Date: 20080306
Docket: T-1799-06
Citation: 2008
FC 313
Toronto, Ontario, March 6, 2008
PRESENT: Madam Prothonotary Milczynski
BETWEEN:
NYCOMED
CANADA INC. and
NYCOMED GMBH
Applicants
and
NOVOPHARM LIMITED and
THE MINISTER OF HEALTH
Respondents
REASONS FOR ORDER AND ORDER
[1]
This is a
motion by the Respondent Novopharm Limited (“Novopharm”) for an order
dismissing the application for prohibition with respect to Novopharm’s 20 and
40 mg pantoprazole sodium enteric coated tablets (“Novopharm tablets”), pursuant
to s.6(5) of the Patented Medicines (Notice of Compliance) Regulations,
(“Regulations”).
[2]
The issue
on the motion is whether or not the only patent at issue in the application,
Canadian Patent No. 2,109,697 (“’697 Patent”) is eligible for listing on the
Canadian Patent Register (“Register”) with respect to the Applicants’
(collectively “Nycomed’s”) 20 and 40 mg pantoprazole sodium enteric coated
tablets (“Nycomed tablets”). Presently, the Nycomed tablets are marketed in Canada under the brand name
PANTOLOC.
[3]
The
determination of this issue for the purposes of s.6(5)(a) of the Regulations
requires:
(i)
an
identification of the “patented invention” disclosed by the ‘697 Patent; and
(ii)
an
analysis, for each Supplemental New Drug Submission (“SNDS”) or New Drug
Submission (“NDS”) upon which a listing was obtained, as to whether there is a
sufficiently relevant link between the SNDS or NDS, the Notice of Compliance
(“NOC”) that resulted from the submission, and the patented invention disclosed
by the ‘697 Patent. (Wyeth Canada v. ratiopharm Inc. (2007), 60 C.P.R. (4th) 375
(F.C.A.)
[4]
The
standard and burden of proof under s.6(5) of the Regulations are also
set out in Wyeth:
The factual elements of the motion must
be decided on the basis of the normal standard of proof in civil matters, the
balance of probabilities. As to the burden of proof, it lies where it normally
does, on the party filing the motion (the generic drug manufacturer). However,
to the extent that the respondent (the innovator) fails to produce relevant
evidence that is under its sole control, there may be a basis for drawing an
adverse inference.
[5]
The ‘697
Patent is entitled “Oral-Administration Forms of a Medicament Containing
Pantoprazole” and is owned by Nycomed. It was filed on June 13, 1992, claiming
priority to an application filed in Switzerland
on June 17, 1991. The ‘697 Patent issued on November 22, 2005 and will expire
on June 13, 2012.
[6]
The ‘697
Patent was submitted for listing on the Register on the basis of five SNDSs and
one NDS made by Nycomed in respect of PANTOLOC. Schedule A to these reasons,
sets out a chart indicating each SNDS or NDS number, date and the reason for
filing.
[7]
For the
reasons set out below, I find that on a balance of probabilities, none of these
submissions can be said to relate to the invention of the ‘697 Patent.
Patented Invention Disclosed by the ‘697
Patent
[8]
Nycomed
submits that the ‘697 Patent has two aspects. First, that it claims new oral
formulations of the medicine pantoprazole. Second, that it claims the use of
these new formulations of the medicine pantoprazole to inhibit a particular
enzyme. Inhibiting the enzyme causes a reduction in a patient’s stomach acid,
which is necessary for the treatment of various gastrointestinal disorders.
[9]
As set out
in Nycomed’s evidence: the affidavits of Drs. McGinity and Wolman, Nycomed
submits that the ‘697 Patent is directed towards new oral formulations of the
medicine pantoprazole and the use of these formulations as an inhibitor of the
enzyme H+K+-ATPase in the treatment of gastrointestinal disorders. Such
inhibitors are also known as “proton pump inhibitors” or PPIs. With respect to
formulation, claims 1 and 32 are important claims directed towards the new
formulations of the medicine, and claims 31, 96 and 97 are claims for the use
of the new formulations as a PPI, which, Nycomed submits, a clinician of
ordinary skill would understand to mean as use of the new formulations in the
treatment of various gastrointestinal disorders that require the reduction of
gastric juice in the stomach.
[10]
For
Novopharm’s part, there does not seem to be significant disagreement with the
above interpretation in respect of what is taught or disclosed by the ‘697
Patent regarding formulation. More specifically, that the new formulation is
as a result of the “new knowledge” contributed by the ‘697 Patent identified in
claims 1, 32 and 64, disclosing a formulation for pantoprazole comprising: (i)
a core containing pantoprazole and its physiologically tolerated salts, (ii) at
least one water-soluble intermediate layer surrounding the core, and (iii) an
outer layer which is resistant to gastric juice.
[11]
In his
affidavit filed on behalf of Nycomed, Dr. Wolman states that certain aspects of
the ‘697 Patent concern the use of pantoprazole formulations to inhibit
H+K+-ATPase, namely claims 31, 96 and 97. He also states that the use aspect
of the ‘697 Patent is directed to clinicians and that the inhibition of
H+K+-ATPase is the basis for using pantoprazole in the treatment of reflux esophagitis,
gastro-esophageal reflux disease (“GERD”) and gastrointestinal lesions induced
by NSAIDs.
[12]
On
cross-examination, however, Dr. Wolman confirmed that there is nothing in the
disclosure of the ‘697 Patent that relates to the clinical indications of
pantoprazole or is directed to a clinician. The only portions of the
disclosure that Dr. Wolman thought might be relevant to clinicians were the
mention of H+K+-ATPase, which was already known, and that the formulations
could be made into tablets. Dr. Wolman also admitted on cross-examination that
there is no mention anywhere in the ‘697 Patent of the use of pantoprazole for
the treatment of GERD, reflux esophagitis, gastrointestinal lesions induced by
NSAIDs, or in combination with appropropriate antibiotics, the eradication of Helicobacteror
infection associated with an active duodenal ulcer.
[13]
The
cross-examination of Dr. McGinity also confirmed that the “new knowledge”
contributed by the inventors of the ‘697 Patent is new formulations of
pantoprazole with increased stability. Dr. McGinity specifically identified
independed Claims 1, 32 and 64 as describing the “new knowledge” contributed by
the ‘697 Patent. The only use aspects of the ‘697 Patent identified by Dr.
McGinity were reference to H+K+-ATPase in a statement on page 3 of the patent,
comparing the water content of prior art formulations with the patented
formulations and dependent claims 96 and 97.
[14]
As set out
in paragraph 47 of Novopharm’s written representations, in finding that the
invention of the ‘697 Patent does not relate to any new use of pantoprazole,
but relates to formulations of pantoprazole, it is also worth noting:
-
there is
no claim in the ‘697 Patent for the medicine pantoprazole or any of its
physiologically tolerated salts;
-
as of the
priority date of the ‘697 Patent, the existence of pantoprazole and its use as
a PPI were known;
-
the
invention disclosed and claimed in the ‘697 Patent does not relate to
particular strengths of the patented formulations;
- the
invention disclosed and claimed does not relate to the adverse effects of
pantoprazole on patients or to testing of pantoprazole in humans (clinical
trials) - The disclosure of the ‘697 Patent does not mention the clinical
indications for pantoprazole and is not directed to a clinician;
-
the
invention disclosed and claimed in the ‘697 Patent does not relate to the use
of the patented formulation for the treatment of H. pylori infections,
reflux esophagitis, GERD, or the prevention of gastrointestinal lesions induced
by NSAIDs; and
-
if the
invention of the ‘697 Patent was directed to the use of the patented
formulation as an antimicrobial for the treatment of H. pylori
infections, reflux esophagitis, or for the treatment of GERD or the prevention
of gastrointestinal lesions induced by NSAIDs, there would have to be at least
some information or mention of those uses in the disclosure or in the claims.
Neither the disclosure nor the claims contain any actual information about such
uses of pantoprazole.
[15]
Reviewing
the patent as a whole, contrary to Nycomed’s submissions, I agree with
Novopharm, that the invention of the ‘697 Patent is in respect of the new
formulations, not new uses of pantoprazole. The fact that the words “for the
use of inhibiting H+K+ -ATPase or variations thereof are added or tagged onto
dependent claims 31, 96 and 97 do not lead to the conclusion that the patented
invention in the ‘697 Patent includes the use of the disclosed formulation. The
use of pantoprazole as a PPI was already known as of the priority date of the
‘697 Patent. Adding the known use onto claims 31, 96 and 97 does not add
anything to the invention claimed. As stated by the Federal Court of Appeal in
Abbott Laboratories v. Canada (Minister of Health), (2007), 59 C.P.R. (4th) 1
(FCA) at para. 43:
Although the Court should strive to
construe claims which do not bear the same words differently, Heneghan J. was
on solid ground in this case, when she held that the words “for use as an
antibiotic” at the end of claim 31, do not add anything to the invention
claimed. At best, these words describe the utility of Form II once made in
accordance with the claimed invention. The fact that clarithromycin in Form II
is used as an antibiotic was well known. Saying, in effect, that an antibiotic
is used as an antibiotic adds nothing to the invention.
[16]
Similarly,
in the case of the ‘697 Patent, the purported new formulations can still be
used to do what pantoprazole was already known to do, namely, inhibit H+K+
-ATPase. This is confirmed by Dr. Signorino during his cross-examination, who
goes on to say that the use of the claimed formulations to inhibit H+K+-ATPase
simply establishes their utility
Is the Patented Invention Relevant to any
SNDS and NOC against which it is listed?
[17]
Each of
submissions and resulting NOCs: 055738 (“‘738”), 066552 (“‘552”), 087266
(“‘266”) and 101809 (“‘809”) relate only to new uses that are not disclosed or
claimed in the ‘697 Patent and do not form part of the patented invention
disclosed by the ‘697 Patent. There is no linkage between these submissions
and the patented invention.
[18]
NOC ‘738
was for a new indication for Nycomed’s 40 mg tablets, the treatment of H.
pylori infections associated with an active duodenal ulcer when used in
combination with appropriate antibiotics. The ‘697 Patent is directed to
particular formulations of pantoprazole. The ‘697 Patent makes no mention or
claims for the treatment of H. pylori.
[19]
NOC ‘552
was for a new indication for Nycomed’s tablets for the treatment of symptomatic
GERD, such as acid regurgitation and heartburn. The ‘697 Patent does not
mention or claim the treatment of symptomatic GERD.
[20]
NOC ‘266
issued for a new indication for Nycomed’s 20 mg tablets for the prevention of
gastrointestinal lesions induced by NSAIDs in patients requiring continuous
NSAID therapy. The ‘697 Patent does not claim or mention this indication.
[21]
NOC ‘809
issued in respect of revisions to the product monograph for PANTOLOC. A
comparison of the product monograph before and after NOC ‘809 was issued shows
that the revisions did not relate to any new formulation. The revisions were
limited to updates to the adverse reactions, clinical trials, reference and
dosing sections of the product monograph. The new formulations of pantoprazole
indicated by the ‘697 Patent are not relevant to these non-formulation,
administrative changes.
[22]
Submission
057926 (“’926”) was for: (1) a new dosage strength of PANTOLOC – 20 mg, and (2)
a new indication, namely the maintenance treatment of reflux esophagitis.
There is nothing in the ‘697 Patent, however, regarding the use of pantoprazole
for this new indication or for the formulation of pantoprazole into 20 mg
tablets. The subject matter of the submission is not part of the patented
invention and accordingly, the required linkage between the submission and the
‘697 Patent is also absent. On this point, I would add that while there was
some conflicting evidence, there was insufficient reliable evidence to draw any
conclusion as to what the 20 mg formulation was at the time SNDS ‘926 was filed
and whether it was proportional to the 40 mg formulation.
[23]
The NOC
issued in respect of NDS 104828 was for a manufacturer name change for
Nycomed’s tablets. This type of administrative change cannot and does not
support a patent listing – the ‘697 Patent is not relevant to the NDS or NOC.
Other Issues
[24]
Nycomed
adduced evidence that while the ‘697 Patent was not listed against the original
NDS for PANTOLOC, it was listed against the original NDS for PANTO-BYK. This
is irrelevant to this proceeding.
[25]
The
reference product in respect of which the bioequivalence comparison was made
for Novopharm pantoprazole sodium enteric coated tablets is PANTOLOC – not
PANTO-BYK. PANTOLOC and PANTO-BYK 20 mg and 40 mg strength tablets have
different Drug Identification Numbers. Under section 5 of the Regulations,
it is acceptable for the generic manufacturer to chose which approved drug they
wish to reference or use as comparator to establish bioequivalence. Since
Novopharm referenced PANTOLOC in its Abbreviated New Drug Submission and Notice
of Allegation, they are not a “second person” with respect to PANTO-BYK, a
different drug, and need not address the patents listed against it.
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