Ex Parte Hyde et al

Patent Trial and Appeal Board

Jul 11, 2016

11900051 (P.T.A.B. Jul. 11, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
111900,051 0910712007 Roderick A. Hyde
80118 7590 07112/2016
Constellation Law Group, PLLC
P.O. Box 580
Tracyton, WA 98393
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.
SEl-0907-US 1624
EXAMINER
BRUSCA, JOHNS
ART UNIT PAPER NUMBER
1631
MAILDATE DELIVERY MODE
07/12/2016 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 RODERICK A. HYDE,
MURIEL Y. ISHIKAWA, ERIC C. LEUTHARDT,
DENNIS J. RIVET, and LOWELL L. WOOD, JR.
Appeal2014-005452
Application 11/900,051
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
TA WEN CHANG, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a method
of determining, in a computing device, a similarity or a dissimilarity
between at least one aspect of epigenetic information of a first individual
and at least one aspect of epigenetic information of a second individual. The
Examiner rejected the claims as obvious. We have jurisdiction under 35
U.S.C. § 6(b). We affirm.
1 Appellant identifies the Real Party in Interest as Searete LLC (see
App. Br. 5).
Appeal2014-005452
Application 11/900,051
Statement of the Case
Background
"Epigenetic information may include, for example, information
regarding DNA methylation, histone states or modifications, DNA structure,
transcriptional activity, RNAi, protein binding or other molecular states"
(Spec. 8:8-10). "Epigenetic phenotype information may be stable over time
in multiple assays or it may alter over time" (Spec. 9: 16-17).
The Claims
Claims 1, 3---6, 14, 15, 17-20, 24, 25, 28, 29, 31-34, 38, 39, 43--48,
50, 51, 53, 55, 56, 59 and 61---64 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A method comprising:
determining, in a computing device, a similarity or a
dissimilarity between at least one aspect of
epigenetic phenotype information regarding at
least one first individual and at least one aspect of
epigenetic phenotype information regarding at
least one second individual, wherein the at least
one second individual had been previously
influenced by at least two epigenetic influencing
events including both a medical radiation therapy
and an environmental event including exposure to
one or more pollutants;
statistically correlating the at least one aspect of
epigenetic phenotype information regarding at
least one second individual with previous
epigenetic information regarding the at least one
second individual, wherein the previous epigenetic
information was ascertained prior to both of the at
least two epigenetic-influencing events; and
communicating the similarity or the dissimilarity and the
statistical correlation to at least one user.
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The Issues
A. The Examiner rejected claims 1, 3, 5, 6, 14, 15, 17, 19, 20, 24, 25, 28,
29, 31, 33, 34, 38, 39, 43--46, 48, 50, 51, 53, 55, 56, 59, 61 and 62 under 35
U.S.C. 103(a) over Esteller 20092, Hegi3, Esteller 20004 and Sutherland5
(Ans. 3-8).
B. The Examiner rejected claims 1, 4, 15, 18, 29 and 32 under 35 U.S.C.
103(a) over Esteller 2009, Hegi, Esteller 2000, Sutherland and Li6 (Ans. 8-
10).
C. The Examiner rejected claims 63 and 64 under 35 U.S.C. 103(a) over
Esteller 2009, Hegi, Esteller 2000 and Digel7 (Ans. 10-14).
Because the same issues are dispositive for all three rejections, we
will consider them together.
The issue with respect to these rejections is: Does the evidence of
record support the Examiner's conclusion that Esteller 2009, Hegi and
2 Esteller, US 2009/0047214, published Feb. 19, 2009.
3 Hegi et al., MGMT Gene Silencing and Benefit from
Temozolomide in Glioblastoma, 352 NEW ENGLAND J. MED. 997-
1003 (2005).
4 Esteller et al., Inactivation of the DNA-Repair Gene MGMT and
the Clinical Response of Gliomas to Alkylating Agents, 343 NEW
ENGLAND J. MED. 1350-1354 (2000).
5 Sutherland et al., Epigenetics and the Environment, 983 ANNALS
NEWYORKACAD. SCI. 151-160 (2003).
6 Li et al., Epigenetic Changes in Prostate Cancer: Implication for
Diagnosis and Treatment, 97 J. NAT'L CANCER INST. 103-115
(2005).
7 Digel et al., DNA methylation disturbances as novel therapeutic
target in lung cancer: Preclinical and clinical results, 55 CRITICAL
REV. ONCOLOGY/ HEMATOLOGY 1-11 (2005).
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Application 11/900,051
Esteller 2000, combined with either Sutherland, Sutherland and Li, or Digel,
render the claims obvious?
Findings of fact
1. The Specification teaches that "epigenetic phenotype
information includes information regarding DNA methylation, histone states
or modifications" (Spec. 9: 12-13).
2. The Specification teaches that
an "epigenetic-influencing event" includes an event that
influences the epigenetic phenotype of at least one cell within at
least one individual ... An epigenetic-influencing event may be
part of a medical therapy, for example an epigenetic-
influencing event may include one or more medications, or one
or more treatments. An epigenetic-influencing event may
include at least one medical therapy including one or more
energy-based procedures, for example radiation therapy ... An
epigenetic-influencing event may include one or more
environmental events, such as but not limited to, exposure of an
individuai to radiation, one or more poHutants, or one or more
toxins.
(Spec. 8: 16-23).
3. The Specification teaches that "'mosaicism' ... denotes ...
situations where two or more subtypes originate with the first cell of an
organism" (Spec. 11 :27-28).
4. Esteller 2009 teaches that
for cancers such as colorectal cancer, the presence of aberrant
methylation at the WRN promoter predicts improved survival
in those patients treated with topoisomerase inhibitors such as
irinotecan, a treatment commonly used in this neoplasm. These
findings, as discussed in the experimental section below,
underline the significance of WRN as a caretaker of our
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Application 11/900,051
genome with tumor suppressor activity, and identify epigenetic
silencing of WRN as one key step in cancer development that
may have an important clinical impact for the treatment of these
patients .... Accordingly, in a first aspect, the invention
provides a method for predicting the likelihood of successful
treatment of cancer with a topoisomerase inhibitor and/or a
DNA damaging agent and/or a DNA methyltransferase
inhibitor and/or a HDAC inhibitor comprising determining the
methylation status of a RecQ helicase family gene in a sample
obtained from a subject, wherein if the RecQ helicase family
gene is hypermethylated the likelihood of successful treatment
is higher than if the RecQ helicase family gene is unmethylated,
or methylated to a lesser degree. Preferably, the methylation
status of at least the WRN gene is determined.
(Esteller 2009 i-fi-1 7-8).
5. Esteller 2009 teaches that
we assessed if the presence of WRN promoter
hypermethylation was a predictive marker of response to
irinotecan in colorectal cancer patients treated with this drug.
We selected a similar number of WRN-hypermethylated (n=45)
and unmethylated (n=43) primary colorectal tumors from
patients treated with irinotecan where a long clinical follow-up
was available. We found that the median time to the death of
the patient was 39.4 months for WRN methylated colon tumors
and just 20. 7 months for WRN unmethylated colon tumors.
Thus, the presence of WRN CpG island promoter
hypermethylation was a significant strong predictor of
increased overall survival in colon cancer patients treated with
irinotecan (Kaplan-Meier p=0.00005; 95% confidence interval
25.4-35.2)
(Esteller 2009 i-fi-1209-210).
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Application 11/900,051
6. Esteller 2009 teaches that "[a]ll statistical analyses were
performed using the SPSS version 10.1 program" (Esteller 2009
ii 196).
7. Esteller 2000 teaches that:
In our study, methylation of the MGMT promoter was
associated with responsiveness to carmustine and an increase in
overall survival at the time to progression of disease.
Moreover, the methylation status of the promoter was more
predictive of the outcome of carmustine treatment than the
grade of tumor, the Kamofsky performance status, or the
patient's age.
(Esteller 2000 1353, col. 1 ).
8. Figure 3 of Esteller 2000 is reproduced below:
A
B h '!!I \~ ... Me~hyia!ed
~ .!':! 60 .____,___,
a ro
5
P<0.001 '1_
~ °' 0 i
.0...<.i- AA ~ ~
.£- 20 l ~
; ~ ;;j L.t',nmethyl;rt.,d ~
j-
1
; • > • • t i t t t t • , b < , t t t t • , , t t '> ! • • • ' • t
() 5 12 18 u 30 36
Months Months
No. oF SueJECTs No. o~ Su SJEtTs
Methylat~ci 18 19 19 18 1:'l Meihy1~1ed 19 1s 18 14 9 3
Unmethyloteci 28 28 16 19 5 U"methyla!ed 28 lZ 7
Figure 3 depicts:
Overall Survival (Panel A) and Time to the Progression of
Disease (Panel B) among Patients with Gliomas Treated with
Carmustine, According to the Methylation Status of the MGMT
Promoter. Both overall survival and the time to the progression
of disease were significantly greater in the group of patients
with methylation of the MGMT promoter than in the group
without methylation.
(Esteller 2000 1353, col. 2).
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Application 11/900,051
9. Esteller 2000 teaches
Statistical Analysis ... In univariate analyses, methylation of
the promoter was positively correlated with the clinical
response and with overall and disease-free survival ... The lack
of methylation was associated with a much higher risk of death
(hazard ratio, 9.5; 95 percent confidence interval, 3.0 to 42.7;
P<0.001) (Fig. 3A). In univariate analysis, no other factor had
a statistically significant relation with survival.
(Esteller 2000 1352, col. 1-2).
10. Esteller 2000 teaches that "Analyses were performed with the
use of JMP software (version 3.1, SAS Institute, Cary, N.C.) and Stata
software" (Esteller 1352, col. 2).
11. Esteller 2000 teaches that "[t]umor specimens were obtained by
resection or biopsy peformed before the initiation of treatment with radiation
and chemotherapy ... The response to treatment was evaluated after the
patients had completed therapy" (Esteller 2000 1351, col. 1-2).
12. Hegi teaches that
Our data suggest that the methylation status of the MGMT
promoter may have prognostic value and, in addition, may be a
clinically significant predictor of benefit from temozolomide
chemotherapy ... Determination of MGMT promoter
methylation status by methylation-specific PCR may allow the
selection of patients most likely to benefit from temozolimide
treatment; patients whose tumors are not methylated at the
MGMT promoter appear to derive little or no benefit from the
addition of temozolimide to radiotherapy ... Stratification
according the MGMT promoter methylation status may be
considered in future trials in which temozolomide or other
alkylating agents are used.
(Hegi 1002, col. 1-2).
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13. Hegi teaches that
among patients with promoter methylation who were assigned
to receive both temozolomide and radiotherapy ... two-year
survival rate was 46.0 percent, as compared with 22.7 percent
among those with MGMT promoter methylation who were
assigned to radiotherapy alone. Kaplan-Meier estimates of
overall survival in these two subgroups were significantly
different (P=0.007 by the log-rank test) ... In the group of
patients whose tumors contained a methylated MGMT
promoter, those who received temozolomide and radiotherapy
had a median progression-free survival of 10.3 months, as
compared with 5.9 months for patients who received
radiotherapy alone (P=0.001). Among the patients whose
tumors contained an unmethylated MGMT promoter, those who
received temozolomide and radiotherapy had a median
progression-free survival of 5.3 months, as compared with 4.4
months for patients who were treated with radiotherapy alone
(P=0.02)
(Hegi 1000, col. 1-2).
14. Sutherland teaches "[ n ]ickel is a potent human carcinogen that
has been shown to alter DNA methylation patterns and affect histone
acetylation ... it has been proposed that arsenic metabolism may deplete
intracellular methyl group stores and thereby lead to changes in DNA
methylation that may be involved in carcinogenesis." (Sutherland, abstract).
15. Table 1 of Li teaches that "epigenetic aberrations in prostate
cancer" include "[h ]istone methylation" (Li 104, Table 1 ).
16. Digel teaches that "[ e ]xposure to tobacco carcinogens has been
associated with DNA methylation .... Tobacco-specific carcinogens further
induced methylation of the p 16 promoter region in adenocarcinomas . . . In
this experimental rat model, the prevalence of p 16 methylation increased
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Application 11/900,051
with disease progression from cell hyperplasia to metaplasia and then to
carcinoma in situ" (Digel 4, col. 1-2).
Principles of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR!nt'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability." Id. at 417.
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 3-14; FF 1-15) and agree that the
claims are rendered obvious by Esteller 2009, Hegi and Esteller 2000,
combined with either Sutherland, Sutherland and Li, or Digel. We address
Appellants' arguments below.
Claim 1
We have considered, but are not persuaded by Appellants' arguments
that "the Examiner did not establish a prima facie case of obviousness
against independent claim 1 for the reason that he failed to show that the
entirety of all three clauses of the claims are taught by any of the five cited
references, taken alone or in combination" (App. Br. 21 ).
Esteller 2009 teaches comparing at least one aspect of epigenetic
information (FF 4). Specifically, Esteller 2009 teaches determining
hypermethylation by analyzing "a similar number of WRN-hypermethylated
(n=45) and unmethylated (n=43) primary colorectal tumors from patients
treated with irinotecan" (FF 5) and statistically finding that "promoter
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Application 11/900,051
hypermethylation was a significant strong predictor of increased overall
survival" (FF 5). Esteller 2009 teaches that these statistical analyses were
performed using a computer software program (FF 6). Esteller 2009
communicates the result and statistical correlation to the reader (FF 4---6).
Thus, Esteller 2009 performs a method with a "determining" step, a
"statistically correlating" step, and a "communicating" step that analyze
epigenetic phenotype information regarding multiple individuals (FF 4---6).
As the Examiner notes, Esteller 2009 differs from claim 1 in the specific
"epigenetic-influencing events" and in making an analysis prior to the
"epigenetic-influencing events" (see Ans. 5).
Esteller 2000 also analyzes epigenetic information, specifically
regarding the MGMT promoter (FF 7) in different patient populations (FF 8)
using statistical methods (FF 9) and computer software (FF 10).
Esteller 2000 specifically teaches obtaining and evaluating specimens
before and after radiation and chemotherapies (FF 11) where radiation and
chemotherapy expressly fall within the scope of "epigenetic-influencing
events" as defined by the Specification (FF 2), rendering it obvious to
compare tumor specimens before and after treatment using the epigenetic
information of Estell er 2000.
Hegi also teaches that DNA methylation may be influenced by
medications or radiation therapy, and similarly teaches comparing
methylation status of individuals in association with radiation (FF 12-13).
Sutherland teaches that environmental pollutants and carcinogens, such as
nickel and arsenic, similarly lead to changes in DNA methylation (FF 14).
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The Examiner reasons that it would have been obvious "to measure
epigenetic information prior to initiation of a medical therapy because
Esteller et al. 2000 shows measurement of epigenetic information prior to
initiation of therapy, and because such measurement would allow for
determination of the suitability of a medical therapy for a patient" (Ans. 7).
The Examiner further explains that the prior art "provide guidance that
further study of association of methylation of promoters of either the WRN
promoter or the MGMT promoter is desirable to establish prognostic assays
for cancer patients that undergo chemotherapy combined with radiation
therapy" (Ans. 7). Therefore, the Examiner has provided "articulated
reasoning with some rational underpinning to support the legal conclusion of
obviousness," see In re Kahn, 441F.3d977, 988 (Fed. Cir. 2006), cited with
approval inKSR, 550 U.S. at 417-18 (2007).
We recognize that Appellants repeatedly contend that the Examiner
fails to demonstrate teachings of the prior art for the limitations of claim 1 at
pages 22-36 of the Appeal Brief, but our careful review of Appellants'
arguments finds them unpersuasive, 8 in particular as they fail to address the
prior art in combination. "Non-obviousness cannot be established by
attacking references individually where the rejection is based upon the
teachings of a combination of references .... [A reference] must be read, not
8 We must separately note that the clause 3 argument is particularly
spurious, given that each of the references themselves represent
widely published communications that detail statistical correlations
regarding epigenetic information in different patient populations
(FF 5, 9, 13-16).
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in isolation, but for what it fairly teaches in combination with the prior art as
a whole." In re Merck& Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Claims 3-6 and 14
We are further not persuaded by Appellants' allegations that "the
Examiner failed to establish a prima facie case of obviousness for any of
claims 3---6 and 14 by any combination of references" (App. Br. 37).
Specifically, regarding claim 3, the cited prior art is replete with
teachings regarding DNA methylation information including teachings by
Esteller 2009 regarding DNA methylation (FF 4). Regarding claim 4, we
note that the Examiner addressed this rejection further in view of Li, which
teaches epigenetic information regarding histone structure (FF 15). We
further agree with the Examiner's rationale, regarding claim 5, that it would
have been "obvious to analyze multiple loci because Esteller 2009 shows the
relevance of the WRN promoter methylation to chemotherapy, and Hegi et
al. and Esteller et al. 2000 show the relevance of methylation of a second
locus, the MGMT promoter, to chemotherapy" (Ans. 7). Regarding claim 6,
per Appellants' definition of mosaicism (FF 3), Esteller 2009, Hegi and
Esteller 2000 all show evidence of mosaicism (FF 4--12). Regarding claim
14, Esteller 2009 further teaches an intervention strategy (FF 4).
Claim 15
We recognize, but find unpersuasive Appellants' argument that "the
Examiner did not make a prim a facie case of obviousness for independent
claim 15 or its dependent claims over any combination of references" (App.
Br. 37).
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The skilled artisan would have found it obvious that analysis using
JMP software and Stata software, as taught by Esteller 2000 (FF 11 ),
employs a system comprising at least one computer program on recordable-
type media for use with at least one computer system and wherein the
computer program includes a plurality of instructions. Moreover, it would
have been obvious to employ a computer in the method of claim 1, already
found obvious above, in order "to update it using modem electronic
components in order to gain the commonly understood benefits of such
adaptation, such as decreased size, increased reliability, simplified operation,
and reduced cost." Leapfrog Enterprises Inc. v. Fisher-Price Inc., 485 F.3d
1157 (Fed. Cir. 2007).
Claims 17-20, 24, 25 and 28
We are further not persuaded by Appellants' allegations that "the
Examiner failed to establish a prima facie case of obviousness for any of
claims 17-20, 24--25, and 28 by any combination of references" (App. Br.
57).
Specifically, dependent claims 17-20 and 28 mirror information as
addressed above for dependent claims 3---6 and 14. Regarding claim 24,
Esteller 2009 (FF 4), Esteller 2000 (FF 7) and Hegi (FF 13) teach
medication. Per claim 25, Sutherland teaches exposure to one or more
toxins (FF 14). Thus, the ordinary artisan would have reasonably employed
information, as recited by claims 17-20, in a system with instructions for
epigenetic-influencing events, as recited by claims 24 and 25, and for giving
instructions for suggesting an intervention strategy, as recited by claim 28,
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consistent with the Examiner's reliance on Esteller 2009, Esteller 2000, Hegi
and Sutherland alone, or further in view of Li (see Ans. 3-10).
Claim 29
We recognize, but find unpersuasive Appellants' argument that "the
Examiner did not make a prim a facie case of obviousness for independent
claim 29 or its dependent claims over any combination of references" (App.
Br. 58) for the reasons given above.
Claims 31-34, 38 and 39
We recognize, but find unpersuasive Appellants' argument that "the
Examiner failed to establish a prima facie case of obviousness for any of
claims 31-34 and 38-39 by any combination of references" (App. Br. 77)
because the rejection relied on a combination of prior art references, which
in their combined teachings would have suggested to a person of ordinary
skill in the art the claimed invention.
Specifically, dependent claims 31-34 and 45 mirror information as
addressed above for dependent claims 3---6 and 25. Regarding claim 44,
Hegi teaches radiation (FF 12). Thus, the ordinary artisan would have
reasonably employed information, as recited by claims 31-34, in a system
with instructions for epigenetic-influencing events, as recited by claims 38
and 39, consistent with the Examiner's reliance on Esteller 2009, Esteller
2000, Hegi and Sutherland alone, or further in view of Li (see Ans. 3-10).
Claim 43
We recognize, but find unpersuasive Appellants' argument that "the
Examiner did not make a prima facie case of obviousness for independent
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Application 11/900,051
claim 43 or its dependent claims over any combination of references" (App.
Br. 77) for the reasons given above.
Claims 44-46 and 48
We recognize, but find unpersuasive Appellants' argument that "the
Examiner failed to establish a prima facie case of obviousness for any of
claims 44--46 and 48 by any combination of references" (App. Br. 95)
because the rejection relied on a combination of prior art references, which
in their combined teachings would have suggested to a person of ordinary
skill in the art the claimed invention.
Specifically, dependent claims 44--46 mirror information as addressed
above for dependent claims 3 8, 25 and 3. Regarding claim 48, Hegi teaches
that methylation status may have prognostic value (FF 12). Thus, the
ordinary artisan would have reasonably employed information, as recited by
claim 46, in a system with instructions for epigenetic-influencing events, as
recited by claims 44 and 45, and predicting at least one epigenetic event, as
recited by claim 48, consistent with the Examiner's reliance on Esteller
2009, Esteller 2000, Hegi and Sutherland (see Ans. 3-8).
Claim 50
We recognize, but find unpersuasive Appellants' argument that "the
Examiner did not make a prima facie case of obviousness for independent
claim 43 or its dependent claims over any combination of references" (App.
Br. 77) substantially for the reasons given above. Regarding clause 2 of this
claim, we note that it nearly completely mirrors clause 2 of claim 15, which
we addressed above, but in addition specifies the epigenetic influencing
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events to be medical radiation and exposure to pollutants, which we
addressed above in relation to claims 38 and 25.
Claims 51, 53 and 55
We recognize, but find unpersuasive Appellants' argument that "the
Examiner failed to establish a prima facie case of obviousness for any of
claims 51, 53 and 55 by any combination of references" (App. Br. 111)
because the rejection relied on a combination of prior art references, which
in their combined teachings would have suggested to a person of ordinary
skill in the art the claimed invention.
Specifically, dependent claim 53 mirrors information as addressed
above for dependent claims 3. Regarding claim 55, intervention therapy was
addressed for at least claims 14 and 28. Regarding claim 51, we note that it
combines information addressed above for claims 24 and 3 8.
Claim 56
We recognize, but find unpersuasive Appellants' argument that "the
Examiner did not make a prim a facie case of obviousness for independent
claim 56 or its dependent claims over any combination of references" (App.
Br. 111) for the reasons given above.
Claims 59, 61 and 62
We recognize, but find unpersuasive Appellants' argument that "the
Examiner failed to establish a prima facie case of obviousness for any of
claims 59, 61 and 62 by any combination of references" (App. Br. 127).
Specifically, dependent claims 59 mirrors information as addressed
above for dependent claims 3. Regarding claim 62, intervention therapy was
addressed for at least claims 14 and 28. Regarding claim 61, we note that
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Sutherland teaches that arsenic may lead to changes in DNA methylation
and may be involved in carcinogenesis (FF 14), which is indicative of
predicting an environmental event influencing an individual.
Claim 63
We recognize, but find unpersuasive Appellants' argument that "the
Examiner did not make a prim a facie case of obviousness for independent
claim 63 or its dependent claims over any combination of references" (App.
Br. 127) for the reasons given above.
In particular regarding limitation 4, intervention therapy was
addressed for at least claims 14 and 28, and the skilled artisan would have
found this information pertinent for comparison between multiple patients.
Digel also discloses that exposure to tobacco carcinogens has been
associated with DNA methylation, that the prevalence of p 16 methylation
increased with disease progression from cell hyperplasia to metaplasia and
then to carcinoma in situ, and that tobacco smoking leads to frequent
epigenetic silencing of the p 16 gene in non-small cell lung cancers (FF 16).
Claim 64
We recognize, but find unpersuasive Appellants' argument that "the
Examiner did not make a prim a facie case of obviousness for independent
claim 64 or its dependent claims over any combination of references" (App.
Br. 145) for the reasons given above.
Technical rationale to combine
Appellants further contend failure to articulate a technical rationale to
combine (App. Br. 159), but articulates facts that seem to belong to a
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different case, i.e. reference to nine references, reference to treating patients
with UV radiation. According, these arguments are not deemed pertinent.
Logical consistency
We recognize, but find unpersuasive Appellants' contention of a lack
of logical consistency in view of the Examiner's rejections based on
different combinations of references (App. Br. 160). The Examiner
provided detailed reasoning explaining the rationale behind the rejections
(see Ans. 3-14).
Rule 104
We are further not persuaded by Appellants' arguments that the
Examiner failed to "'clearly explain' '[t]he pertinence of the six cited
references"' (App. Br. 161). We find that the Examiner met the required
burden of presenting "articulated reasoning with some rational underpinning
to support the legal conclusion of obviousness", see In re Kahn, 441 F.3d at
988, based on the combination of references (see Ans. 3-14).
SUMMARY
We affirm the rejection of claims 1, 3, 5, 6, 14, 15, 17, 19, 20, 24, 25,
28, 29, 31, 33, 34, 38, 39, 43--46, 48, 50, 51, 53, 55, 56, 59, 61 and 62 under
35 U.S.C. § 103(a) as obvious over Esteller 2009, Hegi, Esteller 2000 and
Sutherland.
We affirm the rejection of claims 1, 4, 15, 18, 29 and 32 under 35
U.S.C. § 103(a) as obvious over Esteller 2009, Hegi, Esteller 2000,
Sutherland and Li.
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We affirm the rejection of claims 63 and 64 under 35 U.S.C. § 103(a)
as obvious over Esteller 2009, Hegi, Esteller 2000 and Digel.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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