Ex Parte Wuitschick et al

Patent Trial and Appeal Board

Aug 21, 2018

14015251 (P.T.A.B. Aug. 21, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/015,251 08/30/2013
134069 7590 08/23/2018
Casimir Jones, S.C.
2275 DEMING WAY, SUITE 310
MIDDLETON, WI 53562
FIRST NAMED INVENTOR
Jeffrey D. Wuitschick
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.
ABBTT-32875/US-2/0RD 7864
EXAMINER
HANEY, AMANDA MARIE
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
08/23/2018 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):
docketing@casimirjones.com
pto .correspondence@casimirjones.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JEFFREY D. WUITSCHICK and SHIRAI HUANG
Appeal2017-009266
Application 14/015,251 1
Technology Center 1600
Before FRANCISCO C. PRATS, ELIZABETH A. LA VIER,
and RYAN H. FLAX, Administrative Patent Judges.
LA VIER, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellants seek review of the
Examiner's rejections of claims 29, 32, 35--41, 44, 51-55, 57---60, and 68-
70. We have jurisdiction under 35 U.S.C. § 6(b ). For the reasons set forth
below, we AFFIRM.
BACKGROUND
The Specification relates to molecular assays for the detection and
analysis of PRAME (Preferentially Expressed Antigen in Melanoma), and
the use thereof in cancer diagnosis and prognosis. See Spec. 1: 8-26.
1 Appellants state the real party in interest is Abbott Molecular Inc. Appeal
Br. 3.
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Claim 29, the only independent claim on appeal, recites:
29. A method of detecting the presence or amount of PRAME
(Preferentially Expressed Antigen in Melanoma) mRNA in a
sample comprising:
a) contacting a sample suspected of containing PRAME mRNA
with a first primer and a second primer under conditions such
that a first cDNA amplification product is generated, wherein
said first primer hybridizes to Exon 3 of said PRAME mRNA,
and wherein said second primer hybridizes to Exon 4 of said
PRAME mRNA and wherein-said first and second primers are
a primer pair selected from the group consisting of: SEQ ID
NOs: 3 and 7; SEQ ID NOs: 4 and 8; SEQ ID NOs: 5 and 9;
and SEQ ID NOs: 6 and 10 wherein said contacting does not
generate detectable amplicons from genomic PRAME;
b) providing at least one probe that is complementary to said
first cDNA amplification product wherein said probe comprises
a label; and
c) detecting said first cDNA amplification product, thereby
determining the presence and/or amount of said PRAME in said
sample.
Appeal Br. 28 (Claims Appendix) (emphasis and some formatting added).
REJECTIONS MAINTAINED ON APPEAL
1. Claims 29, 32, 35, 36, 38, 44, 54, 55, 57, 58, 68, 69, and 70 stand
rejected under 35 U.S.C. § 103(a) as unpatentable over Pollack2
2 Pollack et al., NYES0-1/LAGE-ls and PRAME Are Targets for Antigen
Specific T Cells in Chondrosarcoma following Treatment with 5-Aza-2-
Deoxycitabine, 7 PLoS ONE 1 (2012) (e32165).
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and Mansfield, 3 as further evidenced by GenBank. 4 Ans. 2; Final
Action 4.
2. Claims 37 and 39-41 stand rejected under 35 U.S.C. § I03(a) as
unpatentable over Pollack, Mansfield, and Sorge, 5 as further
evidenced by GenBank. Ans. 16; Final Action 9-10.
3. Claims 51-53 and 59 stand rejected under 35 U.S.C. § I03(a) as
unpatentable over Pollack, Mansfield, and Colbeigh, 6 as further
evidenced by GenBank. Ans. 19; Final Action 11.
4. Claim 60 stands rejected under 35 U.S.C. § I03(a) as unpatentable
over Pollack, Mansfield, Colbeigh, Chen, 7 and Palma, 8 as further
evidenced by GenBank. Ans. 21-22; Final Action 12-13.
DISCUSSION
The Examiner's thorough findings and analysis of the§ 103 rejections
are set forth in pages 4--14 of the Final Action and are further explained in
pages 2-24 of the Answer. Having considered Appellants' arguments, we
discern no reversible error in the Examiner's conclusions in regard to any of
3 Mansfield et al., WO 2005/070086 A2, published Aug. 4, 2005.
4 GenBank, Homo sapiens preferentially expressed antigen in melanoma
(PRAME), transcript variant 1, mRNA, Accession No. NM_006115 GI
4659365 (2004).
5 Sorge, US 2007/0015180 Al, published Jan. 18, 2007.
6 Colbeigh et al., Tumor Gene Expression and Prognosis in Breast Cancer
Patients with 10 or More Positive Lymph Nodes, 11 CLIN. CANCER RES. 8623
(2005).
7 Chen et al., US 2006/0269967 Al, published Nov. 30, 2006.
8 Palma et al., US 7,374,927 B2, issued May 20, 2008.
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Rejections 1--4, supra, for the reasons already of record and as further
explained below.
A. Rejection 1
Pollack notes that PRAME is a promising target for T cell therapy in
the treatment of chondrosarcoma, and reports that PRAME expression can
be induced following treatment with 5-Aza-dC. 9 Pollack Abstract. The
Examiner makes the following findings in regard to exemplary claim 29:
Pollack teaches a method of detecting the amount of PRAME
mRNA in chondrosarcoma samples and melanoma cell lines.
Pollack teaches contacting the samples with a primer pair and
performing quantitative real time PCR (with SYBR green as the
reporter) to detect the amount of PRAME mRNA in the
samples (page 2, col 2). Pollack discloses PRAME specific
primers (see Table 1 ). As evidenced by GenBank the first
primer 5'-GCTTCAAAATGGAACGAAGG-3' is 100%
identical to nucleotides 242-261 of the GenBank sequence and
hybridizes to exon 3 (nucleotides 152-270). The second primer
5'-TGCCAGCTCCACAAGTGTC-3' is 100% complementary
to nucleotides 339-321 of the GenBank sequence and
hybridizes to exon 4 (nucleotides 271-573). Thus Pollack
teaches a method comprising contacting a sample suspected of
containing PRAME mRNA with a first primer and a second
primer under conditions such that a first cDNA amplification
product is generated, wherein the first primer hybridizes to
Exon 3 and the second primer hybridizes to Exon 4; and
detecting the first cDNA amplification product thereby
determining the presence and/or amount of PRAME mRNA in
the sample.
Final Action 4--5. The similarity of the claimed primers and those of the
prior art can be seen readily in the GenBank sequence as annotated by the
9 5-Aza-2-Deoxycitabine.
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Examiner, which illustrates the relationships between Pollack's primers
(underlined) and the claimed primers (bolded), along with the exon 3/exon 4
junction (starred):
4$1 t t{~a(:\~·tq,::_;:t;:~ tr~c~<~t,~tqgg og t--qz:~tg~1tq ~~':tqqq~<.~~Q(~ a tr~t t,~.:;~,~ct qgiiq a{x.~t t.(::·
54 ,l a~ag.ctqtgc t t~1~rt::g9~.ct. t.qa tqt9<'tc cttg\~cc~9.:J a:J:Jt t(:'gccc c~.g9~~1qtqq
Id. at 5. The annotated sequence above illustrates the relationships between
the prior art and claimed primers.
The Examiner acknowledges that Pollack's PRAME primers are not
the same as SEQ ID NOs: 3 and 7 of claim 29, 10 and Pollack does not teach
that its primers do not generate detectable amplicons from genomic PRAME
(claim 29) or from known PRAME-like genes or mRNAs in the human
genome (claim 70). Id. at 5. But the Examiner finds it would have been a
matter of routine experimentation, with "more than a reasonable expectation
of success," for the ordinarily skilled artisan to design primers which, like
those of Pollack, would amplify across the PRAME exon 3/4 junction. Id. at
6. The motivation for doing so would have been "to obtain additional
primers that could be used to measure the level of PRAME mRNA by
amplifying across the exon 3/4 junction of PRAME and identify primers
10 The Examiner notes that "Appellants elected the primer pair of SEQ ID
NOs: 3 and 7 for examination and that the claims have only been examined to
the extent that they read on the elected primer pair (SEQ ID NOs: 3 and 7).
The additionally recited primer pairs have been withdrawn from consideration
as being directed to nonelected subject matter." Ans. 3.
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with improved properties." Id. Further, the Examiner finds that "it is a
property of the claimed primers that they do not generate detectable
amplicons from genomic PRAME and that they do not generate detectable
amplicons from known PRAME-like genes or mRNAs in the human
genome." Id.
As Pollack does not teach using a labeled probe complimentary to the
amplification product as required by claim 29, the Examiner turns to
Mansfield. See Final Action 7-9. Mansfield generally describes methods
for determining whether a subject has a graft-tolerant phenotype, including
by measuring gene expression through assaying a nucleic acid transcript of
the gene. See Mansfield 2:21-3:1. To this end, Mansfield provides a
protocol for TaqMan-based quantitative RT-PCR and sequences for various
labeled probes, including a PRAME probe. See id. 24:26-25: 12. The
Examiner finds:
Mansfield teaches a TaqMan probe 5'FAM-
CGTTTGTGGGGTTCCATTCAGAGCC-NFQ3' for detecting
PRAME (see pages 24--25). The part that is not underlined
hybridizes to exon 3 and the part underlined hybridizes to exon
4. The probe of Mansfield shares 85% sequence identity with
SEQ ID NO: 11.[ 11 ] The probe of Mansfield is 25 base pairs
long and comprises nucleotides 5-26 of SEQ ID NO: 11.
Because one uses multiple copies of the same probe in TaqMan
PCR, one copy of the probe can be interpreted as a first primer
that hybridizes to Exon 3 of PRAME and another copy of the
probe can be interpreted as a second primer that hybridizes to
11 SEQ ID NO: 11 is among the sequences listed in claim 55, which ultimately
depends from claim 29 and recites: "The method of claim 54, wherein said
probe comprises at least 70% sequence identity with a sequence selected from
the group consisting of SEQ ID NOs: 11-16." Appeal Br. 30 (Claims
Appendix).
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exon 4 of PRMAE [sic]. It is noted for the record that the probe
is labeled at it[ s] 5' end with FAM with is a fluorescent dye and
labeled at its 3' end with NFQ which is a non-fluorescent
quencher.
Final Action 7-8. As with the primers discussed above, the sequence data as
annotated by the Examiner are useful in visualizing the similarity of
Mansfield's probe (underlined) and the claimed probe SEQ ID NO: 11
(bolded), in relationship to the PRAME exon 3/4 boundary (starred):
-~~ 81 t t c·act: t.<:1t,::-,::,::- Lt>::>::~~ tt~ tQ\Jq aq t~Jc t>:J.1. tq .. 1a~J(j(l=:1-~x:>,:~ ,~~-gg;:1g-=:1t>=:1-=:1
Final Action 8. The annotated sequence above illustrates the relationships
between the prior art and claimed probes.
Accordingly, the Examiner concludes:
As demonstrated by Mansfield TaqMan-based quantitative RT-
PCR was routinely used in the art at the time of the invention to
detect the level of PRAME mRNA in a sample. Thus the
substitution of one assay that detects gene expression (the syber
green assay of Pollack) for another assay that also detects gene
expression (the TaqMan PCR assay of Mansfield) would have
yielded predictable results to one of ordinary skill in the art at
the time of the invention . . . . A skilled artisan would be
motivated to have designed and tested new probes to obtain
additional probes that could be used to measure the level of
PRAME mRNA by detecting the exon 3/4 junction of PRAME
and identify probes with improved properties.
Id. at 8-9; see also Ans. 14--15.
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Appellants' arguments to the contrary (see generally Appeal Br. 17-
24; see also Reply Br. 3-11) are not persuasive. Appellants first take issue
with the Examiner's determination that the claimed primers and probes are
"equivalent" to the prior art. Appeal Br. 19-20; see also Reply Br. 5---6. But
the Examiner provides an extensive, well-reasoned, and persuasive analysis
in the Answer:
The primer pair of the present invention was considered by the
Examiner to be equivalent to the primer pair of Pollack because
both primer pairs are used to amplify PRAME mRNA, both
primer pairs comprise a first primer that hybridizes to exon 3 of
PRAME and a second primer that hybridizes to exon 4 of
PRAME, both primer pairs do not generate detectable
amplicons from genomic PRAME, both primer pairs are
considered to be specific for PRAME, and the first primer of
Pollack is substantially identical to SEQ ID NO: 3. Thus it is
maintained that the primer pair of Pollack is equivalent to the
claimed primer pair for at least these reasons.
Ans. 6. 12
Relatedly, Appellants maintain that "[t]here are untold millions of
possible primer pairs that could be tested," and thus selecting the claimed
primers and probes would not have been obvious to try, nor the result of
routine experimentation or optimization. Appeal Br. 20. Appellants
overstate the case; primer selection is constrained by various considerations,
12 Appellants characterize the design of R T-PCR primers as "laborious and
error prone," and thus not a matter of routine experimentation (Reply Br. 6),
quoting a supporting reference, Cui, cited in Pollack and discussed by the
Examiner in the Answer (and earlier in the record) (see Ans. 4 (citing Cui et
al., qPrimerDepot: a primer database for quantitative real time PCR, 35
NUCLEIC Acrns REs. D805 (2007)). But this quotation comes from Cui's
introduction, and is not a description of Cui's own methodology. It is the
latter on which the Examiner relies. See Ans. 4.
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both as a general matter and in regard to the design of primers to bridge the
exon 3/exon 4 boundary of PRAME, and similarly in regard to probe design:
Designing probes which are equivalent to those taught in the art
is considered routine experimentation particularly since the
nucleic acid sequence of the PRAME mRNA was known in the
art as demonstrated by GenBank. The prior art is replete with
guidance and information necessary to permit the ordinary
artisan to design probes for measuring the level of PRAME
mRNA by detecting the exon 3/4 junction of PRAME. The
ordinary artisan would have had more than a reasonable
expectation of success of making probes for measuring the level
of PRAME mRNA by detecting the exon 3/4 junction of
PRAME. Thus at the time of the invention, the skill in the art,
the computer software available (PrimerDepot, BLAST, etc.),
and the guidance provided by the prior art would have made
selecting the probes recited in the claimed method obvious. A
skilled artisan would be motivated to have designed and tested
new probes to obtain additional probes that could be used to
measure the level of PRAME mRNA by detecting the exon 3/4
junction of PRAME and identify probes with improved
properties. Further the skilled artisan would have found it
obvious to try the probes recited in the claimed method because
the artisan would have had a finite number of identified,
predictable sequence options for the probes, and the artisan
would have had good reason to pursue these known options,
which were within the artisans technical grasp.
Final Action 9; see also id. at 6, Ans. 7-8.
Indeed, another panel of the Board rejected a similar argument
alleging the non-obviousness of selecting particular primers from known
sequences:
Thus, if [In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009)]
finds that cloning an unknown gene sequence had a "reasonable
expectation of success," we conclude that it is more than
reasonable to find that selection of particular real-time primer
sequences from a known sequence using commercially
available software "would have had a resoundingly 'reasonable
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expectation of success' in deriving the claimed invention in
light of the teachings of the prior art." Kubin, 561 F.3d at 1360.
Ex parte Kostrikis, Appeal No. 2010-001111, 2010 WL 2694707, at *7 (July
2, 2010). 13 We concur with our colleagues that selecting particular primers
from known sequence data ( and in light of known equivalent primers)
cannot confer patentability to otherwise obvious claims, at least not in the
absence of persuasive contrary evidence. Even though a great many primer
or probe sequences may be theoretically possible, selecting particular
primers or probes from a known sequence, especially those so similar to
prior art primers/probes, 14 is a matter of routine experimentation
nonetheless, on the current record. As the Examiner puts it: "[t]he
Appellants have not established that the primers/probes are non-obvious
with persuasive evidence by merely asserting that the probability of picking
the claimed primer pair and probe would have been unlikely." Ans. 7-8.
Appellants' related assertion that the Examiner bears the burden to
provide evidence that "Pollack's primers do not generate detectable
amplicons form known PRAME-like genes or mRNAs" (Reply Br. 5
( discussing claim 70)) is likewise unpersuasive. The rejection relies on the
Examiner's inference that because Pollack's primers are so close in
13 The art cited to support the obviousness rejection appealed in Kostrikis
included a large number of functional primer pairs (see 2010 WL 2694707, at
*4), whereas here, Pollack teaches a single pair of PRAME primers across the
exon 3/4 boundary (see Pollack Table 1 ). Nonetheless, as discussed above,
the Examiner's finding that Pollack's primers are equivalent to the claimed
primers is well-supported.
14 As the Examiner emphasizes: "the first primer of Pollack is substantially
identical to SEQ ID NO: 3 and [] the probe of Mansfield overlaps the probe
of SEQ ID NO: 11." Ans. 8.
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sequence to the claimed primers, Pollack's primers would share functional
characteristics with the claimed primers, i.e., non-generation of unwanted
amplicons (be they from genomic PRAME or PRAME-like genes or
mRNAs ). See Ans. 5 ("Considering that the first primer of Pollack is
substantially identical to SEQ ID NO: 3, there was a reasonable expectation
in the art that the first primer of Pollack will also have the same property of
SEQ ID NO: 3 of not generating detectable amplicons from known PRAME-
like genes or mRNAs."); see also Final Action 5---6. This inference is
reasonable, and shifts the burden to Appellants to produce evidence to the
contrary:
[W]here the Patent Office has reason to believe that a functional
limitation asserted to be critical for establishing novelty in the
claimed subject matter may, in fact, be an inherent
characteristic of the prior art, it possesses the authority to
require the applicant to prove that the subject matter shown to
be in the prior art does not possess the characteristic relied
on .... Whether the rejection is based on 'inherency' under 35
U.S.C. § 102, on 'prima facie obviousness' under 35 U.S.C.
§ 103, jointly or alternatively, the burden of proof is the same,
and its fairness is evidenced by the PTO' s inability to
manufacture products or to obtain and compare prior art
products.
In re Best, 562 F.2d 1252, 1254-55 (CCPA 1977) (footnote omitted)
(citations omitted). Appellants have not done so, and thus the Examiner's
inference stands. Accordingly, Appellants' further assertion that the
Examiner cannot rely on the inherent properties of the claimed primers to
satisfy the claim limitations of not generating detectable amplicons from
genomic PRAME (claim 29) or from known PRAME-like genes or mRNAs
in the human genome (claim 70), because "[t]here is no guidance in the cited
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art that seeks this goal, or that accomplishes it" (Appeal Br. 20; see also
Reply Br. 3-5) is equally unpersuasive.
Appellants next argue that Pollack's methods lack utility and that
Pollack provides a different solution to a different problem than the claimed
invention. See Appeal Br. 21-24. We are not persuaded. As the Examiner
explains ( describing Pollack):
PRAME was expressed in the untreated cell lines at a relatively
low level. However PRAME expression was increased
significantly following 5-Aza-dC treatment. The SAME
methodology and primers were used to measure PRAME
expression before and after treatment with 5-Aza-dC. The fact
PRAME expression levels were relatively low in the
chondrosarcoma cell lines prior to treatment with 5-Aza-dC is
due to the fact that this is a property of the sample-it is NOT
attributable to the methodology or primers that were used by
Pollack. If it had been attributable to the methodology or
primers that were used by Pollack then Pollack would not have
been able to detect the significant increase in PRAME
expression that was observed after the treatment with 5-Aza-dC
(see Fig lB). Further Pollack would have wanted to avoid
generating amplicons from PRAME-like genes or mRNAs
because Pollack was interested in determining whether
treatment with 5-Aza-dC could specifically induce PRAME
express10n.
Ans. 10-11. We also note that to the extent Appellants' arguments critique
Pollack as being insufficient to detect increased PRAME expression "in cells
from patient samples" (Appeal Br. 24), claim 29 does not specify that the
sample must contain intact patient cells.
Further as to Mansfield, Appellants assert the rejection engages in too
much picking and choosing, and offers no rationale for combining such
diverse references. See Appeal Br. 24. According to Appellants, "[t]he
Office provides no evidence that Mansfield's probe configured for
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determining a graft tolerant phenotype in the circulating blood of a subject
provides a working method in combination with Pollack's methods and
reagents for determining targets for antigen specific T-cells in
chondrosarcoma." Id. Appellants emphasize that "Mansfield's method of
detecting PRAME expression uses a labeled target hybridized to a cDNA
microarray, not a labeled probe." Reply Br. 7 (citing Mansfield 11:10-18).
These arguments are not persuasive. First, they largely focus on Mansfield
individually rather than the combination of references. See In re Keller, 642
F.2d 413,426 (CCPA 1981) ("But one cannot show non-obviousness by
attacking references individually where, as here, the rejections are based on
combinations of references."). Second, as the Examiner explains, Mansfield
provides data showing differential PRAME expression, and provides a
method for detecting it:
Figure 1 of Mansfield provides Table 1, which lists 200
representative genes whose expression differs in operationally
tolerant (OT) patients relative to those with chronic graft injury
(see page 5 lines 26-27 and Fig 1). PRAME is listed in Table 1
as having a 2.80 fold difference in expression between OT
patients and those with chronic graft injury. Based on the
PRAME data presented in the disclosure of Mansfield the
skilled artisan would have concluded that the methodology and
primers/probe of Mansfield did in fact work to detect PRAME
express10n.
Ans. 14. Further, Pollack and Mansfield are analogous art because both
teach detecting PRAME mRNA in a sample by different methods, and thus
it would have been obvious to substitute "one assay that detects gene
expression (the syber green assay of Pollack) for another assay that also
detects gene expression (the TaqMan PCR assay of Mansfield)" (Final
Action 8; see also Ans. 15).
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Having considered Appellants' arguments for the patentability of
claims 29 and 70, we are not persuaded of any reversible error by the
Examiner. We thus affirm the rejection of claims 29 and 70 under§ 103(a).
Claims 32, 35, 36, 38, 44, 54, 55, 57, 58, 68, and 69 are not argued
separately, and fall with claims 29 and 70. See 37 C.F.R. § 4I.37(c)(l)(iv).
B. Rejection 2
Appellants' arguments specific to these claims 15 begin by reciting
what Sorge does not teach (see Appeal Br. 25), i.e., anything PRAME-
specific, but the Examiner does not rely on Sorge for any such teachings,
and so this argument unpersuasively argues the references individually
instead of in combination. See Keller, 642 F.2d at 426.
Appellants then argue that the ordinarily skilled artisan would have
had no reason to combine Sorge with the other references, and that "[t]he
Office provides no evidence that Sorge's oligonucleotide pair 'complex'
could be combined with Pollack, Mansfield and GenBank with a reasonable
expectation of success at arriving at the methods of the present claims, or a
working method of any kind." Appeal Br. 25; see also Reply Br. 12. This
argument is likewise not persuasive, especially given the narrow purposes
for which the Examiner employs Sorge:
In the rejection, Sorge is only being relied upon to teach probes
that are labeled with Cy5 or Quasar as required by claim 3 7,
probes that comprise the quencher BHQ or BHQ2 as required
by claim 39, and probes that have binding enhancers such as
minor groove binders as required by claims 40 and 41. It is
reiterated for the record that Pollack teaches detecting PRAME
15 Appellants argue the claims subject to Rejection 2 as a group. See Appeal
Br. 24--25.
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mRNA in a sample using a SYBR Green based quantitative real
time PCR assay and that Mansfield teaches detecting PRAME
mRNA in a sample using a TaqMan based quantitative real
time PCR assay. The TaqMan based method of Mansfield uses
a probe that is labeled at its 5' end with FAM which is a
fluorescent dye and labeled at its 3' end with NFQ which is a
nonfluorescent quencher to detect amplification. The skilled
artisan would have been motivated to look at the relevant prior
art of Sorge because this reference discloses numerous
fluorophores and quenchers that are known in the art and can be
used to detectably label oligonucleotide probes (see paras 0058-
0063).
Ans. 17; see also Final Action 9-11.
Accordingly, we affirm the rejection of claims 37 and 39-41.
C. Re} ection 3
As with Rejection 2, Appellants begin their separate arguments
regarding Rejection 316 with a recitation of what Cobleigh does not teach,
and continue by arguing that there would have been no reasonable
expectation of success in combining Cobleigh with the other references. See
Appeal Br. 25-26; see also Reply Br. 13. Again, these arguments are not
persuasive to the extent they argue Cobleigh individually. See Keller, 642
F.2d at 426. As to the combination, we are not persuaded; again, the
additional reference is only employed for narrow purposes and the Examiner
offers a thorough rationale:
Cobleigh is only being relied upon to teach detecting PRAME
in a sample that is a formalin fixed and/or paraffin embedded
sample as required by claim 51, detecting PRAME in a tumor
sample as required by claim 52, detecting PRAME in a breast
16 Appellants argue the claims subject to Rejection 3 as a group. See Appeal
Br. 25-26.
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cancer sample as required by claim 53, and using beta-actin as a
housekeeping mRNA as required by claim 59. It is reiterated
for the record that Pollack teaches detecting PRAME mRNA in
a sample using a SYBR Green based quantitative real time PCR
assay and that Mansfield teaches detecting PRAME mRNA in a
sample using a TaqMan based quantitative real time PCR assay.
The skilled artisan would have been motivated to look at the
relevant prior art of Cobleigh because this reference also
teaches detecting PRAME mRNA in a sample using a TaqMan
based quantitative real time PCR assay (see page 8624).
Ans. 19--20; see also Final Action 11-12.
Accordingly, we affirm the rejection of claims 51-53 and 59.
D. Rejection 4
Appellants' arguments specific to claim 60 begin by reciting what
Chen and Palma do not teach. See Appeal Br. 25-26. These arguments are
not persuasive because the Examiner does not rely on Chen or Palma for
such teachings. See Keller, 642 F.2d at 426. Appellants further argue that
"the Office provides no evidence that the skilled artisan interested in the
primer pairs of the present claims would be motivated to combine Chen's
primer sequence with Palma's probe sequence, or do so with a reasonable
expectation of success in arriving at the claimed primer pairs." Appeal Br.
27 (emphases omitted); see also Reply Br. 14. We are not persuaded. As
the Examiner explains, Chen and Palma are only relied upon for teaching
specific primers for amplifying beta-actin mRNA as required by claim 60.
See Ans. 22-23; see also Final Action 12-14. As with the design of the
PRAME primers and probes discussed above with regard to Rejection 1, the
Examiner is on similarly solid footing in concluding that "[b ]ased on the
teachings in the prior art the ordinary artisan would have had more than a
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reasonable expectation of success of making primers for amplifying beta
actin." Final Action 14.
Accordingly, we affirm the rejection of claim 60.
CONCLUSION
The Examiner's rejections of claims 29, 32, 35--41, 44, 51-55, 57---60,
and 68-70 under 35 U.S.C. § 103(a) are each affirmed.
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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