Date: 20110816
Docket: A-206-10
Citation: 2011 FCA 236
CORAM: SHARLOW
J.A.
TRUDEL
J.A.
STRATAS
J.A.
BETWEEN:
APOTEX INC.
Appellant
and
PFIZER CANADA INC. and PHARMACIA
ATKIEBOLAG
and
THE MINISTER OF HEALTH
Respondents
REASONS FOR JUDGMENT
TRUDEL J.A.
Introduction
[1]
The
question on this appeal turns on whether Heneghan J. of the Federal Court (the
Applications Judge) erred in her construction of Canadian Patent 1,339,132 (the
‘132 patent or Patent ‘132 or the patent).
[2]
In
a judgment dated April 26, 2010 (2010 FC 447), the Applications Judge granted
Pfizer Canada Inc. and Pharmacia Atkiebolag (together Pfizer) an order
prohibiting the Minister of Health from issuing a Notice of Compliance to
Apotex Inc. (Apotex), pursuant to section C.08.004 of the Food and Drug
Regulations, C.R.C., c. 870, until the expiry of the ‘132 patent in 2014.
[3]
The
‘132 patent claims, inter alia, a compound known as latanoprost used in
the treatment of glaucoma and ocular hypertension. Latanoprost, in the form of
a 50 microgram/ml ophthalmic solution, is sold in Canada under the
name of Xalatan®.
[4]
Apotex
served its Notice of Allegation (NOA) on Pfizer on March 4, 2008, alleging that
each of the claims of the ‘132 patent was invalid on the following grounds: double
patenting, lack of novelty and inventiveness, including anticipation and
obviousness, overbreadth and inutility. Moreover, Apotex asserted that its
generic version of Xalatan®, Apo-Latanoprost, would not infringe Patent ‘132
under the Gillette defence doctrine (appeal book, volume 1, tab 3, at page 69).
Finally, Apotex argued that Patent ‘132 did not meet the conditions for a valid
selection patent (ibidem, at pages 140 and following). At the hearing of
this appeal, all these grounds remained, except for overbreadth and inutility,
which were no longer pursued by Apotex.
[5]
I
need not address all these grounds of invalidity. I agree with Apotex that the
Applications Judge erred in her construction of the promise of the ‘132 patent,
an error which affected the rest of her analysis. As a result, she never fully
considered whether the promised utility was soundly predicted. Having
considered the patent’s factual basis and the evidence as a whole, I conclude
that the ‘132 patent fails to meet the requirements for sound prediction.
Therefore, I would allow this appeal for the reasons that follow.
The Patent
[6]
The
‘132 patent, entitled “Prostaglandin Derivatives for the Treatment of Glaucoma
or Ocular Hypertension” was filed on September 12, 1989. As such, it falls
under the purview of the Patent Act, R.S.C. 1985, c. P-4 (the Act), as
it read prior to October 1, 1989. The patent was issued on July 29, 1997 and
will expire on July 29, 2014.
[7]
The
patent addresses certain prostaglandin derivatives and their use in the
treatment of glaucoma or ocular hypertension. Prostaglandins
are naturally occurring substances found in human and animal tissues. PGF2
, is a type of
prostaglandin that can be esterified into PGF2-isopropyl ester. Latanoprost, the compound
claimed in the ‘132 patent, is a prostaglandin derivative that has the
following chemical formula: 13,14-dihydro-17-phenyl-18,19,20-trinor
PGF2-isopropyl ester. Latanoprost is obtained by
modifying PGF2 in the following manner (reasons for judgment,
at paragraph 6):
i. removing the
last 3 carbons of the omega chain (“18,19,20-trinor”);
ii. attaching a
phenyl ring to carbon 17 (“17-phenyl”);
iii.
changing the double bond to a single bond between carbon 13 and carbon 14
(“13,14-dihydro”); and
iv. esterifying
the carboxylic acid to an isopropyl ester.
[8]
The ‘132 patent contains 38 claims. On appeal, only claims 12, 19,
31, 37 and 38 are at issue. The relevant claims read as follows:
1. A therapeutic
composition for topical treatment of glaucoma or ocular hypertension, containing
a prostaglandin PGA, PGB, PGD, PGE or PGF in an amount sufficient to reduce
intraocular pressure without causing substantial ocular irritation and an
ophthalmologically compatible vehicle, which the omega chain of the
prostaglandin has the formula:
(13)
(14)
(15-24)
C - B -
C -
D -
R2
wherein
C is a carbon atom
(the number is indicated within parenthesis);
B is a single
bond, a double bond or a triple bond;
D is a chain with
1-10 carbon atoms, optionally interrupted by hetero atoms O, S, or N, the
substituents on each carbon atom being H, alkyl groups, lower alkyl groups with
1 - 5 carbon atoms, an oxo functionality or a hydroxyl group;
R2 is a ring structure selected from the group
consisting of phenyl and phenyl having at least one substituent, said
substituent being selected from C1-C5 alkyl groups, C1-C4 alkoxy groups, trifluoromethyl groups, C1-C3aliphatic
acylamino groups, nitro groups, halogen atoms, and phenyl group; or an aromatic
heterocyclic group having 5-6 ring atoms, selected from the group consisting of
thiazol, imidazole, pyrrolidine, thiopene and oxazole; or a cycloalkane or a
cycloalkene with 3-7 carbon atoms in the ring, optionally substituted with
lower alkyl groups with 1-5 carbon atoms.
12. An
ophthalmological composition according to claim 1, wherein the prostaglandin
derivative is 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2-isopro-pylester.
18.
13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2-alkyl-ester, in
which the alkyl group has 1-10 carbon atoms.
19. Compound of
claim 18, wherein the alkyl group is isopropyl.
31. The use of
13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2-isopropylester in
the treatment of glaucoma or ocular hypertension.
37. The use of
13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2-alkyl-ester, in
which the alkyl group has 1-10 carbon atoms for the treatment of glaucoma or
ocular hypertension.
38. The use of
13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2-isopropyl-ester
in the treatment of glaucoma or ocular hypertension.
Glaucoma, Ocular
Hypertension and Latanoprost
[9]
The
eye is a closed sphere that produces a clear fluid called aqueous humor. This
fluid is essential to the functioning of the eye as it not only conveys
nutrients to it, but also removes from it waste products and contaminants. The
drainage of aqueous humor assists in avoiding an increase in intraocular
pressure, thus reducing the risk factor for disorders of the eye, including
glaucoma and ocular hypertension.
[10]
Ocular
hypertension describes an intraocular hypertension without damage to the optic
nerve. Glaucoma describes a group of disorders characterized by damage to the
optic nerve that results in loss of vision if the condition is left untreated.
There is no cure for glaucoma but it, as well as ocular hypertension, can be
managed by reducing intraocular pressure. This is achieved by use of drugs in one
of two ways: reduction in the production of aqueous humor; or, with
latanoprost, increase in the outflow of aqueous humor.
[11]
A
high level of compliance is needed by patients treating their glaucoma with
drugs. Therapies with less frequent doses are preferred because they contribute
to patients’ compliance, as does the tolerability of the drugs used. The
tolerability of the drug is usually measured in terms of side effects, which
may be systemic (occurring throughout the body) or localized (around the eye).
[12]
Prior
to the advent of latanoprost, other drugs were available for the treatment of
glaucoma and ocular hypertension. They, however, caused undesirable effects,
ranging from tingling and hyperaemia to emphysema and death. Latanoprost was
claimed to “reduce intraocular
pressure without causing substantial ocular irritation” (claim 1 of the
‘132 patent).
[13]
According
to Apotex, this claimed utility, correctly construed, means that chronic use
of latanoprost will “reduce intraocular pressure without causing substantial
ocular irritation”: glaucoma is a chronic disease, the management of which
requires chronic treatment.
[14]
The
gist of Apotex’s argument is that at the time of the filing of the ‘132 patent,
the inventors had only conducted single dose studies, yet promising that the
compounds can be used chronically without eliciting unwanted side effects. As a
result, Apotex argues that the ‘132 patent is not based on demonstrated
utility, but rather on a prediction of chronic treatment without substantial
side effects. Because the ‘132 patent fails to disclose a sound line of
reasoning to bridge the gap between the factual basis of the patent (the one dose
studies) and its promise, it must fail. This is the pivot of Apotex’s arguments.
[15]
The
Applications Judge went on to methodically examine the parties’ arguments and
all the invalidity grounds raised by Apotex. In view of my conclusion above and
for ease of reference, I will only refer to the relevant part of her reasons in
my analysis.
Standard of Review and De
Novo Determination
[16]
This
appeal is mostly concerned with the construction of the claims of the ‘132
patent. As claims construction is a matter of law, the standard of review is
that of correctness (Whirlpool Corp. v. Camco Inc., 2000 SCC 67, [2000]
2 S.C.R. 1067, at paragraph 61 [Whirlpool]; Housen v. Nikolaisen,
2002 SCC 33, [2002]
2 S.C.R. 235,
at paragraph 8).
[17]
Like
claims construction, the promise of the patent is also a question of law (Eli
Lilly Canada Inc. v. Novopharm Ltd., 2010 FCA 197 [Eli Lilly]). In
this particular case, the Applications Judge, assisted with expert evidence,
needed to purposively ascertain the promise of the patent “within the context
of the patent as a whole, through the eyes of the person of skill in the art
(POSITA) in relation to the science and information available at the time of
filing” (Eli Lilly, at paragraph 80).
[18]
In
view of my conclusion that the patent is not based on demonstrated utility, it becomes
necessary to determine whether the promised utility of the ‘132 patent was
soundly predicted. Soundness of the prediction is a question of fact (Apotex
Inc. v. Wellcome Foundation Ltd., 2002 SCC 77, [2002] 4 S.C.R. 153, at
paragraph 71 [Wellcome AZT]). Absent an overriding and palpable error,
the Applications Judge’s conclusion shall not be disturbed.
[19]
Here,
having dismissed the “chronic use” construction advanced by Apotex, the
Applications Judge rapidly addressed and dismissed Apotex’s ensuing argument
about the unsoundness of the patent (reasons for judgment, at paragraphs 179 to
186), because in her view, Apotex’s argument was unsupported by its own expert
evidence (ibidem, at paragraph 185). I respectfully disagree. I find
that there was strong and convincing evidence on record supporting Apotex’s
claim for lack of sound prediction.
[20]
As
a result, this Court will have to make some findings of fact. Following the
methodology adopted by Rothstein J. in Apotex Inc. v. Sanofi-Synthelabo
Canada Inc., 2008 SCC 61, [2008] 3 S.C.R. 265, at paragraph
72 [Sanofi], and because the record is complete and the parties have
fully argued the point before us and below, I propose to examine Apotex’s
argument de novo rather than remit the matter to the Applications Judge
for redetermination.
Analysis
A.
Claims Construction
[21]
After
setting up the background of the proceeding, the Applications Judge construed
the patent at paragraphs 64 to 83 of her reasons. As already mentioned, the
parties were agreed that only claims 12, 19, 31, 37 and 38 were relevant to the
disposition of Pfizer’s application. The Applications Judge found no compelling
reason not to construe the claims as she had done in a previous case (Pfizer
Canada Inc. v. Canada (Minister of Health), 2009 FC
1294; aff’d 2011 FCA 102). Pfizer notes
correctly that the construction of the ‘132 patent, as stated by the
Applications Judge in the previous proceeding, was upheld on appeal.
[22]
However,
it does not follow that Apotex, which was not a party to the previous
proceeding, is precluded in this case from asserting a different construction
of the patent based on an issue that was not previously raised. Pfizer does
not say that the point of patent construction raised by Apotex in this case was
in issue in the previous case. Indeed, it is not clear from the reasons of the
Applications Judge in the previous case whether the construction of the ‘132
patent was in dispute at all between the parties. In the appeal of the
previous case, there was a challenge to the correctness of the construction
adopted by the Applications Judge. The issue was whether she failed to
construe claim 12 of the ‘132 patent because she made no finding as to the
meaning of the phrase <substantial ocular irritation> in claim 1 on which
it depended. That point is not in dispute in the present application.
[23]
Coming
back to the Applications Judge’s construction of the patent, with the teachings
of the Supreme Court of Canada in Free World Trust v. Électro Santé Inc.,
2000 SCC 66, [2000] 2 S.C.R. 1024 in mind, she held that claim 19 is
a compound per se claim while claims 31, 37 and 38 are claims for the
use of the compound in claim 19. She also held that claim 12 is limited by the
reference in claim 1 to the reduction of intraocular pressure “without causing
substantial ocular irritation” (reasons for judgment, at paragraphs 74 to 82).
Apotex does not attack the Applications Judge’s approach to claims construction
nor the legal principles she referred to or applied.
[24]
For the
Applications Judge, Apotex’s position that the promise of the patent is chronic
use of the compound amounted to a “mistaken premise” upon which Apotex
wrongly relied for its case. At paragraph 192 of her reasons, she held that
Apotex “was unable to show that its basic premise was sound” and dismissed the
argument. I agree with Apotex that, in so doing, the Applications Judge
overlooked Pfizer’s own evidence that glaucoma, at the time of filing, would
have been known by the POSITA to be a chronic condition that required chronic
treatment.
[25]
Dr.
Fechtner, expert for Pfizer, conceded that when speaking of treatment of
glaucoma, the POSITA would know that one is referring to chronic use (cross-examination
of Dr. Fechtner, appeal book, volume 3, tab 50, at page 1086). When asked whether
the claims 37 and 38 of the patent would contemplate chronic treatment, he answered:
“For me, implicit in treatment of glaucoma or ocular hypertension is chronic
treatment” (cross-examination of Dr. Fechtner, appeal book, volume 3, tab 50,
at page 1086). Dr. Stjernschantz, one of the two inventors of the patent,
concurred that glaucoma, perhaps with the exception of acute glaucoma, was a
chronic disease. He and two other experts for Pfizer also agreed that the use
of a topical treatment to treat glaucoma requires chronic use
(cross-examination of Dr. Stjernschantz, appeal book, volume 3, tab 3, at page
1147; cross-examination of Dr. Neufeld, appeal book, volume 3, tab 54, at page
1196; cross-examination of Dr. Wolff, appeal book, volume 3, tab 55, at page
1240).
[26]
Pfizer
disagrees with this proposed construction which, in its opinion, confuses claim
construction with medical treatment of a disease. For Pfizer, the fact that a
disease requires long term treatment is a matter for physicians and not for
this Court tasked with the determination of claims construction (respondent’s
memorandum, at paragraph 50). At the hearing, Pfizer emphasized that adopting
Apotex’s construction would amount to “reading in” a chronic element into the
claims.
[27]
I
disagree. The POSITA was defined by the Applications Judge as “a medicinal or
organic chemist or a pharmacologist, holding at least a Bachelor’s degree, with
some familiarity with prostaglandins and the ophthalmological field, as well as
a medical doctor specializing in ophthalmology” (reasons for judgment, at
paragraph 137). Defined as such, there is uncontested evidence that the POSITA would
have known that glaucoma is a chronic disease. I see it as an error to construe
the promise of the ‘132 patent without consideration as to the nature of the
disease it purports to treat effectively. This conclusion was expressly drawn
by Dr. Fechtner (cross-examination of Dr. Fechtner, appeal book, volume 3, tab
50, at page 1089):
Q. But do you
realize – we’ve discussed this already – the compounds being analyzed in this
patent were intended to be used chronically?
A. That is the
promise of the patent.
[28]
In
my view, the Applications Judge erred in law in failing to consider the
evidence as a whole in her construction of the promise of the patent. Had she done
so, she would have found that the patent fails for lack of sound prediction.
B. Non-Demonstrated
Utility
[29]
Relying
on several findings of fact, the Applications Judge held that the patent
demonstrated utility as of September 12, 1989 (reasons for judgment, at
paragraphs 167 to 175). Having dismissed Apotex’s chronic use argument, her
findings were informed by her previous construction that the promise of the
patent did not include chronic treatment. As I disagree with the Applications
Judge on this point, I will look at the issue of demonstrated utility and sound
prediction from the perspective that the promise of the patent is chronic use
of the compound for a chronic medical condition.
[30]
Section
2 of the Act requires that the subject matter of a patent be new and useful. The
granting of a patent is dependant upon the disclosure of how the patent intends
to fulfill its promise (Pfizer Canada Inc. v. Canada (Minister of
Health),
2008 FCA 108, [2009] 1 F.C.R. 253, at paragraph
34; Wellcome
AZT, at
paragraph 66).
The general principle is that, as of the date of the filing, a patent must
disclose either an actually achieved result (i.e., prove that it does what it
claims) or a basis for sound
prediction of the result (i.e., show that it is likely to do what it claims). There
is no requirement to prove demonstrated utility in the disclosure of the
patent; so long as the disclosure makes reference to a study demonstrating that
the patent does what it promises to do, this criteria is met (Pfizer Canada
Inc. v. Novopharm Ltd., 2010 FCA 242, at paragraph 90). In our case,
utility would be demonstrated if the patent disclosed studies showing that
latanoprost, when administered on a chronic basis, reduced intraocular pressure
without causing substantial side effects.
[31]
However,
at the time of filing, the uncontested evidence was to the effect that the
inventors had only conducted “single dose” studies on animals and healthy
humans; latanoprost had not been tested on patients with glaucoma or on a
chronic basis. The evidence from experts on both sides also reveals that the ‘132
patent was based on a prediction of utility, i.e., that which was
observed in the single dose study could soundly be predicted to apply to
chronic use (cross-examination of Dr. Fechtner, appeal book, volume 3, tab 50,
at page 1091; cross-examination of Dr. Wolff, appeal book, volume 3, tab 55, at
pages 1240 and 1242; Leibowitz’s affidavit, appeal book, volume 8, tab 69, at
page 3321). Dr. Stjernschantz confirmed that, at the time of filing, the
utility of the patent was not demonstrated (cross-examination of Dr.
Stjernschantz, appeal book, volume 3, tab 53, at pages 1149 and 1154):
Q. I understand.
And by the time of this patent’s filing, which – take my word for it – is
September 1989, you had not tested any of the compounds in the invention so as to
demonstrate that the compounds could treat chronic glaucoma without side
effects in humans?
A. We had not
tested any of the drugs in patients suffering from glaucoma.
Q. Right. And in
so far as the patent claim claims the treatment of people who had, as an
ailment, glaucoma, it was a prediction?
A. Yes. It was a
prediction yes.
[32]
The
evidence leads me to the conclusion that the utility of the ‘132 patent, as of
its filing date, is based not on a demonstration of utility but on a
prediction. The question that must now be answered is whether this prediction
is a sound one. I agree with Apotex that the patent fails for not meeting the
test for sound prediction.
C. Sound Prediction
[33]
The
doctrine of sound prediction seeks
to balance two competing public interests: the desirable early disclosure of
new and useful inventions, even though their utility has not been fully
verified by tests, and the need to ensure that patent rights are not granted in
exchange for misinformation (Sanofi, at paragraph 105; Wellcome AZT,
at paragraph 66). Thus, if a patentee can articulate a sound prediction
as to the utility of his invention, he should be entitled to base a claim on it.
And although patents shall not be granted in exchange for misinformation, mere
speculation or lucky guesses, a sound prediction does not amount to certainty (Wellcome
AZT, at paragraph 69; Monsanto
Co. v. Canada (Commissioner of Patents),
[1979] 2 S.C.R. 1108, at page 8).
[34]
The doctrine of sound prediction has three components, as listed
in Wellcome AZT (at paragraph 70). All must be met for a patent to
survive the test:
1) There must
be factual underpinnings for the prediction;
2) There must
be an articulable and “sound” line of reasoning from which the desired result
can be inferred from the factual basis; and
3) There must
be proper disclosure.
[35]
I
will first deal with the Applications Judge’s finding that Apotex did not meet
its evidentiary burden as to the gap between the factual basis and the promise
of the patent (the “gap issue”). She dismissed Apotex’s argument as follows
(reasons for judgment, at paragraph 185):
At
the hearing, the Respondent alleged that the ‘132 patent failed to address the
gap between the single dose studies found within the patent and the fact that
the treatment of glaucoma or ocular hypertension requires chronic use of
medication, i.e., long-term and usually life-time treatments. None of the
Respondent’s expert made reference to this in their affidavits nor did they
address this factor when speaking about the NOA prior art.
[36]
However,
Dr. Leibowitz, expert for Apotex, precisely addressed the gap issue in his affidavit (appeal book, volume 8, tab
69, at page 3325):
Further, the use
of single dose observations is at odds with the expected daily lifetime use of
the compound. Data derived only from a single dose does not establish a lack of
irritating effect of a compound designed for repeated and prolonged use.
[37]
Moreover,
the gap issue was also addressed by Pfizer’s experts (cross-examination of Dr. Fechtner, appeal
book, volume 3, tab 50, at page 1082; cross-examination of Dr. Wolff, appeal
book, volume 3, tab 55, at page 1241; cross-examination of Dr. Stjernschantz,
appeal book, volume 3, tab 53, at page 1154). There was, therefore, evidence on
both sides on the gap issue. The fact that the Applications Judge ignored or
overlooked this evidence certainly cut short her analysis of sound prediction.
[38]
I will now
turn to the test for sound prediction. The first element of the analysis for
sound prediction is whether there is a factual basis supporting the patent’s
prediction. It bears repetition that the promise of the patent was to treat
glaucoma and intraocular hypertension on a chronic basis without causing substantial
side effects.
[39]
The ‘132
patent discloses studies that tested a number of prostaglandins derivatives for
topical use in the lowering of intraocular pressure. The studies
consisted of putting a single dose of the compounds in the eye of the animal
and human models. The tests were broken down so that the efficacy of the
compounds was tested in monkeys and humans, whereas toxicity (irritation and
hyperaemia) was tested in rabbit and cat models (tables 3 to 6 of the 132
patent; cross-examination of Dr. Stjernschantz, volume 3, tab 53, at pages 1150
and following).
[40]
However, the factual basis supporting the
promise of the patent is clearly not a chronic use study. None of the
studies used multiple doses,
as confirmed by Dr. Neufeld (appeal book, volume 3, tab 54, at page 1197):
Q.
Okay, but the studies in the patent that have been included are not chronic
studies.
A.
Correct.
Q.
And they are all – all of them are one-time uses of the medicines?
A.
Yes.
(See
also cross-examination
of Dr. Fechtner, appeal book, volume 3, tab 50, at page 1088.)
[41]
I
will now turn to
the second element of the test for sound prediction, i.e., whether there is an
articulable and sound line of reasoning between the factual basis and the
patent’s promise.
[42]
The inventor’s
line of reasoning is nowhere to be found in the disclosure of the ‘132 patent.
When asked where, in the patent, was disclosed the line of reasoning, Dr. Wolff
could not point to any excerpt (cross-examination of Dr. Wolff, volume 3, tab
55, at page 1243). Dr. Fechtner’s was led to the same conclusion (cross-examination
of Dr. Fechtner, appeal book, volume 3, tab 50, at page 1091):
Q.
Yes. So can you point me in the patent where the inventor say here’s the
rational from Point A, one time single use, the tables, to Point B, lifelong
chronic use, the claims? Where’s the description of that rational in the
patent?
[…]
A.
I don’t find explicitly what you’re describing.
[43]
At the hearing,
counsel for Pfizer argued that the line of reasoning was to be found in the
studies listed in the “References” section of the patent (Patent ‘132, at pages
30 and 31). Pfizer also took the position that a POSITA, taking the prior art
as a whole, would be able to infer that multiple doses of latanoprost would
give the same results as the single dose studies.
[44]
This position
seems at odds with the concept of disclosure in patent law. In Wellcome AZT,
Justice Binnie stated that if utility is not demonstrated at the time of
filing, the quid pro quo the applicant offers in exchange for the patent
monopoly is a sound prediction of utility (Welcome AZT, at paragraph 70).
As the applicant is the one who will benefit from the monopoly, I am of the
view that only he, and not the authors or inventors of the prior art, can
discharge himself of the obligation of disclosure. Besides, our Court found in Eli
Lilly Canada Inc. v. Apotex Inc., 2009 FCA 97, at
paragraph 17 that a patent that provides no more disclosure than is
available in the prior art does not provide a sound basis for the prediction.
[45]
Moreover, Pfizer
pointed to no evidence on the record supporting its position. None of Pfizer’s
experts bridged the gap between the single doses studies and the claimed
chronic use. Dr. Stjernschantz and Dr. Fechtner limited their comments to the
suitability of cat and rabbit models to test toxicity – the cat eye is more
sensitive than the human eye, which makes it a good model for predicting ocular
discomfort; the rabbit eye has a pronounced tendency to hyperaemic reactions
and makes it a sound model for screening drugs for hyperaemic solution – and
the suitability of monkey models to predict intraocular pressure in human –
their eyes are anatomically and physiologically similar to the human eye
(affidavit of Dr. Stjernschantz, volume 2, tab 40, at page 879; affidavit of
Dr. Fechtner, volume 1, tab 10, at page 381; affidavit of Dr. Neufeld, appeal
book, volume 2, tab 39, at page 831).
[46]
Dr. Wolff also
discussed the line of reasoning between tests conducted on healthy patients and
predictions in glaucomatous patients (affidavit of Dr. Wolff, appeal book,
volume 3, tab 46, at page 969). Pfizer pointed to none of its experts
explaining how and why single dose studies could provide a sound basis for the
prediction that latanoprost, used on a chronic basis, would treat glaucoma and
ocular hypertension without substantial side effects.
[47]
There is
substantial evidence, however, showing that single dose studies may not predict
long-term effects of a compound. Dr. Leibowitz, cited at paragraph 35 supra.,
affirmed that data derived only from a single dose does not establish a lack of
irritating effect of a compound designed for repeated and prolonged use. His view is supported by the
prior art, an excerpt of which reads (appeal book, volume 5, tab 64(35), at
page 2288):
When 0•5 μg PGF2α was given twice daily for two
weeks there was a tendency towards increasing discomfort during the study.
Although the discomfort was mild even at the end of the study, this
observation suggests that side effects may increase with repeated treatment.
[48]
Even Pfizer’s
experts expressed doubts that a sound prediction existed. Dr. Wolff cautioned that
results obtained for a single dose may change under chronic administration (cross-examination
of Dr. Wolff, appeal book, volume 3, tab 55, at page 1241). Dr. Fechtner, who
was of the same opinion, said (cross-examination of Dr. Fechtner, appeal book,
volume 3, tab 50, at page 1089):
Q.
And you’d agree that the onset of adverse effects may not manifest itself after
a single administration. Is that fair?
A.
I would agree with that.
[49]
In light of the
record as a whole, I have not been persuaded by Pfizer that the inventors had,
at the time of filing, an articulable and sound line of reasoning bridging the
gap between the factual basis and the promise of the patent. Therefore, I
conclude that the patent does not meet the second prong of the test for sound
prediction.
[50]
I am mindful of
Pfizer’s position that Apotex’s gap argument could mean that only long term
testing in diseased humans would satisfy the test for sound prediction
(respondent’s memorandum, at paragraph 102). It seems to me, however, that the
information required for sound prediction is case specific and needs to be
established in light of the evidence. Suffice it to conclude that in the
present case, the evidence was insufficient to soundly predict that latanoprost
would fulfill its promise.
[51]
I will now turn to
the third element of the test for sound prediction: proper disclosure. When
examining this element, the Court must determine whether the specification
provides a full, clear and exact description of the nature of the invention and
the manner in which it can be practised (Wellcome AZT, at paragraph 70).
Of course, the disclosure requirement rests on the first two requirements of
the test for sound prediction.
[52]
The amount of
disclosure required to meet the third prong of the test for sound prediction
has been discussed in Eli Lilly Canada Inc. v. Apotex Inc., 2008 FC 142; aff’d on this point in
2009 FCA 97. Justice Noël, writing in appeal, held that when a patent
is based on a sound prediction, the disclosure must include the
prediction (at paragraph 15). Most recently, our Court has held that
"(w)hen utility is based on sound prediction, disclosure of its factual
foundation goes to the essence of the bargain with the public underlying
patentability" (Eli Lilly and Company v. Teva Canada Limited, 2011
FCA 220, at paragraph 51). Pfizer has not persuaded me that there is
sufficient evidence, in the patent and on the record, to support its position.
[53]
I conclude that
Pfizer has not proven, on a balance of probabilities, that Apotex’s allegation
of lack of sound prediction was unjustified.
Conclusion
[54]
The
Applications Judge made an error in her construction of the promise of the
patent which sent her down the wrong path. Had she properly construed the
patent as promising treatment through chronic use of the compounds, she would
have found it invalid for failing to make a sound prediction of utility. As such, I need not look at
the other grounds of invalidity raised by Apotex. Pfizer’s application for a
prohibition order fails on this basis alone.
[55]
For these
reasons, I would allow the appeal
and set aside the judgment of the Federal Court. Rendering the judgment which
ought to have been rendered, I would dismiss the application. I
would also allow Apotex its costs both in this Court and in the Federal Court.
"Johanne
Trudel"
“I
agree
K. Sharlow J.A.”
“I
agree
David Stratas J.A.”
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