Date: 20070426
Docket: T-1711-06
Citation: 2007 FC 444
Ottawa, Ontario, April 26,
2007
PRESENT: The Honourable Madam Justice Mactavish
BETWEEN:
ABBOTT LABORATORIES and
ABBOTT LABORATORIES LIMITED
Applicants
and
THE ATTORNEY GENERAL OF CANADA and
THE MINISTER
OF HEALTH
Respondents
REASONS FOR JUDGMENT AND JUDGMENT
[1]
By
this application, Abbott Laboratories and Abbott Laboratories Limited (referred
to collectively in this decision as “Abbott”) seek to judicially review a
decision of the Minister of Health refusing to add Canadian Letters Patent No.
2,250,736 (the ’736 patent) to the Patent Register.
[2]
Abbott
says that in refusing to list ’736 patent on the Patent Register, the Minister
erred by relying on irrelevant considerations, by making incorrect factual
assumptions about how the food and drug approval system works, and by
erroneously interpreting the Patented Medicines (Notice of Compliance)
Regulations, SOR 93/133.
[3]
For
the reasons that follow, I am not persuaded that the Minister erred as alleged
by Abbott. As a consequence, the application for judicial review will be
dismissed.
Background
[4]
On
January 12, 1990, Abbott filed a New Drug Submission (“NDS”) for BIAXIN®.
BIAXIN® is an antibiotic used in the treatment of mild to moderate
infections caused by strains of designated micro-organisms. The primary active
ingredient in BIAXIN® is clarithromycin.
[5]
A
Notice of Compliance was issued to Abbott on May 8, 1996, which identifies the
product to which the NOC relates as “BIAXIN®”. The NOC further
identifies the “Medicinal Ingredient(s)” as “Clarithromycin Film-Coated Tablets
250 mg”.
[6]
Abbott
subsequently filed a number of supplemental NDSs to allow it to market new
dosage forms and strengths of clarithromycin under the BIAXIN® brand
name, including BIAXIN® 125 mg/5 mL, BIAXIN® BID 500 mg
and BIAXIN® XL500 mg, and obtained additional Notices of Compliance
so as to permit it to do so.
[7]
These
subsequent NOCs all continue to identify the product name as “BIAXIN®”,
and each identifies the Medicinal Ingredient(s) simply as “Clarithromycin”.
[8]
On
April 25, 2006, Abbott applied to have the ’736 patent listed on the Patent
Register with respect to seven Supplementary New Drug Submissions (“SNDS”)
relating to new dosage forms and strengths of clarithromycin sold under the
BIAXIN® brand name.
[9]
The
’736 patent claims compounds that are produced during the synthesis of
clarithromycin, when certain solvents are used in that process. These
compounds have chemical structures that are different from that of clarithromycin.
One of these compounds is an oxime of erythromycin (the “Oxime”).
[10]
According
to Abbott, the Oxime is a “medicine”, in that it is an active pharmaceutical
ingredient made in the process of synthesizing clarithromycin, which is
contained in BIAXIN®.
[11]
Abbott
thus says that as Notices of Compliance have been issued for BIAXIN®,
a drug containing the Oxime medicine, and given that the ’736 patent contains a
claim to that medicine, it follows that the ’736 patent should be listed on the
Patent Register in relation to BIAXIN®.
The Minister’s
Provisional Decision
[12]
By
letter dated May 2, 2006, the Minister provisionally refused to list the ’736
patent in the Patent Register. In this regard, the relevant portion of the
letter states:
The ’736 patent does not
contain a claim to the medicine clarithromycin, or its use. Rather, the ’736
patent contains claims directed towards intermediate or derivative compounds
which are not the medicine clarithromycin. Therefore, pursuant to the authority
vested in the Minister of Health by subsection 3(1) of the Regulations,
the ’736 patent will not be added to the Patent Register, subject to any
written representations.
Abbott’s Further
Submissions
[13]
Representatives
of Abbott met with the Associate Director of the Office of Patented Medicines
and Liaison on July 21, 2006 to discuss this matter, and further written
representations were provided by Abbott in a letter dated August 4, 2006.
[14]
These
representations included a summary of the opinion of Dr. Jerry Atwood, a Professor
of Chemistry, who has experience in organic and pharmaceutical chemistry. It
was Dr. Atwood’s view that the synthesis of clarithromycin will inevitably
result in the production of clarithromycin, as well as the Oxime.
[15]
Dr.
Atwood was further of the view that the steps taken to purify the
clarithromycin will not completely remove all of the Oxime, and that, as a
result, some Oxime will inevitably be present in the final product.
[16]
Finally,
it was Dr. Atwood’s opinion that the Oxime had therapeutic value, and is thus a
“medicine”.
The Minister’s Final
Decision
[17]
By
letter to Abbott dated August 25, 2006, the Minister responded to Abbott’s
written submissions, maintaining the position that the ’736 Patent was
ineligible for listing on the Patent Register.
[18]
In
this regard, the Minister stated that the ’736 patent did not contain a claim
for clarithromycin, or for the use of clarithromycin, as is required by
paragraph 4(2)(b) of the PM(NOC) Regulations.
[19]
In
particular, the Minister disagreed with Abbott’s assertion that a “claim for a
medicine itself” includes a single active ingredient or a combination of
substances, and could include a product not identified in or approved by the
NOC.
[20]
In
this regard, the Minister distinguished the decisions in Hoffmann-La Roche
Ltd. v. Canada (Minister of National Health and Welfare) (1995), 67
C.P.R. (3d) 25 (F.C.A) and Eli Lilly Canada Inc. v. Canada (Minister of
Health),
2003 FCA 24, [2003] 3 F.C. 140, 237 F.T.R. 160, which had been relied upon by
Abbott. The Minister observed that in those cases, the medicine claimed
corresponded with the medicine in the drug, which was not the case here.
[21]
Moreover,
the Minister was of the view that the only medicine that had been approved for
use by the NOCs granted to Abbott with respect to its BIAXIN® products
was clarithromycin, and not any derivatives, by-products or impurities which
were not the medicine itself.
[22]
The
Minister observed that the medicine clarithromycin in the BIAXIN® product
did not correspond with the medicine claimed in the ’736 patent, nor was it
pharmaceutically equivalent to the medicine claimed in that patent. That is, a
generic manufacturer with a drug containing the compounds claimed in the ’736
patent, would not be able to use BIAXIN® as the reference product.
[23]
Ultimately,
the Minister found that the Oxime derivative was not “the medicine”, and that
only clarithromycin had been approved for use through the issuance of the NOC
for BIAXIN®.
[24]
The
Minister concluded by saying that if Abbott chose to apply for a NOC for the
’736 Patent, it could be added to the Patent Register at that time, subject to
the provisions of the PM(NOC) Regulations.
[25]
As
a consequence, the Minister refused to list the ’736 patent on the Patent
Register. It is this decision that Abbott now seeks to judicially review.
Legislative Regime
[26]
In
order to put Abbott’s arguments into context, it is first necessary to have an
understanding of the legislative regime governing the listing of patents on the
Patent Register.
[27]
The
sale of pharmaceuticals in Canada is regulated by the Food and Drug
Regulations, C.R.C. c. 870.
[28]
An
innovator company (or “first person”) may not manufacture and sell a new drug
without the regulatory approval of the Minister of Health. If, after
completing the review process contemplated by the regulatory process, the
Minister is satisfied that a drug is safe, effective and otherwise complies
with the Food and Drug Regulations, then a Notice of Compliance will be
issued to the first person.
[29]
The
Patented Medicines (Notice of Compliance) Regulations in issue in this
proceeding are those that were in place prior to the October, 2006 amendments
(SOR/2006-242).
[30]
Section
4 of the Regulations allows a first person to file patent lists with the
Minister. Under the PM(NOC) Regulations, a patent owner may submit a
patent list in respect of any drug containing a "medicine" for which
a Notice of Compliance has been issued or is being sought.
[31]
Section
2 of the PM(NOC) Regulations defines a “medicine” as:
[A] substance intended or
capable of being used for the diagnosis, treatment, mitigation or prevention of
a disease, disorder or abnormal physical state, or the symptoms thereof.
[32]
The
result of listing a patent is to allow the first person to use the PM(NOC)
Regulations to shield the innovator company’s product against competition
from generic manufacturers.
[33]
Subsection
3(1) of the PM(NOC) Regulations empowers the Minister of Health to
determine which patents are added to the Patent Register. The Minister is
under a mandatory duty to maintain the register, and has the prima facie
obligation to include patent lists submitted by patent holders on the
register. However, the Minister may refuse to add a patent to the register if
it is ineligible for inclusion.
[34]
Also
of relevance is subsection 3(3) of the PM(NOC) Regulations, which states
that “No information submitted under section 4 shall be included on the
register until after the issuance of the Notice of Compliance in respect of
which the information was submitted.”
[35]
The
criteria to be used in determining whether or not a patent should be listed on
the Patent Register are set out in section 4 of the PM(NOC) Regulations.
The criterion in issue in this proceeding is that contained in paragraph
4(2)(b) of the Regulations, namely that in order to be eligible for listing on
the Patent Register, the patent must contain a claim for the medicine, or for
the use of the medicine, for which the particular Notice of Compliance was
granted.
Issues
[36]
The
central issue in this application is whether the ’736 patent meets the
requirements of paragraph 4(2)(b) of the Patented Medicines (Notice of
Compliance) Regulations, and thus whether the Minister's interpretation of
this statutory provision was correct.
[37]
Abbott
also asserts that the Minister erred by relying on an irrelevant and erroneous
consideration in refusing to list the ’736 patent, namely the belief that in
seeking to have the ’736 patent listed on the Patent Register, Abbott was
trying to “evergreen” its other patents relating to BIAXIN®.
Standard of Review
[38]
It
appears to be settled law that the standard of review for a decision such as
this is correctness (see Eli Lilly Canada Inc. v. Canada (Minister of
Health), previously cited, and AstraZeneca Canada Inc. v. Canada (Minister of
Health),
2006 SCC 49, [2006] 2 S.C.R. 560,
at ¶ 25.
Analysis
[39]
The
crux of this case is the extent to which the “medicine” referred to in the
Notices of Compliance issued with respect to BIAXIN® must correspond
to the innovation claimed in the patent sought to be listed, namely the ’736
patent.
[40]
Abbott
asserts that it has Notices of Compliance for BIAXIN®, and that
BIAXIN® contains the Oxime. As attested to by Dr. Atwood in his
affidavit filed in support of this application, the Oxime has therapeutic value
and is thus a “medicine”, as defined in the PM(NOC) Regulations. Given
that the ’736 patent relates to the Oxime, it therefore follows, Abbott says,
that Abbott is entitled to list the ’736 patent on the Patent Register in
relation to BIAXIN®.
[41]
According
to Abbott, it is fundamentally incorrect to suggest that by issuing Notices of
Compliance for BIAXIN®, that Health Canada has approved the use of
any particular medicine. In this regard, Abbott submits that the term
“medicine” in the PM(NOC) Regulations is not defined by reference to
ingredients “approved through the issuance of” a Notice of Compliance.
[42]
Rather,
Abbott says, the approval process for new drugs in Canada covers the
drug as a whole in the final dosage form as it is used or sold, which drug may
contain more than one substance capable of treating a disease.
[43]
In
this regard, Abbott relies on the evidence of Dr. Albert Liston, the former
Assistant Deputy Minister of the Health Protection Branch of Health Canada. Dr. Liston
has a doctorate in stereochemistry, and spent much of his career at Health Canada, in
positions of increasing responsibility involving the drug approvals process.
[44]
According
to Dr. Liston, prior to issuing a Notice of Compliance for BIAXIN®,
Health Canada would have
evaluated BIAXIN® as a whole, in order to ensure that the drug is
safe and effective. While conceding that the consideration of the active
medicinal ingredient in a drug and its properties is a major part of the
assessment, Dr. Liston nevertheless says that Health Canada’s evaluation would
not have been limited to the primary medicinal ingredient in the drug, namely
clarithromycin.
[45]
That
is, Dr. Liston says that the approval process would have covered the entire
process of manufacture that results in the incorporation of the active
pharmaceutical ingredient and any other compounds into the formulated drug
product.
[46]
I
do not accept Abbott’s arguments.
[47]
A
review of the legislative scheme indicates that Notices of Compliance are
issued in relation to drugs that contain specifically stated medicines.
[48]
This
is confirmed by the wording of subsection 4(1) of the PM(NOC) Regulations,
which provides that:
4. (1) A person who files or
has filed a submission for, or has been issued, a notice of compliance in
respect of a drug that contains a medicine may submit to the Minister a
patent list certified in accordance with subsection (7) in respect of the drug.
[Emphasis added]
[49]
Moreover,
paragraph 4(2)(b) of the PM(NOC ) Regulations is quite clear that, to be
eligible for listing on the Patent Register, the patent in question must
contain a claim for “the medicine”, or for the use of “the medicine”, for which
the particular Notice of Compliance was granted.
[50]
In
subsection 5(1) of the PM(NOC) Regulations, generic manufacturers must
make allegations with respect to specific medicines. It would not be possible
to do this, and considerable confusion would result, if the “medicines” in
question were not specifically identified in New Drug Submissions and
subsequently issued Notices of Compliance.
[51]
As
Justice Hughes observed in “Hughes and Woodley on Patents” (Second
Edition) 1 LexisNexis Canada Inc. 215 at § 23:
A patent is placed on the list
in respect of a particular drug, not a particular application. In order for a
patent to be listed, it must claim a drug containing the same active ingredient
– it may be of a different formulation or crystal structure – as the medicine
for which a Notice of Compliance was given. The patent must pertain to the same
active ingredient as that for which the Notice of Compliance pertains ….
[52]
This
very point was made in earlier litigation between these parties involving
BIAXIN®. That is, in Abbott Laboratories v. Canada (Minister of
Health),
2006 FC 120, [2006] 4 F.C. 41, rev’d on other grounds: 2007 FCA 73, Justice
Harrington stated that:
… In any event, a patent may
be listed on the register if it claims a drug containing the same medicine
for which the notice of compliance was given, even though that medicine may
be in a different form or crystal structure. [at ¶ 40, emphasis added]
[53]
Finally,
in Ferring Inc. v. Canada (Minister of Health), 2007 FC
300, Justice Hughes stated at that:
The criteria as to whether a
patent is to be listed or not are set out in section 4 of the Regulations.
There are a number of criteria, the most important of which for purposes of
this discussion is that the patent contains a claim for the medicine or use of the
medicine for which the particular NOC was granted, section 4(2)(b) of the
pre-October 5, 2006 … regulations. [at ¶ 24, emphasis added]
[54]
In
this case, the Notices of Compliance issued in relation to BIAXIN®
are clear, on their face, that the only medicinal ingredient covered by the
Notices of Compliance is clarithromycin. While Notices of Compliance can clearly
be issued in relation to drugs containing more than one medicinal ingredient,
no other medicinal ingredient is identified in the NOCs issued in relation to
BIAXIN®.
[55]
I
also do not accept Abbott’s contention that the fact that the Minister of Health
issued Notices of Compliance for BIAXIN® means that the Minister
would, of necessity, have considered and assessed the safety and efficacy of
the Oxime as an active medicinal ingredient in that drug.
[56]
In
this regard, I would note that while arguing that the Minister of Health would
have carefully examined the safety and efficacy of the Oxime as an active
ingredient in BIAXIN® in the context of Abbott’s New Drug Submission
for that drug, Abbott chose not to include a copy of its NDS in its application
materials. Thus we have no way of knowing whether the Oxime was ever
identified as an active medicinal ingredient by Abbott in its NDS, or whether
the Oxime was ever assessed as such by the Minister of Health.
[57]
We
do know, however, that the only active medicinal ingredient identified by the
Minister in the NOCs granted to Abbott for its BIAXIN® products is
clarithromycin.
[58]
Moreover,
nowhere in the materials before me, apart from Dr. Atwood’s affidavit, is the
Oxime identified as a medicine. In this regard, I note that a review of
Abbott’s product monograph for BIAXIN® discloses that the only
medicinal ingredient identified or discussed in the monograph is
clarithromycin. Similarly, Abbott itself acknowledges that the Oxime is not
mentioned in either the European or American Pharmacopeia.
[59]
In
these circumstances, I am prepared to draw an adverse inference against Abbott,
and do not accept its submission that the NDS provided by Abbott to the
Minister identified the Oxime as a medicine in BIAXIN®.
[60]
This
is not surprising. Even if I accept Dr. Atwood’s evidence that the Oxime has
some therapeutic value, the fact is that the Oxime was not something that was
specifically included in the drug formulation for BIAXIN® because of
its therapeutic value.
[60]
[61]
That
is, as Dr. Atwood explained, the Oxime is a by-product of one of the
manufacturing processes used to synthesize clarithromycin. It does not appear
that it is a desirable by-product, as Dr. Atwood himself stated that the
manufacturer would try to remove as much of the Oxime as possible from the
formulation. Dr. Atwood then went on to state that the complete elimination of
all of the Oxime from the finished clarithromycin product would not be
possible, with the result that some Oxime would inevitably be present in the
final product.
[62]
Moreover,
it is clear that the Oxime is not always created during the synthesis of
clarithromycin, and its creation is dependent on the choice of solvent used
during the synthetic process. According to Dr. Atwood, it is only when isopropyl
acetate is used as a solvent that the Oxime will be produced. However,
isopropyl acetate is only one of many chemical solvents that can be used in the
synthesis of clarithromycin. Similarly, oximation is only one of the methods
that can be used in the synthesis of clarithromycin.
[63]
Given
the foregoing, it is hardly surprising that the Oxime was not identified as a
medicinal ingredient in BIAXIN®.
[64]
As
a consequence, I do not accept Abbott’s contention that the Oxime has
previously been approved for use as a medicine through the Notices of
Compliance issued in relation to BIAXIN®, or that it was ever even
considered as such by Health Canada.
[65]
Finally,
I am not persuaded that the decision in Apotex v. Canada (2000), 181
D.L.R. (4th) 404, (F.C.A.) dictates that Abbott is entitled to have the ’736
patent added to the Patent Register, as it is an intermediate with therapeutic
value, which is thus a “medicine”.
[66]
Firstly,
from the evidence of Dr. Atwood, it appears that the Oxime is not a true
intermediate, in that it is not transient, but is rather the by-product of one
of the synthetic routes that can be followed in the manufacture of
clarithromycin.
[67]
More
importantly, a review of the Apotex decision discloses that while the
Federal Court of Appeal stated that “it is certainly arguable that an
intermediate with therapeutic value might be a medicine”, the Court was very
careful to preface this comment by saying “For the purpose of this appeal, it
is sufficient that there is no definitive finding that intermediates cannot, in
any circumstances, meet the requirements of paragraph 4(2)(b).” Thus Apotex
does not decide the issue one way or another.
[68]
Moreover,
in the more recent decision in Merck Frosst Canada & Co. v. Canada
(Minister of Health) (2000), 7 C.P.R. (4th) 522 (F.C.T.D), aff’d 2001 FCA
136, the Federal Court of Appeal held that the Minister did not err in refusing
to list patents on the Patent Register where those patents related to
metabolites of a medicine identified in a Notice of Compliance, and made no
claim to the medicine itself.
[69]
It
was in this context that Federal Court of Appeal observed that to disregard the
terms of the Notice of Compliance by treating the drug in question as
containing both the medicine specifically identified in the Notice of
Compliance and its metabolites “could compromise the ability of the Minister to
discharge the important statutory responsibilities for ensuring the
effectiveness and safety of new drugs”. [at ¶ 9]
[70]
While
we are not dealing with a metabolite of the “medicine” in this case, but are
dealing instead with a product of one of the synthetic routes than can be used
to manufacture clarithromycin, the same point may nevertheless be made about
the Oxime in issue in this case.
The Minister’s Reliance
on an Irrelevant or Erroneous Consideration
[71]
Finally,
Abbott says that that the Minister erred by relying on an irrelevant
consideration in relation to the ’736 patent, namely the erroneous assumption
that in seeking to have the ’736 patent listed on the Patent Register, Abbott
was seeking to “evergreen” Abbott’s other patents relating to BIAXIN®.
[72]
While
I accept Abbott’ submission that this is not a case of attempted evergreening
on Abbott’s part, given that the ’736 patent will expire prior to the expiry of
the other patents relating to BIAXIN®, I do not accept that the
decision refusing to list the ’736 patent should be set aside on the basis that
the Minister took irrelevant matters into consideration in concluding that the
’736 patent was not eligible for listing.
[73]
Whether
the Minister thought that this was a case of attempted evergreening or not, the
fact of the matter is that the Minister’s interpretation of paragraph 4(2)(b)
of the PM(NOC) Regulations was correct. The ’736 patent was not
eligible for listing, and no other decision was possible in this case.
Conclusion
[74]
For
these reasons, this application for judicial review is dismissed.
Costs
[75]
Both
parties agree that the costs of this application should follow the event, and I
so order.
JUDGMENT
THIS COURT
ORDERS AND ADJUDGES that this application for judicial review is
dismissed, with costs.
“Anne
Mactavish”
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