The first is
Canadian Patent No. 2,325,014 (the '014 Patent) owned by Schering Corporation,
the other Applicant in this matter (Schering Corporation and Schering Plough
are collectively referred to as “Schering” or “the Applicants”). The second
listing is Canadian Patent No. 2,267,136 (the '136 Patent) owned by
Sepracor Inc. (Sepracor) and for which Schering‑Plough holds a licence.
[2]
Pharmascience Inc. (Pharmascience) wishes to
manufacture and sell a product it describes as “desloratadine tablets, 5 mg of
desloratadine per tablet, for the treatment of nasal and non-nasal symptoms of
allergic rhinitis”. Pursuant to the relevant Patented Medicines (Notice of
Compliance) Regulations, S.O.R./93-133 (NOC Regulations),
Pharmascience has applied to the Minister of Health (the Minister) for approval
to sell its product into Canada.
As required by the NOC Regulations, Pharmascience served a Notice of
Allegation (NOA) dated October 17, 2007, addressed to Schering-Plough, wherein
Pharmascience alleged that: (a) no claim of the '136 Patent or the '014 Patent
would be infringed by the making, construction, using or selling by
Pharmascience of its product; and (b) the claims of the '136 and '014 Patents
are not valid.
[3]
In response to the NOA, as the holder of the
notice of compliance for AERIUS, Schering commenced (by way of Notice of
Application filed with the Court on December 3, 2007) an application for
prohibition pursuant to s. 6(1) of the NOC Regulations. After litigation
that ended with the decision of the Federal Court of Appeal in Sepracor Inc.
v. Schering-Plough, 2008 FCA 230, [2009] 2 F.C.R. 237, Sepracor, named as a
Respondent in this application, was permitted to participate in this
application in support of Schering. On the eve of the hearing of this
application, Sepracor advised the Court that it would not appear at the hearing
and that it would rely on its written submissions.
[4]
If the application is allowed in full, the
Minister will be prohibited from issuing a Notice of Compliance (NOC) to
Pharmascience, thereby preventing Pharmascience from marketing its product
until the expiry of the '136 Patent and the '014 Patent.
[5]
For the reasons set out in the following, I have
concluded that the application will be dismissed in respect of both patents.
The determinative findings – stated in summary terms – are that, on a balance
of probabilities, the following allegations of Pharmascience are justified:
1.
Pharmascience does not infringe Claim 23 of the '136
Patent;
2.
Claims 1, 6 and 9 of the '136 Patent were
anticipated by certain of the prior art;
3.
Claims 1, 6, 9 and 23 of the '136 Patent are
obvious;
4.
Claim 23 of the '136 Patent is overbroad; and
5.
Pharmascience does not infringe Claims 1 and 38
of the '014 Patent.
2.
CONTENTS
[6]
To assist the reader, I am including an outline
of these Reasons, noting the beginning paragraph of each topic.
INTRODUCTION .............................................................................................. [1]
CONTENTS ........................................................................................................ [6]
ISSUES ................................................................................................................ [7]
WITNESSES ..................................................................................................... [10]
BACKGROUND OF AERIUS ......................................................................... [14]
PHARMASCIENCE PRODUCT .................................................................... [18]
THE '136 PATENT ........................................................................................... [24]
Construction of the '136 Patent ................................................................. [25]
General Principles of Construction ................................................ [25]
Person Skilled in the Art ............................................................... [28]
Application of the principles to construction of the '136 Patent
Claims ......................................................................................... [29]
Infringement ............................................................................................. [56]
Validity .................................................................................................... [62]
Anticipation of Claims 1, 6 and 9 by Aberg and Cho ..................... [64]
Obviousness of Claims 1, 6, 9 and 23 of the '136 Patent ............... [97]
Overbreadth of Claim 23 ............................................................ [131]
THE '014 PATENT ......................................................................................... [140]
Construction of the '014 Patent ............................................................... [141]
Application of the principles to the '014 Patent claims................... [141]
Infringement of the '014 Patent ............................................................... [185]
Validity of Claims 1 and 38 of the '014 Patent ......................................... [190]
Lack of Utility, Sound Prediction and Inoperable Species ............ [191]
Obviousness .............................................................................. [196]
Overbroad Claiming ................................................................... [211]
Conclusion on validity allegations ................................................ [216]
OVERALL
CONCLUSION ........................................................................... [217]
3.
ISSUES
[7]
There are two sets of issues to be addressed in
this proceeding -- one set for each of the patents.
[8]
With respect to the '136 Patent, the issues are
as follows:
·
What is the proper construction of Claims 1, 6,
9 and 23 of the '136 Patent?
·
Has Schering met its burden of satisfying this
Court that Pharmascience’s allegation of non-infringement of claims 1 and 9 of
the '136 Patent is not justified?
·
Has Pharmascience led sufficient evidence to
rebut the presumption of validity of Claims 1, 6, 9 and 23 and has Schering, in
turn, failed to meet its burden of showing that the allegation of invalidity is
not justified?
[9]
With respect to the '014 Patent, the issues are
as follows:
·
What is the proper construction of Claims 1 and
38 of the '014 Patent?
·
Has Schering met its burden of satisfying this
Court that Pharmascience’s allegation of non-infringement of claims 1 and 38 of
the '014 Patent is not justified?
·
Has Pharmascience led sufficient evidence to
rebut the presumption of validity of Claims 1 and 38 and has Schering, in turn,
failed to meet its burden of showing that the allegation of invalidity is not
justified?
4.
WITNESSES
[10]
Each of Schering, Sepracor and Pharmascience
provided affidavit evidence from a number of witnesses whose evidence addressed
both technical and factual matters. Those witnesses who provided expert or fact
evidence of the most significance in this application are described below.
[11]
Schering’s expert witnesses include:
1.
Dr. Louis Cartilier, Professor with the Faculty
of Pharmacy at the University
of Montreal. Dr. Cartilier
researches and teaches in the area of drug design and manufacturing of
pharmaceutical dosage forms and consults to pharmaceutical companies on
formulation issues. His first affidavit was directed to the issue of claims
construction and infringement. In his Reply Affidavit, he addressed the issue
of invalidity raised by Pharmascience.
2.
Dr. Gilbert Banker, now retired. Dr. Banker’s lengthy
academic career was completed as Dean and John L. Lach Distinguished Professor
of Drug Delivery at the University of Iowa College of Pharmacy from 1992-1999. Although
his entire career has been in academia, Dr. Banker has acted as a consultant to
pharmaceutical companies. He is co-editor with Dr. Christopher Rhodes on Modern
Pharmaceutics, 4th ed. (New York: Marcel Dekker, Inc., 2002), a textbook about the formulation of
drugs. Dr. Banker’s first affidavit was directed to the issue of claims
construction and infringement. In his Reply Affidavit, he addressed the issues
of invalidity raised by Pharmascience
3.
Dr. Jerry Atwood, Professor and Chairman of the
Department of Chemistry at the University of Missouri-Columbia. Dr. Atwood has
focused his entire academic, research and teaching career on solid state
chemistry. He was asked to opine on the affidavits of Drs. Rhodes and Fiese. In
particular, Dr. Atwood was very critical of what he called the
“oversimplification”, by Pharmascience’s experts, on the role of the Maillard
reaction. Dr. Atwood also responded to the Pharmascience experts’ opinions on
patent validity issues. Finally, he provided a short opinion responding to Dr.
Rhodes’s reply affidavit on certain limited issues related to formulation and
the Food and Drug Administration (FDA) practices.
[12]
Pharmascience’s expert witnesses include:
1.
Dr. Christopher Rhodes, Professor Emeritus at
the University of Rhode Island
and co-editor with Dr. Banker on Modern Pharmaceutics. For over 30
years, Dr. Rhodes has been involved with the design and evaluation of drug
products. Dr. Rhodes provided opinions on claims construction, the state of the
prior art, obviousness, overbreadth, inoperability and utility for both patents
in issue.
2.
Dr. Eugene Fiese, a pharmaceutics consultant
with Fiese Pharmaceutics Consulting. Of particular relevance and assistance,
Dr. Fiese has extensive and direct laboratory experience in drug formulation.
He provided opinions on the issues of claims construction, the state of the
prior art, obviousness and utility for both patents in issue.
[13]
Sepracor presented, as a fact witness, Mr.
Stephen Wald, one of the named inventors of the '136 Patent.
5.
BACKGROUND OF AERIUS
[14]
As noted, the key ingredient in AERIUS is DCL.
DCL is a molecule with medicinal properties as an antihistamine. As compared to
other antihistamines known in the art, DCL is non-drowsy and avoids some other
negative side effects. A number of patents relating to DCL have been filed over
the years and prior to the patents in issue. This application is not about the
invention of DCL. However, two of the earlier patents have particular
significance for this application:
·
U.S. Patent No. 4,659,716 with a patent date of
April 21, 1987 (the Villani Patent) is a product patent that discloses and
claims DCL itself and several of its compositions.
·
U.S. Patent No. 5,595,997 (the Aberg Patent)
with a patent date of January 21, 1997 is a use patent that discloses and
claims methods of treating allergies with DCL while avoiding certain side
effects of other antihistamines.
[15]
Schering and Sepracor claim that, working
independently, they invented a form of DCL that was sufficiently stable to
bring to market. Each of Schering and Sepracor submits that, prior to the work
carried out by the inventors of the '014 and the '136 Patents, it was not known
that DCL would degrade when formulated with acidic excipients such as lactose,
one of the most common fillers or excipients and a compound that was “taught”
by the Aberg Patent.
[16]
Thus, Schering asserts that the first
“invention” or discovery reflected in the two patents was that DCL degrades and
is highly reactive in the presence of acidic excipients, including lactose.
Having identified the problem, the inventors of the two patents independently
came up with solutions to the problems.
[17]
In simple terms, the Schering inventors came up
with a DCL composition where the “carrier medium” was free of acidic excipients
and contained a “basic salt” ('014 Patent). Sepracor’s invention was a
composition where the carrier was lactose free or a composition that was
anhydrous (the '136 Patent).
6.
PHARMASCIENCE PRODUCT
[18]
Pharmascience, in its NOA, alleges that its
product will not infringe either the '014 or the '136 Patent. While
acknowledging that its composition contains a therapeutically effective amount
of DCL with a pharmaceutically acceptable carrier, Pharmascience alleges that:
1.
With respect to the '014 Patent, its product
“does not contain a DCL-protective amount of a pharmaceutically acceptable
basic salt and is not substantially free of acidic excipients, as those terms
are used in the '014 Patent”; and
2.
With respect to the '136 Patent, its product “is
not entirely free or substantially free of reactive excipients and is not
substantially free of unbound water, as those terms are used in the '136
Patent”.
[19]
For purposes of establishing whether
Pharmascience’s allegation of non-infringement is justified, it is necessary to
understand the Pharmascience product. Pharmascience declined to give samples of
its product to Schering for purposes of this application. As a result of
Prothonotary Aronovitch’s Order, dated June 11, 2008, Pharmascience did provide
the details of the complete manufacturing process. Schering contracted with the
Toronto Institute of Pharmaceutical Technology (TIPT) to perform the
formulation described in the produced documentation. Mr. Frank Martinuzzi, Manager
– General Operations & Laboratory of TIPT, was engaged to create a “recipe”
for formulating tablets that, as closely as scientifically possible, would
match those made by Pharmascience, and to carry out the formulation.
Subsequently, Mr. George Kretschmann, an engineering technologist at the University of Toronto, subjected the tablets to scanning electron microscopy (SEM) to
establish the structure of the particles.
[20]
From the experiments of Mr. Martinuzzi and the
SEM conducted by Mr. Kretschmann, as interpreted by other experts, I am
satisfied that Pharmascience uses a three-step process to manufacture its
tablets:
1.
[Confidential Step One] In this first process,
DCL and [Confidential Compound One] are mixed. After the addition of other
excipients, the mixture is formed into [forms] which contain the following:
a.
DCL [.
. .]
b.
[Other compounds including Confidential Compound
One and Confidential Compound Two] [. . .]
2.
Blending and compression. The above [forms],
once dried, are formed into tablets. As part of this step, additional
excipients are added, one of which, as acknowledged by Pharmascience, is
lactose anhydrous.
3.
Coating. At the final stage, the tablets are
coated.
[21]
Pharmascience does not deny that lactose is
added at step two of the procedure. The question of where the lactose is
located within the tablet is critical.
[22]
Dr. Banker opined that the [forms] of step one
survive Pharmascience’s manufacturing process and are found in its tablets (Application
Record of the Applicants [A.R.], vol. 3, Tab. 10, p. 487). Dr. Cartilier
provided further details in support of his similar conclusion that the [forms] of
step one “survive compression and exist intact in tablets made according to the
Pharmascience process” (A.R., vol. 2, Tab. 6, p.186). Dr. Cartilier described
the Pharmascience tablets as being made up of three compartments: the [forms] comprising
DCL and [excipients within the form]; the [space outside the form] comprising
the [excipients outside the form] and potentially discrete fragments of some
broken [forms]; and, the coating (A.R., vol. 2, Tab. 6, p.188). It follows from
this that, on a balance of probabilities, any lactose in the Pharmascience
tablets is contained outside the step one [form]. In other words, the DCL is
separated from the lactose, except for some inconsequential amounts where the
step one [forms] are broken during the tableting process.
[23]
I observe that the step one [forms] are designed
to be anhydrous and to contain [Confidential Compounds One and Two]. Each of
these elements is relevant to the question of whether Pharmascience’s
allegation of non-infringement is justified and is considered later in these Reasons.
7.
THE '136 PATENT
[24]
I turn first to consider the issues with respect
to the '136 Patent.
7.1.
Construction of the '136
Patent
7.1.1.
General Principles of Construction
[25]
As taught by the jurisprudence, my first task is
to undertake a "purposive construction" of the claims in issue. There
is no disagreement and thus no need to set out an exhaustive list of the
well-established principles of claims construction (see, principally, Free
World Trust v. Electro Sante Inc., [2000] 2 S.C.R. 1024, 9 C.P.R. (4th)
168, and Whirlpool Corp. v. Camco Inc., [2000] 2 S.C.R. 1067, 9 C.P.R.
(4th) 129). In overarching terms:
The key to
purposive construction is therefore the identification by the court, with the
assistance of the skilled reader, of the particular words or phrases in the
claims that describe what the inventor considered to be the
"essential" elements of his invention
(Whirlpool,
above at para. 45).
[26]
The Court must objectively construe the claim
through the eyes of the hypothetical skilled person in the art, and decide how
this person would have understood the patent at the relevant time (Whirlpool,
above, at paras. 45, 53).The Court should construe the claims in light of the
description in the specification, assisted, where necessary, by experts as to
the meaning of technical terms, if they cannot be understood by the Court from
reading the specification (Shire Biochem Inc. v. Canada (Minister of Health),
2008 FC 538, 328 F.T.R. 123 at para. 22; Whirlpool, above, at para. 45).
[27]
Finally, it is also important to recognize that
purposive construction should be directed at the points at issue between the
parties (see Shire Biochem, above, at para. 21).
7.1.2.
Person Skilled in the Art
[28]
In this case, there is no dispute between the
parties as to the notional skilled person. The skilled person for purposes of
construction of both patents in issue will hold a BSc in chemistry or a related
field with an emphasis on pharmaceutical formulations and solid oral dosage
forms along with four years of experience in this field.
7.1.3.
Application of the principles to construction
of the '136 Patent claims
[29]
The first patent in issue is the '136 Patent.
The '136 Patent was published on August 13, 1998; this is the date for
determining the proper construction of the patent.
[30]
The '136 Patent is entitled “Lactose-free,
non-hygroscopic and anhydrous pharmaceutical compositions of
descarboethoxyloratadine”. As acknowledged in the patent specification, an
earlier patent (the Aberg Patent) disclosed that DCL, “while providing
effective, non-sedating antihistamic therapy, also avoids many, often severe,
adverse side-effects commonly associated with the administration of [other antihistamines]”.
[31]
As set out in the specification, beginning at page
3, the inventors first identify a manufacturing “problem”, that being the
undesirable degradation of DCL in the presence of lactose or “other similar
reactive excipients, such as mono- or di-saccharides”:
Recognizing the
desirability of DCL-containing pharmaceutical compositions, we have concluded
that under typical manufacturing and storage conditions, DCL is not stable and
degrades in the presence of lactose, a compound commonly used as a filler in
various pharmaceutical dosage forms, such as tablets, capsules or powders. Over
time, the lactose and DCL compound form a brown-colored product, and there is a
high degree of DCL degradation. The intensity of the brown color is typically
dependent on the amount of DCL present, the conditions of storage, such as
humidity and temperature, as well as the length of storage time.
[32]
The inventors continue on to describe two
aspects of their intervention that are of interest for purposes of the claims
in issue before the Court. The first element of their invention is, quite
simply, the avoidance of lactose. At page 4 of the specification, the inventors
describe their invention as follows:
The present
invention relates to stable pharmaceutical compositions of DCL wherein DCL is
in intimate admixture with one or more excipient(s), including, but not limited
to, blended, granulated or compressed dosage forms, that avoid the
incompatibility between DCL and reactive excipients, such as lactose and other
mono- or di-saccharides.
[33]
In the specification, the inventors describe
certain "preferred embodiments” of this first invention, all of which
avoid the use of lactose or the describe ways in which the interaction of
lactose with DCL may be avoided.
[34]
The second aspect of their invention is the
problem associated with water in the pharmaceutical compound. The inventors
disclose, at page 5, that "our studies have also shown that in the absence
of unbound water very little to no degradation occurs in DCL compositions that
include lactose”. Recognizing that lactose "is among the best of all
direct compression filters in fluidity and is very effective for low dose
formulations", the inventors disclose an embodiment of the present
invention that encompasses "non-hygroscopic pharmaceutical compositions”
comprising DCL and "at least one pharmaceutically acceptable
excipient". The inventors contemplate that, where an overall composition
is substantially non-hygroscopic or anhydrous, such excipients may include
lactose and other reactive excipients such as mono- or di-saccharides.
[35]
The specification includes the “Results of
Excipient Compatibility Studies" (beginning at page 16 of the
specification), following which, various examples or embodiments are described.
The inventors specifically comment, at page 19, that the examples "are
provided by way of illustration and not by way of limitation".
[36]
This brings me to the specific claims in issue.
Schering raises Claims 1, 6, 9 and 23 of the '136 Patent.
[37]
I pause to consider the position of Sepracor. In
its Memorandum of Fact and Law, Sepracor asserted that, in addition to those
claims focused on by Schering, Pharmascience’s allegation was not justified
insofar as Claims 2, 3 and 31. As noted above, Sepracor withdrew from the oral
hearing of the application. This leaves the Court in an odd position. The
Applicant before me is Schering who seeks the remedy of prohibition until
expiry of the '014 and the '136 Patents. Schering does not take a position with
respect to these additional claims raised by Sepracor. Given Schering’s failure
to assert that Pharmascience’s allegations are not justified in respect of
Claims 2, 3 and 31, I can see no reason why I need or should consider the
merits of those allegations.
[38]
Accordingly, I will only construe the claims
relied on by Schering – Claims 1, 6, 9 and 23. Those claims are as follows:
1. A
pharmaceutical composition in blended or granulated form for the treatment of
histamine-induced disorders, comprising a therapeutically effective amount of descarboethoxyloratadine,
or a pharmaceutically acceptable salt thereof, and a pharmaceutically
acceptable inert carrier.
6. The
pharmaceutical composition of claim 1 further comprising a therapeutically
effective amount of an analgesic.
9. The
pharmaceutical composition of claim 1 wherein the composition is present in one
of tablet or capsule form.
23. The
anhydrous pharmaceutical composition of claim 22 wherein the composition is
present in tablet form.
[39]
Claim 23 is dependent on Claim 22 which, in turn,
is dependent on Claim 16. Claim 16 covers:
16. An
anhydrous pharmaceutical composition in granulated or blended form for the
treatment of histamine-induced disorders, comprising a therapeutically
effective amount of descarboethoxyloratadine, or a pharmaceutically acceptable
salt thereof, and a pharmaceutically acceptable carrier.
[40]
Claims 1, 6 and 9 relate to the alleged
invention of the avoidance of lactose. Claim 6 adds an analgesic to the
elements of Claim1, and Claim 9 limits Claim 1 to a tablet or a capsule form.
By the time of oral arguments, the parties no longer disputed that the term
“pharmaceutical composition” meant anything other than the final dosage form.
Thus, the only construction issue in dispute for Claims 1, 6 and 9 is whether
the term “pharmaceutically inert carrier” encompasses everything in the
“pharmaceutical composition” (or final dosage form) or is restricted to only
the materials in intimate admixture with the DCL.
[41]
It is not disputed that lactose is a reactive
excipient rather than an inert carrier.
[42]
Pharmascience argues that “carrier” represents
the vehicle for delivering or administering the active ingredient DCL to the
body. Drs. Rhodes and Fiese opined that “carrier” refers to all of the
components of the final dosage form other than DCL. Thus, to Pharmascience,
“inert carrier” represents that the final dosage must be free of lactose or any
acidic excipient. In support of this construction, Pharmascience argues that
the '136 Patent includes, in the definition of “carrier” or “inert carrier”,
all manner of excipients, including diluents, lubricants, binders, and coating
agents (Patent '136 at p. 10, 14, 15). Since, coating agents are used at the
end of the process, it must certainly mean that “carrier” encompasses all
excipients of the final dosage form.
[43]
In contrast, Schering relies on Drs. Banker and
Cartilier in submitting that a “pharmaceutically acceptable inert carrier”
refers solely to the excipients in “intimate admixture” with the DCL, and not
those outside. Thus, the “inert carrier” must be lactose free, even though the
pharmaceutical composition can include some lactose (A.R., vol. 3, Tab 10, p.
463-464; A.R., vol. 2, Tab 6, p. 176-177)., In my view, the construction
offered by Schering and its experts is to be preferred.
[44]
The first problem with Pharmascience’s
interpretation is with its reference to the coating agents. On reading the '136
Patent, one can see that the inventors set out several ways to solve the
problem of DCL’s degradation when in contact with lactose. One such solution,
“coating DCL”, is found at page 7 of the Patent’s specification. This is where
DCL is first granulated with inert excipients, and then the [forms] are coated
with inert coating agents. Finally, in the tableting process, these [forms],
already protected, can be blended with other excipients, including lactose. As
stated at p. 7, lines 25-30:
Once the
particles or granulated formulations of DCL are coated with the inert coating agent, the coated DCL may be formulated
using standard techniques, including, but not limited to blending, granulation,
compression and combinations thereof, with other inert and reactive excipients,
such as lactose, to make various dosage forms, for example, tablets,
caplets, capsules, torches, and the like.
[Emphasis added.]
[45]
This embodiment of the invention shows that
“coating agents” do not always have to be used at the end process, and thus,
this argument of Pharmascience fails.
[46]
Next, I observe that all of the experts appear
to accept that the word “comprising” is not limiting. That is, what follows the
word “comprising” does not necessarily identify everything that is included in
the composition. In the case of Claim 1, when the inventors describe the
composition as “comprising” DCL with an inert carrier, the skilled person would
know that other things could be included in the composition. (For further
discussion of the word “comprising”, see paragraphs [150]-[151] below.)
[47]
Furthermore, while “pharmaceutical composition”
is used often in the specification to represent the final dosage form to be
administered to patients, “carrier” is never used synonymously or
interchangeably with “pharmaceutical composition” or with “dosage form”. This
differentiation is included in the language of the claims, where the inventors
state that the “pharmaceutical composition” comprises DCL together with a
“pharmaceutically acceptable inert carrier”.
[48]
Drs. Cartilier and Banker state that “inert
carrier” is that which is intimately admixed with DCL. They rely on the
following paragraph found at page 4, lines 3 to 7 of Patent '136:
The present
invention relates to stable pharmaceutical compositions of DCL wherein DCL is
in intimate admixture with one or more excipients, including, but not
limited to, blended, granulated or compressed dosage forms, that avoid the
incompatibility between DCL and reactive excipients, such as lactose and other
mono- or di-saccharides.
[49]
I prefer the opinions of Drs. Cartilier and
Banker that the skilled person would understand that, in order to protect DCL,
those excipients that are in admixture with the DCL must not include “reactive
excipients”. According to Dr. Cartilier, this passage is “consistent with the
purpose of the invention which is to provide a formulation in which DCL will
not be decomposed or discoloured” (A.R., vol. 2, Tab. 6, p.177). Dr. Cartilier
continued by saying “the ‘136 Patent recognizes that some pharmaceutical
product have different ‘compartments’ or sections” (A.R., vol. 2, Tab 6, p.178).
He also stated: “The disclosure tells the Skilled Formulator that a formulation
(or product) with multiple compartments is contemplated by the ‘136 Patent” (A.R.,
vol. 2, Tab 6, p.178). Dr. Cartilier pointed to the language of the patent that
states (‘136 Patent, p. 7, lines 25-29):
Once the particles
or granulated formulations of DCL are coated with the inert coating agent,
the coated DCL may be formulated using standard techniques, including,
but not limited to, blending, granulation, compression and combinations
thereof, with other inert and reactive excipients, such as lactose, to
make various dosage forms, for example, tablets, caplets, capsules, troches,
and the like.
[50]
On the other hand, Dr. Rhodes stated that the
reference to “intimate admixture”, by Schering’s experts, would lead the
skilled person “to apply an unusual interpretation of the commonly used term
‘carrier’” (Application Record of the Respondent, Pharmascience Inc. [R.R.], vol.
1, Tab 1, p.43). According to Dr. Rhodes, carrier represents the whole dosage
form, not an inner [form]. Dr. Rhodes justified this interpretation by stating
that inventors included “coating agents” in their list of excipients that may
comprise the carrier (R.R., vol. 1, Tab 1, p. 43). I do not agree with
this interpretation. As I have stated previously (at paragraphs [45]-[46] of this decision), coating agents do
not have to be used at the end process.
[51]
The essential element of Claims 1, 6 and 9 is
that the DCL must be in intimate admixture only with inert carriers, thus
avoiding the intimate mixture of DCL with reactive excipients. The claims are
silent on what excipients can be used outside the carrier but still within the
“pharmaceutical composition”. I believe that this is a reasonable construction
of the words of Claim 1. The construction of Claims 6 and 9 would follow.
[52]
The only issue with respect to Claim 23 – and
Claim 16 on which Claim 23 depends – is what is meant by the term “anhydrous
pharmaceutical composition”. And, as I read the submissions of Schering and
Pharmascience, I am not persuaded that there is a material difference in their
proposed constructions. Each of Pharmascience and Schering acknowledge that the
term “anhydrous” would not be read by the skilled person to mean absolutely no
water present in the composition. According to Dr. Cartilier, the person
skilled in the art would know that “pharmaceutical compositions are never
anhydrous in an absolute sense” and 100 percent water free (A.R., vol. 2, Tab
6, p.180). Dr. Rhodes, for Pharmascience, agreed and stated that the skilled
person would read “anhydrous” as referring “to an amount of unbound water that
may be greater than zero, but still insufficient to initiate or accelerate the
degradation reaction” (R.R., vol. 1, Tab 1, p.11). In cross-examination, Dr.
Atwood stated: “It’s very difficult to make a pharmaceutical tablet that
doesn’t have some water but some water could be parts per million” (R.R., vol.
5, Tab 10, p.1053, q. 151). Thus, the question is what the patent teaches about
the amount of water that could be contained in the composition.
[53]
The term “anhydrous” is defined in the '136
Patent, at page 11, lines 24-27, as:
The amount of
unbound water present, if any, is insufficient to initiate and/or accelerate
the incompatibility between DCL and reactive excipients, such as lactose.
[54]
The term “unbound water”, as stated by the
inventors, at page 11, lines 22-24, refers to “water that is not present in the
form of a stable hydrate of one or more components of the pharmaceutical
composition, e.g., α-lactose monohydrate.”
[55]
The inventors have not set out any absolute
limit of water content that would meet the requirement to be “anhydrous”.
Rather they have defined the amount of water content by its function. Stated
simply, a composition of DCL appears to satisfy Claims 16 and 23 if it remains
stable in the presence of lactose. If the composition with lactose degrades, it
is not anhydrous. If it does not degrade, it is anhydrous. Dr. Rhodes accepted
this construction, but he raised several concerns: “the person of ordinary
skill in the art would not know, from reading the ‘136 Patent, either how much
unbound water will be acceptable, nor even how to measure or determine this
amount” (R.R., vol. 1, Tab 1, p.11). I agree. While I accept the construction
of “anhydrous” as an insufficient amount of unbound water to initiate or
accelerate the degradation process, I find that it raises significant questions
on: (a) how one measures infringement; and (b) the allegations of invalidity.
These questions are discussed below.
7.2.
Infringement
[56]
Based on these constructions, I turn to the
question of whether Pharmascience’s allegation of non-infringement is
justified.
[57]
As discussed above, the Pharmascience tablets
contain [forms] that are free of reactive excipients such as lactose. The
lactose in the Pharmascience tablets is situated outside the [form] or
“carrier”. I am satisfied that the allegation of non-infringement of Claims 1,
6 and 9 is not justified.
[58]
The question with respect to Claim 23 is more
difficult to answer. While Claims 1, 6 and 9 require, in effect, that the carrier
be free of lactose, Claim 23 (through Claim 16) refers to the entire
formulation or tablet as being anhydrous. The final tablets made according to
the Pharmascience specifications contain water in the amount of [confidential]%
of the total weight. This amount has been confirmed by Dr. Fiese (R.R., vol. 3,
Tab 4, p.789), and Dr. Banker (A.R., vol. 3, Tab 10, p. 501). According to Dr. Rhodes,
“under typical manufacturing conditions, a tablet will normally contain less
than about 2% of total water and will rarely if ever exceed about 3%” (R.R., vol.
1, Tab 1, p.50). Dr. Atwood, in cross examination, acknowledged that while
some tablets can be higher than 3% of unbound water, the normal level of water
ranges from 1 to 3% in pharmaceutical products that undergo usual manufacturing
processes (R.R., vol. 5, Tab 10, p.1053-1054). Nevertheless, the tablets are
stable; they do not degrade. Thus, it appears that the tablets contain
insufficient water to initiate or accelerate the incompatibility between DCL
and reactive excipients, such as lactose. If this is correct, the allegation of
non-infringement of Claim 23 is not justified.
[59]
In my view, however, this is an
overly-simplified approach to the question of infringement.
[60]
Claim 16 is a “functional” claim. According to
Justice Noël in Burton Parsons Chemicals Inc v. Hewlett-Packard (Canada) Ltd. (1972) 7 C.P.R. (2d) 198 at p. 215: “functional claiming, in the
sense of claiming in terms of a desired result, is in principle permissible in
this country”. Implicit in Claim 16 is that a stable or non-degrading
composition is a function of the avoidance of water. As I see it, this is not a
simple question to answer. For example, the '136 Patent teaches at least two
ways of avoiding degradation – avoidance of lactose or avoidance of water. The '014
Patent discloses another method – the avoidance of lactose together with the
use of a basic salt. How would one know that the stability of any Pharmascience
product is as a result of an infringement of Claim 16? Could the stability be
due to the use of a different excipient? There is no simple way to establish
that a lack of degradation is due to the avoidance of water rather than to some
other variable in the formulation. Schering did not, it appears, perform any
testing to determine what effect, if any, the amount of water in
Pharmascience’s tablets – as opposed to other elements in its composition – had
on the stability of the final product. Accordingly, I am not persuaded that
Schering has met its burden to show that the Pharmascience product would
infringe Claims 16 and 23. I find that Pharmascience’s allegation of
non-infringement of these claims is justified.
[61]
Even if I am wrong in this conclusion, I am also
satisfied that Pharmascience’s allegation that Claim 16 (and hence Claim 23) is
invalid due to obviousness or overbreadth is justified. This is discussed
below.
7.3.
Validity
[62]
In its NOA, Pharmascience makes a number of
allegations related to the validity of Claims 1, 6, 9 and 23. For purposes of
these reasons, I will focus on those allegations that appear to have the most
merit; specifically:
1.
Claims 1, 6, 9 and 23 were anticipated or
rendered obvious as of February 7, 1997 by the prior art or common general knowledge;
and
2.
Claim 23 is overbroad.
[63]
I find Pharmascience’s allegations regarding a
failure by the inventors to demonstrate the utility or sound prediction of
their invention (either avoidance of lactose or avoidance of water) to not be
justified.
7.3.1. Anticipation of Claims 1, 6 and 9 by Aberg and Cho
[64]
I turn to the first argument of Pharmascience –
that of anticipation. In its NOA, Pharmascience relies on, inter alia,
United States Patent No. 5,595,997 (the Aberg Patent) and United States Patent
No. 4,990,535 (the Cho Patent), to allege that “[t]he subject matter of claims
1 to 36 of the '136 Patent was . . . disclosed to the public prior to the claim
date of the '136 Patent . . .” and that, “[t]herefore, each of the claims 1 to
36 of the '136 Patent are invalid for lacking novelty (i.e. for being
anticipated) pursuant to section 28.2 of the Act”.
[65]
In its final submissions, Pharmascience narrowed
its allegations to argue that Claim 9 of the '136 Patent was anticipated by
certain of the teachings of both the Aberg Patent and the Cho Patent.
7.3.1.1.
Principles of Anticipation
[66]
I begin this section of the Reasons by referring
to the general legal principles of anticipation.
[67]
The concept of anticipation arises from s. 28.2
of the Patent Act, R.S.C. 1985, c.P-4. In short, this provision requires
that the subject matter of a claim must not have been disclosed to the public
before the claim date.
[68]
Until the decision of the Supreme Court in Apotex
v. Sanofi-Synthelabo, 2008 SCC 61, [2008] 3 S.C.R. 265, the test for anticipation
followed by the Courts was as described in Beloit Canada Ltd. v. Valmet Oy
(1986), 8 C.P.R. (3d) 289 (F.C.A.), at p. 297:
One must, in
effect, be able to look at a prior, single publication and find in it all the
information which, for practical purposes, is needed to produce the claimed
invention without the exercise of any inventive skill. The prior publication
must contain so clear a direction that a skilled person reading and following
it would in every case and without possibility of error be led to the claimed
invention.
[69]
In Sanofi-Synthelabo, at paragraph 23,
the Supreme Court determined that the trial judge, by using the Beloit test, “overstated the stringency
of the test for anticipation that the ‘exact invention’ has already been made
and publicly disclosed”. The Supreme Court concluded that the issue of whether
an invention is anticipated by the prior art requires that the Court have
regard to two questions:
1.
Was the subject matter of the invention
disclosed to the public by a single disclosure?
2.
If there has been such a clear disclosure, is
the working of the invention enabled by that disclosure?
[70]
At the first step of the analysis, the Supreme
Court provided the following guidance (at para. 25):
When considering
the role of the person skilled in the art in respect of disclosure, the skilled
person is "taken to be trying to understand what the author of the
description [in the prior patent] meant" (para.32). At this stage, there
is no room for trial and error or experimentation by the skilled person. He is
simply reading the prior patent for the purposes of understanding it.
[71]
Once disclosure has been made, the question of
enablement was described by the Supreme Court (at para 27):
Once the subject
matter of the invention is disclosed by the prior patent, the person skilled in
the art is assumed to be willing to make trial and error experiments to get it
to work. While trial and error experimentation is permitted at the enablement
stage, it is not at the disclosure stage. For purposes of enablement, the
question is no longer what the skilled person would think the disclosure of the
prior patent meant, but whether he or she would be able to work the invention.
[72]
In Abbott Laboratories v. Canada (Minister of Health) 2008 FC 1359, 337 F.T.R. 17, aff’d 2009 FCA 94, 387 N.R. 347
(referred to as Abbott, Hughes J), Justice Hughes undertook a helpful
survey of the law of anticipation as it exists after Sanofi-Synthelabo,
above. He summarized the legal requirements for anticipation as follows (at
para. 75):
1. For there to be anticipation there must be both
disclosure and enablement of the claimed invention.
2. The disclosure does not have to be an "exact
description" of the claimed invention. The disclosure must be sufficient
so that when read by a person skilled in the art willing to understand what is
being said, it can be understood without trial and error.
3. If there is sufficient disclosure, what is disclosed must
enable a person skilled in the art to carry out what is disclosed. A certain
amount of trial and error experimentation of a kind normally expected may be
carried out.
4. The disclosure when carried out may be done without a
person necessarily recognizing what is present or what is happening.
5. If the claimed invention is directed to a use different
from that previously disclosed and enabled then such claimed use is not
anticipated. However if the claimed use is the same as the previously disclosed
and enabled use, then there is anticipation.
6. The Court is required to make its determinations as to
disclosure and enablement on the usual civil burden of balance and
probabilities, and not to any more exacting standard such as quasi-criminal.
7. If a person carrying out the prior disclosure would
infringe the claim then the claim is infringed.
7.3.1.2.
The Aberg Patent
[73]
Turning to the facts of the application before
me, I first consider the teachings of the Aberg Patent. The parties before me
appear to be agreed that, if the Aberg Patent is a single disclosure of the
subject matter of Claim 9 of the '136 Patent, the working of the invention
disclosed in Claim 9 is enabled by that disclosure.
[74]
In the disclosure, the inventors of the Aberg
Patent state that the invention “is further defined by reference to” a number
of examples. One of those examples is Example 8, entitled “Soft Gelatin
Capsules”:
A mixture of
active ingredient in a digestible oil such as soybean oil, lecithin, cottonseed
oil or olive oil is prepared and injected by means of a positive displacement
pump into gelatin to form soft gelatin capsules containing 0.1 to 10 milligrams
of the active ingredient. The capsules are washed and dried.
[75]
The “active ingredient” referred to in Example 8
is DCL. The product described in Example 8 would be lactose free.
[76]
Soft gelatin tablets are contemplated by the '136
Patent. At page 13 of the specification, the inventors state that, “Suitable
dosage forms include tablets, troches, cachets, capsules, including hard and
soft gelatin capsules, and the like.” [Emphasis added.] Claim 9 of the '136
Patent specifically claims capsules:
The
pharmaceutical composition of claim 1 wherein the composition is present in one
of tablet or capsule form.
[Emphasis added.]
[77]
The key question to be asked is whether Example
8 of the Aberg Patent falls within Claims 1 and 9 of the '136 Patent. I am
satisfied that it does. This was the unequivocal opinion of Dr. Fiese (R.R.,
vol. 2, Tab 2, p.437) and Dr. Rhodes (R.R., vol. 1, Tab 1, p.58).
[78]
First, Claim 9 captures either tablet or capsule
forms of the “pharmaceutical composition of claim 1”. No expert appears to
dispute that conclusion.
[79]
Next, I turn to an examination of whether the
composition described in Example 8 of the Aberg Patent consists of a
“pharmaceutical composition of claim 1”. On this point, I observe that the Example
8 composition is free of lactose or any other reactive excipient. The only
question remaining is whether the composition of Example 8 of the Aberg Patent
is “in blended or granulated form” as set out in Claim 1. It is obvious that
Example 8 of the Aberg Patent is not granulated. But, could it be considered to
be blended?
[80]
On this issue, I turn to the experts. Dr. Fiese,
in his affidavit, opined that the gelatin capsule disclosed in Example 8 of the
Aberg Patent is a “pharmaceutical composition in blended form” [Emphasis
added] (R.R., vol. 2, Tab 2, p.437). Dr. Rhodes, in his affidavit, stated that
the term “blended” used in the patent (and indeed in pharmaceutical technology
generally) simply means mixed together” (R.R., vol. 1, Tab 1, p.36). Dr. Banker
was asked, during cross-examination, whether Example 5 of '136 Patent (which
example is almost identical to Example 8 of the Aberg Patent) would fall within
Claim 1 of the '136 Patent. His response was: “The DCL could be in blended
form with the components listed” [Emphasis added]. Only Dr. Atwood appears
to have adopted a different view. During cross-examination, he expressed his
view that a soft gelatin capsule with just DCL in an oil would not be
covered under Claim 1.For Dr. Atwood, a “blend” is something that generally
involves “mixing together things which don’t dissolve one in the other” (R.R.,
vol. 5, Tab 10, p.1045). However, when I read this portion of the transcript, I
note that Dr. Atwood also appears to have accepted that the term “blended” could
be interpreted more broadly (R.R., vol. 5, Tab 10, p.1045, line 14). I believe
that the better view is that the skilled person would understand the product of
Example 8 to be “blended”. Thus, I conclude that, on balance, the composition
of Example 8 meets the requirements of Claim 1 – and thus, Claim 9 – in every
respect.
[81]
Quite simply, if a skilled person were to make a
gel capsule in accordance with Example 8 of the Aberg Patent, he would be
making a capsule that falls within the scope of Claim 9 (and hence, Claim 1) of
the '136 Patent. Stated in other words, the skilled person, by following the
teachings of Example 8 of the Aberg Patent would infringe Claims 1 and 9 of the
'136 Patent.
[82]
For its argument on anticipation, Pharmascience
points to Example 5 of the '136 Patent (p. 21), which states as follows:
Soft gelatin DCL
capsules may be prepared with a mixture of DCL in a digestible oil such as
soybean oil, lecithin, cottonseed oil, or olive oil wherein the mixture is
injected by means of a positive pressure pump into gelatin, such that each
dosage unit contained 0.1 mg to 10 mg of DCL. The capsules are washed and
dried.
[83]
The words of Example 8 in the Aberg Patent and Example
5 of the '136 patent are almost identical. Example 5 of the '136 Patent falls
within Claim 9; so does Example 8 of the Aberg Patent. However, Schering
submits that the similarity of Example 8 of the Aberg Patent and Example 5 of
the '136 Patent ought not to drive my analysis. I agree. The fact that Example
5 is included in the examples of the '136 Patent does not mean that it is
claimed. Anticipation cannot be based on a comparison to something that is not
claimed. Thus, in this discussion of anticipation, I have not relied on the
almost identical wording of the two examples.
[84]
The test for anticipation – even on the most
stringent test of Beloit
– has been met. The allegations of Pharmascience in its NOA that Claims 1 and 9
of the '136 Patent are invalid for anticipation are justified.
[85]
In addition to the argument that the capsules of
Example 8 of the Aberg Patent are not “blended”, Schering puts forward two
additional arguments in response to the allegation:
1.
Examples 7 and 9 of the Aberg Patent are tablets
that have lactose;
2.
Even if the Aberg Patent anticipates the capsule
in Claim 9, s. 27(5) of the Patent Act operates to treat the tablet as a
separate claim.
[86]
On the first of these arguments, Schering points
to Examples 7 (capsules) and 9 (tablets) of the Aberg Patent, both of which
specifically include lactose in their compositions. The argument is that the
“invention” of the '136 Patent does not disclose the avoidance of lactose;
rather it teaches the skilled person to use lactose in Examples 7 and 9. The
simple fact that Example 8 contains no lactose is not, in their submission, a
teaching that the skilled person should avoid lactose.
[87]
This argument, in my view, fails. The fact that
other examples in the Aberg Patent teach other formulations is an irrelevant
factor for assessing the anticipation. According to Justice Hughes in Abbott
the test is (above, at para.75): “If a person carrying out the prior disclosure
would infringe the claim then the claim is infringed.” In other words, by
practising Example 8 of the Aberg Patent – acknowledged by all to be prior art
– a skilled person would infringe Claims 1 and 9 of the '136 Patent. The test
for anticipation is met.
[88]
Schering’s second argument relates to its
interpretation of s. 27(5) of the Patent Act, which provides that:
For greater certainty, where a claim
defines the subject matter of an invention in the alternative, each
alternative is a separate claim for the purposes of sections 2, 28.1 to 28.3
and 78.3
|
Il est entendu que, pour
l’application des articles 2, 28.1 à 28.3 et 78.3, si une revendication
définit, par variantes, l’objet de l’invention, chacune d’elles constitue une
revendication distincte.
|
[89]
Schering argues that Claim 9 defines the subject
matter of the invention in the alternative; the claim describes the composition
as being in “one of tablet or capsule form”. Thus, Schering submits, even if
the capsule referred to in Claim 9 is anticipated by Example 8 of the Aberg
Patent, s. 27(5) applies to treat the tablet form of Claim 9 as a separate
claim. In other words, Schering urges the Court to consider tablets and
capsules in Claim 9 separately as regards to their novelty, non obviousness and
utility. In Schering’s view, s. 27 (5) is a remedial provision where, if the
claim is truly a definition of the invention as an alternative, the invalidity
of one should not cause the invalidity of the others. Pharmascience submits
that s. 27(5) has no application in this case; if one alternative in a claim is
invalid, the entire claim fails.
[90]
I acknowledge that, on its face, s. 27(5)
applies to s. 28.2, which provision, as stated above, is the source of the
requirement that claims not be anticipated by prior art. Nevertheless, I prefer
Pharmascience’s position. Section 27(5) does not save claim 9, if one of the
alternatives in the claim is otherwise invalid for anticipation.
[91]
This very question was considered by Justice
Phelan in Abbott Laboratories v. Canada (Minister of Health), 2005 FC 1332, 45
C.P.R. (4th) 81, aff’d 2007 FCA 153, 361 N.R. 308. In that case – an
NOC application – Abbott argued that s. 27(5) could apply to save certain
alternatives in an individual claim. In rejecting that argument, Justice Phelan
provided the following analysis and conclusion (at paras. 50-57):
50 The
specific wording of s. 27(5) limits its application to three sections of the
Patent Act, evidencing a legislative intention to circumscribe the operation of
the section. S. 27(5) did not say something to the effect of "For all
purposes...".
51 The
sections of the Patent Act to which s. 27(5) refers are (a) section 2 -- the
definition provision; (b) section 28.1 -- the claim date provision; (c) section
28.2 -- the non-prior disclosure provision; (d) section 28.3 -- the non-obvious
provision; and (e) section 78.3 -- transitional provision related to s. 43.
Therefore, the application of s. 27(5) is very limited within the operation of
the Patent Act itself.
52 S. 27(5)
is part of the provisions under the heading "Application for
Patents". The section requires that if there are alternative claims, each
alternative meet the test for patentability -- novelty, utility and
inventiveness. Failure to establish that each alternative meets the test for
patentability would result in the alternative being invalid as well as the
whole of the claim.
53 S. 27(5)
does not direct that alternatives in a claim constitute a separate claim for
purposes of either s. 27 and 58. It is particularly significant that s. 58 is
not included by reference in s. 27(5) because s. 58 allows a court to sever an
invalid claim from a patent and allow the remainder of the patent to survive.
54 The
conflicting interpretations result in Abbott arguing that so long as one
alternative in a claim is valid, the whole claim is saved and Apotex saying
that if one alternative is proven not to be patentable, the whole claim fails.
55 Abbott
makes this argument on the effect of s. 27(5) without reliance on any direct
authority in support. One would have thought that if s. 27(5) had the scope
argued by Abbott, it would have been the subject of at least some learned
writing if not actual decisions of this Court.
56 Given
that alternative claims can result in a vast number of claims and the general
adverse consequences of overclaiming, I interpret the application of s. 27(5)
more narrowly than Apotex. It applies only to the named provisions and is
principally an administrative provision for purposes of a patent application.
57
Therefore, even if the claim (1 or 15) is in the alternative, if Apotex
establishes that an alternative is not patentable, the whole claim fails -- at
least for purposes of an NOC.
[92]
I adopt the reasoning and conclusion of my
brother judge, Justice Phelan, and conclude that the alternative claim to a
tablet set out in Claim 9 is not saved by s. 27(5) of the Patent Act.
[93]
In sum, even without Example 5 of the '136
Patent, the gel capsule made in accordance with Example 8 of the Aberg patent
would fall within Claim 9; such a gel capsule would infringe Claim 9 and Claim
1 of the '136 Patent.
7.3.1.3.
The Cho Patent
[94]
Pharmascience also argues that the '136 Patent
is anticipated by the Cho Patent. The Cho Patent, with a publication date of February
5, 1991, is directed to pharmaceutical compositions containing loratadine or
DCL in combination with ibuprofen (an analgesic), pseudophedrine (a
decongestant) and suitable excipients. Pharmascience summarizes its argument as
follows:
Thus the
preferred DCL tablet of Cho contains an analgesic and decongestant with
[hydroxypropylmethylcellulose (HPMC)] and microcrystalline cellulose in its
core, together with a coating containing DCL, HPMC and [polyethylene glycol
(PEG)]. Such a tablet is a pharmaceutical composition in blended or granulated
form for the treatment of histamine-induced disorders comprising a
therapeutically effective amount of DCL and a pharmaceutically acceptable inert
carrier as claimed by claims 1, 2, 3 and 9 of the '136 Patent.
[95]
Unlike Example 8 of the Aberg Patent, there is
no example or embodiment that would, in my view, constitute a single
disclosure. To move from the Cho Patent to the composition contemplated by
Claim 9 requires a number of choices and assumptions. The skilled person would
need to alter the Cho examples to include DCL. Such a step would allow for
substitution of lactose and sucrose, both of which would take the Cho
compositions outside the '136 Patent. The disclosure is not sufficient “so that
when read by a person skilled in the art willing to understand what is being
said, it can be understood without trial and error” (Abbott, Hughes J,
above, at para. 75).
7.3.1.4.
Conclusion on Anticipation
[96]
I conclude that, on a balance of probabilities,
the allegation of Pharmascience that Claim 9 of the '136 Patent was anticipated
by the teachings of the Aberg Patent is justified. Given this finding, there is
no need to consider the other allegations of invalidity of any of Claims 1, 6
or 9. Nevertheless, in the event that I am mistaken in this conclusion, I will also
consider the allegation of obviousness.
7.3.2. Obviousness of Claims 1, 6, 9 and 23 of the '136 Patent
7.3.2.1.
General Principles of Obviousness
[97]
The term “invention” is defined in s. 2 of the Patent
Act to include “any new and useful . . . composition of matter”.
Pharmascience asserts that Claims 1, 6, 9 and 23 of the '136 Patent would have
been obvious to a person skilled in the art, as of the relevant date.
[98]
The test for obviousness was recently clarified
by the Supreme Court of Canada in Sanofi-Synthelabo. Justice Rothstein,
writing for a unanimous Court, adopted a four-step approach (above, at para.
67):
1. (a) Identify the notional "person skilled in the
art"; and, (b) 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, do those differences constitute steps which would have been obvious to
the person skilled in the art or do they require any degree of invention?
[99]
As part of his analysis, Justice Rothstein
stated that the so-called "obvious to try" test, derived from UK jurisprudence, should be approached
cautiously and with the understanding that "obvious to try" means
"very plain" or "more or less self evident".
... I am of the
opinion that the “obvious to try” test will work only where it is very plain
or, to use the words of Jacob LJ., more or less self evident that what is being
tested ought to work.
For a finding
that an invention was “obvious to try”, there must be evidence to convince a
judge on a balance of probabilities that it was more or less self-evident to
try to obtain the invention. Mere possibility that something might turn up is
not enough.
(Sanofi-Synthelabo,
above, at para 65-66)
[100]
If an "obvious to try" analysis is
warranted, Justice Rothstein proposed a non-exhaustive list of factors that may
apply (Sanofi-Synthelabo, above, at paras. 69-71):
1. Is it more or less self-evident that what is being tried
ought to work? Are there a finite number of identified predictable solutions
known to persons skilled in the art?
2. What is the extent, nature and amount of effort required
to achieve the invention? Are routine trials carried out or is the
experimentation prolonged and arduous, such that the trials would not be
considered routine?
3. Is there a motive provided in the prior art to find the
solution the patent addresses?
4. Another important factor may arise from considering the
actual course of conduct which culminated in the making of the invention.
[101]
In the recent case of Apotex Inc v. Pfizer
Canada Inc., 2009 FCA 8, 385 N.R. 148, at paragraph 29, the Federal Court
of Appeal provided further guidance on the “obvious to try” notion.
The test
recognized is "obvious to try" where the word "obvious"
means "very plain". According to this test, an invention is not
made obvious because the prior art would have alerted the person skilled in the
art to the possibility that something might be worth trying. The invention must
be more or less self-evident.
[Emphasis added.]
[102]
Although the Supreme Court emphasized that
flexibility is required in applying the “obvious to try” test, it appears
well-settled that the Court should address all of the components, and applying
flexibility where appropriate.
7.3.2.2.
The person skilled in the art
[103]
The first step in the analysis is to identify
the notional person skilled in the art. The parties agree that the skilled
person for purposes of this application would hold a BSc in chemistry or a
related field with an emphasis on pharmaceutical formulations and solid oral
dosage forms along with 4 years of experience in this field.
7.3.2.3.
Common General Knowledge
[104]
Next, I must assess the state of the common general
knowledge as of the relevant date. In this application, the common general
knowledge is very similar for both the '136 and '014 Patents.
[105]
In general, it is undisputed that the skilled
person would have knowledge of the Aberg, Cho and Villani Patents. The Aberg
Patent, with its direct claims to DCL, would be of particular relevance.
[106]
One area of disagreement was the knowledge about
the Maillard reaction, a chemical reaction that was first reported in 1912 by
the chemist Louis-Camille Maillard. The reaction is said to occur when compounds
interact with lactose (and similar carbohydrates) to form “a brightly coloured
degradation product – yellow, brown, or pink – readily discernable to the human
eye” (R.R., vol. 1, Tab 1, p.21). All the experts agree that it was general
common knowledge, as of the relevant date, that the Maillard reaction (browning
or degradation) occurs between a primary amine and lactose. However, the
experts come to different conclusions on whether it was common general
knowledge that the Maillard reaction would apply to secondary or tertiary
amines, as well as primary amines.
[107]
Related to the issue of the common general
knowledge and the Maillard reaction, Dr. Cartilier provided his opinion of
the common general knowledge at the relevant date for the '136 Patent (A.R.,
vol. 2, Tab 7, p.302). I would paraphrase Dr. Cartilier’s list as follows:
·
The Maillard reaction was known to occur in the
case of primary amines but would not be understood by the skilled person for
the case of secondary or tertiary amines. DCL is a secondary amine.
·
The Maillard reaction was known to be blocked or
at least hindered in the presence of acids and accelerated in the presence of
bases.
·
The role of lactose in “browning” was uncertain.
·
The Aberg Patent (US ‘997 Patent) and the Villani
(US ‘716 Patent) Patent had shown that lactose was a preferred excipient and
made no mention of the consequences of water being present in a DCL
composition.
·
Many drug products containing lactose or other
amines existed on the market.
[108]
Dr. Atwood was particularly emphatic that this
skilled person would not know of such reaction. In his affidavit, Dr. Atwood
observed that Drs. Rhodes and Fiese had not “provided a single reference which
reports Maillard degradation between a secondary amine [such as DCL] and
lactose prior to the claim date of the '136 Patent” (A.R., vol. 2, Tab 8,
p.346). Dr. Atwood then proceeded to refer to the well-known Handbook of
Pharmaceutical Excipients (the Handbook), R. C.
Rowe, P. J. Sheskey, S. C. Owen, ed., 5th ed. (Chicago: Pharmaceutical Press,
2006) to support his conclusion. In the preface to the Handbook, the
authors state that (A.R., vol. 2, Tab 8, p.440):
If an
incompatibility is not listed it does not mean it does not occur but simply
that it has not been reported or is not well known.
[109]
Dr. Atwood pointed out that the 2006 Handbook
still makes made no mention of an incompatibility of lactose with a secondary
amine. From this omission of any incompatibility between secondary amines and
DCL in 2006, he concludes that, in 1997, any such reaction would most certainly
have been unknown or unreported. Specifically on the Maillard reaction, the
2006 Handbook includes the following (A.R., vol. 2, Tab 8, p.441):
A Maillard-type
condensation reaction is likely to occur between lactose and compounds with
a primary amine group to form brown or yellow-brown-coloured products.
[Emphasis
added.]
[110]
It occurs to me that the Handbook may not be the
most reliable reference. The incompatibility between lactose and DCL was known
as of the publication date of either the '014 Patent and the '136 Patent – as
early as 1997. And yet, the 2006 edition of the Handbook makes no reference to
the incompatibility. This failure by the Handbook authors to refer to an
incompatibility that has been known for the past ten years raises some doubt in
my mind as to the reliability of the information.
[111]
In spite of some reservations, I am prepared to
accept that a reaction between a secondary amine (such as DCL) and lactose
would not have been part of the common general knowledge. Stated in
different words, an understanding that DCL would discolour or degrade in the
presence of lactose (or other acidic excipients) was not likely part of the
common general knowledge as of the relevant date.
[112]
The role of water in degradation was another
area of some dispute. None of the Aberg, Villani or Cho Patents specifically
addresses the issue of how the presence of water could affect degradation. If I
accept that the reaction of DCL and lactose was not part of the common general
knowledge, it follows that ameliorating such a reaction by avoiding water was
also not part of the common general knowledge.
[113]
However, in general terms, it was common general
knowledge that the amount of water in a formulation would be a consideration
for a skilled formulator. Drs. Rhodes, Fiese, Banker and Cartilier seem to
agree that it was known that water would generally speed up degradation. Dr.
Atwood stated that water may speed up, or even slow down the rates of degradation.
In either case, it was known that the amount of water in a formulation could be
a factor in formulation.
[114]
Some mention must be made of the standard
formulation tests and techniques. I think that it is self-evident that a
pharmaceutical company would not market a pharmaceutical composition without
testing its stability. It is also clear that commonly used stability studies,
testing and laboratory techniques would be part of the common general
knowledge. One frequently-mentioned procedure is the use of differential
scanning calorimetry (DSC) to determine chemical incompatibilities.
[115]
Finally, I would include as part of the common
general knowledge the use of lactose as a common and preferred excipient in
drug formulations. Not only is this found at page 5 of the '136 Patent, it was
explicitly stated by Mr. Wald, an inventor of the '136 Patent: “Lactose is a
commonly used filler in various pharmaceutical dosage forms” (Sepracor’s Responding
Application Record, vol. 1, Tab 2, p.30). Dr. Rhodes also acknowledged this
fact (R.R., vol. 1, Tab 1, p.61).
[116]
While the experts all presented me with lengthy
lists of other prior art, the foregoing common knowledge (or lack of knowledge)
informs the obviousness analysis for the '136 Patent.
7.3.2.4.
The Inventive Concept
[117]
Schering submits that the inventive concepts for
the '136 Patent can be divided into two phases or concepts. First, Schering
submits, the inventors of the '136 Patent discovered that DCL discolours or
degrades in the presence of acidic excipients such as lactose. As described in
the final written submissions of Sepracor, based on the evidence of Dr. Wald,
one of the inventors of the '136 Patent:
In beginning the
development process at Sepracor, an excipient compatibility study was conducted
to determine chemical compatibilities of DCL with common excipients using
differential scanning calorimetry. The results of this study demonstrated that
there was no interaction between STARCH 1500 and DCL. However, it did
demonstrate that there was an interaction between lactose (α-lactose
monohydrate) and DCL.
[Emphasis
added.]
[118]
The inventors then proceeded to “solve” this
problem by avoiding lactose in “intimate admixture” with DCL (Claims 1, 6 and
9).
[119]
The second inventive step (which led to Claims
16 and 23) was also described by Sepracor in its written submissions:
A second study
was carried out to determine the stability of a formulation comprising DCL and
lactose, in the presence and absence of 5% water. The only significant
degradation found in the formulations studied was in the vial containing 5%
water along with 80% lactose. Specifically, it did not look like DCL and 80%
lactose, in the absence of 5% water, had the same high degree of degradation. .
. .
[T]he reaction
rate and/or the extent of DCL/lactose interaction, is reduced in the absence of
added water.
7.3.2.5.
Differences between the common general
knowledge and the inventive concepts
[120]
I now move to the next portion of the analysis.
I must 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. It appears to me that the differences or
“gaps” consist of the following:
1.
It was not common general knowledge that the
Maillard reaction would occur between DCL, a secondary amine, and lactose (or
other reactive excipient).
2.
It was not common general knowledge that
reactions between DCL and lactose could be avoided by ensuring that lactose was
not in intimate admixture with the DCL in the pharmaceutical composition.
3.
It was not common general knowledge that the
degradation of DCL in the presence of lactose would be accelerated by water.
Or, stated in the reverse, it was not common general knowledge that the degradation
of DCL when used together with any “pharmaceutically acceptable carrier”
(including lactose) could be reduced by the avoidance of water in the
composition.
7.3.2.6.
Inventiveness of Steps
[121]
Finally, Sanofi-Synthelabo teaches that I
ask: Do those differences constitute steps which would have been obvious to the
person skilled in the art or do they require any degree of invention? Of
particular relevance, at this stage, I must determine whether there is evidence
to convince me, on a balance of probabilities, that it was more or less
self-evident to try to obtain the invention.
[122]
As noted above, pre-formulation experiments
would be conducted before any product is taken to market. To me, the goal of
obtaining a stable formulation is “more or less self-evident”; it is just plain
common sense. No company wants to commercialize a product that will quickly
degrade or discolour.
[123]
Secondly, it is undisputed that lactose is one
of the most commonly-used excipients. As stated by the inventors, lactose was
“among the best of all direct compression filters in fluidity and is very
effective for low dose formulations” (Patent, p. 5). Given this knowledge, it
would be more or less self-evident to run formulation studies to determine the
interaction of lactose and DCL. Thus, even if the Maillard reaction was not
generally known to occur with secondary amines, the skilled person would still
run stability tests with DCL and lactose, a very desirable excipient.
[124]
Mr. Wald, one of the inventors, confirmed that he
came about his “invention” during routine “preformulation work”. The inventors
first conducted the common DCS test with three common excipients –
microcrystalline cellulose, starch and lactose. The routine test revealed the
incompatibility between lactose and DCL (R.R., vol. 4, Tab 9, p.951).
[125]
In response, Schering submits that the '136 Patent
inventors’ work was contrary to the teachings of the prior art. In particular,
Schering points to the Aberg Patent which, Schering asserts, teaches the use of
lactose as an excipient. I agree that certain examples of the Aberg Patent
include lactose as an excipient; but, not all do. Example 8 of the Aberg
Patent, as discussed above, does not include lactose. From reading the examples
of the Aberg Patent, I do not believe that the skilled person would be
persuaded away from carrying out preformulation tests with lactose. And, as
soon as those tests were carried out, the incompatibility of lactose with DCL
would be highlighted to the skilled person. In my view, the step of identifying
the incompatibility was more or less self evident.
[126]
Once the skilled person discovered the
incompatibility of DCL with lactose, he would have two predictable choices.
First, the skilled person would, almost as a matter of routine, try a
formulation that avoided the use of lactose and other reactive excipients.
Thus, he would come to Claims 1, 6 and 9. He would be assisted in that step by
Example 8 in the Aberg Patent.
[127]
The second, and possibly less predictable,
solution would be to try to reduce the degradation. He would ask: Is there a
way that I can reduce or eliminate the reaction? As noted above, the important
role of water in degradation was generally known. In my view, it follows that a
skilled person trying to minimize degradation or discolouration would not
hesitate to try eliminating as much water as possible from the formulation.
Thus, the skilled person would come to the invention of Claims 16 and 23.
[128]
According to Sanofi-Synthelabo, the more
arduous, expensive and prolonged the experimentation, the less obvious the
invention. On the other hand, the more routine the tests, the more the results
are likely to be “obvious to try” (above, at paras. 86-89, 91). The Supreme
Court of Canada examines the tests, rather than the conduct of inventors. In
the case before me, both the tests for incompatibility and the solutions
arrived at would be obvious to try.
[129]
In sum, on this step in the Sanofi-Synthelabo
analysis, I am satisfied that there is evidence to convince me, on a balance of
probabilities, that it was more or less self-evident to try to obtain the invention.
7.3.2.7.
Conclusion on Obviousness
[130]
In summary, I conclude that the allegation of
Pharmascience that the inventions in Claims 1, 6, 9 and 16 were obvious, as of
the relevant date, is justified.
7.3.3. Overbreadth of Claim 23
7.3.3.1.
General Principles of Overbroad Claiming
[131]
Finally, I will consider the allegation that
Claim 23 is overbroad.
[132]
A patent that claims more than that which was
invented or disclosed is invalid for being overly broad (see, for example, Unilever
PLC v. Procter & Gamble Inc. (1995), 61 C.P.R. (3d) 499 at 515 (F.C.A.);
Eli Lilly Canada Inc. v. Apotex Inc., 2009 FC 320, 75 C.P.R. (4th) 165,
at paras. 52-53; Biovail Pharmaceuticals Inc. v. Canada (Min. of Health
& Welfare), 2005 FC 9, 37 C.P.R. (4th) 487, at para 15). An inventor
ought not to claim a result rather than a means of achieving it. As stated in Free
World Trust, above at paragraph. 32:
[T]he ingenuity
of the patent lies not in the identification of a desirable result but in teaching
one particular means to achieve it. The claims cannot be stretched to allow the
patentee to monopolize anything that achieves the desirable result. It is not
legitimate, for example, to obtain a patent for a particular method that grows
hair on bald men and thereafter claim that anything that grows hair on bald men
infringes.
[133]
The consequence of overly-broad claiming is that
the relevant claims will be invalid.
7.3.3.2.
Application to Claim 23 (and 16)
[134]
Schering submits that Claim 16 is an example of
a “functional” claim. A claim that is expressed in a way that leads to a
desired result may be legally permissible (see, for example, Burton Parsons,
above at p. 215; Mobil Oil v. Hercules (1995), 63 C.P.R. (3d) 473 at p. 485,
188 N.R. 382 (F.C.A.), provided that the skilled person would be able to
directly come to the desired result (see Procter & Gamble, above, at
p. 159). Jurisprudence also cautions that functional claiming can put inventors
in dangerous waters. As Justice Noël in Burton Parsons stated:
There may,
however, in doing so, be some danger of claiming either broader than the
invention or of the claims being ambiguous. It is also possible that a
functional claim or clause covers something that is inoperable
(above, at p.
215).
[135]
The reading of Claim 16, which Schering appears
to have adopted, is that every DCL compound that is stable is, by the
definitions of the patent, “anhydrous”. While functional claims may certainly
exist, Claim 16, in my view, is beyond any acceptable functional claim.
[136]
The weakness in Schering’s support for Claim 16
is glaringly apparent when one looks at the Pharmascience tablet. The
Pharmascience tablet contains well over 3% water, which, as indicated by the
experts, is a moderate to high water content in a composition. And yet, because
the tablet is (apparently) stable, Schering would have us conclude that it is
anhydrous and hence infringes Claim 16. There are two possibilities. First, one
can construe the Claim to require that the stability of the DCL and lactose
composition be as a result of the amount of water. In this case, as I have
already stated, Schering has provided no evidence to show that the
Pharmascience tablet would infringe. In the alternative, if I am wrong in my
construction, Claim 16 catches every stable DCL/lactose composition no matter
how or why it is stable.
[137]
This, in my view, is a blatant example of
overbroad claiming. The requirement of stability is analogous to growing hair
on bald men. Just as Justice Binnie in Free World Trust above, at paragraph
32, stated “It is not legitimate, for example, to obtain a patent for a
particular method that grows hair on bald men and thereafter claim that
anything that grows hair on bald men infringes”, one cannot stretch Claim 16 to
cover everything that is stable.
[138]
Quite simply, Claim 23 and Claim 16 are clear
examples of overclaiming and, as stated by Justice Harrington in Biovail,
“To overclaim is to lose everything” (above, at para. 15).
[139]
I conclude that Pharmascience’s allegation that
Claims 16 and 23 are overbroad is justified.
8.
THE '014 PATENT
[140]
I turn to consideration of the '014 Patent. The
general principles of construction and a description of the person skilled in
the art are set out under the analysis for the '136 Patent and need not be
repeated here.
8.1.
Construction of the '014 Patent
8.1.1.
Application of the principles
to the '014 Patent claims
[141]
The date for determining the proper construction
of the claims in issue is the '014 Patent publication date of January 20, 2000.
[142]
At page 1 of the '014 Patent disclosure, the
inventors state that the “invention relates to pharmaceutical compositions
containing [DCL] and substantially free of DCL decomposition products, and
suitable for oral administration to treat allergic reactions”. The inventors
set out a summary of their invention at page 2, where they state that:
It has now been
found that the [DCL] discolors and decomposes in the presence of excipients
disclosed in the prior art. It has been discovered that these problems are
substantially solved when the use of an acidic excipient is avoided and [DCL]
is combined with a pharmaceutically acceptable carrier medium comprising a
DCL-protective amount of a pharmaceutically basic salt. Thus, this invention
provides a pharmaceutical composition comprising an anti-allergic effective
amount of [DCL] in a pharmaceutically acceptable carrier medium comprising a
DCL-protective amount of a pharmaceutically basic salt.
[143]
This statement sets out the two-part thrust of
the claimed invention – avoidance of acidic excipients and use of a “basic
salt” in the “carrier medium”.
[144]
Only Claims 1 and 38 are in issue in this
application:
1. A
pharmaceutical composition for oral administration comprising an anti-allergic
effective amount of descarbonyethoxyloratadine in a pharmaceutically acceptable
carrier medium comprising a DCL-protective amount of a pharmaceutically
acceptable basic salt and at least one pharmaceutically acceptable
disintegrant, wherein the pharmaceutically acceptable carrier medium is
substantially free of acidic excipients.
38. The
pharmaceutical composition of any one of claim 1 to 36, wherein said
composition is a solid oral dosage form and wherein said
descarbonylethoxyloratadine is in an amount of 5 mg.
[145]
Claim 38 is dependent on Claim 1 (the other
claims not being relevant to this application), meaning that Claim 38 narrows
the application of Claim 1 to 5 mg oral-dosage tablets. Accordingly, the
construction of Claim 1 is key to understanding this application.
[146]
Claim 1 covers a “pharmaceutical composition”. The
parties now acknowledge that this term means the entire tablet or other dosage
form. As I read the claim, Claim 1 will cover a tablet that contains DCL if:
(a) the DCL is in a carrier medium; (b) the carrier medium contains enough of a
basic salt to protect the DCL from degradation, including discolouration; and
(c) the carrier medium is substantially free of acidic excipients. All three
elements are essential. This leads me to the terms used in Claim 1 that are in
issue:
1.
Does the term “carrier medium” include the
entire “pharmaceutical composition” other than the DCL, as submitted by
Pharmascience? Or, does the “carrier medium” include only those materials in
association with the DCL and not include those excipients that may exist in the
[space outside the form], as argued by Schering?
2.
Does the term “basic salt” include any ionic
compound, as submitted by Schering? Or, does the term, as used in the '014
Patent, limited to calcium, magnesium and aluminum salts, as asserted by
Pharmascience?
3.
What is meant by the term “DCL-protective
amount”?
4.
What is meant by the term “acidic excipient”?
8.1.1.1.
Carrier Medium
[147]
Pharmascience, relying on opinions from both Dr.
Rhodes (R.R., vol. 1, Tab 1, p.13) and Dr. Fiese (R.R., vol. 2, Tab 2, p.472),
submit that the term “carrier medium” would include all of the components of
the dosage form other than the active ingredient – in this case, the DCL.
Following this line of reasoning, on a proper construction of Claims 1 and 38,
the entire tablet must be “substantially free” of acidic excipients.
[148]
I do not agree that the construction of the term
“carrier medium” proposed by the Pharmascience experts is a fair and purposive
construction of the term. On my reading of Claim 1, there are two strong
indicators that lead to the construction of the words “carrier medium” put
forward by Schering.
[149]
The first is the fact that Claim 1 covers
tablets that contain DCL when the DCL is “in” a carrier medium. The Claim does
not state that the DCL is “in” the composition. From this use of language, I
draw a strong inference that a skilled person would read the term “carrier
medium” as something different from the “pharmaceutical composition”.
[150]
The second indicator is the use of the word
“comprising”. All of the experts accepted that use of the word “comprising”
does not mean “limited to”. As stated by Dr. Jerry Atwood, in his affidavit (A.R.,
vol. 2, Tab 8, p.353-354):
The first occurrence
of the word “comprising” makes clear that the pharmaceutical composition can
include other things apart from the DCL in its carrier medium . . . There can
be other materials that “comprise” the contents of the pharmaceutical
composition but they are not the pharmaceutically acceptable carrier medium
referred to in the claims.
[151]
During cross-examination on his affidavit, Dr.
Rhodes acknowledged that a person skilled in the art, as of the relevant date,
would know that the word “comprising” could “include other things” (A.R., vol.
8, Tab 19, p.1989).
[152]
Thus, when Claim 1 states that the
pharmaceutical composition comprises DCL in a carrier medium, it logically
follows that the pharmaceutical composition as a whole may contain other
ingredients. This could be the end of the analysis. Where the language of a
claim is clear, “it is necessary to look no further to discover the nature of
an infringement (Procter & Gamble, above, at para. 10). However,
even if I consider the arguments of Pharmascience based on certain words in the
specification, I remain unconvinced of the Pharmascience’s proposed
construction.
[153]
In support of its construction, Pharmascience submits
three key references – at pages 6, 7 and 10 – in the specification that, in its
view, demonstrate that “carrier medium” should be given the same construction
as “pharmaceutical composition”. I will consider each of these.
[154]
Pharmascience’s expert, Dr. Fiese (R.R., vol. 2,
Tab 2, p. 470), points to the language used at page 7 of the specification,
where the “inert pharmaceutically acceptable carrier medium includes one or
more substances which may also act as diluents, flavouring agents,
solubilizers, lubricants…encapsulating materials”. Pharmascience argues that,
since lubricants and encapsulating materials are used after granulation, then
“carrier” does not refer only to the inner [form], but to the entire final
dosage form.
[155]
I am not persuaded by this argument. In my view,
Dr. Fiese has taken the excerpt on page 7 out of context. I first observe that
the entire passage is under the heading of “Pharmaceutical Composition”, which
is presented by the inventors as the final dosage form. Contained in this
“composition”, is the “carrier”, which provides a capsule for the active
ingredient. It follows that the active ingredient is surrounded by the carrier
medium; and thus, in association with it. Further, on the same page, the
inventors define “carrier medium” excipients as including basic salt,
cellulose, etc. The inventors then say that these excipients “may also act as”
lubricants or encapsulating materials – thus, another way to coat or protect
the active ingredient.
[156]
Another argument of Pharmascience relies on a
reference in the specification to the inclusion of talc in the carrier medium.
Dr. Fiese refers to page 6 of the specification where the inventors describe a
preferred embodiment where the “carrier medium” contains talc. Dr. Fiese then
turns to the manufacturing process described at pages 8-10 of the
specification. There, talc is added after the granulation but before tableting.
Thus, Dr. Fiese concludes that “carrier medium” must mean the entire tablet
(R.R., vol. 2, Tab 2, p. 472). The problem with this assertion is that Dr. Fiese
has selected one embodiment out of many contained in the specification. Many
other embodiments do not require talc to be in the carrier medium. Dr. Fiese’s
extraction of one embodiment to prove his point is not an example of purposive
construction.
[157]
A third argument of Pharmascience is centred on
a statement at page 10 of the specification where the inventors describe the
tableting process for the tablets as follows:
The tablets may
be film-coated by charging the compressed tablets into suitable coating equipment
having a rotating pan and heater. The tablets of the rotating pan are contacted
at a temperature of about 30-50°C with a coating solutions [sic] formed by dissolving clear or
colored coating materials in purified water. After the tablets are completely
coated, a polishing powder may be added to the coated tablets to provide
polished coated tablets. Alternatively, the colored coating material may be
added as a dry powder in step 5 or 10, preferably step 5 of the Granulation
phase of the process. It is preferred that the colored coating material is
preferably substantially free, i.e., < about 1%, or more preferably
completely free of offensive excipients such as lactose.
[158]
Pharmascience submits that this paragraph
contains language that directly equates the carrier with the composition. The
“coating” reference, in its view, must be to the exterior of the tablet,
supporting its construction. Schering, on the other hand, puts forth an
alternative interpretation of this manufacturing step where the “coating”
reference could be to a coating for the [forms]. In my view, the paragraph at page
10 could support either interpretation. In the face of this ambiguity and given
the wording of Claim 1 itself, where there is a distinction drawn between
“carrier medium” and “pharmaceutical composition”, the more purposive
construction is that put forward by Schering.
[159]
Moreover, I observe that Pharmascience and its
experts have ignored a number of references in the specification to a clear
division between “pharmaceutical composition” and “carrier medium”. Nowhere are
they made equivalents. For example, the inventors, at page 6, state:
Unexpectedly, we
discovered that when descarbonyl-ethoxyloratadine was combined with a
carrier medium comprising a dibasic calcium phosphate, and
70microcrystalline cellulose – in the absence of prior art excipients such as
stearic acid or lactose – we produced a pharmaceutical composition that
was stable to discolouration when stored for 4 weeks in open petri dishes at a
temperature of 40 degrees Celsius and relative humidity of 75%.
[Emphasis added].
[160]
In sum, I conclude that a skilled person would
interpret “carrier medium” as the substance or mixture of substances containing
the DCL-protective amount of a pharmaceutically acceptable basic salt which is
mixed with or associated with the DCL. Thus, the “carrier medium” includes only
those materials in association with the DCL and does not include those
excipients that may exist in the [space outside the form].
8.1.1.2.
Pharmaceutically Acceptable Basic Salt
[161]
The next disagreement occurs over the meaning of
the term “basic salt” in Claim 1. At page 5 of the '014 Patent specification,
the term “pharmaceutically acceptable basic salts” is defined to mean:
. . . a calcium,
magnesium or aluminum salt, or mixtures thereof, including, but not limited to
carbonates, phosphates, silicates and sulfates of calcium, magnesium or
aluminum. Typically, suitable pharmaceutically acceptable basic salts include
calcium sulfate anhydrous, hydrates of calcium sulfate, such as calcium sulfate
dihydrate, magnesium sulfate anhydrous, hydrates of magnesium sulfate, dibasic
calcium phosphate, dibasic calcium phosphate anhydrous, tribasic calcium
phosphate, calcium silicate, magnesium silicate, magnesium trisilicate, aluminum
silicate, and magnesium aluminum silicate. The use of calcium phosphate salt is
preferred. The use of dibasic calcium phosphate hydrates is more preferred. The
use of dibasic calcium phosphate dehydrate is most preferred.
[162]
The specification makes no explicit mention of [compounds
of the type of Confidential Compound One] or of [Confidential Compound One].
The specific question, for this application, is whether the term “basic salt”
includes [Confidential Compound One].
[163]
Schering’s expert, Dr. Cartilier, opines that
the person skilled in the art would understand that the term “pharmaceutically
acceptable basic salt” would include “[Confidential Compound One], together
with many other salts of calcium, magnesium and aluminum” (A.R., vol. 2, Tab 6,
p.190). Dr. Cartilier refers to the definition of “salt” in publications by the
International Union of Pure and Applied Chemistry (IUPAC). According to
Schering, IUPAC is the foremost authority on nomenclature in chemistry, used by
undergraduate chemistry students, and thus within the common general knowledge
of the person skilled in the art. The IUPAC defines salt as: “a chemical
compound consisting of a combination of cations and anions”. In Dr. Cartilier’s
opinion, this necessarily includes [Confidential Compound One] in its
definition, as [Confidential Compound One] is composed of [confidential] (A.R.,
vol. 2, Tab 6, p.191). Dr. Cartilier further states that “[Confidential
Compound One] presents a basic character” (A.R., vol. 2, Tab 6, p.191).
[164]
Dr. Banker expressed a similar view when he
opined that the person skilled in the art “would understand the term ‘pharmaceutically
acceptable basic salt’ to mean any pharmaceutically acceptable calcium,
magnesium or aluminum salt (or mixture thereof) that has a basic pH” (A.R., vol.
3, Tab 10, p.478). Dr. Banker relies on the same IUPAC publication as Dr.
Cartilier.
[165]
In contrast, Dr. Fiese and Dr. Rhodes provide a
contrary view. In his affidavit (R.R. vol. 2, Tab 2, p.479), Dr. Fiese
opines that the inventor did not intend to include all basic ionic compounds
within the term “pharmaceutically acceptable basic salt”. Dr. Fiese refers to
the extensive list of examples provided with the definition and notes that “no
reference is made in the patent to the use of [compounds of the type of
Confidential Compound One] or a [confidential] as a ‘pharmaceutically
acceptable basic salt’, even though a [confidential] such as [confidential] .
. . is known to be a basic compound suitable in pharmaceutical formulations”
(R.R. vol. 2, Tab 2, p.479).
[166]
On balance, I prefer the opinions of Drs. Rhodes
and Fiese on this point. The inventors of the '014 Patent provided the skilled
reader with an explicit definition of the term “basic salt”. Regard must be
given to the entire definition. Drs. Cartilier and Banker provide an
interpretation that is based only on a general definition of “salt” contained
in IUPAC. They do not appear to have considered the extensive examples offered
by the inventors that, in my view, clarify what the inventors meant by the
term. I agree that, on a purely academic level, [Confidential Compound One] may
meet the definition of “salt” contained in chemistry textbooks. I also
acknowledge that the inventors attempt to generalize by using words such as
“including, but not limited to” and “typically”. However, such language cannot
disguise the fact that the inventors do not include [compounds of the type of
Confidential Compound One] in their lengthy list of typical “basic salts” in
their definition. From the omission, I infer that the inventors either did not
have [compounds of the type of Confidential Compound One] and [confidential] in
mind, or had rejected the use of such “salts”.
[167]
During cross-examination on this point, Dr.
Rhodes admitted: “I fully understand that the IUPAC is the ultimate definition”
(A.R., vol. 8, Tab 18, p.1914-1915). However, with respect, the IUPAC
definition is not the point. A skilled reader of the '014 Patent could very
well accept the IUPAC definition of “salt” but still conclude that the inventors
did not intend to claim every possible “combination of cations and anions”. A
skilled person would respect the definition provided by the inventors.
[168]
I conclude that the term “pharmaceutically
acceptable basic salt”, as used in Claim 1 of the '014 Patent, is a subset of
the broadest class of all ionic compounds that would meet the definition of
“salt” under IUPAC references. It includes the classes of salts described at page
5 of the specification. Of particular relevance to this application, the term
does not include [compounds of the type of Confidential Compound One].
8.1.1.3.
DCL-protected Amount
[169]
As set out in Claim 1, the amount of basic salt
that must be used is described as a “DCL-protective amount”. This provides
little guidance to the person skilled in the art who is attempting to
understand the claim. The term is not defined in the specification, as is the
case with the term “pharmaceutically acceptable basic salt”. The only specific
guidance is supplied at page 5 of the specification, where the inventors state
the following:
The
DCL-protective amount of the pharmaceutically acceptable basic salt used in the
compositions of the present invention is normally about 50% by weight of the
total composition; with a weight to weight ratio of basic salt to DCL in the
range of 5:1 to 60:1, preferably 7:1 to about 11:1, and most preferably about
10:1 to about 11:1.
[170]
The question is whether the ratios suggested at
page 5 should be incorporated into Claim 1, thereby setting limits on the
amounts of basic salt to be used.
[171]
Pharmascience submits that the specification of
the '014 Patent provides a percentage range for what constitutes a
“DCL-protective amount” of basic salt. This construction, in Pharmascience’s
view, is supported by Examples 1-5 of the Patent, where the basic salt was from
53 to 5.3 times the weight of DCL. In essence, Pharmascience argues that an
essential element of Claim 1 is that the ratio of basic salt to DCL will fall
within the ranges set out on page 5 of the specification.
[172]
Schering argues, relying on Drs. Cartilier and
Banker, that the “protective amount” is “a non-zero amount”. In essence, basic
salt can be present in any amount, so long as it protects DCL from degradation.
As stated by Dr. Cartilier (A.R., vol. 2, Tab 6, p.165-166):
The Skilled
Formulator would read claim 1 of the '014 Patent as not limiting the
DCL-Protective amount to any specific amount or ratio of amounts. A review of
the claims dependant on claim 1 supports my construction, since specific ratios
are found in some of those dependent claims, but not in claim 1 itself.
. . .
[B]ecause the
amount of the basic salt which will be DCL protective depends on a number of
factors about the particular composition being considered, the Skilled
Formulator would know that the phrase “DCL-Protective Amount simply means “that
amount of the pharmaceutically acceptable basic salt which is sufficient to
protect DCL from discoloration or decomposition in a given composition” and
would read the claim in that way.
[173]
Dr. Banker provided a similar opinion. Dr.
Banker also referred to those claims in the '014 Patent where specific ratios
are set out (for example, claims 3-5 and 9-11).
[174]
Dr. Fiese, on the other hand, opined that the
inventor of the '014 Patent provided “a clear direction” in the specification
as to the ratios to be used (R.R., vol. 2, Tab 2, p.473). Dr. Rhodes expressed
a similar opinion (R.R., vol. 1, Tab 1, p.85). However, neither of these
experts suggested that a skilled person could not carry out the step of
determining an operable ratio for any particular salt. Neither expert explained
why, if their interpretation is to be adopted, there was any need to set out
explicit ratios in Claims 3-5 and 9-11.
[175]
Have considered the evidence before me, I
conclude that the skilled person would understand that the term “DCL-protective
amount” includes whatever amount of a salt is necessary to prevent degradation
of the DCL. Claim 1 does not limit the ratio of salt to DCL to any particular
amount. In particular, it is not limited to the ratios set out on page 5 of the
specification.
[176]
First, I accept that the amount of salt needed
to protect the DCL will vary with the specific salt that is used and the amount
of DCL. I also believe that a person skilled in the art would be able to
ascertain the amount of any particular salt required to provide the necessary
DCL protection, through formulation procedures that would have been known as of
the relevant date. Further, the use of the words “normally” and “about” in the
explanation make it clear that the ratios set out at page 5 of the
specification are meant to provide guidance or examples to the skilled person
and not necessarily direction. Moreover, use of specific ratios in some of the
claims leads to an inference that Claim 1 includes any and all ratios that
would protect the DCL from degradation.
[177]
Finally, Pharmascience, in effect, seeks to read
a limitation into Claim 1 that is simply not present. In Whirlpool Corp. v.
Camco Inc., [2000] 2 S.C.R. 1067, at paragraph 52, Justice Binnie commented
that:
In my view, it
was perfectly permissible for the trial judge to look at the rest of the
specification . . . to understand what was meant by the word “vane” in the
claim, but not to enlarge or contract the scope of the claim as written
and thus understood.
[Emphasis
added.]
[178]
The construction proposed by Pharmascience would
limit Claim 1 in a way not written and understood.
8.1.1.4.
Substantially Free of Acidic Excipients
[179]
It is accepted by all parties that lactose is an
acidic excipient for purposes of the '014 Patent. However, the term is not
defined in the '014 Patent and led to some disagreement with respect to other
possible excipients. Does the term include any excipient that has a pH in water
that is less than 7.0 – in particular [Confidential Compound Two]?
[180]
Pharmascience uses [the type of compounds of
Confidential Compound Two] in association with the DCL in its tablets. Unlike
the lactose, this ingredient is [within the form], or in association with the
DCL. As stated in its NOA:
The term “acidic
excipients” as used in the claims is also properly construed to include
excipients such as corn starch and pregelatinized starch, given that corn
starch and pregelatinized starch have a pH in water that is less than 7
(Boylan, et al, Handbook of Pharmaceutical Excipients, American
Pharm. Assoc. & the Pharma. Society of G. Britain: 289-293, 296-297 (1986)).
[181]
The commonly-used definition of an acid is a
compound with pH less than 7.0. All the experts agree that the [Confidential
Compound Two] used by Pharmascience has a pharmacopeial range of pH 4.5-7.0.
Thus, at a pH of 7.0, [Confidential Compound Two] could be weakly basic.
[182]
Drs. Banker and Cartilier opined that [Confidential
Compound Two] would not be considered an acidic excipient in general or as
those words would be understood by the skilled person. According to Dr. Banker,
[Confidential Compound Two] “has a pharmacopoeial pH range of 4.5 to 7.0”,
which includes neutrality (A.R., vol. 3, Tab 10, p.509). Dr. Cartilier
concurred: “[Confidential Compound Two] that may be obtained with a pH below
7.0 are only weakly acidic and would not be regarded as acidic excipients in
the ordinary language or understanding of a Skilled Formulator reading the
patent” (A.R., vol. 2, Tab 6, p.194). Their view is that the term “acidic
excipient” would not include compounds that are only weakly acidic or that have
pH ranges that include neutrality at their upper end. I agree with their
evidence on this point. Dr. Fiese, while stating otherwise in his affidavit,
agreed, during cross-examination, that [Confidential Compound Two] was not an
acidic excipient for purposes of Claim 1.
8.1.1.5.
Conclusion for the Construction of
Claim 1 and 38 of the '014 Patent
[183]
Having considered the submissions of the parties
and the experts, I conclude that the person skilled in the art would understand
that Claim 1 will cover a dosage form that contains DCL where: (a) the DCL is
in a carrier medium; (b) the carrier medium contains enough of a
basic salt to
protect the DCL from degradation; and, (c) the carrier medium is substantially
free of acidic excipients. The terms in issue in this application would be
understood as follows:
1.
“Pharmaceutically acceptable carrier medium”
refers only to those excipients in association with the DCL and does not
include those excipients that may exist in the [space outside the form] of the
pharmaceutical composition;
2.
“Basic salt” means a calcium, magnesium or
aluminum salt, or mixtures thereof, including but not limited to carbonates,
phosphates and sulfates of calcium, magnesium or aluminum; [Confidential
Compound One] is not included in that definition;
3.
A “DCL-protective amount” is that amount of the
pharmaceutically acceptable basic salt which is sufficient to protect DCL from
discolouration or decomposition in a given composition; and
4.
The term “acidic excipient” would not include
those excipients, such as [Confidential Compound Two], that would normally have
a range of pH levels with an upper limit of 7.0 or higher.
[184]
Claim 38 would be read in the same manner, but
limited to solid dosage forms (that is, tablets) of 5mg.
8.2.
Infringement of the '014
Patent
[185]
Having construed the claims in issue, I turn to
the question of whether Pharmascience’s allegation of non-infringement of Claims
1 or 38 of the '014 Patent is justified. All three essential elements of Claim
1 must be met for infringement to be found.
[186]
A description of Pharmascience’s tablet is set
out above. Given my construction of “carrier medium” in Claim 1 and 38, it
follows that Pharmascience does not include lactose – an acidic excipient – in
the carrier medium of its tablets. Rather, its lactose is outside the [form] that
form the “carrier medium” of its tablets. Further, the [Confidential Compound
Two] that is used in association with the DCL by Pharmascience is not an
“acidic excipient” as that term is used in Claim 1. Thus, the carrier medium of
Pharmascience’s tablets does not include an acidic excipient and meets the
first essential element of Claim 1.
[187]
However, Pharmascience uses [Confidential
Compound One] in its tablets. I have concluded that, as that term is used in
Claim 1, [Confidential Compound One] is not a “pharmaceutically acceptable
basic salt”. Thus, Pharmascience does not meet this essential element of Claim
1 or 38.
[188]
Accordingly, Pharmascience’s allegation that it
does not infringe Claims 1 or 38 of the '014 Patent is justified.
[189]
Since I have found that the allegation of
non-infringement is justified, there is no need to consider whether the
allegations of invalidity are justified. However, since it may be helpful for
me to make some brief comments on these allegations, I will do so. Only if I am
found to be wrong on the issue of infringement, would these comments become
relevant.
8.3.
Validity of Claims 1 and 38 of the '014
Patent
[190]
Pharmascience alleges that the relevant claims
of the '014 Patent are invalid on a number of grounds:
1.
Lack of utility/inoperable species;
2.
Obviousness; and
3.
Overbroad claiming.
I will consider
each of the allegations.
8.3.1. Lack of Utility, Sound Prediction and Inoperable Species
[191]
There is no dispute that, as of the date of the
invention, an invention must either have utility or have a sound prediction of
utility.
[192]
As I understand it, the essence of
Pharmascience’s arguments on lack of utility, sound prediction and inoperable species
is that the inventors of the '014 Patent do not disclose any reaction with an
acidic excipient other than lactose. Claim 1 sets out that the carrier medium
must be “substantially free of acidic ingredients”; it is not limited to
lactose. Pharmascience submits that the inventors of the '014 Patent have
provided no data or basis for concluding that avoiding other acidic excipients
– such as stearic acid, providone or crospovidone – would have any utility in a
pharmaceutical composition containing DCL. Thus, Pharmascience argues, the
inventors had no basis for making a sound prediction that degradation would
occur in the presence of any acidic expedient other than lactose.
[193]
The flaw in this argument is that Pharmascience
has misconstrued the promise of the '014 Patent. The patent promises that, if
one follows the teachings of the inventors, the resulting composition will not
degrade. In other words, use of a basic salt combined with the avoidance of
acidic excipients will result in a composition that will not degrade. The
patent does not promise that any acidic excipient will cause the
composition to degrade. Thus, whether a particular acidic excipient would
actually cause degradation is of no great moment. Claim 1 meets the promise of
the patent.
[194]
In any event, the patent specification and the
expert evidence are to the effect that other acidic excipients would indeed
cause degradation. At page 4 of the specification, the inventors disclose that
exposure of DCL to many other acids – such as stearic acid, povidone,
crospovidone, and sodium benzoate – resulted in degradation. At page 12,
specific mention is made of stearic acid.
[195]
If necessary to do so, I would conclude that
Pharmascience’s allegation of invalidity on this ground is not justified.
8.3.2. Obviousness
[196]
The principles of obviousness are discussed
above in the discussion of the '136 Patent. As with the '136 Patent I will
consider the allegation of obviousness on the basis of the four-step analysis
set out in Sanofi-Synthelabo. For the '136 Patent, the relevant date for
assessing obviousness is July 10, 1998.
8.3.2.1.
The person skilled in the art
[197]
As with the '136 Patent, the skilled person
would hold a BSc in chemistry or a related field with an emphasis on
pharmaceutical formulations and solid oral dosage forms along with 4 years of
experience in this field.
8.3.2.2.
Common General Knowledge
[198]
With only minor amendments, the common general
knowledge cited for the '136 Patent is applicable to the '014 Patent. I refer
the reader to my earlier assessment of relevant knowledge and consider, in this
section of the reasons, only those additional references.
[199]
The most significant difference between the '136
and '014 Patent is the use of a “basic salt” in the '014 Patent. On the
question of basic salt to protect DCL, I am not persuaded that the use of a
basic salt to protect the DCL was within the common general knowledge of the
person skilled in the art. Dr. Cartilier, for Schering, has referred to the
Handbook, and has stated that Maillard reaction or “browning reaction is base-catalyzed
and may, therefore, be accelerated if alkaline lubricants are used” (A.R., vol.
2, Tab 7, p. 317). This means that bases can sometimes cause or speed up the
Maillard effect rather than retard it. Dr. Fiese, for Pharmascience, has stated
that the use of basic salt “would be less obvious than removing the unsuitable
excipients”, especially since the amount had to be “protective” (R.R., vol. 2,
Tab 2, p.494). Thus, I conclude that using basic salt to protect DCL was not,
as of the relevant date, within the general common knowledge of the person
skilled in the art.
8.3.2.3.
The inventive concept
[200]
The inventive concept for the '014 Patent begins
in the same manner as that of the '136 Patent. First, the inventors of the '014
Patent discovered that DCL discolours or degrades in the presence of acidic
excipients such as lactose. From there, the inventors of the two patents took
different routes to achieve the goal of a stable DCL product. The solution
discovered by the inventors of the '014 Patent was more complex that that of
Mr. Wald and his fellow inventors of the '136 Patent. The inventive concept of
the '014 Patent consists of avoiding lactose and other acidic excipients as the
carrier medium and using a basic salt to stabilize the composition.
8.3.2.4.
Differences between common general
knowledge and the inventive concepts
[201]
I now move to the next portion of the analysis.
I must 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. Reviewing the common general knowledge
referred to, it appears to me that the differences consist of the following:
1.
It was not known that the Maillard reaction
would occur between DCL, a secondary amine, and lactose (or other reactive
excipient).
2.
It was not common general knowledge that
reactions between DCL and lactose could be avoided by ensuring that lactose was
not in intimate admixture with the DCL in the pharmaceutical composition.
[202]
In addition, the gap between the state of the
art and the inventive concept regarding basic salt use is significant. As
stated previously, Dr. Fiese opined that the use of basic salt to protect DCL
is “less obvious” than the removal of lactose, or acidic excipients (R.R., vol.
2, Tab 2, p.494). Furthermore, the Handbook (A.R., vol. 2, Tab 7, p.317),
and the Blaug and Huang article used by Pharmascience (A.R., vol. 3, Tab 11, p.597-598),
both state that degradation can occur in basic environments.
8.3.2.5.
Inventiveness of Steps
[203]
Finally, Sanofi-Synthelabo teaches that I
ask: Do those differences constitute steps which would have been obvious to the
person skilled in the art or do they require any degree of invention? Of
particular relevance, at this stage, I must determine whether there is evidence
to convince me, on a balance of probabilities, that it was more or less
self-evident to try to obtain the invention.
[204]
As noted above in the discussion of the '136
Patent, pre-formulation experiments would be conducted before any product is
taken to market. For the same reasons and based on the same evidence as for the
'136 Patent, I conclude that the step of identifying the incompatibility was
more or less self-evident.
[205]
However, the situation with respect to the use
of basic salt is more complicated. The use of basic salt to protect DCL was
arguably not “obvious to try” in 1998. As previously stated, the use of basic
salt to slow down the Maillard reaction is disputed by texts and scholars in
the field. Experts of both sides cite the Handbook and agree that basic
substances can speed up degradation.
[206]
Dr. Rhodes took a strong position in his opinion
that the invention was obvious. However, Dr. Rhodes’ logic and reasoning is somewhat
contradictory. Dr. Rhodes opines that preformulation tests examining pH of
substances are not novel – it is known that basic or acidic environment can
accelerate degradation. Thus, the outcomes of the tests were obvious (R.R.,
vol. 1, Tab 1, p.96-97). But, how can a result be “more or less self evident”
when either bases or acids can either cause or retard degradation? Thus, if
following Dr. Rhodes’ logic, there is only “a possibility of finding the
invention” that basic salt can protect DCL. According to the Supreme Court,
this is not enough.
[207]
One of the areas of examination that can
potentially assist the Court is the course of conduct followed by the
inventors. If the course of conduct involved complex studies and testing, it is
more likely that the resulting invention was not obvious.
[208]
In this case, Pharmascience argues that the
tests conducted by the inventors of '014 Patent were routine, quick, simple and
inexpensive – thus, lacking inventive skill. In contrast, Dr. Banker describes
the “numerous formulation experiments” carried out by the inventor, Dr. Jim Kou
(see A.R., vol. 3, Tab 11, p.600-611):
(a)
Dr. Kou’s notebook details numerous formulation
experiments and stability studies carried out over many months.
(b)
Dr. Kou made tablets through direct compression
and granulation techniques, and monitored the characteristics of the tablets
over time.
(c)
Dr. Kou examined a variety of conditions to
determine specifications for coating of the tablets.
(d)
The inventor was concerned with the formulation
of an N-formyl degradant in the formulation of DCL. He monitored the formation
of the N-formyl degradant over time (up to 8 months are disclosed) at a variety
of accelerated conditions. These studies also examined whether coated tablets
had similar degradation issues.
(e)
Results are disclosed assaying the potency of
DCL for different batches at a variety of different accelerated conditions.
(f)
Certificates of analysis demonstrate that the
inventor monitored the presence of N-Formyl degradant over time right up to the
time when the first patent was filed in relation to the invention claimed in
the '014 Patent.
[209]
While the steps may have taken time, I am not
persuaded that they were overly arduous or complex. Rather, they appear to have
been rather routine pre-formulation experiments. Thus, this factor would tend
to operate in favour of a finding of obviousness, although not strongly so.
8.3.2.6.
Conclusion on Obviousness
[210]
In weighing all of the evidence before me, if
necessary to do so, I would conclude that there is insufficient persuasive
evidence to convince me that the use of a basic salt to stabilize the
pharmaceutical composition was obvious. Thus, Pharmascience’s allegation of
obviousness would not be justified.
8.3.3. Overbroad Claiming
[211]
Pharmascience argues that Claim 1 is the
equivalent of a claim for “anything that grows hair on bald men” and should be
found to be invalid on the principle of overly broad claiming. The principles
of overbroad claiming are discussed above in the context of the '136 Patent.
The argument, as explained during oral argument, focuses on that part of the
claim that deals with the DCL-protective amount. The argument is that, if
DCL-protective amount is construed as broadly as suggested by Schering, the
claim is overbroad.
[212]
In my view, this argument would not succeed. The
invention of the '014 Patent includes the protection of DCL by the use of a
basic salt, together with the avoidance of acidic excipients. Claim 1 includes
the requirement that the pharmaceutical composition avoid acidic excipients and
contain “a DCL-protective amount of a pharmaceutically acceptable basic salt”.
The ingenuity of the '014 Patent lies in teaching one particular means of
achieving the result of reducing degradation of DCL.
[213]
Schering described this aspect of Claim 1 as a
“functional claim”. That is, the amount of basic salt needed to protect the DCL
is a function of the particular salt that is used by the formulator. As noted
earlier in these Reasons in connection with the '136 Patent, a claim that is
expressed in terms that lead to a desired result is permissible (see, for
example, Burton Parsons, above, at p. 215; Mobil Oil, above, at
p. 485), provided that the skilled person would be able to directly come to the
desired result (see Proctor & Gamble, above at p. 159). Each of Dr.
Cartilier and Banker appear to have accepted that a person skilled in the art
would have the knowledge to determine the stability of any particular basic
salt to DCL ratio. As stated by Dr. Cartilier (A.R., vol. 2, Tab 6, p.169):
[S]ince the '014
Patent is directed to a practical solution the Skilled Formulator would understand
that the desired absence of decomposition or discoloration should be maintained
within acceptable limits over the anticipated shelf life of the product.
[214]
In sum, the fact that the specific amount of
basic salt is not set out in Claim 1 does not turn the claim into “anything
that grows hair on bald men”. The situation with Claim 1 and “DCL-protective
amount” is far different than the “anhydrous” claim of the '136 Patent. In my
view, Claim 1 is no broader than the invention.
[215]
If necessary to do so, I would conclude that
Pharmascience’s allegation of invalidity on this ground is not justified.
8.3.4. Conclusion on validity allegations
[216]
In sum, if I were required to make findings, I
would conclude that Pharmascience’s allegations of invalidity of Claims 1 and 38
of the '014 Patent are not justified.