Apotex
Inc. v. H. Lunbeck A/S, 2013 FC
192

Apotex
sought a declaration of invalidity against Lundbeck’s Canadian patent 1,339,452
(‘452) covering the serotonin reuptake inhibitor (+)-Citalopram marketed in
Canada as CIPRALEX. Lundbeck counterclaimed that Apotex has infringed the
patent.

The patent
is valid.

Apotex is
permanently enjoined from infringing, and is ordered to account for its profits
arising from infringement. Punitive damages are not appropriate.

Patent
as a Bargain

A patent
represents a bargain between the inventor and the state. In consideration of
the grant of a monopoly, the inventor must fully and properly disclose the
invention so that when the monopoly expires, others may reproduce the product
or process involved without undue difficulty. The Patent Act requires
the applicant to provide a specification which discloses what has been invented
and how to replicate it.

Construction

It is not
for the skilled reader to tell the Court what the patent means; it is for the
Court to tell the parties what it means. A patent is not an ordinary document.
It meets the definition of a “regulation” in the Interpretation Act, and
must be read to assure the attainment of its objects.

Skilled
Person

The skilled
addressee in patent law does not exist. He or she is a judicial creation.

In this
case the skilled person is a medicinal chemist, probably with a doctorate, and
has spent at least a few years in a laboratory. The addressee is either part of
or has access to a team, which includes analytical chemists, familiar with the
principles of organic chemistry and techniques then available which could be
used in an effort to separate racemic mixtures into their two enantiomers.
Access would also be had to pharmacologists, psychiatrists and to drug
formulators.

INVALIDITY

The patent
is valid.

Anticipation

The claimed
invention was not anticipated.

There were
previous patents, issued more than two years before the application, which
disclosed Citalopram. However, the working of prior art patents would
inevitably result in a racemic mixture, not in separate enantiomers. There was
no prior disclosure in that the prior patents did not teach how to resolve
Citalopram into optically-pure enantiomers and did not disclose the therapeutic
effects of (+)-Citalopram.

Obviousness

The
invention was not obvious.

The Court
applied the four-step obviousness framework set out by the Supreme Court in Sanofi,
and performed the obvious-to-try analysis in the fourth step. The Court held
that the innovative concept of the claim was a substance, (+)-Citalopram,
useful as an anti-depressant, a substance which had never been created before.
The prior state of the art did not explain how to achieve (+)-Citalopram and
did not disclose the qualities of the two enantiomers. These differences
constituted steps which would not have been obvious to the person skilled in
the art. They required a degree of invention. It was not more or less evident
that what was done ought to have worked. Furthermore, a mosaic or assembly of
literature which might have led to (+)-Citalopram involved a considerable
degree of inventiveness.

Inutility

The
allegation of inutility is dismissed.

Apotex
alleged that the pamoic salt of (+)-Citalopram is toxic. Claims 1 through 5 all
encompass this salt. Therefore, it follows that the patent falls for inutility.

Lundbeck
submitted evidence that the salt was not toxic in rats. Apotex led no evidence
on toxicity of the pamonic salt. The Court dismissed the allegation of
inutility on the basis that the evidence, while scant, favored Lundbeck.

Insufficiency

The
allegation of insufficiency is rejected.

The
specification discloses that “results upon administration to human beings have
been very gratifying”. That statement is untrue as the enantiomers had not been
tested on human beings until after the patent application was filed in June
1989. As a consequence, Apotex argued, the patent should be declared to be void
under subsection 27(3) of the Act, as it was, provided that “The
specification of an invention must (a) correctly and fully describe the
invention and its operation or use as contemplated by the inventor…”

The Court
distinguished the Supreme Court Viagra decision: in Viagra Pfizer
claimed 260 quintillion compounds for the treatment of erectile dysfunction in
impotent males. The patent did not disclose that the compound which actually
worked was sildenafil and that the remaining compounds had not been found to be
effective. This was the needle in a haystack type of case. In this case, the
invention, (+)-Citalopram and how to get there, was properly disclosed. In
addition, notwithstanding its disclosure, (-)-Citalopram was not claimed.

Furthermore,
the Court held that the sentence “Results upon administration to human beings
have been very gratifying” is not a technical one, is not essential, and not
detrimental to the survival of the patent.

Sound
Prediction

Apotex’s
allegation of lack of sound prediction is rejected.

Lundbeck
had a sound basis for predicting that (+)-Citalopram would be useful in the
treatment of depression in humans. The racemate had already proved useful, and
the same type of in vivo and in vitro tests to which Citalopram
had been subjected were run on (+)-Citalopram. They indicated that
(+)-Citalopram had a greater potency than Citalopram itself.

However,
Apotex argued that Lundbeck promised in the disclosure that (+)-Citalopram had
greater therapeutic effect than Citalopram. This promise could only be
demonstrated by testing upon humans, and so the patent must fall unless there
was a sound basis for making it.

The Court
rejected Apotex’s construction of the patent’s promise. Apotex inferred this
promise from a statement in the disclosure that “almost the entire 5-HT uptake
inhibition resided in the (+)-Citalopram enantiomer” and from a table showing
pharmacological test results in vivo and in vitro on rats and
mice. The table indicates that (+)-Citalopram is far more potent, some 60 times
more than (-)-Citalopram and about 1.6 times more than Citalopram itself.

The Court
held that the claim portion of the specification takes precedence over the
disclosure portion in that the disclosure is read so as to understand what is
meant by the claims but not to enlarge or contract the scope of the claims as
written and thus understood. The table illustrated that most of the inhibition
was found in the (+) enantiomer. The insertion of Citalopram as a point of
reference cannot be taken as a promise. These was no prediction that
(+)-Citalopram was better than Citalopram.

INFRINGEMENT

Apotex had
admitted that if the patent is found to be valid, it has infringed it.

Punitive
Damages

Punitive
damages are not appropriate in this case.

The
evidence showed that Apotex stockpiled (+)-Citalopram in the expectation that
the Minister would not be prohibited from issuing a notice of compliance. Its
prediction was wrong, both in first instance and in appeal. Thereafter, as it
was prohibited from marketing (+)-Citalopram in Canada, it sold some of the
product to affiliates in the Czech Republic and Australia. Dr. Sherman,
Apotex’s chairman, testified that once he found out the stockpiled product was
being sold overseas, he immediately put a stop to it.

Accounting
of Profits

Apotex must
account for its profits arising from infringing Lundbeck’s patent.

Apotex
argued that this remedy should not be granted in this case because Lundbeck
would be given an inequitable windfall were it to claim Apotex’s profit on the
Australian and Czech Republic sales, as Lundbeck led no evidence that it had
competed in those markets.

The Court
held that the fact that Lundbeck led no evidence as to its position in the
Australian and Czech Republic markets is irrelevant. It may be that Lundbeck
suffered little or no damage in those markets. The fact is, however, that
Apotex made a profit and must account for it.

Furthermore,
good faith on Apotex’s part is not relevant either. Apotex is not being
punished. It made use of Lundbeck’s intellectual property rights and must turn
over the profits it made. It would be completely unreasonable to hold that the
only consequence of infringement over several years would be to declare the
patent valid and to enjoin Apotex from continuing what it should not have done
in the first place.

Delivery-Up
or Destruction

Apotex
still has in its possession 8.34 kilos of (+)-Citalopram. Apotex argued if it
were found to have infringed, it should be able to work out an appropriate
protocol with Lundbeck. The Court agreed.

Permanent
Injunction

Lundbeck is
entitled to an order prohibiting Apotex, directly or indirectly, as well as its
officers and directors, and the servants, employees or agents of any of them,
and any other person, corporation or entity acting under their instructions or
control, from making, selling, distributing, advertising, exposing for sale,
offering for sale, stockpiling or possessing for the purposes of the foregoing
or importing into Canada (+)-Citalopram prior to the expiration of patent
1,339,452.