Date:
20130305
Docket:
T-2012-10
Citation: 2013
FC 232
Ottawa, Ontario,
March 5, 2013
PRESENT: The
Honourable Mr. Justice O'Keefe
BETWEEN:
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ASTRAZENECA CANADA INC. and
ASTRAZENECA AB
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Applicants
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and
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RANBAXY PHARMACEUTICALS CANADA
INC. and THE MINISTER OF HEALTH
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Respondents
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REASONS FOR JUDGMENT
AND JUDGMENT
[1]
This
is an application brought by Astrazeneca Canada Inc. and Astrazeneca AB (the
applicants) under section 5 the Patented Medicines (Notice of Compliance)
Regulations,
SOR/93-133,
defending the validity of Canadian Patent No. 2,170,647 (the ‘647 patent)
against the notice of allegation of Ranbaxy Pharmaceuticals Canada Inc. (the
respondent).
[2]
The
sole issue in this proceeding is whether the invalidity allegation against the ‘647
patent is justified.
[3]
The
applicants claim that the respondent alleges each and every claim of the ‘647
patent to be invalid, while the respondent claims that only certain claims of
that patent are at issue. Given that it is the respondent who is responsible
for an allegation of invalidity, therefore, only those claims of the ‘647
patent identified by the respondent are at issue: Claims 1 to 8, 11 to 13, 15
to 17, 20 and 21, 23 to 27 and 33 to 36.
[4]
The
applicants seek that the Court order that the invalidity allegation against the
‘647 patent is not justified and prohibit the Minister of Health from issuing a
notice of compliance to the respondent for the Ranbaxy tablets in 20mg and 40mg
strengths until the expiry of the ‘647 patent.
Background
[5]
The
application for the ‘647 patent was filed on June 7, 1995, taking priority from
an application filed in Sweden on July 8, 1994. The ‘647 patent was published
on January 25, 1998 and expires on June 7, 2015. This patent is entitled
“Multiple Unit Tableted Dosage Form I” and includes 40 claims. All of the
claims impugned by the respondent in this proceeding relate to tableted dosage
forms of omeprazole, S-omeprazole, or alkaline salts thereof.
[6]
In
a letter dated October 15, 2010, the respondent alleged that each claim of the ‘647
patent is invalid for obviousness. The respondent also alleged non-infringement
of claims of several patents. These allegations are no longer part of this
application.
[7]
On
December 2, 2010, the applicants brought an application disputing the
allegation of invalidity. A third company, Takeda Pharmaceutical Company
Limited, was initially also a respondent to this application, but has since
been removed. The Minister of Health is formally a respondent but played no
role in this proceeding.
Related Orders
from the Court
[8]
Prothonotary
Kevin Aalto sat as Case Management Judge for this matter. He issued a protective
order on February 7, 2011, defining which information from this matter is to be
treated as confidential and the conditions on its disclosure.
Applicants’
Written Submissions
[9]
The
applicants argue that the inventors of the ‘647 patent made possible for the
first time a multiple unit tableted enteric dosage formulation of an acid
sensitive drug, omeprazole, and that there was nothing in the prior art
indicating that such a creation was obvious.
[10]
The
applicants submit there is general agreement between the parties on the
construction of the claims of the ‘647 patent and the nominal skilled person
through whose eyes the claims are construed.
[11]
The
applicants submit that the relevant test for obviousness contains four
questions, as described by the Supreme Court of Canada in Apotex
Inc. v Sanofi-Synthelabo Canada Inc., 2008 SCC 61 at paragraph 67,
[2008] 3 S.C.R. 265:
(1)
(a) Identify the notional “person skilled in the
art”;
(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?
[12]
The
applicants emphasize that every invention is obvious after it has been made and
cautions against employing hindsight analysis.
[13]
The
applicants submit that in answer to the first question of the obviousness test,
the parties are in agreement that the relevant skilled person is a pharmaceutical
formulator, with a Bachelor’s degree in pharmaceutics or a related science and
at least two or three years of experience in formulation development, including
some exposure to delayed and controlled release formulation.
[14]
The
applicants argue that both parties’ expert witnesses are in general agreement
as to how the skilled person would understand the claims of the ‘647 patent in
answer to the second question.
[15]
The
applicants also submit that there is general agreement in answer to the third
question: that the ‘647 patent for the first time provides a multiple unit tableted
enteric coated dosage for an acid sensitive drug, namely omeprazole.
[16]
The
applicants identify the fourth question of the obviousness test as the main
area of disagreement. The applicants argue that the prior art would have
directed the skilled person away from concluding that an acid sensitive drug,
such as omeprazole, could have been formulated into a multiple unit tableted
enteric dosage form. The applicants argue that the skilled person would have
either selected hard gelatine capsules or another final dosage form.
[17]
The
applicants argue that the views of the respondent’s expert witness, Dr. Elder,
that this formulation was simply a matter of routine investigation, are
inconsistent with prior and post art. The applicants point to Dr. Bodmeier’s
affidavit evidence as to why the prior art references teach away from the
conclusion that an acid sensitive drug such as omeprazole could be formulated
into a multiple unit tableted enteric dosage form.
[18]
The
applicants argue the Drugs Made in Germany (Klaus Lehmann et al, “Fast
Disintegrating Controlled Released Tablets from Coated Particles” (1994) 37(2) Drugs
Made in Germany 53) reference contradicts Dr. Elder’s evidence that the
invention is routine, since it used L30-D55 combined with NE300, instead of
L30-D55 alone. That reference’s process also resulted in an 82 percent gastric
acid resistance, when no more than a 10 percent reduction in resistance in
compression is required. This reference teaches that even non-acid sensitive
pellets could not be compressed successfully, so the skilled person would not
be led to believe that omeprazole enteric coated pellets could be so
compressed.
[19]
The
applicants dispute that the Dechesne (JP Dechesne, “A new enteric tablet of
acetylsalicylic acid. I. Technology aspects” (1987) 37 International Journal of
Pharmaceutics 203) reference speaks to the obviousness of the ‘647 patent,
since a skilled person would view the high release of a drug to be unacceptable
when dealing with a highly acid sensitive drug. The applicants catalogue Dr.
Bodmeier’s evidence rejecting the usefulness of other prior art, including Canadian
Patent No. 1,292,693 (the ‘693 patent), European Patent Application No. 0519144
(the ‘144 patent), European Patent Application No. 0257310 (the ‘310 patent)
and European Patent Application No. 0255725 (the ‘725 patent). The applicants
argue the Seitz (Seitz et al, “Tablet Coating” in Leon Lachman et al, eds, Theory
and Practice of Industrial Pharmacy, 3rd ed (Philadelphia: Lea &
Fibeger, 1986) article does not teach the claim of the ‘647 patent as it makes
no reference to compressibility of enteric coated pellets during the tabletting
process.
[20]
In
the applicants’ submission, developing the claimed formulation is not the
result of a routine investigation or optimization. Even if the skilled person
were to attempt to make a multiple unit tableted enteric dosage formulation of
an acid sensitive drug, the skilled person would have known this would be
difficult to achieve and would have believed the process would take years. The
applicants cite a 1997 article by Dr. Bodmeier (Roland Bodmeier, “Review:
Tableting of coated pellets” (1997) 41 European Journal of Pharmaceutics and
Biopharmaceutics 1) and a 2011 article by Rok Dreu et al, entitled “Development
of a multiple-unit tablet containing enteric-coated pellets”, (2011) 16(2)
Pharmaceutical Development and Technology 118, describing such challenges and dispute
Dr. Elder’s dismissal of the latter due to its origin in Slovenia. The applicants highlight the fact that Dr. Elder admitted he only knew of five
examples of multiple unit formulations with enteric coated pellets making it to
market.
[21]
The
applicants dispute the credibility of Dr. Elder based on his improper criticism
of the 2011 article and the fact that the six pieces of prior art cited in his
affidavit are the same six pieces listed in Ranbaxy’s notice of allegation.
Respondent’s
Written Submissions
[22]
The
respondent’s position is that omeprazole is an old drug and that by 1994, it
was well known that it was an acid labile drug that needed to be formulated with
a protective enteric coating and there is nothing inventive about the nature of
the tablet formulation claimed in the ‘647 patent. The respondent submits that
the merits of this proceeding are no different than the opposition proceeding
involving the corresponding European patent, which was revoked for having no
inventive step over the teachings of the European equivalent to the ‘693
patent.
[23]
The
respondent argues that Dr. Elder’s evidence should be preferred to Dr.
Bodmeier’s as the former is an experienced pharmaceutical formulator while the
latter is an academic with little industry experience.
[24]
The
respondent agrees that the parties and their experts are in agreement as to the
skilled formulator’s understanding of the claim of the ‘647 patent. The ‘647
patent does not claim an enteric coating with a specific plasticizer or a
specific quantity of plasticizer, except to require an “effective amount”.
[25]
The
respondent argues that the state of the art and common general knowledge as of
July 1994 shows the ‘647 patent to be obvious. The skilled person would have
had knowledge of the use of a plasticizer with polymer in the enteric coating
in a preferred ratio and would have used routine experimentation to determine
the suitable combination.
[26]
The
respondent points out that the ‘693 patent taught that multiple unit tablets of
enteric coated pellets of omeprazole were possible. The inventors of the ‘647
patent acknowledged that the ‘693 patent states that the manufactured
omeprazole pellets of the ‘693 patent may be formulated into tablets. By 1994,
the skilled formulator would have been motivated to develop a multiple unit
tablet dosage due to omeprazole’s sensitivity to moisture, heat and light and
the lower expense of tablets. The formulator would have been aware of design
mechanisms to reduce cracking of enteric coatings.
[27]
The
respondent cites the Dechesne article to support its claims that by 1994, the
skilled formulator would have known that enteric coated pellets could be formulated
into a tablet and that the amount of plasticizer recommended by this article is
the same percentage used in examples in the ‘647 patent.
[28]
In
the respondent’s submission, Dr. Bodmeier was evasive and refused to concede straightforward
points or agree with basic concepts. The respondent alleges Dr. Bodmeier did
not swear his affidavit properly. The respondent describes Dr. Elder as candid
and forthcoming under cross-examination and notes that he pointed out passages
in Dr. Bodmeier’s article acknowledging that formulations coated with flexible
polymer and plasticized could be compressed into tablets without significant
damage.
[29]
In
applying the test from Sanofi-Synthelabo above,
the
respondent agrees with the applicants as to the characteristics of the relevant
skilled person in answering the first question. The respondent submits that Dr.
Elder is the ideal person to comment on the views of the skilled person.
[30]
As
to the second question, the respondent identifies the inventive concept of the ‘647
patent as the formulation of a tablet of enteric coated pellets of omeprazole,
whose pellets can retain their acid resistance after tablet compression.
[31]
According
to the respondent, the ‘693 patent previously disclosed that an enteric coated
multiple unit dosage form of omeprazole could be formulated into tablets
comprising a polymer and a plasticizer in the enteric coating. Therefore, in
answering the third question, the respondent argues that the only difference
between the ‘693 patent and the inventive concept of the ‘647 patent was the
actual making of the multiple unit tableted enteric coated dosage form of
omeprazole.
[32]
In
answering the fourth question, the respondent submits that this difference
would have been obvious to the skilled person. While the applicants argue that
only a small number of multiple unit tablet formulations have been brought to
market, the respondent argues this is because a multiple unit tablet
formulation is not desirable for most drugs. The person skilled in the art
would view the making of a tablet formulation of enteric coated omeprazole
pellets to be something that could be accomplished directly and without
difficulty using routine formulation and optimization techniques known at the
time.
[33]
The
respondent points out that in answering the fourth question, the “obvious to
try” test may be relevant in fields that are routinely advanced by
experimentation. The skilled formulator would have approached the task of making
a multiple unit tablet formulation of omeprazole by optimizing the formulations
disclosed in the ‘693 patent or the Dechesne article.
[34]
The
respondent points out that the European equivalent of the ‘647 patent was
revoked based on the teaching of the European equivalent of the ‘693 patent.
Analysis and
Decision
Burden
[35]
In
a notice of compliance proceeding, an applicant bears the burden of proving on
a balance of probabilities that the respondent’s allegations of invalidity are
not justified (see GlaxoSmithKline Inc v Pharmascience, 2011 FC 239 at
paragraphs 43 and 44, [2011] FCJ No 287). The respondent, however, has an
initial evidentiary burden to give its allegations an air of reality.
Legal Framework
[36]
Section
28.3 of the Patent Act, RSC 1985, c P-4, sets out the criterion of
non-obviousness for the subject matter of a patent claim.
[37]
The
Supreme Court of Canada set out the four questions of obviousness analysis in Sanofi-Synthelabo
Canada above, at paragraph 67, adopting the approach of the Court of Appeal
for England and Wales in Windsurfing International International Inc. v
Tabur Marine (Great Britain) Ltd., [1985] RPC 59 (CA), as excerpted above
at paragraph 11 of these reasons.
[38]
In
answering the fourth question, a court must consider whether the “obvious to
try” test is warranted. The Supreme Court held that this test may be
appropriate in fields that are advanced by experimentation (paragraph 68). Mr. Justice
Marshall Rothstein noted the pharmaceutical industry as an example, due to the
“many chemically similar structures that can elicit different biological
responses and offer the potential for significant therapeutic advances”.
[39]
The
applicability of this test to the case at bar is discussed below.
Summary of
Expert Testimony
Respondent’s
Expert Witness
[40]
The
respondent’s expert witness is Dr. Edmund J. Elder, director of the Lenor Zeeh
Pharmaceutical Experiment Station at the University of Wisconsin at Madison. He obtained his PhD in pharmaceutical sciences from the University of South Carolina in 1989. He was previously pharmaceutics director and global technical leader,
then global product development director, of the BioAqueous Solubilization Services
offering of the Dowpharma business unit of the Dow Chemical Company. Prior to
working at Dowpharma, Dr. Elder held various positions in product development
at Glaxo (now GlaxoSmithKline).
[41]
In
his affidavit, Dr. Elder sets out his belief that there is nothing surprising
about the composition claimed in the ‘647 patent and that it would have been
arrived at directly from the knowledge of the person skilled in the art as of
1994. Such a person would have known that omeprazole was an acid labile drug
and would have therefore been motivated to formulate omeprazole as an enteric
coated delayed release dosage form.
[42]
At
paragraphs 17 to 24 of his affidavit, Dr. Elder describes the two types of
solid oral dosage forms: capsules and tablets. A capsule has a gel-like casing
that houses the active ingredient and the drug within the capsule is released
to the body upon disintegration of the capsule shell. A tablet is solid
material, formed of compressed medicinal ingredients. Tablets are less
expensive to produce and package than capsules and are advantageous for
medicines sensitive to moisture and light. A skilled formulator would be able
to obtain the optimal characteristics for the desired solid oral dosage form by
understanding the elastic, plastic and brittleness properties of its
components. These and other adjustments would be a matter of routine
experimentation.
[43]
At
paragraphs 25 to 31, Dr. Elder describes several types of dosage forms. An
immediate release dosage does not contain a mechanism to delay absorption,
whereas a controlled release dosage form is designed to alter the timing and
release of the drug substance into the body. A controlled release dosage could
be either a sustained released dosage or a delayed release dosage. These two
types share a common physical architecture: a membrane that contains both a
polymer and a plasticizer. Delayed release oral dosage forms are typically used
with acid labile drugs; those that are sensitive to the gastric acid juices of
the stomach. Such formulations include a protective enteric coating that allows
the formulation to pass through the stomach without being destroyed.
[44]
At
paragraphs 32 to 36, Dr. Elder sets out his belief that the skilled formulator
would have known to follow the general approach to developing an enteric
coating by screening polymers and plasticizers for compatibility and perform
routine experimentation. At paragraphs 37 to 42, Dr. Elder argues that by 1994,
it was well known that an enteric coating was preferred for omeprazole and that
a tablet form would have been of keen interest.
[45]
At
paragraphs 43 to 59, Dr. Elder describes the architecture of delayed release
dosage forms and the rise of multiple unit formulation oral dosage forms. By
1994, the pharmaceutical formulator would have been well aware of the advantage
of this form and the ’693 patent disclosed that an enteric coated multiple unit
dosage form could be formulated into tablets.
[46]
At
paragraphs 60 to 64, Dr. Elder describes the preparation of multiple unit
tablets and methods available in 1994 to reduce cracking in enteric film
coatings.
[47]
At
paragraphs 65 to 101, Dr. Elder describes his opinion of the ‘647 patent and
its claims. In his opinion, the enteric coating tablet formulation was not
surprising in view of the common general knowledge discussed above and the
prior art including the ‘693 patent and the corresponding U.S. patent. He does
not agree that the skilled person would view the Drugs Made in Germany reference
as supporting the conclusion that the copolymer L30D-55 without the addition of
copolymer NE30D could not withstand the compression of tablet formulation,
since that person would be aware of the ability to overcome mechanical concerns
associated with cracking by altering the polymer-to-plasticizer coating. He
gives his view of how a person skilled in the art would understand the ‘647
patent’s claims (with the exception of claims 29 to 32 and claims 37 and 40).
[48]
In
paragraphs 102 to 138, Dr. Elder turns to the prior art of the ‘693 patent, the
‘144 patent, the ‘310 patent, the ‘725 patent, the Dechesne article and the Seitz
article. Dr. Elder is of the opinion that the skilled person would have been
led to the claims of the ‘647 patent by these references.
[49]
The
‘693 patent describes the preparation of omeprazole containing powder cores
which are formulated into small beads which are used for further processing
into tablets or capsules. The ‘144 patent discloses enteric coated omeprazole
pellets that comprise a polymer and plasticizer in the enteric coating for use
in gelatine capsules. The ‘310 patent describes a tablet for oral
administration with sustained release active ingredient formed by compressing
microcapsule and teaches the importance of using a plasticizer with a polymer
in the enteric coating in order to achieve sufficient flexibility. In Dr.
Elder’s opinion, by July 1994, it was only a matter of routine testing to
determine the amount of plasticizer to use for a given controlled release
dosage form.
[50]
The
‘725 patent describes the problem of high pressure compression in creating
multiple unit tablets and teaches that this problem can be overcome by forming
a protective coating. The Dechesne article describes the importance of having
30 percent plasticizer in the enteric coating of tablets of acetylsalicylic
acid. Dr. Elder’s view is that the person skilled in the art would draw that
conclusion of looking to levels of plasticizer greater than 20 percent for
enteric coated films on drug granules. The Seitz article describes techniques
for modifying enteric coated films.
[51]
In
summary, Dr. Elder argues at paragraph 131 that all aspects of the ‘647 patent
were known to the person skilled in the art, namely:
1. Formulations
of enteric coated tablets of omeprazole;
2. A
composition comprising a multiple unit tablet oral dosage form that comprises
enteric coated pellets of omeprazole;
3. The use of
plasticizer along with polymer in the enteric coating to add greater
flexibility and to reduce the risk of cracking and damage to the dosage form
during tabletting; and
4. The use of
preferred ratios of polymer to plasticizer in enteric coating in the range of
20 percent to 50 percent by weight plasticizer to polymer.
Applicants’
Expert Witness
[52]
The
applicants’ expert witness is Dr. Roland Bodmeier, a professor at the Institute
für
Pharmazie, Freie Universität Berlin since 1994. He was awarded a PhD in
pharmaceutics in 1986 by the University of Texas at Austin and an additional
doctorate from the Universität Regensburg in Germany. He is an editor of
several pharmaceutical science journals and a member of scientific advisory
boards of several pharmaceutical firms. He has published 160 articles and is an
expert in pharmaceutical formulation. Due to the order of evidence being
reversed, his affidavit responds to the affidavit of Dr. Elder.
[53]
At
paragraphs 12 to 23 of his affidavit, Dr. Bodmeier describes why the invention
of the ‘647 patent would have been surprising to the skilled person because of
various challenges in the tabletting process because of compression.
[54]
At
paragraphs 24 to 41, Dr. Bodmeier offers his construction of the claims of the ‘647
patent, which he describes as generally in agreement with those of Dr. Elder.
[55]
At
paragraph 42, Dr. Bodmeier takes issue with a list of alleged errors in the
background section of Dr. Elder’s affidavit. In his opinion, the compression of
coated pellets into tablets continues to be a complex issue and far from
routine experimentation. He disputes Dr. Elder’s description of the pH level of
the intestine. He disputes that the skilled formulator would investigate all
possible formulations given the time and resources required to test hundreds of
possible combinations.
[56]
At
paragraphs 43 to 68, Dr. Bodmeier analyzes the prior art set out by Dr. Elder.
The ‘693 patent never mentions the compression of enteric coated omeprazole
pellets, nor does it suggest how such compression could be done. Pellets
prepared according to the ‘693 patent do not keep their acid resistance after
compression. The ‘144 application refers to the use of plasticizer, but
provides no guidance on how to achieve a multiple unit tableted dosage form
without significantly affecting gastric acid resistance. A person skilled in
the art would have considered the ‘310 patent irrelevant as it refers to
compressed microcapsules instead of pellets and ethyl cellulose coating instead
of enteric coating.
[57]
The
‘725 patent does not disclose the challenge of compression of enteric coated
pellets into tablets. The Dechesne article refers to a different drug which is
not acid-sensitive. A person skilled in the art would have learned from this
reference that the compression enterically coated omeprazole pellets could not
be accomplished because of the high acid sensitivity of omeprazole.
[58]
The
Seitz article is concerned with single unit dosage forms instead of multiple
unit dosage forms and does not pertain to the compressibility of coating during
the tabletting process. The Drugs Made in Germany article would teach
away from compressing enteric coated pellets as it shows that non-acid
sensitive pellets could not be compressed successfully.
[59]
At
paragraphs 69 to 76, Dr. Bodmeier sets out his opinion that the prior art
showed obstacles to multiple unit tableted dosage of enteric coated omeprazole
tablets. The prior art indicated that enteric coated multiparticulates cannot
be compressed into tablets because of the poor mechanical properties of the
enteric polymers. If the skilled person had attempted compression of enteric
coated pellets, the result would have been an unacceptable loss in acid
resistance. The daunting task of testing combinations of multiparticulates,
polymer compositions and plasticizers would have deterred the skilled person
from proceeding.
Application of
the Test
[60]
Turning
to the Sanofi-Synthelabo above test, I find that the parties are in
general agreement as to the answers of the first two questions. The skilled
person is a pharmaceutical formulator, with a Bachelor’s degree in
pharmaceutics or a related science and at least two or three years of
experience in formulation development, including some exposure to delayed and
controlled release formulations and the associated general knowledge.
[61]
The
inventive concept in the ‘647 patent claims, as understood by the skilled
person, is the formulation of a tablet of enteric coated pellets of omeprazole,
whose pellets can retain their acid resistance after tablet compression.
[62]
As
to the third question, identifying the inventive concept, while the parties use
different language to describe the concept, I do not consider there to be
significant factual dispute. The respondent suggests the “only” difference is
the actual making of the multiple unit tableted enteric coated dosage form of
omeprazole contemplated by the ‘693 patent, while the applicants argue that
this very creation is the surprising inventive step at issue. The significance
of this step is best addressed in answer to the fourth question.
[63]
At
the fourth stage, it is necessary to consider whether the “obvious to try” test
is appropriate in this case. “Obvious to try” does not mean “worth a try”, but
obvious in the sense of “very plain” or “more or less self-evident” (see Pfizer
Canada Inc v Apotex Inc, 2009 FCA 8 at paragraphs 28 and 29, [2009] FCJ No
66). As Mr. Justice Rothstein explained in Sanofi-Synthelabo above, at
paragraph 81:
At this stage, it must be determined whether the
nature of the invention in this case is such as to warrant an “obvious to try” test.
The discovery of the dextro-rotary isomer and its bisulfate salt came after
experimentation. There were interrelated variables with which Mr. Badorc had to
experiment. An “obvious to try” test in this case would recognize the evidence
of the expert witnesses as to the discovery of the beneficial properties of the
dextro-rotary isomer and its bisulfate salt and the methods for finding them.
[64]
In
the present case, experimentation was required to determine the appropriate composition
of enteric coating. As presented, a suitable coating required experimentation
to determine the appropriate type, content and composition of plasticizer. As
well, the coating agent, quantity of coating agent, size of the sub-unit,
external additives, rate and magnitude of pressure applied during tabletting
needed to be examined to determine the most suitable composition. All of this
must be done in the context of pharmacopoeial standards which impose additional
criteria that must be considered.
[65]
It
is therefore necessary to use the “obvious to try” test from Sanofi-Synthelabo
above. The test has been set out below:
66 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.
. . .
69 If
an “obvious to try” test is warranted, the following factors should be taken
into consideration at the fourth step of the obviousness inquiry. As with
anticipation, this list is not exhaustive. The factors will apply in
accordance with the evidence in each case.
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?
70 Another
important factor may arise from considering the actual course of conduct which
culminated in the making of the invention. It is true that obviousness is
largely concerned with how a skilled worker would have acted in the light of
the prior art. But this is no reason to exclude evidence of the history of the
invention, particularly where the knowledge of those involved in finding the
invention is no lower than what would be expected of the skilled person.
71 For
example, if the inventor and his or her team reached the invention quickly,
easily, directly and relatively inexpensively, in light of the prior art and
common general knowledge, that may be evidence supporting a finding of
obviousness, unless [page295] the level at which they worked and their
knowledge base was above what should be attributed to the skilled person. Their
course of conduct would suggest that a skilled person, using his/her common
general knowledge and the prior art, would have acted similarly and come up
with the same result. On the other hand, if time, money and effort was expended
in research looking for the result the invention ultimately provided before the
inventor turned or was instructed to turn to search for the invention,
including what turned out to be fruitless "wild goose chases", that
evidence may support a finding of non-obviousness. …
[66]
I
will address the “obvious to try” test as set out in the three questions above.
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?
[67]
The
first stage of the “obvious to try” test requires an analysis of whether it is
more or less self-evident that the method employed will work. As discussed by
Mr. Justice Rothstein in Sanofi-Synthelabo above, at paragraphs
83 to 85, a difference exists between the existence of methods for creating
the product and whether those methods would be self-evident to a person skilled
in the art.
[68]
In
the present case, it is clear that producing an enteric coating presented
unique challenges from a manufacturing point of view. The methods for creating
such a product may have existed at the time, but as revealed through the
expert’s evidence, the solutions would not have been self-evident to a person
skilled in the art. Both experts agree that there are numerous variables which
must be accounted for including: the amount of plasticizer, the composition of
plasticizer, what coating agent should be used, what quantity of coating agent
should be used, the size of the sub-unit, what external additives, the rate and
magnitude of pressure applied during tabletting, the quantity and composition
of cushioning material, and whether all of this complies with pharmacopeial
standards.
[69]
In
Sanofi-Synthelabo above, Mr. Justice Rothstein states at paragraph 85:
Just because there are known methods of separating a
racemate into its isomers does not mean that a person skilled in the art would
necessarily apply them. The fact that there are such known methods of
separation will be of no account if the evidence does not prove that it was
more or less self-evident to try them. It is true that at the relevant time there
was evidence that a skilled person would know that the properties of a racemate
and its isomers might be different. However, a possibility of finding the
invention is not enough. The invention must be self-evident from the prior art
and common general knowledge in order to satisfy the “obvious to try” test.
That is not the evidence in this case. (emphasis added)
[70]
Mr.
Justice Rothstein indicated that the invention must be self-evident from the
prior art. In this case, the need for a solution is evident from the prior art;
namely, an enteric coating suitable for dispersed omeprazole delivery, however,
that solution is not provided for in the prior art. The prior art teaches away
from the existence of such a solution or alternately indicates that such a
solution is extremely complex and technically difficult to produce. Therefore,
the enteric coating is not self-evident and so it is necessary to move on to
the second stage of the “obvious to try” test.
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?
[71]
The
extent of the effort required to achieve the invention was best summarized in the
2011 article. This article indicates the level of difficulty in creating a
suitable enteric coating for pellets. This article obviously published
recently, indicates that the process for developing these delivery mechanisms
is highly complex. From the article, it is clear that only a few tablets have
actually reached market with an enteric coating formulation.
[72]
I
largely agree with Dr. Bodmeier’s expert testimony and give his evidence more
weight than that of Dr. Elder. Several important facts come to light that were
not challenged by the respondent. First, that it is rare to find a coating
which suitably allows pressing of tablets in conformity with the pharmacopoeial
requirements. This was confirmed in the 2011 article which identifies five
drugs that have gone to market in enteric coated pellet format. The same
article indicates that as a result of the numerous considerations “…production
of such a dosage form [is] technologically an extremely complex process.”
[73]
These
facts point to a significant amount of effort required to obtain the desired
result.
[74]
The
nature of the effort required to achieve the invention was significant
scientific research. This is supported in both the applicants’ record (the
2011 article) as well as by Dr. Bodmeier’s affidavit. Presumably manufacturing
and drug delivery technology have advanced between 1994 and 2011. It is
therefore reasonable to presume that in 1994, development of such dosage forms
remained at least an extremely complex process.
[75]
It
therefore follows that not only was the process extremely complex but it was
also time consuming. The 1997 article by Dr. Bodmeier supports this position by
identifying the numerous challenges that still needed to be overcome in producing
tablets of coated pellets. The final paragraph of the article is most
informative as it indicates that “…only [a] few studies have addressed the
compaction of matrix-type pellets”.
[76]
In
other words, the experimentation required was prolonged, complex and as
evidenced by the limited number of studies investigating the process, far from
routine.
Is there a motive provided in the prior
art to find the solution the patent addresses?
[77]
I
agree with the respondent that there is a motive provided in the prior art to
find the solution the patent addresses. The ‘693 patent specifically
contemplates the compression of multiple unit tablets of enteric coated pellets
of omeprazole. While the applicants are correct that significant resources are
required to move from the ‘693 patent techniques to the ‘647 patent techniques,
that the former provides motivation for the latter is clear.
[78]
In
answering this question, the Supreme Court noted that selection with respect to
genus patents are expected. In the present case, enteric coatings are not a
genus patent. They are unique preparations of drugs in conjunction with their
delivery method.
[79]
The
question from Sanofi-Synthelabo above, at paragraph 90, is whether there
is motivation disclosed in the prior patent:
However, nothing in the ‘875 patent or common
general knowledge provided a specific motivation for the skilled person to
pursue the ‘777 invention. The prior patent was a genus patent, and selection
might be expected. However, the prior patent did not differentiate between the
efficacy and the toxicity of any of the compounds it covered. This suggests
that what to select or omit was not then self-evident to the person skilled in
the art.
[80]
While
there is limited analysis informing the above paragraph, a recent decision by Mr.
Justice Roger Hughes has provided additional insight into the interpretation of
the third prong of the “obvious to try” test. From this judgment, it is clear
that strong motivation to produce a comparable or better product is a positive
factor in considering the “obvious to try” test.
[81]
In
Allergan Inc. v Canada (Minister of Health), 2012 FC 767, [2012] FCJ No
906, Mr. Justice Hughes stated at paragraph 177:
I am satisfied that the evidence is compelling that
prior to April 2002 there was sufficient motivation to provide a combination
drug for use in treating glaucoma. One combination product, COSOPT, was already
on the market. A competitor would have been strongly motivated to come up with
a comparable or better product.
This judgment was appealed (see
2012 FCA 308, FCJ No 1467) but the Federal Court of Appeal made no finding in
relation to the adequacy of the “motivation” portion of the analysis.
[82]
In
Allergan above, a finding that there is motivation disclosed in a prior
patent was indicative of a competitive marketplace and so was a factor supportive
of the validity of the patent. In the context of the “obvious to try” test,
motivation disclosed in the prior patent would be indicative of a marketplace
that would actively seek the (subsequently) patented solution. If other parties
were motivated to find the solution and yet were unable or unwilling to do so
prior to the patent being obtained, this factor would point to a solution that
was not “obvious to try”.
[83]
In
Janssen-Ortho Inc. v Novopharm Ltd., 2006 FC 1234, [2006] FCJ No
1535 at paragraph 114, Mr. Justice Hughes stated:
There appears to be no motivation exhibited by any
outside persons to explore Ofloxacin enantiomers. Competitors, on the evidence
in this Court, showed no interest. There appears to have been no interest in
the scientific or academic community in this pursuit. Without Daiichi there may
well never have been levofloxacin.
[84]
In
that case, specific motivation was held to increase the inventiveness of the
concept since, absent Daiichi’s motivation, “there may well never have been
levofloxacin”.
[85]
This
is best reflected in the 2011 article which indicates that as a result of the
numerous considerations “…production of such a dosage form [is] technologically
an extremely complex process.” In 2011, to a person skilled in the art, producing
enteric coatings on tablets was technologically an extremely complex process.
It is therefore reasonable to conclude that, even if the prior art provided
sufficient motivation, there remained “a lion in the path” (see MedImmune
Ltd. v Novartis Pharmaceuticals UK Ltd., [2012] EWCA Civ 1234 at paragraph
129) significant enough to dissuade the person skilled in the art.
[86]
Patentability
is justified since the complexity and technical difficulty identified in the
prior art would have dissuaded the hypothetical skilled person and, absent the
work of the inventors, the development of an enteric coated pellet would have
at least been delayed.
[87]
Therefore,
even if it was obvious to seek a solution for enteric coating for omeprazole,
it was not an easy solution and would likely have dissuaded a person skilled in
the art.
[88]
Considering
all of the evidence, I am of the view that the “obvious to try” test has not
been satisfied as it was not “. . . more or less self-evident to try to obtain
the invention” (see Sanofi-Synthelabo above, at paragraph 66) As well,
in Sanofi-Synthelabo above and as earlier noted, the Supreme Court
stated at paragraph 85:
The
invention must be self-evident from the prior art and common general knowledge
in order to satisfy the “obvious to try” test. . . .
[89]
In
conclusion, I am of the view that the patent for an enteric coating of
omeprazole was not invalid due to obviousness. As a result, the allegation that
the ‘647 patent is invalid for obviousness is not justified.
[90]
The
applicants’ application for an order prohibiting the Minister of Health from
issuing a notice of compliance to Ranbaxy for the Ranbaxy tablets in 20 mg and
40 mg strengths until the expiry of the ‘647 patent is granted.
[91]
The
applicants shall have their costs of the application.
JUDGMENT
THIS
COURT’S JUDGMENT is that:
1. The
applicants’ application for an order prohibiting the Minister of Health from
issuing a notice of compliance to Ranbaxy for the Ranbaxy tablets in 20 mg and
40 mg strengths until the expiry of Canadian Patent No. 2,180,647 is granted.
2. The
applicants shall have their costs of the application.
“John A. O’Keefe”
ANNEX
Relevant
Statutory Provisions
Patent Act, RSC, 1985, c P-4
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2. In
this Act, except as otherwise provided,
. . .
“invention”
means any new and useful art, process, machine, manufacture or composition of
matter, or any new and useful improvement in any art, process, machine,
manufacture or composition of matter;
27.
(3) The specification of an invention must
(a) correctly
and fully describe the invention and its operation or use as contemplated by
the inventor;
28.3 The
subject-matter defined by a claim in an application for a patent in Canada must be subject-matter that would not have been obvious on the claim date to a person
skilled in the art or science to which it pertains, having regard to
(a) information
disclosed more than one year before the filing date by the applicant, or by a
person who obtained knowledge, directly or indirectly, from the applicant in
such a manner that the information became available to the public in Canada
or elsewhere; and
(b) information
disclosed before the claim date by a person not mentioned in paragraph (a) in
such a manner that the information became available to the public in Canada or elsewhere.
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2. Sauf
disposition contraire, les définitions qui suivent s’appliquent à la présente
loi.
. . .
«
invention » Toute réalisation, tout procédé, toute machine, fabrication ou
composition de matières, ainsi que tout perfectionnement de l’un d’eux,
présentant le caractère de la nouveauté et de l’utilité.
27.
(3) Le mémoire descriptif doit :
a) décrire
d’une façon exacte et complète l’invention et son application ou
exploitation, telles que les a conçues son inventeur;
28.3 L’objet
que définit la revendication d’une demande de brevet ne doit pas, à la date
de la revendication, être évident pour une personne versée dans l’art ou la
science dont relève l’objet, eu égard à toute communication :
a) qui
a été faite, plus d’un an avant la date de dépôt de la demande, par le
demandeur ou un tiers ayant obtenu de lui l’information à cet égard de façon
directe ou autrement, de manière telle qu’elle est devenue accessible au
public au Canada ou ailleurs;
b) qui
a été faite par toute autre personne avant la date de la revendication de
manière telle qu’elle est devenue accessible au public au Canada ou ailleurs.
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Patented Medicines (Notice of Compliance)
Regulations,
SOR/93-133
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5. (1) If
a second person files a submission for a notice of compliance in respect of a
drug and the submission directly or indirectly compares the drug with, or
makes reference to, another drug marketed in Canada under a notice of
compliance issued to a first person and in respect of which a patent list has
been submitted, the second person shall, in the submission, with respect to
each patent on the register in respect of the other drug,
(a) state
that the second person accepts that the notice of compliance will not issue
until the patent expires; or
(b) allege
that
(i) the
statement made by the first person under paragraph 4(4)(d) is false,
(ii) the
patent has expired,
(iii) the
patent is not valid, or
(iv) no
claim for the medicinal ingredient, no claim for the formulation, no claim
for the dosage form and no claim for the use of the medicinal ingredient
would be infringed by the second person making, constructing, using or
selling the drug for which the submission is filed.
. . .
(3) A
second person who makes an allegation under paragraph (1)(b) or (2)(b) shall
(a) serve
on the first person a notice of allegation relating to the submission or
supplement filed under subsection (1) or (2) on or after its date of filing;
(b) include
in the notice of allegation
(i) a
description of the medicinal ingredient, dosage form, strength, route of
administration and use of the drug in respect of which the submission or
supplement has been filed, and
(ii) a
detailed statement of the legal and factual basis for the allegation;
(c) include
in the material served a certification by the Minister of the date of filing
of the submission or supplement; and
(d) serve
proof of service of the documents and information referred to in paragraphs
(a) to (c) on the Minister.
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5. (1) Dans
le cas où la seconde personne dépose une présentation pour un avis de
conformité à l’égard d’une drogue, laquelle présentation, directement ou
indirectement, compare celle-ci à une autre drogue commercialisée sur le
marché canadien aux termes d’un avis de conformité délivré à la première
personne et à l’égard de laquelle une liste de brevets a été présentée — ou y
fait renvoi —, cette seconde personne doit, à l’égard de chaque brevet ajouté
au registre pour cette autre drogue, inclure dans sa présentation :
a) soit
une déclaration portant qu’elle accepte que l’avis de conformité ne sera pas
délivré avant l’expiration du brevet;
b) soit
une allégation portant que, selon le cas :
(i) la
déclaration présentée par la première personne aux termes de l’alinéa 4(4)d)
est fausse,
(ii) le
brevet est expiré,
(iii) le
brevet n’est pas valide,
(iv) elle
ne contreferait aucune revendication de l’ingrédient médicinal, revendication
de la formulation, revendication de la forme posologique ni revendication de
l’utilisation de l’ingrédient médicinal en fabriquant, construisant,
utilisant ou vendant la drogue pour laquelle la présentation est déposée.
. . .
(3) La
seconde personne qui inclut l’allégation visée à l’alinéa (1)b) ou (2)b) doit
prendre les mesures suivantes :
a) signifier
à la première personne un avis de l’allégation à l’égard de la présentation
ou du supplément déposé en vertu des paragraphes (1) ou (2), à la date de son
dépôt ou à toute date postérieure;
b) insérer
dans l’avis de l’allégation :
(i) une
description de l’ingrédient médicinal, de la forme posologique, de la
concentration, de la voie d’administration et de l’utilisation de la drogue
visée par la présentation ou le supplément,
(ii) un
énoncé détaillé du fondement juridique et factuel de l’allégation;
c) joindre
à la signification une attestation par le ministre de la date du dépôt de la
présentation ou du supplément;
d) signifier
au ministre la preuve de toute signification des documents et renseignements
visés aux alinéas a) à c).
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