Date: 20070717
Docket: T-840-05
Citation: 2007 FC 753
Vancouver, British Columbia, July 17, 2007
PRESENT: The Honourable Mr. Justice O'Reilly
BETWEEN:
ABBOTT LABORATORIES and
ABBOTT LABORATORIES LIMITED
Applicants
and
THE MINISTER OF HEALTH
and APOTEX INC.
Respondents
REASONS FOR JUDGMENT AND JUDGMENT
(Edited for
public release)
[1]
Abbott owns patents for an antibiotic called clarithromycin which
it markets under the name “Biaxin”. Although Abbott’s patents do not expire for
a number of years, Apotex wishes to market its own clarithromycin tablets.
[2]
Abbott seeks an order prohibiting the
Minister of Health from issuing to Apotex a Notice of Compliance under the Patented
Medicines (Notice of Compliance) Regulations, SOR/93-133 until two of its
patents expire. The Notice of Compliance would permit Apotex to put its tablets
on the market. Apotex alleges that Abbott’s patents are invalid and, therefore,
that Abbott is not entitled to the prohibition order it seeks. Further, Apotex
alleges that even if Abbott’s patents were valid, it would not be infringing
them by producing its own version of clarithromycin. To obtain a prohibition
order Abbott must prove that Apotex’s allegations are unjustified.
I.
Issue
Has Abbott
established that Apotex’s allegations of invalidity and non-infringement of
Canadian Patents No. 2,419,729 (‘729) and No. 2,471,102 (‘102) are unjustified?
[3]
I have found that Abbott has
failed to prove that Apotex’s allegations of invalidity are unjustified.
Therefore, I need not deal with Apotex’s allegations of non-infringement.
II. Analysis
(a) Proceedings under the Notice of Compliance (NOC) Regulations
[4]
Proceedings under these Regulations serve the limited
purpose of providing an expeditious means of determining issues relating to the
validity and scope of drug patents within the regulatory scheme governing
manufacturers' rights to market their products in Canada: Biovail Corporation v. Canada (Minister of National
Health and Welfare), 2006 FC 784, [2006] F.C.J. No. 1179 (T.D.) (QL).]
(b) Burden of
proof
[5]
Abbott bears the legal burden of proving on a
balance of probabilities that Apotex’s allegations of invalidity are
unjustified. Apotex shoulders an evidentiary burden. If it has presented
sufficient evidence to give its allegations an air of reality, then it has
rebutted the presumption that Abbott’s patents are valid (Patent Act,
R.S.C. 1985, c. P-4, s. 43(2); see Annex).
[6]
Apotex has clearly met its evidentiary burden
through the reports of its experts and references to scholarly articles and
other patents. I cannot presume, therefore, that Abbott’s patents are valid. I
must determine whether Abbott has proved that Apotex’s allegations are
unjustified: Abbott Laboratories v. Canada (Minister of Health), 2007 FCA 153,
[2007] F.C.J. No. 543 (C.A.) (QL).
(c) The
Abbott Patents
[7]
The two Abbott patents in issue here have much in common. They describe two
forms (Forms I and II) of clarithromycin and their respective properties, set
out in detail the process of methylation, crystallization and recrystallization
by which the base molecule (erythromycin) is converted to clarithromycin Forms
I and II, cite the United States patents in which those procedures were
previously disclosed, give numerous examples of the means by which Form I or
Form II can be achieved, and provide graphs of the X-ray powder diffraction
pattern (XRPD), infrared spectra (IR) and differential scanning calorimetry
(DSC) for the two crystal forms of clarithromycin.
[8]
The two patents differ in the following respects:
(i) The ‘729
Patent
[9]
Abbott relies on claim 8 of the ‘729 patent. It
claims Form I when prepared by the process described in claim 1 of the patent.
That process involves the crystallization of clarithromycin from a syrup or
semi-solid with the resulting product containing at least one residual solvent.
Abbott asserts that its ‘729 patent contains a valid claim to Form I, when prepared
in the prescribed manner.
[10]
The specification of the ‘729 patent says that
one embodiment of the invention is the process for producing Form I from a
syrup or semi-solid, with the product containing at least one residual solvent.
It also refers to a further embodiment of the invention being Form I itself,
when prepared according to the prescribed process. These embodiments line up with
claims 1 and 8 of the patent. It is agreed, however, that claim 1, being a
claim for a process rather than for a medicine or for the use of a medicine,
cannot be the subject of proceedings under the Regulations. Accordingly, I need
only deal with claim 8.
(i)
The ‘102 Patent
[11]
Abbott relies on claim 9 of the ‘102 patent. It
claims the use of Form II clarithromycin, with specified impurities, as an
antibiotic.
[12]
The specification of the patent states that one
embodiment of the invention is Form II with impurities. In a preferred
embodiment, the impurities are certain alkylated compounds. In a more preferred
embodiment, the impurities are situated at specified locations of the
clarithromycin molecule. In the most preferred embodiment, the impurities are
identified and reside at three particular loci of the molecule. Abbott asserts claim
9 as it relates to the use of one of the most preferred embodiments of the
patent as an antibiotic.
(d) Apotex’s
allegations of invalidity
[13]
Apotex has presented numerous arguments suggesting that Abbott’s patents
are invalid. In broad terms, Apotex alleges that Abbott’s patents do not
disclose any invention. It makes the following more particular arguments:
(i)
Anticipation: Others had disclosed the subject matter of Abbott’s
patents in public documents prior to the relevant date of July 29, 1996.
Further, Abbott had disclosed its own invention to the public by virtue of its
sale of Biaxin prior to 1996;
(ii)
Obviousness: The subject-matter of Abbott’s patents was an obvious derivation
from common knowledge in the field;
(iii)
Double-patenting: Abbott had already obtained patents for the same ostensible
inventions and cannot get other valid patents without adding anything new;
(iv)
Inutility: The subject matter of Abbott’s patents is not patentable
because it lacks the essential requirement of usefulness;
(v)
Insufficiency: The Abbott patents do not disclose a means of producing
what is claimed.
[14]
In addition, in relation to the ‘729 patent, Apotex argues that Abbott’s
claim for Form I is invalid because Form I was a known product at the relevant
date. It submits that one cannot obtain a valid patent for an old product even
if the product is made by a new process. Apotex does not accept that the ‘729
patent sets out a new process but, even if it did, Apotex says the claim for
Form I is untenable.
(e) Abbott’s
application for prohibition
[15]
Abbott would be entitled to an order of prohibition
only if Apotex failed to meet its evidentiary burden or if it proved that none
of Apotex’s allegations was justified. If Abbott failed to satisfy its burden
in respect of any of Apotex’s sustainable allegations, it could not obtain the requested
order.
[16]
I am not satisfied that all of Apotex’s
allegations are unsupportable or unjustified. Therefore, I cannot grant the
order Abbott seeks. I am satisfied that at least one allegation of invalidity
is justified in relation to each patent. Abbott has not discharged its burden
to prove otherwise.
(f) Validity of the ‘729
Patent
[17]
The ‘729 patent makes clear that the process of
creating clarithromycin was not invented by Abbott. The patent refers to
various prior United States
patents owned by the Taisho Pharmaceutical Company. Further, the patent
describes a process of crystallizing and recrystallizing clarithromycin for
purposes of purification which follows standard chemical practices of
dissolution in a solvent, heating, filtering, cooling and drying. When
particular solvents are used this process yields clarithromycin in Form I.
[18]
Further, Form I was disclosed well before July
29, 1996. For example, a European patent (no. 0041355), filed in 1981 and held
by Taisho, described a process of crystallization and recrystallization using
chloroform and diethyl ether. A similar process using chloroform and isopropyl
ether was described in Morimoto, S., et al., “Chemical
Modification of Erythromycins. I. Synthesis and Antibacterial Activity of
6-0-Methylerythromycins A” (1984) Vol. 37: No. 2, Journal of Antibiotics,
187-189.
[19]
Apotex’s experts state that the processes described in these
documents yield clarithromycin Form I. Dr. Peter Stang, Professor of Chemistry
at the University of Utah, concluded that the chloroform/diethyl ether
combination created Form I given that the XRPD, IR and DSC data for the
resulting crystal correspond with the figures provided for Form I in the ‘729
patent. He also concluded that the chloroform/isopropyl ether combination
yielded Form I on the same reasoning. Dr. Robin Harris, Professor Emeritus of
Chemistry at Durham University, England, agreed with both of those conclusions.
Dr. Robert McClelland, retired Professor of Chemistry at the University of Toronto,
also agreed. Apotex’s experts also cited numerous occasions on which Abbott’s
experts had conceded that persons following the prior art would produce Form I
when they recrystallized clarithromycin in ethanol.
[20]
It is clear, therefore, that Form I was a known
compound well before July 29, 1996. The question arises, therefore, whether
Abbott can have a valid patent for a known product, even if it had developed a
novel process for producing it (which is disputed). This same issue arose in
another case dealing with an Abbott clarithromycin patent: Abbott Laboratories
v. Canada
(Minister of Health), 2005 FC 1332, [2005] F.C.J.
No. 1721 (T.D.) (QL). There, Justice Michael Phelan concluded that both Form II
clarithromycin and the processes for making it were known well before 1996. He
found the Abbott patent before him invalid on that basis. The Federal Court of
Appeal upheld that conclusion (2007 FCA 153, [2007] F.C. No. 543 (C.A.) (QL)),
relying on the reasoning in the case of Hoffmann-La Roche & Co. v. Canada (Commissioner of Patents), [1955] S.C.R. 414. In Hoffman-La Roche, the Supreme Court
of Canada held that a patent for a known product was invalid even if the
process by which it was made was novel. The product would not meet the
definition of an “invention” (although the process would). Justice Rand stated:
The definition
clause furnishes no warrant for treating a well known substance as being a “new
and useful . . . composition of matter” because it has been produced by a
certain process. The assumption is that the product of different processes is
identical and no such constructive attribute can render the substance itself
either new or useful. (At p. 417.)
[21]
In the Federal Court of Appeal, Justice Karen Sharlow
made it clear that the principle in Hoffmann-La Roche still applies in
Canadian law. She held that Abbott could not have a valid claim to Form II
clarithromycin, even if it was created by a novel process, because Form II was
a known product. Abbott argued that those who followed the prior art would not
know which form of clarithromycin they had produced. But Justice Sharlow held
that “the absence of that knowledge is legally irrelevant” given that “well
established analytical techniques would have disclosed its presence if anyone
had cared to look at the appropriate moment” (at para. 22).
[22]
Justice Sharlow determined that a product was
“known” if a hypothetical claim for its invention would be invalid for
anticipation. In other words, if a person could get a valid patent for the
product in issue, then it could not be said that the product was known. By that
analysis, Abbott argues that its claim for Form I as created by the process set
out in claim 1 of the patent is valid. It submits that a hypothetical patent
for Form I would be valid because, although Form I had been disclosed in
earlier publications, the disclosure was not enabling; that is, the prior
references did not contain sufficient information to permit a person of
ordinary skill and knowledge to understand “the nature of the invention and
carry it into practical use without the aid of inventive genius but purely by
mechanical skill” (Free World Trust v. Électro-Santé Inc., [2000]
2 S.C.R. 1024, at para. 26, quoting H.G. Fox, The Canadian Law and Practice
Relating to Letters Patent for Inventions (4th ed. 1969), at pp.
126-7).
[23]
In my view, Abbott does not have a valid patent for Form I even if it
was produced by a novel process. Form I is an old
product. There are numerous prior art sources, cited above, that contained
sufficient information to enable skilled workers to make it. The fact that they
would not have known that they had made that particular form of clarithromycin
is, according to the Federal Court of Appeal, “legally irrelevant”.
[24]
Therefore, Abbott has failed to discharge its
burden of proof in relation to the ‘729 patent.
(f)
Validity of the ‘102 patent
[25]
Abbott concedes that Form II clarithromycin was
a known substance before the relevant date of July 29, 1996. Indeed, as
mentioned, the Federal Court of Appeal recently upheld a Federal Court finding
that Form II was an old product as of that date: Abbott Laboratories v.
Canada (Minister of Health), above. The prior art showed that heating
Form I created Form II on the way to the melting point of clarithromycin,
around 225°C (Morimoto, S., et al., “Chemical Modification of
Erythromycins. I. Synthesis and Antibacterial Activity of
6-0-Methylerythromycins A”, (1984) Vol. 37: No. 2, Journal of Antibiotics,
187-189). In addition, numerous other sources described the creation of
clarithromycin Form II by crystallization in various solvents. Justice Phelan
referred to the existence of five European patent applications dating back to
1980, as well as numerous articles in the Journal of Antibiotics from
1984 to 1993 that described how to make Form II.
[26]
It is also clear on the evidence that the prior
art disclosed clarithromycin containing the same impurities that are identified
in the various embodiments and claims of the ‘102 patent. Dr. Stang concluded
that “it would be obvious to a person skilled in the art that any prior
preparation of clarithromycin . . . would have the same alkylated
clarithromycin impurities recited in . . . the ‘102 patent”. Dr. McClelland agreed.
He was of the view that the process described in Morimoto S., et al.,
above, as well as in other prior art documents, would have yielded
clarithromycin (whether Form I or Form II) in the presence of the same
impurities as identified in the ‘102 patent.
[27]
Abbott does not dispute this evidence. Its principal
argument is that, while Form II was known, no one had recognized its use as an
antibiotic. Apotex suggests that this use was obvious since all of the prior
art was inspired by the promising anti-bacterial activity of clarithromycin. Accordingly,
using Form II clarithromycin as an antibiotic was not an invention and should
not be patentable: GlaxoSmithKline Inc. v. Canada (Minister of Health), 2004 FC 116,
[2004] F.C.J. No. 191 (T.D.) (QL), at para. 28. In reply, Abbott suggests that
while both the antibiotic properties of clarithromycin generally and the existence
of Form II were well-known, no one had, in effect, put “two and two together”. Accordingly,
Abbott maintains that no one knew that Form II could be used as an antibiotic.
[28]
The argument on this point arose from the recent
decision of Justice Sharlow, described above. That decision amounts to a
binding conclusion that Form II was an old product and anticipated by prior art.
Abbott attempted to save its patent by arguing that the use of Form II
was an invention even if Form II itself was not. Given that this issue was
raised for the first time during oral argument, there is little evidence in the
record directly on point.
[29]
Apotex points to articles in which Form II was
disclosed and its antibacterial effects were described (see Y. Watanabe,
et al., “Chemical Modification of Erythromycins. IX. Selective
Methylation at the C-6 Hydroxyl Group of Erythromycin A Oxime Derivatives and
Preparation of Clarithromycin” (1993) Vol. 4b: No. 4, Journal of Antibiotics,
647-660; S. Morimoto, et al., “Chemical Modification of Erythromycins
II. Synthesis and Antibacterial Activity of O-alkyl Derivatives of Erythromycin”,
(1990) Vol. 4.3: No. 3, Journal of Antibiotics, 286-294). It also asked
me to draw a common-sense inference from the fact that all of the prior art was
devoted to the development of clarithromycin for use as an antibiotic. Its use
as an antibiotic was obvious to all of those involved in its study. In fact, it
was the only known use for clarithromycin. Apotex refers to Abbott
Laboratories v. Canada (Minister of Health), 2007 FCA 187, in which Justice
Marc Noël stated in relation to Form II: "Saying, in effect, that an
antibiotic is used as an antibiotic adds nothing to the invention" (para.
43).
[30]
In my view, Abbott cannot succeed in its argument that it
invented the use of Form II as an antibiotic. First, there is nothing in the
‘102 patent itself that supports the contention that use of Form II as an
antibiotic was an aspect of the invention. Nowhere is this claim reinforced by
any discussion, disclosure, examples or data. In fact, the patent states that
Forms I and II exhibit excellent and identical antibacterial activity. The only
difference between them is that Form I dissolves more quickly. The patent notes
that drugs currently on the market contain Form II and suggests that Form I
would be a more economical and effective product. I see nothing that supports Abbott’s
assertion that the use of Form II as an antibiotic was an aspect of the
invention disclosed by the '102 patent.
[31]
Second, Abbott bears the onus of proof on the issue of validity
and it has not tendered evidence supporting its position. For its part, Apotex
has met its evidentiary burden by directing me to evidence showing that the use
of Form II as an antibiotic was obvious in light of the prior art. Abbott has
not proved that this allegation is unjustified.
[32]
Abbott relies solely on the assertion that different crystal
forms of a given substance can have different properties. For example, it notes
that graphite and diamonds are both crystal forms of carbon, but obviously have
different characteristics. Accordingly, Form II clarithromycin could have
different chemical properties from Form I (and other crystal forms of
clarithromycin). Abbott cites the following passage in another
clarithromycin-related proceeding in support of this argument:
Dr. Atwood
points out that a substance may take on millions of crystalline forms. Although
that substance may in itself be a medicine, some of the crystalline forms may
not, because they cannot dissolve in the body. They may be no more beneficial
than a penny swallowed by a child. Form 0 did not need to have medical value,
as long as it could be converted into Form II which does. (Abbott
Laboratories v. Canada (Minister of Health), 2006 FC 120,
[2006] F.C.J. No. 256 (T.D.) (QL), at para. 62); reversed on other grounds:
2007 FCA 73, [2007] F.C.J. No. 233 (C.A.) (QL)).
[33]
Dr. Jerry Atwood, Professor of Chemistry at the
University of Missouri-Columbia, whose opinion is cited in the passage quoted
above, advises that it is not obvious that one crystal form of clarithromycin
would be useful as an antibiotic just because another one was. I accept that
different crystals can have different properties. But Abbott has offered no
evidence to support its alleged invention. It has not shown that it discovered any
particular therapeutic characteristics of Form II or any other properties that
would be make it suitable for use as an antibiotic. Again, the patent itself
suggests otherwise.
[34]
In my view, therefore, Abbott has failed to
discharge its burden of proof in relation to the ‘102 patent.
III. Disposition
[35]
Abbott has not proved that the allegations of
invalidity discussed above are unjustified. Therefore, I must dismiss Abbott’s
request for an order of prohibition with costs.
JUDGMENT
THIS COURT’S
JUDGMENT IS THAT:
1. Abbott’s request for an order of prohibition
is dismissed with costs to be calculated at the mid-point of Column IV.
2. The parties shall make any submissions
regarding the need to edit these reasons before public release within ten days.
“James
W. O’Reilly”
Annex “A”
|
Patent Act,
R.S.C. 1985, c. P-4
Validity of patent
43. (2) After the patent is issued, it shall, in the absence of any
evidence to the contrary, be valid and avail the patentee and the legal
representatives of the patentee for the term mentioned in section 44 or 45,
whichever is applicable.
|
Loi sur les brevets, L.R. 1985, ch. P-4
Validité
43. (2) Une fois délivré, le brevet est, sauf preuve
contraire, valide et acquis au breveté ou à ses représentants légaux pour la
période mentionnée aux articles 44 ou 45.
|
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