Date: 20101110
Docket: T-175-09
Citation: 2010 FC 1123
Ottawa,
Ontario, November 10, 2010
PRESENT: The Honourable Mr. Justice Barnes
BETWEEN:
|
|
JANSSEN INC. AND
JANSSEN PHARMACEUTICA N.V.
|
|
|
|
Applicants
|
|
and
|
|
|
MYLAN PHARMACEUTICALS ULC AND
THE MINISTER OF HEALTH
|
|
|
|
Respondents
|
|
|
|
|
REASONS FOR JUDGMENT AND
JUDGMENT
[1]
This
application was brought by Janssen Inc. and Janssen Pharmaceutica N.V. (collectively
Janssen unless otherwise indicated) against Mylan Pharmaceuticals ULC (Mylan) and
the Minister of Health (Minister) under the Patented Medicines (Notice of
Compliance) Regulations, SOR 93-133 (NOC Regulations). Janssen seeks an
order prohibiting the Minister from issuing a Notice of Compliance (NOC) to Mylan
until the expiry of Canadian Letters Patent No. 2,310,950 ('950 Patent).
Janssen Pharmaceutica N.V. is the owner of the '950 Patent which it has
licensed to Janssen Inc.
[2]
The
'950 Patent was filed on June 27, 2000 and it is listed on the Minister’s
Patent Register in respect of Janssen’s galantamine product, Reminyl, in
strengths of 8 mg, 16 mg and 24 mg extended release capsules. A NOC for
Reminyl ER was issued to Janssen by the Minister on April 8, 2005.
[3]
On
December 27, 2008 Janssen received Mylan’s Notice of Allegation (NOA)
challenging the validity of the '950 Patent on several grounds including
obviousness, insufficient disclosure, non-utility, ambiguity and
non-patentability (as a method of medical treatment).
The Patent
Claims
[4]
The
'950 Patent concerns the use of the cholinesterase inhibitor galantamine to
treat Alzheimer’s disease, but the patent claims in issue are limited to
Janssen’s discovery of an optimal dosage regimen for the compound. As the '950
Patent acknowledges, galantamine was a known compound that had been previously
used and patented for the treatment of Alzheimer’s disease. Accordingly, the
inventive concept of the '950 Patent is limited to Janssen’s claimed discovery
that the slow titration of galantamine improved patient tolerability for the
drug, by reducing side-effects and resulted in the ability to use a lower
maintenance dose than had previously been shown to be effective.
[5]
The
only claims that are in issue in this proceeding are claims 3, 5, 6, 7 and 8
(the relevant claims):
3. A use of galantamine from a
first dosage of about 8 mg/day to a final dosage of about 16 mg/day to 24
mg/day for treating Alzheimer’s Disease wherein said first dosage is for use
for a period from about two weeks to about ten weeks; and wherein the use of
the first dosage from about two weeks to ten weeks results in a lower final
dosage.
***
5. The use of any one of Claims 1
to 4 wherein the galantamine is for use at a first dosage of about 8 mg/day, a
second dosage of about 16 mg/day, and a final dosage of about 24 mg/day;
wherein said first dosage is for use for a period from about two weeks to about
four weeks, said second dosage is for use for a period from about two weeks to
about four weeks and said final dosage is for use thereafter.
6. The use of Claim 5 wherein the
first dosage is for use for about four weeks and said second dosage is for use
for about four weeks.
7. The use of any one of Claims 1
to 4 wherein the galantamine is for use at a first dosage of about 8 mg/day and
a final dosage of about 16 mg/day; wherein the first said dosage is for use
from about two weeks to about four weeks and said final dosage is for use
thereafter.
8. The use of Claim 7 wherein
said first dosage is for use for about four weeks.
Claim 3 has the following elements:
1. the use of
galantamine to treat Alzheimer’s disease;
2. in a first
dosage of about 8 mg per day for about 2-10 weeks;
3. followed by a
final dosage of about 16-24 mg per day thereafter; and
4. wherein the
use of such a slow-dose regimen results in a lower final dosage.
Claims 5 and 6 are dependant on claim 3. They
both describe a dosing regimen starting with 8 mg per day of galantamine
working up to 16 mg per day, and ending with 24 mg per day. The proposed
titration schedule in these claims is somewhat variable with the administration
of galantamine in each of the initial stages having a duration of two to four
weeks. Claims 7 and 8 are also dependant on claim 3 and differ only to the
extent that the final dose of 16 mg per day is achieved after the completion of
the first titration stage having a duration of two to four weeks.
Clinical
Studies
[6]
The
evidence establishes that leading up to the '950 Patent, galantamine had been
the subject of a modest number of clinical trials which focussed on its
efficacy as an Alzheimer’s drug. During the trials, galantamine was
administered by titration in varying doses to patients with Alzheimer’s
disease. Those studies demonstrated that daily doses of galantamine of 24 mg
and higher were efficacious but problems with patient tolerability and
compliance were quite common.
[7]
It
was during a further Phase III clinical trial (the Patent Study) that Janssen
established that the use of a slower titration rate could reduce the frequency
and severity of side-effects from galantamine. This finding was the foundation
for Janssen’s inventive assertion in the '950 Patent that its method of slow
titration effectively reduced the adverse side-effects that would otherwise be
experienced from galantamine.
[8]
The
Patent Study also demonstrated that galantamine was almost equally efficacious
at daily dosages of 16 mg and 24 mg. Notwithstanding the absence of any stated
finding in the Patent Study that the efficacy of 16 mg of galantamine was
caused by the titration method employed, Janssen drew that conclusion by comparing
the results of the Patent Study to an earlier study by Wilkinson and Murray
(the Prior Study). In the Prior Study it had been found that an 18 mg daily
dose of galantamine was, in terms of efficacy, sub-optimal. The Prior Study
discussed the significance of its data in the following passage:
Galantamine is an effective and
well-tolerated symptomatic treatment for AD. Over a period of 12 weeks,
galantamine produced an improvement in cognitive performance, as assessed by
the primary efficacy variable, ADAS-cog. The largest treatment effect was seen
for galantamine 24 mg/day (4.2 points on the PP analysis and 3 points on the
more conservative ITT analysis). Both the 18 and 36 mg/day doses of
galantamine produced significant benefits on cognitive function on PP
analysis. Although not powered to detect changes in secondary outcome
measures, galantamine produced a significantly better outcome than placebo on
quality of life and global response to treatment.
[9]
In
an interim version of the Prior Study report, the authors also discussed the
value of slower titration as a means of achieving higher levels of patient
compliance:
The interim results obtained from this
ongoing Phase II study confirm and extend earlier reports that galanthamine
hydrobromide holds promise as an effective and well-tolerated treatment for
cognitive impairment in patients with SDAT. The data presented indicate that
galanthamine (30 mg/day) administered over a period of 12 weeks to patients
with SDAT effects a statistically highly significant improvement in cognitive
performance. Excellent overall tolerability to the drug with a low withdrawal
rate was observed in this study. Although final conclusions must await completion
and full statistical analysis of the study, it appears that optimal patient
benefit has been achieved at a daily dose of 30 mg. Dosage adjustment during
initial exposure to the drug, i.e. a more gradual dose escalation and the
permitted use of anti-nauseants, may be expected to further improve compliance,
and a four-week titration period has been incorporated in the current Phase III
studies. These interim findings demonstrate a very promising potential for
galanthamine in the treatment of Alzheimer’s disease.
I. Issues
[10]
Burden
of proof?
[11]
Obviousness,
utility and claims construction?
[12]
What
is a method of medical treatment?
[13]
Are
the relevant claims a method of medical treatment and, if so, can that
subject-matter be patented?
[14]
Costs?
II. Analysis
Burden of
Proof
[15]
The
parties are in agreement and it is well established that the ultimate burden of
proof on this application rests with Janssen to establish on a balance of
probabilities that Mylan’s allegations of invalidity are not justified.
Obviousness,
Utility and Claims Construction
[16]
The
issue that is determinative of this application is whether the relevant claims
constitute a method of medical treatment and are, on that basis, unpatentable.
Because I have concluded that the relevant claims constitute unpatentable
subject-matter, it is unnecessary for me to resolve the other substantive
issues that were raised by Mylan’s NOA and addressed in the evidence. Suffice
it to say that I have no doubt whatsoever that Janssen’s claim to have
discovered that the slow titration of galantamine reduced patient side-effects
was well-known in the prior art and therefore would have been obvious to a
person of skill at the relevant time.
[17]
I
also do not accept Janssen’s other inventive premise that the proposed method
of slowly titrating galantamine can lead to a lower maintenance dose (16 mg) than
would otherwise be required. This is an unwarranted and unsound conclusion
that cannot be drawn or predicted by comparing the clinical study underlying
the '950 Patent with the results of an earlier non-comparative clinical study
which, according to the '950 Patent, found a dose of 18 mg of galantamine to be
“sub-optimal”.
[18]
In
the field of pharmaceutical research, it is common that the results of one
clinical study are not replicated in another, even where the study designs are
equivalent. In the absence of a well-designed head-to-head study of
galantamine comparing different approaches to titration, no one could
reasonably conclude that these marginally different study outcomes were caused
by the slowed titration of galantamine and not for some other reason.
[19]
I
am satisfied that the relevant claims are open to being construed and that they
are not invalid on the basis of ambiguity. Because the determinative issue of
whether the claims cover a method of medical treatment does not turn on the
meaning of the disputed language, it is unnecessary for me to precisely resolve
that point.
What is a
Method of Medical Treatment?
[20]
On
at least two occasions the Supreme Court of Canada has addressed the issue of
subject-matter patentability in relation to an asserted method of medical
treatment.
[21]
In
Tennesse Eastman Co. v. Canada (Commissioner of
Patents),
[1974] S.C.R. 111, 8 C.P.R. (2d) 202 the Court considered the question in
relation to the use of a compound with known essential qualities (an adhesive)
for a novel and practical medical use (the closure of surgical incisions). The
question before the Court was whether the proposed method of use fell within
the definition of an “invention” in s. 2 of the Patent Act, R.S.C.
1952, c. 203 (now R.S., 1985, c. P-4) (Act) and, in particular, whether it was
a patentable “art” or “process”. The Court further refined the question before
it to “whether a new use for surgical purposes of a known substance can be
claimed as an invention” [para. 11]. In holding that this adaptation of the
adhesive product to a surgical use was not a patentable invention, the Court
considered the problem in the context of the administration of medicinal substances:
It is clear that a new substance that is
useful in the medical or surgical treatment of humans or of animals is an
"invention". It is equally clear that a process for making such a
substance also is an "invention". In fact, the substance can be claimed
as an invention only "when prepared or produced by" such a process.
But what of the method of medical or surgical treatment using the new
substance? Can it too be claimed as an invention? In order to establish the
utility of the substance this has to be defined to a certain extent. In the
case of a drug, the desirable effects must be ascertained as well as the
undesirable side effects. The proper doses have to be found as well as methods
of administration and any counter-indications. May these therapeutic data be
claimed in themselves as a separate invention consisting in a method of
treatment embodying the use of the new drug? I do not think so, and it appears
to me that s. 41 definitely indicates that it is not so.
The Court concluded by holding that a
method of surgical treatment was also excluded from the term “process” found in
s. 2 of the Act. This was a conclusion that was based in part on s. 41 of the
Act (repealed in 1987) which prohibited the patenting of “inventions relating
to substances prepared or produced by chemical processes and intended for food
or medicine”.
[22]
In
Apotex Inc. v. Wellcome Foundation Ltd., 2002 SCC 77, 21 C.P.R. (4th)
499 (hereinafter referred to as AZT ) the Supreme Court of Canada
distinguished its decision in Tennessee Eastman, above, holding that the
discovery of a wholly new use for a medicinal compound was patentable.
Nevertheless, the decision did not cast doubt upon the essential point from Tennesse
Eastman that monopolies over methods of medical treatment are not
permitted, pointing out that “[h]ow and when, if at all, AZT is employed
is left to the professional skill and judgment of the medical profession”
[para. 50].
[23]
In
Visx Inc. v. Nidek Co (1999).,181 F.T.R. 22, 3 C.P.R. (4th) 417
affirmed by the Federal Court of Appeal at 2001 FCA 215, 16 C.P.R. (4th)
251, Justice Jean-Eudes Dubé considered the method of medical treatment issue
in connection with a patent over a medical device used for performing eye
surgery. He held that an apparatus used to assist a surgeon in the exercise of
professional skill is patentable. This is consistent with a number of
authorities which have held that patent claims directed at vendible products
are recognized: see the discussion by Justice Roger Hughes in Merck
& Co. v. Nu-Pharm Inc., 2010 FC 510, 85 C.P.R. (4th) 179 at
paras. 109 to 114.
[24]
More
recently, in Axcan Pharma Inc. v. Pharmascience Inc., 2006 FC 527, 50
C.P.R. (4th) 321, Justice Sean Harrington considered the problem in the context
of a patent claim for a dosage range for a medicinal compound. After reviewing
the relevant prior authorities, including Tennessee Eastman, above,
Justice Harrington held that a patent claim over a dosage range is not a
vendible product and, therefore, not patentable. Justice Harrington went on to
find that, notwithstanding the intervening repeal of s.41 of the Act, Tennessee
Eastman, above, was still good law in Canada.
[25]
To
the same effect is the decision by Justice Hughes in Merck & Co. v.
Nu-Pharm Inc., above, where he confirmed that a patent claim for a method
of treatment that did not exclude the exercise of medical professional skill or
judgment was not patentable in Canada, although a claim to a fixed dosage amount
may be patentable: see para. 114.
[26]
What
I take from the above authorities is that a patent claim over a method of
medical treatment that, by its nature, covers an area for which a physician’s
skill or judgment is expected to be exercised is not patentable in Canada. This would
include the administration of a drug whereby the physician, while relying upon
the dosage advice of the patentee, would still be expected to be alert and
responsive to a patient’s profile and to the patient’s reaction to the compound.
The Witnesses
[27]
Dr.
Joel Sadavoy is a professor of psychiatry at the University of Toronto
and Head of the Geriatric Psychiatry Programs and Community Psychiatry Programs
at Mount
Sinai
Hospital in Toronto. He has an
active clinical practice in geriatric medicine, which includes the treatment of
patients with Alzheimer’s disease. Dr. Sadavoy has published widely in the
area of geriatric psychiatry and he is the author of the 2004 textbook
“Psychotropic Drugs and the Elderly: Fast Facts”.
[28]
Dr.
Murray Raskind is the Director of the Alzheimer’s Disease Research Centre at
the University of Washington. His
medical practice includes the treatment of 200 to 300 patients with Alzheimer’s
disease. He also has considerable experience in the management of clinical
trials that evaluate treatments for Alzheimer’s disease, including a clinical
trial of galantamine. He has an lengthy curriculum vitae which includes
contributions to over 240 publications. He also has had a professional
consulting relationship with Janssen and has previously testified on its behalf
in American patent litigation.
[29]
Dr.
Serge Gauthier is a neurologist. He teaches in the Departments of Psychiatry,
Neurology and Neurosurgery at McGill University. He is also the Director of
the Alzheimer’s Disease and Related Disorders Unit at the McGill Centre for
Studies in Aging. Dr. Gauthier has worked in the field of Alzheimer’s disease
for over 31 years as a treating physician, an investigator and scientific
advisor and is widely published in this area of medicine. He has considerable
experience working with galantamine.
[30]
Dr.
Edward Sellers is a Professor Emeritus of Medicine, Pharmacology and Psychiatry
in the faculty of Medicine at the University of Toronto. He has a
Ph.D. in Pharmacology from Harvard University and he is widely
published in that field.
[31]
Dr.
Peter Lin is a primary care physician practising in two Toronto family
practice groups. He is involved extensively in developing and delivering
continuing medical education programs to other primary care physicians, albeit
Alzheimer’s disease is the topic of only a small portion of that work. It is
in the context of his clinical practice that Dr. Lin has had experience in
treating Alzheimer’s disease with galantamine. He purports in his affidavit to
offer an opinion with respect to “most primary care physicians who
prescribe…galantamine”.
The Evidence
[32]
As
to whether the relevant claims constitute a method of medical treatment,
Janssen relied principally on the evidence of Drs. Lin and Gauthier.
Nevertheless, this issue was also addressed by Drs. Sellers and Raskind both in
their affidavits and in their testimony. I have, therefore, considered all of
their evidence on the point without distinction. Mylan’s only witness on this
issue was Dr. Sadavoy.
[33]
Dr.
Sadavoy was asked to provide an opinion as to whether the relevant claims in
the '950 Patent are distinguishable from the work of a physician. He concluded
that the '950 Patent “severally encroaches on the skill of a clinician” because
it overlaps with areas of clinical judgment
bearing on individualized treatment. This
point is expressed at paras. 261, 262, 263 and 264 of his affidavit:
261. The Relevant C1aims of the 950
Patent cover the first two components of care: they dictate the amount of drug
to be given each day, and the speed at which the drug dose is titrated upwards.
262. In my opinion this severely
encroaches on the skill of a clinician, as set out throughout this affidavit,
treatment with galantamine must be individualized, based on interacting factors
made up of patient characteristics (including the health of the patient and his
or her tolerance for negative side effects), together with drug characteristics
(including the anticipated and actual effects of the drag, both positive and
negative).
263. Armed with this evaluation, the
clinician then plans the best starting dose, titration rate and final dose.
During treatment, it is the clinician’s responsibility to monitor the patient,
evaluate his or her response to the drug and manage any side effects. Based on
these ongoing evaluations, the clinician will adjust the dosage amount and
titration rate.
264. The dosage amount that I
prescribe to my patients is determined in part based on the dosages available,
and in part on the patient’s tolerance of the drug and his or her response to
treatment.
[34]
Dr.
Sadavoy was examined on this evidence and the following passages provide a
useful summary of his position:
387 Q. So “start
low and go slow” is not enough information to treat a patient?
A. As I
said, “start low and go slow” is a principle. It has to be applied in the specifics
to a given patient.
388 Q. And some
of those factors that you’ve just identified are: Pharmacokinetics and
pharmacodynamics of the drug, correct?
A. That and the known
effect of the drug at a clinical level. So pharmacokinetics and
pharmacodynamics are very detailed analyzes of a drug’s action and the effect
of the body on the drug and the drug on the body.
From
a clinical perspective, knowledge of how the individual reacts to the drug as a
result of those pharmacokinetics and pharmacodynamics is also important
information.
So,
for a given drug, the side effect profile, for example, the way in which that side
effect profile emerges will be critical information. And then integrating that
knowledge with the understanding of how the patient may be modifying the
response to the drug because of their physical condition is equally crucial
information for any physician. [p. 1051 to 1052]
All
of that is taken into consideration in evaluating the “start low, go slow”
principle.
[…]
393 Q. So if we
imagine a circumstance where a person skilled in the art is in his clinic and
is given a bottle of geriatric medicine, without more description, if I said to
the doctor: “Please administer this to the patient according to the cornerstone
principle of geriatric psychiatry, namely, ‘start low and go slow,’” would you
have enough information?
A. You
would have the initial guidance. As I said before, the essential information
for implementing “start low and go slow” is, who is this patient? What is their
ability to metabolize this particular drug at this particular time?
What
are the competing factors that may interfere with the - - with this drug or
enhance it? What are the - - what are the qualities of this drug which may be
particularly beneficial or toxic or noxious to this particular patient?
And
what is the dosage range for the drug? What are the recommended starting
dosages? What are the prudent starting dosages? What is the range of options
available for thinking about how to initiate a drug? And so on.
So,
as I said before, practitioners are highly trained and they’re highly trained
for a reason, because this is a complex process.
So
“start low and go slow” is the headline. The content of the article, so to
speak, under that headline is a complex mix of all of those things and is
individualized to every patient. [p. 1053 to 1055]
[35]
The
affidavit evidence from Dr. Gauthier and Dr. Raskind is that the '950 Patent
does not interfere with the exercise of a physician’s judgment because it
provides helpful information to the physician that will routinely be used in
prescribing galantamine.
[36]
This
was explained in para. 45 of Dr. Gauthier’s affidavit:
45. The '950 Patent does not
interfere with a physician’s ability to treat patients; rather, it helps
clinicians use galantamine in the most effective manner. The ability to
provide patients with a cholinesterase treatment that is proven effective at a
lower dose with less side-effects results in improved patient compliance and
lessens the burden on care-givers.
Dr. Gauthier’s affidavit must be assessed
in the context of his testimony under examination. There, he willingly
acknowledged that an individual approach to treatment with galantamine was
recommended. This included considerations such as body weight, prior history,
tolerability to drugs generally and patient reaction. Dr. Gauthier accepted
that dosage adjustments may be required in the face of adverse reactions:
A. Yes, that’s what’s written. I
just may want to qualify that. Sometimes the titration that has been
recommended in the monograph does not apply to an individual patient. So there
may be side effects at a dose that you would expect would be well-tolerated so
you may, for that individual patient, extend the time of titration by going
back to the previously well-tolerated lower dose and then try again later the
minimum effective dose. [p. 1742]
[37]
Dr.
Sellers had a slightly different take on this issue. His evidence was that the
'950 Patent claims are not directed at a method of medical treatment because
they set out specific dosing regimens for the use of galantamine to treat
Alzheimer’s disease. According to Dr. Sellers, the claimed dosages and
titration periods are “immutably linked” and do not call upon the exercise of a
physician’s professional judgment in consultation with the patient. Dr. Sellers
went on to dispute Dr. Sadavoy’s view that dosing regimens are devised by
physicians to treat individual patients. This criticism was based on the
notion that physicians do not “experiment” on their patients and instead rely
upon guidelines or instructions for appropriate dosing based on clinical
research. Dr. Sellers went so far as to describe Dr. Sadavoy’s approach as “a
form of therapeutic anarchy” [p. 3886].
[38]
Dr.
Lin provided an affidavit similar to that of Dr. Sellers. He, too, deposed
that most physicians treating Alzheimer’s disease with galantamine do
not design individual dosage regimens and rely instead on the product
monograph. He criticised Dr. Sadavoy for supposedly ignoring the
evidence-based data. This point is captured at para. 28 ad 29 of Dr. Lin’s
affidavit:
28. At paragraph 265 of
his Affidavit, Dr. Sadavoy states “[w]hen considering the rate of titration, I
rely on the drug manufacturer’s suggestions for titrating the drug, my clinical
experience with common patient responses and reactions, and my observations of
the specific patient’s response and tolerance of each dose level.”
29. I disagree that Dr.
Sadavoy’s clinical experience is better than the evidence-based data that
resulted in the Patented Dose Regimen. Dr. Sadavoy is not conducting
systematic experiments on his patients capable of establishing the degree of
results required to establish the Patented Dose Regimen. When there is no
clinical data on a dosing regimen, then a physician’s clinical experience would
be appropriate. However, once a trial has been conducted on several hundred
patients, the evidence-based results from this trial take precedence over a
physician’s experience.
[39]
Both
Dr. Lin and Dr. Sellers suggest that the exercise of professional judgment is
absent from the treatment protocol outlined in the '950 Patent because no
prudent physician would ever deviate from it. According to Dr. Lin, in
prescribing galantamine a physician’s clinical experience is only ever brought
to bear when there is no available clinical data. This was his explanation for
the presence of several patient-specific cautions found in Janssen’s product
monograph directed to physicians who are treating patients with Reminyl (eg. weight,
co-morbidity, side-effects, drug interactions). According to Dr. Lin these areas
of professional judgment are all addressed to patient populations that had yet to
be studied. Accordingly, it was only for such patients that professional
judgment needed to be applied to dosing decisions. This distinction is perhaps
medically interesting but it does not apply to the '950 Patent which is not
limited to any particular patient group or profile. It claims a monopoly for
the administration of galantamine to patients suffering from Alzheimer’s
disease, whether or not they have been the subject of clinical study.
[40]
Some
parts of Dr. Lin’s affidavit evidence are inconsistent with his own practices
in treating patients with Alzheimer’s disease. Under examination he acknowledged
that the dosing information provided by the product monograph was the “starting
point” and provided “helpful information to guide our practice” [p. 2412]. He
also testified that doctors are “used to following guidelines because they sort
of summarized things for us” [p. 2414].
Dr. Lin went on to acknowledge that Janssen’s product monograph guidance to
physicians to remain flexible in the titration of galantamine applied but only
to a small percentage of patients who had more extreme adverse reactions.
Nonetheless and whatever the numbers may be, Dr. Lin conceded that a physician
is required to be vigilant and to make individual dosing decisions as required
based on a patient’s response to the drug. This is clearly an exercise involving
professional judgment.
[41]
Dr.
Sellers similarly conceded that “[t]here may be individual patients where you
might want to make such an adjustment...” [p. 3878].
[42]
Both
Dr. Sellers and Dr. Lin mischaracterize Dr. Sadavoy’s evidence about the role
of physicians in prescribing medicine. Dr. Sadavoy did not suggest that a
physician would design a dosing regimen mindless to the dosing guidelines of
the manufacturer. What he did say was that, in designing a dosing regimen for
a patient, a treating physician would be alert to many factors including the
product monograph but also to patient profile and response. The fact that some
physicians like Dr. Lin may be more heavily dependant upon the product
monograph for dosing advice does not mean that physicians like Dr. Sadavoy who
may be more attentive to other factors are not practising good medicine. Dr. Sellers’
description of Dr. Sadavoy’s approach as “a form of therapeutic anarchy” is
unfair and it reflects a profound lack of objectivity. It is simply not a
valid argument that, in the face of a manufacturer’s dosing recommendation, the
exercise of all professional judgment by treating physicians goes out the window.
To the extent that Drs. Lin and Sellers suggest otherwise, I reject their
evidence.
[43]
My
overall assessment of Dr. Raskind’s evidence is that he repeatedly sidestepped
the question of individualized care by retreating to the idea that, in the clinical
setting, the therapeutic value of galantamine is almost impossible to assess. While
that may be the case, it does not detract from the common-sense approach
adopted by Dr. Sadavoy, which maintains that adjustments to dosing might still
be justified because of the patient’s profile, or tolerance to the drug. Dr.
Raskind exhibited a troubling dogmatism on this issue. This was coupled with
occasional use of injudicious language in the criticism of Dr. Sadavoy that he
was forced to withdraw under cross-examination.
[44]
I
do not accept Dr. Raskind’s evidence on this issue for another reason. During
Dr. Raskind’s examination, he was confronted with evidence he gave in an
earlier U.S. proceeding that
concerned a patent for galantamine. In the American proceeding, Dr. Raskind
was asked about the ability of a physician to effectively use galantamine in
the absence of precise dosing information in the patent. In testifying on
behalf of Janssen and in support of the assertion of enablement he gave
evidence that a physician would be able to work the invention through the
application of professional judgment.
He also testified that the titration “mantra” that would be brought to bear by
a physician was “start low, go slow” – in other words, through a titration method
generally similar to the process described in the '950 Patent. The specific
exchange in the U.S. proceeding was as follows:
Q. “Question: The dosing from the patent?
Answer, yes. Question: Have you looked at the dosing of the patent? Answer:
Yes, I have. Questions: In your opinion would a person of ordinary skill in
the art be able to administer galantamine in a therapeutically-effective dose
in 1986, a person of ordinary skill in the art” - - let me start the question
over. I think it reiterates about three times.
“Would a person of ordinary
skill in the art in 1986 reading the patent be able to administer galantamine
in a therapeutic dose? Answer, Yes, they would. Question: How would he or
she do so? Answer: Well, they would start at a low dose, as described in the
patent, and then they would gradually titrate the dose upward to a point where
they either saw therapeutic effects or the patient developed adverse effects
which were troublesome enough to stop any further increase of the medication.
Question: And was that technique of titration, was that well-known to a person
of ordinary skill in the art in 1986? Answer: Yes. In geriatric medicine, the
mantra is start low and go slow but go, so we often make a mistake in geriatric
medicine because we are so worried about the side effects starting with a low
dose and forgetting to titrate. That’s one of the things that we constantly
have to keep in mind, you know, it’s always a balance between therapeutic
effects and adverse effects, but you have to remember that you are trying to
get therapeutic effects.
[p. 1997-1999]
[45]
The
above testimony is in marked contrast to what Dr. Raskind said initially under
cross-examination in this proceeding. When asked whether in 1996 there was “a
mantra” in geriatric medicine “start low and go slow” he stated:
I don’t accept that mantra. What do you
mean by “mantra”. What is a mantra?
Then after being impeached by his United
States
testimony Dr. Raskind retreated from his Canadian evidence in the following
exchange:
Q. Now, were you asked those
questions and did you give those answers?
A. I did, and I did.
Q. So going back to the word
“mantra”, this is a word that you used in the answer to a question about
whether a person skilled in the art - - whether the technique of titration was
well-known to a person of ordinary skill in the art in 1986, and you used it in
the context of that answer.
So I'm suggesting to you that
the answer indicates that it was a well-known practice in geriatric medicine to
use this technique of start low and go slow.
Do you agree with me?
A.
I
agree.
Q.
And
specifically in relation to galantamine?
A.
I
agree.
[p. 1999-2000]
[46]
What
is very clear from Dr. Raskind’s United States testimony is that he accepted
the importance of a physician exercising judgment in the administration of
galantamine to ensure that a balance be maintained between therapeutic and
adverse effects. I do not accept his later evidence in this proceeding that
this area of professional judgment was wholly eclipsed by the inventive promise
of the '950 Patent.
[47]
Dr.
Raskind went on to retract his description of Dr. Sadavoy’s approach as “seat
of one’s pants” and he acknowledged, albeit reluctantly, that some professional
judgment was needed in prescribing galantamine, at least for assessing adverse
reactions to the drug [p. 2010].
[48]
Considering
the material and stark nature of the contradictions between Dr. Raskind’s
testimony in the two proceedings involving galantamine, his testimonial
evasiveness in this proceeding and his close association with Janssen, I reject
his testimony on this issue.
[49]
I
have no difficulty with Dr. Gauthier’s testimony concerning method of medical
treatment. Under examination he was willing to concede the obvious and his testimony
did not substantially differ from that provided by Dr. Sadavoy. In the end,
though, Dr. Gauthier did not support Janssen’s position that, in the face of
the clinical study underlying the '950 Patent, no room remained for the
exercise of clinical judgment in the administration of galantamine to Alzheimer’s
patients.
[50]
What
is clear from the evidence is that prudent physicians like Dr. Sadavoy who are
attempting to manage the administration of drugs carrying side effects in the
treatment of geriatric patients do so by considering a number of individualized
factors. Contrary to the affidavit evidence put forward by Janssen’s
witnesses, this does not begin and end with the manufacturer’s dosing advice.
In this context, the titration regimen claimed by Janssen can only be seen as a
recommendation to physicians. Effective patient management may require on-going
individualized surveillance and concomitant dosing adjustments.
[51]
The
argument by Janssen and its witnesses that the '950 Patent is helpful to physicians
and therefore does not interfere with their skill and judgment misses the point
of concern in the authorities. The concern with the patenting of a dosage regimen
is that the physician may be prevented from exercising skill and judgment in
using a known compound for an established purpose absent a license from the
patentee. It is surprising to me that the Janssen witnesses failed to address
the problem of imposing a monopoly over the prescribing practices of the
medical profession. When Dr. Gauthier was asked about this, it was evident
that he had no idea that the enforcement of the '950 Patent might impose
practice limitations on physicians attempting to prescribe galantamine. When
counsel for Mylan pressed Dr. Gauthier on this point, Janssen’s counsel
responded that this was really a question of law that the witness was not
qualified to answer. While there is undoubtedly a legal aspect to this
question, all of Janssen’s witnesses could have been asked to comment on how the
‘950 Patent’s proposed monopoly over a medicinal dosing regimen using an old
drug for an established purpose might affect the ability of physicians to
appropriately treat their patients. It is only within that framework that the question
of whether the '950 Patent covers a method of medical treatment could be fairly
and properly addressed - and here the Janssen witnesses failed to squarely speak
to it.
[52]
In
conclusion, I have no doubt whatsoever that the '950 Patent relevant claims
cover a method of medical treatment. By attempting to monopolize an effective
titration regimen for galantamine, the '950 Patent interferes with the ability
of physicians to exercise their judgment in the administration of generic
versions of the drug. This is because, absent a license from Janssen, any
physician attempting to administer a generic version of galantamine to treat
Alzheimer’s disease by the method claimed by the '950 Patent would infringe. Indeed,
in theory, any physician who attempted to prescribe Reminyl to a patient
without Janssen’s permission in the manner claimed by the '950 Patent would also
infringe.
Should the Ratio in Tennessee Eastman Be Reconsidered in
Light of The Repeal of S. 41 of the Act and Having Regard to the Decision in Amazon.com,
Inc. v. Canada and the Commissioner of
Patents, 2010
FC 1011?
[53]
Janssen
argues that the ratio of Tennessee Eastman, above, should be revisited
in light of the subsequent repeal of s. 41 of the Act – a provision which
Janssen says was the foundation for the decision. As noted above, this is an
argument that has been raised before and consistently rejected in this Court.
Notwithstanding the intervening repeal of s. 41, Tennessee Eastman,
above, remains good law in Canada because the policy concerns it recognized
continue to be valid. Quite apart from the problem of “evergreening”, the
rationale for excluding such patents is that, for ethical and public health
reasons, physicians should not be prevented or restricted from applying their
best skill and judgment for fear of infringing a patent covering a pure form of
medical treatment (as distinct from a vendible medical or pharmaceutical
product). This is a particularly obvious concern in a case like this where the
'950 Patent effectively blocks the use of a known compound (galantamine) for an
established purpose (treating Alzheimer’s disease) using a well-known treatment
methodology (titration). Indeed, the '950 Patent claims a monopoly over a
method of treatment that, in the United States patent proceeding, Dr.
Raskind and Janssen maintained was available and workable by any practicing
physician who wanted use galantamine to treat Alzheimer’s disease.
[54]
This
situation is closely analogous to the circumstances addressed by the United
States Court of Appeals for the Federal Circuit in King Pharmaceuticals,
Inc. v. Eon Labs, Inc., 09-1437 (Fed. Cir. 2010). That case
involved a patent claim over the administration of a known drug (metaxalone)
for a known use (muscle relaxant) and the “unexpected” finding that its
bioavailability was enhanced when taken with food. The prior art had
recommended that the drug be taken with food but only as a means of reducing
nausea. The Court held that a patent was not available for the discovery of a
previously unknown benefit that was inherent in the already known and practised
use of the drug. The Court stated that “[t]o hold otherwise would remove from
the public a method of treating muscle pain that has been performed for
decades”. I appreciate that the principles of patent law in the United
States
are different from those applicable here, but that does not make the Court’s
policy concern any less compelling.
[55]
Janssen
maintains that the recent decision by my colleague Justice Michael Phelan in Amazon.com,
Inc., above, concerning the patentability of business methods ought to
inform my approach to the '950 Patent. While I have no difficulty with Justice
Phelan’s analysis in that case, it does not present a helpful legal analogy.
Indeed, Justice Phelan recognized that there are areas of discovery that, on
grounds of public policy, cannot be monopolized. The extension of patent
protection over some business methodologies involves issues largely of a
commercial nature and does not raise the kinds of public policy concerns that
apply to the provision of medical care to patients whose lives or wellbeing may
be dependent upon it.
III. Conclusion
[56]
The
relevant claims cover a method of medical treatment that cannot be monopolized
under a Canadian patent. Janssen’s application for prohibition is, therefore,
dismissed with costs payable to Mylan. I will accept written submissions from
the parties concerning costs. Mylan will have 30 days to outline its claim to
costs and Janssen will have 15 days to respond. Mylan may reply within a
further 7 days. The primary submissions shall not exceed 10 pages in length
and Mylan’s reply shall not exceed 3 pages.
JUDGMENT
THIS COURT ADJUDGES that this application for prohibition is dismissed with costs
payable to Mylan Pharmaceuticals ULC in an amount to be determined upon further
submissions from the parties.
THIS COURT FURTHER
ADJUDGES that the style of cause in this proceeding is amended to reflect
the Respondent’s name change from Genpharm ULC to Mylan Pharmaceuticals ULC and
the Applicant’s name change from Janssen-Ortho Inc. to Janssen Inc.
“ R. L. Barnes ”
Email this Content