Ex Parte Roder et al

Patent Trial and Appeal Board

May 26, 2015

13373336 (P.T.A.B. May. 26, 2015)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/373,336 11/11/2011 Heinrich Roder 08-775-CON4 9710
20306 7590 05/26/2015
MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP
300 S. WACKER DRIVE
32ND FLOOR
CHICAGO, IL 60606
EXAMINER
XU, XIAOYUN
ART UNIT PAPER NUMBER
1797
MAIL DATE DELIVERY MODE
05/26/2015 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte HEINRICH RODER, MAXIM TSYPIN, and
JULIA GRIGORIEVA
1

____________

Appeal 2013-006884
Application 13/373,336
Technology Center 1700
____________

Before KAREN M. HASTINGS, GEORGE C. BEST, and
WESLEY B. DERRICK, Administrative Patent Judges.

DERRICK, Administrative Patent Judge.

DECISION ON APPEAL
Appellants appeal under 35 U.S.C. § 134(a) from the Examiner’s
decision rejecting claims 6–8 and 10–12 under 35 U.S.C. § 103(a) as
unpatentable over Zhao et al. (US 2005/0048547 A1, published March 3,
2005) (“Zhao”) in view of Mazet et al. (Background Removal Spectra by
Designing and Minimizing a Non-Quadratic Cost Function, 76
CHEMOMETRICS & INTELLIGENT LAB. SYS. 121–133 (2005)) (“Mazet”) and
Xiao et al. (Serum Proteomic Profiles Suggest Celeocoxib-Modulated
Targets and Response Predictors, 64 CANCER RES. 2904–2909 (2004))
(“Xiao”) and claim 9 under 35 U.S.C. § 103(a) as unpatentable over Zhao in
view of Mazet, Xiao, and Lynch et al. (Activating Mutations in the

1
Appellants identify Biodesix, Inc. as the Real Party in Interest. App. Br. 1.
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Epidermal Growth Factor Receptor Underlying Responsiveness of Non-
Small-Cell Lung Cancer to Gefitinib, 350 NEW ENG. J. MED. 2129–2139
(2004)) (“Lynch”). We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM-IN-PART.
STATEMENT OF CASE
Appellants’ invention relates to a process of analyzing a test mass
spectrum including comparison to class mass spectra and determining
whether a patient with a disease or disorder will be responsive to a drug
based on the relation of the test mass spectrum to class mass spectra. Spec.
Abstract.
Independent claim 6 and dependent claim 9 are illustrative of the
claimed invention:
6. A method of analyzing a mass spectrum, comprising the
steps of:
a) obtaining a mass spectrum of a blood-based
sample from a human patient;
b) subtracting background contained in the mass
spectrum to produce a background subtracted spectrum,
wherein the subtracting step comprises (i) estimating, in a
moving window comprising a range of m/z values in said mass
spectrum using robust asymmetric estimates, non-constant
levels of background and (ii) subtracting the estimated
background from the mass spectrum;
c) normalizing the background subtracted spectrum;
d) aligning the normalized, background subtracted
spectrum to a predefined mass scale, the predefined mass scale
associated with common peaks or peak clusters identified from
a group of other mass spectra from other blood-based samples;
and
e) classifying the mass spectrum using a training set
comprising class-labeled mass spectra of blood-based samples
of other human patients.
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9. The method of claim 6, wherein the mass spectrum is
obtained from a non-small cell lung cancer patient in advance
of treatment with an epidermal growth factor receptor targeting
drug and wherein the method further comprise the step of
predicting whether the patient is likely to obtain benefit from a
drug targeting an epidermal growth factor receptor pathway
based on the results of the classification step.

Appellants argue the patentability of claims subject to the rejection of
claims 6–8 and 10–12 on the basis of independent claim 6 (with separate
arguments as to dependent claims 10–12) and the patentability of claim 9 on
the basis of its dependence from claim 6 and limitations from claim 9. We
decide this appeal based on claims 6 and 9–12. 37 C.F.R. § 41.37(c)(1)(iv).
OPINION
We have thoroughly reviewed the Examiner’s rejections in light of
Appellants’ arguments that the Examiner has erred. We have considered in
this Decision only those arguments Appellants actually raised in the Briefs.
Any arguments that Appellants did not make in other than a conclusory
fashion in the Briefs are waived. Except as provided below, we find
Appellants’ arguments unpersuasive and adopt as our own the findings and
conclusions set forth in the Examiner’s Answer. We add the following for
emphasis.

Claims 6–8 and 10–12
In addressing the Examiner’s rejection of independent claim 6,
Appellants focus on step d), arguing that the references to not teach or
suggest aligning the recited spectrum to a “predefined mass scale” as recited
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in the claim because the “predefined mass scale” does not encompass peaks
from calibrant (a specialized compound of known mass) added to sample
prior to obtaining the mass spectrum (App. Br. 4–10; Reply Br. 3–6).
Appellants’ principal argument is that the Examiner has erred in
construing the claims to encompass using peaks from calibrants added to
samples as the “predefined mass scale” for alignment. App. Br. 5–6.
Appellants ground their argument on the Specification describing that the
Applicants appreciated it is sometimes difficult to add calibrants to samples.
Furthermore, Applicants knew that it often was not desirable or necessary to
do so because it is possible to use common peaks or peak clusters found in
groups of other spectra for spectral alignment at the time of classification of
the sample. Id. (citing Spec. 24–25; Figs. 8A, 8B); see also Reply Br. 3–6.
Appellants argue that the Specification distinguishes spectral alignment
using common peaks or peak clusters from use of added calibrants (Reply
Br. 4–5) and “in essence disclaims the use of calibrants” (id. at 5).
Appellants further argue that that none of the cited references teach or
suggest step d) as properly understood in light of the Specification. App. Br.
6–10; Reply Br. 2.
We find Appellants’ arguments unpersuasive of reversible error both
because we do not find the Examiner erred in construing the claims to
encompass use of added calibrants (Ans. 8) and because we do not find
Appellants’ arguments persuasive the Examiner erred in concluding one of
ordinary skill in the art would find it obvious to use peaks or peak clusters
common to the spectra to align spectra for classification, even in the absence
of added calibrants (id. at 10–11).
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We first address the Examiner’s interpretation of the claim. “During
. . . examination, the PTO must give claims their broadest reasonable
construction consistent with the specification.” In re Suitco Surface, Inc.,
603 F.3d 1255, 1259 (Fed. Cir. 2010). “Construing claims broadly during
prosecution is not unfair to the applicant (or, in this case, the patentee),
because the applicant has the opportunity to amend the claims to obtain
more precise claim coverage.” In re Am. Acad. of Sci. Tech. Ctr, 367 F.3d
1359, 1364 (Fed. Cir. 2004) (appeal from reexamination proceeding).
Having carefully considered the Specification and Appellants’
arguments, we find no clear requirement that added calibrant is excluded.
See, e.g., Spec. 23–25 (cited by App. Br. 5–6; Reply Br. 3–6). Our
reviewing Court has “repeatedly held that the fact that the specification
describes only a single embodiment, standing alone, is insufficient to limit
otherwise broad claim language.” Howmedica Osteonics Corp. v. Wright
Med. Tech., Inc., 540 F.3d 1337, 1345 (Fed. Cir. 2008) (declining to impute
a limitation into a disputed claim term in the absence of a clear requirement
in the specification, even where “every disclosure of [the disputed term] in
the specification shows [the alleged limitation]”); see also Phillips v. AWH
Corp., 415 F.3d 1303, 1323 (Fed. Cir. 2005) (“[W]e have expressly rejected
the contention that if a patent describes only a single embodiment, the claims
of the patent must be construed as being limited to that embodiment.”).
As to the Examiner’s conclusion that one of ordinary skill in the art
would find it obvious to use common peaks or peak clusters in aligning
spectra for classification, we find no persuasive merit to Appellants’
arguments—even under Appellants’ proffered interpretation of “predefined
mass scale”—that the Examiner erred reversibly. The Examiner finds, inter
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alia, that “known common peaks of spectra can be peaks from sample itself”
(Ans. 8) and that Xiao teaches aligning common peaks or peak clusters of
mass spectra used from blood-based samples to align spectra (id. at 10, “the
new spectrum must align with the training set, using the predefined common
peak or peak clusters identified in the training set as predefined mass scale.”)
In other words, the Examiner finds that one of ordinary skill in the art,
knowing peaks and peak clusters in spectra from can be used to align the
spectra, would have found it obvious at the time of the invention to have
aligned spectra as set forth in step d) of claim 6.
Appellants’ arguments that the references do not teach spectral
alignment without an added calibrant in classifying a given test spectrum
focus on the individual references, first Zhao—arguing it uses added
calibrants (App. Br. 6–8)—and then Xiao—arguing it does not disclose
aligning a given test spectrum, even though Appellants concede training sets
are aligned with one another using common peaks and peak clusters using
spectral alignment (id. at 8–10). Because these arguments fail to address the
combination of teachings actually relied upon by the Examiner, we do not
find them persuasive of reversible error. Further, Appellants’ arguments do
not “take account of the inferences and creative steps that a person of
ordinary skill in the art would employ.” KSR Int’l Co. v. Teleflex Inc., 550
U.S. 398, 418 (2007); see also id. at 421 (“A person of ordinary skill is also
a person of ordinary creativity, not an automaton.”).
For the reasons discussed above, therefore, we affirm the rejection of
claim 6 as obvious over the combination of Zhao, Mazet, and Xiao. Finding
they stand or fall with claim 6 because they were not separately argued, we
also affirm the rejection of claims 7 and 8.
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In addressing the Examiner’s rejection of claim 10 (Ans. 6, 11–12;
Final Action 4), Appellants argue that the Examiner erred in rejecting
claim 10 because (a) ¶¶ 77 and 78 of Zhao relate to spectral peaks for use as
biomarkers, (b) there is no suggestion of their use for spectral alignment
(App. Br. 14; Reply Br. 9–10), and (c) neither the cited portions of Zhao nor
Xiao suggest peaks or clusters be selected that “are close in m/z position and
well separated from each other in the m/z axis” as a basis for spectral
alignment (App. Br. 14–15).
Appellants’ arguments are not persuasive of reversible error where the
Examiner finds, inter alia, that Xiao teaches peaks and peak clusters are
used to align spectra (Ans. 10)—also conceded by Appellants with regard to
classifier development (App. Br. 9)—and Appellants do not dispute that the
disclosed peaks, “biomarkers” in Zhao, include those that are both close in
m/z position and well separated from each other in m/z axis (id. at 14–15;
Reply Br. 9–10).
Accordingly, we affirm the rejection of claim 10 as obvious over the
combination of Zhao, Mazet, and Xiao.
In addressing the Examiner’s rejection of claims 11 and 12 (Ans. 6–7,
12; Final Action 4), Appellants separately argue that the Examiner erred in
rejecting claims 11 and 12 because, inter alia, the peak clusters recited in the
claims are not suggested by Xiao’s disclosure of a peak at m/z position
16,961.4 (App. Br. 14–17; Reply Br. 10–11).
On the record before us, we are unable to sustain the Examiner’s
rejection of claims 11 and 12. The Examiner bears the initial burden of
establishing a prima facie case of obviousness. In re Oetiker, 977 F.2d
1443, 1445 (Fed. Cir. 1992). Because the Examiner has not adequately
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explained how the peak or peak cluster at m/z position 16,961.4 (Ans. 6–7,
12) meets the recited m/z position limitations or renders the recited m/z
positions obvious (Final Act. 4), we find the Examiner has failed to establish
a prima facie case.
Accordingly, we reverse the rejection of claims 11 and 12 as obvious
over the combination of Zhao, Mazet, and Xiao.

Claim 9
The Examiner relies on the combined teachings of Zhao, Mazet, Xiao,
and Lynch in the rejection of claim 9. The Examiner relies on Zhao for
teaching the use of biomarkers detected by mass spectrometry to classify the
disease state of cancer patients for more effective treatment. Ans. 7.
The Examiner finds Xiao teaches use of mass spectra of serum
samples from colorectal cancer patients can be used to predict whether a
patient is likely to benefit from treatment with the drug celecoxib. Id. The
Examiner finds Xiao uses mass spectra from subjects who did not respond to
the drug (nonresponders) and those who responded strongly to identify a
peak cluster (m/z 16,961.4) present in nonresponders and absent in strong
responders. Id. (citing Xiao Fig. 3A; 2906, ¶ 4; 2907, last line to 2908, ¶ 1).
The Examiner finds Lynch teaches using biomarkers—specifically,
mutations in EGFR—to identify a non-small-cell lung cancer patient as
being either likely or unlikely to benefit from treatment with a drug targeting
an EGFR pathway. Id. (citing Lynch 2129, ¶¶ 3, 4). The biomarkers in
Lynch were “[s]omatic mutations . . . in the tyrosine kinase domain of the
EGFR gene” (Lynch, ¶ 3) and were “correlate[d] with clinical
responsiveness to the tyrosine kinase inhibitor gefitinib” (id. ¶ 4).
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The Examiner reasons that mutations of genes create differences that a
skilled artisan would expect to be reflected in the serum proteomic profile of
serum samples from patients with different genetic variants of non-small-cell
lung cancer because Xiao found differences in the serum proteomic profile
of serum samples from colorectal cancer patients. Ans. 8. Based on this, the
Examiner concludes that
at [the] time of the invention, a skilled artesian [sic] would have
been motivated to use Xiao’s method to analyze proteomic
profile (peak cluster) in mass spectra of serum sample from a
non-small cell lung cancer patient to predict whether the patient
is likely to obtain benefit from the treatment of a drug with [a]
reasonable expectation of success.

Id. The Examiner emphasizes that the criteria for the relied on basis of the
rejection—the proffered modification of Xiao—is a “reasonable expectation
of success, not guaranteed success.” Id.; see also Final Action 5, 6.
On the record before us, we find the Examiner’s findings, reasoning,
and conclusions well-founded.
Appellants argue that the method of claim 9 is not obvious from the
combination of Zhao, Mazet, Xiao, and Lynch because none of the
references suggest the claimed approach is possible, that there is no
reasonable expectation of success, and because Lynch, teaching testing for
mutations in the EGFR gene in tumor tissue samples, teaches away from the
claimed method. App. Br. 11–14; Reply Br. 6–9. We address each
argument in turn.
Appellants’ arguments that the references fail to suggest the claimed
approach is possible are grounded on two separate lines of argument: first,
that mass spectrometry is unable to detect genetic mutations; and second,
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that the Examiner has not shown genetic mutations result in serum protein
components leading to different proteomic profiles.
As to mass spectrometry not detecting genetic mutations—Appellants
argue Lynch “is directed to discovery of genetic mutations in NSCLC cells
which may be responsible for clinical responsiveness to the EGFR tyrosine
kinase inhibitor gefitinib . . . [but] requires sequencing the EGFR gene from
NSCLC tumor tissue samples and determining whether certain mutations are
present.” App. Br. 12. On this basis, Appellants argue that even if
combined, mass spectrometry of blood-derived samples (or even tissue-
based samples) would not detect Lynch’s genetic mutations. Id. at 13.
In the Reply Brief, Appellants further argue that “Xiao does not
suggest, let alone demonstrate, that mutations within a particular gene can be
detected from mass spectroscopy.” Reply Br. 7. And in regard to the
Examiner’s finding that “Xiao has shown that the gene difference is
reflected in the serum proteomic profile of a serum sample from a colorectal
cancer patient” (Ans. 8), Appellants argue, inter alia, that “genetic mutations
are not detectable by mass spectrometry of blood-derived samples . . .
Nucleotide sequence information indicative of ‘normal’ cells vs. cells with
the mutations described in Lynch et al. is not preserved in mass
spectroscopy” (Reply Br. 8). In regard to Lynch, “[t]hese genetic mutations
per se are not detectable by mass spectroscopy.” Id. at 7.
We find these arguments wholly without persuasive merit because
they do not address the basis of the Examiner’s rejection, namely, that a
skilled artisan would expect significant genetic differences (as opposed to
silent mutations) to be reflected in differences in the proteins present in
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serum samples from patients with different genetic variants of non-small-cell
lung cancer.
As to the whether the identified genetic mutations result in serum
protein components leading to different proteomic profiles—Appellants
argue that the Examiner erred in finding “the mutation of EGFR gene [from
Lynch et al.] would reflect in the changes of a biomarker profile of a serum
sample” because “[n]o factual basis for this statement is provided in the
office action.” App. Br. 12 (citing In re Zurko, 258 F.3d 1379 (Fed. Cir.
2001).
In the Reply Brief, Appellants’ further argue that the Examiner has
erred in finding “that ‘Xiao has shown that the gene difference is reflected in
the serum proteomic profile of a serum sample from a colorectal cancer
patient’.” Reply Br. 8. Appellants argue that “Xiao is describing detection
of changes due to the drug interactions in the body, not genetic mutations.”
Id.; see also id. at 7 (“The explicit assumption made in Xiao . . . is that
celecoxib-modulated changes in the body may be reflected in the alteration
of the serum proteomic profile.”).
We find Appellants’ arguments unpersuasive of reversible error
because, as the Examiner found, Xiao demonstrates differences in mass
spectra obtained prior to treatment with the drug reflected differences in the
response to the drug (Ans. 7; citing Xiao Fig. 3A; 2906, ¶ 4; 2907, last line
to 2908, ¶ 1), not merely, as Appellants argue, that treatment results in
changes in the serum profile (e.g., Xiao 2904, col. 2, ¶ 2). Accordingly, on
the record before us, we are not persuaded that the Examiner’s findings are
not supported by substantial evidence. In re Zurko, 258 F.3d at 1384
(“Substantial evidence is ‘such relevant evidence as a reasonable mind might
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accept as adequate to support a conclusion’ . . . and it is generally considered
to be more deferential than the clearly erroneous standard of review.”).
Appellants argue that Xiao is directed to different patients and a
different class of drug, namely, to prediction of colorectal cancer patient
benefit from the COX-2 inhibitor celecoxib (App. Br. 13) and that “the
references do not provide a reasonable expectation of success” where:
Neither Lynch nor Xiao suggest that such genetic mutations
would be reflected in a serum profile, or that mass spectral
analysis of a serum would uncover peaks that could be used for
prediction of EGFR targeting drugs. The references do not
suggest that such peaks exist, or could be discovered.

(Reply Br. 7).
Appellants’ arguments are not convincing of reversible error because
they are both grounded in errors as to what is taught by the relied on
combination of references, as explained above, and because a finding of
obviousness does not require certainty. See, e.g., In re O’Farrell, 853 F.2d
894, 903–904 (Fed. Cir. 1988) (“Obviousness does not require absolute
predictability of success. . . . all that is required is a reasonable expectation
of success.”). Further, “obviousness cannot be avoided simply by a showing
of some degree of unpredictability in the art so long as there was a
reasonable probability of success.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d
1348, 1364 (Fed. Cir. 2007). Here, we determine that there was a reasonable
probability of success based on the teachings of Xiao that using mass spectra
of proteins from serum to identify differences in serum profile can be used to
predict whether patients may benefit from treatment with a particular drug,
particularly where Lynch teaches somatic mutations of EGFR, i.e.,
mutations that result in different protein sequences being expressed in EGFR
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protein, are associated with differences in clinical responsiveness to a drug
targeting EGFR protein.
2

As to whether Lynch teaches away from the invention because
detecting genetic mutations requires samples of tumor tissue, rather than
blood or serum, and genomic methods, such as PCR and gene sequencing
methods, rather than monitoring proteins (App. Br. 13), we find Appellants’
argument without persuasive merit. Dystar Textilfarben GMBH & CO
Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1364 (Fed. Cir. 2006)
(“We will not read into a reference a teaching away from a process where no
such language exists.”).
For the reasons discussed above, therefore, we affirm the rejection of
claim 9 as obvious over the combination of Zhao, Mazet, Xiao, and Lynch.

DECISION
We REVERSE the Examiner’s rejection under 35 U.S.C. § 103(a) of
claims 11 and 12.
We AFFIRM the Examiner’s rejection under 35 U.S.C. § 103(a) of
claims 6–10.
Accordingly, the Primary Examiner’s decision is affirmed-in-part.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).
AFFIRMED-IN-PART
bar

2
While not necessary for our decision, we note that claim 9 does not require
that the classification be based on mass spectral data arising from EGFR
protein. Claim 9.