Ex Parte Stroh et al

Patent Trial and Appeal Board

Dec 31, 2018

13378711 (P.T.A.B. Dec. 31, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/378,711 12/16/2011
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. CONFIRMATION NO.
M88724 lOlOUS (0001.1) 6941
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
Appeal 2017-011384 1
Application 13/378,711
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 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 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 under 35 U.S.C. § 6(b ). The Examiner's decision is
AFFIRMED.
STATEMENT OF THE CASE
Claims 1-3, 6, 9-15, 22-28, and 46-53 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. 6. The
Examiner states that the claims are "directed to the natural correlation
between expression levels of prognostic genes or gene expression products,
including VA V3 and TGF A[,] and responsiveness to treatment to EGFR
antibody," without reciting "additional elements that amount to significantly
more" than the correlation. Id.
Claim 1, which is illustrative of the claimed subject matter, is
reproduced below (additional indenting added for clarity). All Appellants'
arguments are focused on this claim. Consequently, claims 2, 3, 6, 9-15,
22-28, and 46-53 stand or fall with claim 1.
1. An in vitro method for predicting the likelihood that a
patient suffering from KRAS wild type EGFR expressing
tumor, who is a candidate for treatment with an anti-EGFR
antibody, will respond to the treatment with said anti-EGFR
antibody, the method comprising
measuring the expression level of VA V3 and TGF A in a
KRAS wild type EGFR expressing colorectal cancer (CRC) or
metastatic colorectal cancer (mCRC) tumor tissue sample
obtained from said patient by subjecting a nucleic acid sample
from the tumor sample from the patient to PCR or an RNA or
DNA array,
wherein (i) higher expression of VA V3, compared
to a reference value, indicates that the patient is
likely to respond to said treatment, and (ii) lower
expression of TGF A, compared to a reference
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value, indicates that the patient is likely to respond
to said treatment,
wherein the reference value is the mean expression level
of VA V3 and the mean expression level of TGF A, respectively,
obtained from a reference patient or a patient group, and
wherein said anti-EGFR antibody is administered to said
patient upon a finding that said patient will likely respond to the
treatment with said anti-EGFR antibody, wherein the anti-
EGFR antibody is c225 ( cetuximab ).
CLAIM 1
The claims are directed to predicting the likelihood that a patient
suffering from a KRAS wild type EGFR ( epidermal growth factor receptor)
expressing colorectal cancer will respond 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. 2 K-ras is specifically is
involved in the EGFR signaling cascade. Spec. 14:8-10. Mutated KRAS
has been identified in several different cancers. 3 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 "has proved to be a disappointing
biomarker for the efficacy of EGFR-targeted treatment in CRC." Id. at
2 See https://ghr.nlm.nih.gov/gene/KRAS (last visited November 16, 2018).
3 See https://www.cancer.gov/publications/dictionaries/cancer-
terms/ def/kras-gene (last accessed November 16, 2018).
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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. 4 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 the biomarkers called VA V3 and TGFa can be
used to predict the response to anti-EGFR antibodies in patients with
colorectal cancer expressing wild-type KRAS. Id. at 6: 17-20. VA V3 is the
abbreviation for Vav Guanine Nucleotide Exchange Factor 3 which has a
role in cell signaling pathways. 5 TGFa is a growth factor that is a ligand for
the epidermal growth factor receptor which is encoded by the TGF A gene. 6
The inventors found that VA V3 is predictive for a positive response and
TGFa is predictive for a negative or negligible response. Spec. 6: 17-20.
4 Khambata-Ford et al., 2007, J. Clin. Oneal., 25(22):3230-3237 (listed on
IDS provided by Appellants on Jan. 25, 2016).
5 See https://www.ncbi.nlm.nih.gov/gene/10451 (last accessed November
16, 2018).
6 See https://www.ncbi.nlm.nih.gov/gene/7039 (last accessed November 16,
2018).
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Claim 1 comprises measuring the expression levels of VA V3 and
TGF A in a KRAS wild type EGFR expressing colorectal cancer (CRC) or
metastatic colorectal cancer (mCRC) tumor tissue sample. The levels are
measured using PCR or an RNA or DNA array. As indicated above, (i)
higher expression of VA V3, compared to a reference value, indicates that
the patient is likely to respond to anti-EGFR antibody treatment, and (ii)
lower expression of TGF A, compared to a reference value, indicates that the
patient is likely to respond to the antibody treatment. The reference values
are the mean expression values obtained from a reference patient or patient
group. The antibody is administered to a patient upon finding that the
patient will likely respond to the antibody treatment. Thus, the claim does
not require anti-EGFR antibody administration in all cases in which VA V3
and TGFa 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 response is determined based on TGF and
VA V3 levels. The claim also requires the antibody to be cetuximab.
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. 6. The Examiner found that the claims are directed to the "natural
correlation" between expression levels of VA V2 and TGFA and the cancer's
responsiveness to treatment with an EGFR antibody, which the Examiner
characterized as a natural law or natural phenomenon. Id. The Examiner
further found that the claim does not include additional elements that are
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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
disclosure in the patent publication by Ford. 7 The Examiner found that Ford
describes using genetic biomarkers to determine whether a patient having
colorectal cancer will be responsive to an anti-EGFR antibody. Final Act.
10.
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 VA V3 and TGF A expression levels [ following
exposure] of a KRAS wild-type EGFR expressing CRC or mCRC tumor [to
an anti-EGFR antibody and the] responsiveness to treatment of the tumor
with" that anti-EGFR antibody. Id. at 6. Appellants explain that the claims
require a "a particular technique for measuring the expression of VA V3 and
TGFA" 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.
7 Ford et al., WO 2007 /025044 A2, published March 1, 2007 (hereinafter
"Ford").
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Pty. Ltd. v. CLS Bank Int'], 134 S.Ct. 2347 (2014), claim 1 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).
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.
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.
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Rejected claim 1 is similar to the Mayo claim in that biomarkers
produced by the body through a natural process are used to inform a doctor
about treatment considerations. Specifically, the level of a biomarker is used
to tell the doctor whether to administer cetuximab 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 1 sets forth a law of nature,
namely, a natural relationship or natural correlation between the levels of a
biomarker in a patient expressed by colorectal cancer tissue and the
likelihood that the patient responds to treatment with the anti-EGFR
antibody. The fact that the rejected claims involve measurement of the
biomarkers in a tissue sample outside the body, 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 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
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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. 8
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
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.
8 We note that claim 1 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 VA V3 and TGFa 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 1 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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The rejected claims in this appeal stand on similar footing. The step
of measuring the expression levels of the VA V3 and TGF A biomarkers is
analogous to the "determining the level of 6-TG" step of the Mayo claim,
because both are directed to measuring a biomarker from a biological sample
for the same purpose of informing the doctor of the appropriate therapy to
administer to the patient. As in Mayo, the measuring step "simply tell[ s]
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.
The method by which the VA V3 and TGF A levels were determined in
the patient's tissue was found by the Examiner to be disclosed in Ford,
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. 4, 8. 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. 5. 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 VA V3 and TGF A expression levels following
exposure of a KRAS wild-type EGFR expressing" colorectal cancer tumor
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to an anti-EGFR antibody and the responsiveness to treatment of the tumor
with that anti-EGFR antibody. Id. at 6. The reason, Appellants explain, is
that they use a specific technique to measure the VA V3 and TGF A, namely
"PCR or a DNA or RNA array," and a narrowly tailored therapy. Id. 9
This argument does not persuade us that the Examiner erred.
The claim covers RNA and DNA arrays and PCR for measuring
expression levels of VA V3 and TGFA. Ford discloses that microarray
technologies had been used in the prior art to identify molecular markers to
predict patient outcome. Ford 2:9--27. Ford also describes the use of arrays
in its own work. Id. at 6:25, 10:17-20, 43:4--23. The Specification cites
prior art publications which used microarrays to measure expression of
biomarkers in CRC tumors. Spec. 18: 13-19. Ford also describes using PCR
technology to measure biomarkers. Ford 6:25, 7: 16, 11 :26-30. The
Specification also describes prior art publications using PCR technology to
measure biomarker levels in KRAS wild-type tumors. Spec. 18: 17-18.
Ford also discloses measuring both VA V3 and TGFA expression levels
utilizing commercially available arrays. Id. at 47:1-11, 48--49 (Table 2), 57
(Table 4), 49: 10-11. Thus, the evidence establishes that arrays and PCR, the
same techniques which are claimed, were routinely used prior to the
invention to identify and determine levels of a biomarker in a cancer.
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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Despite this explicit disclosure, Appellants contend that the "Office
has not provided any evidence that it was routine in the art to measure the
VA V3 and TGF A expression of EGFR-expressing CRC or mCRC tumors in
order to determine responsiveness to treatment" with the anti-EGFR
antibody. Appeal Br. 9. However, as discussed above, a preponderance of
the evidence before us shows that it was routine in the art to measure
expression levels ofbiomarkers in cancerous tumors using arrays and PCR.
Appellants have not provided objective evidence to the contrary. Indeed,
Ford actually measured the levels of VA V3 and TGF A in colorectal tumor
tissues using arrays. Ford 48--49 (Table 2), 57 (Table 4), 49: 10-11.
With regard to whether the colorectal cancer expresses EGFR as
required by claim 1, Ford teaches that EGFR expression is detected in
colorectal cancer. Ford 3:15-27. Thus, the technique described by Ford is
applicable to CRC in which EGFR is detected.
Appellants state that "the use of markers for predicting treatment
responsiveness was not actually routinely or conventionally used by
clinicians." Appeal Br. 9. Appellants also contend that Ford's technique,
described in one patent publication, is not sufficient to establish it as
"conventional activity" already engaged in by the scientific community
(Mayo), citing guidance materials provided by the USPTO. Appeal Br. 10-
11.
This argument is not persuasive. Both Ford and the Specification in
their descriptions of the prior art provide evidence that gene expression
levels are routinely utilized in the prior art to identify biomarkers associated
with cancer and to predict drug responses. Spec. 1:31-2:7; Ford 2:5-27,
4:25-27, 4 7: 1-11, 48--49 (Table 2), 57 (Table 4 ), 49: 10-11. This evidence
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has been discussed above. Furthermore, as also discussed above, the
claimed PCR and array techniques for measuring gene expression were also
well-known in the art and Ford actually measured the levels of VA V3 and
TGFA in colorectal tumor tissues using arrays. Ford 48--49 (Table 2), 57
(Table 4), 49:10-11. The point is that claim 1 has not added anything
significantly more than what was already available in the prior art to one
who sought to measure VA V3 and TGF A 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. 175
(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. In sum, claim 1 uses arrays
in exactly the same way as described by Ford, namely to predict a response
to an anti-EGFR antibody by measuring levels of VA V3 and TGF A.
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. 10.
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
described in Ford and the Specification had not gained acceptance in the
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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 array and PCR technologies address the need
for "[ n Jew prognostic and predictive markers [to] facilitate an
individualization of therapy for each patient, []to accurately predict patient
response to treatments, such as small molecule or biological molecule drugs,
in the clinic." Ford 1:23-26; 2:9-27. Thus, the same gene expression
technologies which are claimed were "already in use" to measure levels of
biomarkers in cancerous tumors and thus do 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 1 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 VA V3 and decreased
expression of TGF A. 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. 10-11.
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Appellants 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 does not require that an antibody be administered to a patient.
The claim specifies that the anti-EGFR antibody is administered "upon a
finding" of higher VA V3 expression and lower TGF A expression as
compared to reference values indicating "that said patient will likely respond
to the treatment with said anti-EGFR antibody." The claim, however, does
not require administering antibody when the recited reference values are not
met. 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 tumor ... will
respond to the treatment with said anti-EGFR antibody." The "likelihood"
of a response is a reflection of the natural levels of the VA V3 and TGF A
biomarker in the specific cancer type and therefore the claim as a whole is
directed to a natural law. For this reason, while we reviewed Appellants'
arguments regarding antibody administration, we do not find it necessary to
address them.
10 Appellants don't explain the inconsistency with statement in the
Specification that approval was obtained in 2004.
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Appellants' contention that Ford does not teach anti-EGFR antibody
administration to CRC tumors is not persuasive because, as discussed above,
claim 1 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 VA V3 and TGFA 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 tumor. The
additional step of measuring the levels of the VA V3 and TGF A is not
significantly more than the natural law, itself, because this step merely
informs the doctor to apply the correlation to the patient when determining
whether to administer antibody. The claimed techniques to do so were the
routinely used in the industry to measure biomarkers expressed in tumors as
established by the disclosures in Ford and the Specification.
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 1 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
cryopreserved hepatocytes comprising steps of subjecting the cells to density
gradient fractionation, recovering the viable cells, and cryopreserving them.
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CellzDirect, 827 F.3d at 1046. In contrast, rejected claim 1 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 1, the so-called
manipulative steps recited in the claim are carried out to measure the VA V3
and TGF A levels which are used to determine whether to administer the
antibody. The end result is an "observation" about the levels of the
biomarker. Claim 1 does not even require antibody administration if the
expression levels of VA V3 and TGF A do meet the recited reference values.
Rather, the claim is an in vitro method for predicting the likelihood of a
response to anti-EGFR antibody.
For the foregoing reasons, the rejection of claim 1 under 35 U.S.C. §
101 is affirmed. Claims 2, 3, 6, 9--15, 22-28, and 46-53 were not argued
separately and fall with claim 1.
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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