Date: 20000530
Docket: T-1599-98
Between:
MERCK FROSST CANADA INC. and MERCK & CO., INC.,
Applicants,
- and -
THE MINISTER OF HEALTH AND ALCON CANADA INC.,
Respondents.
REASONS FOR ORDER
Muldoon, J.
[1] This is an application, heard in Vancouver and Ottawa, pursuant to section 55.2 of the Patent Act, R.S.C. 1985, Chap. P-4 and section 6 of the Patented Medicines (Notice of Compliance) Regulations SOR/93-133. The applicants seek an order prohibiting the Minister of Health from issuing to the respondent Alcon Canada Inc. a notice of compliance for Timolol Maleate Ophthalmic Gel Forming Solution 0.25% and 0.5% until after the expiry of Canadian letters patent no. 1,280,367. The applicants also seek an order for their costs.
Facts
[2] The second applicant Merck & Co., Inc. (hereinafter Merck & Co.) owns Canadian patent no. 1,280,367 (the "367 patent). The first applicant, Merck Frosst Canada Inc. (hereinafter Merck Frosst), is the sole licensee of the patent. In June of 1995, the two companies began marketing Timoptic-XE, an eyedrop medication used to treat glaucoma, which relies on the invention disclosed in the "367 patent.
[3] The invention described in the patent relates to a pharmaceutical composition containing at least one polysaccharide in aqueous solution of the type which undergoes a liquid to gel phase transition under the effect of an increase in ionic strength. Claim 1 of the patent provides:
| 1. Pharmaceutical composition intended for contacting with a physiological liquid characterized in that said composition is intended to be administered as a non-gelled liquid form and is intended to gel in situ, this composition containing at least one polysaccharide in aqueous solution, of the type which undergoes liquid-gel phase transition gelling in situ under the effect of an increase in the ionic strength of said physiological liquid. |
When used in an ophthalmic solution, the ions, or salts, which are supposed to transform the solution into a gel are to be found in one"s lacrimal fluid or tears. The invention"s use in eye drops, such as Timoptic-XE, allow the eye drops to gel on the surface of an eye as opposed to being quickly washed away by blinking.
[4] In the late 1990s, the respondent, Alcon Canada Inc. (hereinafter Alcon), sought to market products similar to Timoptic-XE called Timolol Maleate Ophthalmic Gel Forming Solution 0.25% and 0.5% (hereinafter TGFS). To this end, it submitted an Abbreviated New Drug Submission to Health Canada referencing Timoptic-XE and served a notice of allegation (NOA) dated June 10, 1998 on Merck Frosst. In the NOA, Alcon alleged, in part, that its TGFS would not infringe the "367 patent and that the patent was, in any event, invalid.
[5] In respect of its allegation concerning non-infringement, Alcon claimed that TGFS contains xanthan gum and asserted that this gum is not a type of polysaccharide which undergoes a liquid to gel phase transition, gelling in situ under the effect of an increase in ionic strength. It alleged that Merck & Co. had admitted as much in some of its written submissions dated December 7, 1988, made during the legal proceedings concerning the American counterpart of its "367 patent.
[6] In respect of its allegations concerning invalidity, Alcon alleged first, that claim 1 of the "367 patent cannot be validly construed as having a scope broad enough to include xanthan gum without also including prior art ophthalmic compositions, such as U.S. patents no. 4,136,177 and no. 4,136,173. Second, Alcon claimed that, prior to the filing date of the "367 patent, ophthalmic compositions containing an ophthalmic drug and xanthan gum were known. It also claimed that timolol and timolol maleate and their use as beta blockers to reduce ophthalmic hypertension were similarly known prior to the filing date of the "367 patent. Third, Alcon claimed that, insofar as the claims of the "367 patent include xanthan gum, such claims are invalid either for inoperability or lack of utility. The applicants, of course, take exception to all of these claims and arguments.
[7] The evidence adduced by both sides in support of their respective allegations is voluminous. Suffice it to say that the applicants started out with evidence from Prof. Neumann of the University of Toronto, a specialist in applied surface thermodynamics and biomedical and biotechnological problems. During cross-examination, he claimed expertise with polysaccharides. Alcon countered with the evidence of Prof. Ross-Murphy of the University of London, whose research focus has been on the structure and properties of polymers and polysaccharides, including xanthan gum, especially as the structure and properties relate to gelation. Soon the applicants were countering with the evidence of Prof. Edwin Morris recently of Cranfield University in England, whose research experience rests with the functional properties of natural polymers and, in particular, commercial polysaccharides which are used as gelling agents, such as xanthan and gellan gum. He also claims experience with the use of polysaccharides in structuring ophthalmic solutions. Both parties also relied on test results from their respective laboratories. To all of this, Alcon added test results from the laboratory of its foreign parent company, Alcon Laboratories Inc., conducted under the supervision of an employee, Mr. Bhagwati Kabra.
Legal Issues
[8] The parties raised several preliminary matters. The first two concern whether the respondent"s NOA is too vague and whether Alcon is barred, as a result, from advancing some of the issues it relies on in defence of its NOA. The third and final preliminary issue concerns the propriety of certain parts of the evidentiary landslide under which each party buried the Court. The two substantive issues concern the proper construction of the "367 patent and Alcon"s allegation of non-infringement. As will become apparent, the issue of invalidity in respect of the patent needs not to be addressed.
[9] In respect of the first preliminary matter, the applicants take exception to Alcon"s NOA, charging that it contains allegations of non-infringement that are not detailed enough for the purposes of paragraph 5(3)(a) of the Patented Medicines (Notice of Compliance) Regulations SOR/93-133 (the Regulations). This paragraph provides:
| 5. (3) Where a person makes an allegation pursuant to paragraph (1)(b) or subsection (2) the person shall [...]
|
5. (3) Lorsqu'une personne fait une allégation visée à l'alinéa (1)b) ou au paragraphe (2), elle doit : [...]
|
As noted in Syntex (U.S.A.) Inc. v. Novopharm Ltd. (1996), 65 C.P.R. (3d) 499 (F.C.T.D.), the statement of facts in an NOA must be detailed enough that, if assumed to be true or proven, the whole would justify the allegations of non-infringement made in the NOA.
[10] In response to the applicants" charge, counsel for Alcon pointed to several allegations of fact in the NOA which, he alleged, could ground a claim of non-infringement, if assumed to be true. In particular, he pointed to the following allegations: that Alcon"s product contains xanthan gum, that xanthan gum does not undergo a liquid to gel phase transition in situ , that any gelation does not occur due to the presence of ions and that the applicants have admitted the second alleged fact. As the applicants submit, these allegations are not fraught with precision. They do, however, suit the purposes of paragraph 5(1)(a) of the Regulations. This is because they support, assuming them to be true, Alcon"s claim of non-infringement. They also define the issues or the arena in which the applicants would have to fight Alcon"s claim of non-infringement if they were so to choose. The claim of non-infringement, in other words, is not a mere bald assertion.
[11] The applicants also take exception to the corporate respondent"s seeking refuge in Prof. Ross-Murphy"s definition of gel, stating that the definition of a gel was not one of the grounds of non-infringement laid out in the NOA. The struggle surrounding the term "gel", however, was initiated by the applicants, through the first affidavit of Prof. Morris, in order to help disprove Alcon"s allegation in its NOA that xanthan gum does not undergo a liquid to gel phase transition in situ . Alcon had, therefore, every right to adduce Prof. Ross-Murphy"s competing definition of "gel" as a defence. To conclude otherwise would be to strip a respondent in a section 5 proceeding of any ability to defend itself. It would also force a respondent first, to prophesy down which path an applicant will march in construing the patent so as to attack the NOA and second, predict what scientific evidence it will need to guard the ramparts. Such a process, however, would be inefficient and serve no purpose. In addition, because defining the word "gel" is a matter of patent construction and, as such, a necessary precursor to any discussion of non-infringement or validity, the applicants cannot now argue that they were unaware that it would rear its head. The rationale underlying the rule against additional allegations, therefore, can be considered satisfied in the circumstances.
[12] As for whether Alcon may now allege that its xanthan gum gels due to proteins and not ions, the issue of what causes gelation was laid out, albeit barely, in the NOA and taken up by the applicants. The Court is not, however, unsympathetic to the applicants" concerns. Though respondents in section 5 proceedings may make further, detailed allegations in respect of the broad ones already in their NOAs which have come under attack, there is a point where the allegations will, like the branches of a sturdy baobab tree, take root and a separate life of their own. This is when the allegations must be cut. Counsel has not persuaded the Court, however, that the allegations have reached this stage.
[13] As the final preliminary issue the applicants ask that Alcon"s evidence or, at least its last two affidavits, most of which was filed after the deadlines set first by order of Mr. Justice Teitelbaum"s order dated October 15, 1998 as amended by Mr. Justice Evans" order dated January 25, 1999, not be admitted. Alcon submits that Prof. Morris" first affidavit should be excluded or, in the alternative, that all evidence of both parties should be admitted.
[14] In support of their respective positions, each party argues that the other party breached the directives of this Court as to when and what was to be filed. The applicants also argue that they have been prejudiced, in particular by the late filing of the final affidavit of Prof. Ross-Murphy and by that of Mr. Kabra. Yet, this Court notes that the order of Teitelbaum J. clearly envisions that the parties may need to file further evidence, an option which both pursued whole-heartedly and to which Assistant Senior Prothonotary Giles gave his blessing in orders dated July 15 and August 4, 1999. As for Alcon"s last wave of affidavits, the fact that the applicants were not allowed to respond to them, in light of the summary nature of these proceedings, works little prejudice on them. Finally, it should be noted that both parties have, as Dubé J. stated in an interlocutory order, travelled a long and unruly procedural road. As Prothonotary Lafrenière observed, both have consistently operated outside of the time limits provided under the Federal Court Rules, 1998 SOR/98-106. Neither can be considered, therefore, to have clean hands in the matter. All of the evidence will, albeit reluctantly, be admitted.
Claim 1 includes both weak & strong gels.
[15] As the first substantive issue, both parties agree that the Court must properly construe the patent. The issue of construction relates, in particular, to the meaning of the phrase "polysaccharide [...] of the type which undergoes liquid-gel phase transition gelling in situ" as it is found in claim 1. The applicants submit that this phrase refers to any polysaccharide which changes from a solution to a gel, whether the gel is a weak one or a strong one. Alcon submits that claim 1 does not refer to polysaccharides which only convert to weak gels. The essence of this dispute concerns whether the definition of the word "gel", as used in claim 1, covers weak gels and strong gels or simply strong gels. Alcon also briefly disputed the meaning of the last 10 words of claim 1 but, as this argument has no roots in the NOA, it does not need to be considered.
[16] In respect of the term "gel", the applicants point to its ordinary meaning to suggest that it includes weak gels. The common parlance can carry but little weight in this debate, however, considering that marketing agencies, which seem to drive the ordinary meaning, use the term "shower gel" to describe what Alcon tested as a solution. Nor is this Court inclined, in the circumstances, to make a finding based on textbook, encyclopaedia or popular science articles. Physical samples of various gels and weak gels also simply threatened to confuse matters. More helpful are the learned articles and expert opinions adduced by both parties, which reveal that gels and weak gels have many different characteristics. For instance, gels and weak gels respond differently to high stress levels, the former breaking into pieces, the latter flowing like a viscous solution. Prof. Ross-Murphy"s attempt to distinguish weak gels by also calling them solutions is questionable, however, in light of his article "Non-linear Viscoelasticity of polysaccharide solutions. 2: Xanthan polysaccharide solutions", International Journal of Biological Macromolecule , 1987, vol.9, October, 257-264 at 263, in which he suggests that xanthan gum weak gels are not true solutions. Of greater help is the professor"s unshakable belief that the term "liquid-gel phase transition" in claim 1 does not refer to the transition which a polymer solution undergoes to become a mere weak gel. In the end, however, Prof. Ross-Murphy and Prof. Morris could not agree on what a liquid-gel phase transition is, other than that it involves percolation. No critical measurement of viscosity, storage modulus, no requisite number of cross-linked polymer chains or defining character trait, other than G" (elastic response) > G" (viscous response) was agreed on. The attempt to describe a liquid-gel phase transition only served, therefore, to render more confusing the exact definition of a gel.
[17] A better clue to the meaning of a gel is the fact that gels and weak gels share a mechanical spectrum and certain characteristics: the manner in which they respond to low stress levels and hold solvents like a sponge (storage modulus). It is difficult to conclude, therefore, that there is any clear dividing line between the two. If anything, these similarities suggest that the difference between the two may be one of degree and not kind.
[18] Alcon suggests that claim 1 cannot be referring to weak gels as these would not be a useful ingredient for the patent. In particular, Prof. Ross-Murphy claims that a weak gel, if used in eye drops, would quickly break down under constant blinking and be cleared from the eye. The Court is not persuaded that this is necessarily so, however, as the professor eventually admitted under cross-examination that it was quite possible to form a weak gel in the eye. In fact, he has championed for years the ability of weak gels to re-form their structure quickly after having been broken apart under stress. Alcon also pointed to some statements made by Merck & Co. in the 1990s concerning the lack of ophthalmic utility of xanthan gum (a weak gel) but for the purposes of construing the patent no resort can be made to these statements as they are part of the "367 patent"s file history; P.L.G. Research Ltd. v. Jannock Steel Fabricating Co. (1991), 35 C.P.R. (3d) 346 (F.C.T.D.), affd 41 C.P.R. (3d) 492 (F.C.A.). Nor can estoppel serve to allow this evidence. As for Alcon"s argument that weak gels do not need to be formed in situ to be useful, and that claim 1, therefore, cannot be referring to them, Prof. Neumann was adamant that, even if one could administer a weak gel volumetrically, as Prof. Morris admitted has been done in the past, it would come out in "unequal plops and drops" unless it was watery enough. This suggests that applying a watery polymer solution (which will only gel in situ ), as opposed to a stiffer weak gel may have the advantage of allowing for more reproducible and more accurate dosing and may, therefore, be (relatively) useful.
[19] As for the patent itself, it occasionally describes the gels which are to be used as "semi-solid". This term is also used at page 3, line 1 to refer to the non-flowing gels of the U.S. patent 4,188,373 and at page 4, line 29, to describe gels which cannot be administered by volumetric means. The suggestion from counsel for the respondent (paragraphs 259-262 of the respondent"s memorandum) was that this, along with other indicia, suggests that the patent does not refer to weak gels. Counsel for the respondent (paragraphs 279-282, 264-266 of the respondent"s memorandum) pointed out, for instance, the test results revealed in figure 2 of the patent and the praise given to gellan gum, at page 6, line 16, for changing from a liquid to a "solid" phase. Counsel for the respondent (paragraph 263 of the respondent"s memorandum) also noted that the patent nowhere refers to xanthan gum, a known weak gel but, rather, refers only to gellan gum, a known strong gel. Finally, in support of his stand against weak gels, he cited (pages 397-399 of the February 2-4, 2000 transcript) among other things, claims 4, 5 and 6 of the patent and their applicability solely to gellan gum.
[20] On the other hand, the patent consistently teaches the use of polysaccharides in general which gel in situ under the effect of ions, without expressly restricting itself to certain brands of gel or to those forming strong gels. In addition, the scientists Prof. Morris" affidavit #1 paragraph 57 and affidavit #2 paragraph 63; Prof. Ross Murphy"s cross-examination pages 185-187 agree that the steady shear method used in figure 2 of the patent to measure the rheology of a sample gel is not suitable to measuring strong gel rheology. Construed as a whole, and despite the existence of claim 4, 5 and 6, the patent points to the inclusion of weak gels. Favouring one or two curious though isolated references to strong gels, what Lord Russell of Killowen would, in Electrical & Musical Industries Ltd. v. Lissen Ltd. (1938), 56 R.P.C. 23 (H.C.), have called "stray phrases", would constitute not only too technical a reading of the patent"s disclosure but a reading which would be both unreasonable and unfair to the patentee. As such, this Court finds that a person skilled in the art of preparing ophthalmic compositions would interpret claim 1 as including polysaccharides which form a weak gel in situ , not just those, such as gellan gum, renowned for forming strong gels.
Allegations of non-infringement.
[21] The patent having been construed to include weak gels, it falls to the Court to consider, next, whether the allegations of non-infringement by Alcon in respect of its TGFS are unjustified. The applicants submit that claims 1, 2, 3 and 6 to 15 have been infringed on the basis of test results showing that the mechanical spectra of TGFS in simulated tear fluid, to which ions have been added, match those of a weak gel. The respondent counters these results, which come from the laboratory of Prof. Morris, with results from separate tests conducted under the supervision of Prof. Ross-Murphy and of Mr. Kabra. These latter tests determined that TGFS, when awash in ions, does not undergo a liquid to gel phase transition but that it merely experiences an increase in viscosity. Before attending to these tests, however, this Court must address an evidentiary matter.
[22] As noted above, Alcon referred the Court to previous statements Merck & Co. made during legal proceedings concerning its American companion to the "367 patent and during its 1998 Chastaing patent application, seeking to admit them as admissions against interest, as prior inconsistent statements and seeking to estop the applicants from contradicting them. The statements in question were, respectively, (1) that xanthan gum does not experience a solution to gel phase transition and (2) is not much affected by changes in ionic strength. It is not clear, however, that counsel for the respondent may rely on the first statement, having made a formal admission on the opening day of the hearings (page 68 of the February 2-4, 2000 transcript) to the effect that TGFS, which contains xanthan gum, gels.
[23] As for the second statement, made during the Chastaing patent application, it is clear that, for purposes other than construing a patent, extrinsic evidence has repeatedly been accepted; Laboratoire Pentagone Ltee. v. Parke, Davis & Co., [1968] S.C.R. 307 and Foseco Trading A.G. v. Canadian Ferro Hot Metal Specialities, Ltd. (1991), 36 C.P.R. (3d) 35 (F.C.T.D.). As such, the second statement may be considered as an admission (not an admission against interest or a prior inconsistent statement) and as proof of its contents; Sopinka et al., The Law of Evidence in Canada, 2nd ed., Toronto: Butterworths, 1999 at 286-291. In respect of the contents, counsel for the applicants failed to persuade the Court that the Chastaing statements, which refer to xanthan gum in general terms, should be considered as anything else than an admission covering all xanthan gums and not merely covering the Keltrol brand of xanthan gum.
[24] Alcon also argues that the applicants should be estopped from contradicting the Chastaing statement. It is not clear, however, whether Alcon argues estoppel in pais, the American file wrapper estoppel, the English estoppel against approbating and reprobating or all three. As for the first estoppel - in pais, Alcon did not plead that Merck & Co.
i) understood its statements to be false, ii) intended that they should be acted upon by Alcon or iii) conducted itself in such a way that would lead a reasonable person to understand that it had intended the statements in question to be acted upon. The closest it came was to have counsel for its foreign parent (Mr. Ryan) aver (paragraph 15 of his affidavit), ambiguously, that all applicants for patents in the United States are well aware of the significance and importance of all statements made to that country"s patent office during prosecutions. This, however, is not enough. As for file wrapper estoppel, counsel for the respondent failed to point this Court to a single Canadian decision in which this type of estoppel has been applied and not merely alluded to. Nor did counsel offer up any reasons why the Court should sow this foreign seed in its yard. Finally, the principle barring approbating and reprobating is not applicable in this case as we are dealing with inconsistent factual allegations made by Merck & Co., not inconsistent courses of conduct taken by it to which this species of estoppel might apply; Lord Hailsham of St. Marylebone, Halsbury"s Laws of England, 4th ed., London: Butterworths: 1992 at paragraph 957. That counsel for the respondent dressed Merck & Co."s factual allegations up in terms of "taking a factual position" does not help his cause.
[25] And what of the test results? The applicants have failed to show, using the tests of Prof. Morris, that Alcon"s claim of non-infringement is unjustified. This is, in part, because of the questions which Alcon has raised in respect of the experiment design adopted by Prof. Morris. In particular, this Court has concerns that the TGFS tested for the applicants was found to have changed into a weak gel only after being saturated with an unusually large number of ions. Prof. Morris" assertion that his tests were designed using well established principles and his confusing explanations in respect of ratios and dilution were not enough to answer these concerns. The question raised, in essence, was whether TGFS will gel in the presence of the approximate number of ions present in the eye at the time of application or soon thereafter. Prof. Morris" tests provided no answer to this question and, as a result, failed to push the applicants over the relatively low bar which is described in Merck Frosst Canada Inc. v. Canada (Minister of National Health and Welfare) (1998), 84 C.P.R. (3d) 492 (F.C.T.D.) and which the applicants had to clear. The admissions made during the Chastaing patent application to the effect that xanthan gum is not greatly effected by changes in ionic strength also serve to cast doubt on Prof. Morris" test results.
[26] All this is not to say that the Court has no concerns vis à vis Prof. Ross-Murphy"s tests. In particular, this Court considers that the professor"s use of rotational tests is, as he himself admitted (Ross-Murphy cross-examination pages 55-57, 69-70), a second best approach to determining whether TGFS forms a weak gel. This Court will not go so far as to agree with the applicants, however, that the TGFS should not have been diluted to the degree that it was or that the low temperature at which the tests were preformed biased their results. As for Mr. Kabra"s tests, the applicants cast a slight shadow over them by noting the fact that Mr. Kabra knew his employers were seeking results different from Prof. Morris" and by pointing out that his TGFS, Rhodigel Clear and Keltrol T xanthan gum samples were mixed together with their respective liquids at relatively high temperatures. The applicants also alleged that the tests had been rushed but the Court is not satisfied tht this was so. Otherwise, the applicants did not seriously challenge the results of the Kabra tests, merely noting that they differed from those of Professors Morris and Ross-Murphy. The Court is satisfied, therefore, of the tests" reliability and validity, even to the extent that Alcon"s tenuous claim about how proteins in the eye play some unknown and unstated role in the gelation of TGFS may be safely ignored.
Conclusion
[27] Having concluded that Alcon"s claims of non-infringement have not proved to be unjustified, this Court does not need to consider the matter of validity. It suffices that the applicants have failed in their first task and the applications are dismissed. The corporate respondent is entitled to its party-and-party costs incurred in these proceedings in an amount agreed, or if agreement be not possible, as officially assessed.
"F.C. Muldoon"
Judge
FEDERAL COURT OF CANADA
TRIAL DIVISION
NAMES OF COUNSEL AND SOLICITORS ON THE RECORD
COURT FILE NO.: T-1599-98
| STYLE OF CAUSE: Merck Frosst Canada Inc. and Merck & Co., Inc., v. The Minister of Health and Alcon Canada Inc., |
PLACE OF HEARING: Ottawa, Ontario
| DATE OF HEARING: February 16, 2000 |
REASONS FOR ORDER OF
THE HONOURABLE MR. JUSTICE MULDOON
DATED MAY 30, 2000
APPEARANCES:
Mr. William H. Richardson for the Applicants
Mr. Gunars Gaikis for the Respondent (Alcon)
Ms. Joanne Fox for the Respondent (Minister of Health)
Dept. of Justice
2 First Canadian Place
Suite 3400, Exchange Tower
Toronto, ON M5X 1K6
SOLICITORS OF RECORD:
McCarthy Tétrault
Suite 4700
Toronto-Dominion Centre
Toronto, ON M5K 1E6 for the Applicants
Smart & Biggar
438 University Avenue, Suite 1500
Toronto, ON M5G 2K8 for the Respondent (Alcon)
Morris Rosenberg
Deputy Attorney General of Canada for the Respondents (Minister of Health)