Docket: T-1095-13
Citation:
2015 FC 770
Ottawa, Ontario, June 19,
2015
PRESENT: The
Honourable Mr. Justice O'Reilly
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BETWEEN:
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NOVARTIS
PHARMACEUTICALS
CANADA INC.
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Applicant
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and
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TEVA CANADA
LIMITED AND
MINISTER OF
HEALTH
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Respondents
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and
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NOVARTIS AG
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Respondent/Patentee
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JUDGMENT AND REASONS
I.
Overview
[1]
The applicant, Novartis Pharmaceuticals Canada
Inc, seeks an order prohibiting the Minister of Health from granting the
respondent, Teva Canada Limited, a Notice of Compliance (NOC), which would
permit Teva to enter the pharmaceutical market with a generic version of
Novartis’s patented product called EXJADE. EXJADE contains an active ingredient
called deferasirox (DFS) which acts as an iron chelator – that is, it binds to
iron, and it can therefore be used to treat conditions that involve an excess
of iron. Novartis’s patent, Canadian Patent No 2,255,951 (the ‘951 patent), was
filed in 1997 and will expire on June 24, 2017. The patent covers DFS and other
similar compounds, as well as their use in treating conditions involving excess
iron.
[2]
By way of a notice of allegation (NOA) served on
Novartis in 2013, Teva alleged that the ‘951 patent is invalid on a number of
grounds: inutility, obviousness, insufficiency of disclosure, overbreadth, and
ambiguity. At the hearing, the issues were narrowed to inutility, obviousness,
and insufficiency.
[3]
I am satisfied that most of Teva’s allegations
are unjustified. In particular, with respect to utility, I am not persuaded by
Teva’s allegation that the ‘951 patent expresses an explicit and overarching
promise that the compounds described in it have been found to be useful in
treating iron overload disorders in humans. In fact, the stated utility of the
novel compounds of the ‘951 patent is more modest – that the compounds markedly
bind to iron, are soluble, and induce excretion of iron in animal tests. On the
other hand, I accept Teva’s assertion that the claims of the ‘951 patent
relating to the use of the compounds of the patent to reduce iron overload
conditions in humans do contain an explicit promise of a specific result, one
which was neither demonstrated nor soundly predictable at the filing date (June
24, 1997). Accordingly, Teva’s allegation of inutility in respect of the use
claims of the patent is justified, but not its parallel allegation in respect
of the novel compounds of the ‘951 patent.
[4]
In addition, I am not satisfied that Teva’s
allegations of obviousness and insufficiency are justified. Considering the
state of the art and the common general knowledge of the skilled person at the
filing date, the novel compounds of the ‘951 patent were not obvious. Further,
Novartis has not, as Teva contends, hidden the real invention by failing to
identify DFS as the compound that would ultimately make it onto the market. In
my view, Novartis sufficiently disclosed its invention by identifying 30
compounds that displayed the useful properties described in the patent –
binding to iron, solubility, and inducing excretion.
[5]
Therefore, I must grant the order Novartis
seeks.
[6]
The issues are:
1.
Has Novartis shown that Teva’s allegation of
inutility is unjustified?
2.
Has Novartis shown that Teva’s allegation of
obviousness is unjustified?
3.
Has Novartis shown that Teva’s allegation of
insufficiency is unjustified?
II.
Background
[7]
Excess iron in the body can cause serious health
issues, particularly organ damage. A surplus of iron can be caused by repeated
blood transfusions (eg, to treat anemia) or by the excessive
absorption of iron from food. Primates, unlike some other species, do not have
an efficient mechanism to excrete excess iron. An effective iron chelator can
bind to iron and allow any excess to be excreted.
[8]
There are certain challenges involved in finding
a suitable iron chelator. The compound must be capable of entering the body and
binding to the iron located there. The resulting union between the iron and the
chelator, often referred to as the “coordination complex”, must also be
sufficiently soluble to be excreted. Further, compounds that can cause toxic
effects must obviously be avoided.
[9]
Novartis’s predecessor, Ciba-Geigy, first
marketed an iron chelator, called desferrioxamine (DFO), in the 1960s. DFO has
certain shortcomings – it can be administered only by way of daily infusions
lasting from 8 to 12 hours. To overcome this problem, researchers naturally
sought a chelator that could be administered orally. Many orally-administered
chelators tested over the years were found either to be too toxic or
insufficiently effective to be useful.
[10]
Ciba-Geigy began exploring potential iron
chelators in the 1980s. It tested hundreds of compounds and found a class
called bis-hydroxyphenyl-triazoles worthy of further study. Thirty of these
compounds come within the claims of the ‘951 patent. They were all found to
bind markedly to iron in vitro. Eighteen of those thirty were tested in
vivo in rats and were found to induce iron excretion. Eleven of those
eighteen compounds were then tested in monkeys, and all of them were found to
cause iron excretion.
[11]
The ‘951 patent specifically relates to
compounds called 3,5-diphenyl-1,2,4-triazoles Some of them were known; others were
novel. The inventors state that the compounds have useful pharmaceutical
properties as active iron chelators and, as such, they can be used in the
treatment of iron overload in warm-blooded animals.
[12]
The patent describes iron overload conditions
and the state of the art in their treatment, namely, the use of DFO and its
corresponding shortcomings. It goes on to state – and this is the key phrase
whose meaning is disputed by the parties – that the patented compounds were
found to “have valuable pharmaceutical properties when
used in the treatment of disorders which cause an excess of metal in the human
or animal body or are caused by it, primarily a marked binding of trivalent
metal ions, in particular those of iron.” The patent then mentions the
rat and monkey studies, and provides citations for published papers that
describe in detail those experiments.
[13]
The patent specifically states that the
invention relates to certain known compounds (referred to as “formula I”
compounds) for use in the treatment of diseases in humans. These known
compounds had previously been used for other purposes, for example, as herbicides.
The patent also describes certain novel compounds, a subset of the formula I
compounds, referred to as “formula II” compounds. The patent goes on to explain
the procedures for synthesizing the claimed compounds and preparing pharmaceutical
formulations of them.
[14]
The patent’s claims cover the so-called formula
I compounds, that is, the compounds that were previously known, for use in the
treatment of a disease involving excess iron in a human or animal body (claims
1 to 4). The claims also cover the novel formula II compounds (claims 5 to 37),
including DFS (claim 32), pharmaceutical preparations of them (claims 38 and
39), and their use in the treatment of excess iron in a human or animal body
(claims 40 to 42).
III.
Teva’s Allegations
[15]
Teva’s position on utility flows entirely from its
interpretation of the promise of the patent. Again, the key phrase in the ‘951
patent that frames the dispute between the parties is the following:
It has now been found that certain substituted
3,5-diphenyl-1,2,4-triazoles have valuable pharmaceutical properties when used
in the treatment of disorders which cause an excess of metal in the human or
animal body or are caused by it, primarily a marked binding of trivalent metal
ions, in particular those of iron.
[16]
Teva maintains that this sentence makes an
explicit promise of a specific result, namely, that the patented compounds had
not only been tested in humans, but they had been found to be valuable in the
treatment of iron-excess disorders in humans by virtue of their capacity to
bind markedly to iron. Teva contends that this broad promise applies across all
of the patent’s claims, including the bare claims for novel compounds, whether
or not the claims actually include any reference to any particular utility.
According to Teva, the doctrine of claim differentiation should not apply in
light of the ‘951 patent’s overarching promise.
[17]
Based on this construction of the patent, Teva
goes on to argue that the promise, that is, the stated utility of the ‘951
patent, had not been demonstrated because no testing in humans had actually been
carried out. That utility, Teva says, could not even have been soundly
predicted based only on Novartis’s tests in rats and monkeys.
[18]
Further, Teva suggests that if its construction
of the patent is incorrect, and the utility of the compounds is merely their
capacity to bind to iron, then the compounds of the invention are obvious
considering the state of the art and common general knowledge of the skilled
person at the relevant time.
[19]
Finally, Teva argues that the patent’s
disclosure is insufficient since a skilled reader of the ‘951 patent would not
realize that the real invention was DFS, buried as it is in claim 32.
IV.
Construction of the ‘951 Patent
[20]
The patent must be construed through the eyes of
the skilled person, before considering any issues relating to the patent’s
validity. The parties disagree on who the skilled person should be for purposes
of this exercise. Novartis says that the skilled person is a medicinal chemist
with knowledge of iron overload conditions. Teva says that the skilled person
has the aptitudes of a team made up of a chemist, a physician familiar with
iron overload conditions, and a person knowledgeable about pharmacological
testing of iron chelators.
[21]
In my view, the ‘951 patent is directed to a
person with a background in medicinal chemistry who would be familiar with
conditions involving excess iron and their treatment, including the properties
that an orally-administered iron chelator should have. This person could be a
physician, but need not be.
[22]
I find that the key phrase in the ‘951 patent
would be read by the skilled person as describing the desirable properties
possessed by the compounds of the invention, namely, their distinct ability to
bind to iron, their solubility, and their capacity to induce excretion. Those
properties would make the compounds valuable when used in the treatment of iron
excess disorders. I do not read the contested passage, as Teva would have me
do, as amounting to an assertion that the compounds had been tested in humans
and found to be valuable in treating iron overload conditions in humans.
[23]
Admittedly, the contested statement is
infelicitous. But its meaning can be arrived at by reading it in context. Again:
It has now been found that certain substituted
3,5-diphenyl-1,2,4-triazoles have valuable pharmaceutical properties when used
in the treatment of disorders which cause an excess of metal in the human or
animal body or are caused by it, primarily a marked binding of trivalent metal
ions, in particular those of iron.
[24]
The reference to “valuable
pharmaceutical properties” at the beginning of the sentence is completed
by the identification at the end of the sentence of what those properties are:
primarily a marked binding to trivalent metals, particularly iron. So, the
compounds have valuable properties, most importantly, a striking affinity to
iron. The middle of the sentence explains why those properties are valuable: “they are valuable when used in the treatment of iron excess
disorders”. It is those properties that are said to be valuable when
used in the treatment of iron excess disorders; the patent does not say that
the compounds have been used for that purpose.
[25]
Teva would have me read the sentence as stating
that the patented compounds were found to have valuable properties, including
iron chelation, when they were used in the treatment of iron excess disorders.
I concede that that is a possible construction of the sentence, but it is not
the most likely.
[26]
It is clear from the patent’s abstract, for
example, what the invention is. It says that the patented compounds “have useful pharmaceutical properties and are particularly
active as iron chelators. They can be used for the treatment of an iron
overload in the body of warm-blooded animals. Certain of these compounds are
novel.”
[27]
In this context, the words “useful” and
“valuable” are equivalent. The abstract makes clear that compounds with those
useful properties can be used for the treatment of iron overload
conditions. It does not say that they have been used for that purpose,
and it makes no reference to use in humans.
[28]
Further, immediately after the disputed
statement, in the same paragraph, the patent mentions tests in rats and
monkeys. It states that “for example, in an animal model”
the compounds are able “to prevent the deposition of
iron-containing pigments and in the case of existing iron deposits in the body
cause excretion of the iron”. There is no mention of any testing in
humans, and no reference to any treatment of iron overload conditions. I do not
see how a skilled reader could conclude from this information that the
compounds of the invention were tested in humans and found to provide valuable
treatment of iron overload conditions.
[29]
Teva points to other passages in the patent that
it says confirm its construction. For example, the patent says that the invention
relates to “the use of compounds of the formula I . . .
in the treatment of diseases which cause an excess of metal in the human or
animal body . . . in particular, in a method for the therapeutic treatment of
the human body”. Further, the patent also states that pharmaceutical
preparations containing compounds of formula I are for enteral and parenteral
administration “to warm-blooded animals, especially to
man”.
[30]
In my view, these passages do not advance Teva’s
assertion that the patent promises that all compounds of the invention have
been tested in humans and found to be useful in treating iron overload
disorders. The statements cited by Teva support the patent’s use claims in
respect of formula I compounds. As mentioned, the formula I compounds were
known. The patent claims these compounds (in claims 1 to 4) “for use in treatment of a disease which causes an excess of
metal in a human or animal body or a disease which is caused by the excess of
metal in the human or animal body.” Therefore, the passages merely
confirm what is stated in the claims themselves in respect of the formula I
compounds. Those passages, in my view, do not help in the construction of the
claims as a whole. In particular, they do not suggest that the claims for the
novel compounds of formula II should be read as including an overarching
promise of their utility in the treatment of iron excess disorders in humans.
[31]
Teva also submits that the patent’s reference to
the rat and monkey studies should not permit Novartis to resile from a clear
statement that the patented compounds had been found to offer valuable
treatment of iron overload conditions in humans. In principle, Teva is right. A
patentee cannot shrink from its express promise by pointing to the limitations
of its own work. As Justice Donald Rennie has noted, “to
circumscribe the scope of the promise based on what is demonstrated in the
patent makes it impossible to ever conclude that a patent is invalid for lack
of utility” (Astrazeneca Canada Inc v Apotex Inc, 2014 FC 638 at
para 128).
[32]
However, as discussed, I do not find in the
patent the express promise that Teva must rely on to make this point. Further,
the reference to the rat and monkey studies helps explain what the stated
utility of the patent is. I do not rely on those references to permit Novartis
to undercut the scope of its own promise but rather to understand what the
stated utility of the patent is (Apotex Inc v Allergan Inc et al, 2015
FCA 137 at para 7(i)).
[33]
Accordingly, through the eyes of the skilled
person, I would construe the compound claims of the patent as follows: Claims 5
to 37 relate to the novel formula II compounds, including DFS (claim 32), which
are useful for their marked iron-binding characteristics as shown both in
vitro and, in animal studies, in vivo. The latter confirm that the
compounds are sufficiently soluble to induce excretion of the iron complex. I
would not read into those claims the elevated promise advanced by Teva – that the
compounds have been tested and found to be valuable in the treatment of iron
excess disorders in humans.
[34]
I believe this approach to construction is
supported by well-accepted principles of patent law. Generally speaking, the
utility requirement represents a fairly low threshold. The exception is where
the inventors explicitly promise a specific result, particularly if the stated
utility is set out in the claims as opposed to the disclosure. An explicit
promise set out in the disclosure can apply to all claims but, at the same
time, it may be appropriate to distinguish between the promise of the compound
claims, on the one hand, and the promise of the use claims, on the other (Apotex
Inc v Pfizer Canada Inc, 2014 FCA 250 at paras 64, 65, 71, 77, 87, 88).
[35]
Here, as will be discussed further below, the
‘951 patent does contain an explicit promise of a specific result, but only in
respect of the particular uses referred to in the use claims of the patent.
There is no such promise in respect of the compound claims. Accordingly, the
usual, relatively low, utility requirement applies to those claims.
V.
Issue One – Has Novartis shown that Teva’s
allegation of inutility is unjustified?
[36]
Teva has submitted sufficient evidence to put
the issue of inutility into play. Accordingly, Novartis bears the burden of
establishing that Teva’s allegations are unjustified.
[37]
As mentioned, Teva alleges that the explicit
promise of the ‘951 patent is that the claimed compounds had been shown to be valuable
in the treatment of disorders involving excess iron in humans, by virtue of
their capacity to bind to iron. Obviously, says Teva, the inventors are telling
skilled readers of the patent that they had carried out sufficient tests in
humans to allow them to make that claim. Since there is no evidence that any
such tests were conducted, Teva contends that the stated utility of the patent
had not been demonstrated; nor could any sound prediction be made that that
utility could be achieved.
[38]
In addition, based on that construction of the
patent, Teva alleges that the utility of the invention must also include an
absence of toxicity, an acceptable level of solubility, and suitability for
administration for chronic conditions. Otherwise, Teva says, the compounds
could not be said to possess the kind of valuable pharmaceutical properties
that a drug used in the treatment of iron overload conditions would have to
have.
[39]
I am satisfied that these allegations are
unjustified. In my view, as discussed above, Teva has overstated the stated utility
of the ‘951 patent (at least in respect of the compound claims). In respect of
those claims, the stated utility is simply the compounds’ capacity to bind markedly
to iron both in vitro and, in animal studies, in vivo, and that
they were sufficiently soluble to induce iron excretion. The inventors’ goal
was surely to achieve a method for treating iron overload in human patients,
but they were not there yet.
[40]
In respect of the compounds that had been tested
in animals, the stated utility had clearly been demonstrated as of the filing
date of the patent. Further, since all of the compounds tested in animals showed
the same effects, it was soundly predictable that the other claimed compounds
tested only in vitro would achieve similar results. As Dr Desi Raymond Richardson
states, “[w]hile a minority of the 30 compounds were not
studied in an animal model, it would be reasonable to predict that they would
also have some activity in these models” (see Annex II for a summary of
experts’ qualifications). Therefore, I am satisfied that Teva’s allegation of
inutility is unjustified in respect of the compound claims.
[41]
However, in respect of the use claims, Teva’s
allegations have merit. As Novartis’s own experts acknowledge, those claims do contain
an explicit promise of a specific result. Dr Richardson states “it is clear from reading the patent that the only explicit
promise of a specific utility is found in claims 1 and the other use claims”.
Similarly, Dr Thomas Baillie says of the word “treatment” “I do not see how there can be an explicit promise of a
specific result apart from manner in which it is used in claim 1 and claims
40-42”. In my view, that utility had not been demonstrated. Nor, the
experts agree, could it have been soundly predicted from the animal studies.
Those studies serve as an excellent screen for drug development and might tell the
skilled person that the tested compounds would likely have some activity in
humans, but that is a long way from actual treatment of iron overload disorders
in humans. As Dr Victor Gordeuk agreed, hundreds of promising iron chelators
had been tried and tested over the years, and almost all of them were abandoned
for toxicity or ineffectiveness. A lot of work, he said, would be needed to
find a compound that could actually be used in treatment. Dr René Lattman also
observed that most iron chelators are toxic at doses needed for pharmacological
action.
[42]
In this context, Teva’s allegations that the
compounds must be non-toxic, reasonably soluble, and suitable for chronic
administration have greater force. However, overall, I am satisfied that Novartis
has met its burden of showing that Teva’s broad allegation that the ‘951 patent
as a whole is invalid for inutility is unjustified. Teva’s allegations in
respect of the compound claims of the ‘951 patent are not justified.
VI.
Issue Two – Has Novartis shown that Teva’s
allegation of obviousness is unjustified?
[43]
Teva has submitted sufficient evidence to put
the issue of obviousness into play. Accordingly, Novartis bears the burden of
establishing that Teva’s allegations are unjustified.
[44]
In the event that its submissions on the promise
of the ‘951 patent were unsuccessful, Teva argues that the compounds of the
‘951 patent are obvious because they are virtually identical to compounds
disclosed in some prior publications. Those compounds were shown to be effective
metal chelators and, says Teva, based on the skilled person’s common general
knowledge and the state of the art, he or she would not have had to take any
inventive step to arrive at the invention set out in the patent.
[45]
I disagree.
[46]
The test for obviousness is well-settled (Apotex
v Sanofi-Synthelabo Canada, 2008 SCC 61, [2008] 3 S.C.R. 265 at para 67). It
involves a comparison between the state of the art and common general knowledge
of the skilled person, on the one hand, and the inventive concept of the
patent’s claims, on the other. If there is no difference between the two
comparators, the claims are obvious. If there is a difference, the claims are
obvious if the skilled person would not need to take any inventive steps to
bridge the gap. In pharmaceutical cases, it will often be useful also to
consider whether the steps taken by the inventors were “obvious
to try”. Relevant factors to take into account would include: whether
there was a motive to find the solution that the patent teaches; whether it was
more or less self-evident that the steps taken would work; and whether routine
trials were carried out, as opposed to prolonged and arduous experimentation.
[47]
Teva’s position on this issue depends on a
substantially diminished construction of the invention contained in the ‘951
patent. Here, Teva says that if the patent does not contain an explicit,
overarching promise of a specific result (ie treatment of iron overload
conditions in humans), then it should be read as teaching a group of compounds
that simply bind to iron. In other words, according to Teva, the inventive concept
of the ‘951 patent would be no more than a set of compounds with an affinity
for iron.
[48]
Based on that statement of the inventive
concept, Teva then says that the compounds of the invention are obvious in light
of the state of the art and common general knowledge of the skilled person. In
particular, similar compounds with like properties were disclosed in the prior
art.
[49]
Based on my construction, described above, I
would describe the inventive concept of the ‘951 patent as a class of compounds
with a capacity to bind to iron, which are soluble in vivo and capable
of inducing excretion of the iron complex. There is no evidence that compounds
with these properties would have come within the common general knowledge of
the skilled person, or that they were disclosed in the prior art.
[50]
The prior art references on which Teva relies do
not reveal any compounds with the characteristics of those claimed in the ‘951
patent. Those references disclose
(i) A method for synthesizing compounds that come within the formula I
compounds of the ‘951 patent for use as light stabilizers (Ryabukhin (1983)).
This paper contains no information about iron chelation but is referred to in
the patent in relation to a method for making the compounds of the invention.
(ii) A method for synthesizing polymeric compounds that bind to copper,
nickel, and cobalt for use as antifriction materials (Ryabukhin (1987/1988)).
This paper contains information about chelation to divalent metals, not
trivalent metals, such as iron.
(iii) A patent
relating to starting materials for compounds that can bind to certain bivalent metals,
not including iron, resulting in complex compounds that are heat-resistant,
mouldable, and mechanically strong (US 3,113,942).
(iv) A patent
relating to chelates of metal ions that yield compounds that are heat-resistant
and mouldable (US 3,211,698).
(v) Papers describing use of the rat model to test chelators (analogues
of desferrithiocin) through oral administration (Bergeron 1991, 1994).
(vi) A paper
describing iron chelators, tested in vitro, that could be used in
treating iron overload diseases or cancer (Richardson, 1995).
[51]
I have considerable doubt whether some of these
sources form part of the relevant prior art. For example, the Ryabukhin
papers were published in obscure journals and would likely not have been
located by the skilled person looking for information on iron chelators. While
Dr Alvin Crumbliss, Teva’s expert, said he was aware of the Ryabukhin papers,
and the first of them was known to Dr Lattman, one of the inventors, that is
not sufficient to characterize them as being within the common general
knowledge of the hypothetical skilled person looking for compounds that would
markedly bind to iron for potential use in treating iron overload disorders.
In my view, that person would likely be looking for sources specifically on the
chelation of iron and trivalent metals, not chelation in general. While, as Dr
Crumbliss points out, the difference between the compounds in Ryabukhin
1987/1988 and DFS is small (the latter contains a carboxylate group to
improve solubility), that, too, is not sufficient to make DFS an obvious choice
as a compound to develop for an entirely different purpose – treatment of iron
overload disorders.
[52]
Similarly, like the compounds in the Ryabukhin
references, the two US patents related to chelators that bind to bivalent
metals, not trivalent metals such as iron. It is possible, as Dr Crumbliss
observes, that those compounds would also bind to iron, but it is not obvious
that they would do so markedly, or at all. Dr Lattman explains that while DFS
will also bind to other metals, it is especially selective for iron. For
example, its affinity for iron is 16 orders of magnitude higher than it is for
copper. Further, these sources, as well as Richardson, do not say
anything about the ability of the respective compounds to be active iron
chelators in vivo, or to be sufficiently soluble to induce excretion.
[53]
Teva argues that the Patent Act (s 28.3;
see Annex I for provisions cited) no longer requires that the relevant prior
art be discoverable on a reasonably diligent search – it merely has to be
publicly available. Teva cites Barrigar, et al, Canadian Patent Act
Annotated, 2nd ed loose-leaf (consulted on 1 April 2015 (Aurora, Ont:
Canada Law Book, 1994) at PA-341 where the authors raise a question whether s
28.3 supersedes the previous case law on the accessibility of prior art. Teva
also relies on the Federal Court of Appeal’s discussion on anticipation in Wenzel
Downhole Tools Ltd v National-Oilwell Canada Ltd, 2012 FCA 333 at paras
68-70 and argues this should apply to the law of obviousness. However, there
is case law applying the usual “reasonably diligent search” criterion even
after the enactment of s 28.3 (Dow Chemical Company v NOVA Chemicals
Corporation, 2014 FC 844 at paras 232-236; Eurocopter v Bell Helicopter Textron
Canada Limitée, 2012 FC 113 at para 80, aff’d 2013 FCA 219; Eli Lilly
and Company v Apotex Inc, 2009 FC 991 at para 532; Takeda Canada Inc v
Canada (Minister of Health), 2015 FC 570 at paras 59-60). I see no reason
to take a different approach here.
[54]
Even assuming that Teva has identified the
relevant prior art, there is a significant gap between those sources and the
inventive concept of the ‘951 patent. In my view, the evidence demonstrates the
inventors of the ‘951 patent had to apply inventive ingenuity to bridge that
gap. Therefore, the subject matter of the ‘951 patent is not obvious.
[55]
Further, I note that the inventors spent many
years testing hundreds of compounds before they arrived at the compounds of the
‘951 patent. The iron chelation project began in 1980, but it was not until the
mid-1990s that the focus turned to the bis-hydroxyphenyl-triazoles, of which
DFS is a member. In all, five groups and between 700 and 800 individual
compounds were synthesized and tested over that time frame. This evidence
suggests that the inventive concept of the ‘951 patent was far from obvious; indeed,
there is nothing in the prior art that would suggest that this class of
compounds was even obvious to try.
VII.
Issue Three – Has Novartis shown that Teva’s
allegation of insufficiency is unjustified?
[56]
Teva alleges that the disclosure of the ‘951
patent does not allow a skilled person to work the invention. In its NOA, Teva
alleged that a skilled worker would not know which of the 30 novel compounds
claimed would be effective in treating iron overload disorders. It suggests
that the real invention was buried in claim 32.
[57]
This argument proceeds from a construction of
the patent that I rejected above. Other than the claims relating to the use of
the compounds, the patent relates to novel compounds that bind markedly to
iron, are soluble in vivo, and induce excretion of the resulting iron
complex. All thirty of the claimed novel compounds were demonstrated or soundly
predicted to have those properties, and the patent describes how to synthesize
all of them. The patent also provides the skilled person with information about
the tests that were used to assess the compounds’ activity in vivo (ie,
the animal studies). In my view, therefore, Novartis has shown that it met
the requirements of s 27(3) of the Patent Act by providing a skilled
person with a description of the invention and instructions on how to put it
into practice (Cobalt Pharmaceuticals Company v Bayer Inc, 2015 FCA 116
at paras 64-67).
[58]
Teva also raises other issues relating to
sufficiency. Novartis says that these issues were not set out in Teva’s NOA
and, therefore, that they are not properly before me. Since I find that these
additional allegations can easily be dismissed, I will address them briefly.
[59]
Teva points out that the patent does not
specifically identify the compounds that had been tested in vivo, so a
skilled reader would not know which of them would work. Further, the patent
does not tell the skilled person that one of the compounds tested in a rat
might have been toxic. Finally, while the patent states that iron excretion had
been achieved in animal models at doses beginning at 5 μmol/kg, there is
no evidence of any testing done at that dose.
[60]
As discussed above, all of the thirty claimed
novel compounds had been demonstrated or soundly predicted to have the stated
utility set out in the patent. A skilled person would have had no difficulty making
and using any one or more of those compounds based on the information in the
patent.
[61]
It is true that one rat died after receiving one
of the claimed compounds (claim 22). However, there is no evidence that the
death was the result of a toxic event. It is equally plausible that the
compound that was administered was overly effective and removed too much iron
from the animal. In the absence of evidence of toxicity, the inventors had no
obligation to inform the skilled reader about that isolated event.
[62]
The patent states that the compounds of the
invention were effective at reducing iron in the animal models “in doses from approximately 5 μmol/kg”.
In fact, no tests were done at that dose. However, the skilled reader would not
be mislead by that statement. There is no evidence that the compounds of the
invention would not be active at that dosage. If a skilled person were to
attempt to work the invention at that dosage, he or she might well find some effect.
But the skilled person would surely want to test the compounds at higher
dosages, since the patent identifies only a minimum, not a definitive dose or
dosage range.
[63]
Therefore, I do not find Teva’s additional
allegations on sufficiency to be persuasive. I am satisfied that Novartis has
shown that the disclosure in the ‘951 patent was sufficient.
VIII.
Conclusion and Disposition
[64]
I have found that Novartis has met its burden of
showing that Teva’s various allegations relating to the validity of the ‘951
patent are unjustified. Accordingly, I must grant the order Novartis seeks
prohibiting the Minister of Health from issuing an NOC to Teva, with costs.
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