two processes in claim 1 of patent "158 that are relevant for the purposes of this proceeding, step (a) and step (c). Step (a) claims the oxidation of sulfide IV to a sulfoxide III. Step (c) claims reacting compounds VII and VIII to give compound IV which is then oxidized to compound III. Claim 8 covers the compounds described in claim 1 when made using one of the claim 1 processes or an obvious chemical equivalent.
[38] In his affidavit, Dr. Wuest attached a chart which reveals that the overall reaction scheme in both the respondent"s and applicants" processes is the same.16 Both processes comprise three basic steps: nucleophilic substitution; oxidation of a sulfide to form a sulfoxide; purification and/or further synthesis of the sulfoxide to form omeprazole. The parties are agreed that under both processes oxidation is the key step in the synthesis of omeprazole.
[39] That the processes are so remarkably similar is consistent with the evidence of Dr. Slemon on cross-examination. Dr. Slemon acknowledged that in developing the Torcan process, his research was posited on the information disclosed in the "158 patent. His task was to devise some modification to the "158 process sufficient to justify an allegation of non-infringement.
[40] The modification which Dr. Slemon eventually incorporated into the Torcan process involves the addition of 2 steps to the "158 process. These steps allow for the introduction of a carboxamide group to the sulfide intermediate and its removal following oxidation. It is the respondent"s position that the presence of the carboxamide group in the Torcan process creates new and unexpected chemistry.
[41] In support of that position, the respondent initially filed the affidavits of Drs. Hendrickson and McClelland. In their affidavits, both asserted that as a result of the carboxamide group, the Torcan process was different from the "158 process in two significant ways.
[42] The first difference identified by Drs. Hendrickson and McClelland relates to the physical state of the sulfide intermediate in the two processes. According to Drs. Hendrickson and McClelland, the Torcan sulfide, compound D, is a crystalline solid, whereas the "158 sulfide, compound IV, is an oil. Compound D was thus said to purify more easily than compound IV.
[43] The second difference identified by Drs. Hendrickson and McClelland relates to purported advantages of the Torcan process in terms of purification following oxidation. Whereas Dr. Hendrickson affirmed that the oxidation of the sulfide in both the "158 and Torcan process leads to coloured impurities, Dr. McClelland was of the view that under the Torcan process the sulfoxide, compound E, was obtained in colourless form. However, both took the position that omeprazole could be much more easily purified under the Torcan process because of the solubility characteristics of compound E.
[44] On cross-examination, the accuracy of Drs. Hendrickson and McClelland"s evidence on the above matters was found wanting. Both admitted to having never actually carried out either the Torcan or "158 process. Both acknowledged that they had simply assumed that the applicants" compound IV was an oil and that their opinions would change if this were incorrect. On that point, Dr. Hendrickson stated:
| What we"re getting at is how did I know that these things are not crystalline and difficult to purify. I can"t answer that; I don"t know how I knew it.17 |
Dr. McClelland, for his part, acknowledged that his assumption regarding the physical state of compound IV was exclusively based on the disclosure of the "730 patent:
| Q. Otherwise you have no knowledge as to whether it"s a solid or an oil or what its physical state is? |
| A. At the time of swearing this affidavit I had no such knowledge.18 |
Finally, I note that Dr. Hendrickson admitted that at the time he swore his affidavit he did not in fact know whether the oxidation of compound IV led to coloured bi-products.19
[45] In response to the evidence led by Drs. Hendrickson and McClelland, the applicants filed, inter alia, the affidavit of Dr. Berntsson. Regarding the physical state of compound IV, Dr. Berntsson produced laboratory notes which correspond with his assertion that "the sulfide compound IV used to give omeprazole is a solid crystalline substance - not an oil...".20
[46] With respect to the purification issue, Dr. Berntsson maintained that the "158 process conditions of low temperature and low acidity minimized any discolouration resulting from degradation. Furthermore, according to Dr. Berntsson, any impurities that may arise using the "158 process are easily purified through recrystallization. Dr. Berntsson also made the point that any alleged improvement which the introduction of the carboxamide group may bring to the Torcan process in terms of purification is negated by the additional process steps required for its removal. As evidence of this assertion, Dr. Berntsson noted the very low yield for the conversion of compound E to omeprazole in the Torcan process. According to Dr. Berntsson, the yield of finished omeprazole under the Torcan process is approximately one half that obtained under the "158 patent.21
[47] With regard to the differences that the carboxamide group is said to bring to the Torcan process relative to the physical state of the intermediates and the comparative ease of purification which is said to result, I accept the evidence of Dr. Berntsson over that of Drs. Hendrickson and McClelland. Neither Dr. Hendrickson nor Dr. McClelland have personally experienced the processes at issue and their affidavits are the product of conjecture. I also accept Dr. Berntsson"s evidence as to the difference in the yield obtained under the two processes. In my view, the lower yield obtained under the Torcan process militates against the respondent"s assertion that under the "158 process omeprazole is much more difficult to purify. Indeed, on cross-examination Dr. McClelland himself recognized that under conventional purification techniques omeprazole under the "158 process is readily purified.22
[48] Dr. Slemon, in his affidavit filed after the above mentioned affidavit of Dr. Berntsson, did not take issue with the contention that compound IV is a crystalline solid. Indeed, on cross-examination, Dr. Slemon qualified the entire question of solid vs. oil as a "tempest in a teapot". Dr. Slemon"s position on this question is thus inconsistent with the initial position advanced by the respondent in support of its notice of allegation. Furthermore, Dr. Slemon conceded that the passage in the "730 patent where it is claimed that compound IV is an oil and is therefore difficult to purify, was not intended to be a categorical statement but one based on Torcan"s own results in experimenting with the "158 process. I am compelled to take note of the fact that the representations which led to the issuance of patent "730 were not so limited.23
[49] In his affidavit Dr. Slemon advances new grounds in an apparent attempt to reestablish the advantages of the Torcan process over that of the applicants. He explains that unlike the applicants" process, the Torcan process does not synthesize omeprazole directly from the sulfide. According to Dr. Slemon, the oxidation of compound D to yield compound E takes place as the next to last step in the Torcan process. This allows excess oxidant to be removed before compound E is isolated and purified. Only then is the carboxamide group removed from compound E and omeprazole formed.
[50] Dr. Slemon contends that under the applicants" process the oxidizing agent remains when omeprazole is produced. As a result, the applicants" omeprazole is susceptible to over-oxidation and degradation. According to Dr. Slemon, in order to control over oxidation and degradation, the synthesis of omeprazole under the applicants" process must take place under a "burdensome cooling capacity". This is to be contrasted with the Torcan technology which Dr. Slemon insists does not need strong cooling for any step.
[51] Dr. Slemon"s assertions with respect to cooling are not borne out by the record. First, patent "730, like patent "158 is not limited by process conditions. This suggests that persons skilled in the art would understand how the process works in both instances without the need to be referred to temperature conditions which suggests in turn that it would have been obvious to any such person that under either process you keep the temperature low to avoid excessive oxidation. Furthermore, the "730 patent in the description of the preferred embodiments also specifies cooling to pre-determined temperatures.24 The "730 patent therefore does not support the distinction which Dr. Slemon sought to make between the two processes with respect to cooling.
[52] Dr. Slemon did attempt to develop support for this distinction by reference to process specifications which he devised after the litigation began.25 However, these specifications also provide for cooling to avoid over oxidation. When questioned about this during cross-examination, Dr. Slemon explained that:
| In a number of place we cool but that is not because there is any heat being generated inside; it is simply a matter that we feel that when we"re about to do a filtration, say if we want to do that filtration at a lower temperature to boost the yields, so one would then lower the temperature.26 |
Yet the process specifications in question which Dr. Slemon devised himself state:
| ... the reaction mixture is cooled to 0-5C and the reaction checked for completion. The reaction is mildly exothermic and the reactor is cooled as needed to maintain the temperature range. After the specified period the reaction is cooled effectively stopping further reaction.27 |
[53] There is no evidentiary support on the record before me for the suggestion made by Dr. Slemon that the "158 process in contrast with the process which he devised requires a "burdensome cooling capacity".
[54] Dr. Slemon also referred to patent "032 as evidencing the problems inherent in the "158 process. However, patent "032 is a patent on an improvement. It relates to a method which optimizes the procedure already taught in patent "158. Specifically, it improves the method for the synthesis of omeprazole by placing a limitation on the pH at the point where oxidation is carried out under the "158 process. The existence of patent "032 evidences the fact that patent "158 can be improved upon. But it does not establish that the "158 process does not work or is not viable as it is.
[55] As noted earlier, although Dr. Slemon"s affidavit was purportedly filed in order to reply to issues raised by the applicants" response to the evidence of Drs. Hendrickson and McClelland, the bulk of the material it canvasses relates to a matter not previously alluded to by either party, namely, the Pummerer rearrangement. In his affidavit Dr. Slemon appears to rely on the Pummerer rearrangement as evidence of the fact that the use of the respondent"s sulfoxide intermediate could not have been contemplated by the "158 patent. Dr. Slemon claims that persons skilled in the art would expect compound E to be unstable and therefore useless as a process intermediate for making omeprazole.
[56] In this connection, Dr. Slemon pointed to a memo written after he was asked to bypass the "158 claims but prior to setting out on that task in which he recorded his doubts as to whether a sulfoxide amide intermediate is a viable process ingredient given its susceptibility to a Pummerer rearrangement.28 Counsel explained that Dr. Slemon decided to experiment with the sulfoxide despite his recorded misgivings because he thought it was nevertheless "worth a try". It will be recalled that Dr. Slemon"s persistence led to what he described as the "unexpected" and "surprising" discovery that compound E was stable.29
[57] The applicants dispute Dr. Slemon"s interpretation of the significance of the Pummerer rearrangement. The applicants observe that Dr. Slemon quotes selectively from articles some of which were written by scientists who purposely sought to induce the Pummerer rearrangement. Moreover, according to the applicants, these same articles demonstrate that the sulfinyl compounds are not susceptible to a Pummerer rearrangement where the combination of elevated temperatures and acidity is avoided.
[58] The applicants note that omeprazole itself is susceptible to a Pummerer rearrangement. It follows that it would be obvious to a chemist skilled in the art that the synthesis of omeprazole must be carried out under the conditions necessary to avoid the Pummerer rearrangement when dealing with compound E. The evidence of Dr. Durst illustrates this point. Dr. Durst, upon being shown compound D and asked his opinion as to the viability of its oxidation to compound E, said the following:
| ...it was obvious to me that the compound could be oxidized to the corresponding sulfoxide. In expressing this opinion I appreciated that the resulting sulfoxide could, under certain reaction conditions, undergo a Pummerer rearrangement. However, as the Pummerer rearrangement typically occurs under the combination of acidic reaction and higher temperature conditions, it was and remains obvious to me that the rearrangement could be avoided by avoiding such conditions. |
| Furthermore, it was and is my opinion that the average person skilled in the art of the Hassle patents, presented with the same compound and question would express the same opinion with respect to the oxidization of the compound and the avoidance of the Pummerer rearrangement. |
| The reason for this opinion is that the Pummerer rearrangement is so well known that the average person skilled in the relevant art would be aware of it and the reaction conditions under which the rearrangement may occur. Hence, such a person would also know the reaction conditions which avoid the rearrangement. In particular, such a person would know that the Pummerer rearrangement can be avoided by using lower temperatures and less acidic reaction conditions.30 |
Consistent with Dr. Durst"s opinion on this point is the fact that both Drs. Hendrickson and McClelland, when presented with only a flow chart of the Torcan process, were content to opine that the process worked. It follows that neither Dr. Hendrickson nor Dr. McClelland saw the Plummerer rearrangement as a problem. Their reaction establishes in the most convincing way possible that the Plummerer rearrangement is well known to persons skilled in the art and that the means of avoiding it are so obvious as not to be worth mentioning.
[59] Although Dr. Slemon purported to give evidence as an expert, he offered his opinion with respect to the process which he devised himself with the view of avoiding the claims made in the "158 patent. He was therefore opining on the question as to whether he was successful in his efforts to bypass the "158 patent.
[60] It is clear to me that Dr. Slemon lacks the necessary independence to be treated as an expert in the present proceeding. Dr. Slemon was committed to developing a non-infringing process and having it upheld by the Court. When the initial grounds advanced by the respondent"s two independent experts collapsed, he attempted to rescue the project by reference to novel grounds and process refinements which he devised after the "730 patent had been issued and indeed after the notice of allegation had been given in this matter. As he was an inventor, it is not surprising that he had more to say about the process than Drs. McClelland and Hendrickson. I accept his evidence insofar as it serves to establish facts of relevance. However, his personal interest in this matter and the circumstances in which he became involved preclude me from treating him as an expert. To the extent that the opinions he expressed were considered to be essential to the respondent"s case, they should have been advanced by someone else.
[61] Considering the Torcan process in light of the evidence properly before me, it is clear that the addition and removal of the carboxamide group devised by Dr. Slemon does not facilitate in any way the oxidation reaction, the key step underlying the "158 patent. What it does is add two steps to the procedure while substantially reducing the yield. I agree with the opinion expressed by Dr. Wuest that the Torcan process would have no material effect on the way the "158 patent works; it achieves nothing useful.
[62] In conclusion, I adopt the opinion expressed by the three experts acting on behalf of the applicants that the Torcan process is an obvious chemical equivalent of the process disclosed in the "158 patent and claimed in (a) and (c) of claim 1 of that patent. It follows that the respondent"s allegation insofar as patent "158 is concerned has not been made out.
[63] For these reasons, an order is issued prohibiting the Minister from issuing an NOC with respect to omeprazole including omeprazole capsules 20 mg and 40 mg until after the expiration of patent "158. The application is otherwise dismissed.
Marc Noël
Judge
OTTAWA, ONTARIO
February 20, 1998
SCHEDULE I
CLAIM 1
A process for preparing a compound of the general formula III
or a therapeutically acceptable salt thereof in which R1and R2are the same or different and are selected from the group consisting of hydrogen, alkyl, halogen, carbomethoxy, carbethoxy, alkoxy and alkanoyl in any position, R6is selected from the group consisting of hydrogen, methyl, and ethyl, R3, R4and R5are 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, R4and R5are not all hydrogen, and the further proviso that when two of R3, R4and R5are hydrogen, the third of R3, R4and R5is not methyl, which process comprises:
(a) oxidizing a compound of formula IV
whereinR1 , R2, R6,R 3, R4and R5are as defined above to form a compound of formula III;
(c) reacting a compound of formula VII
wherein R1and R2are as defined above and Z1is SH, or a reactive esterified
hydroxy group, respectively, with a compound of formula VIII
wherein R6, R3, R4and R5are as defined above and Z2is a reactive esterified hydroxy group or SH, respectively to form an intermediate of formula IV, which then is oxidized to give a compound of formula III;
CLAIM 8
A compound of formula III as defined in claim 1 or a therapeutically acceptable salt thereof when prepared by a process according to claim 1 or an obvious chemical equivalent thereof.
[64] SCHEDULE II
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2 The applicants have indicated that they are not seeking relief in this proceeding in respect of patent "417, without prejudice to their rights on appeal. The reason for this concession is that this patent is for an intermediate with no therapeutic value and should therefore not have been included in the Patent Lists. (see Eli Lilly v. Apotex 68 C.P.R. (3d) 126 (FCA)). The respondent recognizes that that is the basis upon which its allegation must be accepted insofar as this patent is concerned.
4 The order reads in part: "Apotex Inc. is precluded from relying on any further notice of allegation other than the one dated April 27, 1993, in respect of the medicine omeprazole and the six patents listed in the Patent Lists dated April 8, 1993." This order has been appealed.
5 The order was appealed by the respondent, and the appeal remains pending.
6 [1997] 125 F.T.R. 57 at p 64.
8 Order of Joyal J. dated August 14, 1996.
9 Counsel for the respondent indicated in open Court that upon a show cause being issued by the Court of Appeal compelling him to explain why the appeal in question should not be struck for failure to prosecute, he was able to satisfy the Court that his appeal ought to proceed. That does not change the fact that his appeal has been pending for some five years in circumstances where the respondent appears throughout to have been flaunting the order of Dubé J.
10 The patent names Dr. Slemon and another individual as the inventors. Torcan appears as the assignee. The application for its issuance was filed November 4, 1993.
11 AT & T Technologies Inc. v. Mitel Corp. (1989), 26 C.P.R. (3d) 238 (F.C.T.D.) at 249 per Reed J. See also Eli Lilly and Co. v. Novopharm Ltd. (1995), 60 C.P.R. (3d) 417 (F.C.T.D.) at 435.
12 Catnic Components Limited v. Hill & Smith Limited, [1982] R.P.C. 183 (H.L.). See also O"Hara Manufacturing Ltd. v. Eli Lilly & Co. (1989), 26 C.P.R. (3d) 1 (FCA).
13 Beecham Canada Ltd. v. Proctor & Gamble Co. (1982), 61 C.P.R. (2d) 1 at p. 27, per Urie J.A.
14 Beloit Canada Ltd. et al. v. Valmet OY (1986), 8 C.P.R. (3d) 289 at p. 294.
15 The relevant portions of claims 1 and 8 are reproduced as Schedule I to these Reasons.
16 The chart in question is reproduced as Schedule II to these Reasons.
17 Cross-examination of Dr. Hendrickson, Applicants" Application Record, vol. IV, p. 784.
18 Cross-examination of Dr. McClelland, Applicants" Application Record, vol. IV, p. 923. This answer is particularly damaging to the respondent"s case given Dr. Slemon"s subsequent comments regarding the disclosure of the "730 patent with respect to the physical state of compound IV. See paragraph 48 of these Reasons.
19 Cross-examination of Dr. Hendrickson, Applicants" Application Record, vol. IV, p. 799.
20 Affidavit of Dr. Peder Berntsson, Applicants" Application Record, vol. I, p. 181.
21 This assertion is essentially unchallenged.
22 Cross-examination of Dr. McClelland, Applicants" Application Record, vol. IV, p. 939-940.
23 This is material as the oil state of compound IV is the basis upon which it is said in patent "730 that "it is very difficult to purify", (line 7, column 2 of patent "730). The oil state is again referred to to highlight the fact that crystalline solids, "as opposed to oils" are readily purified (line 52, column 2 of patent "730). Applicants" Application Record, vol. I, p. 102 et seq.
24 Column 7, line 25 of the "730 patent, Applicants" Applications Record, vol. I, p. 106.
25 "Steps of Manufacture", Exhibit 4 to the affidavit of Dr. Slemon, Applicants" Application Record, vol. II, p. 251. The process outlined in these specifications was said to optimize patent "730.
26 Cross-examination of Dr. Slemon, Applicants" Application Record, vol. V, p. 1126. see also p. 1127.
27 Footnote 25, (supra ) at p. 252.
28 Handwritten note signed by Dr. Slemon bearing the date "April 93". Exhibit 22 to the affidavit of Dr Slemon, (Applicants" Application Record, vol. II, p. 493).
29 Affidavit of Dr. Slemon, Applicants" Application Record, vol. II, p. 240, paragraph 40. The element of surprise is of course an essential component of a true discovery and counsel for the respondent was quick to add that the fact that Dr. Slemon believed that it was "worth a try" did not make the end result "obvious" based on recent case law with the result that Dr. Slemon would have been throughout his quest to avoid patent "158 possessed with the perfect state of mind of the non-infringing inventor. See Bayer Aktiengesallschaft v. Apotex Inc. (1995), 60 C.P.R. (3d) 58 at pages 81 and 82.
30 Affidavit of Dr. Tony Durst, Applicants" Application record, vol. II, p. 495 at p.496. It is significant that Dr. Durst expressed this view without being shown any documents or provided with any information other than the structure of the compound.