Ex Parte STROH et al

Patent Trial and Appeal Board

Dec 31, 2018

14668268 (P.T.A.B. Dec. 31, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/668,268 03/25/2015
26158 7590 01/03/2019
WOMBLE BOND DICKINSON (US) LLP
ATTN: IP DOCKETING
P.O. BOX 7037
ATLANTA, GA 30357-0037
FIRST NAMED INVENTOR
Christopher STROH
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO.
M88724 1010US.D1
(0002.9)
CONFIRMATION NO.
8165
EXAMINER
GALISTEO GONZALEZ, ANTONIO
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
01/03/2019 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
IPDocketing@wbd-us.com
BostonPatents@wbd-us.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CHRISTOPHER STROH
and ANJA VON HEYDEBRECK
Appeal2017-011373 1
Application 14/668,268
Technology Center 1600
Before RICHARD M. LEBOVITZ, TA WEN CHANG, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to methods for predicting the
likelihood that a patient suffering from KRAS wild type EGFR expressing
metastatic colorectal cancer will respond therapeutically to treatment with an
anti-EGFR antibody. The Examiner rejected the claims under 35 U.S.C.
§ 101 as patent-ineligible because they are directed to a natural law or a
natural phenomenon. Pursuant to 35 U.S.C. § 134, Appellants appeal the
Examiner's determination that the claims are unpatentable. We have
1 The Appeal Brief ("Appeal Br.") identified Merck Patent Gesellschaft mit
beschrankter Haftung as the real party in interest.
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jurisdiction for this appeal under 35 U.S.C. § 6(b). The Examiner's decision
is AFFIRMED.
STATEMENT OF THE CASE
Claims 17-25 stand rejected by the Examiner under 35 U.S.C. § 101
as directed to a judicial exception (i.e., a law of nature, a natural
phenomenon, or an abstract idea). Final Act. 4. The Examiner states that
the claims "are directed to the natural correlation between expression levels
of EREG before and after exposure to the EGFR antibody and
responsiveness to treatment with EGFR antibody" without reciting
"additional elements that amount to significantly more" than the correlation.
Id.
Claim 17, the only independent claim on appeal, is reproduced below.
All Appellants' arguments are focused on this claim. Consequently,
dependent claims 18-25 stand or fall with claim 1 7.
1 7. An in vitro method for predicting the likelihood that a
patient suffering from KRAS wild type EGFR expressing
metastatic colorectal cancer (mCRC) will respond
therapeutically to the treatment with an anti-EGFR antibody,
compnsmg:
(a) measuring by diagnostic means and/ or diagnostic
apparatus in a KRAS wild type EGFR expressing metastatic
colorectal cancer (mCRC) biopsy tissue sample from tumor
tissue or plasma of said patient the expression level of EREG
(b) exposing ex-vivo said tissue sample from tumor or
plasma of said patient to said anti-EGFR antibody,
(c) following exposure to said anti-EGFR antibody,
measuring in said exposed tissue sample of step (b) the
expression level of EREG, and
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( d) calculating the differences in expression levels
measured in steps (b) and ( c ), [2J
wherein an increase in the expression level of EREG
obtained in step ( c) compared to step (a) indicates an increased
likelihood that said patient responds therapeutically to the
treatment with said anti-EGFR antibody, and wherein a
decrease in the expression level of EREG obtained in step ( c)
compared to step (a) indicates a decreased likelihood that said
patient responds therapeutically to the treatment with said anti-
EGFR antibody; and
wherein said anti-EGFR antibody is administered to said
patient upon a finding in step ( d) of an increased likelihood that
said patient responds therapeutically to the treatment with said
anti-EGFR antibody.
CLAIM 17
The claims are directed to predicting the likelihood that a patient
suffering from KRAS wild type EGFR ( epidermal growth factor receptor)
expressing metastatic colorectal cancer (mCRC) will respond therapeutically
to treatment with an anti-EGFR antibody.
KRAS is a gene which makes the k-ras protein, a signaling protein
involved in signaling pathways in human cells. 3 KRAS is involved in the
EGFR signaling cascade. Spec. 14:8-10. Mutated KRAS has been
2 Step ( d) of the claim calculates a difference in expression levels between
steps (b) and ( c ). Expression levels are not measured in step (b ). They are
measured in steps (a) and (c). While the Examiner did not raise an objection
to the claim, we do not understand how a difference in expression levels
between (b) and ( c) can be calculated when expression levels are not
measured in (b ). From the subsequent "wherein" clause of the claim,
Appellants may have intended the claim to calculate the difference between
(a) and (c).
3 See https://ghr.nlm.nih.gov/gene/KRAS (last visited November 16, 2018).
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identified in several different cancers. 4 The claims, however, are drawn to
the class of patients having colorectal cancer expressing the "wild-type" or
normal form of the KRAS gene and EGFR on the cell surface.
Cetuximab is an example of an "anti-EGFR antibody," as claimed,
which had been used prior to the invention to treat cancer tumors which
express EGFR. Spec. 2:25-27.
EGFR expression on cancer cells, however, "has proved to be a
disappointing biomarker for the efficacy of EGFR-targeted treatment in
CRC." Id. at 14:5-7. A cancer tumor may express EGFR on its surface, but
not respond to anti-EGFR antibody therapy. As a result, scientists have
looked for other biomarkers which predict the response to anti-EGFR
antibody therapy. 5 The Specification discloses that the "mutation status of
KRAS" has been found "to be a powerful predictive biomarker for
cetuximab activity in CRC, allowing the exclusion from treatment of a
subpopulation unlikely to derive a significant benefit." Spec. 14: 17-19.
Tumors in which KRAS is wild-type also do not always respond to
cetuximab. Spec. 14:20-23. The Specification states that therefore "there is
a need for the identification and use of further biomarkers that can be used in
addition to the KRAS mutation status to better predict the clinical outcome
of cetuximab treatment in CRC patients." Id. at 14:24--26. The inventors
found that the expression of a biomarker called EREG can be used to predict
the response to anti-EGFR antibodies in patients with colorectal cancer
4 See https://www.cancer.gov/publications/dictionaries/cancer-
terms/def/kras-gene (last visited November 16, 2018).
5 Khambata-Ford et al., 2007, J. Clin. Oneal., 25(22):3230-3237 (listed on
IDS provided by Appellants on Jan. 25, 2016).
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expressing wild-type KRAS. EREG is the abbreviation for epiregulin.
Epiregulin is a ligand for EGFR. 6
Claim 1 7 comprises step (a) of measuring the expression level of
EREG in a biopsy sample from a KRAS wild type EGFR expressing mCRC
patient. The claim further comprises exposing the biopsy sample to anti-
EGFR antibody (step (b)) and then measuring the expression ofEREG (step
( c)) after exposure to the antibody. The differences in EREG expression
levels before and after exposure to the anti-EGFR antibody are determined
in step (d).
Increased EREG expression as compared to expression before
exposure to the antibody "indicates an increased likelihood that said patient
responds therapeutically to the treatment with said anti-EGFR antibody."
App. Br. 13, Claims App.
Decreased EREG expression as compared to expression before
exposure to the antibody "indicates a decreased likelihood that said patient
responds therapeutically to the treatment with said anti-EGFR antibody." Id.
The claim further requires that anti-EGFR antibody is administered
when an increased likelihood of patient therapeutic response is found. Thus,
the claim does not require anti-EGFR antibody administration in all cases in
which EREG levels are measured. Furthermore, it does not require
treatment of the patient with a therapeutic amount of anti-EGFR antibody
even if an increased likelihood of a patient therapeutic response is
determined based on EREG levels.
6 Id. at 3233.
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ISSUE
The Examiner rejected all of the claims in this appeal on the basis of
the claims being directed to a law of nature or natural phenomenon, which
are judicial exceptions to eligibility for patenting under 35 U.S.C. § 101.
Final Act. 4. The Examiner found that the claims "are directed to the ...
correlation between ( 1) expression levels of EREG before and after exposure
to the EGFR antibody" and (2) the cancer's "responsiveness to treatment
with an EGFR antibody," which the Examiner characterized as natural law
or natural phenomenon. Id. The Examiner further found that the claim does
not include additional elements that are significantly more than the judicial
exception. Id. Rather, the Examiner found that the additional steps in the
claims were routine and conventional at the time of the invention. As
evidence of this, the Examiner cited the patent publication by Ford, 7 for its
disclosure of the recited steps of exposing a biological sample ex vivo to an
anti-EGFR antibody and measuring the levels of a biomarker as an indicator
of whether the cancer will respond to the antibody. See Ford 5: 11-2; see
also Final Act. 6-7 (referring to steps (b }-(d) of claim 17).
Appellants argue that "the additional elements amount to a claim as a
whole that adds meaningful limits on the use of the exception (the
correlation and critical thinking step)." Appeal Br. 4. Appellants contend
that the rejected claims "do not foreclose the public from taking advantage
of the correlation between ex-vivo EREG expression levels following
exposure of a KRAS wild-type EGFR expressing CRC or mCRC tumor to
7 Ford et al., WO 2007 /025044 A2; published March 1, 2007 (hereinafter
"Ford").
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an anti-EGFR antibody and the responsiveness to treatment of the tumor
with that anti-EGFR antibody." Id. at 5. Appellants state that the claims
require a "a particular technique for measuring the expression of EREG" and
"a very specific therapy targeted to the individual subpopulation of patients
with KRAS wild-type expressing CRC or mCRC tumors." Id.
DISCUSSION
We have considered Appellants arguments, but are not persuaded that
the Examiner erred in concluding that, under the two-step test of Alice Corp.
Pty. Ltd. v. CLS Bank Int'], 134 S.Ct. 2347 (2014), claim 17 is directed to
patent-ineligible subject matter.
The Alice Court stated that "[i]n Mayo Collaborative Services v.
Prometheus Laboratories, Inc., [132 S.Ct 1289 (2012)] ... we set forth a
framework for distinguishing patents that claim laws of nature, natural
phenomena, and abstract ideas from those that claim patent-eligible
applications of those concepts." Alice Corp., 134 S.Ct. at 2355. The Alice
Court described the Mayo test as follows:
First, we determine whether the claims at issue are directed to
one of those patent-ineligible concepts. If so, we then ask,
"[ w ]hat else is there in the claims before us?" To answer that
question, we consider the elements of each claim both
individually and "as an ordered combination" to determine
whether the additional elements "transform the nature of the
claim" into a patent-eligible application. We have described
step two of this analysis as a search for an "'inventive concept"'
- i.e., an element or combination of elements that is "sufficient
to ensure that the patent in practice amounts to significantly
more than a patent upon the [ineligible concept] itself."
Id. ( citations omitted).
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The Mayo Court applied its test to claims that are similar to the
rejected claims in this appeal. In Mayo, the claimed invention was a
"method of optimizing therapeutic efficacy for treatment of an immune-
mediated gastrointestinal disorder" comprising administering a thiopurine
drug to a patient and then determining the subsequent level of 6-thioguanine
(6-TG). Mayo, 132 S.Ct at 1295. 6-TG was a known metabolite of the drug.
Mayo, Id. at 1295. The claim recited that the level of 6-TG below or above
certain amounts indicated a need to increase or decrease the drug dosage.
Rejected claim 17 is similar to the Mayo claim in that an administered
anti-EGFR antibody modulates EREG production through a natural process
in the patient's biopsied tissue, in the same way that administering the
thiopurine drug naturally elicits the 6-TG metabolite. Claim 17 uses the
level of EREG, as modulated by the antibody drug, to determine whether to
administer the drug to a patient. Thus, the level of a biomarker - 6-TG in
Mayo and EREG in claim 17 - is used similarly to tell the doctor about the
effect of administering a drug to the patient.
For this reason, the Mayo Court's conclusion that the claims at issue
in that case "set forth laws of nature - namely, relationships between
concentrations of certain metabolites in the blood and the likelihood that a
dosage of a thiopurine drug will prove ineffective or cause harm" are
applicable here. Mayo, 132 S.Ct. at 1296. That is, rejected claim 17 sets
forth a law of nature, namely, a natural relationship or natural correlation
between the levels of a biomarker in a patient after anti-EGFR antibody
administration and the "likelihood that said patient responds therapeutically
to the treatment with said anti-EGFR antibody." The fact that the rejected
claims involve ex vivo modulation of biomarker expression outside the body,
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while the Mayo claims involved the in vivo production of the biomarker
inside the body, does not change the analysis because in both cases a
biomarker is being used for the same diagnostic purpose to determine
parameters of drug administration to a patient. For this reason, we conclude
that under the first step of the Alice/Mayo test, claim 1 7 on appeal is directed
to a law of nature or natural phenomenon.
The Mayo Court next turned to the question of"[ w ]hat else is there in
the claims before us?" Mayo, 132 S.Ct. at 1297. The claims in Mayo
included an "administering" step, a "determining" step, and a "wherein"
clause. Id. The Court found that "the 'determining' step tells the doctor" to
determine the level of the relevant metabolites in the blood, through
whatever process the doctor or the laboratory wishes to use, which the Court
determined in their case to be "well-understood, routine, conventional
activity previously engaged in by scientists who work in the field." Id. at
1297-1298. Relying on earlier case law, the Court stated that "conventional
or obvious" activity "is normally not sufficient to transform an unpatentable
law of nature into a patent-eligible application of such a law." Id. at 1298.
The Court considered all three steps as "an ordered combination" and
found that "the combination amounts to nothing significantly more than an
instruction to doctors to apply the applicable laws when treating their
patients." Mayo, 132 S.Ct. at 1298. The Court stated:
The upshot is that the three steps simply tell doctors to gather
data from which they may draw an inference in light of the
correlations. To put the matter more succinctly, the claims
inform a relevant audience about certain laws of nature; any
additional steps consist of well-understood, routine,
conventional activity already engaged in by the scientific
community; and those steps, when viewed as a whole, add
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nothing significant beyond the sum of their parts taken
separately.
Id. at 1298. The Court concluded that "the steps are not sufficient to
transform unpatentable natural correlations into patentable applications of
those regularities." Id.
The rejected claims in this appeal stand on similar footing. Steps (a)
through ( d) of claim 17 involve measuring the amount of the EREG
biomarker in a tissue sample from a patient before and after exposure to the
anti-EGFR antibody and then calculating the difference. These steps are
analogous to the "determining the level of 6-TG" step of the Mayo claim,
because both are directed to measuring a biomarker modulated by a drug for
the same purpose of informing the doctor of the appropriate therapy to
administer to the patient. As in Mayo, the steps "simply tell doctors to
gather data from which they may draw an inference in light of the
correlations," which in this case is whether or not to administer the anti-
EGFR antibody. See Mayo, 132 S.Ct. at 1298. 8
The method by which the EREG levels were determined in the
patient's tissue was found by the Examiner to be the same as those in Ford,
8 We note that claim 17 is not directed to a method of treatment. The claim
preamble does not recite a method of treatment. Moreover, the wherein
clause concerning administration of anti-EGFR after determining the
expression levels of EREG does not recite that a therapeutically effective
amount of anti-EGFR is administered, nor does it recite administration of a
particular amount or dosage range of anti-EGFR to administer. Thus, we do
not find claim 17 to be like the claims found patent eligible in Vanda
Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed.
Cir. 2018).
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providing evidence that the activity was "well-understood, routine,
conventional activity already engaged in by the scientific community."
Mayo, 132 S.Ct. at 1297-1298; see also Final Act. 6-7. Thus, the Examiner
had basis to conclude that they added "nothing significant beyond the sum of
their parts taken separately." Mayo, 132 S.Ct. at 1298.
Appellants contend that "when viewed 'as a combination' it is clear
that the claims are not 'directed to' the natural correlation, but integrate the
correlations into a method of measuring and treatment that adds significantly
more to the natural correlation." Appeal Br. 4. Appellants argue that the
"significantly more" test in Mayo "aims to ensure that patent claims recite
meaningful limitations such that the public is not foreclosed (i.e., preempted)
from taking advantage of what exists in nature." Id. at 5. Appellants state
that the "instant claims do not foreclose the public from taking advantage of
the correlation between ex-vivo EREG expression levels following exposure
of a KRAS wild-type EGFR expressing" colorectal cancer tumor "to an anti-
EGFR antibody and the responsiveness to treatment of the tumor with that
anti-EGFR antibody." Id. The reason, Appellants explain, is that they use a
specific technique to measure the EREG and a narrowly tailored therapy. Id.
at 5---6. Specifically, Appellants refer to the order of the steps involving ex
vivo exposure to the anti-EGFR antibody. Id. at 5. 9
This argument does not persuade us that the Examiner erred.
9 Notably absent from Appellants' argument regarding "a narrowly tailored
therapy" is any assertion that the claims require a therapeutically effective
amount of the specific anti-EGFR antibody be administered or that a
particular dosage range of the specific anti-EGFR antibody be administered
to treat the cancer.
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First, claim 17 does not recite a specific technique to measure EREG
levels in the biopsy sample. Thus, Appellants' argument that the claim
utilizes a particular technique to measure EREG is unavailing.
Second, the order of the steps involving ex vivo exposure to the anti-
EGFR antibody is also not new. The Ford publication cited by the Examiner
shows that one of ordinary skill in the art had used the same steps as claimed
to determine the differences in EREG levels before and after antibody
administration. Ford discloses:
In one aspect, the invention provides a method for predicting
the likelihood a mammal will respond therapeutically to a
method of treating cancer comprising administering an EGFR
modulator, wherein the method comprises: (a) measuring in the
mammal the level of at least one biomarker selected from
epiregulin [EREG] and amphiregulin; (b) exposing a biological
sample from the mammal to the EGFR modulator; ( c) following
the exposing of step (b ), measuring in the biological sample the
level of the at least one biomarker, wherein an increase in the
level of the at least one biomarker measured in step ( c)
compared to the level of the at least one biomarker measured in
step (a) indicates an increased likelihood that the mammal will
respond therapeutically to the method of treating cancer.
Ford 5:11-20 (emphasis added).
Thus, these steps, as in Mayo, "consist of well-understood, routine,
conventional activity already engaged in by the scientific community."
Mayo, 566 U.S. at 79-80.
Despite this explicit disclosure, Appellants contend that the "Office
has not provided any evidence that it was routine in the art to measure the
EREG expression ofEGFR-expressing CRC or mCRC tumors ex-vivo
following exposure to an anti-EGFR antibody in order to determine
responsiveness to treatment with the anti-EGFR antibody." Appeal Br. 9.
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However, the above-reproduced disclosure shows that Ford disclosed
measuring EREG in a cancer following exposure to an EGFR modulator.
Ford also discloses that an EGFR modulator can be an anti-EGFR antibody
("EGFR binding monoclonal antibodies"). Ford 5:7-10. Ford further
discloses that in one embodiment "the EGFR modulator is cetuximab [ an
anti-EGFR antibody] and the cancer is colorectal cancer." Id. at 5:30-31.
Thus, as in rejected claim 17, EREG expression elicited by an anti-EGFR
antibody is disclosed by Ford to determine "increased likelihood that the
mammal will respond therapeutically to the method of treating cancer."
With regard to whether the colorectal cancer expresses EGFR as required by
claim 17, Ford teaches the EGFR expression is detected in colorectal cancer.
Ford 3:15-27.
While Appellants state that "the use of markers for predicting
treatment responsiveness was not actually routinely or conventionally used
by clinicians," (Appeal Br. 9), clearly the same technique as claimed of
exposing a sample from a patient to an EGFR modulator, such as an EGFR
antibody, and then measuring EREG levels, is described in Ford. We do not
see how adopting a technique described in the prior art for determining a
sample's responsiveness to an anti-EGFR antibody and using that
responsiveness (an increase in the levels ofEREG) to determine whether to
administer anti-EGFR to a patient could transform the natural correlation
between EREG levels and responsiveness to a drug into a patent-eligible
application of the natural correlation.
Appellants contend that Ford's technique, described in one patent
publication, is not sufficient to establish it as "conventional activity already
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engaged in by the scientific community," citing guidance materials provided
by the USPTO. Appeal Br. 9--10.
Claim 17 uses Ford's technique in exactly the same way as does Ford,
namely to predict a response to an anti-EGFR antibody by modulating the
production of EREG in a sample from the patient and assessing the
expression levels of the EREG before and after administration of the
antibody. Ford 5: 11-20 (reproduced above). Appellants did not adequately
distinguish the steps in claim 17 from those described by Ford. The point is
that claim 17 has not added anything significantly more than what was
already available in the prior art to one who sought to utilize EREG levels as
an indicator of responsiveness to anti-EGFR antibody. Mayo did not strictly
limit what is "significantly more" to transform an ineligible claim to
anything that is not conventional or routine, but rather considered factual
scenarios where steps that were "obvious" or "already in use" could be
insufficient, as well. Mayo, 132 S.Ct. at 1299. As explained in Mayo, a
process of using a mathematical equation was found to be patent eligible in
Diamond v. Diehr, 450 U.S. 17 5 (1981 ), because it "nowhere suggested that
all these steps, or at least the combination of those steps, were in context
obvious, already in use, or purely conventional." Mayo, 132 S.Ct. at 1299.
We considered Appellants' argument that "the use of gene expression
markers for tumor diagnosis was still gaining acceptance and approval, both
in the medical community and within government agencies at the time the
application was filed," but are not persuaded by it. Appeal Br. 9.
First, Appellants did not direct us to evidence that government
approval is necessary to establish that a technique is conventional. Second,
Appellants have not provided evidence that measuring biomarkers as
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described in Ford had not gained acceptance in the industry as a useful tool
to predict a response to a drug. Indeed, the Specification discloses that one
such marker, HER2, had been used clinically to select patients for antibody
treatment. Spec. 2:3--4. An argument made by counsel in a brief does not
substitute for evidence lacking in the record. Estee Lauder, Inc. v. L 'Orea!,
S.A., 129 F.3d 588, 595 (Fed. Cir. 1997).
Ford specifically teaches using the same EREG biomarker and the
same steps as claimed to determine a cancer's response to an anti-EGFR
antibody. The same gene expression technology which is claimed was
"already in use" to measure levels of a biomarker in cancerous tumors and
thus does not add "significantly more" to the claimed natural correlation.
Mayo, 132 S.Ct. at 1298-1299. Appellants have not provided evidence that
actual clinical use is necessary to establish that the steps in a claim do not
add significantly more to an otherwise ineligible natural law.
Appellants also attempt to distinguish claim 17 on the basis of the
anti-EGFR antibody administration. Appellants argue:
Ford et al. does not demonstrate routine administration of an
anti-EGFR antibody to a subpopulation of CRC or mCRC
tumors having increased expression of EREG following ex-vivo
exposure of the tumor sample to the anti-EGFR antibody. In
fact, Ford et al. does not teach administration of an anti-EGFR
antibody at all. Instead, the reference is directed solely to
predicting the likelihood of response to any EGFR modulator.
Appeal Br. 10.
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Appellants also contend that the market approval in 2004 10 does not
provide an indication for KRAS wild type colorectal tumors and thus cannot
be evidence of routine use. Reply Br. 3. Appellants provided an FDA label
from 2012 in which they assert establishes this fact. Id.
Claim 1 7 does not require that an antibody be administered to a
patient. The claims specifies that the anti-EGFR antibody is administered
"upon a finding in step ( d) of an increased likelihood that said patient
responds therapeutically to the treatment with said anti-EGFR antibody."
The claim, however, does not require administering antibody when the
recited "decreased likelihood" of a response to therapeutic treatment of the
antibody is determined. Appellants' attempt to distinguish the claim based
on antibody administration is not persuasive because the claim as a whole
does not require an antibody to be administered. Consistently, the claim
preamble recites that it is "[ a ]n in vitro method for predicting the likelihood
that a patient suffering from KRAS wild type EGFR expressing metastatic
colorectal cancer (mCRC) will respond therapeutically to the treatment with
an anti-EGFR antibody." The "likelihood" of a response is a reflection of
the natural levels of the EREG biomarker in the specific cancer type and
therefore the claim as a whole is directed to natural law. For this reason,
while we reviewed Appellants' arguments regarding antibody
administration, we do not find it necessary to address them.
10 Appellants do not explain the inconsistency with statement in the
Specification that approval was obtained in 2003.
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Appellants' contention that Ford does not teach anti-EGFR antibody
administration to CRC tumors (Appeal Br. 10) is not persuasive because, as
discussed above, claim 1 7 does not require antibody administration, but
rather is a method of predicting the likelihood of a response to the anti-
EGFR antibody. When certain biomarker parameters are not met, the
antibody is not administered.
Because the claim is neither directed to administration of a therapeutic
amount of antibody nor requires such administration, the issue before us is
whether the claim is directed to a natural law, namely, the natural correlation
between EREG levels and anti-EGFR response and its predictive value in
determining whether to administer the antibody to a patient suffering from
KRAS wild type EGFR expressing mCRC. The additional steps of
determining the levels of the EREG are not significantly more than the
natural law, itself, because these steps merely inform the doctor to apply the
correlation to the patient when determining whether to administer antibody.
The Mayo claim held to be patent ineligible also measured the metabolite
biomarker after exposure to the drug, which along with Ford, show the
conventionality of using measuring biomarker levels after exposure to a drug
to gauge how much of it to administer, if any.
Appellants cite Rapid Litigation Management Ltd and In Vitro, Inc. v.
CellzDirect, Inc. as holding that claims which "merely 'involved' a natural
phenomenon" are patent eligible. Appeal Br. 6. Appellants argue that such
analysis applies here since claim 17 does not just measure a metabolite, but
utilizes a particular procedure with several manipulative steps. Id. at 7.
This argument does not persuade us that the Examiner erred. In
CellzDirect, the claims were directed to a method of producing
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cryopreserved hepatocytes comprising steps of subjecting the cells to density
gradient fractionation, recovering the viable cells, and cryopreserving them.
CellzDirect, 827 F.3d at 1046. In contrast, rejected claim 17 is directed to a
"method for predicting the likelihood that a patient suffering from KRAS
wild type EGFR expressing metastatic colorectal cancer (mCRC) will
respond therapeutically to the treatment with an anti-EGFR antibody"; no
cell based product is produced.
In CellzDirect, the claims were found eligible for a patent because the
"end result of the '929 patent claims is not simply an observation or
detection of the ability of hepatocytes to survive multiple freeze-thaw cycles.
Rather, the claims are directed to a new and useful method of preserving
hepatocyte cells." CellzDirect, 827 F.3d at 1048. In claim 17, the so-called
manipulative steps recited in the claim are carried out to measure the EREG
levels which are used to determine whether to administer the antibody. The
end result is an "observation" about the levels of EREG before and after
antibody exposure. Claim 1 7 does not even require antibody administration
if the expression levels of EREG do not increase in comparison to
expression prior to exposure to the antibody. Rather, the claim is an in vitro
method for predicting the likelihood of a therapeutic response to anti-EGFR
antibody.
For the foregoing reasons, the rejection of claim 17 under 35 U.S.C. §
101 is affirmed. Claims 18-25 were not argued separately and fall with
claim 17.
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Application 14/668,268
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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