Date: 20090626
Docket: T-876-08/T-886-08
Citation: 2009 FC 671
OTTAWA, ONTARIO,
JUNE 26, 2009
PRESENT: The Honourable Mr. Justice de Montigny
BETWEEN:
PFIZER CANADA INC., PFIZER LIMITED,
AND PFIZER IRELAND PHARMACEUTICALS
Applicants
and
APOTEX INC. AND THE MINISTER
OF HEALTH
Respondents
PUBLIC VERSION OF THE CONFIDENTIAL
REASONS FOR ORDER AND ORDER
ISSUED JUNE 26, 2009
[1]
This is an appeal
from an Order of Prothonotary Martha Milczynski, dated March 10, 2009, by which
she dismissed Apotex’s motions to strike Pfizer’s application to prohibit the
Minister of Health from issuing Notices of Compliance (“NOCs”) to Apotex for
two new products: amlodipine base tablets and amlodipine maleate tablets.
Apotex initially brought these motions pursuant to paragraph 6(5)(b) of the Patented
Medicines (Notice of Compliance) Regulations, SOR/93‑133 (the “Regulations”),
which empowers the Court to dismiss an application where it is redundant,
scandalous, frivolous or vexatious or is otherwise an abuse of process. Having
considered the evidence of non-infringement filed by Apotex, the Prothonotary
found that it was inadmissible hearsay, and that in any event it would not have
been sufficient to grant the relief sought. While the motions brought by the
Respondent, Apotex, are in the nature of an appeal from the Order of the
Prothonotary, the motions are to be determined in this Court de novo.
BACKGROUND
[2]
Pfizer obtained a Notice of Compliance
for a medicine known as amlodipine besylate, sold under the trade name of
Norvasc. Pfizer has listed two patents on the Register maintained by the
Minister of Health pursuant to the Regulations against that drug, namely
the 1,321,393 (‘393) patent and the 2,170,278 (‘278) patent.
[3]
At all material
times, amlodipine and its salts were known as medicines which were among the
group of calcium channel blockers and indicated for use in the treatment of
hypertension and angina. Amlodipine is a racemic mixture that consists of the
R(+) enantiomer and the S(-) enantiomer. A “racemate” or “racemic mixture”
contains an equal amount of two enantiomers. While having the same physical
properties, such as melting point, solubility, etc., enantiomers are chemical
compounds that are non-superimposable mirror images of each other; in other
words, each enantiomer of a racemic mixture rotates a plane of polarized light
by the same angle in opposite directions. Because of that characteristic, two
enantiomers of a drug substance will interact differently with their biological
targets.
[4]
As a result, the R(+)
and S(-) enantiomers of amlodipine are molecules that are identical except for
their three-dimensional configuration and biological effect. Whether
amlodipine exists as the besylate salt, the free base or the maleate salt makes
no difference. Amlodipine besylate, amlodipine free base and amlodipine
maleate contain the same enantiomers.
[5]
It was
known that the calcium channel-blocking activity of amlodipine was
substantially confined to the S(-) form and the racemic mixture of R(+) and
S(-) forms, and that the R(+) isomer had little or no calcium channel-blocking
activity. It was also known that calcium channel blockers in general tend to
inhibit smooth muscle cell migration, and would therefore be useful in the
treatment of artherosclerosis
(a condition characterized by the narrowing and hardening of blood vessels).
Indeed, the ‘278 patent begins by acknowledging these properties.
[6]
The invention to
which the ‘278 patent purports to relate is the discovery that “the R(+) isomer
of amlodipine, despite its lack of calcium channel blocking activity, is a
potent inhibitor of smooth muscle cell migration”. The ‘278 patent describes
as its discovery that R(+) amlodipine inhibits smooth muscle cell migration while
not producing channel-blocking effects. This unique property of R(+)
amlodipine is not shared by racemic amlodipine or other calcium channel
blockers, and gives ‘278 patent its stated utility: “[A] means of treating
conditions invoking smooth muscle cell migration without any concomitant
cardiovascular effects…it is therefore applicable to patients for whom
reduction of blood pressure would be undesirable.”
[7]
Further, the ‘278
patent directly contrasts its invention – the administration of R(+) amlodipine
– from the administration of racemic amlodipine on the basis that only the
former avoids cardiovascular (i.e., blood pressure lowering) effects:
For administration to man in
the curative or prophylactic treatment of conditions involving smooth muscle migration,
oral dose of R(+) amlodipine or its salts may be in the range of 2-10 mg daily
for an average adult patient (weighing 70 kg), that is a range similar to that
used for amlodipine in the treatment of hypertension. However, the absence of
cardiovascular effects allows administration of much larger doses than would be
recommended for the calcium channel blocker or the racemate, with a
correspondingly greater effect on cell migration.
‘278 patent, p. 6
[8]
The ‘278
patent purports to contain the results of assays conducted using, as separate
test compounds, racemic amlodipine, R(+) amlodipine, S(-) amlodipine, and known
calcium channel blockers nitrendipine and verapamil. The assays indicate that
all five compounds inhibit smooth muscle cell migration, but only R(+)
amlodipine (free of the racemate) is “substantially free” of calcium channel-blocking
activity. From these results, the inventors conclude that “the R(+) enantiomer
of amlodipine is effective in inhibiting smooth muscle cell migration even
though its activity as a calcium channel blocker is negligible”. The report of
the study indicates that the racemate does not share the unique, desired
biological effect of R(+) amlodipine.
[9]
Patent
‘278 is comprised of eight claims. Claims 1 to 3 relate to the R(+) isomer of
amlodipine for “use in the treatment”, “for making a medicament for treatment”,
and “for treatment” of conditions requiring inhibition of vascular smooth
muscle cell migration. Claims 4 to 7 relate to a pharmaceutical composition, and
to unit doses of that composition, containing the R(+) amlodipine for use in
the treatment of these same conditions. Claim 8 relates to a commercial
package containing the R(+) isomer of amlodipine for the treatment of these
same conditions.
[10]
There is a
dispute over the proper construction of this patent. Apotex alleges that the
claims of the ‘278 patent exclude racemic amlodipine, and that the term “R(+)
enantiomer of amlodipine” found in the various claims of the patent should be
given its plain meaning, as a compound distinct from racemic amlodipine.
Pfizer, on the other hand, urges a construction that would encompass the R(+)
and S(-) enantiomers. I shall return to this debate about the proper
construction of the ‘278 patent shortly.
[11]
As for the
‘393 patent, there seems to be no dispute over the construction of its relevant
claims. According to that patent, the besylate salt shows a unique combination
of good solubility, good stability, non-hygroscopicity and good processibility
which makes it “outstandingly suitable” for the preparation of pharmaceutical
formulations of amlodipine (‘393 patent, p. 6). The ‘393 patent is comprised
of 22 claims. Claims 1 to 10 relate to the processes for preparing the
besylate salt of amlodipine, a pharmaceutical composition, a tablet
formulation, a capsule formulation and a sterile aqueous solution of the besylate
salt. Claims 11 to 2 are directed to the selection of the besylate salt of
amlodipine from a class of pharmaceutically acceptable salts. Claim 11 covers
the compound amlodipine besylate. It is listed on the Patent Register in
respect of amlodipine besylate tablets for oral administration in 2.5, 5 and 10
mg dosage strengths. The only issue is whether Apotex’s products contain or,
at any point in the manufacturing process, use the besylate salt, and infringe
the ‘393 patent.
[12]
On June
26, 2007 and January 30, 2008, Apotex filed two New Drug Submissions (“NDS”) in
respect of tablets respectively containing as the medicinal ingredient
amlodipine and amlodipine maleate. In those submissions, Apotex compared its
tablets to Pfizer’s Norvasc tablets. At the time these submissions were filed,
Apotex also filed Form Vs with the Minister, indicating its acceptance that it
would not be issued a Notice of Compliance until after the Pfizer patents had
expired.
[13]
Pursuant to paragraph
5(3)(a) of the Regulations, Apotex sent two letters purporting to be
notices of allegation (“NOAs”) relating to the ‘278 patent to Pfizer by
registered mail. Then, on April 25, 2008, Apotex sent two letters purporting
to be NOAs relating to the ‘393 patent to Pfizer by registered mail. These
letters gave notice to Pfizer that Apotex had filed submissions with the
Minister of Health seeking approval for tablets containing amlodipine and amlodipine
maleate in strengths equivalent to 5 mg and 10 mg of Pfizer’s amlodipine
besylate for use as antihypertensive-antianginal medicines. These letters were
received respectively by Pfizer on April 22 and April 29, 2008.
[14]
In the first two
NOAs, Apotex alleges that no claim for the medicinal ingredient, no claim for
the formulation, no claim for the dosage form and no claim for the use of the
medicinal ingredient found in the ‘278 patent would be infringed by its making,
constructing, using or selling its amlodipine or amlodipine besylate tablets.
In the latter two NOAs, Apotex makes the same allegation with respect to
the’393 patent.
[15]
With
respect to the’278 patent, Apotex submits that its claims are limited to the
R(+) isomer of amlodipine, and that therefore there will be no infringement
because its tablets will contain amlodipine racemate, not the R(+) isomer.
Apotex also undertakes to ensure that the NOC issued by the Minister will not
include, until the expiry of this patent, an indication for the treatment of
conditions requiring inhibition of vascular smooth muscle cell migration, and
that it will not make, construct, use, or sell its tablets for such use.
[16]
As for the
factual and legal basis for the NOAs relating to the ‘393 patent, Apotex alleges
that claims 1 to 10 are process claims only and are thus not relevant, while
claims 11 to 22 are specifically limited to the besylate salt of amlodipine or
a composition or formulation comprising same and are therefore not infringed by
its tablets since they will not comprise the besylate salt of amlodipine nor
will amlodipine besylate be used in any way in the manufacture of their tablets
or in the amlodipine used in their tablets.
[17]
On April
28, 2008, Apotex transmitted further Form Vs to the Minister of Health in
respect of the ‘278 patent and the ‘393 patent. In these revised Form Vs,
Apotex alleged that no claim for the medicinal ingredient, no claim for the
formulation, no claim for the dosage form and no claim for the use of the
medicinal ingredient would be infringed by Apotex’s making, constructing, using
or selling the drug for which the submission was filed.
[18]
In
response to the NOAs sent by Apotex, Pfizer commenced, on June 4 and 5, 2008,
two applications for judicial review. Pfizer sought an order prohibiting the
Minister of Health from issuing a Notice of Compliance in respect of the two
drug products made by Apotex containing amlodipine and amlodipine maleate.
[19]
Initially,
Pfizer was unaware that Apotex had not made “an allegation” as required by the Regulations.
However, in response to Pfizer’s requests for production, Apotex provided
Pfizer with copies of the original Form Vs in which Apotex elected to accept
that NOCs would not issue until the expiry of the ‘278 and ‘393 patents. Pfizer
subsequently brought a motion for leave to amend its notices of application to
plead that Apotex had not made an allegation as required by the Regulations
and that the NOAs were therefore nullities. In response to Pfizer’s motion, which
was eventually granted, Apotex produced the additional Form Vs.
[20]
By Notice
of Motion dated October 17, 2008, Pfizer also moved that Apotex produce
portions of its NDSs filed with the Minister in support of its request for an
NOC, pursuant to paragraph 6(7)(a) of the Regulations. Before the
motion was heard, Apotex voluntarily disclosed to Pfizer a good portion of
those submissions. Prothonotary Alto ordered that these productions be deemed
to have been made pursuant to subsection 6(7), required Apotex to promptly
produce any changes that were made thereto, and ordered that the Minister
verify that these productions, and any changes thereto, corresponded fully to
the information on file with him. There was no appeal from those findings.
[21]
Pfizer was
also seeking the entire Chemistry and Manufacturing Section contained in
Apotex’s NDSs, even though parts thereof had already been voluntarily
produced. This motion was rejected, as Prothonotary Aalto was not persuaded
that the information sought was relevant, important or required. That decision
was upheld by my colleague Justice Harrington on March 4, 2009 (Pfizer
Canada Inc. v. Apotex Inc., 2009 FC 226). That decision is now
under appeal (Notice of Appeal dated March 16, 2009).
[22]
Relying
upon paragraph 6(5)(b) of the Regulations, Apotex sought the accelerated
disposition of Pfizer’s two applications on July 31, 2008. The purpose of the
motion, in Apotex’s words, is to stop a proceeding that is clearly doomed to
fail. This is clearly the purpose behind that provision. As noted by
Prothonotary Mylczynski in her decision, “[s]ection 6(5)(b) of the Regulations
provides a kind of safety valve to deal with pointless applications that serve
only to keep a generic competitor off the market for a little longer” (Pfizer
Canada Inc. v. Apotex Inc., 2009 FC 250, at para. 3). It is the
decision of the Prothonotary dismissing its motion that Apotex now appeals.
THE IMPUGNED DECISION
[23]
The
Prothonotary first dealt with the appropriate burden of proof on subsection 6(5)
motions. She stated that the burden is entirely and exclusively on the moving
party, and that the standard is a high one, thereby dismissing Apotex’s
submission that a NOA must be taken as true until shown otherwise through the
prohibition proceeding. In other words, she dismissed the notion that the
burden shifts to Pfizer to satisfy the Court on this motion that Apotex’s
allegations of non-infringement are not justified. The Prothonotary stated
that Apotex was mistaken in its approach:
It is not for Pfizer to make
out its case at this juncture, and where the evidence has not even been filed
in the main application, it is not for the Court to anticipate or speculate on
what the strength of that evidence might be. It is for Apotex to show on this
motion that Pfizer cannot possibly make out its case and will not be able to
satisfy the Court should the hearing proceed on the merits. In the within
application, in respect of Apotex’s allegations of non-infringement of the ‘278
and ‘393 Patents, it is for Apotex to show on this motion that Pfizer cannot
and will not establish that Apotex’s allegations of non-infringement are not
justified. Apotex cannot shift the burden to Pfizer and transform a motion under
ss. 6(5) of the Regulations into a full hearing on the merits.
[24]
The
Prothonotary then observed that Apotex can only satisfy the Court on its motion
by putting its best evidentiary foot forward. She noted that in the present
case, Apotex vigorously resisted disclosure, and succeeded in satisfying the
Court (before Prothonotary Alto and on appeal before Justice Harrington) that
there was no need to produce such items as the “Chemistry and Manufacturing
Section” of its NDS. But since it is for the respondent to show, on a balance
of probabilities but with clear and cogent evidence, that it is not possible
for the applicant to prevail, the respondent will resist disclosure at its own
peril. As the Prothonotary wrote, “How better to do so than being as fulsome
as possible to assist the Court in making a determination of whether or not the
application should proceed and whether it has any chance of success?”
[25]
Finally,
the Prothonotary reviewed the evidence and came to the conclusion that Apotex
had failed to discharge its burden by failing to lead any admissible evidence
to support its allegations of non-infringement of the ‘278 and ‘393 patents.
Apotex had relied on the affidavit of Dr. Batey, an expert who was provided
with, and was asked to comment upon, a copy of a portion of Apotex’s
submissions to the Minister provided to him by counsel for Apotex. Since Dr.
Batey was not involved in and did not have any knowledge of the preparation of
the documents that were filed with the Minister, the Prothonotary came to the
conclusion that this was hearsay evidence as it had not been established that
the documents attached to Dr. Batey’s affidavit were part of the documents
submitted to the Minister. As such, she found that evidence inadmissible.
[26]
In any
event, the Prothonotary was also of the view that Dr. Batey’s opinion and the documents
attached to it would have been insufficient to grant the relief sought. With
respect to the’393 patent, she agreed with Pfizer that it was impossible to
dismiss entirely the possibility that amlodipine besylate may be used or formed
as an intermediate during the manufacture of Apotex’s tablets. She recognized
that those speculations, inevitable in the absence of relevant information, may
not be enough for Pfizer to obtain a prohibition order. On the other hand, she
was not prepared to accept either that speculating about what might happen on
the main hearing satisfies the test to arrest the proceeding immediately,
“particularly when Pfizer’s evidence is not yet filed” (para. 28).
[27]
As for the
‘278 patent, the Prothonotary concluded that, in the absence of an evidentiary
record upon which to make findings regarding the ability of Pfizer to make out
its case that Apotex’s allegations of non-infringemnt of the ‘393 and ‘278 patents
are not justified, the proper construction of the ‘278 patent was better left
to the hearings judge.
[28]
On the
strength of these conclusions, Prothonotary Milczynski refused to deal with the
other issues raised by Pfizer relating to the validity of the NOAs, the
possibility to amend Form Vs, and various estoppel arguments. She dismissed
the motion, on the narrow ground that it was not plain and obvious that
Pfizer’s case was bereft of any chance of success.
ISSUES
[29]
The only
issue raised by this appeal is whether the Prothonotary erred in dismissing
Apotex’s motion and in finding that it is not plain and obvious that Pfizer’s
application should be dismissed as being clearly futile.
ANALYSIS
[30]
It is now
settled law that discretionary decisions of prothonotaries ought not be
disturbed on appeal, unless the questions raised in the motion are vital to the
final determination of the case, or the orders are clearly wrong: Merck
& Co. v. Apotex Inc., 2003 FCA 488, at para. 19; Canada v. Aqua-Gem Investments
Ltd., [1993] 2 F.C. 425 (F.C.A.).
The parties agree that the decision of a prothonotary to dismiss, or not to
dismiss, a motion under paragraph 6(5)(b) of the Regulations is vital to
the final issue in the proceeding as such a decision has the potential to
finally determine the proceeding. As such, an appeal from any decision in such
a motion is assessed de novo, and the standard of review is that of
correctness: Sanofi-Aventis Canada Inc. v. Novopharm Ltd. (2006),
56 C.P.R.(4th) 242, at para. 17; Novartis Pharmaceuticals Canada
Inc. v. Apotex Inc. (2002), 20 C.P.R.(4th) 300, at para.
16; AstraZeneca AB v. Apotex Inc. (2002), 23
C.P.R.(4th) 213, at para. 6; Sanofi-Aventis Canada Inc. et al. v. Apotex
Inc., 2008 FC 628, at paras. 8-9;
Sanofi-Aventis Canada Inc. v. Canada, 2008 FC 129, at paras. 1-2; Pfizer
Canada Inc. v. Apotex Inc. (1999), 1 C.P.R.(4th) 358, at
paras. 23-26; AstraZeneca Canada Inc. v. Apotex Inc. (2002), 23
C.P.R.(4th) 378, at para. 7.
[31]
Paragraph
6(5)(b) of the Regulations provides that a second person, such as
Apotex, may move to dismiss an application for prohibition under the Regulations
in whole or in part on the ground that the application is frivolous or abusive
in respect of one or more patents.
|
RIGHT OF
ACTION
6. [. . . ]
(5) Subject to
subsection (5.1), in a proceeding in respect of an application under subsection
(1), the court may, on the motion of a second person, dismiss the application
in whole or in part
[. . . ]
(b) on the ground that it is redundant, scandalous, frivolous or vexatious
or is otherwise an abuse of process in respect of one or more patents.
|
DROITS
D’ACTION
6. [. . . ]
(5) Sous réserve du paragraphe (5.1), lors de l’instance
relative à la demande visée au paragraphe (1), le tribunal peut, sur requête
de la seconde personne, rejeter tout ou partie de la demande si, selon le
cas :
[. . . ]
b) il conclut qu’elle est inutile, scandaleuse, frivole ou
vexatoire ou constitue autrement, à l’égard d’un ou plusieurs brevets, un
abus de procédure.
|
[32]
Paragraph
6(5)(b), which was added to the Regulations in 1998, finds its source
Rule 221 of the Federal Courts Rules, 1998 SOR/98-106. Indeed, the
Federal Court of Appeal suggested that judicial review proceedings could be
summarily dismissed in exceptional cases by analogy to former Rule 419 of the Federal
Court Rules, C.R.C. 1978, c. 663, prior to the enactment of paragraph
6(5)(b): Pharmacia Inc. v. Canada (Minister of National Health and
Welfare), (1994), 58
C.P.R.(3d) 209,
at p. 217. As a result, this Court has adopted the principles developed in the
context of these Rules in interpreting paragraph 6(5)(b) of the Regulations
(see, for example, Pfizer Canada Inc. v. Apotex Inc. (1999), 1
C.P.R.(4th) 358), and this reasoning has been approved by the Court
of Appeal (see Sanofi-Aventis Canada Inc. v. Novopharm Limited et al.
(2007), 59 C.P.R.(4th) 416, at
para. 36).
[33]
Again,
there is no dispute between the parties that Apotex, the moving party, bears
the entire burden of proof in a motion brought pursuant to paragraph 6(5)(b) of
the Regulations. It is well established that a moving party must show
that it is “plain and obvious” that the application discloses no reasonable
cause of action and is “so clearly futile” that it does not have the slightest
chance of success. This is clearly a very high onus: Nycomed GmbH v. Canada (Minister of Health) (2008), 64 C.P.R. (4th)
388, at paras. 4, 77.
[34]
A motion
to dismiss an application before a hearing is an extraordinary remedy that
should only be available in narrowly defined circumstances. This will be the
case, for example, where there has been previous NOC litigation between the
same parties respecting the same patents: e.g., Janssen-Ortho Inc.
v. Novopharm Ltd. (2005), 46 C.P.R.(4th) 46 (F.C.); AB
Hassle v. Apotex Inc. (2005), 38 C.P.R.(4th) 216. Similarly,
the Court of Appeal has confirmed that where a patent has been held invalid in
a previous proceeding on the same ground of invalidity raised by the generic in
a second proceeding, it would be an abuse of process to continue the second
proceeding: Sanofis-Aventis Inc. v. Novopharm Ltd. (2008), 59 C.P.R.(4th)
416, (appl. for leave dismissed, [2007] S.C.C.A. No. 311). Such a high
standard is necessary to protect a party from being “driven from the judgment
seat”. For this reason, a motion to dismiss is not intended to be a forum for
a determination of the merits of an application. Rather, in considering a
motion to dismiss, any doubt as to whether the moving party has met its burden
must be resolved in favour of the responding party: Sanofi-Aventis Canada
Inc. v. Novopharm Ltd. (2006), 54 C.P.R. (4th) 22, at
para. 11 (F.C.), rev’d on other grounds (2007), 59 C.P.R. (4th) 24
(F.C.A.); AB Hassle v. Canada (Minister of National Health and Welfare) (2000), 9 C.P.R. (4th)
79, at paras. 11-13 (F.C.).
[35]
Motions
under paragraph 6(5)(b) are not intended to provide second persons with the
first of two opportunities to argue the merits of their case. Except in the
clearest of cases, substantive arguments regarding the non-infringement of a
patent are properly addressed at the hearing of the merits of a prohibition
proceeding – not on a paragraph 6(5)(b) motion. Proceedings under the Regulations
are already summary in nature and expeditiously determined. It is therefore
inappropriate to summarily dismiss such a proceeding in the absence of clear
and cogent evidence.
[36]
Prothonotary
Milczynski applied these principles and found that Apotex had not satisfied
this very high burden, and could not merely shift the burden by making an
allegation and contending that it shall be presumed to be true. Just as on the
motions below, Apotex argues not only that its allegations of non-infringement
are presumed to be true, but also that Pfizer has not led any evidence that
would be capable of overcoming this presumption.
.
[37]
I completely
agree with the Prohonotary when she states that on a motion under ss. 6(5), the
burden rests with Apotex to show that Pfizer cannot possibly make out its case.
Apotex is no doubt correct in pointing out that the allegations of fact
contained in an NOA are presumed to be true unless proven to the contrary by
the applicant: Merck Frosst Canada Inc. v. Canada (1994), 55
C.P.R. (3d) 302, at 319 (F.C.A.); Eli Lilly Canada Inc. et al. v. Apotex
et al., 2009 FC 320, at para. 41. It is equally true to say that to rebut
such a presumption, clear and non-speculative evidence is required: Pfizer
Canada Inc. v. Novopharm Limited (2005), 42 C.P.R. (4th)
97, at paras. 19-25, 27‑28 (F.C.A.). These principles hold true,
however, in the context of an application for prohibition; they cannot find
application at the preliminary stage of a paragraph 6(5)(b) motion to dismiss
the application. Because of the dire consequences of such a motion, the second
person must go further than merely “finger pointing” the patent holder; it bears
the burden of convincing the Court that the application for prohibition stands
no chance of being granted. The Prothonotary aptly recognized that distinction
between the two stages of the proceedings in the following words:
[4] A motion under ss. 6(5)(b)
of the Regulations, however, is not the same as a hearing on its merits.
Whereas the burden of proof is on the applicant in the hearing on its merits,
in a motion under ss. 6(5)(b), the burden is entirely and exclusively on the
moving party – in this case Apotex – and the standard of proof is a high one.
(…)
[9] In this respect, the PMNOC
Regulations create a curious and unhappy regime. From an applicant’s
perspective, an arguable case need only be shown on the motion, but an arguable
case may not suffice at the hearing. An applicant may well not be able to
satisfy a Judge hearing an application on its merits that allegations of
non-infringement were not justified. An applicant may not ultimately have much
to go on except whatever expert evidence it can adduce, opining on whatever disclosure
it obtained through a motion under ss. 6(7) of the PMNOC Regulations or on what
otherwise it obtained or was disclosed by a respondent.
[38]
Apotex
rightly pointed out that the Federal Court of Appeal, in Novopharm Limited
v. Sanofi-Aventis Canada Inc. et al. (2007), 59 C.P.R. (4th)
24, did grant a motion to dismiss the first person’s prohibition application on
the basis that the argument supporting an infringement of the patents was
entirely speculative. In the NOA that led to the prohibition application by
Sanofi in that case, Novopharm had alleged that its proposed product would not
infringe Sanofi’s patents because its product would not be made or sold for any
of the uses claimed in those patents. There was clearly nothing in the product
monograph or in any of the other documents in the record that was capable of
establishing that Novopharm would infringe the patents, either directly or by
inducing infringement by others. Yet, Sanofi was arguing that “something”
might emerge on cross-examination. The Court found that such an argument ought
to be rejected as it was entirely speculative.
[39]
The
situation dealt with in that case, though, is entirely different from the facts
as they stand in the present motions. In the Sanofi case, the evidence
on the merits of the application had already been filed. Both Sanofi and
Novopharm had filed their affidavits, as well as the product monograph. The
same is not true in the present motions. Apotex chose to bring its motions
prior to evidence being filed on the merits and, as noted by the Prothonotary,
it has resisted Pfizer’s motion for further disclosure. Moreover, Pfizer’s
appeal from the decision of Justice Harrington seeking further disclosure is
still pending. Finally, there has been no previous determination of any issue
relating to the ‘278 patent or to Apotex’s amlodipine or amlodipine maleate
products. In those circumstances, the burden on Apotex is understandably all
the heavier, and the Prothonotary was correct in finding that Apotex must show
that Pfizer cannot possibly adduce sufficient evidence to be successful on its
application (see, by way of analogy, Nycomed Canada Inc. and Nycomed GmbH
v. The Minister of Health and Sandoz Canada Inc., 2008 FC 541, at para.
42).
[40]
Bearing in
mind, therefore, that Apotex has the burden of proof, has it been established,
on a “plain and obvious standard”, that Pfizer’s applications are futile and
stand no chance of being granted? I shall first look at the arguments relating
to the ‘393 patent, and then at the submissions linked to the’278 patent.
- The ‘393 patent
[41]
As
previously mentioned, there is no dispute between the parties regarding the
construction of the ‘393 patent. The only issue is whether Apotex’s products
contain or, at any point in the manufacturing process, use the besylate salt
and infringe the ‘393 patent.
[42]
In their NOAs,
Apotex asserts that their tablets “will not comprise the besylate salt of
amlodipine nor will amlodipine besylate be used in any way in the manufacture
of tablets or the amlodipine used in our tablets.” It further asserts that
their tablets will comprise only amlodipine or amlodipine maleate as the
medicinal ingredient.
[43]
During the
course of the proceedings and before the motion was heard, Apotex voluntarily
disclosed to Pfizer a good portion of its NDSs filed with the Minister. According
to Apotex, these disclosures clearly show that Apotex’s amlodipine base and
amlodipine maleate will not contain or be made using amlodipine besylate or
R(+) amlodipine (covered by the ‘278 patent).
[44]
Apotex
relies on the affidavit of Dr. Robert A. Batey, a Professor of Chemistry at the
University of
Toronto, to
support its argument. Based on his review of the above documents, he came to
the conclusion that “there is no indication” the amlodipine and amlodipine
maleate tablets of Apotex contain amlodipine besylate, or that Apotex or its
manufacturers employ amlodipine besylate at any stage of the synthesis of the
amlodipine base.
[45]
As already
mentioned, the Prothonotary found that evidence inadmissible on the basis that
it is hearsay. She found that the documents attached as Exhibit B to the Batey
affidavit were submitted without evidence from anyone with knowledge of what
they were, how they were prepared and by whom. In fact, Dr. Batey had no knowledge
of them; the documents were provided to him by counsel for Apotex. It has not
been established that they were part of the NDSs.
[46]
Apotex
submitted that the Prothonotary erred in law by ignoring this procedure and
finding the documents to have been inadmissible. I fail to see how subsection
6(7) of the Regulations could be interpreted as relieving the second
party from the normal rules of evidence. There is nothing in that provision
explicitly or implicitly setting aside the hearsay rule. Moreover, Apotex
offered no explanation as to why it chose not to adduce evidence from anyone
with knowledge of the documents filed with the Minister. There is no evidence
as to who provided these documents to Apotex’s counsel or whether they
correspond with the information on file with the Minister. Apotex has stated
on this appeal that the Minister has verified that the documents produced
correspond to the information on file with Health Canada, but has offered no proof of that
assertion. Consequently, I agree with the Prothonotary that Dr. Batey’s
opinion is not admissible as it is, at best, double hearsay.
[47]
This
conclusion, in and of itself, would be sufficient to dispose of the appeal.
But I also find myself in agreement with the Prothonotary’s alternative
findings that in any event, the opinion of Dr. Batey and the documents filed as
Exhibit B would not have been sufficient to grant the relief sought by Apotex.
[48]
In order
to succeed on this appeal in relation to the ‘393 patent, Apotex must establish
that Pfizer’s application is clearly futile, in that the evidence adduced by
Apotex clearly establishes that the making, construction, use or sale of the
Apotex tablets will not infringe the ‘393 patent. It is undisputed that
claim
11 of the’393 patent claims the compound, amlodipine besylate. Apotex is only
entitled to the extraordinary remedy it seeks if it establishes that it is
“plain and obvious” that it will not infringe this claim. In so doing, Apotex
has to establish not only that the Apotex tablets will not contain amlodipine
besylate, but also that amlodipine besylate is not utilized as an intermediate
or starting material during the process to make the Apotex tablets: Abbott
Laboratories Ltd. v. Canada (Minister of Health) (2006), 56 C.P.R. (4th)
387, at paras. 16, 21 (F.C.A.); leave to appeal ref’d [2006] S.C.C.A. No. 292; Pfizer
Canada Inc. v. Canada (Minister of Health), 2007 FC
898, 61 C.P.R. (4th) 137, at para. 37 (F.C.).
[49]
Pfizer
contends that the documents disclosed by Apotex do not support Apotex’s
allegations of non-infringement, for two reasons. First, these documents are
said to refer specifically to amlodipine besylate.
[50]
I
agree with Apotex that the mere description of amlodipine besylate in what
purports to be Apotex’s submission documents cannot constitute evidence that
amlodipine besylate may be used or formed as an intermediate during the
manufacture of the Apotex tablets. Nowhere do the NDS disclosures indicate
that Apotex’s products will contain or be made using amlodipine besylate.
[51]
More
problematic is the reference in the NDS disclosures attached to the Batey
affidavits to alternative manufacturing processes and reprocessing steps that
are not otherwise described in the produced documents. This information is
only provided in the closed part of each of the Drug Master Files.
[52]
The
closed part of the Drug Master Files is not attached to the Batey affidavits.
Pfizer submits that without seeing them, neither Pfizer nor the Court can
determine whether amlodipine besylate is used at any stage of the process for
manufacturing Apotex’s tablets.
[53]
Apotex
counters that there is no evidence on this motion to establish that there
actually exists any alternative processes. First of all, this submission
seems to contradict the assertion made above referring to the closed part of
the Drug Master Files for alternate processes. Secondly, Apotex has only
itself to blame for this lack of evidence: on a 6(5)(b) motion, it is not for
Pfizer to put forward any evidence of infringement, but merely to show that it
has an arguable case to make on the merits of the application.
[54]
Apotex
further argues that in any event, it must be presumed to use the available,
non-infringing process. It points to a number of cases where that presumption
was upheld, adding that if a generic drug company’s NDS contains inaccurate or
misleading information, a patentee always has a common law action for an
infringement of patent, an injunction and punitive damages after the product
reaches the market. It would accordingly be insufficient for Pfizer merely to raise
the possibility of infringement, or to speculate on how infringement may occur,
because these arguments cannot determine the application on its merits. The
issue to be determined by the Application Judge is whether the process Apotex
states it will use would infringe, not whether some other process might
infringe.
[55]
I
agree with Pfizer’s counsel that the cases cited by Apotex in support of its
propositions do not go as far as submitted. At their highest, these cases
stand for the proposition that at the hearing of an application on its merits,
if there is evidence of only one process, the Court will not entertain
arguments from an applicant that the respondent could infringe the relevant
patent using a process that is not in evidence because such arguments are
tantamount to an allegation of fraud: see, for example, Pfizer Canada Inc.
v. Novopharm Ltd., 2005 FCA 270, at para. 24; SmithKline Beecham Inc.
v. Apotex Inc. (1999), 1 C.P.R. (4th) 99, at paras. 39-40.
[56]
That
is not the case here. In these proceedings, there is evidence of multiple
processes and of the possibility that one or more of these alternate processes
could infringe the ‘393 or the ‘278 patents. Pfizer is seeking production of
relevant documents that Apotex has refused to produce from its submissions to
assess this possibility.
[57]
It
may well be that Pfizer will not be able to make out its case on the merits of
its application, as mere speculation and hypothesizing will not be sufficient
at this stage. But, as noted by Prothonotary Milczynski, it would be premature,
on a motion to arrest the proceeding brought pursuant to paragraph 6(5)(b) of
the Regulations, to attempt to foresee what might occur on the main
hearing, particularly when Pfizer’s evidence is not yet filed, and when the
Court of Appeal has yet to rule on Pfizer’s appeal to obtain further production
of Apotex’s NDSs. On the basis of the evidence that was before her, the
Prothonotary did not err in finding
that it was not plain and obvious that Pfizer’s applications were bereft of any
chance of success.
- The ‘278 patent
[58]
As already
mentioned, there is a dispute between the parties as to the proper
interpretation of the ‘278 patent. It is common ground that claims 4 to 7 of
the ‘278 patent are limited to the R(+) enantiomer of amlodipine. Apotex
contends, however, that claims 1 to 3, when properly construed, similarly
exclude racemic amlodipine, whereas Pfizer is of the opposite view.
[59]
The
determination of the meaning of a patent is a question of law for the court.
Construction is a purposive exercise wherein the court examines the meaning of
the words chosen by the inventor in the context of the patent as a whole and in
accordance with the intent of the invention: Whirlpool Corp. v. Camco
Inc., [2000] 2 S.C.R. 1067; Free World Trust v. Electro Sante
Inc., [2000] 2 S.C.R. 1024; H.G. Fox, The Canadian Law and Practice
relating to Letters Patent for Inventions (4th ed.), Carswell,
1969, pp. 215-217.
[60]
Claims 1
through 4 read as follows:
Claim 1: “The R(+) isomer of
amlodipine or a pharmaceutically acceptable salt thereof for use in the
treatment of conditions requiring inhibition of vascular smooth muscle cell
migration.”
Claim 2: “Use of the R(+)
isomer of amlodipine or a pharmaceutically acceptable salt thereof for making a
medicament for treatment of conditions requiring inhibition of smooth muscle
cell migration.”
Claim 3: “Use of the R(+)
isomer of amlodipine or a pharmaceutically acceptable salt thereof for
treatment of conditions requiring inhibition of smooth muscle cell migration.”
Claim 4: “A pharmaceutical
composition for use in the treatment of conditions requiring inhibition of
vascular smooth muscle cell migration, comprising an effective amount of the
R(+) isomer of amlodipine or a pharmaceutically acceptable salt thereof and a
pharmaceutically acceptable carrier or diluent, said composition being
substantially free of calcium channel-blocking activity.
[61]
Claims 5
through 7 are dependent on claim 4. There is need to reproduce them as they
therefore contain the same limitation as claim 4.
[62]
Apotex
makes a number of arguments in support of its interpretation that the ‘278
patent excludes the racemic amlodipine. First, it submits that a plain reading
of claims 1 to 3 indicate that they relate to the R(+) enantiomer of amlodipine
and not to the racemic amlodipine. Since the ‘278 patent carefully
distinguishes between R(+) amlodipine and racemic amlodipine throughout the
‘278 patent, the inventor could simply have written “amlodipine” instead of the
more laborious “the R(+) enantiomer of amlodipine” had claims 1 to 3 been
intended to embrace the racemate.
[63]
Second,
Apotex submits that a proper contextual analysis makes manifest the intention
of the inventor to exclude racemic amlodipine from the scope of the claims of
the ‘278 patent. The patent begins by acknowledging that racemic amlodipine,
R(+) amlodipine and S(-) amlodipine, along with other calcium channel blockers,
were known inhibitors of smooth muscle cell migration. The invention to which
the ‘278 patent purports to relate is the discovery that “the R(+) isomer of
amlodipine, despite its lack of calcium channel blocking activity, is a potent
inhibitor of smooth muscle cell migration”. The ‘278 patent describes as its
discovery that R(+) amlodipine inhibits smooth muscle cell migration while not
producing channel-blocking effects. Therefore, to read the phrase “the R(+)
isomer of amlodipine” in claims 1 to 3 as encompassing racemic amlodipine would
be to defeat the very purpose of the patent, so the argument goes, as a patient
receiving racemic amlodipine would suffer the “concomitant cardiovascular
effects” the patent was directed to avoid. In addition, such an interpretation
of claims 1 to 3 would amount to interpreting these claims so as to cover what
the patent itself identifies as prior art.
[64]
As
compelling as these arguments may seem at first sight, I do not think that they
satisfy the high burden that Apotex must meet in showing that Pfizer’s
applications are so clearly futile that they do not have the slightest chance
of success. First of all, the alternative interpretation of the ‘278 patent
offered by Pfizer is not so far fetched as to make it plain and obvious that
Apotex’s reading must be preferred. If Pfizer’s construction of claims 1 to 3
is accepted, Apotex will infringe claims 1 to 3 of the ’278 patent because the
Apotex tablets contain, by Apotex’s own admission, racemic amlodipine. And
even if Apotex’s construction of these claims is preferred, it is not entirely
clear that it will not infringe them based on the evidence that is before the
Court at this stage of the proceeding. I will deal in turn with each of these
aspects.
[65]
At the
outset, it is fair to say that the claims of the ‘278 patent have not yet been
construed by this Court. Apotex argued that Pfizer is estopped from arguing
that claims 1, 2, and 3 of the ‘278 patent cover racemic amlodipine as this
Court has previously held that a claim for the R(+) enantiomer of amlodipine
does not encompass a claim for the racemate: see Pfizer Canada Inc. v. Canada (Minister of Health), 2007 FC 187; Pfizer
Canada Inc. v. Canada (Minister of Health) (2007), 59 C.P.R. (4th)
166. But the application of the doctrine of issue estoppel within the context
of the Regulations requires that: (a) the same question has been
decided; (b) the judicial decision which is said to create the estoppel was
final; and (c) the parties to the judicial decision were the same as the
parties to the proceedings in which the estoppel is raised: Danyluk v. Ainsworth
Technologies Inc., [2001] 2 S.C.R. 460, at 477; AB Hassle v. Apotex
Inc. (2005), 38
C.P.R. (4th)
216, at paras. 66-67 (F.C), aff’d (2006), 47 C.P.R. (4th) 329
(F.C.A.); Procter & Gamble Pharmaceuticals Canada Inc. v. Canada (Minister of Health) (2003), 33 C.P.R. (4th)
193, at para. 17 (F.C.A.).
[66]
I agree
with counsel for the applicants that the issues before this Court in the two
cases relied upon by the respondents were entirely different. Both of these
cases dealt with an entirely different patent, Canadian Patent No. 2,355,493
(‘493 patent), on the basis of an entirely different evidentiary record. The
‘278 patent was not before the Court in these previous proceedings, and it
would be improper to consider the ‘493 patent in construing the ‘278 patent.
Moreover, patent construction is to be conducted as at the date of publication
of the patent – in this case, March 1995. The Supreme Court of Canada has made
it clear that the claims of a patent are to be construed within the context of
the patent specification, and not in the context of extrinsic evidence. Apotex
is using the ‘493 patent as extrinsic evidence to construe the claims of the
‘278 patent. This is inappropriate, especially since the ‘493 patent was
published seven years after the ‘278 patent.
[67]
The only
evidence on these records as to how claims 1 to 3 of the ‘278 patent would be
understood by a person of ordinary skill in the art is that of Dr. Roush, the
expert who gave evidence on behalf of Pfizer. The expert called by Apotex, Dr.
Batey, did not offer an opinion on claims 1 to 3. As he stated in his
affidavit, he is unable to comment on these claims as they pertain to a subject
matter beyond his expertise.
[68]
Dr. Roush
states in his affidavit that a person of ordinary skill in the art would
understand that racemic amlodipine contains the R(+) enantiomer of amlodipine
and has an inhibitory effect on smooth muscle cell migration. As a result,
racemic amlodipine can be used in the treatment of conditions for which an inhibitor
of smooth muscle cell migration is required. A skilled person would also
understand that claims 1, 2 and 3 of the ‘278 patent encompass racemic
amlodipine, in that racemic amlodipine contains a smooth muscle migration
inhibitory amount of the R(+) enantiomer. According to Dr. Roush, there is
nothing in these claims that excludes the presence of the S(-) enantiomer or,
indeed, any other therapeutic agent.
[69]
In his
view, the presence of limiting language in claims 4 through 7 (i.e.,
requiring optically pure R(+) amlodipine) further supports a permissive reading
of claims 1, 2 and 3 which do not contain such a limitation. That the patentee
did not impose this limitation in claims 1, 2 and 3 indicates that racemic
amlodipine would achieve the desired result (i.e., contain an effective
amount of the R(+) enantiomer to inhibit smooth muscle cell migration).
[70]
I
recognize that expert opinion, as helpful as it may be in construing a patent,
does not relieve this Court of its ultimate responsibility: patent construction
is a matter of law, it is for the Court to interpret the claims of a patent.
As the Supreme Court said in its seminal decision of Whirlpool Corp. v. Camco
Inc., supra, at para. 57, “…the role of the expert [is] not to
interpret the patent claims but to put the trial judge in the position of being
able to do so in a knowledgeable way.”
[71]
I am also
mindful of the counter arguments put forward by counsel for the respondent,
according to whom Dr. Roush erred in several respects. For example, it was
alleged that Dr. Roush misunderstood the inventive concept of the ‘278 patent,
that he improperly used the product monograph for Norvasc to construe the
claims of the ‘278 patent, and that he ignored the fact that claims 1 to 3
relate to a compound (R(+) amlodipine) while claim 4 relates to a composition
that contains R(+) amlodipine along with other things.
[72]
These
conflicting views and arguments about the proper construction of the ‘278
patent are clear evidence that this issue is far from being free of doubt, and
is better left to the judge who will be hearing Pfizer’s application. It would
be most inappropriate for this Court to rule definitively and for the first
time on the proper construction of a patent in the content of a motion made
under paragraph 6(5)(b) of the Regulations. Whatever may be my views as
to the cogency of the arguments made by both parties, I have not been convinced
that this case should not proceed to a full consideration of the merits.
[73]
In any
event, Apotex could infringe the ‘278 patent on the basis of either
construction of that patent. If Pfizer’s construction of claims 1 to 3 is
preferred, Apotex will infringe claims 1 to 3 of the ‘278 patent because the
Apotex tablets contain, by Apotex’s own admission, racemic amlodipine. But
even if Apotex’s construction of these claims is preferred, Apotex could still
infringe them on the basis that the Apotex tablets will contain an excess of
the R(+) enantiomer of amlodipine.
[74]
Apotex relies
on Exhibit “B” to each of the affidavits of Dr. Batey, which purport to be
copies of portions of Apotex’s submissions to the Minister, to show that the
Apotex tablets will not contain the R(+) enantiomer. For the reasons already
developed above in relation to the ‘393 patent, these documents are, at best,
double hearsay. Apotex clearly relies on these documents for the proof of
their contents. However, for reasons known only to Apotex, it chose not to
adduce evidence from anyone with knowledge of these submissions. Dr. Batey has
no knowledge of them, as these documents were given to him by Apotex’s
counsel. There is no evidence as to who provided these documents to Apotex’s
counsel or whether they correspond with the information on file with the
Minister.
[75]
Further,
the documents attached to the Batey affidavits in what purports to relate to
Apotex’s amlodipine free base submission (T-876-08) identify a certain impurity
produced in Apotex’s manufacturing process. Dr. Roush is of the view that the
only way such an enantiomer could arise would be if the starting material was
not racemic. This reasoning suggests to Dr. Roush that the medicine in the
Apotex tablets may contain an uneven mixture of enantiomers.
[76]
In
response, Apotex argues that the impurity must be racemic because it is the by-product
of a synthetic process that employs only racemic materials to prepare the
amlodipine. Apotex also claims that certain physical properties of the Apotex tablets,
such as its optical rotation, are consistent with the conclusion that it is
racemic.
[77]
As can be
expected, these arguments are strongly contested by Pfizer. I agree with
counsel for Pfizer that many of these arguments, offered through the affidavit
of Dr. Golberg, principal scientist in the Analytical Operations Division of
Apotex, constitute hearsay evidence. It is also true that Dr. Goldberg has not
put forward any information or documentation to support his statement that
Apotex’s provider only employs racemic materials in its synthetic route to
prepare the amlodipine base. But there is no need, at this stage, to go any
deeper in the assessment of these various arguments, as they are mostly based
on speculations (as far as Pfizer is concerned) and on hearsay evidence and on
an incomplete record (in the case of Apotex). This is far from enough to
satisfy the Court that Pfizer’s application is frivolous and abusive, and it
would be remiss of me to conclude that Apotex has met its heavy burden pursuant
to subsection 6(5) of the Regulations on the basis of the evidence
before the Court. I agree with the Prothonotary that in these circumstances it
is far more appropriate to leave it to the judge hearing the application to
decide these matters on the basis of a more complete evidentiary record. Not
only has the Court of Appeal not yet ruled on the motion of Pfizer seeking the
disclosure of the entire Chemistry and Manufacturing Section contained in
Apotex’s NDSs, but Pfizer has not delivered its evidence on the merits either.
Accordingly, this Court is in no position to cut short Pfizer’s application; on
the basis of the record that is before me, it is impossible to conclude that it
does not have at least an arguable case.
[78]
Just as it
did before the Prothonotary, Pfizer also made a number of other arguments to
resist the motion filed by Apotex pursuant to paragraph 6(5)(b) of the Regulations.
They range from a submission that the NOAs are nullities because Apotex did not
make an allegation at the time it served its notices, to the further argument
that even if Apotex is entitled to make an allegation, it did not do so before
serving on Pfizer the letters purporting to be NOAs with respect to the ‘278
patent. Furthermore, Pfizer alleges that Apotex is estopped from arguing that
it is plain and obvious that Pfizer has no chance of success as it did not oppose
the merits of Pfizer’s motions to amend its notices of application.
[79]
The
Prothonotary declined to rule on these issues, being of the view that these
matters are best left to the hearing judge. I agree. Having concluded that
Apotex failed to establish that Pfizer’s applications are frivolous and
abusive, there would be no point to discuss at this stage the more procedural
arguments raised by Pfizer, some of which are novel and have not yet been
authoritatively decided. These issues, like the others discussed above, are
better left to the judge who will be hearing in full the applications filed by
Pfizer.
[80]
For all of
the foregoing reasons, this appeal is dismissed, with costs to Pfizer.
ORDER
THIS COURT ORDERS that this appeal is dismissed,
with costs to Pfizer.
"Yves
de Montigny"
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