Date: 20100729
Docket: A-281-09
Citation: 2010 FCA 204
CORAM: NADON
J.A.
SHARLOW
J.A.
LAYDEN-STEVENSON
J.A.
BETWEEN:
PFIZER LIMITED
Appellant
and
RATIOPHARM INC.
Respondent
REASONS FOR JUDGMENT
LAYDEN-STEVENSON J.A.
[1] The
respondent (Ratiopharm), pursuant to the provisions of the Patent Act,
R.S.C. 1985, c. P.4 (the Act), commenced an action in the Federal Court with
respect to the appellant’s (Pfizer) Canadian Letters Patent No. 1,321,393 (the
'393 Patent). Ratiopharm requested, among other things, a declaration that the
'393 Patent is invalid. A Federal Court judge (the trial judge) granted
Ratiopharm’s request.
[2] Following a four-week trial
involving 20 witnesses (eight of whom were experts), the trial judge concluded
that the '393 Patent is invalid for obviousness. He also found, in obiter,
that the patent is invalid on a number of other grounds. Specifically, he
found: the '393 Patent lacked utility; its disclosure was insufficient; it was
misleading and invalid under section 53 of the Act; and it failed to meet the
criteria for a valid selection patent.
[3] Pfizer appeals from
the Federal Court judgment. To succeed, Pfizer must demonstrate a reviewable
error with respect to each of the grounds upon which the trial judge ruled. For
the reasons that follow, I have not been persuaded that the trial judge erred
in concluding that the '393 Patent was obvious. Consequently, Pfizer’s appeal
must fail.
Amlodipine besylate
[4] The '393 Patent is
entitled “Besylate Salt of Amlodipine”. Only Claim 11 is in issue. That claim
reads: “The besylate salt of amlodipine.” Amlodipine was invented by Pfizer. It
is a calcium channel blocker and is an anti-hypertensive compound. A broad
class of amlodipine and its pharmaceutically acceptable acid addition salts
were disclosed in Pfizer’s prior European Patent Application 089167 (EP 167).
Amlodipine besylate, marketed under the tradename NORVASC, is used to treat
high blood pressure and angina. The therapeutic effects of amlodipine besylate
are provided by amlodipine.
[5] Before a drug can be
sold, it must be produced in a form suitable for manufacture, storage,
transportation and administration to patients. The
properties required to achieve a pharmaceutically acceptable form include
solubility (absorption into the patient’s bloodstream), stability (minimal
changes during manufacture), non-hygroscopicity (attracts little water) and
processability (does not stick to manufacturing equipment).
[6] To achieve these
properties, it is often necessary to convert the free base drug into a salt. A
salt is an ionic compound that is formed when a base (such as amlodipine) is
combined with an acid. The '393 Patent covers the besylate salt (benzene
sulphonate, a sulphonic acid) of amlodipine. It is common ground that
amlodipine besylate is a pharmaceutically acceptable salt.
Development of amlodipine besylate
[7] Pfizer initially
attempted to formulate amlodipine in the form of the maleate salt. However,
during the regulatory approval process, amlodipine maleate exhibited problems
with stability and processability. Consequently, Pfizer began to search for a
different salt of amlodipine through an accepted process known as salt
screening. Pfizer tested seven salts: acetate, succinate, mesylate, besylate,
salicylate, hydrochloride and tosylate. It decided to proceed with the besylate
salt. The trial judge described the salt screening process at paragraph 50 of
his reasons:
[T]he procedure followed
by [Pfizer scientists] Dr. Wells and Mr. Davison was essentially a classic mid
1980s salt screening process for a pharmaceutical candidate…It was somewhat
rough and ready, time was an essential constraint, certain salts only were
selected, not entirely at random, for testing. Once one or two or three
sufficiently useful candidates were identified, there was no effort to test all
possible salts. The selected candidate(s) were settled upon and passed on to
the next stage, that of final formulation for regulatory approval.
[8] In a memorandum dated 25
November 1985, Pfizer scientist and inventor Dr. James Wells described his
findings in contemplation of a patent. The content of the memorandum is quoted
at paragraph 103 of the trial judge’s reasons:
We recommend a patent
filing to protect the besylate and tosylate salts of UK-48,340 because there
is:
(a) improved
shelf life of solid dosage forms due to improved solid state stability of the
besylate and tosylate salts;
(b) improved
processing of tablets and capsules because sticking is considerably reduced by
the besylate and tosylate salts. This allows economic tableting by direct
compression whereas although wet massing reduces stickiness it compromises
stability;
The mesylate salt
probably also merits protection since its stability and processing properties
are excellent. However, it is isolated in the anhydrous form and upon exposure
to moisture rises rapidly to the monohydrate. The besylate and tosylate are
however non-hygroscopic and anhydrates.
The memorandum refers to
the improvements (advantages) of amlodipine besylate and other sulphonates.
[9] Pfizer filed its
Canadian patent application on April 2, 1987, claiming priority from its UK patent application filed on April 4,
1986. The '393 Patent issued on August 17, 1993 and will expire on August 17,
2010. It is a selection patent.
The Trial Judge’s Reasons
[10] The trial judge provided
detailed, cogent and articulate reasons for his findings. He identified and
described each witness and his impression of the witness’s testimony. He noted
the conflicting expert evidence, stated which evidence he preferred and
provided the reasons for his preferences.
[11] He described the
qualifications of the person skilled in the art (POSITA) and identified the
relevant dates for the application of the POSITA’s evidence.
He construed the pertinent claim and concluded that the claimed invention is “a
particular salt form, besylate, of a known pharmaceutical compound,
amlodipine.” The claim is “unrestricted as to any particular use and
unrestricted as to any particular form of the compound.”
[12] The trial judge
discussed the development of pharmaceutical products in the 1980s, particularly
the stage known as salt selection or salt screening, and included references to
the testimony of the witnesses. Then, in 55 paragraphs, he detailed the
development and patenting of amlodipine besylate, again with references to the
evidence. He construed the promise of the patent and found it promised that besylate
amlodipine possessed a unique combination of properties making it particularly
and outstandingly suitable for preparation of pharmaceutical formulations of
amlodipine. Next, he devoted an additional 40 paragraphs to a comparison
between what the '393 Patent said and “what actually happened” and made a
number of factual conclusions which he set out at paragraph 153 of his reasons.
He then turned to the legal issues, the first of which was obviousness.
The Standard of Review
[13] The standard of review
is articulated in Housen v. Nikolaisen, [2002] 2 S.C.R. 235. There,
the Supreme Court reiterated that an appeal is not a
re-trial of a case. Questions of law are to be determined on a standard of
review of correctness. This means that an appellate court is at liberty to
replace the opinion of the trial judge with its own. The standard of review for
findings of fact is palpable and overriding error, that is, the factual
findings cannot be reversed in the absence of an error that is plainly seen.
Obviousness
The Trial Judge’s Reasoning
[14] In addressing the issue
of obviousness, the trial judge acknowledged that he must look at the claim as
properly construed. At paragraph 159 of his reasons, he set out the approach to
obviousness adopted by the Supreme Court of Canada in Apotex Inc. v.
Sanofi-Synthelabo Canada Inc., [2008] 3 S.C.R. 265 (Sanofi):
(1) (a) Identify
the notional “person skilled in the art”;
(b) Identify the relevant common general knowledge of
that person;
(2) Identify
the inventive concept of the claim in question or if that cannot readily be
done, construe it;
(3) Identify
what, if any, differences exist between the matter cited as forming part of the
“state of the art” and the inventive concept of the claim or the claims as construed;
(4) Viewed
without any knowledge of the alleged invention as claimed, do those differences
constitute steps which would have been obvious to the person skilled in the art
or do they require any degree of invention?
[15] The trial judge, at
paragraph 160 of his reasons, specified the questions that provide guidance at
the fourth stage of the Sanofi approach when the court ascertains
whether an invention is “obvious to try”:
1. Is
it more or less self-evident that what is being tried ought to work? Are there
a finite number of identified predictable solutions known to persons skilled in
the art?
2. What
is the extent, nature and amount of effort required to achieve the invention?
Are routine trials carried out or is the experimentation prolonged and arduous,
such that the trials would not be considered routine?
3. Is
there a motive provided in the prior art to find the solution the patent addresses?
He then noted this Court’s decision in Apotex Inc. v.
Pfizer Canada Inc., [2004] 4 F.C.R. 223 and correctly concluded that “worth
a try” and “obvious to try” are not synonymous.
[16] The trial judge summarized
the relevant circumstances at paragraphs 167 and 168 of his reasons and
concluded that what Pfizer had done was routine for a POSITA at the time. He
further concluded that the claimed invention, a besylate salt of amlodipine,
was obvious.
Pfizer’s Allegations of Error
[17] Pfizer alleged that the
trial judge erred in two respects. It characterized one error as a legal error
and the other as a palpable and overriding factual error. Regarding the factual
error, Pfizer asserted that the trial judge erred in finding the POSITA “would
have had every reason to test the besylate salt.” Pfizer complained that its
cross-examination of Dr. Cunningham (where Pfizer ostensibly demonstrated that
the six pieces of art referred to by Dr. Cunningham did not support such a conclusion)
was either forgotten or ignored by the trial judge. This, in Pfizer’s view,
ascended to the level of palpable and overriding error.
[18] The alleged legal error
related to the manner in which the trial judge applied, as Pfizer put it, the “test
for obviousness” as enunciated by Sanofi. Specifically, in its written
submissions, Pfizer argued that the trial judge erred by focussing on the
process the inventors used in developing the invention rather than the outcome
or result of the process. Pfizer submitted that, when an invention is arrived
at through testing, it is not necessarily obvious merely because the utilized
tests were within the knowledge and capacity of the POSITA. The invention is
obvious only if its result was obvious.
[19] Pfizer accepted that
mere verification of known properties of a common substance does not constitute
an invention and therefore cannot be patented, but it relied on the statement
of this Court in Pfizer Canada Inc. v. Canada (Minister of Health), 2006
FCA 214, [2007] 2 F.C.R. 137 (Pfizer NOC) that “the formulation
properties of any salt of amlodipine could never have been expected but must be
determined empirically.” It contended that the trial judge simply adopted the
findings of the United States Court of Appeals for the Federal Circuit in Pfizer
Inc. v. Apotex Inc. (2006), 480 F. 3d 1348 (U.S. authority) that “it
was routine in the art to verify the expected physiochemical characteristics of
each salt…and Pfizer’s scientists used standard techniques to do so.” Thus,
according to Pfizer, the trial judge’s error was based on this erroneous
reliance and required the intervention of this Court.
[20] At the hearing, counsel
for Pfizer suggested that the question for obviousness fell to be determined by
asking whether there was mere verification or whether there was inventiveness.
If there was more than mere verification, then there is an invention and no
obviousness. The two sides of the equation were said to be mutually exclusive.
Counsel reiterated the relevant question as whether the result (rather than the
process) was more or less self-evident, that is, was it predictable?
[21] In sum, Pfizer
maintained that the trial judge asked whether the process was more or less self-evident
(or predictable) when the appropriate question was whether the result was self-evident
(or predictable). Accordingly, in Pfizer’s view, the trial judge misdirected
himself as to the law.
Analysis
[22] The alleged factual
error can be addressed summarily. I agree with Ratiopharm that Dr. Cunningham’s
evidence was based not only on the art, but on his experience in the industry,
his knowledge with respect to salt selection and the functionalities of various
known groups of salts. Further, Dr. Atwood’s evidence corroborated that of Dr.
Cunningham.
[23] At its core, this
alleged error is a complaint that the trial judge was insufficiently persuaded
by Pfizer’s cross-examination. It does not demonstrate palpable and overriding
error.
[24] Pfizer’s argument that the
trial judge erroneously relied upon and adopted the conclusion from the U.S. authority ties into its argument with
respect to mere verification and obviousness.
[25] First, Pfizer grounds
its position on a factual conclusion from Pfizer NOC, a case arising out
of the Patented Medicine Notice of Compliance Regulations, S.O.R./93-133
(NOC Regulations). This Court has repeatedly stated that what I will refer to
as “NOC proceedings” do not operate as res judicata. While Pfizer may be
correct that the factual basis in the NOC proceeding is the same as that in
this action, it does not follow that the evidentiary basis is the same. Factual
findings are derived from the evidence that is before the court in the
particular proceeding.
[26] The trial judge was
aware of the previous NOC proceedings in relation to the '393 Patent and
considered them to be instructive (reasons at para. 18). However, he was not
and could not be bound by the factual determinations in a prior NOC proceeding.
Rather, it was incumbent upon the judge to arrive at his findings on the basis
of the evidence that was before him.
[27] Second, it is clear that
the trial judge properly identified the legal criteria set out in Sanofi
regarding the “obvious to try” issue. The criteria in this respect are
concerned with the solution (or result). Because the '393
Patent is a selection patent, the result to be assessed is the advantage(s) of
amlodipine besylate over amlodipine and its maleate salts. It does not
necessarily follow from the trial judge’s factual finding, that the properties
of the besylate salt could not have been predicted, that there must have been
more than “mere verification.” Parenthetically, I note that, although Pfizer
relies heavily on the term “mere verification”, there is no reference to it in
the trial judge’s analysis.
[28] The pivotal factual
finding that the result of the besylate salt screening (its advantages) was
predictable or obvious to try is found at paragraph 170 of the trial judge’s
reasons where he stated:
I agree in particular
with Dr. Cunningham in his conclusions as set out in paragraph 179 of his
report, Exhibit 17, a person skilled in the art would be motivated to test
sulphonic acid salts in general and would have every reason to test the
besylate salt as this had already been shown to offer advantages over other
salts in terms of stability.
[29] This factual determination is
sufficient to dispose of Pfizer’s argument. However, I also disagree that the
trial judge adopted the findings contained in the U.S. authority. Early in his reasons, the trial judge
noted that the United
States authorities
were not binding and were based on law that may in some respects be different
than Canadian law (reasons at para. 17).
[30] More importantly, it is
readily apparent from his reasons that the trial judge independently arrived at
his conclusion with respect to whether the testing of the besylate salt and the
result was obvious to try. After making that factual finding, he noted that the
U.S. Court of Appeals had reached the same determination. The trial judge’s
observation does not constitute either reliance or adoption. Technically, his
comment in this respect is obiter.
[31] In summary, Pfizer’s
arguments essentially amount to a disguised attempt to challenge factual
determinations by characterizing them as errors of law. Pfizer has not
persuaded me that the trial judge made any palpable and overriding error with
respect to his factual findings. There was an evidentiary basis upon which the
findings could be made. Nor have I been persuaded, for the foregoing reasons,
that the trial judge erred in law.
Alternative Grounds
[32] It is not necessary to
address in detail the trial judge’s alternative grounds for invalidating the
'393 Patent. However, two observations are in order.
[33] In relation to the ground
entitled “Selection Patent” in his reasons, the trial judge expressed
reservation as to whether a category of “selection” patent exists (reasons at
para. 180). He concluded that, if it did, the patent is invalid for this reason
as well. This Court has since released its reasons for judgment in Eli Lilly
Canada Inc., v. Novopharm Limited, 2010 FCA 197 and has determined that the
conditions for a valid selection patent do not constitute an independent basis
upon which to attack the validity of a patent.
[34] Pfizer expressed concern
that the trial judge’s determination pursuant to subsection 53(1) of the Act
was based on an overly broad interpretation of that subsection. I am of the
view that the determination is confined to the unique and particular
circumstances of this matter. It has limited, if any, value as a precedent.
Conclusion
[35] I would dismiss the
appeal with costs to Ratiopharm.
"Carolyn
Layden-Stevenson"
“ I
agree
M. Nadon J.A.”
“I
agree
K. Sharlow”
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