Hoffmann-La Roche v. Canada (Minister of National Health and Welfare), docket T-1742-95

Date: 19981126

Docket: T-1742-95

BETWEEN:

     HOFFMANN-LA ROCHE and SYNTEX

     PHARMACEUTICALS INTERNATIONAL LIMITED,

     Applicants,

     - and -

     THE MINISTER OF NATIONAL HEALTH AND

     WELFARE and NU-PHARM INC.,

     Respondents.

     REASONS FOR ORDER

MULDOON, J.

[1]      The court is here considering proceedings under the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, (hereinafter: the Regulations).

[2]      Hoffmann-La Roche and Syntex are applying for prohibition to stop the Minister from issuing a notice of compliance (NOC) to Nu-Pharm in respect of the medicine flunisolide, including the medicine flunisolide nasal solution 0.025%, until after the expiration of each of Canadian patents 1,075,228, 1,083,963 and 1,288,048. (Because their three suffix numbers are all different, they will herein be referred to by such numbers.)

[3]      The applicants assert the following grounds:

1.      Syntex Pharmaceuticals International Limited is the owner of Canadian Patent Nos. 1,075,228 ("228"); 1,083,963 ("963"); and 1,288,048 ("048") (collectively, "Patents"), each of which includes a claim for a medicine itself. The 048 patent also includes a claim for the use of the medicine.

2.      Pursuant to Section 4 of the Regulations, a patent list pertaining to flunisolide, and in particular flunisolide nasal solution, and including reference to the Patents, was submitted to the Minister by Syntex Inc. ("Syntex").

3.      On January 1, 1995, Syntex and Hoffmann-La Roche amalgamated to form Hoffmann-La Roche.

4.      Hoffmann-La Roche received a letter dated June 26, 1995 from Nu-Pharm stated to be a "notice of allegation" and alleging with respect to flunisolide nasal solution 0.025% and the Patents, that "no claim for the medicine itself and no claim for the use of the medicine would be infringed by the making, constructing, using or selling by us of flunisolide nasal solution 0.025%. Nu-Pharm also alleges that the 963 and 048 patents are invalid. The aforesaid letter included the following, which was stated to be a "factual and legal basis for the aforesaid allegation":

Patent 1075228

The claims of the patent relate only to a new crystalline form. We will use only anhydrous flunisolide powder and not the new crystalline form of flunisolide covered by the claims of this patent. Accordingly, our product will not infringe.

Patent 1083963

The claims relate to particular compositions containing flunisolide in particles of size less than 100 microns combined with an aerosol or a liquid solution. Our product will not contain any flunisolide in particle form but will contain flunisolide only in solution. In addition, the flunisolide used to make the solution will not be of the crystalline form disclosed in the patent but will be anhydrous powder. Accordingly our product will not infringe.

The claims of this patent are invalid in that they claim more than the invention disclosed, contrary to s.34(2) of the Patent Act. The invention purports to be limited to a new crystalline form of flunisolide; the claims are not so limited but include every particular form of flunisolide of size less than 100 microns; furthermore flunisolide was at all material times a known substance, known for the treatment of inflammatory conditions.

Patent 1288048

The claims for the patent are invalid in that:

(a)      the patent does not disclose nor claim any invention.

(b)      the invention purports to relate to non-stinging nasal administrable formulations. It is obvious that formulations which do not sting should be made by omitting whatever excipients are known to cause stinging.

(c)      there is no disclosure in the specification of how to manufacture or use any composition which does not sting or of how to distinguish between compositions which sting and compositions which do not sting.

(d)      the claims are ambiguous in that they do not define the non-stinging characteristics of the composition so that the invention may be distinguished from that which has been done before.

Our product will not infringe this patent because it will not be substantially non-stinging.

In addition, in the event that the other allegations contained herein as to invalidity and non-infringement are not deemed sufficient, we will make and sell only compositions that are outside the scope of the claims of this patent by reasons of not containing propylene glycol.

5.      Pursuant to the Regulations and the jurisprudence thereunder, Nu-Pharm was required to provide a detailed statement of the legal and factual basis for its allegation at the time it served its notice of allegation on Hoffmann-La Roche. Nu-Pharm has not complied with this requirement.

6.      No further legal or factual information or allegations have been provided by Nu-Pharm. Nu-Pharm is limited in this proceeding to the legal and factual bases for its allegations set out in its aforesaid letter. Hoffmann-La Roche has relied on the specific legal and factual bases provided or not provided by Nu-Pharm, as the case may be, in commencing this proceeding.

7.      Pursuant to the Regulations, this Court shall make an order prohibiting the Minister from issuing an NOC to Apotex in respect of a patent that is the subject of one or more allegations if it finds that none of those allegations is justified. None of the allegations made by Nu-Pharm is justified.

8.      With respect to the 963 and 048 patents, Nu-Pharm's allegation of invalidity is not justified. The 963 and 048 patents are presumed valid under the Patent Act, in the absence of any evidence to the contrary. As Nu-Pharm has not provided "evidence" to the contrary, its allegation of invalidity is not justified.

9.      With respect to each of the Patents, Nu-Pharm's allegation of non-infringement is not justified. The facts alleged in support of the allegations of non-infringement are denied, and in any event, do not support an allegation of non-infringement.

10.      The Applicants have no knowledge, nor access to knowledge relevant to the composition or active ingredient, or to the processes used to manufacture the composition or active ingredient of Nu-Pharm's proposed flunisolide nasal solution 0.025%. It is only Nu-Pharm and the Minister who have such knowledge. As a result, the burden of proving all facts alleged in its aforesaid notice of allegations in support of its allegation is imposed on Nu-Pharm.

11.      Furthermore, with respect to each of the Patents, the Minister is, by virtue of an order of this honourable Court dated June 21, 1995 in Court File No. T-1325-94, already prohibited from issuing a notice of compliance to Nu-Pharm in respect of the flunisolide nasal solution for which it has filed a submission until after the expiration of the Patents.

12.      As a result of the aforesaid order of this honourable Court, Nu-Pharm is unable to rely on the aforesaid notice of allegation.

13.      Furthermore, the aforesaid notice of allegation is, in respect of the 048 patent, an abuse of process.

14.      By virtue of the Regulations, any allegation made by Nu-Pharm with respect to a patent is in respect of a "submission for a notice of compliance in respect of a drug". By virtue of the Food and Drugs Act and Regulations, Nu-Pharm is required to specify all of the ingredients which will be contained in the product for which it seeks an NOC.

15.      As a result, Nu-Pharm's statement that "in the event that the other allegations contained herein as to invalidity and non-infringement are not deemed as sufficient, we will make and sell only compositions that are outside the scope of the claims of this patent by reason of not containing propylene glycol", is an abuse of process. Nu-Pharm's submission for an NOC either specifies that it will contain propylene glycol or that it will not contain propylene glycol. Nu-Pharm's attempt to vary its factual basis for its allegation in respect of a specific product is abusive, and indicates that Nu-Pharm's factual basis for its allegations is speculative and ought not to be believed by this Court.

16.      Syntex Pharmaceutical International Limited, as the owner of the patents, is a party to the applications pursuant to s.6(4) of the Regulations.

[4]      The applicants' originating notice is supported by Lorenzo Biondi's affidavit, and "the pleadings and proceedings in Court file No. T-1325-94". The three patents are exhibited in the affidavit, as is a copy of Nu-Pharm's "further Notice of Allegation" [NOA] in regard to the applicants' same three patents, pursuant to the Regulations.

[5]      The reference to a "further" NOA links previous litigation of these same parties under the regulations, in regard to the same three patents. The previous case, in T-1325-94, concluded with the reasons and order pronounced by Mr. Justice Noël in the Trial Division.

[6]      Noël, J. wrote, (1995) 62 C.P.R. (3d) 58 at pp. 74 and 75:

As confirmed by the decision in Deprenyl, supra, the Governor in Council chose to exclude from the ambit of the protection afforded by the Regulations a patented "process claim". This was done in clear terms by limiting the claims protected under the Regulations to those which "claim for the medicine itself". A "process claim" makes no such claim. If it had also been intended to exclude pharmaceutical formulations, the Governor in Council would not have been so timid and ambivalent as to attempt this by the construction which Nu-Pharm suggests. Keeping in mind that the Regulations are intended to prevent infringements, and that the defined meaning of the word "medicine" is a substance or substances capable of therapeutic effect, I must conclude that a claim for such substance or substances in the form of a composition is "a claim for the medicine itself".

As the substance or substances claimed in each of patents 228, 963 and 048 are intended or capable of being used for the treatment of a disorder or disease, they are a "medicine" within the meaning of the Regulations, and as each patent includes a claim for such substance or substances, they make a "claim for the medicine itself". Furthermore, as patent 048 includes a claim for the use of substance or substances for treating inflammation of the nasal mucosa without inducing stinging, it also contains a claim for the "use of the medicine".

Finally, in the event that it later be found that only an original active ingredient is a "medicine" as Nu-Pharm contends, I find that the active substance Form A as claimed by the 228 patent is such an ingredient. The 228 patent includes claims to various polymorphic crystalline forms of flunisolide including the ideal hemydrate Form A flunisolide when produced by processes particularly described in the patent. The inventive ingenuity of the patent is that Form A is purer (it is not a chlorate or solvate), that it has a uniform crystalline size with no propensity to clog spray dispensers, and that it does not cause stinging of the nasal mucosa. As such, Form A is an active ingredient distinct from flunisolide, and as patent 228 makes a claim to that ingredient itself, it makes a "claim to the medicine itself".

Based on the foregoing and as Nu-Pharm has advanced no evidence with respect to the composition or the process for making the drug for which it has sought an NOC, I must conclude in so far as patents 228, 048 and 963 are concerned that none of the allegations made by Nu-Pharm are justified. An order prohibiting the Minister from issuing an NOC until the expiration of the said patents is accordingly issued with costs to the applicants.

Nu-Pharm appealed in a case cited as Nu-Pharm Inc. v. Hoffmann-La Roche Ltd. & al. (1996) 67 C.P.R. (3d) 25, a one-paragraph unanimous judgment expressed by the late Mr. Justice MacGuigan, thus:

We have not been persuaded that Noël J. committed any reviewable error in considering the application for an order of prohibition. In particular, we are all agreed that he was right in rejecting the appellant's argument that the term "claim for the medicine itself" in s.2 of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, is not restricted to a claim for a single substance as the active ingredient to the exclusion of a claim for a composition which includes the active ingredient. In our view, as in that of Noël J., such a claim comes within the ambit of the regulations whether it is the form of a single active ingredient or in that of a composition. It follows that the appeal must be dismissed with costs.

Nu-Pharm's application for leave to appeal to the Supreme Court of Canada was refused: [1996] 3 S.C.R. xi.

[7]      The respondent Nu-Pharm's NOA, addressed to Syntex Inc., exhibit E to the Biondi affidavit sworn August 14, 1995, runs as follows:

June 26, 1995

Re: Flunisolide Nasal Solution 0.025%

This is a further Notice of Allegation pursuant to the * * * Regulations.

With respect to patents 1075228, 1083963 and 1288048, we allege that no claim for the medicine itself and [no] claim for the use of the medicine would be infringed by the making, constructing, using or selling by us of flunisolide nasal solution 0.025%. We also allege that patents 1083963 and 1288048 are invalid.

The factual and legal basis for the aforesaid allegation is as follows:

Patent 1075228

The claims of the patent relate only to a new crystalline form. We will use only anhydrous flunisolide powder and not the new crystalline form of flunisolide covered by the claims of this patent. Accordingly, our product will not infringe.

Patent 1083963

The claims relate to particular compositions containing flunisolide in particles of size less than 100 microns combined with an aerosol or a liquid solution. Our product will not contain any flunisolide in particle form but will contain flunisolide only in solution. In addition, the flunisolide used to make the solution will not be of the crystalline form disclosed in the patent but will be anhydrous powder. Accordingly, our product will not infringe.

The claims of this patent are invalid in that they claim more than the invention disclosed, contrary to S.34(2) of the Patent Act. The invention purports to be limited to a new crystalline form of flunisolide; the claims are not so limited but include every particulate form of flunisolide of size less than 100 microns; furthermore flunisolide was at all material times a known substance, known for the treatment of inflammatory conditions.

Patent 1288048

The claims for the patent are invalid in that:

(a)      The patent does not disclose nor claim any invention.

(b)      The invention purports to relate to non-stinging nasal administrable formulations. It is obvious that formulations which do not sting should be made by omitting whatever excipients are known to cause stinging.

(c)      There is no disclosure in the specification of how to manufacture or use any composition which does not sting or of how to distinguish between compositions which sting and compositions which do not sting.

(d)      The claims are ambiguous in that they do not define the non-stinging characteristics of the composition so that the invention may be distinguished from that which has been done before.

Our product will not infringe this patent because it will not be substantially non-stinging.

In addition, in the event that the other allegations contained herein as to invalidity and non infringement are not deemed sufficient, we will make and sell only compositions that are outside the scope of the claims of this patent by reason of not containing propylene glycol.

This NOA is signed by A. van Doornik, Vice President, Scientific Affairs.

[8]      The allegation of invalidity of patents '963 and '048 is new to the present case - not included in T-1325-94 - and the allegations of non-infringement while similar, their legal and factual bases are arguably different from what was alleged in the previous case, T-1325-94.

[9]      It may be noted that there is in place herein, a "protective order" regarding confidential materials, (doc. 10) made on September 12, 1995.

[10]      It should also be noted that the '228 and '963 patents have each expired before the hearing of this prohibition application.

[11]      On October 27, 1995, Bernard Charles Sherman, the Chairman of Apotex Inc., swore by affidavit that Apotex had agreed to supply Nu-Pharm with flunisolide nasal solution 0.025%. The implication being that Apotex could do so because it had lawful permission to supply it, without infringing the applicants' patent or patents. Exhibit A to Dr. Sherman's affidavit is a copy of Apotex' master formula for the composition, it was said.

[12]      However, it was later discovered that Dr. Sherman's exhibit A was wrong; and ultimately Mr. Justice Pinard, on March 7, 1997, rendered an order (doc. 50) permitting Nu-Pharm "to file [on or before March 18, 1997] a further affidavit of Dr. Bernard Sherman which will explain that he made a mistake in filing his first affidavit and which will append as an exhibit the documents attached as exhibit B to the confidential affidavit of H.B. Radomski sworn February 18, 1997". Naturally, the applicants were extended time, until May 19, 1997, to file further affidavit evidence.

[13]      Dr. Sherman swore a second affidavit on March 18, 1997, (applicants' record [AR], vol. II, p. 250) in which he asserted:

2.      As a result of an inadvertent error, the document that I attached as Exhibit "A" to my previous affidavit was not, in fact, the correct master formula. If Nu-Pharm's allegation with respect to the validity of Claim 1 of Canadian Letters Patent No. 1,288,048 is determined to be justified, Apotex will manufacture for Nu-Pharm flunisolide by using either or both of the processes disclosed in the master formulae attached hereto as exhibits "A-1" and "A-2". If Nu-Pharm's allegation with respect to the validity of Claim 1 of Canadian Letters Patent No. 1,288,048 Patent is determined not to be justified, Apotex will manufacture for Nu-Pharm flunisolide only by using the process disclosed in the master formula attached hereto as exhibit "A-2".

Exhibits A-1 and A-2 differ of course, but significantly the ingredients in A-1 (AR II, p. 251) include propylene glycol USP, whereas such an ingredient is not among those in A-2 (AR II, p. 254).

[14]      Claim 1 of the '048 patent, upon which the other claims essentially depend, runs:

1.      A substantially non-stinging aqueous anti-inflammatory steroid formulation suitable for intranasal administration, which formulation comprises:

an anti-inflammatory steroid in an amount between about 0.01% and about 0.05% (w/v);

propylene glycol in an amount between about 2% and about 10% (w/v);

PEG 400 in an amount between about 10% and about 25% (w/v)

polysorbate 20 in an amount between about 1% and about 4% (w/v); and water.

Propylene glycol is an essential and common ingredient. Because the Nu-Pharm formula A-2 contains no such ingredient, it is non-infringing.

[15]      The applicants and Nu-Pharm engaged in serious contention over the validity of the '048 patent. Because the Court's finding in paragraph [14] above means that the applicants' prohibition application must fail, it is not strictly necessary for this Court to make a finding on Nu-Pharm's assertion of invalidity. However this Court finds insufficient evidence tendered by Nu-Pharm to displace the statutory presumption of validity of the '048 patent conferred by section 77 of the Patent Act, R.S.C. 1985, Chap. P-4.

[16]      In light of the finding of non-infringement demonstrated in formulation A-2, and the provisions and tenor of the Regulations, the applicants' arguments against this Court's jurisdiction herein must fail. Additionally, the Court is not concerned with any new drug submission filed with the Minister by Nu-Pharm.

[17]      These reasons are somewhat sketchy and imperfect. The applicants' solicitors, by letter dated March 2, 1998, estimated the time for hearing at "1.5 days". Two days, June 17 and 18, 1998, were fixed for the hearing and it commenced as scheduled. The applicants' counsel alone addressed the Court during all of both days. He seemed to lack confidence in his written material and elaborated on it at length. He seemed to believe that he needed to read jurisprudence in extenso at the judge. As a result, two more days, August 20 and 21, 1998, being available and convenient to counsel, were fixed for resumption of the hearing. This judge was hospitalized unexpectedly on those two days. Counsel on each side were unable to agree upon any 2-day period from then until now. The Court then peremptorily fixed times for written submissions: the corporate respondents' response not later than October 22, 1998 and the applicants' written reply, if any, not later than November 4, 1998. Along it came on that very day, together with the applicants' second supplementary book of authorities. This judge has been heavily engaged, including travelling since then. The 30-month limitation period as extended expires this day.

[18]      Because success is divided no costs are awarded to any party hereto.

[19]      The Minister will be formally, and is now, prohibited from issuing a Notice of Compliance to Nu-Pharm in regard to formulation A-1. The applicants' application to prohibit the Minister similarly in regard to formulation A-2 is dismissed, as an exception (on new grounds) to Mr. Justice Noël's order dated June 21, 1995, in file No. T-1325-94.

                                

                                 Judge

Ottawa, Ontario

November 26, 1998