Date: 20101125
Dockets: A-129-09
A-135-09
A-139-09
Citation: 2010 FCA 320
CORAM: NOËL
J.A.
PELLETIER J.A.
TRUDEL
J.A.
Docket: A-129-09
BETWEEN:
APOTEX INC.
Appellant
and
LUNDBECK
CANADA INC.
Respondent
and
THE MINISTER OF HEALTH
Respondent
and
H. LUNDBECK A/S
Respondent
Docket: A-135-09
BETWEEN:
MYLAN PHARMACEUTICALS ULC
(formerly
Genpharm ULC)
Appellant
and
LUNDBECK
CANADA INC.
Respondent
and
THE MINISTER OF HEALTH
Respondent
and
H. LUNDBECK A/S
Respondent
Docket: A-139-09
BETWEEN:
COBALT
PHARMACEUTICALS INC.
Appellant
and
LUNDBECK CANADA INC., H. LUNDBECK A/S
and THE MINISTER OF HEALTH
Respondents
REASONS FOR
JUDGMENT
NOËL J.A.
[1]
These
are three appeals from judgments rendered by Harrington J. of the Federal Court
(the Applications Judge) granting the applications brought by Lundbeck Canada
Inc. (the respondent or Lundbeck) to prohibit the Minister of Health (the
Minister) from issuing a Notice of Compliance (NOC) to Apotex Inc. (Apotex), Mylan
Pharmaceuticals ULC, formerly Genpharm ULC (Genpharm) and Cobalt Pharmaceuticals
Inc. (Cobalt) (collectively the appellants) pursuant to section 6 of the Patented
Medicines (Notice of Compliance) Regulations, SOR/93-133, in respect of
each of the appellants’ generic version of the drug containing escitalopram for
use as an antidepressant, until after the expiration of Canadian Patent No.
1,339,452 (the ‘452 patent).
[2]
The
applications before the Federal Court were heard consecutively over a
three-week period from December 1 to December 18, 2008. Although they were
never joined, the Applications Judge opted to dispose of the applications on
the basis of a single set of reasons. The following reasons dispose of the
three appeals.
[3]
The
issue in the three appeals is whether the Applications Judge properly held that
the appellants’ respective allegations of invalidity regarding the ‘452 patent
were not justified and that accordingly they had failed to show that their
generic version of escitalopram would not infringe this patent. For the reasons
which follow, I am of the view that the appeals should be dismissed.
BACKGROUND
[4]
Apotex,
Genpharm and Cobalt filed Notice of Allegations (NOAs) on April 20, January 23 and
June 18, 2007 respectively, making a number of allegations, some common and
some specific to the particular applicant. At the core of each NOA is the
allegation that the ‘452 patent is an invalid selection patent and that the
alleged invention was both obvious and anticipated. Also raised are allegations
that the ‘452 patent lacks utility, fails to soundly predict the invention
(Apotex), provides insufficient disclosures (Apotex, Genpharm and Cobalt) and
is ambiguous (Apotex and Genpharm).
[5]
The
‘452 patent, entitled “Enantiomers of Citalopram and Derivatives Thereof”, was
applied for in June 1989 by the respondent, based on a United Kingdom priority
date of June 1988. The patent was granted in 1997 and expires in 2014. It
claims escitalopram as a useful antidepressant and describes two methods of
obtaining it.
[6]
The
claims at issue are claims 1 and 3, as well as claim 5, insofar as it is dependent
on claim 3:
- 1
-
A compound selected from
substantially pure (+)-1-(3-Dimethylaminopropyl)-1-(4’-fluorophenyl)-1,
3-dihydroisoben-zofuran-5-carbonitrile and non-toxic acid addition salts
thereof.
[…]
- 3
-
A pharmaceutical composition
in unit dosage form useful as an antidepressant comprising a
pharmaceutically-acceptable diluent or adjuvant and, as an active ingredient,
an effective amount of a compound as defined in [c]laim 1.
[…]
- 5
-
A pharmaceutical composition
in unit dosage form, useful as an antidepressant according to claim 3 or 4,
wherein the active ingredient is present in an amount from 0.1 to 100 milligram
per unit dose.
[7]
It
is also useful to set out claim 2:
A compound
of [c]laim 1 being the pamoic acid salt of
(+)-1-(3-dimethylaminopropyl)-1-(4’-fluorophenyl-1, 3-dihydroisobenzofuran-5-carbonitrile.
[8]
The
‘452 patent notes that citalopram was disclosed in the now expired U.S. patent
number 4,136,193 (U.S. patent ‘193). U.S. patent ‘193 disclosed a
formula which might produce a few hundred compounds and specifically claimed
citalopram as a useful antidepressant.
[9]
The
‘452 patent also indicates that a precursor of citalopram, a diol, was
disclosed in U.S. patent number 4,650,884
(U.S. patent ‘884), filed in
August 1985 and entitled “Novel Intermediate and Methods for Its Preparation”.
[10]
The
Applications Judge provided a useful summary of the relevant chemistry with
which the parties do not take issue (Reasons, paras. 22 to 28). It can be seen
from this summary that the chemical compound at issue in this case,
escitalopram, is one of the two enantiomers of citalopram, a racemate.
Escitalopram is also known as (+) citalopram and S-citalopram.
[11]
Carbon-centered
molecules, like the compound at issue, have a three-dimensional structure. If
that carbon atom is bonded to four different atoms or groups of atoms, as is
the case here, the molecule is described as having an asymmetric centre. These
chemical compounds are identical save that they exist in two space-occupying
forms called “enantiomers,” which are non-superimposable mirror images of one
another. Such asymmetric molecules are called chiral, coming from the Greek
word for hand, as a left hand and a right hand are mirror images of each other
but are not superimposable. When a molecule with these characteristics is
synthesized, both enantiomers are produced in equal proportions. This mixture
is called a racemate or a racemic mixture.
[12]
When
a drug is a racemate, although the two enantiomers of the drug have the same
molecular formula, they can interact differently within the human body. Just
like the key and lock analogy, the racemate and each of its enantiomers can
dock in different ways with biomolecules in the body; the consequence being
that they can have pharmacological properties of their own.
[13]
Because
of their identical chemical formula, two unrelated nomenclatures are used to
identify enantiomers. The first nomenclature is based on the direction in which
the enantiomer directs the plane of polarized light. If the plane is turned
clockwise, the enantiomer is identified as (+), d or dextro-rotary; if the
plane is turned counter-clockwise, it is identified as (-), l or levo-rotary.
Escitalopram is the (+) enantiomer of citalopram: it thus directs the plane of
light in a clockwise direction. Because a racemate is a mixture of two enantiomers
that rotate polarized light in opposite directions, it is designated as (+/-).
[14]
The
second nomenclature is the Cahn-Ingold-Prelog convention which specifies
absolute configuration. The substituents around the chiral centre are “sized”
according to their atomic numbers. If the sequence from the largest to the
smallest flows in a clockwise direction, the enantiomer is assigned the R or rectus
designation. Otherwise it is assigned the S or sinister designation. A
racemate is designated (R, S). Escitalopram is the S-enantiomer of citalopram.
[15]
The
above summary is drawn from the expert evidence of Professor Davies who was called
by Lundbeck in the three proceedings and Dr. Newton who was called by both
Genpharm and Cobalt in their respective proceedings (Reasons, para. 28). Seven
other experts were called: Professor Clark testified on behalf of Lundbeck in
all three proceedings; Dr. Keana, Dr. McClelland and Professor Ward appeared on
behalf of Apotex; Professor Chong and Dr. Collicott on behalf of Genpharm; and
Dr. Kissinger on behalf of Cobalt.
[16]
Each
expert advanced views on racemates, the methods to resolve them and the degree
of difficulty which this can present (Reasons, paras. 63 to 72). In the end,
the Applications Judge came to the view that the opinions of Professors Davies
and Clark who testified on behalf of Lundbeck in all three proceedings were to
be preferred.
RELEVANT
LEGAL PROVISIONS
[17]
Given
the date on which the ‘452 patent was applied for, the Patent Act, R.S.C.
1985, c. P-4 (the Patent Act) as it read prior to October 1, 1989,
applies. The term “invention” is defined in section 2 as follows:
|
[…]
any new and useful art, process, machine, manufacture or composition of
matter, or any new and useful improvement in any art, process, machine, manufacture
or composition of matter;
|
Toute réalisation, tout procédé, toute machine, fabrication ou
composition de matières, ainsi que tout perfectionnement de l'un d'eux,
présentant le caractère de la nouveauté et de l'utilité.
|
[18]
Subsection
27(1) regarding disclosure reads:
|
Subject
to this section, any inventor or legal representative of an inventor of an
invention that was
(a) not
known or used by any other person before he invented it,
(b) not described in any patent or in any publication printed in Canada
or in any other country more than two years before presentation of the
petition hereunder mentioned, and
(c) not
in public use or on sale in Canada for more than two years prior to his
application in Canada,
may,
on presentation to the Commissioner of a petition setting out the facts, in
this Act termed the filing of the application, and on compliance with all
other requirements of this Act, obtain a patent granting to him an exclusive
property in the invention.
|
Sous
réserve des autres dispositions du présent article, l’auteur de toute
invention ou le représentant légal de l’auteur d’une invention peut, sur
présentation au commissaire d’une compétition exposant les faits, appelée
dans la présente loi le « dépôt de la demande », et en se conformant
à toutes les autres prescriptions de la présente loi, obtenir un brevet qui
lui accorde l’exclusive propriété d’une invention qui n’était pas :
a) connue ou utilisée par une autre
personne avant que lui-même l’ait faite;
b) décrite dans un brevet ou dans une
publication imprimée au Canada ou dans tout autre pays plus de deux ans avant
la présentation de la pétition ci-après mentionnée;
c) en usage public ou en vente au Canada
plus de deux ans avant le dépôt de sa demande au Canada.
|
[19]
Subsection
34(1) concerning the specification reads as follows:
|
An application shall in the
specification of the invention
(a) correctly
and fully describe the invention and its operation or use as contemplated by
the inventor;
(b) set out clearly the various steps in a process, or the method
of constructing, making, compounding or using a machine, manufacture or
composition of matter, in such full, clear, concise and exact terms as to
enable any person skilled in the art or science to which it pertains, or with
which it is mostly closely connected, to make, construct, compound or use it;
…
|
Dans le mémoire descriptif, le
demandeur :
a) décrit d’une façon exacte et complète
l’invention et son application ou exploitation, telles que les a conçues
l’inventeur;
b) expose clairement les diverses phases
d’un procédé, ou le mode de construction, de confection, de composition ou
d’utilisation d’une machine, d’un objet manufacturé ou d’un composé de
matières, dans des termes complets, clairs, concis et exacts qui permettent à
toute personne versée dans l’art ou la science dont relève l’invention, ou
dans l’art ou la science qui s’en rapproche le plus, de confectionner,
construire, composer ou utiliser l’objet de l’invention;
…
|
THE FEDERAL
COURT DECISION
[20]
Although
seized with distinct applications, the Applications Judge opted to issue one
set of reasons. He explained that counsel for the appellants were invited to
attend all three hearings, that memoranda of fact and law in all three
applications were exchanged and that the commonality of the applications
greatly surpassed their distinctiveness (Reasons, para. 20). He added that the
relevant distinctions would be made in the course of his reasons (Reasons,
para. 21).
[21]
The
Applications Judge noted at the beginning of his analysis that patent
construction was at the heart of the dispute and outlined the applicable
principles as set out by the Supreme Court in Free World Trust v. Électro
Santé Inc., 2000 SCC 66, [2000] 2 S.C.R. 1024 [Free World Trust] and
Whirlpool Corp. v. Camco Inc., 2000 SCC 67, [2000] 2 S.C.R. 1067.
[22]
According
to the Applications Judge, the invention disclosed in the ‘452 patent relates
to the two novel enantiomers of citalopram including their pharmaceutically
acceptable salts and their use as an antidepressant. The ‘452 patent also notes
that previous attempts at resolving citalopram, which the patent states were
disclosed in the U.S. patent ‘193, had failed and that it was discovered that a
precursor of citalopram, a diol disclosed in U.S. patent ‘884, could be resolved
into its enantiomers and then converted to the enantiomers of citalopram in a
stereoselective way. The ‘452 patent describes two methods to obtain
escitalopram (Reasons, para. 41).
[23]
With
respect to the selection patent issue, the question was whether escitalopram
had a special or unexpected advantage over citalopram (Reasons, para. 37). The
Applications Judge found that escitalopram was at best 1.6 times more potent
than citalopram. This was not sufficiently unexpected to serve as the
foundation for a selection patent “[s]ince it was well within the
realm of possibility that more, and indeed sometimes all, of the desired
biological activity of a racemate might rest within one enantiomer rather than
in the other” (Reasons, para. 43). He thus concluded that if the ‘452 patent was
a selection patent, it was invalid.
[24]
However,
the Applications Judge held that the ‘452 patent was not a selection patent. He
found instead that it was a patent for a new substance: substantially pure
escitalopram. He reached that conclusion based on the fact that this particular
compound was not disclosed let alone claimed in either U.S. patents ‘193 or
‘884 (Reasons, para. 42). In coming to this conclusion, the Applications Judge dismissed
the argument that a patent for a racemate automatically discloses and claims
the two enantiomers (Reasons, para. 47).
[25]
With
respect to anticipation, the Applications Judge after reviewing the evidence
held that the documents put into evidence by the appellants including the prior
patents did not disclose escitalopram as a useful antidepressant and could not
therefore form the basis for an allegation of anticipation by prior disclosure.
Although it was known to the skilled addressee that within citalopram were two
enantiomers, and that it might not be a surprise that one might be more potent
than the other, one would not know the qualities of the two enantiomers without
separating and testing them (Reasons, paras. 50 to 52).
[26]
Turning
to obviousness, the Applications Judge applied the four-step approach
identified by the Supreme Court in Apotex Inc. v. Sanofi-Synthelabo Canada
Inc., 2008 SCC 61, [2008] 3 S.C.R. 265 [Sanofi]. First, he found
that the skilled addressee was a “team centered around a medicinal chemist who
had access to and makes use of others with different skill sets such as
analytical chemists and psychiatrists” and that “theoretical knowledge of, and
practical experience in, the methods of resolving racemate were essential”
(Reasons, paras. 36 and 53 to 58).
[27]
Dealing
with the second step, the Applications Judge found that the construction of the
relevant claims posed no difficulty, i.e. claim 1 was for substantially
pure escitalopram and non-toxic additional salts thereof, claim 3 was for a
chemical composition in unit dosage form useful as an antidepressant, and claim
5 was for a unit dosage form wherein the active ingredient ranged from 0.1 to
100 milligrams per unit dose. He noted that the ‘452 patent did not claim that
escitalopram was better than citalopram (Reasons, para. 59).
[28]
As to
the difference between the prior art and the inventive concept underlying the
‘452 patent, the Applications Judge found that the prior art disclosed
citalopram to be useful as an antidepressant, but that it neither disclosed its
two enantiomers nor predicted that either would be useful as an antidepressant.
He held that the inventive step was the resolution of citalopram in sufficient
quantity to permit the testing disclosed in the patent; without it, it was
impossible to determine the usefulness of the enantiomers (Reasons, para. 60).
[29]
Turning
to the fourth step – i.e. whether the claimed invention was obvious to
the skilled addressee – the Applications Judge after reviewing the expert
testimony considered the methods for resolving citalopram available in 1988,
the route taken by Lundbeck to resolve citalopram and the allegation that the
prior art disclosed the resolution of citalopram (Reasons, paras. 63 to 74). He
first noted that motivation is not instructive in this case (Reasons, paras. 79
to 83). Concerning the resolution of citalopram, or of its precursor (the diol
which is a racemate), the Applications Judge described the two methods
available to resolve citalopram at the claim date: the classical method of
fractional crystallization and chiral high pressure liquid chromatography
(HPLC) (Reasons, paras. 84 to 88). The Applications Judge later referred to
Lundbeck’s eight-year quest to resolve citalopram (Reasons, paras. 90 to 102). He
found that it was not obvious to try to resolve citalopram and that in any
event, it was certainly not obvious that what was being tried would work
(Reasons, para. 103).
[30]
The
Applications Judge went on to hold that an inventive step was required to
resolve citalopram with the result that the allegation of obviousness was not
made out (Reasons, para. 124).
[31]
The
Applications Judge then addressed Genpharm’s contention that escitalopram was
anticipated on the theory that the body resolves citalopram by itself into the
two enantiomers. According to Genpharm, the instruction to ingest citalopram in
U.S. patents ‘193 and ‘884 results
in the production of escitalopram in the body. Genpharm made this proposition
on the basis of the decision of the House of Lords in Merrell Dow
Pharmaceuticals Inc. v. HN Norton and Co. Ltd., [1995] UKHL 14, [1996] RPC
76 [Merrell Dow] (Reasons, paras. 125 to 128).
[32]
The
Applications Judge distinguished Merrell Dow and held that Genpharm’s
contention that the body resolves citalopram into substantially pure
escitalopram was based on conjecture (Reasons, para. 129).
[33]
The
Applications Judge then dealt with Genpharm’s allegation that claim 1 was
ambiguous because it did not define what it meant by “substantially pure
escitalopram”. The Applications Judge found no ambiguity since the examples
given showed purity in excess of 99%; one expert asserted that “substantially
pure” would mean at least 95% since a standard method only detects impurities
if they are present at a level of at least 5% (Reasons, para. 130). The
Applications Judge also dismissed Apotex’s suggestion that the +/- nomenclature
used is ambiguous because different solvents may rotate light in a different
way thus altering the +/- designation. He pointed out that the solvents to be
used were fully described in the patent (Reasons, para. 131).
[34]
The
Applications Judge also dismissed Apotex’s argument that the ‘452 patent did
not offer a sound prediction of utility because it was based on studies
conducted on rodents. According to the Applications Judge the testing done on
rodents, which was the same as had been done for citalopram, soundly predicted
that escitalopram would be useful as an antidepressant in humans. The
Applications Judge concluded that “[u]sefulness was promised, usefulness was
predicted and usefulness was delivered” (Reasons, para. 134).
[35]
Finally,
the Applications Judge dismissed Apotex’s contention that escitalopram lacked
utility on the basis that the pamoic salt of escitalopram in claim 2 was toxic.
Relying on Burton Parsons Chemicals, Inc. v. Hewlett-Packard (Canada) Ltd., [1976] 1 S.C.R. 555, [Burton
Parsons], he held that the skilled addressee would not use a toxic salt
(Reasons, para. 139).
ALLEGED ERRORS
Issues common to all
three appellants
The ‘452 patent is an
invalid selection patent
[36]
All
three appellants submit that the ‘452 patent is an invalid selection patent.
They argue that the ‘452 patent is a selection because escitalopram was
disclosed in U.S. patent ‘193 which
claimed citalopram and its use as an antidepressant. Although expressed in a
different way, both Apotex and Genpharm submit that the Applications Judge
misapprehended and misapplied the law of selection patents by requiring a prior
enabling disclosure or claim for escitalopram in order to characterize the ‘452
patent as a selection patent.
[37]
The
appellants submit, relying primarily on the decision of the Supreme Court in Sanofi,
that courts have treated patents for enantiomers as selection patents even
though the enantiomers were not anticipated. As well, they refer to the
decision of this Court in Pfizer Canada Inc. v. Canada
(Minister of Health), 2008 FCA 108 [Pfizer] to show that patents claiming an
enantiomer of a previously disclosed racemate have been held to be selection
patents. The decisions of the Federal Court in Janssen-Ortho
Inc. v. Novapharm Ltd., 2004 FC 1631 [Janssen-Ortho I]
and Janssen-Ortho Inc. v. Novapharm Ltd., 2006 FC 1234 [Janssen-Ortho
II] are also referred to.
[38]
Genpharm
for its part emphasizes the fact that the ‘452 patent describes escitalopram as
a “surprising discovery”. According to Genpharm, the “surprise” is the “special
quality” that would validate escitalopram as a selection from citalopram.
[39]
Apotex
argues that the Applications Judge erred in construing the claims contained in U.S. patent ‘193 from the
perspective of a patent lawyer. By observing that it would be unwise to draft
U.S. patent ‘193 so as to include untested compounds because to do so would
leave the patent open to an overclaim attack, the Applications Judge took the
perspective of the patent draftperson instead of the person of ordinary skill
in the art and made inquiries which are not permissible when construing the
patent.
[40]
Apotex
contends that by describing the subject matter of U.S. patent ‘193 in terms of
a chemical formula without reference to optical information, the draftsperson
intended to encompass all compounds having the same chemical formula: the
racemate, R-citalopram and S-citalopram. It follows that U.S. patent ‘193 discloses
and claims escitalopram.
Anticipation
[41]
All
three appellants argue that escitalopram was anticipated by U.S. patent ‘193. Apotex
alleges that escitalopram is formed “always”, “inevitably” and “with no
possibility of error” upon making citalopram and that the Applications Judge
found as such when he noted that anyone making escitalopram would infringe on
U.S. patent ‘193 (Reasons, para. 83). Genpharm also relies on this passage.
[42]
Cobalt
submits that the Applications Judge’s finding that U.S. patent ‘193 did not
disclose the enantiomers of citalopram is inconsistent with his finding that an
undergraduate student in organic chemistry would have known that citalopram was
made up of two enantiomers. Since the person skilled in the art would be
reading with a mind willing to understand the patent, Cobalt alleges that U.S. patents ‘193 and ‘884
disclosed and enabled both enantiomers of citalopram.
[43]
Genpharm
contends that escitalopram was anticipated because both U.S. patents ‘193 and ‘884
provided instruction to ingest citalopram which, if followed, would lead to the
production of substantially pure escitalopram in the body. Genpharm submits
that the Applications Judge erred in rejecting the evidence adduced on this
point as “outright conjecture” without analyzing it.
Issues common to
Genpharm and Cobalt
Obviousness
[44]
With
respect to obviousness, Genpharm submits that there was no difference between
the state of the art and the ‘452 patent. In particular, Genpharm contends that
since U.S. patents ‘193 and ‘884
disclosed to the person skilled in the art citalopram and its two enantiomers
and, as their usefulness as an antidepressant was known, the ‘452 patent
contributes nothing to the existing body of knowledge. In any event, it was
more or less evident that what was being tried ought to work.
[45]
Genpharm
further alleges that the Applications Judge erred in assuming that 100
milligrams of escitalopram were required for testing. With respect to the
resolution of citalopram using chiral HPLC, Genpharm submits that the
Applications Judge made a palpable and overriding error in concluding that
analytical columns could not have produced sufficient material for detection
and for the biological testing required by the ‘452 patent. Genpharm also
submits that it would have been obvious in 1988 to use the intermediate diol,
disclosed in U.S. patent ‘884, to obtain
substantially pure escitalopram.
[46]
With
respect to the Applications Judge’s finding that the experts were operating
with hindsight, Genpharm submits that the Applications Judge failed to
distinguish between inevitable and impermissible hindsight. Genpharm further
alleges that, due to the U.S. Food and Drug Administration 1987 Guidelines
(1987 FDA Guidelines), drug companies were motivated to resolve racemates so as
to obtain information on the properties of the enantiomers. Finally, Genpharm
submits that Dr. Bøgesø, the co-inventor of citalopram, had built-in biases
which prevented him from quickly resolving citalopram; the person skilled in
the art would not have such biases.
[47]
Cobalt
also submits that it was obvious for Lundbeck to resolve citalopram because
citalopram and its enantiomers were known to the person skilled in the art as
was their use as an antidepressant. It would therefore have been self-evident
to Lundbeck to pursue escitalopram and it had a fair expectation of success.
Procedural fairness
and inadequacy of reasons
[48]
Genpharm
and Cobalt allege that the Applications Judge erred in using evidence that was
not led in their respective proceeding and in issuing one set of reasons for
three different proceedings.
[49]
Genpharm
contends that the Applications Judge’s reasons do not adequately identify the
specific findings with respect to Genpharm regarding anticipation and
obviousness. According to Genpharm, this makes “meaningful review impossible
and prevents [it] from properly arguing its appeal” (Genpharm’s memorandum of
fact and law, para. 48).
[50]
Cobalt
further argues that since Lundbeck had access to the documents filed in all
three proceedings and made submissions comparing the evidence, Lundbeck had a
tactical advantage that was prejudicial to it.
Issues specific to
Apotex
Sound prediction
[51]
Apotex
argues that the utility of escitalopram was not soundly predicted. In
particular, there was “nothing in the ‘452 patent to correlate the ability of
citalopram to cause changes in mouse motor function and rat brain-cell effects
with its clinical antidepressant effect in humans” (Apotex’s memorandum of fact
and law, para. 68). Apotex contends that without this correlative information,
there can be no factual basis for sound prediction.
[52]
Apotex
also contends that the ‘452 patent lacks utility because it covers a toxic
pamoate salt which Lundbeck admitted is toxic in a 2004 patent application.
Further, Apotex submits that the Applications Judge erred in construing claim 1
of the ‘452 patent as excluding such salt because it would be obvious to a
person skilled in the art not to use toxic salt. According to Apotex, the
Applications Judge’s task was to determine how the person skilled in the art
would interpret the words of claim 1 – “non-toxic acid addition salts” – at the
date of issue of the ‘452 patent. Apotex submits that the Applications Judge
erred in his construction of claim 1.
Ambiguity
[53]
Apotex
submits that the ‘452 patent does not teach the person skilled in the art how
to use the solvents to obtain escitalopram. Since there was no such indication,
it cannot be said that the patent was defined in “full, clear, concise and
exact” terms (section 34 of the Patent Act).
Insufficiency of disclosure
[54]
Finally,
Apotex submits that the disclosure in the ‘452 patent is insufficient for
laying a false trail regarding human administration of escitalopram and that
the Applications Judge “erroneously understood Apotex’s allegation to be made
pursuant to section 53 of the Patent Act” rather than section 34 (Apotex’s
memorandum of fact and law, para. 90). Apotex contends that had the proper
inquiry been made, the allegation of insufficiency would have been justified.
ANALYSIS AND DECISION
[55]
Before
embarking on the analysis, it is useful to recall that questions of law are to
be ascertained on a standard of correctness and that factual findings cannot be
reversed absent a palpable and overriding error (Housen v. Nikolaisen,
2002 SCC 33, [2002] 2 S.C.R. 235). The identification of the legal requirements
for the existence of a selection patent as well as the construction of the
relevant claims in the patents considered by the Applications Judge give rise
to questions of law. The remaining issues are for the most part factual.
[56]
The
appellants essentially reiterate on appeal the arguments which they made before
the Applications Judge. The reasons which follow address most of these issues.
With respect to those that are not addressed, I endorse the reasons of the
Applications Judge in disposing of them.
Selection patent
[57]
The
selection patent issue, which is central to each of the appellants’ case, presents
itself in simple terms: the appellants maintain that the ‘452 patent is a
selection patent and as the Applications Judge found that the selected compound
had no special advantage, the patent is invalid.
[58]
The
Applications Judge held that the ‘452 patent was not a selection patent because,
in his view, escitalopram was an original compound which was not selected from a
previously patented compound. He therefore conducted his analysis on the basis
that the ‘452 patent was an ordinary patent for an original compound and as he
found this compound to be both novel and useful (see the definition of
“invention” in section 2 of the Patent Act), he held the patent to be
valid. At the same time, he made it clear that escitalopram’s claimed
usefulness was no greater than citalopram’s and that therefore the invention,
as claimed, had no special advantage over citalopram.
[59]
The
question whether the ‘452 patent is a “selection patent” depends on the legal
meaning to be given to these words. The term “selection patent” is not found in
the Patent Act. However, the Supreme Court in Sanofi held that a
system of genus and selection patents is acceptable in principle under the Patent
Act, on the line of authority stemming from in I.
G. Farbenindustrie A. G.’s Patents (1930), 47 R.P.C. 289 (Ch.
D.) [Farbenindustrie]. The Supreme Court refers to that case to circumscribe what
is to be considered as a selection patent (Sanofi, para. 9):
The locus
classicus describing selection patents is the decision of Maugham J. in [Farbenindustrie].
At p. 321, he explained that in the field of chemical patents (which would of
course include pharmaceutical compounds), there are often two “sharply divided
classes”. The first class of patents, which he called originating patents, is
based on an originating invention, namely, the discovery of a new reaction or a
new compound. The second class comprises patents based on a selection of
compounds from those described in general terms and claimed in the originating
patent. Maugham J. cautioned that the selected compounds cannot have been
made before, or the selection patent “would fail for want of novelty”. But if
the selected compound is “novel” and “possess[es] a special property of an
unexpected character”, the required “inventive” step would be satisfied (p.
321). At p. 322, Maugham J. stated that a selection patent “does not in its
nature differ from any other patent”.
[My
emphasis]
[60]
In
accepting that a system of genus and selection patents was acceptable under
Canadian law, the Supreme Court explained that its application was consistent
with the Patent Act (Sanofi, para. 31):
Section
27(1) of the Act requires as a condition for obtaining a patent that the
invention was not “known or used” and was not “described” in any patent or any
publication more than two years before the patent application was filed. In the
context of genus and selection patents, in E. I. Du Pont de Nemours &
Co. (Witsiepe’s) Application, [1982] F.S.R. 303 (H.L.), Lord Wilberforce
stated, at p. 311:
It is the
absence of the discovery of the special advantages, as well as the fact of
non-making, that makes it possible for such persons to make an invention
related to a member of the class.
The compound
made for the selection patent was only soundly predicted at the time of the
genus patent. It was not made and its special advantages were not known. It is
for those reasons that a patent should not be denied to the inventor who made
and discovered the special advantages of the selection compound for the first
time.
[61]
It
is apparent from the foregoing that a selection patent must be preceded by a
prior patent – referred to as a genus or originating patent – which, in the
words of Maugham J. in Farbenindustrie, describes in general terms and
claims compounds from which a selection is made. That the selection is made
from compounds generally described and claimed in a prior patent does not
necessarily mean that the selected compound is anticipated (Sanofi, para.
19). So long as the selected compound is new – in that it has never been made –
and has a special advantage that was not previously known and that is peculiar
to it, patent protection may be available (Sanofi, paras. 10 and 31). However,
a definitive conclusion cannot be reached absent a complete analysis (Eli
Lilly Canada Inc. v. Novopharm Limited, 2010 FCA 197, paras. 27 to 33 [Eli
Lilly]). In this respect, it is worth repeating that a selection patent
does not differ from any other patent (Sanofi, para. 9).
[62]
Against
this background, the first question which has to be answered is whether U.S. patents ‘193 and ‘884,
together or singly, describe in general terms and claim compounds from which
escitalopram was selected. In this respect, the recent decision of this Court
in Eli Lilly on which the parties made supplemental submissions is of limited
assistance since it was accepted that the compound in issue in that case had
been selected from a previously patented class of compounds (Eli Lilly,
para. 7).
[63]
The Applications Judge answered this question in the
negative. In particular, he found that U.S.
patent ‘193 claims citalopram and that this claim did not encompass
escitalopram. Apotex made the point that escitalopram was nevertheless within
the claim because the subject matter of that patent was described in terms of a
chemical formula without optical information distinguishing the racemate from
the enantiomers.
[64]
However,
the Applications Judge held that the person skilled in the art would have read
the formula, as of the claim date, as referring to the compound produced by the
formula, i.e. the racemate, and nothing else. He came to this conclusion
because no stereochemical information was provided. Given this, he held that
the skilled addressee would not have read U.S. patent ‘193 as claiming anything
other than the racemate (see Professor Davies’ affidavit at para. 85, A-129-09
Appeal Book, Vol. 4, p. 934; A-135-09 Appeal Book, Vol. 4, p. 1099; A-139-09
Appeal Book, Vol. 4, p. 1337).
[65]
In so holding, the Applications Judge acknowledged that
citalopram’s chemical structure – and the chemical formula reflecting it –
reveals the existence of the enantiomers. However, he rejected the argument
that this in itself was sufficient to read U.S.
patent ‘193 as claiming the enantiomers. In particular, he rejected the submission that Sanofi
is authority for the proposition that a claim for a racemate is ipso facto
a claim for its two enantiomers (Reasons, para. 47).
[66]
I
can detect no error in this regard. Contrary to what is asserted, the Supreme
Court in Sanofi did not hold that a claim for a racemate automatically
includes a claim for its enantiomers. The conclusion in Sanofi that the
genus patent also claimed the enantiomers is based on claims 1 and 14 thereof
which specifically claimed the racemate and the two enantiomers (Sanofi,
paras. 101 and 103).
[67]
The
appellants made the further argument that the decision of this Court in Pfizer
shows that a patent claiming an enantiomer of a previously disclosed racemate
can be viewed as a selection patent. No doubt that is so. However, this depends
on the particularities of the patents in issue. In Pfizer, the patent
labeled as a selection patent (the ‘546 patent) states that the enantiomer in
question was among compounds previously claimed in the prior (i.e.
genus) patent (Pfizer, para. 47). No such statement appears in the ‘452
patent.
[68]
With
respect to the decision of the Federal Court in Janssen-Ortho II, it is
significant that Hughes J., who heard the infringement action, did not deal
with the patent in issue in that case as a selection patent even though the
relevant claim was for an enantiomer of a previously disclosed racemate. In so
doing, he declined to follow the approach of Mosley J. in Janssen-Ortho I
who treated the same patent as a selection patent in the context of an earlier
NOC proceeding. However, Mosley J. held the patent to be a selection patent only
after finding that the knowledge required to separate the two enantiomers was
common to the person skilled in the art (Janssen-Ortho I, para. 53), a
finding that was not shared by Hughes J. on the evidence in the infringement
action (Janssen-Ortho II, para. 104).
[69]
Apotex
further submits that the Applications Judge erred in making the existence of a
selection patent dependent on specific disclosure or claim of the selected
compound in a prior patent. The decision of the Federal Court, Trial Division
in Pfizer Canada Inc. v. Apotex Inc. (1997), 77 C.P.R. (3d) 547, page
556 is relied upon. With respect, the Applications Judge did no such thing. A
selection patent, by definition, is directed at a compound which comes within
those generally described and claimed in a prior patent. What the Applications
Judge found is that escitalopram did not come within such a description because
it was not amongst those previously described and claimed.
[70]
In
construing the claims of U.S. patent ‘193, the
Applications Judge noted that it was known at the relevant time that some
enantiomers are toxic and that escitalopram’s utility could not be ascertained
without first resolving citalopram, which had yet to be done. After pointing
out that one who overclaims stands to loose everything, he concluded that the
skilled person would not have read the relevant claims as extending to the
enantiomers (Reasons, para. 48):
… If to
claim a racemate useful in the treatment of depression is to claim the same
usefulness for each of the two enantiomers then in such circumstances the
inventor would have overclaimed and lost everything. …
[71]
The
only attack of significance against this reasoning is Apotex’s contention that
in so holding the Applications Judge did not construe the claims from the
perspective of the person skilled in the art, but from that of a patent agent
or lawyer concerned that it would be imprudent to claim the two enantiomers.
[72]
The
criticism is justified. A claim should not be construed with an eye to issues
of validity or infringement. However, if one moves away from the perspective of
the draftsperson concerned with issues of validity, it remains that the person
skilled in the art would not read the claim as extending to compounds which
were not known to have the promised utility. The Applications Judge having
found as a fact that it was impossible to know at the claim date which, if either,
of the two enantiomers of the racemate would be useful in treating depression,
read the claim as not extending beyond the compound which was known to achieve
the promised result and which was specifically claimed for that purpose, i.e.
the racemate. Although the appellants take issue with the finding which
underlies this conclusion, it was open to the Applications Judge on the record
before him (see Dr. Bøgesø’s affidavit at para. 24, A-129-09 Appeal Book, Vol. 2,
p. 245; A-135-09 Appeal Book, Vol. 2, p. 202; A-139-09 Appeal Book, Vol. 4, p.
1054; see also Professor Clark’s affidavit, A-129-09 Appeal Book, Vol. 3, p.
513; A-135-09 Appeal Book, Vol. 3, p. 464; A-139-09 Appeal Book, Vol. 5, p.
1492).
[73]
Genpharm
made the further argument that the ‘452 patent was framed by the inventor as a
selection patent and therefore should be treated as such. In this respect,
Genpharm points to wording which appears under the heading “Summary of
invention” as follows: “… it was shown to our surprise that almost all [the
activity] resided in [escitalopram]”. The Applications Judge qualified these
words as “puffery” after noting that no promise is made that escitalopram is
better than citalopram (Reasons, para. 59).
[74]
Genpharm’s
argument on this point appears to be that since a selection patent must claim a
particular advantage described as a “surprise”, the claim to a surprising
result supports the view that the patent in issue is a selection patent.
However, it remains that the surprise must be in relation to an advantage over
a previously patented compound.
[75]
In
the present case, it does not follow from the statement “… to our surprise …
almost [all the activity] resided in [escitalopram]” that the compound is
better than citalopram as an antidepressant. This explains why nowhere is it
asserted in the patent that escitalopram is superior to citalopram. Indeed, the
evidence shows that as of the claim date and up to 1992, Dr. Bøgesø, the
co-inventor,
was of the
view that citalopram and escitalopram were equipotent (see the article
published by Dr. Bøgesø
in 1992, A-135-09 Appeal Book, Vol. 24, p. 7562). In this respect, the
Applications Judge twice noted in the course of his judgment that it was only
post the ‘452 patent that escitalopram was found to be more potent than citalopram
(Reasons, paras. 50 and 133). It is clear that no special advantage is claimed
in express terms in the ‘452 patent and it is equally clear that no such claim can
be inferred from the statement relied upon by Genpharm.
[76]
In
further support of their contention that escitalopram is a selection patent, Apotex
and Genpharm seized on a passage from the reasons of the Applications Judge
that appears at first blush to be at odds with his analysis as a whole. In considering
the degree of motivation to come up with the invention, the Applications Judge
stated (Reasons, para. 83):
There is
also evidence from Dr. Newton in the Genpharm and Cobalt applications that
pharmaceutical companies were not particularly interested in resolving
racemates which were covered by a patent issued to a competitor. There was no
bonhomie about this. Not only would the patentee likely have a head start on
resolving the racemate, but at best one would end up in cross licensing
agreements. If a competitor produced escitalopram, it probably could not use it
because it infringed the citalopram patent. On the other hand, Lundbeck
could not use escitalopram. Research and development may well have been
directed to other molecules as suggested by Professor Davies. Suffice it to say
that I do not consider the evidence respecting motivation helpful in
considering whether the invention of escitalopram was obvious.
[Emphasis
by the appellants]
[77]
Apotex
and Genpharm both suggest that this should be read as a finding that the ‘452
patent did infringe one or the other U.S. patents or both, which can only mean that
escitalopram had been previously disclosed and claimed. In my view, such a
finding would run counter to the analysis and make the reasons incoherent.
[78]
While
the words could have been better chosen, the Applications Judge was simply saying
that competitors were not motivated to pursue the resolution of citalopram
because of the concern that producing escitalopram might infringe the
citalopram patent. When considered in the context of the reasons, the passage cannot
be read otherwise.
[79]
In
my view therefore, the Applications Judge correctly held that the ‘452 patent is
an ordinary patent for an original compound and that its validity was to be
assessed on that basis.
Anticipation
[80]
Apotex
and Cobalt submit that the ‘452 patent is anticipated by the prior art, in
particular by the two U.S. patents. For its part, Genpharm submits,
relying on the English case Merrell Dow, that the ‘452 patent is
anticipated because the instructions to ingest citalopram in U.S. patents ‘193
and ‘884 provided directions which, if followed, resulted in the production of
substantially pure escitalopram in the body.
[81]
The
test for anticipation was re-stated in Sanofi where Rothstein J. noted
that an invention is anticipated – i.e. lacks novelty – when it is
disclosed and enabled. Referring to the reasons of Lord Hoffman in Synthon
B.V. v. SmithKline Beecham plc, [2006] 1 All ER 685, [2005] UKHL 59,
Rothstein J. stated that disclosure “means that the prior patent must disclose [the]
subject matter, which, if performed, would necessarily result in infringement
of that patent …” (Sanofi, para. 25). At the disclosure stage, the
person skilled in the art “is simply reading the prior patent for the purposes
of understanding it” and there is no trial and error (Sanofi, para. 25).
Enablement “means that the person skilled in the art would have been able to
perform the invention” (Sanofi, para. 26). Enablement needs to be
considered only if the invention is found to be disclosed. Trial and error is
permitted at this stage (Sanofi, para. 27).
[82]
The
Applications Judge followed this approach. He held that escitalopram was not
disclosed (and therefore not anticipated) by the two U.S. patents. He came
to this conclusion because “if the subject matter of either prior U.S. patent were
worked, the result would be a racemate, not an enantiomer” (Reasons, para. 46).
I can detect no error in this regard. Otherwise, the Applications Judge
correctly dismissed the contention that U.S. patents ‘193
and ‘884 automatically claimed the two enantiomers (see para. 66 above).
[83]
Turning
to Genpharm’s allegation of anticipation, the submission is that the ingestion
of citalopram results in the production by the body of substantially pure
escitalopram. Relying on the reasoning in Merrell Dow, Genpharm
maintains that this shows that escitalopram was anticipated, and contends that
the Applications Judge erred in dismissing its evidence as “outright
conjecture”. According to Genpharm, the Applications Judge had a duty to
analyze this evidence and erred in not doing so. Specifically, he failed to appreciate
the difference between a conclusion based on conjecture because it is
unsupported by the evidence, and a rational conclusion based on evidence (R.
v. Hehn, 2008 BCCA 170, paras. 20 and 26).
[84]
It
is not necessary to dwell on this issue or on Lundbeck’s submissions
challenging the application of the Merrell Dow decision on the facts of
this case because in any event, the Applications Judge found, after considering
the evidence, that the human body only produces partially resolved citalopram
(Reasons, para. 129). In so holding, he relied on two articles written in 1995
which indicate that a chiral HPLC column had to be used after the extraction of
blood samples to resolve citalopram (see Professor Davies’ affidavit, paras.
103 to 106, A-135-09 Vol. 4, pp. 1103 and 1104; see also Rochat articles, A-135-09
Vol. 21, pp. 6525 to 6538). The finding that the human body does not produce
substantially pure escitalopram was open to the Applications Judge on the
evidence before him.
Obviousness
[85]
Both
Genpharm and Cobalt challenge the Applications Judge’s conclusion that
escitalopram is not obvious. Although Apotex did not take issue with this
aspect of the decision in its memorandum of fact and law, counsel for Apotex
made supporting arguments during the hearing.
[86]
In
Sanofi, Rothstein J. laid out the approach for obviousness as developed
in the English cases Windsurfing International Inc. v. Tabur Marine (Great
Britain) Ltd., [1985] R.P.C. 59 (C.A) and Pozzoli SPA v. BDMO SA,
[2007] F.S.R. 37, [2007] EWCA Civ 588 (Sanofi, para. 67):
(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 claim 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?
[87]
Rothstein
J. added that an “obvious to try” test might be appropriate in “areas of
endeavour where advances are often won by experimentation”, such as in the
pharmaceutical industry (Sanofi, para. 68). He listed a number of
non-exhaustive factors to be applied in “accordance with the evidence of each
case” (Sanofi, para. 69):
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?
In addition the “actual course of conduct
which culminated in the making of the invention” may be considered (Sanofi,
para. 70).
[88]
The
Applications Judge followed this approach and found that substantially pure
escitalopram was not obvious.
[89]
First,
the Applications Judge determined that the person skilled in the art was “a team centred around a medicinal chemist who has access to
and makes use of others with different skill sets such as analytical chemists
and psychiatrists” and that “[t]heoretical knowledge of, and practical
experience in, the methods of resolving racemates is essential” (Reasons,
paras. 36 and 58). Although the Applications Judge did not explicitly identify
the common general knowledge possessed by this team, it is not in dispute that such
knowledge encompassed the underlying principles of chemistry applicable to the
subject matter of the ‘452 patent, including chirality, enantiomers,
stereoisomers, racemates and optical activity, and knowledge of, and experience
with, methods of resolving racemates.
[90]
Second, the Applications Judge identified the invention as being
substantially pure escitalopram and non-toxic additional salts thereof, as
stated in claim 1 of the ‘452 patent. He also concluded that claims 3 and 5 were
easily understood. In this respect, Genpharm and Cobalt took the position that
the Applications Judge identified the invention as being “the resolution of the
racemate in sufficient quantity to permit the testing disclosed in the patent”
(Reasons, para. 60). With respect, this is inaccurate. A fair reading of the
relevant passage shows that the Applications Judge found the invention to be
substantially pure escitalopram and its useful therapeutic effect. The
inventive step was the resolution of citalopram since this is what allowed for
the making of this compound and the identification of its properties.
[91]
Third, the Applications Judge identified the difference between
the state of the art and the invention. He found that while the prior art
disclosed that the racemate – citalopram – was useful as an antidepressant, it
did not disclose or enable its enantiomers or even predict whether either of
them would be useful as an antidepressant (Reasons, para. 60). In particular, the
prior art did not teach how to resolve citalopram in order to obtain
substantially pure escitalopram.
[92]
Fourth, the Applications Judge applied the factors outlined in Sanofi
for the “obvious to try” test and found that the difference between the inventive
concept and the state of the art did not constitute steps that would have been obvious
to the person skilled in the art. In applying this test, the Applications Judge
found motivation not to be instructive (Reasons, para. 79).
[93]
Genpharm and Cobalt take issue with this last conclusion. Genpharm
for its part, points to the 1987 FDA Guidelines which made it clear that
information concerning properties of enantiomers could be required before
marketing approval was granted for the racemate. This, according to Genpharm, was
compelling evidence of motivation and the Applications Judge erred in
dismissing it.
[94]
The existence and extent of the motivation to come up with an
invention is one of fact. The Applications Judge observed that the evidence
relating to the 1987 FDA Guidelines was thin and that no regulatory body had
made it a requirement that details of the enantiomers be disclosed (Reasons,
para. 79). As such, he refused to attribute to the 1987 FDA Guidelines the
effect which Genpharm contends it should have. I can detect no error in this
regard.
[95]
Cobalt
also criticizes the Applications Judge for failing to take into account his
finding that the respondent had downplayed its interest in resolving citalopram.
The Applications Judge says so much at paragraph 82 of his reasons. However, the
Applications Judge did not discard motivation as a factor; he simply held that this
was not “helpful” in this case (Reasons, para. 83).
[96]
Genpharm on the other hand takes issue with the Applications
Judge’s finding as to the extent of the effort required to resolve citalopram
and his conclusion that the use of chiral HPLC and the resolution of the diol
were not obvious steps. With respect to the effort required to resolve
citalopram, Genpharm submits that the Applications Judge erred in conducting
his analysis on the basis that 100 milligrams were required for testing.
According to Genpharm, 1.25 milligram was sufficient. In my view, it was open
to the Applications Judge to find that 100 milligrams were necessary for
testing (see Dr. Newton’s cross-examination and the report referred to therein,
A-135-09 Appeal Book, Vol. 29, pp. 9465 and 9569).
[97]
With respect to the available methods of resolution, Genpharm
contends that the evidence establishes that the skilled person would have
decided to pursue chiral HPLC with a reasonable expectation that it would work
and would have selected columns that would generate sufficient material to
perform the biological testing required by the ‘452 patent. In this respect, Genpharm
submits that the evidence clearly shows that analytical columns could have
produced the required material testing. Indeed, it contends that the Chiralcel
OD and the β-Cyclobond columns were available prior to the relevant date
and subsequently were used to resolve citalopram. The issue is again whether
the Applications Judge could, on the evidence, conclude that the use of chiral
HPLC was not obvious.
[98]
The Applications Judge found that “[a]n analytical column
will allow one to analyze which compounds and impurities are present in a given
reaction mixture but, unlike a preparative HPLC, cannot be used to obtain
much of the desired compound” (Reasons, para. 100 [my emphasis]). In other
words, analytical columns, such as the ones referred to by Genpharm, would not
have produced enough material for the testing required by the ‘452 patent. The
Applications Judge further noted that even if the expert called by Genpharm
stated that he could have resolved citalopram at the relevant time, “[t]he fact
of the matter is that not one of the [the experts] had ever attempted to resolve
citalopram, and it is now a fairly straightforward task” (Reasons, para. 106). In
my view, it was open to the Applications Judge to find that the use of chiral
HPLC was not obvious.
[99]
Genpharm
further contends that the Applications Judge erred in finding that the
resolution of citalopram using the diol was not obvious and that there was no
basis for using Mosher’s acid. Genpharm submits that using the diol, which was
disclosed in U.S. patent ‘884, was a
logical starting point and that one of its experts had used Mosher’s acid as a
reagent at the relevant time.
[100] As to the use of the
diol, the Applications Judge said (para. 103):
… In
fractional crystallization, the logical starting point was citalopram itself.
If that failed, one might then try to resolve other molecules such as the diol.
The experts retained by the respondents did not sufficiently divorce themselves
from the knowledge they had of the alleged invention as claimed. Why select the
diol disclosed in the ‘884 patent rather than the five precursors disclosed in
the ‘183 patent (sic)? Without going into the chemistry, which was intensely
debated, the closure of the diol ring and its timing was a crucial process
which led to discussions of SN1 and SN2 reactions. Furthermore, there was an
almost infinite combination of reagents and conditions to draw from.
[101] As to the use of
Mosher’s acid, the Applications Judge found that there was no basis for
believing that as part of routine testing, the acid in question would play a
major role in the ring closure reaction. This was not part of the common
general knowledge or of the prior art (Reasons, para. 110). In my view, the
conclusion reached by the Applications Judge both as to the use of the diol and
Mosher’s acid was open to him on the evidence.
[102] Finally, Genpharm
contends that the rejection of its experts because they used a measure of
hindsight in expressing their opinions was also made in error. The decision of
this Court in Apotex Inc. v. Bayer AG, 2007 FCA 243, paragraph 25 is
relied upon. However, what the Applications Judge found is that reliance had
been placed by these experts on knowledge that was not available at the claim
date (Reasons, paras. 106 to 111). I can detect no error in this regard.
[103] It
has not been shown that the Applications Judge erred in holding that the
escitalopram was not obvious.
Utility
[104] Apotex takes issue with
the Applications Judge’s rejection of the allegation that the ‘452 patent
lacked utility because it covers the pamoic acid salt of escitalopram which has
since been found to be toxic. The argument arises from a patent application
made by the respondent in Denmark in 2004 in which it is said that the U.S. patent equivalent to
the ‘452 patent:
… describes the free base of escitalopram
as an oil, the oxalic acid salt, pamoic salt and L-(+)-tartaric acid addition
salt of escitalopram. Due to the toxicity of pamoic acid addition salts they
are not suitable in pharmaceuticals.
[My emphasis]
[105] In the absence of any
explanation on the part of the respondent (none of which was given), this
statement amounts to an admission that the pamoic acid salt of escitalopram is
toxic to the point that it is not suitable in pharmaceuticals. The Applications
Judge conducted his analysis on this basis. However, relying on Burton
Parsons, he refused to invalidate the ‘452 patent on that ground because,
in his view, the skilled person would have avoided using such a salt (Reasons,
paras. 139 and 140).
[106] There is no doubt that
if the pamoic acid salt of escitalopram cannot be used in pharmaceuticals,
claim 2 of the ‘452 patent fails for lack of utility since that is precisely
what it claims (claim 2 is reproduced at paragraph 7 of these reasons). I agree
with Apotex that the question which had to be addressed is whether the pamoic
acid salt also came within claim 1 when construed from the perspective of the
skilled addressee in which case claim 1 would also fail. The Applications Judge
answered this question in the negative (Reasons, para. 139).
[107] According to Apotex
there is no reason to exclude the pamoic acid salt from the ambit of claim 1 since,
as of the claim date, there was no suggestion that pamoate salt was toxic.
Beyond this, Apotex argues that the inventor necessarily envisaged that claim 1
would comprise the pamoic acid salt since it is listed as being within the
preferred “non-toxic addition salts”. Furthermore, excluding pamoate salt from
the ambit of claim 1 would render claim 2, which is dependent on claim 1,
meaningless.
[108] Claim 1 when looked upon
on its own is clear and unambiguous: it claims substantially pure escitalopram
and non-toxic acid addition salts thereof. A claim that can only be read one
way cannot be altered by reference to the disclosure or the specifications. The
person skilled in the art aware that some acid addition salts are toxic and
that others are not, would read claim 1 for what it says, i.e. a claim
for substantially pure escitalopram and the addition salts thereof that are “non-toxic”
[my emphasis]. As the pamoic acid salt of escitalopram is toxic, it is excluded
from the ambit of claim 1.
[109] Apotex nevertheless
argues, relying on Halford v. Seed Hawk Inc., 2004 FC 88, (2004) 31
C.P.R. (4th) 434 at paragraphs 90 to 96 (rev’d on appeal but not on
this point) [Halford], that claim 1, being the claim on which claim 2 depends,
must be given a meaning which is consistent with claim 2.
[110] The exact proposition
for which Halford stands is that an independent claim cannot be given a
meaning which renders a dependent claim redundant (Halford, para. 98). Reading claim 1 as including a
claim for the pamoic acid salt, as Apotex suggests, would render claim 2
redundant. Claim 1 must be read for what it says. The evidence shows that the
inventor was wrong about the properties of pamoic acid salt with the result
that claim 2 is a self-inflicted wound of the type described in Free World
Trust (para.51). This does not detract from the clear and unambiguous
meaning of claim 1.
[111] It has not been shown
that the Applications Judge erred in rejecting Apotex’s allegation that claim 1
fails for lack of utility based on the toxicity of pamoic acid salts.
[112] Apotex
further submits that the utility of escitalopram was not soundly predicted by
the ‘452 patent. In this respect, Apotex argues that there was nothing in the
‘452 patent to correlate the effect of citalopram on rodents and its effect on
humans.
[113] As noted by
the Applications Judge, a sound prediction is dependent upon a factual basis.
The inventor must have an articulate and sound line of reasoning from which the
promised result can be inferred from that factual basis and there must be
proper disclosure (see Apotex Inc. v. Wellcome Foundation Ltd., 2002 SCC
77, [2002] 4 S.C.R. 453).
[114] Using this
approach, the Applications Judge noted that the test conducted on rodents was
the same as that which had been conducted with respect to citalopram. Since
citalopram proved to be a useful antidepressant when ingested by humans, it
followed that the prediction with respect to escitalopram was sound (Reasons,
para. 133).
[115] I can
detect no error in this reasoning.
Sufficiency of disclosure
[116] Apotex
submits that the ‘452 patent is ambiguous because it does not teach the person
skilled in the art the solvents to be used to obtain escitalopram; the suggestion
being that the patent does not set out the method of using the invention in
“full, clear, concise and exact” terms as contemplated by subsection 34(1) of
the Patent Act. The Applications Judge dismissed this argument on the
basis that the solvents were fully described (Reasons, para. 131). Indeed, the ‘452
patent indicates the concentration with which to use the solvents in question. The
question whether the wording of the patent sets out the method of using the
invention in sufficiently clear and exact terms is one of fact. I can see no
error in the Applications Judge’s conclusion on this issue.
[117] Apotex also argues
that the disclosure in the ‘452 patent is insufficient because it lays a false
trail by reason of the following statement (Reasons, para. 147): “[r]esults
upon administration to human beings have been very gratifying”. The
Applications Judge agreed that this statement was false since escitalopram had yet
to be administered to human beings at the relevant time. However, he held that (ibidem):
“[g]iven that the patent has two full pages of evaluation of escitalopram upon
rodents together with a table of pharmacological test results, I do not
consider that the one-liner misled anyone. Furthermore, there is no evidence of
an effort to mislead”. I can see no basis for interfering with this conclusion.
[118] Apotex nevertheless
argues that this does not address its contention that the invention was not
correctly described and therefore is in breach of section 34 of the Patent
Act. In my respectful view, it was open to the Applications Judge to hold that
as no one was misled, the invention was correctly described.
Procedural fairness and adequacy
of reasons
[119] Genpharm
submits that the Applications Judge erred in considering evidence from other
proceedings and also takes issue with the fact that he rendered one set of
reasons to dispose of the three applications. With respect to the evidence,
Genpharm contends that the Applications Judge could not, on the record as
constituted in the application that relates to it, find that 100 milligrams
were necessary for the testing required by the ‘452 patent, that 40,000 runs
would be necessary to obtain a sufficient quantity of material (Reasons, para.
112) and that Mosher’s acid was not known and used as a chiral agent (Reasons,
para. 110).
[120] With regard,
the Applications Judge could make those findings based on the Genpharm record.
On cross-examination, Dr. Newton, Genpharm’s expert, acknowledged writing in a
report that 100 milligrams of escitalopram would be sufficient to conduct the
testing required by the ‘452 patent (A-135-09 Appeal Book, Vol. 29, p. 9467).
The figure of 40,000 was put to Dr. Collicott, another Genpharm’s expert, on
cross-examination on the basis of the Rochat paper (A-135-09 Appeal Book, Vol.
28, pp. 9076 to 9083). As for Mosher’s acid, although Professor Chong stated
that Mosher’s acid was a “standard reagent for the derivatization of chiral
alcohols and amines”, Dr. Newton, another expert called by Genpharm,
acknowledged on cross-examination that he had never used Mosher’s acid for
preparative work and that prior to 1988 he had never seen Mosher’s acid used in
a preparative work (A-135-09 Appeal Book, Vol, 29, pp. 9533 to 9535).
[121] Turning to
the adequacy of the reasons, Genpharm submits that the Applications Judge’s
reasons are not sufficiently intelligible to provide a basis for meaningful
appellate review in that they do not adequately distinguish between the three
proceedings (Via Rail Canada Inc. v. National Transportation Agency,
[2001] 2. F.C. 25 (CA)). According to Genpharm, it is impossible to determine
the basis for some of the findings made against it.
[122] During the hearing of
the appeal, counsel for Genpharm gave as an example the Applications Judge’s
conclusion that Professor Clark’s analysis was “well balanced” (Reasons, para.
111). According to counsel, such a conclusion could not have been reached on
the record that relates to Genpharm. The suggestion is that the Applications
Judge must have relied on evidence in the other proceedings.
[123] The argument so put does
not go to the adequacy of the reasons so much as to the absence of an
evidentiary foundation for the findings made. If counsel believes that the
evidence does not support the Applications Judge’s findings, it is incumbent
upon him to make this demonstration. In this respect, the Applications Judge
noted with respect to Professor Clark’s evidence in the Genpharm record
(Reasons, para. 111):
… he was
careful to distinguish what was known and available in 1988 as compared to
later developments, with new generations of columns, with better packing material
which improved resolution capacity and preparative scales. These improvements,
he explained, allowed for the separation of sufficient quantities of material
to allow for biological testing and not simply detection.
This finding which underlies the Applications
Judge’s assessment of Professor Clark’s analysis is based on evidence in the
Genpharm record (see A-135-09 Appeal Book, Vol. 3, pp. 467 to 470).
[124] Cobalt also
takes issue with the adequacy of the reasons. For instance, it claims that in
criticizing the “experts” (Reasons, paras. 103 and 106 to 109), the
Applications Judge failed to particularize his complaint with the result that
it is unable to determine the evidence which was relied upon in discarding the
opinion of its experts. The suggestion again is that evidence from the other
proceedings may have been used. However, the ultimate conclusion reached by the
Applications Judge as a result of his assessment of the opinions expressed by
these various experts is that citalopram could not have been resolved at the
time absent inventiveness. In so holding, he relied on the evidence of
Professors Davies and Clark both of whom were called by Lundbeck in the Cobalt
application (Reasons, paras. 108 and 109).
[125] Along the
same line, Cobalt contends that the Applications Judge used Dr. Chong’s
(Genpharm) critique of a study conducted by Rhodia ChiRex to find the study
inconclusive. However, the Applications Judge refers to Dr. Chong as one
amongst others: “Dr. Chong, for one, also notes …” (Reasons, para. 115
[my emphasis]). His finding, at paragraph 114, that the study did not
demonstrate obviousness because it “was only a screening” and “optimization of
the best candidates identified would thereafter be necessary” is supported by
evidence other than Dr. Chong’s critique of the study.
[126] Cobalt also
takes issue with the Applications Judge’s rejection of the Elati article
published in 2007. In this respect, the Applications Judge did rely on
admissions made by Dr. Newton (Genpharm) and Dr. McClelland (Apotex). However,
he also identified grounds for rejection which are wholly independent from
these admissions. The Applications Judge said, at paragraph 118, that he gave
“no weight whatsoever to the Elati article” because even if it lists various
ways to resolve racemates, it does not make reference to any article published
before 1990 and “Elati even claims a patent on his process.” He added that it
“is certainly not plain and obvious that such a step would have been taken or
that the Elati process would have been used” (Reasons, para. 119). Significantly,
it is only after making these findings that the Applications Judge observed
that “[i]n any event, there were flaws in the Elati article as admitted by Drs.
Newton and McClelland” (Reasons, para. 119).
[127] As to the
alleged improper use of Dr. Newton’s evidence (Genpharm), the Applications
Judge did rely on his assertion that when a racemic drug is ingested, its two
enantiomers exist as separate compounds in solution and react with receptors
within the body at different rates (Reasons, para. 126). However, he did so
while discussing anticipation by prior use, an allegation that Cobalt did not
pursue (Reasons, para. 125).
[128] With respect
to the reliance placed by the Applications Judge on the statement by Dr.
McClelland (Apotex) that he had no problem understanding the invention
(Reasons, para. 142), this again was done in the context of an issue that was
not raised by Cobalt, i.e. whether the ‘452 patent contained so much
linguistic imperfection that it could not be understood.
[129] Cobalt makes
a number of additional submissions aimed at demonstrating that it was
prejudiced by the Applications Judge’s decision to issue a single set of
reasons. Although it would have been preferable for the Applications Judge to
issue separate reasons, if only because it would have avoided this last series
of attack against his judgment, I am satisfied that he was mindful of the
common and distinct points raised by the appellants throughout his review and that
no injustice results from the fact that he issued a single set of reasons.
[130] I would dismiss the
three appeals, with costs in favour of Lundbeck in each case.
“Marc
Noël”
“I
agree.
J.D. Denis Pelletier J.A.”
“I
agree.
Johanne Trudel J.A.”
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