Date:
20110317
Docket:
A-22-10
Citation: 2011 FCA 102
CORAM: NOËL
J.A.
TRUDEL J.A.
MAINVILLE
J.A.
BETWEEN:
PHARMASCIENCE
INC.
Appellant
and
PFIZER CANADA INC., PHARMACIA ATKIEBOLAG
and THE
MINISTER OF HEALTH
Respondents
REASONS FOR
JUDGMENT
NOËL J.A.
[1]
This
is an appeal from a judgment of Heneghan J. of the Federal Court (the
Applications Judge), wherein she granted the application brought by Pfizer
Canada Inc. and Pharmacia Atkiebolag (the respondents) to prohibit the Minister
of Health (the Minister) from issuing a Notice of Compliance (NOC) to
Pharmascience Inc. (the appellant) pursuant to section 6 of the Patented Medicines
(Notice of Compliance) Regulations, SOR/93-133, until the expiry of Canadian
Patent No. 1,339,132 (the ‘132 Patent).
[2]
The
‘132 Patent claims, inter alia, a compound known as latanoprost for use
in the treatment of glaucoma and ocular hypertension. A 50 microgram/ml
ophthalmic solution of latanoprost is marketed in Canada under the name
Xalatan®.
[3]
A
Notice of Allegation (NOA) was served on the respondents on November 2, 2007.
In it, the appellant alleged that the ‘132 Patent was invalid on eleven grounds
including anticipation, lack of utility, and the failure to soundly predict the
“invention”. The appellant also alleged that whether the patent was valid or
not, its version of latanoprost would not infringe the patent.
[4]
On
December 20, 2007, the respondents sought an order prohibiting the Minister
from issuing a NOC to the appellant. Following a three-day hearing, the Applications
Judge held that none of the allegations made in the NOA had been established
and issued the prohibition order. The appellant maintains that in so holding,
the Applications Judge made a number of legal and factual errors.
[5]
For
the reasons which follow, I am of the view that the appeal should be dismissed.
FACTUAL BACKGROUND
The ‘132 Patent
[6]
The
‘132 Patent is entitled “Prostaglandin Derivatives for the Treatment of
Glaucoma or Ocular Hypertension”. It was filed on September 12, 1989 – it thus
falls under the purview of the Patent Act, R.S.C. 1985, c. P-4, as it
read prior to October 1, 1989 – and was issued on July 29, 1997. The patent
addresses certain prostaglandin derivatives and their use in the treatment of
glaucoma or ocular hypertension.
[7]
Prostaglandins
are naturally occurring substances found in human and animal tissues. PGF2α, is a type of prostaglandin that can be
esterified into PGF2α-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
PGF2α-isopropyl ester. Latanoprost is obtained by modifying PGF2α in the following manner (reasons at para. 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. Claim 12 claims a composition and is dependent on claim 1, claim
19 is a compound per se claim that depends on claim 18, and claims 31,
37 and 38 claim various uses. 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-PGF2α -isopropylester.
18.
13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α-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-PGF2α-isopropylester in the
treatment of glaucoma or ocular hypertension.
37. The use of
13,14-dihydro-17-phenyl-18,19,20-trinor- PGF2α-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- PGF2α-isopropyl-ester in the
treatment of glaucoma or ocular hypertension.
[9]
The
promised utility – i.e. the treatment of glaucoma or ocular hypertension
without substantial ocular irritation – is based inter alia on test
results from three animal models and human tests conducted on employees of
Pharmacia Atkiebolag, one of the respondents (‘132 Patent at pp. 18-29).
The eye, glaucoma and
ocular hypertension
[10]
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 conveys nutrients to the
eye and removes waste products and contaminants. The drainage of aqueous humor
assists in avoiding an increase in intraocular pressure.
[11]
An
elevated intraocular pressure is one of the strongest risk factors for
disorders of the eye, including glaucoma and ocular hypertension. Ocular
hypertension consists of an intraocular hypertension without damage to the
optic nerve. Glaucoma is a group of disorders characterized by damage to the
optic nerve that results in a loss of vision if the condition is left
untreated. There is no cure for glaucoma. However, it and ocular hypertension
can be managed by reducing intraocular pressure, which can be achieved with
drugs in one of two ways: production of aqueous humor or increase in the
outflow of aqueous humor. Latanoprost is the first compound which treats
glaucoma by increasing the rate at which aqueous humor is drained from the eye.
[12]
The
successful management of glaucoma by drugs requires a high level of patient
compliance. Therapies with less frequent dosage contribute to a higher level of
patient compliance as does the tolerability of the drug used. According to the
inventors, there were a number of drugs on the market for glaucoma and ocular
hypertension prior to the introduction of latanoprost. However they also had
numerous undesirable effects. Latanoprost was claimed as a new substance which
treats glaucoma and ocular hypertension without causing substantial ocular
irritation.
DECISION OF THE FEDERAL
COURT
[13]
The
Applications Judge began by summarizing the evidence including the expert
testimony of Drs. Mitra, Podos, Prestwich and Spaeth on behalf of the appellant
and Drs. Buys, Fechtner, Stjernschantz, Maxey and Neufeld on behalf of the
respondents. After having
outlined the anatomy of the eye – as just summarized (paras. 10-12) – and
identified the issues as they arise within the framework of the NOC
Regulations, she turned to the construction of the ‘132 Patent.
[14]
Relying
on the principles of claim construction set out by the Supreme Court of Canada
in Whirlpool Corp. v. Camco Inc., 2000 SCC 67, [2000] 2 S.C.R. 1067 and Free
World Trust v. Électro Santé Inc., 2000 SCC 66, [2000] 2 S.C.R. 1024, the
Applications Judge construed claims 12, 19, 31, 37 and 38. She held that the
“claim for use in claim 12 is limited by the reference in claim 1 to the
reduction of intraocular pressure ‘without causing substantial ocular
irritation’” (reasons at para. 62). She construed claim 19 as a compound per
se claim and claims 31, 37 and 38 as claims for the use of the compound in
claim 19 (reasons at paras. 60, 63-68).
[15]
Turning
to the issue of anticipation, the Applications Judge identified the approach
adopted by Rothstein J. in Apotex Inc. v. Sanofi-Synthelabo Canada Inc.,
2008 SCC 61, [2008] 3 S.C.R. 265, as being applicable. She reviewed a number of
documents, including Canadian Patent No. 986,926 (the ‘926 Patent), and found
that none of them disclosed the chemical composition of latanoprost as defined
in the ‘132 Patent (reasons at para. 95).
[16]
With
respect to utility, the Applications Judge found that the ‘132 Patent
demonstrates utility. The test results on animals and humans disclosed in the
patent show that latanoprost reduces intraocular pressure with minimal
irritative side effects (reasons at paras. 143, 145).
[17]
Even
though she found that utility had been demonstrated, the Applications Judge
briefly addressed the issue of sound prediction. She identified the three elements
of the doctrine of sound prediction set out by Binnie J. in Apotex Inc. v.
Wellcome Foundation Ltd., [2002] 4 S.C.R. 153 at para. 70, i.e.
there must be a factual basis for the prediction; the inventor must have as of
the date of the patent application a sound line of reasoning from which the
desired result can be inferred from the factual basis; and there must be proper
disclosure. The Applications Judge held that the evidence adduced by the
respondents supported a finding of sound prediction (reasons at para. 154).
ALLEGED ERRORS
[18]
At
the hearing of the appeal, counsel for the appellant advised that she was no
longer pursuing the argument that the ‘132 Patent was invalid as a selection
patent but that she was pursuing the remaining five arguments set out in her
memorandum of fact and law.
[19]
The
first is that the Applications Judge failed to construe claim 12 and in
particular the phrase “substantial ocular irritation” found in claim 1, on
which claim 12 depends. The appellant submits that had she construed those
words, “it would have been clear that latanoprost was not better than the prior
art PGF2α-isopropyl ester since neither compound resulted in
patients discontinuing therapy in the reported clinical studies” (appellant’s
memorandum at para. 35).
[20]
Second,
the appellant submits that the Applications Judge erred in her assessment of
anticipation in relation to claim 19, a compound per se claim. It
contends that the Applications Judge erroneously required that the prior art
disclose the use of the compound in treating glaucoma. Furthermore, the
appellant submits that the ‘926 Patent discloses the chemical structure of
latanoprost acid and the method of making it. As such, there is both disclosure
and enablement, and the Applications Judge erred in failing to find that claim
19 was anticipated.
[21]
Third,
the appellant submits that all the claims in issue lack utility and that the
Applications Judge’s failure to so find is due to her improper application of
the relevant test. It argues that the ‘132 Patent does not demonstrate the
promised utility, i.e. that latanoprost is a therapeutically more useful
compound than the known intraocular pressure-lowering prostaglandins and does
not cause substantial ocular irritation.
[22]
The
appellant further submits that the Applications Judge failed to correctly apply
the test for sound prediction. It contends that there was no factual basis for
the prediction, that the testing involving cats was not predictive, and that
the limited human testing was insufficient to predict that the general
population would not suffer from ocular irritation. Furthermore, the appellant
argues that there is no disclosure of human data or head to head testing
against the known PGF2α-isopropyl ester to support the claim of less irritation.
[23]
Finally,
the appellant submits that the Applications Judge failed to consider that
claims 19, 31, 37 and 38 are broader than the invention made or disclosed.
ANALYSIS
[24]
Before
turning to the analysis, it is useful to recall that errors of law are
reviewable on a standard of correctness and that factual findings will not be
altered unless the Applications Judge committed a palpable and overriding error
(Housen v. Nikolaisen, 2002 SCC 33, [2002] 2 S.C.R. 235).
[25]
The
first error alleged is that the Applications Judge failed to properly 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 depends. It
is true that the Applications Judge in construing the ‘132 Patent did not
specifically address this phrase. However, when addressing the issue of
utility, she stated that “substantial ocular irritation” in claim 12 “does not
refer to the elimination of all side effects”, thereby rejecting the position
adopted by the appellant as outlined in the affidavit of Dr. Mitra, one of its
experts (reasons at para. 142).
[26]
The appellant on appeal
does not take issue with this finding. It now adopts the opinion expressed by
Dr. Neufeld according to whom “substantial ocular irritation” means “a level of
ocular irritation or ocular discomfort that would cause a patient to stop
taking latanoprost” (appellant’s memorandum at para. 6). This is consistent
with the view expressed by the Applications Judge. Indeed, it is clear from a
reading of the decision as a whole that the Applications Judge adopted the
position of Dr. Neufeld with which the appellant now agrees. As such, no error
can be said to result from the Applications Judge’s reading of claim 12.
[27]
The
second error alleged is that the Applications Judge read a use limitation into
claim 19 when assessing whether the claim was anticipated even though she
construed claim 19 as a compound per se claim. The appellant further
submits that the chemical structure of “latanoprost acid” and the method for
making it were disclosed in the ‘926 Patent. It also submits that the ‘926
Patent discloses that the invention can be esterified to make alkyl esters, of
which isopropyl is one. The appellant thus contends that the invention claimed
in the ‘132 Patent was disclosed and enabled, and therefore anticipated.
[28]
The
Applications Judge made it clear that claim 19 claims a compound per se
(reasons at para. 58). However, the appellant focuses on a phrase in her
anticipation analysis which suggests that latanoprost is a chemical composition
“for the treatment of glaucoma or ocular hypertension” (reasons at para. 95).
As the appellant properly points out, it is claims 31, 37 and 38 that claim
this specific use for the compound in claim 19.
[29]
However,
this does not alter the Applications Judge’s conclusion that the compound
claimed in the ‘926 Patent is not the same as the compound claimed in claim 19
of the ‘132 Patent. The Applications Judge’s finding is supported by the
evidence. It shows that latanoprost acid is distinct from latanoprost. In his
affidavit, Dr. Maxey stated the following (affidavit, appeal book, vol. 2 at p.
601):
43. In order to call a molecule the
“latanoprost free acid” or the “methyl ester of latanoprost” as Dr. Mitra does,
or “the optically active methyl ester of the 13,14-unsaturated version of
latanoprost” as Dr. Prestwich does, one needs to already know the structure of
latanoprost, which is 13,14-dihydro-17-phenyl-18,19,20-trinor PGF2α isopropyl ester. Put another
way, one can only call these molecules ‘latanoprost’ free acid or ‘latanoprost’
methyl ester or “the optically active methyl ester of the 13,14-unsaturated
version of latanoprost” with hindsight. Neither Dr. Mitra nor Dr. Prestwich
opine that 13,14-dihydro-17-phenyl-18,19,20-trinor
PGF2α isopropyl ester
(latanoprost) was previously known.
…
48.
Similarly, Canadian Patent 986,926 (PMS Document #25) does not disclose
latanoprost. Dr. Mitra states that latanoprost “as an acid and as an alkyl
ester (which would include isopropyl ester)” is disclosed. My discussion at
paragraph 43 is equally applicable here. I see no discussion in Document #25
that teaches the compound 13,14-dihydro-17-phenyl-18,19,20-trinor
PGF2α isopropyl ester.
[Footnote omitted]
[30]
Dr.
Neufeld opined in the same direction (affidavit, appeal book, vol. 3 at p.
772):
43. Amongst the numerous compounds
disclosed in Canadian Patent No. 986,926, I cannot find
13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α-IE,
now known as latanoprost. Furthermore, none of the molecules that are disclosed
in Canadian Patent No. 986, 926 are for ophthalmic use. The “therapeutic” use
for the thousands of compounds disclosed in Canadian Patent No. 986,926 is
induction of labour or control of the oestrus cycle, which relates to the
reproductive cycle. Nothing about these uses would lead one skilled in the art
to an ophthalmic use, such as treating glaucoma or ocular hypertension.
44. In paragraph 49 of his affidavit, Dr.
Mitra states that “… latanoprost, as an acid and as an alkyl ester …” was
disclosed in Canadian Patent No. 986,926 as a “therapeutic compound”. Latanoprost
does not exist as an acid nor is it an unspecified alkyl ester. Latanoprost is
13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α-IE. This coumpound is
nowhere disclosed in this patent.
[Emphasis
added]
[31]
Based
on the evidence before her, it was open to the Applications Judge to find that
latanoprost was not anticipated by the ‘926 Patent.
[32]
The
third alleged error relates to utility. The appellant submits that the promise
of the patent – that latanoprost is a therapeutically more useful compound that
the known intraocular pressure-lowering prostaglandins as it does not cause
substantial ocular irritation as did the prior art compound – has not been
demonstrated. Specifically, the Applications Judge erred in finding that
“[l]atanoprost will be useful in the treatment of ocular hypertension or
glaucoma”, because the promise of the ‘132 Patent is that latanoprost is more
useful than the prior known compound.
[33]
However,
the conclusion reached by the Applications Judge is that latanoprost had less
side effects that the prior known compound. Indeed, in her discussion relating
to obviousness, the Applications Judge stated that she preferred the evidence
of Dr. Neufeld and specifically referred to paragraph 46 of his affidavit,
which states (reasons at para. 107):
Dr. Johan W. Stjernschantz and Dr. Bahram
Resul, who were working for Pharmacia, invented a new compound, latanoprost
(13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α-IE),
a compound useful for the treatment of patients with glaucoma or ocular
hypertension. This compound had a better side effect profile than PGF2α-IE, i.e. a compound that had
been previously tested in humans (see Document No. 127). Latanoprost
was shown to cause less ocular irritation and hyperemia.
[Emphasis
added]
[34]
Furthermore,
the Applications Judge stated that the ‘132 Patent “itself shows utility”
(reasons at para. 143). She referred to pages 25 to 29 of the ‘132 Patent,
which disclose test results from three animal models (cat, rabbit and monkey)
and one human model. In each of the animal models (Tables III, IV and V in the
‘132 Patent), latanoprost and PGF2α-ispropyl ester were tested and the results demonstrate that
latanoprost causes no ocular irritation (Table III) and less hyperemia than PGF2α-isopropyl ester (Table IV).
[35]
The
appellant correctly points out that the Applications Judge also referred to page 22d
of the ‘132 Patent as disclosing test results on latanoprost. The results
contained on page 22d do not pertain to latanoprost. However, the error is
immaterial as there was ample evidence – including pages 25 to 29 of the ‘132
Patent – by reference to which the Applications Judge could find that utility
had been demonstrated.
[36]
There
is no basis for the appellant’s further argument that the human testing
involving Pharmacia employees who attested to the fact that latanoprost did not
cause substantial ocular irritation should be discarded because they had “a
vested interest in the outcome” (memorandum of the appellant at para. 14). The
contention that these individuals had an interest in effectively misleading
their employer as to the results of the testing is not rationally defensible.
[37]
The
fourth error alleged by the appellant is that the Applications Judge failed to
correctly apply the test for sound prediction as there was no factual basis for
the prediction. In light of my conclusion that the Applications Judge properly
found that there was utility, there is no need to address the appellant’s
submission on sound prediction. Nevertheless, I am satisfied that the evidence
supports her alternative view that the invention was soundly predicted.
[38]
The
final error is that the Applications Judge failed to find that claims 19, 31,
37 and 38 are broader than the invention made or disclosed. This seems to be a
new argument. The argument at trial, which was addressed by the Applications
Judge in her reasons, was that the claims at issue failed for overbreath
because they did not claim a reduction in hyperemia (reasons at para. 159).
[39]
The
novel issue raised on appeal is that the Applications Judge failed to compare
the invention disclosed to the claims (appellant’s memorandum at para. 54). The
theory behind this argument appears to be that the claim must mirror the
disclosure of the patent. No authority has been cited for this proposition.
[40]
The
Applications Judge referred to Lowell Manufacturing Co. and Maxwell Ltd. v.
Beatty Bros. Ltd. (1962), 41 C.P.R. 18 (Ex. Ct.) for the proposition that
(reasons at para. 156):
[i]f the claims read fairly on
what has been disclosed and illustrated in the specification and drawing, …,
they are not wider than the invention …
[41]
This
statement was endorsed by this Court in Pfizer Canada Inc. v. Minister of
Health, 2007 FCA 209, wherein it made clear that a claim will be considered
overbroad if it asserts a right of exclusive property in something which the
inventor did not actually invent or disclose. No such issue arises here.
[42]
It
has not been shown that the Applications Judge erred in failing to find that
the claims are broader than the invention.
[43]
I
would dismiss the appeal with costs.
“Marc
Noël”
“I
agree
Johanne Trudel J.A.”
“I
agree
Robert M.
Mainville J.A.”
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