COMMISSIONER'S DECISION
S.2 Medical Treatment: Claims to a non-medical method of
locating tumors in a subject by means of radiolabeled antibodies
having a high specificity for carcinoembryonic antigens, and
detecting with a photoscanning device the uptake of the antibodies,
were considered to be directed to a diagnostic treatment.
Rejection withdrawn
This decision deals with Applicant's request for review by the Commissioner
of Patents of the Final Action on application 372,233 (Class 167-40) filed
March 3, 1981. It is entitled TUMOR LOCALIZATION AND THERAPY WITH LABELED
ANTIBODIES AND ANTIBODY FRAGMENTS SPECIFIC TO TUMOR-ASSOCIATED MARKERS.
The inventor is Milton D. Goldenberg. The Examines in charge issued a
Final Action on July 3, 1984 refusing to allow the claims of the
application. At the Hearing on June 3, 1987, the Canadian Patent Agent,
Mr. D. Watson represented the Applicant, and Dr. B.D. Saxe, the United
States Patent Attorney, presented technical background of the invention.
After the Hearing, the Agent submitted a letter that referred to certain
Court cases and contained copies of Canadian patents he discussed at the
Hearing, and an affidavit of Dr. Saxe.
The application relates to a method of injecting into a living body certain
types of antibody substances which have a high specific activity and a high
specificity for carcinoembryonic antigens, and that are radiolabeled so
that they are capable of detection by scanning devices, and that are
specific to a variety of tumors, and to treatment thereof.
In refusing all the claims in the Final Action the Examiner said, in part:
. . .
...they are directed to a method which modifies the
metabolism of the human body and is equivalent to a
method of medical treatment which is outside the
definition of invention as given in Section 2 of the
Patent Act and judicially declared unpatentable by
Tennessee Eastman v. Commissioner of Patents (1974)
S.C.R. 111.
Applicant's argument is that the method claimed is not
a medical treatment. This argument is rejected since
the claim defines the step of injecting immunological
reagents into a subject (e.g. human body). It is
obvious that anything that is injected into a human
body will change its metabolism and treats this human
body one way or the other.
In the Court decision of Tennessee Eastman Co. v. The
Commissioner of Patents (62 C.P.R. 117) p. 130, 154,
the judge gave his reasons for holding method of
treatment unpatentable when he said:
Early in the development of patent law in
England it was accepted that a manner of new
manufacture may be a product or may be a
process that can be used in making something
that is, or may be, of commercial value, a
vendible product. Concurrent with that concept
was the principle that a method of treating any
part of the human body does not afford subject
matter for a patent ... (underlining added).
In my view the method here does not lay in the
field of the manual or productive arts nor,
when applied to the human body, does it produce
a result in relation to trade, commerce or
industry, or a result that is essentially (sic)
economic. The adhesive itself may enter into
commerce, and the patent for the process, if
granted, may also be sold and its use licensed
for financial considerations, but it does not
follow that the method and its result are
related to commerce or are essentially economic
in tile sense that those expressions have been
used in patent case judgments: the method lies
essentially in the professional field of
surgery and medical treatment of the human
body, even although it may be applied by per-
sons not in that field. Consequently, it is my
conclusion that in the present state of the
patent law of Canada and the scope of subject
matter for patent, as indicated by authorita-
tive judgments that I have cited, the method is
not an art or process or the improvement of an
apt or process within the meaning of Section
2(d) of the Patent Act.
. . .
In responding to the rejection, the Applicant argues, in part, as follows:
. . .
...it is only patents for medical treatment in the
strict sense that must be excluded. This has led the
Examiner to reject the present claims even though they
are for a diagnostic method which does not involve the
therapeutic treatment of disease.
The Examiner has taken the position that the exclusion
of methods of medical treatment from patentability
under the Tennessee-Eastman decision applies not only
to methods of medical treatment, but methods which are
considered by the Examiner to be "equivalent to a meth-
od of medical treatment". ...There is no legal
authority for this extension and it is submitted
clearly to be contrary to the decision of the Supreme
Court in the Tennessee-Eastman case.
The Examiner has furthermore taken the position that if
anything is injected into a human body, there will be
some change in its metabolism and that there is
therefore a treatment of the human body. Apparently
this principle is to be applied irrespective or whether
the substance injected has a therapeutic effect.
...This position is unsupported by the case law and
contrary to the decision of the Supreme Court in the
Tennessee-Eastman case.
The Examiner has sought to sustain his position by
relying on a quotation from the trial decision of the
Tennessee-Eastman case. ...The quotation is out of
context and seriously misleading as it omits the
previous paragraph making it clear that this is merely
a commentary on the interpretation in England of
wording not found in the Canadian Act.
The Examiner has relied on a quotation from the trial
decision which is not only out of context as indicated
above, but is contrary to the reasoning of the Supreme
Court of Canada in that same decision.... ...The law to
be considered by the Commissioner in relation to
Section 42 of the Patent Act is that of the Supreme
Court and not of some lower court in the same case.
The examiner has taken a position inconsistent with
that of other Examiners.... ...Applicant should not be
refused patent protection where others are being
granted protection for the same type of invention.
. . .
In the decision of the Supreme Court in Tennessee-
Eastman (1973) 8 C.P.R. (2d) 202 at page 209, Pigeon J,
who delivered the judgment of the Court, was reviewing
prior British decisions. He said:
It might be noted that in the latest reported
case brought to our attention, Re Schering
A.G.'s Application, [1971] R.P.C. 337, a case
dealing with a method of contraception by means
of gestagen, the conclusion of the Patents
Appeal Tribunal was at p. 345:
Although, however, on a full consideration
of the matter it seems that patents for
medical treatment in the strict sense must
be excluded under the present Act, the
claims the subject of the application do
not appear to fall within this prohibition
and, on the law as it stands today, they
should, at least at this stage in our judg-
ment, be allowed to proceed. As Swift's
Application (1962) R.P.C. 37 in the Divi-
sional Court of the Queen's Bench Division
clearly established, the Office and the
Patents Appeal Tribunal are at this stage
not deciding the question of "actual
patentability", as the phrase was used in
that case, and unless there is no reason-
able doubt that a manner of manufacture is
not being claimed or the application is
plainly without justification, it is their
duty to allow the claim. The applicants
will then have the opportunity in due
course, if the matter arises, of having
"actual patentability" decided in the High
Court. (Emphasis added).
In this quotation, the emphasis added is by the Supreme
Court to the proposition that it is only patents for
medical treatment in the strict sense that must be
excluded. On this basis, a method of contraception by
means of the administration of gestagen was considered
not to be a method of medical treatment in the strict
sense. The administration of this product would no
doubt have an effect on the metabolism of the body, but
would not involve the therapeutic treatment of disease
and therefore would not be medical treatment in a
strict sense. It is therefore clear that it is only
methods of medical treatment in a strict sense that are
precluded.
. . .
The Applicant refers to Burton-Parsons v. Hewlett Packard (1975) 17 C.P.R.
(2d) 97, and pages 109-110, and argues, in part:
...It was stated "It is clear that such is primarily
and mainly for the taking of electrocardiograms in
routine examinations, not necessarily or mainly in
connection with the treatment of disease." This shows
that the term "medicine" is to be taken as limited to
the treatment of disease and does not include
substances or methods used in diagnostic procedures.
. . .
This reinforces the point made above that in discussing
previous decisions the Supreme Court distinguished
decisions dealing with methods which did not involve
medical treatment in the strict sense. The Examiner is
applying the prohibition not to medical methods in a
strict sense and not even to medical methods in a broad
sense, but even to methods which are not methods of
medical treatment but which in the Examiner's mind are
"equivalent to a method of medical treatment". We
submit that in doing so the Examiner is striking out on
his own in a direction opposite to that of the Supreme
Court.
. . .
The Applicant refers again to the Tennessee-Eastman case as follows:
. . .
... at the bottom of page 208, Pigeon J, who delivered
the judgment of the Court, is commenting on some
British decisions and he says:
"In the second place, what was actually decided
in those cases is not related to a medical or
surgical method. Swift's application dealt
with a method of tenderizing meat by injecting
enzymes into the animal before slaughtering."
This makes it clear that even though substances were
being injected into an animal while it was living which
would have an effect on its metabolism, it was not to
be regarded as a method of medical treatment. It is
well established that methods of medical treatment
include not only human medicine but veterinary medi-
cine. The only distinction therefore is that in
Swift's application, the absence of any therapeutic
effect disqualified the treatment as being a medical
method.
. . . .
The issue before the Board is whether or not the claims are directed to
patentable methods in view of Section 2 of the Patent Act. Claim 1 reads:
A non-medical method for detecting and localizing a
tumor which produces or is associated with a cytoplas-
mic, intracellular or cell-surface marker substance,
without medically treating said tumor, which method
comprises one of the following procedures:
(a) injecting a subject parenterally with an antibody
specific to a cell-surface marker and radiolabeled with
a pharmacologically inert radioisotope capable of
detection using a photoscanning device; concurrently
injecting said subject with normal immunoglobulin from
the same or different species as that used to prepare
said specific antibody, said normal immunoglobulin
being radiolabeled with a different pharmacologically
inert radioisotope from that used to label the specific
antibody and emitting at an energy capable of indepen-
dent detection by said photoscanning device, said
labeled normal immunoglobulin having substantially the
same kinetics of binding, distribution and metabolism
as the labeled specific antibody; and subsequently
scanning the subject with said device, the level of
activity of the labeled normal immunoglobulin being
used to determine the distribution of background
activity due to non-targeted specific antibody, said
background distribution being subtracted from the total
activity of specific antibody, whereby the activity and
the location of substantially only the targeted tumor-
associated antibody is determined; or
(b) injecting a subject parenterally with an antibody
specific to CEA and radiolabeled with a pharmacologic-
ally inert radioisotope capable of detection using a
photoscanning device and subsequently scanning the
subject with said device to determine the location of
the resultant uptake of said labeled antibody by said
tumor; wherein said anti-CEA antibody is a substantial-
ly monospecific antibody having a CEA-specific immuno-
reactivity prior to labeling of at least 70% and a
cross-reactivity to other antigens of less than 15%,
said antibody being radiolabeled to an extent suffi-
cient to reduce its CEA-specific immunoreactivity by
from 5 to 33%; or
(c) injecting a subject parenterally with an antibody
specific to an intracellular marker substance and
radiolabeled with a pharmacologically inert radioiso-
tope capable of detection using a photoscanning device,
and subsequently scanning with said device to detect
and locate the site or sites of uptake of said labeled
antibody by said tumor; or
(d) injecting a subject parenterally with at least one
marker-specific fragment obtained by cleavage of an
antibody specific to a cytoplasmic, intracellular or
cell-surface marker substance and radiolabeled with a
pharmacologically inert radioisotope capable of detec-
tion using a photoscanning device, and subsequently
scanning with said device to detect and locate the site
or sites of uptake of said labeled antibody fragment by
said tumor; or
(e) injecting a subject parenterally With at least two
marker-specific fragments, at least one fragment being
a marker-specific fragment obtained by cleavage of a
first antibody specific to a first tumor associated
marker and at least one other fragment being a
marker-specific fragment obtained by cleavage of a
second antibody specific to a second tumor-associated
marker, each of said at least two fragments being
radiolabeled with a pharmacologically inert
radioisotope capable of detection using a photoscanning
device, and subsequently scanning with said device to
detect and locate the site or sites of uptake of at
least one of said labeled fragments by said at least
one tumor; or
(f) injecting a subject parenterally with a multi-
valent hybrid containing in chemical combination at
least one marker-specific fragment obtained by cleavage
of an antibody specific to a first tumor-associated
marker and at least a second, different marker-specific
fragment obtained by cleavage of an antibody specific
to the same or different tumor-associated marker, said
hybrid being radiolabeled with a pharmacologically
inert radioisotope capable of detection using a photo-
scanning device, and subsequently scanning with said
device to detect and locate the site or sites of uptake
of said labeled hybrid by said at least one type of
tumor.
We look first to the application for an understanding of the invention.
Certain substances are disclosed which are radiolabeled and have low
intensity and are intended to be parenterally injected into bodies solely
to enhance tumor localization and detection. Other kinds of radiolabeled
isotopes chat gather at tumors are described as having an effective
strength that permits them to treat tumors. Several examples are given of
the substances which have been radiolabeled, including a table of
those that may be used for both detection and therapy. Mention is made of
mixtures of radiolabeled antibodies specific to antigens that may enhance
detection, localization, and/or therapy. Specifically it is stated that
radiolabeled marker-specific antibodies or fragments provide tumor
therapy. It is noted that antibodies having a high marker-specific
immunoreactivity will generally be targeted at tumors, and that the
therapeutic aspect of the invention makes use of highly marker-specific
antibodies. Various radionuclides useful in certain concentrations for
therapy are given.
Mr. Watson discusses the significance of the Supreme Court's decision in
the Tennessee-Eastman case. He reasons that its decision establishes the
law in dealing with subject matter similar to that of his client, not the
statements from the lower Court that are interspersed in the Supreme
Court's decision. From our reading of the Tennessee-Eastman case, we
believe the Supreme Court, by commenting on the assessment by the Exchequer
Court, did not express disfavor with those or other statements made by the
lower Court. For example, the Supreme Court, 8 C.P.R. 2(d) page 204,
includes a passage by Kerr J. given in the lower Court which reads, in
part, as follows:
...The method lies essentially in the professional
field of surgery and medical treatment of the human
buds, even although it may be applied at times by
persons not in that field. Consequently, it is my
conclusion that in the present state of the patent law
of Canada and the scope of subject-matter for patent,
as indicated by authoritative judgments that I have
cited, the method is not an art or process or an
improvement of an art or process within the meaning of
s. 2(d) of the Patent Act.
We compare the above opinion to that expressed by Pigeon J. of the Supreme
Court on page 207 as follows:
Having come to the conclusion that methods of medical
treatment are not contemplated in the definition of
"invention" as a kind of "process", the same must, on
the same basis, be true of a method of surgical
treatment.
We see no diversion of opinions in the above passages. The findings by
both Courts is that medical and surgical treatments do not merit patent
protection under Section 2 of the Act which reads:
"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;
Of particular interest as to how the Tennessee-Eastman case is viewed by
the Federal Court is the recent case, Imperial Chemical Industries Ltd. c.
Commissioner of Patents (1986) 9 C.P.R. (3d) 289, hereinafter ICI. On page
296 of ICI, Heald J. set out his understanding of Mr. Justice Pigeon's
pronouncement, as follows:
Coming now to the decision of the Supreme Court of
Canada, Mr. Justice Pigeon delivered the Court's
decision. He commences his reasons by setting out the
agreed statement of facts and issues. At page 204 of
the report, he reproduces, with approval, that portion
of the reasons of Kerr J. set out supra. It is true
that he does discuss the impact of Section 41,
presumably since that case was a subsection 41(1)
case. However, after that discussion, at page 207 of
the report, he states:
Having some to the conclusion that methods of
medical treatment are not contemplated in the
definition of "invention" as a kind of "pro-
cess", the same must, on the same basis, be
true of a method of surgical treatment.
In my opinion, this is a clear and unequivocal state-
ment that '...methods of medical treatment are not
contemplated in the definition of "invention" as a kind
of "process...". That was the sole issue before the
Court and it is here answered in unmistakeable and
unambiguous language. Accordingly, in my view, the
force of that pronouncement cannot be restricted merely
to factual situations where subsection 41(1) of the Act
applies. It follows, therefore, that the Commissioner
did not err in considering himself bound by the ratio
of Tennessee Eastman. (our emphasis)
Mr. Watson discusses other passages in the Tennessee Eastman case. Among
them is that taken from the British decision in Re Schering, namely,
"patents for medical treatment in the strict sense must be excluded", to
which the Supreme Court added particular emphasis. He reasons that Court's
assessment of Schering is that the administration of gestagen, an agent for
contraception, although having an effect on body metabolism, would not be a
therapeutic treatment of disease, and therefore would not be medical
treatment in a strict sense.
Mr. Watson compares the Supreme Court's comments in the Tennessee Eastman
case about Swift's application, to the Applicant's method of localizing
tumors, by referring to the following passage from page 208:
In the second place, what was actually decided in those
cases is not related to a medical or surgical method.
Swift's application dealt with a method of tenderizing
meat by injecting enzymes into the animal before
slaughtering.
Mr. Watson argues the Applicant's claimed method of localizing tumors is
not directed to a medical treatment, just as Swift's method of injecting
enzymes was held not to be directed to a medical treatment. He reasons
that the Tennessee Eastman case indicates that in the absence of a
therapeutic effect, the Applicant's method should not be considered a
medical method.
We understand from the application that antibodies labeled with
radioisotopes are injected into a body for the purpose of attaching
themselves to antigens that are known to exist at a tumor site. At the
discretion of the physician, the radioactive material injected may light up
a tumor for detection by means of a photoscanning device, or, may react on
the suspected tumor to reduce its size. Mr. Watson says the rejected
claims present only a detection method whereas the claims cancelled by
amendment B, such as original claim 69, are directed to therapy.
The Applicant discusses Burton-Parsons, supra, and its conclusion that the
purpose of the conductive cream was "primarily and mainly for the taking of
electrocardiograms in routine examinations, not necessarily or mainly in
connection with treatment of disease".
Dr. Saxe thinks the rejected claims are directed to diagnostic methods and
do not relate any treatment of a patient. He explains the antibody of the
invention has two features, one, it binds to a specific antigen, two, it
carries a special targeting vehicle, namely, a radioisotope. Such
antigens, he continues, are known to be located on the surface of tumors in
the body. The injected antibody circulates through the body, and on
finding an antigen, binds thereto. The signal from the radioisotope
enables location by as exterior scanner. He considers the small amount of
gamma radiation from the imaging isotopes has no therapeutic effect, and
that if isotopes of iodine are used, their dosage would be small, thus
providing only incidental beta radiation with negligible therapeutic
action. The Applicant's method, he relates, is done as a prelude to
treatment such as surgery. He says the method locates tumors that cannot
be located by X-ray or Cat-Scans, for example these masked by organs, or,
in the case where metastisis occurs, the method permits identification of
the small tumors that have spread from the main tumor. He notes this is
something that was not possible before the advent of nuclear medicine. He
adds that, if the antibody finds no antigen, it is excreted and no imaging
occurs.
When Todine 131 is used as a label for imaging body portions other then the
thyroid, Dr. Saxe explains that something is added to the body to prevent
takeup by the thyroid of iodine 131. A solution for this purpose is
identified in the application as Lugol's solution. He notes the
determination of the particular amount of each labeling agent is done by
nuclear medicine physicians in clinical tests of various diagnostic
agents. In this way, they classify the stability of the antibody, the
stability of the label to stay on the antigen surface and not on other
areas, the rate of disposal of the label by the human body so that proper
imaging occurs, and the selective take up of the antibody during
circulation and the effect of the label on tissue. He says the labeled
antibodies are then usually administered by the surgical oncology or
nuclear medicine departments of a hospital, since diagnosis and therapy may
be involved.
Mr. Watson refers to the Commissioner's Decision on H. Brilliant's
application number 880,719 published April 16, 1974 in the Patent Office
Record. He notes the subject matter involved diagnostic techniques, and
was accepted by the Commissioner (Patent 944,693 issued on April 2, 1974 to
Brilliant). He likens the Applicant's method to that of the above
application which was found to be controllable and reproducible. Dr. Saxe
points out in the Applicant's case that clinical trials establish the type
and amount of the radiolabeled antibody that should be administered, based
on the type of tumor. In this manner, Dr. Saxe says in his affidavit that
the Applicant's results are controllable and reproducible, and that the
non-invasive nature of the Applicant's method produces only diagnostic
information.
Mr. Watson refers to the following Canadian patents, from the viewpoint
they protect diagnostic methods. Patent 944,693 (to Brilliant, above)
relates to applying fluorescent dyes on teeth, and Patent 1,087,981 relates
to applying colored dyes on teeth, both to make visible any disease causing
matter. Patent 1,071,102 relates a method for introducing polymeric coated
particles having a radioactive ion exchange core into an animal's
circulatory system and after sacrifice determining the location of the
particles. Patent 1,075,154 describes a method of detecting tumors by
applying a heat sensitive liquid to the skin, heating the area, and
observing for color changes. Patent 1,075,601 presents a method of
determining size and location of myocardial infarction by injecting into
the blood stream a radiolabeled antibody and measuring emissions at the
tissues where uptake occurs. Patent 1,171,952 relates to tumor detection
using ultrasonic images to detect concentrations of circulated microbubbles
in a suspected tumor area. Mr. Watson feels that where there is no
therapeutic effect, an applicant is entitled to a patent.
The examiner considers that Applicant's method of injecting a patient with
a substance having a radioactive material is part of an overall treatment
performed under medical supervision. He reasons that a nuclear medicine
physician by using the Applicant's method is engaged in a medical treatment
of a patient and that only part of the regimen is to find where a tumor is,
the remaining part being to prescribe the amount and type of radioisotope
to be carried by the antibody once localization is determined. He refers
to Imperial Chemical Industries Ltd. v. Commissioner of Patents C.P.R.
(1967) Vol. 51 102 at 107, hereinafter ICI 1967, as follows:
"Halothane" is not a medical drug or agent that cures
per se, but instead is a medical drug or agent used in
medicine in the treatment of patients and is an
integral part of surgical therapy of disease, a part of
a therapeutic regime.
He notes that halothane as an anaesthetic is not a diagnostic agent but as
used is part of a medical treatment in that it produces insensitivity
during treatment. For this reason, he regards the passage above as
indicative that the Applicant's method forms part of the overall treatment
of a patient.
We recall that Dr. Saxe discussed the significance of imaging dosages in
the diagnostic steps in obtaining an identification of radiolabeled
antibodies lodged in parts of a human body. He stresses that such dosages
are known in advance by established testing to ensure that they behave in a
predictable manner. From such available information his view is that no
beneficial therapeutic results would be obtained. In this way, he points
out, the imaging dose is designed to provide only a measurable signal in a
diagnostic procedure. He argues that the term non medical treatment in the
Applicant's claims points to the fact that an imaging dosage is all that is
being defined.
Dr. Saxe says that the Applicant's method is clearly on the side of
diagnosis, even though the diagnostic substance is an injectable. He
suggests that to conclude that merely because something is injected into a
patient's body and that therefore a therapeutic treatment results, is to
blur the reasoning that should be brought to bear on the Applicant's case.
He points out that the rejected claims are directed only to finding
locations of tumors.
We believe that the Supreme court in the Tennessee Eastman case emphasized,
by quoting from the Schering case, that patents for medical treatment in
the strict sense must be excluded under the Patent Act.
In determining whether or not the Applicant's method is a diagnostic method
and therefore patentable, we are unable to find, in reviewing the claims as
they pertain to a non medical treatment using pharmacologically inert
substances within the context of the application, that they are directed to
more than a diagnostic treatment.
In summary, we think the rejected claims may well be directed to a
diagnostic treatment. We recommend therefore that the refusal of the
claims be withdrawn for being directed to non patentable subject matter in
view of Section 2 of the Patent Act.
M.G. Brown S.D. Kot
Acting Chairman Member
Patent Appeal Board
I leave reviewed the findings and the recommendation of the Patent Appeal
Board. Accordingly, I withdraw the refusal to grant a patent containing
the claims of this application, and I remand the application for
prosecution consistent with the recommendation.
J.H.A. Gari‚py
Commissioner of Patents
dated at Hull, Quebec
this 13 day of May 1988