Docket:
T-564-10
Citation: 2012 FC 410
Ottawa, Ontario, April 11, 2012
PRESENT: The Honourable Mr. Justice Barnes
BETWEEN:
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ALCON CANADA INC.
ALCON RESEARCH, LTD. AND
KYOWA HAKKO KIRIN CO., LTD.
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Applicants
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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 AND JUDGMENT
[1]
This
is an application by Alcon Canada Inc., Alcon Research, Ltd. and Kyowa Hakko
Kirin Co., Ltd. (referred to hereafter collectively as Alcon) brought under the
provisions of the Patented Medicines (Notice of Compliance) Regulations,
SOR/93-133. Alcon seeks an Order prohibiting the Minister of Health (Minister)
from issuing a Notice of Compliance (NOC) to Apotex Inc. (Apotex) until the
expiry of Canadian Letters Patent 2,195,094 (the 094 Patent).
Background
[2]
According
to Alcon, the 094 Patent claims the novel use and composition of a topical
ophthalmic solution containing olopatadine for treating allergic eye diseases
by virtue of its previously unrecognized mast cell stabilizing activity in the
human eye. In Canada, Alcon markets olopatadine under the brand name Patanol
in a formulation of 0.1% olopatadine hydrochloride.
[3]
Apotex
has filed an Abbreviated New Drug Submission seeking a NOC from the Minister
for a 0.1% ophthalmic solution of olopatadine hydrochloride for topical
administration in the treatment of allergic conjunctivitis (a common disorder
of the human eye).
[4]
Alcon
brought its application in response to a Notice of Allegation (NOA) delivered
by Apotex by letter dated February 24, 2010. Apotex alleged that its generic
product would not infringe the 094 Patent and, in any event, that the 094
Patent is void for anticipation, obviousness, double patenting, claims broader
than the invention/lack of patentable subject matter and lack of demonstrated
or predicted utility.
[5]
On
the record before me there is no serious issue with respect to infringement.
If the 094 Patent is valid, the Apotex product will infringe.
Olopatadine
and the Treatment of Human Eye Diseases as it was Known in 1995
[6]
There
is no material disagreement among the witnesses about the nature and physiology
of human allergic eye diseases and the known methods for treating them at the
relevant time.
[7]
The
parties are also in general agreement about the notional person of skill. Such
a person could include a pharmacologist, an ophthalmologist, an immunologist or
a medical doctor with an understanding of human allergy pathways and the
treatment of allergic responses including an interest in the development of new
treatments. The person of skill is required to interpret the 094 Patent and
its claims as of the date of issuance, which in this case is December 12, 1996:
see Whirlpool Corp v Camco Inc, 2000 SCC 67 at paras 55-56, [2000] 2 SCR
1067 [Whirpool].
[8]
Allergic
eye diseases are common disorders which affect about 10% of the population.
They include allergic conjunctivitis (AC), giant papillary conjunctivitis (GPC),
vernal conjunctivitis (VC), vernal keratoconjunctivitis (VKC) and atopic
keratoconjunctivitis (AKC). These conditions represent aberrant immune
responses where the body wrongly interprets an allergen to be an invader to be
destroyed or expelled.
[9]
An
allergic reaction in the eye is an immunological response that arises when a
previously sensitized individual is exposed to an allergen or antigen. Such a
person will have formed antibodies which bind to receptors on mast cells in the
eye. In this way, mast cells become sensitized and, on subsequent exposure,
they degranulate, a process that releases a variety of chemical mediators
including histamine. These chemical mediators are the cause of the symptoms of
allergy including itching, redness, swelling and watering.
[10]
While
other mediators are released by mast cells including several neutral proteases,
chemoattractants and interleukins, it is histamine that plays a significant
role in causing allergic symptoms in the eye.
[11]
Histamine
exerts its effects by binding to histamine receptors. An antihistamine works
by binding to those receptors thereby blocking out the histamine. This is
sometimes described metaphorically as putting a false key in the lock.
Antihistamines are a useful form of treatment for an allergic response but they
act after the mediators are released from the mast cells and they only block
the effects of one mediator – histamine.
[12]
Another
means of treating allergic disease is by preventing the degranulation of mast
cells. This is accomplished by the administration of mast cell stabilizing
agents. Mast cell stabilizers (of which olopatadine is one) act by preventing
mediator release from mast cells. This form of treatment blocks the release of
mediators from mast cells and is not limited to the suppression of histamine.
For certain diseases, a mast cell stabilizer would be expected to be more
effective than an antihistamine.
[13]
In
1995, cromolyn had been identified as a mast cell stabilizer in animal models
but its efficacy in humans was in doubt. It was understood at that time that
animal models could usefully predict the efficacy of antihistamines in humans
but not the efficacy of mast cell stabilizers. The inability to predict a mast
cell stabilizing effect from animal testing was understood to arise from the problem
of mast cell heterogeneity, meaning that mast cells from different species and
in different tissues within the same species were sufficiently different that a
compound’s efficacy in one would not predict efficacy in another.
[14]
For
several years leading up to 1995, there was a recognized need for mast cell
stabilizers useful to treat some forms of allergic eye disease. In reaction to
that need, Alcon initiated a search for a compound that was both a mast cell
stabilizer and an antihistamine. By 1995, the 094 Patent inventors and others
working in the field believed that antihistamines were unlikely to be useful as
mast cell stabilizers because, in vitro and at higher concentrations, they were
observed to rupture the cell causing unwanted release of mediators (the
biphasic effect) – a result that was opposite to the desired stabilization
effect.
[15]
One
of the 094 Patent inventors, Dr. John Yanni, and another colleague at
Alcon developed a novel assay which was the first available method to test a
drug for mast cell stabilization in the human conjunctival mast cell (the HCMC
assay). The HCMC assay later formed the subject matter of a United States patent application filed on October 8, 1993.
[16]
Dr. Yanni
set out to test approximately 150 compounds with the HCMC assay. Many of the
compounds obtained by Alcon came from other companies under transfer agreements
and were known to have anti-allergic profiles. Alcon obtained olopatadine in
this way from Kyowa Hakko Kirin Co., Ltd. (Kyowa) in 1991 because it was known
to be an antihistamine useful in treating allergic eye diseases in humans.
Dr. Yanni understood olopatadine to be an antihistamine and was concerned
that it could exhibit a biphasic effect. Upon testing olopatadine, it was discovered
to have mast cell stabilizing properties at certain doses and that this
response was dose dependent. At therapeutic doses, olopatadine was found not to
be biphasic.
[17]
In
1997, Alcon brought olopatadine to market under the trade name Patanol and this
product has achieved considerable commercial success for the treatment of
allergic eye diseases.
Analysis
[18]
The
outcome of this application turns on claims construction. This is an issue of
law for the Court to determine but with the aid of expert witnesses: see Pfizer
Canada Inc v Canada (MOH), 2007 FCA 209 at para 39, [2007] FCJ no 767 (QL).
[19]
The
issue of burden of proof in NOC proceedings has now been settled and I adopt
the following analysis provided by Justice Roger Hughes in the Eli Lilly
Canada Inc v. Apotex Inc, 2009 FC 320 at paras 37-40, 346 FTR 78:
37 The issue as to who bears the burden of proof
in NOC proceedings, as to validity of a patent or infringement of a patent is
an issue that I had thought had been put to rest. Nonetheless the parties in
such proceedings continue to argue the point. It seems that my recent decision
in Brystol-Myers Squibb Canada Co. v. Apotex Inc., 2009 FC 137 has given
fresh ammunition to those continually wishing to stir the pot in this regard.
Let me state emphatically that I did not intend in Brystol-Myers to say
or apply any burden different than I had stated in previous decisions.
38 To be perfectly clear, when it comes to the
burden as to invalidity I canvassed the law, in particular recent Federal Court
of Appeal decisions, in Pfizer Canada Inc. v. Canada (Minister of Health),
(2008), 69 C.P.R. (4th) 191, 2008 FC 11 and concluded at paragraph 32:
32 I do not view the reasoning of the two
panels of the Federal Court of Appeal to be in substantial disagreement.
Justice Mosley of this Court reconciled these decisions in his Reasons in
Pfizer Canada Inc. v. Apotex Inc., [2007] F.C.J. No. 1271, 2007 FC 971 at
paragraphs 44 to 51. What is required, when issues of validity of a patent are
raised:
1. The second person,
in its Notice of Allegation may raise one or more grounds for alleging
invalidity;
2. The first person may in its Notice of Application
filed with the Court join issue on any one or more of those grounds;
3. The second person may lead evidence in the Court
proceeding to support the grounds upon which issue has been joined;
4. The first person may, at its peril, rely simply
upon the presumption of validity afforded by the Patent Act or, more prudently,
adduce its own evidence as to the grounds of invalidity put in issue.
5. The Court will weigh the evidence; if the first
person relies only on the presumption, the Court will nonetheless weigh the
strength of the evidence led by the second person. If that evidence is weak or
irrelevant the presumption will prevail. If both parties lead evidence, the
Court will weigh all the evidence and determine the matter on the usual civil
balance.
6. If the evidence weighed in step 5 is evenly
balanced (a rare event), the Applicant (first person) will have failed to prove
that the allegation of invalidity is not justified and will not be entitled to
the Order of prohibition that it seeks.
39 I stated the matter more succinctly in Pfizer
Canada Inc. v. Canada (Minister of Health), 2008 FC 500 at paragraph 12:
12 Here the only issue is validity. Pharmascience
has raised three arguments in that respect. Each of Pfizer and Pharmascience
have led evidence and made submissions as to those matters. At the end of the
day, I must decide the matter on the balance of probabilities on the evidence
that I have and the law as it presently stands. If, on the evidence, I find
that the matter is evenly balanced, I must conclude that Pfizer has not
demonstrated that Pharmascience's allegation is not justified.
40 The above cases state correctly in my view,
the law as to the burden in NOC proceedings as to invalidity.
[Emphasis in original]
[20]
Alcon
asserts only two of the 25 claims of the 094 Patent, specifically Claim 8 (a
use claim) and Claim 20 (a composition claim) but it acknowledges that, as
dependant claims, they must be read in the context of the claims to which they
are linked (ie. Claims 1 and 13 respectively). For ease of reference all of
the 094 Patent claims are set out below:
CLAIMS:
1. Use of a topically administrable
ophthalmic composition comprising a therapeutically effective amount of 11-(3-dimethylaminopropylidene)-6,
11-dihydrodibenz[b,e]oxepin-2-acetic acid or a pharmaceutically acceptable salt
thereof, together with a pharmaceutically acceptable carrier therefor, for
treating allergic eye diseases.
2. The use of Claim 1, wherein the
composition is a solution and the amount of 11-(3-dimethylaminopropylidene)-6,
11-dihydrodibenz[b,e]oxepin-2-acetic acid is from about 0.0001% to about 5%
(w/v).
3. The use, of Claim 2, wherein the amount of
11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic acid is
about 0.001% to about 0.2% (w/v)
4. The use of Claim 3, wherein the amount of
11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic acid is
about 0.1% (w/v).
5. The use of Claim 1, wherein the 11-(3-dimethylamino-propylidene)-6,
11-dihydrodibenz[b,e]oxepin-2-acetic acid is (Z)-11-(3-dimethylaminopropylidene)-6,
11-dihydrodibenz [b,e] - oxepin-2-acetic acid, substantially free of
(E)-11-(3-dimethyl- aminoproylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid.
6. The use of Claim 5, wherein the amount of
(Z)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.0001 to about 5% (w/v).
7. The use of Claim 6, wherein the amount of
(Z)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.001 to about 0.2% (w/v).
8. The use of Claim 7, wherein the amount of
(Z)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is 0.1% (w/v).
9. The use of Claim 1, wherein the
11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic acid is
(E)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic acid,
substantially free of (Z)-11-(3-dirnethylarninopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid.
10. The use of Claim 9, wherein the amount of
(E)-11-(3-dimethylaminopropylidene)-6,
11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.0001 to about 5% (w/v).
11. The use of Claim 10, wherein the amount of
(E)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.001 to about 0.2% (w/v).
12. The use of Claim 11, wherein the amount of
(E)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is about 0.1% (w/v).
13. A topically administrable ophthalmic
composition for treating allergic eye diseases comprising a therapeutically effective
amount of 11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid, or a pharmaceutically acceptable salt thereof, together with a
pharmaceutically acceptable carrier therefor.
14. The composition of Claim 13 wherein the
amount of 11-(3- dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.0001 to about 5% (w/v).
15. The composition of Claim 14 wherein the
amount of 11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.001 to about 0.2% (w/v).
16. The composition of Claim 15 wherein the
amount of 11-(3-dimethylaminopropylidene)-6, 11-dihydrodlbenz[b,e]oxepin-2-acetic
acid is about 0.1% (w/v).
17. The composition of Claim 13 wherein the
11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic acid is
(Z)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid, substantially free of (E)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodlbenz[b,e]oxepin-2-acetic
acid.
18. The composition of Claim 17 wherein the
amount of (Z)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.0001 to about 5% (w/v).
19. The composition of Claim 18 wherein the
amount of (Z)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.001 to about 0.2% (w/v).
20. The composition of Claim 19 wherein the
amount of (Z)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is about 0.1% (w/v).
21. The composition of Claim 13, wherein the
11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic acid is
(E)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid, substantially free of (Z)-11-(3-dimethylaminopropylidene)-6,
11-dihydrodibenz[b,e]oxepin-2-acetic acid.
22. The composition of Claim 21, wherein the
amount of (E)-11-(3-dimethylaminopropylidene)-6,
11-dihydrodibenz [b,e]oxepin-2-acetic
acid is from about 0.0001 to about 5% (w/v).
23. The composition of Claim 22, wherein the
amount of (E)-11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid is from about 0.001 to about 0.2% (w/v).
24. The composition of Claim 23, wherein the
amount of (E)-11-(3-dimethylaminopropylidene)-6,
11-dihydrodibenz[b,e]oxepin-2-acetic
acid is about 0.1% (w/v).
25. Use of a composition as defined in any one
of claims 13 to 24 for the preparation of a medicament for treating allergic
eye diseases.
[21]
It
is the language of Claims 1 and 13 that is disputed by the parties and, in
particular, the words “treating” and “allergic eye diseases”.
[22]
Because
olopatadine was a known antihistamine useful for treating human allergic eye diseases,
Apotex maintains that, on a plain reading, the 094 Patent asserts a monopoly
over a known compound for an old use. Alcon concedes that, if this
interpretation is adopted, the 094 Patent will fail on the ground of
obviousness.
[23]
Alcon
argues that the 094 Patent claims a novel use of olopatadine in the treatment
of allergic eye diseases by virtue of the discovery of its previously unrecognized
mast cell stabilizing activity in the human eye. Alcon urges a contextual interpretation
of the words “treating” and “allergic eye diseases” which effectively reads
into Claims 1 and 13 a limitation related to the discovery of olopatadine’s usefulness
as a mast cell stabilizer and an antihistamine to treat diseases of the human eye
where mast cell degranulation is implicated. Alcon alleges that this is in
keeping with the spirit of what the 094 Patent disclosed. Accordingly, Alcon
advances the following construction of Claims 8 and 20:
1) a composition tailored
for use in an ocular environment and to be applied to the surface of the eye;
2) containing olopatadine
(or one of its pharmaceutically acceptable salts);
3) having less than 2% of
the trans-isomer of olopatadine present;
4) the concentration of olopatadine being
0.1% (w/v); and
5) having clinically
relevant HCMC stabilizing activity and antihistaminic activity (i.e. a ‘dual
action agent’) for prophylactic and therapeutic treatment in human of an
allergic eye disease wherein mast cell degranulation contributes to the
development of the disease state (such as AC, VC, VKC and GPC).
[Emphasis added]
Applicant’s Outline of Argument – Construction at
para 53.
[24]
Although
the parties agree that the construction of patent claims must be carried out
purposively and in accordance with the principles discussed in Whirlpool,
and Free World Trust v Électro Santé Inc, 2000 SCC 66, [2000] 2 S.C.R. 1024
[Free World], they disagree about how far one can go in construing
claims language on the strength of information that is provided only in the
disclosure. Alcon argues that the skilled reader must draw meaning from the
entire context of a patent. Apotex says a purposive contextual reading does
not permit the claims to be rewritten to include missing essential elements.
[25]
Claims
language is a critical component of the public notice requirement and subsection 27(4)
the Patent Act, RSC 1985, c P-4,, emphasizes its importance:
27. (4) The specification must end with a claim or
claims defining distinctly and in explicit terms the subject-matter of the
invention for which an exclusive privilege or property is claimed.
[26]
The
Supreme Court of Canada emphasized the purpose and importance of requiring clear
language in the drafting of patent claims in Free World, above, at paragraphs
14, 15 and 42:
14 Patent claims are frequently analogized to
"fences" and "boundaries", giving the "fields" of
the monopoly a comfortable pretence of bright line demarcation. Thus, in Minerals
Separation North American Corp. v. Noranda Mines, Ltd., [1947] Ex. C.R.
306, Thorson P. put the matter as follows, at p. 352:
By his claims the inventor puts fences around the
fields of his monopoly and warns the public against trespassing on his
property. His fences must be clearly placed in order to give the necessary
warning and he must not fence in any property that is not his own. The terms of
a claim must be free from avoidable ambiguity or obscurity and must not be
flexible; they must be clear and precise so that the public will be able to
know not only where it must not trespass but also where it may safely go.
15 In reality, the "fences" often
consist of complex layers of definitions of different elements (or
"components" or "features" or "integers") of
differing complexity, substitutability and ingenuity. A matrix of descriptive
words and phrases defines the monopoly, warns the public and ensnares the
infringer. In some instances, the precise elements of the "fence" may
be crucial or "essential" to the working of the invention as claimed;
in others the inventor may contemplate, and the reader skilled in the art
appreciate, that variants could easily be used or substituted without making
any material difference to the working of the invention. The interpretative
task of the court in claims construction is to separate the one from the other,
to distinguish the essential from the inessential, and to give to the
"field" framed by the former the legal protection to which the holder
of a valid patent is entitled.
…
42 The patent system is designed to advance
research and development and to encourage broader economic activity.
Achievement of these objectives is undermined however if competitors fear to
tread in the vicinity of the patent because its scope lacks a reasonable
measure of precision and certainty. A patent of uncertain scope becomes "a
public nuisance" (R.C.A. Photophone, Ld. v. Gaumont-British Picture Corp.
(1936), 53 R.P.C. 167 (Eng. C.A.), at p. 195). Potential competitors are
deterred from working in areas that are not in fact covered by the patent even
though costly and protracted litigation (which in the case of patent disputes
can be very costly and protracted indeed) might confirm that what the
competitors propose to do is entirely lawful. Potential investment is lost or
otherwise directed. Competition is "chilled". The patent owner is
getting more of a monopoly than the public bargained for. There is a high
economic cost attached to uncertainty and it is the proper policy of patent law
to keep it to a minimum.
[27]
Notwithstanding
the above cautions, the law is clear that a purposive approach requires the
Court to examine claim language in the sense that the patentee is presumed to
have used it and not through the lens of strict literalism. Even a term that
appears to be plain and unambiguous may, when read in the context, reasonably
support a different meaning. Whirlpool, above, also counsels that the
search for meaning is not carried out through the eyes of a grammarian but
rather in light of the common knowledge of the person of ordinary skill in the
field to which the patent relates. Thus, it is permissible to look to the
patent disclosure to ascertain the technical meaning of terms used in the
claims.
[28]
I
have no difficulty with the point that purposive construction is capable of expanding
or limiting a literal text: see Whirlpool, above, at para 49. It seems
to me, though, that there is some judicial concern about importing essential
features of an invention from the disclosure to the claims, particularly where
the disclosure is somewhat unclear about the scope of the invention. In other
words, even if one resorts to the disclosure to interpret the claims “the
precise and exact extent of the exclusive property and privileged claims” must always
be identifiable: see Consolboard Inc v MacMillan Bloedel (Saskatchewan) Ltd,
[1981] 1 S.C.R. 504 at para 26, 122 DLR (3d) 203.
[29]
In
BVD Co v Canadian Celanese Ltd, [1937] S.C.R. 441, [1937] 3 DLR 449
[BVD], the Court declined to read into a patent claim an essential
feature of an invention and struck the patent down because the claims, as
written, exceeded the scope of the invention. I take Alcon’s point that this
decision predates the decisions in Whirlpool and Free World, above,
and their elaboration of the principles of purposive construction.
Nevertheless, BVD has not been overruled and it continues to underscore
the importance of ensuring that a patent clearly delineates the subject matter
of an invention and the importance of the claims language in achieving that end:
see also Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61 at para
77, [2008] 3 S.C.R. 265; Amfac Foods Inc v Irving Pulp & Paper, Ltd,
[1986] FCJ no 659 (QL), 72 NR 290 (CA).
[30]
What
I take from the authorities is that resort to the disclosure is permissible,
but only for the purpose of comprehending the meaning of words or expressions
found in the claims. Essential information that is contained in the disclosure
that is not relevant to the search for meaning of claims language cannot be
imported by implication to qualify the claims: see Janssen-Ortho Inc v Canada
(MOH), 2010 FC 42 at para 119, 361 FTR 268 [Janssen-Ortho]. It is
also not appropriate to ascribe meaning to words in the claims by reference to
“stray phrases” found in the disclosure: see Electric & Musical
Industries, Ltd v Lissen, Ltd (1939), 56 RPC 23 at p 41.
[31]
The
first step in a patent suit is to construe the claims without regard to issues
of validity or infringement: see Whirlpool, above, at para 43. Where
there is doubt about the meaning of claims language, one resorts first to the
language of the claims followed by consideration of the disclosure, if
necessary: see Janssen-Ortho, above, at para 116.
[32]
Alcon
argues that a person of skill would, at the relevant time, understand that the
094 Patent claims a new use for olopatadine in the treatment of allergic eye
diseases owing to its discovered activity as a mast cell stabilizer in addition
to its already known value as an antihistamine.
[33]
Alcon
acknowledges that on a plain reading of the claims in issue the use of
olopatadine to treat allergic eye diseases exceeds the scope of its invention.
By resorting to the disclosure, Alcon seeks to read down this expansive
language and to restrict the claims to “clinically relevant HCMC stabilizing
activity and antihistaminic activity (ie. a ‘dual action agent’) for
prophylactic and therapeutic treatment in a human of an allergic eye disease
wherein mast cell degranulation contributes to the development of the disease
state (such as AC, VC, VKC and GPC)”: Applicant’s Outline of Argument –
Construction at para 53.
[34]
The
passages in the 094 Patent disclosure that Alcon’s witnesses rely upon to read
down the language of the claims include the following:
The present invention relates to topical
ophthalmic formulations used for treating allergic eye diseases, such as
allergic conjunctivitis, vernal conjunctivitis, vernal keratoconjunctivitis,
and giant papillary conjunctivitis. More particularly, the present invention
relates to therapeutic and prophylactic topical use of 11-(3-dimethylaminopropylidene)-6,
11-dihydrodibenz[b,e]oxepin-2-acetic acid for treating and/or preventing
allergic eye diseases.
…
Topical ophthalmic formulations which contain
drugs having conjunctival mast cell activity may only need to be applied once
every 12-24 hours instead of once every 2-4 hours. One disadvantage to the
ophthalmic use of reported anti-allergic drugs which in fact have no human conjunctival
mast cell stabilizing activity is an increased dosage frequency. Because the
effectiveness of ophthalmic formulations containing drugs which do not have
conjunctival mast cell activity stems primarily from a placebo effect, more
frequent doses are typically required than for drugs which do exhibit
conjunctival mast cell activity.
…
What is needed are topically
administrable drug compounds which have demonstrated stabilizing activity on
mast cells obtained from human conjunctiva, the target cells for treating allergic
eye diseases. What is also needed are local administration methods for the
treatment of allergic eye disease.
…
The present invention provides a method
for treating an allergic eye disease characterized by administering to the eye
a topical ophthalmic formulation which contains a therapeutically effective
amount of 11-(3-dimethylaminopropylidene)-6, 11-dihydrodibenz[b,e]oxepin-2-acetic
acid (referred to as “Compound A” hereinafter) or a pharmaceutically acceptable
salt thereof.
…
Compound A has human conjunctival mast
cell stabilizing activity, and may be applied as infrequently as once or twice
a day in some cases. In addition to its mast cell stabilizing activity, Compound
A also possesses significant antihistaminic activity. Thus, in addition to a
prophylactic effect, Compound A will also have a therapeutic effect.
…
As Table 1 clearly shows, the
anti-allergic drugs disodium cromoglycate and nedocromil failed to
significantly inhibit human conjunctival mast cell degranulation. In contrast,
Compound A (cis isomer) [olopatadine] produced concentration-dependent
inhibition of mast cell degranulation.
[35]
Alcon
and its opinion witnesses maintain that the above passages would lead a person
of skill to understand that the claims in question did not include the use of
olopatadine generally to treat allergic eye diseases. The disclosure is all
about olopatadine’s capacity to stabilize mast cells in the human eye and its
use to treat diseases where mast cell degranulation is a concern. In addition,
Alcon contends that part of the inventive utility of olopatadine lies in its
potential use as a dual action prophylactic agent. Alcon also relies on prior
art disclaimers in the 094 Patent disclosure that, it says inform a skilled
reader about what is not included in the claims.
[36]
Alcon
urges an interpretation of the word “treating” in Claim 1 that is consistent
with its characterization of olopatadine’s mast cell stabilizing activity as a
new medical use. According to Alcon, the skilled reader would understand that,
when read in context, “treating” is not being used in a general sense and must
mean more than the use of olopatadine as an antihistamine. Alcon also argues
that the use of olopatadine to treat allergic eye diseases as a mast cell stabilizer
does not inherently involve treatment as an antihistamine because the dosage
ranges for each method of treatment do not overlap. Using olopatadine to
prophylactically treat allergic eye diseases is, therefore, distinct from its
understood antihistaminic utility.
[37]
Alcon
similarly urges a narrow interpretation of the words “allergic eye diseases”
which, it argues, do not include disorders that cannot be treated with a mast
cell stabilizer. This would be obvious to the skilled person because the list
of treatable eye diseases in the specification includes only four examples
where, in each case, mast cell degranulation is implicated at least to some
extent. Alcon argues that this unstated common feature should, accordingly, be
read into the relevant claims.
[38]
At
the outset, it is important to recognize that nowhere in the claims is there
any mention of a newly discovered and inventive use for olopatadine. There is
also no reference in the claims to any particular activity or to a dual
activity which might restrict the claimed use of olopatadine. While these
activity profile features are described in the disclosure and quantified with
respect to olopatadine’s mast cell stabilizing property, those references are
similarly not tied to any new form of clinical use. Indeed, the summary of the
invention refers to a method for treating and not to a use. This appears to
conform to the United States priority patent which claimed a method of medical
treatment based on olopatadine’s mast cell stabilizing properties. And despite
Alcon’s considerable reliance in argument on olopatadine’s dual action profile
and the avoidance of a biphasic effect, there is nothing in the specification to
suggest that these features are part of the inventive promise of the 094 Patent.
[39]
The
disclosure passages Alcon relies upon also fail to clearly identify the nature
or the scope of the invention. There is nothing in these passages which
distinctly and explicitly identifies the subject matter of the invention
whether as a new use or otherwise. While there are references to prophylactic
use, dosing frequencies and demonstrated stabilization activity at specific
concentrations, none of those features are clearly identified as an element of
the inventive concept and none of that language is used in a way that would
serve to clearly define the words in dispute in Claims 1 and 13.
[40]
Furthermore,
with respect to Alcon’s reliance on a distinction between prophylactic and
therapeutic uses, the language it has used is notably imprecise. For example, there
are places in the disclosure where therapeutic and prophylactic uses for
olopatadine are distinguished: therapeutic use is said to treat and
prophylactic to prevent. But in other places, the word “treating” is used in
the general sense without distinguishing the means by which the clinical
outcome is achieved and “therapeutic” refers to a dosage (see Claim 1 and Claim
13).
[41]
This
linguistic inconsistency is mirrored by the evidence. According to Alcon’s own
witnesses, there is no bright clinical line that ordains the use of olopatadine
as a preventative therapy.
[42]
The
plain reading of Claim 1 is that olopatadine can be used to treat a broader
class of allergic eye diseases than the four examples provided in the
disclosure and, of course, there is no express statement anywhere in the patent
that the claims are limited to the treatment of disorders where mast cell
degranulation is implicated. The disclosure is open-ended in that respect.
[43]
The
evidence from Alcon’s witnesses concerning the disputed claims language is not
particularly helpful because it is based on disclosure references that are not clear.
Those witnesses also failed to address other disclosure references that
detracted from their views and they attributed an awkward meaning to “treating”
that seems to be more consistent with Alcon’s legal interests than with the
objective views of a skilled reader.
[44]
Dr. Church
provided the following affidavit evidence on these construction issues:
62. What is meant by the phrase “treating
allergic eye diseases” as used in the claims of the 094 Patent would be readily
discerned by the skilled person based on a review of the 094 Patent in its
entirety. As discussed earlier, page 4, lines 11-13 of the patent refers to
“treating allergic eye diseases” in a context of helping target cells, i.e.,
human conjunctival mast cells. The passage states that what is needed is a drug
that has demonstrated stabilizing activity on mast cells obtained from human
conjunctiva, the target cells for treating allergic eye diseases. Hence, a
skilled person would understand that “treating” involves stabilizing human
conjunctival mast cells (i.e., preventing human conjunctival mast cell
degranulation) to a significant level. The phrase “allergic eye diseases” would
have been understood to mean those diseases in which conjunctival mast cell
degranulation is involved, at least in part. On page 1, 11. 10-12 the patent
provides some examples of such types of “allergic eye diseases”. That passage
states that “the present invention relates to topical ophthalmic formulations
used for treating allergic eye such as allergic conjunctivitis, vernal conjunctivitis,
vernal keratoconjunctivitis, and giant papillary conjunctivitis.” Given that a
common feature of these diseases is that, as at December, l996, they were
thought to have mast cell degranulation as all or part of the disease state,
the skilled person would have construed “allergic eye disease” to mean diseases
in which mast cell degranulation is involved.
63. While some of the diseases referred to as
“allergic eye diseases” would not be “cured” by mast cell stabilization, the
skilled person would nonetheless appreciate that the diseases would be “treated”
(perhaps even as an adjunct therapy) by mast cell stabilization.
64. The “treatment” by stabilizing human conjunctival
mast cells would have been understood by the skilled person to be an added activity
over the previously known antihistaminic activity of Compound A. Hence the
skilled person would understand that the word “treating” in the phrase
“treating allergic eye diseases” means prophylactically and/or therapeutically treating
allergic eye diseases in humans by stabilizing human conjunctival mast cells in
a manner that is significant in addition to having antihistaminic activity. The
inventive concept of the claims is that Compound A can be used topically at
clinically relevant concentrations to prevent histamine release from the mast
cells in human conjunctiva in addition to its known antihistaminic activity.
See also Affidavit of Martin K. Church, Ph.D., D.Sc.
(31 May 2011) at paras 5-7: Affidavit of Phil Lieberman (19 January 2011) at
paras 81, 83, 92 [Affidavit of Dr. Lieberman].
Dr. Lieberman’s affidavit
addresses the same point at paragraph 172:
172. At paragraphs 78, 79 and 85 of his
affidavit, Dr. Buckley suggests the 094 Patent describes a mechanism of
action for olopatadine rather than a new use. I disagree. The use claimed in
the 094 Patent is a new use, because it was never used before to treat human
eye allergy or as a human conjunctival mast cell stabilizer. “Treating” as
used in the claims, means apart from being an anti-histamine, also being a
significant conjunctival mast cell stabilizer.
Affidavit of Dr. Lieberman at para 172.
[45]
This
evidence equates the word “treating” with the way in which olopatadine works
(eg. “helping target cells”, “‘treating’ involves stabilizing human
conjunctival mast cells”, “‘treated’ by…mast cell stabilization”). Except for
a reference to a possible use as a prophylaxis, Dr. Church and the other
Alcon witnesses identify no new clinical use for olopatadine that arises out of
the discovery of its mast cell stabilizing properties beyond the sophism that
if olopatadine was never used before as a mast cell stabilizer it therefore must
be a new use. It seems to me that this approach seriously strains the meaning
of the word “treating” and the concept of a new use discovery. The information
discovered by Alcon may be useful but it does not, by that fact alone,
constitute a new use for olopatadine. A clinician treats a patient for an
allergic reaction in the eye by suppressing the troubling or damaging signs and
symptoms of the disorder. In the absence of a new clinical use for an old
drug, new knowledge about how it works is not patentable. Similarly, the
discovery that olopatadine was more effective in the treatment of allergic eye
diseases than initially understood (see Affidavit of Martin K. Church, Ph.D.,
D. Sc. (24 January 2011) at paras 42-43, 46-48 [ Affidavit of Dr. Church]) is
unpatenable because the improved efficacy of the drug was inherent in its known
utility as an antihistamine: see AztraZeneca AB v Apotex Inc, 2007 FC
688 at paras 50-52, 80-88, 314 FTR 177.
[46]
The
evidence from the Apotex witnesses that “treating” means the therapeutic
alleviation of the signs and symptoms of allergic eye diseases without regard
to any mechanism of action is in keeping with the plain language of Claim 1 and
it avoids an unnatural equating of the word to olopatadine’s biological
activity as a mast cell stabilizer.
[47]
Alcon
maintains that Dr. Buckley and Dr. Calder retreated from their
respective affidavits under cross-examination and conceded that Claim 1
incorporated, by implication, the use of olopatadine as a mast cell
stabilizer. I do not agree that either witness made such an unqualified
concession. Dr. Buckley’s answers were given in response to questions
relating to references in the disclosure to the prophylactic and therapeutic
effects of olopatadine but, under further questioning, he stated that the 094
Patent “claims to treat and prevent perhaps, but without claiming the pathway
or the pharmacological mechanisms”: Cross-Examination Upon Oral Examination of
Dr. Roger Buckley (16 August 2011) at p 43 [Cross-Examination of Dr. Buckley].
Inasmuch as Dr. Barney conceded that antihistamines can be used in
preventative ways, this evidence is not particularly probative.
[48]
Dr. Calder’s
evidence under cross-examination is also not as clear as Alcon asserts. Much
of the evidence Alcon relies upon from Dr. Calder is concerned with
statements from the 094 Patent disclosure and not from the claims per se.
Furthermore, much of that questioning was concerned with the “inventive
concept” of the patent and not with the word “treating” in Claim 1. Her
apparent acknowledgement that the list of exemplar diseases in the disclosure
implied a use of olopatadine “as more than simply an antihistamine” does not,
to my mind, detract from her evidence that “treating” in Claim 1 does not mean
treating as a mast cell stabilizer or as a dual action agent. I do not take
her answers under cross-examination to be inconsistent with her affidavit that
Claims 1 and 13 are not limited to the use of olopatadine as a mast cell
stabilizer or as a dual action medicine.
[49]
Alcon
maintains that “allergic eye diseases” should also be read-down by limiting the
claim to diseases which implicate mast cell degranulation. I accept the point
made by Alcon’s expert witnesses that a skilled person may understand without
being told that each of the diseases specified in the disclosure involves, in
some measure, mast cell degranulation. It does not follow, however, that such
a person would read that limitation into the claims. Indeed, it is inconceivable
to me that the draftsman would fail to incorporate any reference to this
essential limiting element in both the claims and the disclosure and thereby
leave the point to be inferred by the reader. Alcon’s failure to close the
category of diseases amenable to treatment with olopatadine implies just the
opposite – that is, that the use of olopatadine was being claimed without any
limitation beyond the general reference to the treatment of allergic eye
diseases. Contrary to Dr. Barney’s affidavit at paragraph 47, the 094
Patent is notably unclear if the intention was to include Alcon’s proposed
limitation. This is particularly the case for diseases like AKC where mast
cell degranulation is only a part of the disease pattern and where olopatadine would
only be an incidental or adjunct form of therapy: see Cross-Examination of Dr. Buckley
at pp 1805-1808; Affidavit of Dr. Church at para 63. This points away
from the idea that a skilled person would infer that the 094 Patent claims are
limited to the treatment of allergic eye diseases involving mast cell
degranulation.
[50]
The
evidence before me provides no basis for ignoring the otherwise plain language
of Claims 1 and 13 and, in my view, it would almost never be appropriate to limit
the language of a patent claim on the strength of such an inference to be drawn
from the disclosure.
[51]
It
would have been a simple exercise to state Alcon’s suggested limitation and to
clearly limit the monopoly to the use of olopatadine as a mast cell stabilizer
in the treatment of diseases where mast cell degranulation was a clinical
concern. It is not reasonable to read in these limitations based on an
inference to be drawn from an unstated common feature of the exemplar diseases
particularly where olopatadine was a known antihistamine and could also be used
on its own or as adjunct therapy in the treatment of the same allergic eye
diseases. This is particularly evident when one considers that several of the
094 Patent claims refer to dosages of olopatadine that, according to the
experimental data set out in Table 1, would not be effective to achieve any
mast cell stabilizing effect. Although Alcon does not assert any of those
problematic claims in this proceeding, the skilled reader is trying to
interpret all of the claims in context and not in isolation. The inference
that would reasonably be drawn by the skilled reader is that Alcon was claiming
the use of olopatadine as something other than a mast cell stabilizer at those
lower dosage levels.
[52]
The
requirement that the subject matter of an invention be distinctly and
explicitly defined is not met in these circumstances. A patentee should not
readily be permitted to discourage competition with an overbroad claim and,
when challenged many years later, retreat from the language it has used by
relying on inferences and disclosure references such as these.
[53]
Alcon
relies on disclaimers in the 094 Patent in support of its argument that that
which is disclaimed is not claimed: see Virgin Atlantic Airways Ltd v
Premium Aircraft Interiors UK Ltd, [2009] EWCA Civ 1062 at para 21, [2010]
RPC 8.
[54]
The
094 Patent does acknowledge the prior art teachings of two Burroughs Wellcome
(BW) patents and a Kyowa patent but at the same time substantially discounts
their significance. For instance, the BW patents are said to have disclosed
olopatadine’s antihistaminic “activity” and an ophthalmic solution formulation,
but the claim for human medical use was said not to have been established by
the animal testing disclosed. The 094 Patent then goes on to state that
the further assertion in the BW patents that olopatadine could be classified as
a mast cell stabilizer was unproven because of the problem of mast cell
heterogeneity. The Kyowa Patent is characterized in a similar way in the 094
Patent by questioning the utility of olopatadine for treating the human eye. According
to Alcon, the field was open to establish olopatadine’s utility as a mast cell
stabilizer in the human eye.
[55]
I
agree with Apotex that the scope of Alcon’s disclaimer is far from clear and provides
less than what was actually known about olopatadine. Alcon now says in its
Memorandum that the 094 Patent contains no criticism of the BW teaching that
olopatadine had antihistaminic “activity” and that the skilled person was being
told that olopatadine was an antihistamine available for the treatment of
allergic eye diseases in humans. This submission, however, goes well beyond
the scope of what the 094 Patent actually acknowledged about the prior art. On
one reading of the disclosure, the impression is left that the utility of
olopatadine as an antihistamine, at least for human use, was unproven and that
Alcon had shown that it “possesses significant antihistaminic activity”.
Nowhere in the 094 Patent is there an unequivocal acknowledgment that
olopatadine was a known antihistamine available for use in the human eye or
that animal testing was known to be predictive of olopatadine’s antihistaminic
efficacy in humans.
[56]
In
my view, the skilled reader would not infer from these incomplete prior art disclaimers
that Alcon was limiting the word “treating” to uses which were intrinsic to
mast cell stabilization and disclaiming olopatadine’s use as an antihistamine.
The failure to make an unequivocal disclaimer with respect to olopatadine’s
antihistaminic utility supports the interpretation that Alcon was attempting to
claim the use of olopatadine generally to treat human allergic eye diseases
through Claim 1.
[57]
Alcon
says that olopatadine’s utility as a mast cell stabilizer is not inherent in
its use as a simple antihistamine because it is only at dosages that far exceed
what would be necessary for antihistaminic use that its mast cell stabilizing
effects would occur. The 094 Patent does not, however, inform the reader of
this distinction or instruct on how one could avoid an infringement by this
means. Instead, the presence of several other claims in the 094 Patent for the
use of olopatadine to treat allergic eye diseases at concentrations much lower than
0.1% belie Alcon’s interpretation. There is also evidence from the prior art
that indicates that antihistamines can be effectively used at dosages
equivalent to 0.1%: see Affidavit of Ines Ferreira, Exhibit “B.11” at p 668.
Alcon’s witnesses conceded that, at such a dosage, a clinician had no control
over olopatadine’s biological activity: see Cross-Examination of Dr. Martin K.
Church (7 September 2011) at p 77; Cross-Examination of Dr. Neal P. Barney,
M.D. (21 September 2011) at pp 41-44 [Cross-Examination of Dr. Barney]; Cross-Examination
of Phil Lieberman, M.D. (2 October 2011) at pp 86-88.
[58]
In
their affidavits, the Alcon witnesses attempted to link the discovery of
olopatadine’s mast cell stabilization properties to its supposedly novel
clinical utility as a prophylactic agent. Although there is a reference in the
disclosure to the therapeutic and prophylactic use of olopatadine, there is
nothing to indicate that this was a newly discovered and inventive utility. Instead,
Claims 8 and 20 refer to a therapeutically effective amount of olopatadine and
none of the claims refer to a prophylactic utility.
[59]
Alcon’s
witnesses did not strongly assert that the inventive concept lay in the use of
olopatadine as a prophylactic agent. For example, Dr. Barney agreed under
cross-examination that antihistamines could also be used in advance to prevent
the appearance of allergic symptoms: see Cross-Examination of Dr. Barney at pp
104-107. His lack of comfort in placing reliance on olopatadine’s utility as a
prophylaxis can also be seen in the following exchanges under cross-examination:
389 Q. Let me show you an article. I
have a copy for you and Mr. Belmore. It’s entitled, “Conjunctival Mast
Cells in Ocular A1lergic Disease,” and you recognize that article, I take it?
A. Yes.
390 Q. And look at Page 121 of your
paper. Right column, you wrote,
“For the majority of individuals with ocular allergy,
topical application of mast cell stabilizing antihistamine drugs are effective
in relieving the symptoms of immediate hypersensitivity, redness, itching,
tearing,”
Do you see that?
A. Yes.
391 Q. And in this portion of
your article, despite talking about mast cell stabilizing effects -- despite
talking about mast cell stabilizing medicines, you speak about the relief of symptoms,
do you see that?
A. Yes.
392 Q. And what you wrote in your
article, I presume. was believed by you to be accurate when you wrote it?
A. Yes.
393 Q. And you knew mast cell stabilizers
also, at least you believed mast cell also had prophylactic effects, correct?
A. Well, prophylactic in
that I believe they have mast cell stabilization effect. I’m not sure how that
means prophylactic.
394 Q. So your use of the term symptomatic
in your article didn’t rule out the possibility of the drug acting as mast cell
stabilizers, correct?
A. That’s correct.
…
479
Q.
My question was do you think that Claim 1 embraces prophylactic use, yes or no?
MR. BELMORE: He has given
you his answer in terms of inhibition of release of antihistamine mediators.
480 Q. That wasn’t my question. It was
something that he was eager to tell me, but my question was whether or not you construe
the claim to embrace prophylactic uses.
A. It doesn’t say
prophylactic, and I would take from this that it’s capable of diminishing signs
and symptoms of allergy.
481 Q. And that would be so for all
of the claims of the patent? Take your time to look at them.
A. All of the claims
relate to Claim 1.
[Emphasis added]
Cross-Examination of Dr. Barney at pp 85-86, 109.
[60]
On
the strength of this evidence and the equivocal and imprecise use of the terms “therapeutic”
and “prophylactic” in the disclosure, I do not accept that this term can be
read into the claims as Alcon maintains.
Conclusion
[61]
For
the foregoing reasons Alcon’s construction of the patent claims in issue is
rejected. Because the 094 Patent purports to claim a monopoly over olopatadine
for its known utility for the treatment of allergic eye diseases it fails on
the ground of obviousness. The 094 Patent is invalid and Alcon’s application
for an order prohibiting the Minister from issuing a NOC to Apotex is dismissed
with costs. If the parties are unable to agree on costs, I will accept further
written submissions from them not to exceed 7 pages in length.
JUDGMENT
THIS
COURT’S JUDGMENT is that application
is dismissed with costs payable to Apotex.
"R.L.
Barnes"
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