Ottawa, Ontario, June 21, 2006
PRESENT: The Honourable Mr. Justice O'Reilly
BETWEEN:
BIOVAIL CORPORATION (d.b.a. BIOVAIL
PHARMACEUTICALS CANADA); BIOVAIL
LABORATORIES INC. and GLAXOSMITHKLINE INC.
and
THE MINISTER OF NATIONAL HEALTH
ANDWELFARE and SANDOZ CANADA INC.
REASONS FOR JUDGMENT AND JUDGMENT
(Edited for public release)
[1] The respondent Sandoz wishes to market a new drug. It maintains that this drug would not infringe patents owned by the applicants (to whom I will refer collectively as Biovail). Biovail disagrees and asks me for an order prohibiting the Minister of National Health and Welfare from permitting Sandoz to put its drug on the market. Sandoz also argues that one of Biovail's patents is invalid.
[2] I am satisfied that the evidence before me supports Sandoz's claim that it will not infringe Biovail's patents. Therefore, I must deny Biovail's request for a prohibition order. In the circumstances, I need not decide the issue of invalidity.
I. Issues
1. Is Sandoz's claim that its proposed drug will not infringe Biovail's Canadian Patent no. 2,142,320 (the '320 patent) unjustified?
2. Is Sandoz's claim that its proposed drug will not infringe Biovail's Canadian Patent no. 2,168,364 (the '364 patent) unjustified?
II. Analysis
A. Overview of proceedings
1. Notice of Compliance (Patented Medicines) Regulations
[3] Proceedings under these Regulations serve a limited purpose. They provide an expeditious means of determining of issues relating to the validity and scope of drug patents within the regulatory scheme governing manufacturers' rights to market their products in Canada. They are not equivalent to a civil action for patent infringement: Hoffmann-La Roche Ltd. v. Canada (Minister of National Health & Welfare), [1996] F.C.J. No. 1333 (C.A.) (QL), at para. 12. The Court's ruling under the Regulations is not binding in any subsequent action between the parties: Fournier Pharma Inc. v. Canada(Minister of Health), 2004 FC 1718, [2004] F.C.J. No. 2149.
2. The Burden of Proof on the Parties
[4] Sandoz alleges that it will not infringe Biovail's patents. It states the grounds for its position in a notice of allegation that was served on Biovail on November 24, 2004. In particular, Sandoz says that it will not infringe the '320 patent because it intends to use a different sustained release agent than the one identified in that patent, and that it will not infringe the '364 patent because it will not use any of the stabilizing agents listed in it.
[5] To obtain the order it seeks in these proceedings, Biovail must prove that Sandoz's allegations are unjustified. For its part, Sandoz must produce evidence showing that its allegations are valid.
3. Judicial Comity
[6] Recently, Justice Sean Harrington decided a case involving the '320 patent: Biovail Pharmaceuticals Inc. v. Canada(Minister of National Health and Welfare), 2005 FC 9, [2005] F.C.J. No. 7. As in this case, one of the main issues there was whether the respondent's use of hydroxypropyl cellulose (HPC) as a sustained release agent would violate Biovail's '320 patent. Justice Harrington concluded that it would not.
[7] Sandoz argues that I should follow Justice Harrington's decision as a matter of judicial comity, unless I am of the view that it was manifestly wrong. Biovail argues that I should resolve the issues relating to the '320 patent on my own, given that the evidence before me is different than that which was before Justice Harrington. It suggests that judicial comity might cause me to follow Justice Harrington on legal issues, but it should not affect my findings of fact.
[8] I agree with Biovail that comity should not influence my analysis of the evidence before me. Further, given that I agree with Justice Harrington's analysis of the prevailing law, I need not consider the degree of deference I might have accorded that analysis had I not fully agreed with it.
B. Is Sandoz's claim that its proposed drug will not infringe Biovail's Canadian Patent no. 2,142,320 (the '320 patent) unjustified?
1. The Evidence
[9] Biovail's '320 patent relates to a tablet that combines bupropion hydrochloride, a well-known anti-depressant, with hydroxypropyl methylcellulose (HPMC). HPMC is used in drugs to obtain a sustained release of the active ingredient. Sandoz proposes to produce a tablet that combines bupropion hydrochloride with hydroxypropyl cellulose (HPC), another sustained release agent.
[10] Each party engaged two experts to consider whether Sandoz's proposed drug would infringe Biovail's patent. The experts agreed on several matters, but differed on the ultimate question whether Biovail's patent would be infringed by Sandoz's new drug. I will first describe the areas of agreement and then the areas of disagreement.
(a) Areas of agreement
(i) The use of cellulose ethers as sustained release agents
[11] Both HPMC and HPC are derivatives of cellulose, a natural constituent of plants. In particular, they are both cellulose ethers. Cellulose ethers have properties that make them suitable for use as sustained release agents in tablets. When they come into contact with a liquid (e.g. stomach fluid), they form a gel on the surface of the tablet. The gel controls the rate at which the active ingredient is released from the tablet and ingested by the patient. The gel dissolves quite slowly, but eventually it disperses and the active ingredient is fully released.
[12] Sustained release agents are useful in many kinds of drugs because they ensure that an appropriate quantity of the drug's active ingredient is ingested by the patient over time. This allows the drug to be effective over an extended period. It also is easier for patients to remember to take one tablet per day, for example, rather than several. With respect to bupropion hydrochloride in particular, patients sometimes suffer seizures if the active ingredient is released too quickly. A sustained release tablet avoids that problem.
(ii) Comparing HPMC and HPC
[13] Both HPMC and HPC consist of chains of cellulose molecules. Both are prepared by combining cellulose with propylene oxide. In the resulting reaction, some of the hydrogen atoms of the cellulose molecules are replaced with hydroxypropyl groups. For HPMC, an additional reaction is required. The cellulose is also combined with methyl chloride. The result is that in HPMC some of the hydrogen atoms of the cellulose are replaced by methoxy groups and some by hydroxypropyl groups. Accordingly, HPMC's chemical make-up is similar to HPC's, but it has an additional ingredient: the methoxy groups.
[14] Both HPMC and HPC are available from various manufacturers in different grades. The grades correspond to varying concentrations of hydroxypropyl and methoxy groups respectively. For example, the '320 patent identifies a grade of HPMC referred to as "2910", which contains 29% hydroxypropyl groups and 10% methoxy groups in place of the hydrogen atoms in the original cellulose.
(b) Areas of disagreement
[15] Biovail's experts maintain that the differences between HPMC and HPC are minimal. The chemical composition of the two substances is virtually identical, the only difference being that HPMC has a certain proportion of methoxy groups, which HPC lacks. They maintain that the existence of methoxy groups does not dramatically affect the manner in which HPMC operates as a sustained release agent. Accordingly, a person skilled in the art of drug formulation would understand that where a patent identified HPMC as a sustained release agent, such as Biovail's '320 patent, HPC could be readily substituted for it. These experts claim, therefore, that Sandoz's proposed new drug would infringe Biovail's patent because it simply replaces the HPMC in it with a well-known substitute.
[16] Sandoz's experts suggest that there are significant differences between HPMC and HPC. They note the chemical difference between the two substances, namely, the presence of the methoxy groups in HPMC. They suggest that the presence of the methoxy groups affects the performance of HPMC as a sustained release agent. Further, they insist that the two substances cannot be automatically substituted for one another. To create a sustained release form of bupropion hydrochloride using HPC, one cannot simply substitute an equivalent amount of HPC for the proportion of HPMC specified in the '320 patent. One would have to conduct tests using various quantities and grades of HPC to arrive at a formulation that would be medically appropriate and effective. These experts claim, therefore, that Sandoz's proposed new drug does not infringe Biovail's '320 patent because it represents a different formulation from that which the patent discloses.
2. The Scope of the '320 Patent
[17] In order to determine whether Sandoz's proposed new drug would infringe Biovail's '320 patent, one must look to the patent itself to see what it claims. The principal claim of the '320 patent (Claim 1) is as follows:
1. A sustained release tablet comprising bupropion hydrochloride and hydroxypropyl methylcellulose the amount of hydroxypropyl methylcellulose to the amount of bupropion hydrochloride being from 0.19:1 to 1.1:1 respectively and the tablet being capable in water of releasing from 20 to 60 percent of the total amount of bupropion hydrochloride in 1 hour, from 50 to 95 percent of the total amount of bupropion hydrochloride in 4 hours and not less than 75 percent of the total amount of bupropion hydrochloride in 8 hours. (Emphasis added.)
[18] The rest of the claims in the '320 patent rely on the contents of Claim 1. The essence of Claim 1 lies in the combination of bupropion hydrochloride with HPMC in a tablet form, with the concentration of HPMC being within a particular range, as measured by weight, which will yield a rate of release of the active ingredient over time.
[19] The question I must answer is whether Biovail has established that Sandoz's allegation that it will not infringe Biovail's patent is unjustified. I must take account of the fact that the '320 patent specifically identifies HPMC as the sustained release agent, to be present in a specified range of concentrations, as well as a certain rates of release of the active ingredient.
[20] Patents often contain both essential and non-essential elements. In basic terms, if a manufacturer replaces a non-essential element in a patent with something equivalent, it might infringe the patent. If it replaces an essential element, it does not infringe the patent. Justice Binnie set out an approach for determining whether an element is essential or non-essential in Free World Trust v. Electro Santé Inc., 2000 SCC 66, [2000] 2 S.C.R. 1024, at para. 55:
For an element to be considered non-essential and thus substitutable, it must be shown either (i) that on a purposive construction of the words of the claim it was clearly not intended to be essential, or (ii) that at the date of the publication of the patent, the skilled addressees would have appreciated that a particular element could be substituted without affecting the working of the invention, i.e., had the skilled worker at that time been told of both the element specified in the claim and the variant and "asked whether the variant would obviously work in the same way", the answer would be yes: Improver Corp. v. Remington, supra, at p. 192. In this context, I think "work in the same way" should be taken for our purposes as meaning that the variant (or component) would perform substantially the same function in substantially the same way to obtain substantially the same result.
[21] Turning to the first possibility, it appears to me, looking at the '320 patent as a whole, that HPMC is an essential element of the invention. It is mentioned in all of the patent's claims. No potential substitutes or equivalents are identified.
[22] Turning to the second way of distinguishing essential from non-essential elements, I believe, based on the evidence tendered by the parties, that a person skilled in the art of drug formulation who read the '320 patent would have realized that it would probably be possible to come up with a similar sustained release formula using HPC. But this is not enough. If that skilled worker had been told that HPMC was being used in the '320 patent to achieve a sustained release of the active ingredient, and was asked whether HPC would obviously work in the same way, the answer would not be yes. At best, the answer might be "perhaps". But it would only be after experimenting with different quantities and grades of HPC that a substantially similar tablet could be developed. I note that the inventors of the '320 patent state that it took three years of testing to arrive at the sustained release formulation using HPMC. In these circumstances, I must conclude that HPMC is an essential element of the '320 patent.
3. Conclusion
[23] I am satisfied that the inventor of the '320 patent, when specifying HPMC as the sustained release agent in the formulation, considered HPMC to be an essential element of the patent and did not contemplate that HPC was included within its terms. Accordingly, I am not persuaded that Sandoz's claim - that its use of HPC would not infringe Biovail's patent - is unjustified.
C. Is Sandoz's claim that its proposed drug will not infringe Biovail's Canadian Patent no. 2,168,364 (the '364 patent) unjustified?
1. The Evidence
[24] Bupropion hydrochloride is prone to degradation. Biovail's '364 patent relates to a tablet that combines bupropion hydrochloride with a stabilizing agent to increase its shelf-life. Acids are often used as stabilizing agents. The '364 patent mentions four particular acids that would be suitable stabilizers. Sandoz proposes to manufacture a bupropion hydrochloride tablet that would not contain any of the stabilizing agents mentioned in the '364 patent.
[25] Each party asked its two experts to consider whether Sandoz's proposed drug would infringe Biovail's '364 patent. Here, there was little common ground. The following are the issues addressed in the experts' reports.
(a) The purpose of dilute hydrochloric acid in Sandoz's formulation
[26] Biovail's experts note that that Sandoz's formulation includes dilute hydrochloric acid (HCl). They believe that the HCl functions as a stabilizing agent in Sandoz's formulation. Accordingly, they suggest that, because the HCl operates similarly to the acids mentioned in Biovail's '364 patent, its inclusion in Sandoz's formulation infringes the patent. Contrary to Sandoz's assertion, Biovail's experts doubt whether all of the HCl would be removed during the manufacturing process.
[27] Sandoz's experts state that the HCl in its formulation serves a purpose other than as a stabilizer. Further, they emphasize, as Sandoz indicated in its notice of allegation, that the HCl is entirely removed during manufacture. Finally, they note that even if HCl were present in Sandoz's formulation and performed a stabilizing function, it is not among the agents specifically mentioned in the '364 patent.
(b) The suitability of hydrochloric acid as a stabilizing agent
[28] Biovail's experts contend that HCl can be used as a stabilizing agent in a drug formulation. It would contribute to an acidic environment in Sandoz's tablet by giving off hydrogen chloride ions, essentially in the same manner as other acids identified in the '364 patent. It is this acidic environment that stabilizes the bupropion.
[29] Sandoz's experts state that even if HCl were present in its formulation, which they deny, HCl would not be a suitable stabilizing agent. HCl is a stronger acid than those named in the '364 patent. Its pH is not within the range specified in the patent's claims. Further, HCl is incompatible with magnesium stearate, which is used as a lubricant in Sandoz's formulation.
2. The Scope of the '364 Patent
[30] Claim 1 of the '364 patent states:
1. A pharmaceutical composition in solid form comprising bupropion hydrochloride and a pharmaceutically acceptable stabiliser or a combination of stabilisers in an effective stabilising amount, in which the composition contains at least about 80% w/w of undegraded bupropion hydrochloride after storage for 6 weeks at about 40 ° C and 75% relative humidity, an aqueous solution of the stabilizer(s) in a concentration of about 6% w/w having a pH of about 0.9 to about 4, and the stabilizer(s) being selected from an organic acid, a carboxylic acid, an acid salt of an amino acid and sodium metabisulphite. (Emphasis added.)
[31] The other relevant claims in the '364 patent also identify the four stabilizers set out in Claim 1.
[32] Again, I must determine whether Sandoz's claim that its formulation will not infringe Biovail's patent is unjustified. I must assume Sandoz's notice of allegation to be true, unless Biovail proves otherwise: Merck Frosst Canada Inc. v. Canada(Minister of Health) (2001), 12 C.P.R. (4th) 447 (F.C.A.), at para. 18. I must also take account of the fact that the patent specifically identifies four stabilizing agents, none of which is HCl.
[33] Sandoz's notice of allegation says that the HCl in its formulation will be removed during the manufacturing process. Biovail's experts question that statement but, other than their skepticism, I have no basis for concluding that it is incorrect.
[34] However, even if some HCl remained in the final product, I would not conclude that Sandoz's claim of non-infringement is unjustified. The '364 patent identifies the stabilizers that comprise the patented invention, none of which is HCl. In a similar context, Justice Barbara Reed concluded that "if the respondent does not use one of the acids listed in the claim, then it seems clear that there is no literal infringement of that claim" Hoffmann-La Roche Ltd. et al v.Canada (Minister of National Health and Welfare) (1996), 67 C.P.R. (3d) 484 (F.C.T.D.) at 502. The Federal Court of Appeal agreed, stating that the patent was "clear and unambiguous" and required no further interpretation: [1996] F.C.J. No. 1333, at para. 15 (QL). I believe this approach is consistent with Justice Binnie's guidance in Free World Trust, above, at para. 51:
The words chosen by the inventor will be read in the sense the inventor is presumed to have intended, and in a way that is sympathetic to accomplishment of the inventor's purpose expressed or implicit in the text of the claims. However, if the inventor has misspoken or otherwise created an unnecessary or troublesome limitation in the claims, it is a self-inflicted wound. The public is entitled to rely on the words used provided the words used are interpreted fairly and knowledgeably.
3. Conclusion
[35] I am satisfied that Sandoz's formulation does not contain HCl. Further, even if it did, I would find that the inventor of the '364 patent, when specifying particular stabilizers, did not contemplate that HCl was included within its terms. Accordingly, I am not persuaded that Sandoz's claim - that its formulation contains none of the stabilizers in Biovail's patent - is unjustified.
III. Disposition
[36] Biovail has not discharged its burden of proving that Sandoz's allegations - namely, that its new drug will not infringe Biovail's '320 and '364 patents - are unjustified. Accordingly, I must dismiss Biovail's application for an order of prohibition, with costs.
JUDGMENT
THIS COURT'S JUDGMENT IS THAT:
1. The application for an order of prohibition is dismissed with costs.
FEDERAL COURT
NAME OF COUNSEL ANDSOLICITORS OF RECORD
DOCKET: T-14-05
STYLE OF CAUSE: BIOVAIL CORP ET AL v. THE MINISTER OF NATIONAL HEALTH AND WELFARE ET AL
PLACE OF HEARING: Toronto, Ontario
DATE OF HEARING: April 3-4, 2006
REASONS FOR JUDGMENT: O'REILLY J.
APPEARANCES:
| Douglas N. Deeth Heather E.A. Watts |
|
| Edward Hore Kevin Zive
|
SOLICITORS OF RECORD:
| DEETH WILLIAMS WALL LLP Toronto, ON |
|
| HAZZARD & HORE Toronto, ON
|