Date: 20020617
Docket: T-568-02
Neutral Citation: 2002 FCT 683
Ottawa, Ontario, this 17th day of June, 2002
PRESENT: THE HONOURABLE MR. JUSTICE BLANCHARD
BETWEEN:
GLAXOSMITHKLINE INC.,
and SMITHKLINE BEECHAM P.L.C.
Applicants
- and -
PHARMASCIENCE INC. and
THE MINISTER OF HEALTH
Respondents
REASONS FOR ORDER AND ORDER
- [1] This is a motion by Glaxosmithkline Inc. and Smithkline Beecham P.L.C. ("GSK") for an order pursuant to subsection 6(7) of the Patented Medicines (Notice of Compliance) Regulations, SOR/98-166, (the "Regulations") requiring the respondent Pharmascience Inc. ("Pharmascience") to produce all relevant portions of its submissions for a notice of compliance filed with the Minister of Health, namely:
(a) those portions of the Pharmascience Abbreviated New Drug Submission ("ANDS") as follows:
1. Any portions showing the character and composition of the bulk paroxetine hydrochloride and, in particular, the amount of solvents and water present in the bulk material;
2. Any portions showing the details of the process used in the formation of the crude paroxetine hydrochloride Form A and all steps utilized in the purification and recrystallization of paroxetine hydrochloride used in the Pharmascience product, including any relevant portions of the Drug Master File ("DMF");
3. Any portions showing the details of the formulation and method of formulation for the Pharmascience product, including the identification and quantity of every component of the formulation;
(b) the Product Monograph; and
(c) samples of the Pharmascience tablets which are reflective of the product it intends to market, which can be satisfied by the tablets used for stability testing, in each dosage strength, sufficient for our testing to evaluate the infringement issues (i.e. 100-200 tablets randomly selected from each batch made to date using Pharmascience's manufacturing and formulation process) as well as a 10 gram sample of the bulk medicine for testing.
- [2] The applicants also request their costs of this motion and such further and other relief as to this Honourable Court may deem just.
Grounds for the Motion by the Applicants
- [3] The applicants submit the following grounds for their motion:
(1) By a letter dated February 20, 2002, Pharmascience Inc. ("Pharmascience") provided to GSK a Notice of Allegation with respect to the six patents of the Applicants, for tablets for oral administration of paroxetine hydrochloride in 10 mg, 20 mg and 30 mag strengths. [The six Canadian patents are: No. 1,287,060 (‘060 Patent), No. 2,168,829 (‘829 Patent), No. 2,210,023 (‘023 Patent), No. 2,211,522 (‘522 Patent), No. 2,178,637 (‘637 Patent) and No. 2,214,575 (‘575 Patent)]
(2) Pharmascience made a number of allegations of non-infringement in respect of these six patents. However, other than broad allegations, Pharmascience provides no data as to the tablets, formulations and processes which are alleged to be non-infringing.
(3) As a result, on March 20, 2002, the Applicants wrote to Pharmascience requesting portions of Pharmascience's Abbreviated New Drug Submission ("ANDS"), copies of documents referred to in the Notice of Allegation, the Product Monograph and samples of the Pharmascience paroxetine hydrochloride tablets and bulk.
(4) On March 25, 2002, counsel for Pharmascience refused to provide any of the materials requested in the Applicants' March 20, 2002 letter.
(5) On April 5, 2002, the Applicants began the present proceeding in response to the Pharmascience Notice of Allegation letter of February 20, 2002.
(6) Subsection 6(7) of the Regulations permits the Court to order a second person to produce any portion of the submission for a notice of compliance filed by a second person that is relevant to the disposition of the issues in the proceeding. Samples of Pharmascience tablets are required under the Food and Drug Regulations as being part of the submission for a notice of compliance filed by Pharmascience.
(7) The Court of appeal has confirmed that the dominant consideration to determine if production should be granted is whether the requested information is relevant. In addition, other factors that can be considered are whether the disclosure is required and whether it is important.
(8) In this case, Pharmascience has alleged non-infringement of the six patents and has supplied only bald allegations of non-infringement.
(9) For instance, one of the key issues in this proceeding is the composition of Pharmascience tablets of paroxetine hydrochloride. Pharmascience has alleged that Claims 9 and 10 of ‘060 Patent are not infringed because Pharmascience tablets are purportedly made using only paroxetine hydrochloride anhydrate and not paroxetine hydrochloride hemihydrate. Claim 4 of the ‘637 Patent is also alleged not to be infringed because Pharmascience tablets are purportedly made using only paroxetine hydrochloride anhydrate and not paroxetine hydrochloride hemihydrate. However, paroxetine hydrochloride anhydrate is known to convert to paroxetine hydrochloride hemihydrate under certain conditions.
(10) The best way to determine whether Pharmascience's paroxetine hydrochloride anhydrate will convert to the claimed paroxetine hydrochloride hemihydrate upon tableting is to test samples of Pharmascience's tablets and bulk medicine for the presence of paroxetine hydrochloride hemihydrate.
(11) As such, these sample tablets and bulk medicine are not only relevant to the issue of conversion and infringement, but the provision of the samples is necessary for the determination of the issue of conversion.
(12) Also relevant to the disposition of these issues, and necessary and important for the determination of the issue of conversion, are the portions of Pharmascience's ANDS which relate to the formulation process used to make the Pharmascience tablets. In particular, an analysis of the tableting method to be used will assist in the determination if the Pharmascience tablets contain, in whole or in part, any paroxetine hydrochloride hemihydrate.
(13) Similarly, Pharmascience has also alleged non-infringement of the claims of certain patents because the Pharmascience product purportedly contains paroxetine hydrochloride anhydrate Form A and does not contain paroxetine hydrochloride anhydrate Form B, Form C or Form D. Production of samples of the Pharmascience tablets and bulk paroxetine hydrochloride and relevant portions of the Pharmascience ANDS will assist in determining the form of paroxetine actually used in the formation and the form present in the final tableted product.
(14) In addition, Pharmascience alleges that Claim 5 of the ‘023 Patent is not infringed because Pharmascience paroxetine hydrochloride in Form A purportedly will not be prepared in accordance with the Claim 1 process. Other than a blanket denial, Pharmascience has provided no details of the process which is in fact used by Pharmascience to make its paroxetine hydrochloride. As such, the portions of the Pharmascience ANDS relevant to the process used by Pharmascience are not only relevant but necessary for the determination of the issues in relation to the Pharmascience allegation of non-infringement of the ‘023 Patent.
(15) Notwithstanding the foregoing, Pharmascience has refused to produce these sample tablets and bulk, as well as any of the relevant portions of its ANDS relating to paroxetine hydrochloride.
(16) Granting the order sought will serve to secure the just, most expeditious and least expensive determination of the proceeding on its merits in accordance with Rule 3 of the Federal Court Rules, 1998.
(17) Rule 3 of the Federal Court Rules, 1998 and subsection 6(7) of the Patented Medicines (Notice of Compliance) Regulations apply.
- [4] By consent, the following information will be produced:
(1) information relating to solvents and water in the bulk materials;
(2) process information;
(3) formulation information, including the amount of microcrystalline cellulose;
(4) with regard to the method of formulation, the type of formulation will be indicated.
At the hearing of this matter, both Pharmascience and GSK confirmed that these portions of the Pharmascience ANDS requested in subparagraphs 1(a)(1) and 1(a)(2) of the notice of motion would be provided by consent. GSK further requests details of the method of formulation for the Pharmascience product as requested in subparagraph 1(a)(3) of the notice of motion.
Issue
- [5] Whether the disclosure of the requested portions of the Pharmascience ANDS that are not consented to by Pharmascience should be ordered.
Analysis
- [6] By order dated April 25, 2002, Madam Prothonotary Aronovitch dismissed a similar motion by the applicants to obtain production of information and samples filed with Health Canada by Pharmascience for failure to file proper evidentiary support for its motion. The motion was denied without prejudice to the right of the applicants to reapply on better affidavit evidence.
- [7] Subsection 6(7) of the Regulations provides for the production of all or part of a submission for a notice of compliance filed by a second person that is relevant to the disposition of the issues in the proceeding. Subsections 6(7) and (8) of the Regulations provide as follows:
6(7) On the motion of a first person, the court may, at any time during a proceeding,
6(7) Sur requête de la première personne, le tribunal peut, au cours de l'instance :
(a) order a second person to produce any portion of the submission for a notice of compliance filed by the second person relevant to the disposition of the issues in the proceeding and may order that any change made to the portion during the proceeding be produced by the second person as it is made; and
a) ordonner à la seconde personne de produire les extraits pertinents de la demande d'avis de conformité qu'elle a déposée et lui enjoindre de produire sans délai tout changement apporté à ces extraits au cours de l'instance;
(b) order the Minister to verify that any portion produced corresponds fully to the information in the submission.
b) enjoindre au ministre de vérifier que les extraits produits correspondent fidèlement aux renseignements figurant dans la demande d'avis de conformité.
(8) A document produced under subsection (7) shall be treated confidentially.
(8) Tout document produit aux termes du paragraph (7) est considéré comme confidentiel.
- [8] The Federal Court of Appeal has determined that relevance of the information sought is a condition precedent to the exercise of discretion pursuant to subsection 6(7) of the Regulations. In exercising discretion, evidence is also to be assessed on a balance of probabilities standard of proof and it is appropriate to consider whether the requested information is "important" or "required". See, Novartis Pharmaceuticals Canada Inc. v. Abbott Laboratories, Ltd. (2000) 7 C.P.R. (4th) 264 at 270 (F.C.A.).
- [9] The applicants, in support of their motion, produced the affidavit of Dr. Gerald Brenner, a person skilled in the art with a PhD in organic chemistry from the University of Wisconsin. In his affidavit Dr. Brenner attests to having read the Notice of Allegation dated February 20, 2002, from Pharmascience relating to the relevant patents. In his affidavit, Dr. Brenner addresses the allegations of non-infringement in respect of all of these patents.
The ‘060 Patent
- [10] Pharmascience has alleged that claims 9 and 10 of the ‘060 Patent are not infringed because Pharmascience tablets are purportedly made using only paroxetine hydrochloride anhydrate and not paroxetine hydrochloride hemihydrate as claimed in Patent ‘060. The ‘637 Patent is also alleged not to be infringed because Pharmascience tablets are purportedly made using only paroxetine hydrochloride anhydrate and not paroxetine hydrochloride hemihydrate as claimed in Patent ‘637.
- [11] The applicants contend, however, that the Pharmascience tablets could contain crystalline paroxetine hydrochloride hemihydrate. In support of this contention, the applicants adduce the evidence of Dr. Brenner who attests that:
(a) The bulk medicine may not be pure anhydrate and may contain some crystalline paroxetine hydrochloride hemihydrate;
(b) During processing of both the bulk medicine and the tablet formulation, conversion of Pharmascience's anhydrate material to crystalline paroxetine hydrochloride hemihydrate may occur; and
(c) Once the Pharmascience product is manufactured, conversion from the anhydrate to crystalline paroxetine hydrochloride hemihydrate may occur over time.
- [12] Dr. Gerald Brenner further attests with regard to conversion of paroxetine hydrochloride anhydrate that:
(a) conversion among crystal forms is a frequently observed occurrence;
(b) Paroxetine hydrochloride anhydrate is known to convert to paroxetine hydrochloride hemihydrate under certain conditions and is taught in the ‘060 Patent;.
(c) Conversion can occur upon compression and over time;
(d) Other factors known to contribute to conversion are the application of heat and exposure to water, in either liquid or gaseous form (i.e., high humidity). Paroxetine hydrochloride anhydrate is known to be hygroscopic, meaning that it attracts water available in a chemical system. The presence or absence of water in a system is therefore important in order to evaluate the degree of conversion from the anhydrate form of paroxetine hydrochloride to the hemihydrate form.
(e) Seeding is another factor that is known to promote conversion from one crystalline form to another. In the event that Pharmascience's bulk paroxetine hydrochloride anhydrate contains some seeds of crystalline paroxetine hydrochloride hemihydrate, then these seeds will be available to promote conversion to the hemihydrate form.
- [13] In light of his observations with regards to the conversion phenomenon, Dr. Brenner attests that in order to evaluate if Claim 10 of ‘060 Patent and Claim 4 of the ‘637 Patent will be infringed by Pharmascience's paroxetine hydrochloride anhydrate tablets, the applicants contend that the following information is required:
(a) Details of the process used to make Pharmascience's bulk paroxetine hydrochloride anhydrate;
(b) Analytical data relating to the bulk material, including the water content of the bulk material;
(c) A sample of the bulk material to determine the presence or absence of seeds of crystalline paroxetine hydrochloride hemihydrate;
(d) Storage conditions for the bulk material (container and temperature/humidity information) to determine opportunities for conversion;
(e) The formulation composition and analytical data relating to the ingredients in order to determine the water content of all ingredients and thus the potential for conversion;
(f) Formulation process details and tablet coating details to determine opportunities for conversion;
(g) Storage conditions for the tablets (container and temperature/humidity information) to determine opportunities for conversion.
(h) Sample tablets to evaluate the degree of conversion, including conversion over time.
- [14] Dr. Brenner further attests that the testing of samples of the bulk and the tablets is "the only way" to determine if conversion has in fact occurred.
- [15] The applicants further contend that the portions of the Pharmascience's ANDS which relate to the formulation process used to make the Pharmascience tablets are relevant to the disposition of these issues and necessary and important for the determination of the issue of conversion. In particular, an analysis of the tableting method to be used will assist in the determination if the Pharmascience tablets contain, in whole or in part, any paroxetine hydrochloride hemihydrate.
The ‘829 Patent
- [16] The applicants contend that Claim 1 of the ‘829 Patent claims paroxetine hydrochloride anhydrate substantially free of bound organic solvent, characterized in Form A as defined by certain specific analytical data including melting point data, infra-red spectral data, DSC thermogram, X-ray diffraction pattern and solid state NMR. Claims 2 to 4 claim paroxetine hydrochloride anhydrate substantially free of bound organic solvent, characterized in Form B, Form C, and Form D, respectively, also defined by specific analytical data.
- [17] The applicants argue that Pharmascience alleges non-infringement because the Pharmascience product purportedly contains paroxetine hydrochloride anhydrate "Form A" and does not contain paroxetine hydrochloride anhydrate Form B, Form C or Form D. Further, in relation to Claim 1 of the ‘829 Patent, Pharmascience has alleged that its paroxetine hydrochloride is not "substantially free of bound organic solvent". Other than this statement, Pharmascience has provided no details of how much bound organic solvent may in fact be present in its paroxetine hydrochloride tablets.
- [18] The applicants therefore argue that in order to evaluate if the ‘829 Patent will be infringed by Pharmascience's paroxetine hydrochloride anhydrate tablets, the following information is required:
(a) Information related to the process used to make the bulk paroxetine hydrochloride anhydrate to determine the precise form of paroxetine hydrochloride used by Pharmascience;
(b) Analytical data relating to the bulk material, including:
(i) Solvent content of the bulk material;
(ii) Melting point data;
(iii) Infra-red spectra;
(iv) DSC thermogram;
(v) X-ray diffraction pattern; and
(vi) Solid state NMR data.
(c) A sample of the bulk material to determine:
(i) Solvent content of the bulk material;
(ii) Melting point data;
(iii) Infra-red spectra;
(iv) DSC thermogram;
(v) X-ray diffraction pattern; and
(vi) Solid state NMR data.
- [19] The applicants contend that relevant portions of the Pharmascience ANDS will allow the applicants to determine the form of paroxetine actually used in the formulation and the form present in the final tableted product, as well as the issues related to the bound organic solvent in the Pharmascience tablets. The applicants therefore argue that these portions of the Pharmascience ANDS are not only relevant but necessary for the determination of the allegation of non-infringement of the ‘829 Patent.
The ‘637 and ‘575 Patents
- [20] Pharmascience also alleges non-infringement of the ‘637 and the ‘575 Patents, which patents provide a solution to an intermittent pink hue problem in the production of paroxetine hydrochloride tablets.
- [21] Pharmascience alleges that Claim 4 of the ‘637 Patent is not infringed because the Pharmascience tablets are said to be made using only paroxetine hydrochloride anhydrate and not paroxetine hydrochloride hemihydrate. The applicants argue that since Claim 4 of the ‘637 Patent relates specifically to paroxetine hydrochloride hemihydrate, and not some other form of paroxetine hydrochloride, all of the information required to properly evaluate infringement issues with respect to the ‘060 Patent is also necessary to evaluate infringement of Claim 4 of the ‘637 Patent.
- [22] The claim in relation to the ‘575 Patent relates to a formulation where microcrystalline cellulose is absent. The applicants argue that information on the list of ingredients and the specific amounts of those ingredients in the Pharmascience tablets would indicate the amount of microcrystalline cellulose in the Pharmascience tablets, and whether such amounts are negligible.
- [23] Dr. Brenner therefore attests that in order to fully evaluate the allegations of non-infringement in respect of the Claims in the ‘575 Patent and Claim 4 of the ‘637 Patent, the formulation process and composition of Pharmascience's tablets is required.
The ‘023 Patent
- [24] Pharmascience alleges that Claim 5 of the ‘023 Patent is not infringed because Pharmascience paroxetine hydrochloride in Form A purportedly will not be prepared in accordance with the process set out in Claim 1 of the ‘023 Patent. Again, the applicants argue that this is but another blanket denial and that Pharmascience has provided no details of the process which is in fact used by Pharmascience to make its paroxetine hydrochloride.
- [25] Dr. Brenner attests that in order to fully evaluate whether the ‘023 Patent will be infringed by Pharmascience's paroxetine hydrochloride anhydrate tablets, the following information is required:
(a) All of the data and samples required to evaluate infringement of the ‘829 Patent, particularly to evaluate the effect of "conventional drying techniques" (as set out in Claim 1); and
(b) The details of the process used to make Pharmascience's bulk paroxetine hydrochloride anhydrate.
- [26] Consequently, the applicants contend that the portions of the Pharmascience ANDS relevant to the form of the anhydrate and the process used to make Pharmascience's bulk paroxetine hydrochloride anhydrate are not only relevant but necessary for the determination of the issues in relation to the Pharmascience allegation of non-infringement of the ‘023 Patent.
The ‘522 Patent
- [27] The ‘522 Patent claims the use of paroxetine hydrochloride anhydrate Forms A, B, C, and D for the treatment of various disorders. Pharmascience alleges that it will not infringe the claims of the ‘522 Patent as it will not be using paroxetine hydrochloride anhydrate for such treatment.
- [28] The applicants argue that the Product Monograph for Pharmascience's paroxetine hydrochloride anhydrate is required in order to see the indications for which Pharmascience is seeking marketing approval.
- [29] The respondents argue that the substantive issue to be decided by the Court in the application is whether the allegations are or are not justified and not to consider the veracity of the facts in the Notice of Allegation.
- [30] The respondents contend that Dr. Brenner is asking for additional material to test the veracity of the Notice of Allegation and that this should not be permitted given that the truth of the Notice of Allegation should be presumed. Further, the respondents argue that Dr. Brenner's evidence is speculative at best and could not establish that the ‘060 Patent relates to the form that Pharmascience is making, namely Form A paroxetine hydrochloride anhydrate.
- [31] I do not accept the respondents' contention. I accept that the allegation of non-infringement is presumed to be true but that is subject to the contrary being indicated. [See Merck Frosst Canada Inc. v. Canada, (1994), 55 C.P.R. (3d) 302 at 319 (F.C.A.).]
- [32] I am also not prepared to categorize Dr. Brenner's evidence as speculative. There is sufficient expert evidence to satisfy me on a balance of probabilities of the relevance and importance and necessity of the requested information and samples.
- [33] I am satisfied that the information and samples sought from Pharmascience are relevant to the question of non-infringement, particularly in light of the applicants' allegation in their notice of application that the formulation of Pharmascience's tablets may be found to infringe by reason that the tablets may be made using paroxetine hydrochloride hemihydrate. As a person skilled in the art, Dr. Brenner attests that the Notice of Allegation is not sufficient to determine whether Pharmascience will infringe the Patents at issue. In particular, his opinion is that notwithstanding the allegations of Pharmascience, paroxetine hydrochloride anhydrate is known to and may convert to Paroxetine hydrochloride hemihydrate under certain conditions. Dr. Brenner further asserts that the only way to determine if conversion has in fact occurred is to test bulk and tablet samples. This can only occur by production.
- [34] This is a motion for disclosure, not the merits of the prohibition proceeding where the Court would have some leeway to engage in patent construction. An order granting the requested disclosure would allow the judge hearing the merits of this application to properly examine whether the Notice of Allegation is justified or whether there is patent infringement by the applicants such that an order should issue to prohibit the Minister from issuing a Notice of Compliance.
- [35] Having concluded on a balance of probabilities that the information and samples sought are relevant, I also conclude, on the same standard, that disclosure of the information and samples sought are important and required for effective disposition of the underlying application. In the exercise of my discretion, I will so order.
- [36] Having determined that production should be granted, there remains the issue of whether samples are compellable under subsection 6(7) of the Regulation. On this issue, I will adopt the finding and reasons of O'Keefe J. in Pfizer Canada Inc. et al. v. Apotex Inc. et al. [2002] FCT 498 where at para. 28 he wrote:
...In my reading of subsection 6(7), samples can be compellable only if they have been provided to the Minister. Subsection 6(7)(b) provides authority for an order that the Minister verify that the portions produced corresponds fully to the information in the submission.
- [37] I am also prepared to proceed on the assumption that samples were provided to the Minister and are compellable under subsection 6(7) of the Regulations. In the event that they were not provided to the Minister, and the Minister can verify that fact, then Pharmascience will not be required to produce samples for the applicants. Any order will reflect this.
- [38] For the above reasons the motion of the applicants will be granted.
- [39] Costs shall be costs in the cause.
ORDER
THIS COURT ORDERS that:
1. Pharmascience shall provide the applicants with the portions of the ANDS that detail:
(a) Any portions showing the character and composition of the bulk paroxetine hydrochloride and, in particular, the amount of solvents and water present in the bulk material;
(b) Any portions showing the details of the process used in the formation of the crude paroxetine hydrochloride Form A and all steps utilized in the purification and recrystallization of paroxetine hydrochloride used in the Pharmascience product, including any relevant portions of the Drug Master File ("DMF");
(c) Any portions showing the details of the formulation and method of formulation for the Pharmascience product, including the identification and quantity of every component of the formulation;
(d) the Product Monograph; and
(e) samples of the Pharmascience tablets which are reflective of the product it intends to market, which can be satisfied by the tablets used for stability testing, in each dosage strength, sufficient for our testing to evaluate the infringement issues (i.e. 100-200 tablets randomly selected from each batch made to date using Pharmascience's manufacturing and formulation process) as well as a 10 gram sample of the bulk medicine for testing;
(f) In the alternative, if Pharmascience did not provide any samples of the tablets which are reflective of the product it intends to market, or of the sample of bulk medicine, in its submissions to the Minister for a Notice of Compliance, Pharmascience is required to disclose this information and will not be required to produce samples for the applicants.
2. Subsection 6(8) of the Regulations with respect to confidentiality shall apply to production made pursuant to this order.
3. All of the information and samples to be provided are to be provided subject to a protective order. The terms of the protective order and timing of the disclosure shall be agreed upon and settled by the parties no later than 10 days from the date of this order. Any dispute arising in that regard shall be determined on the basis of a further notice of motion.
4. With respect to any portions of the ANDS produced by Pharmascience pursuant to paragraph 1, the Minister of Health shall verify that such productions correspond fully to the information in the ANDS pending before the Minister.
5. The time for filing of the applicants' evidence is extended to 60 days following any production made pursuant to this order.
6. Costs shall be costs in the cause.
"Edmond P. Blanchard"
Judge
FEDERAL COURT OF CANADA
TRIAL DIVISION
NAMES OF COUNSEL AND SOLICITORS OF RECORD
DOCKET: T-568-02
STYLE OF CAUSE: Glaxosmithkline Inc. et al. v. Pharmascience Inc. et al.
PLACE OF HEARING: Ottawa, Ontario
DATE OF HEARING: May 28, 2002
REASONS FOR ORDER AND ORDER: BLANCHARD J.
DATED: June 17, 2002
APPEARANCES:
James Mills / Carina DePellegrin FOR PLAINTIFF / APPLICANT
Carol Hitchman FOR DEFENDANT/ RESPONDENT
SOLICITORS OF RECORD:
Gowling, Lafleur Henderson LLP FOR PLAINTIFF/APPLICANT
2600 - 160 Elgin Street
Ottawa, Ontario, K1P 1C3
613-786-0140/8669
Hitchman & Sprigings FOR DEFENDANT/RESPONDENT
80 Richmond Street West, suite 1200
Toronto, Ontario M5H 2A5
416-777-2270
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