Ex Parte Yamada et al

Patent Trial and Appeal Board

Feb 3, 2016

12396308 (P.T.A.B. Feb. 3, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/396,308 0310212009
22878 7590 02/05/2016
Agilent Technologies, Inc. in care of:
CPA Global
P. 0. Box 52050
Minneapolis, MN 55402
FIRST NAMED INVENTOR
N. Alice Yamada
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.
20081081-01 6039
EXAMINER
BHAT, NARAYAN KAMESHWAR
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
02/05/2016 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):
IPOPS.LEGAL@agilent.com
Agilentdocketing@cpaglobal.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte N. ALICE YAMADA, PETER TSANG,
ROBERT A. ACH, and AMIR BEN-DOR
Appeal2013-002764
Application 12/396,308
Technology Center 1600
Before DONALD E. ADAMS, LORA M. GREEN, and
CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL 1
This appeal under 35 U.S.C. § 134(a) involves claims 1-14 (Ans. 3;
Non-Final Rej. 2).2 Examiner entered rejections under 35 U.S.C. § 102(b)
and 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as "Agilent Technologies,
Inc." (Br. 3).
2 All reference to the: (1) Non-Final Rejection (Non-Final Rej.) refers to the
February 16, 2012 Non-Final Rejection and (2) Examiner's Answer (Ans.)
refers to the September 24, 2012 Examiner's Answer.
Appeal2013-002764
Application 12/396,308
STATEMENT OF THE CASE
Appellants' Specification provides "[a] method of sample analysis"
(Spec. 2:7). Claims 1, 4, and 5 are representative and reproduced below.
1. A method of sample analysis, comprising:
a) contacting a genomic sample comprising a plurality of
intact chromosomes with a first set of labeled oligonucleotide
probes under in situ hybridization conditions to produce a
contacted sample comprising a labeled chromosome, wherein:
i. each of said labeled oligonucleotide probes is
complementary to a non-repetitive, unique sequence in a region
that flanks the centromere of said labeled chromosome; and
ii. hybridization of said labeled oligonucleotide
probes to said chromosomes results in labeling of sites on both
arms of said labeled chromosome to produce a distinct labeling
pattern;
b) imaging said labeled chromosome to provide an image
showing the labeling pattern for said labeled chromosome; and
c) enumerating said labeled chromosome based on i. the
emission spectrum of the sites that are labeled on said labeled
chromosome and ii. the proximity of the sites that are labeled
on said labeled chromosome to the centromere of said labeled
chromosome.
4. The method of Claim 1, wherein, for said labeled
chromosome, the labeled oligonucleotide probes bind to a
region that is sufficiently distal to the centromere of said
chromosome that the signals from sister chromatids of said
labeled chromosome are spatially distinct.
5. The method of Claim 1, wherein said enumerating
comprises:
a) determining whether the labeling pattern of said
labeled chromosome comprises a spatially distinct or spatially
indistinct signal; and
b) determining the emission spectrum of said labeling
pattern;
wherein said enumerating is based on whether said
labeling pattern comprises a spatially distinct or spatially
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Application 12/396,308
indistinct signal and the emission spectrum of said labeling
pattern.
Claims 1, 5-7, 9, and 10 stand rejected under 35 U.S.C. § 102(b) as
anticipated by Bastian3 as evidenced by Johanneson4 and Yi-Ling. 5
Claims 1, 2, and 6-8 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Bastian and Barrett. 6
Claims 1, 3, 4, and 11-14 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Bastian and Wolff.7
Anticipation:
ISSUE
Does the preponderance of evidence on this record support
Examiner's finding that Bastian teaches Appellants' claimed invention?
3 Bastian et al., US 6,551,780 Bl, issued Apr. 22, 2003.
4 Bo Johanneson et al., Suggestive Genetic Linkage to Chromosome IIpII.2-
qI2.2 in Hereditary Prostate Cancer Families With Primary Kidney Cancer,
67 THE PROSTATE 732-742 (2007).
5 SI Yi-ling et al., Estrogen Regulation of LRP 16 Gene Expression Involves
SPJ Transcription Factor, 18 CHIN. J. CANCER RES. 251-256 (2006).
6 Barrett et al., US 2007/0238105 Al, published Oct. 11, 2007.
7 Daynna J. Wolff, et al., Molecular Definition of Breakpoints Associated
with Human Xq Isochromosomes: Implications for Mechanisms of
Formation, 58 AM. J. HUM. GENET. 154--160 (1996).
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Application 12/396,308
FACTUAL FINDINGS (FF)
FF 1. Appellants' Figures 1 and 2 are reproduced below:
Fig, 1
l
f 10
\.. ________ '{ _______ _)
2fl
Fig. 2
r
i t
16 {
l
Fig. 1 illustrates a metacentric chromosome 2a, wherein the p arm 4 and q
arm 6 are "roughly equal in length" and an acrocentric chromosome 2b,
wherein "the p arm is much shorter than the q arm" (Spec. 15: 15-17). Fig. 1
further illustrates centromere 8, wherein two sister chromatids 10 are joined
and divided into either the p or q arm (Spec. 12:6-7 and 11: 1-3). Fig. 2
illustrates a method that "involves contacting 12 a genomic sample [16] with
a set of sequence-specific [detectably labeled] oligonucleotide probes 18
under in situ hybridization conditions" to produce labeled chromosomes 20,
wherein the signals from the detectably labeled oligonucleotide probes 18
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Application 12/396,308
are spatially indistinct 22 and 24 or spatially distinct 26 and 28 (Spec.
10:10-19 and 12:10-23).
FF 2. Appellants disclose that:
depending on the location of where the labeled probes bind
along the p or q arms of the two sister chromatids, the signals
from the two sister chromatids of an intact metaphase
chromosome may appear spatially distinct or spatially indistinct
under a microscope used for in situ hybridization experiments.
If the probes are complementary to sequences sufficiently
proximal to the centromere, the signals from the sister
chromatids of the labeled chromosome may appear spatially
indistinct. In other embodiments, if the labeled oligonucleotide
probes bind to a region that is sufficiently distal to the
centromere, the signals from the sister chromatids chromosome
may appear spatially distinct. To demonstrate how spatially
indistinct or distinct signals may appear on labeled intact
metaphase chromosomes, two exemplary chromosomes are
illustrated in Fig. 2 as a hypothetical zoomed image from the
plurality of labeled chromosomes 20. For example, as shown in
Fig. 2, one chromosome has spatially indistinct signals, 22 and
24, from the tv,ro sister chromatids on both the p arms and the q
arms, while the other chromosome has spatially distinct signals
26 and 28 on the p arm and the q arms, respectively.
(Spec. 12:10-23.)
FF 3. Bastian teaches the use of FISH8 to identify 11 p isochromosomes,
wherein a "first probe RPCI-1156c13, which was labeled with FITC and
detected as a green fluorescent signal, maps to chromosome 11 p to a region
adjacent to the centromere, 1lpl1.2" and a "second probe RPCI-11135h08,
which was labeled with Cy3 and detected as a red fluorescent label,
hybridizes to sequences on the q arm of chromosome 11 adjacent to the
centromere at 1lql1" (Bastian 22:60-23:5; Non-Final Rej. 8-9; see also
8 Bastian defines the acronym "FISH" as "[ fJluorescence in-situ
hybridization" (Bastian 58; Non-Final Rej. 8).
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Appeal2013-002764
Application 12/396,308
Non-Final Rej. at 10 ("Bastian teaches[] centromere flanking probes and
detecting the p and the q arm of chromosome 11 based on the green and red
(i.e., emission spectrum) signals ([Bastian,] Example 2, column 23, lines 1-
11 )"); Ans. 5---6; see generally Br. 5).
FF 4. Bastian's FISH method results in "[n]ormal control tissue
[exhibiting] the presence of paired hybridization signals containing two
colors, i.e., the pair of signals included one red signal and one green
signal[,]" whereas the experimental samples exhibited the "presence of
paired hybridization signals of the same color (green) [] demonstrat[ing] the
presence of an 11 p isochromosome" (Bastian 23: 5-11; see Br. 5 ("In
viewing the results of Bastian's method, a 'normal' chromosome 1 should
produce a Cy5 signal and a Cy3 signal, whereas an isochromosome of
chromosome 11 should produce either a pair of Cy5 signals or a pair of Cy3
signals")).
FF 5. Examiner finds that Johanneson establishes that "[a] probe set
hybridizing to the 11p11.1 to 11p11.2 and 11q11.1 to 11q11.2 region of
Bastian flanks the centromere" (Non-Final Rej. 8)
FF 6. Examiner finds that Yi-ling establishes that "[t]he 1lql1 region
compris[es] [the] LRP16 gene" (Non-Final Rej. 8).
ANALYSIS
Claim 1:
Examiner finds, inter alia, that:
detecting chromosome 11 by determining the presence of the
hybridization regions of the centromere flanking probe labeled
with green (i.e., the p arm region) and the red (i.e., the q arm
region) colors encompasses the step of enumerating (i.e.,
detecting) the labeled chromosomes based on [ ( 1)] the emission
spectrum (i.e., the green and the red colors) of the sites that are
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Application 12/396,308
labeled on the chromosome and [(2)] proximity [] to the
centromere because the probes selected are known to hybridize
at sites proximal to the centromere (i.e., the limitation of step
'c(i)').
(Non-Final Rej. 11; see generally Ans. 5---6; FF 1).
Appellants contend that Bastian discloses a color-based method,
wherein "the output [] is essentially an image showing two 'dots' that are
either the same color or different colors" (Br. 5). In this regard, Appellants'
contend that "Bastian does not disclose any method in which the distance of
a hybridization signal to a centromere is evaluated in any way" (id.; see id.
at 6 ("Examiner believes that just because Bastian uses probes that are close
to the centromere then Bastian's enumerating must be based on the
proximity of a signal to the centromere") ). We are not persuaded.
The method of Appellants' claim 1 "does not require the labeled
probes to be at specific distances from the centromere" (Ans. 8). To the
contrary, Appellants' claim 1 merely requires the labeled probes to have
some amount of proximity to the centromere (see Appellants' claim 1 ).
Bastian's method uses two different labeled probes that hybridize at
different regions of chromosome 11, which results in the labeled probes
exhibiting different proximities to the centromere (FF3). In this regard,
Examiner explains that Bastian teaches a method, wherein a labeled
chromosome is enumerated, through the use of labeled probes that
"hybridize to 'p' and 'q' arm regions adjacent to the centromere" (Ans. 8;
FF 2).
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Claim 5:
We recognize, but for the reasons set for by Examiner, are not
persuaded by, Appellants' contentions that: ( 1) "Bastian does not perform
any step that involves determining whether a labeling pattern comprises a
spatially distinct or spatially indistinct signal" or (2) observation of "a
spatially distinct signal and determining whether a labeling pattern
comprises a spatially distinct or a spatially indistinct signal are different
things, and one does not inherently lead to the other" (Br. 6-7; cf Ans. 11 ).
CONCLUSION OF LAW
The preponderance of evidence on this record supports Examiner's
finding that Bastian teaches Appellants' claimed invention.
The rejection of claims 1and5 under 35 U.S.C. § 102(b) as
anticipated by Bastian, as evidenced by Johanneson and Yi-Ling, is
affirmed. Claims 6, 7, 9, and 10 are not separately argued and fall with
claim 1.
Obviousness:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 7. We adopt the Examiner's findings concerning the scope and content
of the prior art (Non-Final Rej. 13-22), and repeat the following findings for
emphasis.
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Application 12/396,308
FF 8. Examiner finds that Bastian fails to disclose probes that comprise
overlapping sequences and relies on Barrett to make up for this deficiency in
Bastian (Non-Final Rej. 17).
FF 9. Examiner finds that "Bastian does not specifically teach the probes
that are distal to the centromere having spatially distinct signal from the
sister chromatids" and relies on Wolff to make up for this deficiency in
Bastian (Non-Final Rej. 19).
FF 10. Examiner finds that Wolff suggests a FISH method using labeled
probes that provide signals from sister chromatids of a labeled chromosome
that are spatially distinct (Non-Final Rej. 20-21; Ans. 13-14; Br. 9).
The combination of Bastian and Barrett:
ANALYSIS
Based on the combination of Bastian and Barrett, Examiner concludes
that, at the time Appellants' invention was made, it would have been prima
facie obvious "to include the overlapping oligonucleotides [of Barrett] in the
FISH method of Bastian with a reasonable expectation of success [and]
expected benefit of having oligonucleotide probes that could be used to map
the chromosomal region or the entire chromosome for high resolution
chromosome mapping as taught by Barrett" (Final Rej. 18).
Having found no deficiency in Bastian, as it relates to Appellants'
claim 1, we are not persuaded by Appellants' contention that "Barrett's
overlapping probes do not meet Bastian's deficiencies" (Br. 8).
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Application 12/396,308
The combination ofBastian and Wolff
ANALYSIS
Based on the combination of Bastian and Wolff, Examiner concludes
that, at the time Appellants' invention was made, it would have been prima
facie obvious to have included Wolff s probes in Bastian's FISH method
"with the expected benefit of having both proximal and distal centromere
probes for better understanding [] the mechanism of [isochromosome]
formation" (Non-Final Rej. 21).
Claim 1:
Having found no deficiency in Bastian, as it relates to Appellants'
claim 1, we are not persuaded by Appellants' contention that "Wolff s
probes do not meet Bastian's deficiencies" (Br. 8).
Claim 4:
Appellants concede that Wolff s probes produce a spatially distinct
signal, but nonetheless contend, that the use of Wolff s probes in Bastian's
method would provide more dots in the resulting image, which would
confuse results" (Br. 9). We are not persuaded. As Examiner explains,
"Bastian and Wolff demonstrate[] that [the] limitations of instant claim 4 are
drawn to well-known method of labeling sister chromatids that are being put
together in such a way as to produce predictable result[s]" (Ans. 13). In this
regard, Examiner finds that a person of ordinary skill in this art would have
optimized W olffs' labeled probes to avoid any confusion when included in
Bastian's method (Ans. 14).
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CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
The rejection of claim 1 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Bastian and Barrett is affirmed. Claims 2 and 6-8
are not separately argued and fall with claim 1.
The rejection of claims 1 and 4 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Bastian and Wolff is affirmed. Claims
3 and 11-14 are not separately argued and fall with claim 1.
TIME PERIOD FOR RESPONSE
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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