Docket: A-106-17
Citation:
2017 FCA 190
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CORAM:
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WEBB J.A.
NEAR J.A.
GLEASON J.A.
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BETWEEN:
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BRISTOL-MYERS
SQUIBB CANADA CO. and BRISTOL-MYERS SQUIBB HOLDINGS IRELAND
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Appellants
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and
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APOTEX INC. and
THE MINISTER OF
HEALTH
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Respondents
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REASONS
FOR JUDGMENT
GLEASON J.A.
[1]
The appellants, Bristol-Myers Squibb Canada Co.
and Bristol-Myers Squibb Holdings Ireland (which I call collectively simply
BMS), developed a compound called dasatinib, a new drug used in the treatment
of a form of leukemia known as chronic myelogenous leukemia or CML. BMS markets
its pharmaceutical preparation of dasatinib as SPRYCEL®.
[2]
On August 25, 2009, BMS obtained a patent, Canadian
Patent No. 2,366,932 (the 932 patent) that contains, as claim 27, a claim to the
compound dasatinib. On July 10, 2012, BMS obtained a subsequent patent, Canadian
Patent No. 2,519,898 (the 898 patent) that, among other things, claims the
oral administration of dasatinib to humans to treat both CML generally and to
treat cases of CML where the patients have become resistant to imatinib, another
drug that is also used to treat CML.
[3]
The respondent, Apotex Inc., developed a generic
version of dasatinib and filed an abbreviated new drug submission (ANDS) with
the respondent Minister of Health, seeking a Notice of Compliance (NOC) for
authorization to sell its generic version of the drug in Canada. In its ANDS,
Apotex named SPRYCEL® as the reference product. As the 932 and 898 patents are
listed against SPRYCEL® in the patent register maintained under the Patented
Medicines (Notice of Compliance) Regulations, SOR/93-133 (the PMNOC
Regulations), Apotex could not obtain an NOC, authorizing the sale of its
APO-Dasatinib product before the expiry of the 932 and 898 patents, unless it claimed
it did not infringe them or challenged their validity and its position was
either not contested by BMS or was found to be justified by the Federal Court.
[4]
Apotex filed Notices of Allegation that, among
other things, challenged the validity of the 932 and 898 patents on May 22,
2015. In response, BMS filed a Notice of Application with the Federal Court on
July 2, 2015 for an order prohibiting the issuance of the NOC pursuant to
subsection 6(1) of the PMNOC Regulations. In a judgment dated March 21,
2017 in Bristol-Myers Squibb Canada and Bristol-Myers Squibb Holding Ireland
v. Apotex Inc. and the Minister of Health, 2017 FC
296, the Federal Court (per Manson, J.) dismissed BMS’ prohibition application
in respect of both patents, finding some of Apotex’ allegations to be justified.
[5]
More specifically, by the time the matter was
argued, infringement had been admitted and the claims in issue narrowed to
claim 27 in the 932 patent and to claims 1 and 3 in the 898 patent. The
Federal Court determined that even though claim 27 in the 932 patent was a bare
composition claim for dasatinib, it nonetheless promised that this compound would
be useful in treating a range of ailments and also in inhibiting enzymes from two
different families of protein tyrosine kinases or PTKs. The Federal Court
further held that Apotex’ allegations regarding the invalidity of the 932
patent were justified as BMS failed to establish that all of these promised utilities
for claim 27 were demonstrated or soundly predicted as of the relevant date. As
concerns the 898 patent, the Federal Court held that Apotex’ allegations
regarding invalidity were justified since BMS had failed to establish that the
two claims in issue were not obvious and not invalid due to double patenting.
[6]
BMS has appealed the Federal Court’s judgment to
this Court, and in its appeal challenges the foregoing findings. As of the date
of this judgment, the Minister of Health has still not made a determination on
Apotex’ application for an NOC for its APO-Dasatinib product so the issues
raised in this appeal remain live ones.
[7]
Following the argument of this appeal, the Supreme
Court of Canada issued its decision in AstraZeneca Canada Inc. v. Apotex
Inc., 2017 SCC 36, 147 C.P.R. (4th) 79 [Esomeprazole], which
fundamentally recasts the principles applicable to assessing whether patents
meet the utility requirement in section 2 of the Patent Act, R.S.C.
1985, c. P-4. That section requires in part that patentable inventions be “useful”. The parties were afforded the opportunity to
make post-hearing submissions as to the impact of the Supreme Court’s decision
in Esomeprazole on the present appeal.
[8]
For the reasons set out below and in light of
the Supreme Court of Canada’s decision in Esomeprazole, I believe that
the Federal Court’s determination regarding the lack of utility of claim 27 in
the 932 patent cannot stand and that, accordingly, this appeal must be granted
in respect of the 932 patent. As concerns the 898 patent, on the other hand, I
do not believe that the Federal Court made a reviewable error in concluding
that claims 1 and 3 of that patent were obvious. This finding is sufficient to
uphold the Federal Court’s dismissal of the prohibition application in respect
of the 898 patent and, as BMS concedes, it is unnecessary to examine the ground
of appeal relating to double patenting.
[9]
It follows that I would allow this appeal in
part, set aside the judgment of the Federal Court in respect of the 932 patent
and, making the decision it ought to have made, would issue an order of
prohibition against the Minister of Health, prohibiting the issuance of an NOC
to Apotex for its APO-Dasatinib product until the 932 patent expires. As
success is divided, I would order that each party bear its own costs before
this Court and the Federal Court.
I.
Background
[10]
It is useful to commence by reviewing some of
the scientific background that was before the Federal Court to put the two
patents in issue into context.
[11]
Dasatinib and the other compounds claimed in the
two patents are inhibitors of PTKs, which are enzymes that are involved in the
activation or deactivation of various functions within a cell. PTKs can be
divided into two categories: receptor and non-receptor PTKs. The difference
between the two has to do with where in the cell the pertinent biochemical
reaction takes place. Two examples of receptor PTKs are enzymes called HER1 and
HER2. Non-receptor PTKs include kinases of the Src-family and the BCR-ABL
kinase, which is linked to leukemia.
[12]
Tyrosine kinases (i.e. the “TK” in “PTK”) are a
subset of protein kinase enzymes that act as cellular regulators. Tyrosine
kinases phosphorylate (or attach a phosphate group to) different proteins and
peptides within a cell. This phosphorylation is essentially a cellular
signalling mechanism. When functioning normally, these kinases provide
phosphate “signals” that trigger cellular
activity such as cell division. When functioning abnormally, the kinases’
regulating role in the cell is compromised and this can lead to the
over-development or uncontrolled division of cells, which can develop into
cancers or other disorders.
[13]
PTK inhibitors act to prevent abnormal
phosphorylation, or more simply, to regulate communication within the cell by
targeting certain enzymes so as to prevent abnormal cellular activity that can
lead to various disorders and diseases in humans, including cancers like
leukemia.
[14]
CML, like all types of leukemia, is a form of
cancer affecting the blood. CML constitutes about 15-20% of adult leukemias
and, if left untreated, will lead to death. CML is believed to be caused by a
genetic mutation that results in the development of an abnormal combined PTK called
BCR-ABL. This tyrosine kinase initially triggers the overproduction of abnormal
myeloid white blood cells in the bone marrow. Over time, these excess abnormal
myeloid cells crowd out healthy cells in the marrow and blood.
[15]
Prior to the discovery of dasatinib, there were
three common treatments for CML: bone marrow transplants, immunotherapy using
interferon and, more recently, treatment with the BCR-ABL inhibitor, imatinib.
There are side-effects associated with bone marrow transplants and interferon.
So the discovery of imatinib represented an important advance in the treatment
of CML. By 1999-2000, however, it became apparent that a significant proportion
of CML patients suffered from forms of the disease that either became or were
always resistant to treatment with imatinib. Dasatinib treats CML and is
effective in patients who have imatinib-resistant CML. Thus, it is an important
new drug in the battle against CML.
II.
The 932 Patent
[16]
The 932 patent was filed on April 12, 2000,
published on October 26, 2000 and issued on August 25, 2009. It has a priority
date of April 15, 1999. The title of the patent is “Cyclic
Protein Tyrosine Kinase Inhibitors”. The Field of the Invention section
in the 932 patent provides:
The present
invention relates to the cyclic compounds and salts thereof, to methods of
using such compounds in treating [PTK]-associated disorders such as immunologic
and oncologic disorders, and to pharmaceutical compositions containing such
compounds.
[17]
The patent contains a section devoted to setting
out the background of the invention. I summarize here only those portions of
this section that are relevant to this appeal. In this regard, in this section
the inventors set out the various types of PTKs, which are said to include:
[…] receptor tyrosine kinases (RTKs),
including members of the epidermal growth factor kinase family (e.g., HER1 and
HER2), platelet derived growth factor (PDGF), and kinases that play a role in
angiogenesis (Tie-2 and KDR); and, in addition, non-receptor tyrosine kinases,
including members of the Syk, JAK and Src (e.g. Src, Fyn, Lyn, Lck and Blk)
families [...].
[18]
The next section of the patent is entitled “Summary of the Invention”. The opening words of this
section state that “[t]he present invention provides
cyclic compounds of the following formula I and salts thereof, for use as [PTK]
inhibitors”, which is followed by a lengthy chemical formula. It is undisputed
that this formula includes millions of compounds.
[19]
The next two sections in the 932 patent set out
the preferred compounds and methods for preparing them. Thereafter, the 932 patent
contains a section entitled “Utility”. It
commences as follows:
The compounds of
the present invention inhibit [PTKs], especially Src-family kinases such as
[followed by a list of several such PTKs], and are thus useful in the
treatment, including prevention and therapy, of [PTK]-associated disorders such
as immunologic and oncologic disorders. The compounds inhibit also receptor
tyrosine kinases including HER1 and HER2 and are therefore useful in the
treatment of proliferative disorders such as psoriasis and cancer. The ability
of these compounds to inhibit HER1 and other receptor kinases will also permit
their use as anti-angiogenic agents to treat disorders such as cancer and diabetic
retinopathy.
[20]
The section on utility continues by defining PTK-associated
disorders and then moves on to state that “[t]he
present invention thus provides methods for the treatment of [PTK]-associated
disorders, comprising the step of administering […] at least one compound of the
formula I in an amount effective therefor”. The section then provides
some examples of possible uses of the compounds to treat various disorders,
noting that the “compounds of the present invention can
also be used for the treatment of proliferative diseases, including psoriasis
and cancer”. A subsequent paragraph in the section contains descriptions
for possible pharmaceutical formulations and details of the assay tests
conducted. Five hundred and eighty (580) compounds are disclosed, which were
said to have been assayed and shown to have been effective to inhibit some PTKs
in the Src-family. One of the compounds disclosed and assayed – example 455 – is
dasatinib. The utility section of the 932 patent also states that “[t]he compounds of the formula I may be administered by any
suitable means, for example, orally […]”.
[21]
The section of the 932 patent following the
section entitled “Utility” sets out the claims. Claim
1 is for the chemical formula for formula I, which comprises the millions of
claimed compounds. Claims 2 to 7 set out cascading claims to various compounds
coming within claim 1. Claim 8 claims the use of “at
least one compound” conforming to the generic formula that differs in
one respect from the formula in claim 1 for the “treatment
of a [PTK]-associated disorder”. Claims 9 to 19 claim various uses of claim
8 for the inhibition of different PTKs and treatment of different
PTK-associated disorders. Claims 10 to 17 claim the use of claim 8 for the
inhibition of specific Src-family PTKs. Claims 18 and 19 claim the use of claim
8 for the inhibition of HER1 and HER2 PTKs respectively. Claims 20 to 22 claim
specific pharmaceutical uses of claim 8.
[22]
Thereafter, the patent makes claims to specific
compounds and their uses. Claim 27 – the only claim at issue in this case – is
a bare composition claim for dasatinib. It provides:
27. The compound
or a salt thereof.
[23]
The patent then makes several claims that are
dependent on claim 27:
•
Claim 28 claims dasatinib for the treatment of
cancer;
•
Claim 29 claims the use of dasatinib in a
medication for the treatment of cancer;
•
Claim 30 claims a pharmaceutical composition
containing dasatinib and a “pharmaceutically acceptable
vehicle or carrier thereof”;
•
Claim 31 claims dasatinib as a treatment of “a [PTK]-associated disorder”;
•
Claim 32 claims the use of dasatinib in a
medication for the treatment of a [PTK]-associated disorder;
•
Claims 35 and 36 repeat claims 28 and 29,
replacing the reference to “a compound of claim 27”
with a picture of the molecule itself (as in claim 27); and
•
Claims 37 to 43 claim the use of claims 35 or 36
in relation to specific types of cancer. CML is not included as one of these
cancers.
III.
The 898 Patent
[24]
The 898 patent was filed on March 23, 2004,
published on October 7, 2004 and was issued on July 10, 2012. It has a priority
date of March 24, 2003. The title of the patent is “Oral
Administration of Cyclic [PTK] Inhibitors”. The specification in the 898
patent is virtually identical to that in the 932 patent, the only difference
being that a few extra paragraphs appear in the 898 patent on preferred dosages
for oral and intravenous administration.
[25]
BMS conducted clinical trials of dasatinib
subsequent to filing the 932 patent. It says that the results of those trials
led it to file the 898 patent, which claims specific oral therapeutic uses for dasatinib.
At issue in this appeal are claims 1 and 3.
[26]
Claim 1 claims:
1. Oral use for treating cancer of a
compound of formula IV or a salt thereof:
where the cancer
is [CML].
The chemical compound identified in claim 1
is dasatinib.
[27]
Claim 3 claims:
3. The use of claim 1 […] wherein the [CML] is resistant to STI-571.
STI-571 is imatinib.
[28]
Thus, claim 1 of the 898 patent claims the oral
use of dasatinib to treat CML, and claim 3 claims the oral use of dasatinib to
treat imatinib-resistant CML.
IV.
Did the Federal Court Err in Finding that
Apotex’ Allegation Regarding the Inutility of the 932 Patent was Justified?
[29]
With this background in mind, I turn now to consider
the 932 patent and commence by reviewing the findings of the Federal Court on
the utility of claim 27.
A.
The Reasons of the Federal Court
[30]
As the Federal Court decided the case prior to
the release of the decision of the Supreme Court in Esomeprazole, the
Federal Court applied the analytical framework that had previously been applied
by this Court and the Federal Court for many years. Under that framework, in
assessing whether a patent met the utility requirement in section 2 of the Patent
Act, a court was required to first determine whether the patent in issue contained
a promise and, if so, what the scope of such promise was. Following this
determination, the court was then called upon to assess whether such promise
was either demonstrated or soundly predicted as of the relevant date.
Sometimes, courts held that no promise was made in the claim(s) in issue, in
which event a mere scintilla of utility would have been sufficient to meet the requirement
that an invention be useful.
[31]
Applying the foregoing framework, the Federal
Court first construed the promise that frames claim 27 and determined that the
932 patent made the following promise of utility across all of the claims,
including claim 27 (Reasons at paras. 97, 110):
[…] the promise is that the compounds will inhibit both a Src-family
PTK and HER1/HER2, and be therapeutically useful in treating a PTK-associated
disorder or useful as anti-angiogenic agents.
[32]
After construing this to be the promise relevant
to claim 27 of the 932 patent, the Federal Court then moved on to consider whether
this promise had been demonstrated or soundly predicted as of the relevant date.
It erroneously selected the priority date of the 932 patent of April 15, 1999
as being the relevant date for assessing utility when the correct date for the
assessment of utility ought to have been the Canadian filing date of April 12,
2000 (see Aventis Pharma Inc. v. Apotex Inc., 2006 FCA 64 at para. 30,
46 C.P.R. (4th) 401). Nothing of relevance to this appeal turns on this error
as to the date in respect of which utility is to be assessed.
[33]
In its assessment of utility, the Federal Court
made three findings. First, as was indeed conceded by Apotex, the Court noted
that the ability of dasatinib to inhibit some Src-family PTKs was demonstrated
as of the relevant date. However, the Court went on to determine that the
ability of dasatinib to also inhibit HER1 or HER2 was neither demonstrated nor
soundly predicted as of that date. Finally, as was conceded by BMS, the Court
held that the ability of dasatinib to treat PTK-associated disorders or to act
as an anti-angiogenic agent was neither demonstrated nor soundly predicted as
of the relevant date.
[34]
The Federal Court thus held that BMS had failed
to establish that the various promises applicable to claim 27 of the 932 patent
were demonstrated or soundly predicted by the relevant date. It therefore
concluded that Apotex’ allegation of inutility in respect of claim 27 in the 932 patent
was justified.
B.
Analysis - the Impact of the Supreme Court’s
Decision in Esomeprazole
[35]
In Esomeprazole, in a unanimous decision,
the Supreme Court abolished the promise doctrine, holding that the doctrine is inconsistent
with the words and scheme of the Patent Act. Thus, in assessing whether
a patent meets the utility requirement set out in section 2 of the Patent
Act, courts are no longer to ascertain whether a patent fulfils the
promise(s) it makes. Rather, according to the Supreme Court, the requisite
utility is to be measured with respect to the subject-matter of the invention
and involves the following (Esomeprazole at paras. 54 and 55):
54. […] First, courts must identify the
subject-matter of the invention claimed in the patent. Second, courts must ask
whether that subject-matter is useful – is it capable of a practical purpose
(i.e. an actual result)?
55. The Act does not prescribe the degree or
quantum of usefulness required, or that every potential use be realized – a
scintilla of utility will do. A single use related to the nature of the subject-matter
is sufficient, and the utility must be established by either demonstration or
sound prediction as of the filing date.
[36]
Applying the foregoing test for utility to claim
27 of the 932 patent therefore involves two steps: first, determining the
subject-matter of the claim and, second, determining whether this
subject-matter was shown to be useful either by demonstration or sound
prediction as of the filing date.
[37]
Insofar as concerns the first point, contrary to
what Apotex asserts in its supplemental written submissions, the subject-matter
of claim 27 of the 932 patent is not the potential therapeutic uses for
dasatinib. Rather, the subject-matter of claim 27 is merely the compound,
dasatinib, itself. This is all that claim 27 claims, and it is erroneous to
expand the subject-matter of the claim beyond what it says. In Esomeprazole,
the Supreme Court found the subject-matter of a similar compound claim to be
simply the compound itself (Esomeprazole at para. 61). Thus, contrary to
what Apotex says, the relevant subject-matter in issue is merely the compound,
dasatinib.
[38]
The second step of the requisite analysis
involves determining whether BMS has demonstrated or soundly predicted as of
the relevant date that dasatinib had at least a scintilla of utility. In my
view, BMS has so demonstrated as it is conceded that as of the filing date it
demonstrated that dasatinib acted to inhibit Src-family PTKs. Such
demonstration is referred to in the specification of the 932 patent, itself (the
932 patent at pp. 50-51), and confirmed in the evidence of the inventors that
BMS filed.
[39]
While conceding that BMS did demonstrate as of
the relevant date that dasatinib acted to inhibit Src-family PTKs, Apotex
nonetheless asserts that such demonstration does not establish a scintilla of
utility as it says that showing “the binding of
dasatinib to certain isolated enzymes in a test tube […] cannot satisfy the
utility requirement” (supplemental written submissions of Apotex at
para. 5).
[40]
I disagree. Establishing that a compound has the
ability to inhibit a biological target implicated in disease is doubtlessly a
useful discovery. Here, it was known as of the relevant date that enhanced
activity of PTK was involved in many diseases, as stated in the specification
and confirmed in the evidence of several of the experts. Thus, discovery of a
substance that acted to inhibit certain PTKs represented an important advance
and certainly meets the minimal utility requirements that are now applicable
following the decision of the Supreme Court in Esomeprazole.
[41]
I parenthetically note that a similar sort of
discovery was found to satisfy the utility requirement in Esomeprazole and
Teva Canada Limited v. Novartis AG, 2013 FC 141, 109 C.P.R. 4th 1,
which dealt with the patent for imatinib. In the latter case, Snider, J.,
writing for the Federal Court, held that the discovery that imatinib was a PTK-inhibitor
was useful.
[42]
Thus, BMS has established that it met the
requirements for utility as they have been reframed by the Supreme Court in Esomeprazole
as it demonstrated that dasatinib acted as a PTK-inhibitor as of the relevant
date. It therefore follows that the Federal Court’s decision in respect of the
inutility of claim 27 of the 932 patent cannot stand.
[43]
Despite this, Apotex says that BMS’ appeal
should be dismissed as it asserts that the 932 patent fails to comply with
the requirements of subsection 27(3) of the Patent Act. However, the
Federal Court found against Apotex on this issue and Apotex did not challenge
this finding on appeal. It cannot now seek to raise this issue in its
supplemental written submissions, in which it was granted leave to only make
submissions with respect to the implications of the decision in Esomeprazole
on the issues in dispute.
[44]
I would accordingly grant BMS’ appeal in respect
of the 932 patent.
V.
Did the Federal Court Err in Finding that
Apotex’ Allegation Regarding Obviousness of the 898 Patent was Justified?
[45]
I turn next to the issues concerning the 898
patent and commence by reviewing the findings of the Federal Court on
obviousness that are relevant to this appeal.
A.
The Reasons of the Federal Court
[46]
The Federal Court commenced its analysis by making
findings as to the common general knowledge as of the priority date of the 898
patent (March 24, 2003) of the person skilled in the art to whom the 898 patent
is directed. The Court held that this common general knowledge included several
pieces of prior art.
[47]
First among them was PCT Application No.
WO/2000/062778 (the 778 Application), the PCT application that led to the 932
patent. Secondly, the Federal Court determined that the common general
knowledge of the person skilled in the art as of the relevant date included PCT
Application No. WO 03/013540 (the 540 Application). The Federal Court noted
that the 540 Application disclosed that compounds (like dasatinib) that inhibited
Src-family kinases were effective in treating leukemia, including CML, and
could be used in treating imatinib-resistant CML, when used either alone or in
combination with imatinib (Reasons at para. 157). Finally, the Federal Court
found that the relevant prior art include several articles, which disclosed,
among other things, that Src-family kinases are involved in BCR-ABL cell
proliferation and that compounds that inhibited Src-family kinases (like dasatinib)
can be used to mediate imatinib resistance (Reasons at paras. 160-164).
[48]
The Federal Court then set out the test
applicable for the assessment of obviousness, as follows:
165. Justice Rothstein set out the four-part test for
obviousness in Sanofi-Synthelabo Canada Inc. v. Apotex Inc., 2008 SCC 61
at paragraph 67 [Sanofi-Synthelabo]:
1) Identify
the notional person skilled in the art and 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,
ask whether those differences constitute steps which would have been obvious to
the person skilled in the art, or do they require any degree of invention.
166. In areas where advances are often found through
experimentation, the fourth part of the obviousness tests may be reframed as
asking whether the experiments were “obvious to try”, using the
following, non-exhaustive, factors (Sanofi-Synthelabo, above, at para.
69):
1) Is it more
or less self-evident that what is being tried ought to work, and/or are there a
finite number of identified predictable solutions that would be known to
persons skilled in the art?
2) What is the extent, nature, and amount of effort required to
achieve the invention (i.e., is the experimentation prolonged and arduous, or
are the trials routine)?
3) Is there a motive provided in the prior art to find the solution
that the patent addresses?
167. The reference for the test of obviousness is a technician, who
is skilled in the art but possesses no scintilla of inventiveness or
imagination (Beloit Canada Ltd v. Valmet OY (1986), 8 CPR (3d) 289 at 294). Obviousness is a difficult test to
meet, because it is necessary to show that the skilled person would have come
directly and without difficulty to the invention (Sanofi-Synthelabo at
paras. 71 and 85). However, the existence of multiple obvious routes to an
invention does not necessarily render the route taken to be non-obvious (Shire
Biochem Inc. v. Canada, 2008 FC 538 at para. 80).
168. Finally, the
Court must assess obviousness keeping in mind that experts in the field may
unknowingly be biased by hindsight (Bridgeview Manufacturing Inc. v. 931409
Alberta Ltd (cob Central Alberta Hay Centre), 2010 FCA 188 at para. 50).
[49]
The Court next considered whether claims 1 and 3
of the 898 patent were obvious. It noted that the parties had agreed that the
inventive concept of claims 1 and 3 of the 898 patent were “the oral use of dasatinib for the treatment of CML and oral
use of dasatinib for the treatment of imatinib-resistant CML, respectively”
(Reasons at para. 169). It then moved on to assess whether it was obvious to
try using dasatinib orally to treat CML and imatinib-resistant CML.
[50]
With respect to claim 1, the Court made the
following findings:
- The 778
Application discloses that the claimed compounds – including dasatinib –
inhibit Src-family kinases (Reasons at para. 175);
•
The 778 Application teaches that the compounds
may be administered by any suitable means, including orally (Reasons at para.
175); and
•
The 540 Application teaches the treatment of CML
in humans using a compound that inhibits specific Src-family kinases (Reasons
at para. 175).
[51]
Based on the foregoing, the Federal Court
determined that the oral administration of dasatinib (as an Src-inhibitor) to
treat CML was obvious to try. In reaching this conclusion, the Federal Court
preferred Apotex’ expert evidence over that of BMS and noted the lack of any
evidence establishing that the BMS inventors had engaged in difficult and
arduous experimentation to arrive at the invention claimed in claim 1 of the
898 patent (Reasons at para. 185).
[52]
The Federal Court came to a similar conclusion
with respect to claim 3. Again, the Federal Court accepted Apotex’ expert
evidence, which it concluded established that although different compounds for
targeting imatinib-resistant leukemia were being pursued, the prior art also established
that the Src-family pathway was involved in imatinib-resistant CML and that dasatinib
was therefore obvious to try because it targeted the Src-family pathway
(Reasons at paras. 189-190, 192, 196, 198). The Federal Court again noted that
the evidence did not reveal that the BMS scientists required any particularly
inventive experimentation to pursue their invention (Reasons at paras.
193-194).
[53]
The Court therefore determined that both claims
1 and 3 of the 898 patent were obvious and hence dismissed BMS’ prohibition
application in respect of the 898 patent.
B.
Analysis
[54]
BMS makes four challenges to the Federal Court’s
reasoning on obviousness, alleging that it committed three legal errors and
made a palpable and overriding factual error, any one of which it says is
sufficient to overturn the Federal Court’s dismissal of the prohibition
application in respect of the 898 patent.
[55]
More specifically, in terms of the alleged legal
errors, BMS first submits that the Federal Court made a legal error by applying
the obvious to try test after noting that both parties had agreed that the
invention was not obvious. It points in this regard to paragraph 173 of the reasons,
where the Federal Court stated:
Both parties
agree that it was not obvious at the relevant date that dasatinib would be an
effective oral treatment for CML and/or imatinib-resistant CML. However, the Respondent
contends that it would have been obvious for the clinician/scientist to try to
improve on existing CML-therapies by administering a Src-family PTK inhibitor.
Further, the Respondent argues that, because dasatinib was identified in the
‘778 Application as a PTK inhibitor that could be used for PTK-associated
diseases, particularly cancer, dasatinib would have been an obvious candidate
to try.
[56]
BMS says that it is incorrect to think of the
test for obviousness and the obvious to try test as distinct and to proceed on
the basis that only the latter needs to be met to invalidate a claim. BMS
supports this point by citing this Court’s recent statement in Bristol-Myers
Squibb Canada Co. v. Teva Canada Limited, 2017 FCA 76 at para. 60, 146
C.P.R. (4th) 216 [Atazanavir FCA] to the effect that “the ‘obvious to try’ test has not displaced all other
inquiries into obviousness”.
[57]
I disagree with BMS’ submission. In the first
place, as it conceded, the entire inquiry before the Federal Court focussed on
whether claims 1 and 3 in the 898 patent were obvious, and Apotex did not ever
admit that they were not. This is evident from the Federal Court’s reasons,
which analyze whether the claims 1 and 3 were obvious from the point of view of
being obvious to try. Secondly, I do not read the passage from Atazanavir
FCA as suggesting that the obvious to try test cannot be applied as a means of
inquiring into obviousness. In Sanofi-Synthelabo, the Supreme Court
indicated that an obvious to try test may well be appropriate “[i]n areas of endeavour where advances are often won by
experimentation” (at para. 68). It was therefore open to the Federal
Court to apply the obvious to try test, and, when one reads its reasons fairly in
their entirety, this is precisely the analysis that the Federal Court
undertook. Thus, while it is difficult to understand what the Federal Court
meant in the first sentence of paragraph 73, it did not commit the first error
that BMS alleges of making inconsistent findings on the issue of obviousness.
[58]
In terms of the second alleged legal error, BMS
says that the Federal Court erred by incorrectly treating the obvious to try
test as a reframed inquiry into whether the necessary experiments were obvious
to try. It more specifically asserts that the Federal Court misdirected itself by
considering whether the experiments to establish that dasatinib was effective
to treat CML and imatinib-resistant CML were obvious to try as opposed to
considering whether it was more or less self-evident that such experiments
would establish the efficacy of dasatinib. In support of this assertion, BMS
relies on the opening portion of the first sentence of paragraph 166 of
the Federal Court’s reasons, where the Court stated “[i]n
areas where advances are often found through experimentation, the fourth part
of the obviousness tests may be reframed as asking whether the experiments were
‘obvious to try’”.
[59]
Once again, I disagree with BMS as it has taken
this sentence in the Federal Court’s reasons out of context. In paragraphs 165
to 168, the Federal Court correctly sets out the test for assessing obviousness
from Sanofi-Synthelabo. Moreover, the Court’s reasoning shows that it
asked itself the right question, namely whether it was more or less
self-evident that routine experiments would establish that dasatinib was
effective to treat CML, including imatinib-resistant CML.
[60]
Third, BMS alleges that the Federal Court erred
by applying the wrong standard for assessing obviousness by equating it to the
test for sound prediction, when they are different concepts that ought not be
conflated. BMS says that this error was made in paragraph 181 of the reasons,
where the Federal Court wrote:
Although I agree
[with BMS’s expert] that the effectiveness of oral administration could not be
predicted prior to performing clinical tests, I do not consider this to be
dispositive of whether an invention was obvious to try. The first question of
the obvious try [sic] analysis asks if it is more or less self-evident
that an approach ought to work, which is a question that is very similar to the
question of sound prediction in the utility analysis. Many patents, including
the ‘898 Patent, have been granted in the absence of clinical data at the claim
date. If the utility of an invention can be predicted based upon the
pre-clinical data, the logical corollary is that a POSITA, having only
pre-clinical information, could find the invention obvious to try, and in this
case, given the common general knowledge, would have found that oral use of dasatinib
to treat CML was obvious to try.
[61]
While I agree with BMS that the tests for
assessing obviousness and sound prediction are different, I do not believe that
the Federal Court committed a reviewable error as the foregoing paragraph is
not central to its reasoning, and the balance of the reasons show that the
Federal Court applied the correct test for obviousness from Sanofi-Synthelabo.
[62]
Finally, BMS says that the Federal Court made a
palpable and overriding factual error by misapprehending the evidence and
ignoring what BMS says were key admissions it obtained during the
cross-examination of Apotex’ experts. It relies in support of this assertion on
passages in the cross-examination where it says the experts conceded that, as
at the appropriate time, the person skilled in the art would have concluded
that there was no more than a possibility that dasatinib would be effective to
treat CML. Having reviewed these passages, I disagree that any such admission
was made and, in any event, note that the passages relied on by BMS are
contradicted by other evidence, including large portions of the testimony of
Apotex’ experts. It was the province of the Federal Court to weigh and assess
such evidence. I do not see that it committed any palpable and overriding error
in so doing as there was more than ample evidence to support the conclusions
that the Federal Court reached.
[63]
I would accordingly dismiss BMS’ appeal with
respect to the 898 patent.
VI.
Proposed Disposition
[64]
In light of the foregoing, I would allow this
appeal in part, set aside the judgment of the Federal Court in respect of the
932 patent and, making the decision the Federal Court ought to have made, would
issue an order of prohibition against the Minister of Health, prohibiting the
issuance of an NOC to Apotex for its APO-Dasatinib product until the 932 patent
expires. As success is divided, I would order that each party bear its own
costs before this Court and the Federal Court.
“Mary J.L. Gleason”
“I agree.
Wyman W. Webb J.A.”
“I agree.
D. G. Near J.A.”
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