ROCHE MOLECULAR SYSTEMS, INC.

Patent Trials and Appeals Board

May 6, 2021

2020005524 (P.T.A.B. May. 6, 2021)

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.
13/714,243 12/13/2012 Paul Frank 27470-US 3418
22829 7590 05/06/2021
Roche Molecular Systems, Inc.
4300 Hacienda Drive
Pleasanton, CA 94588
EXAMINER
PRIEST, AARON A
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
05/06/2021 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):
misty.van_atta@roche.com
north_america.narmspatents@roche.com
pair_roche@firsttofile.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PAUL FRANK, ANDREAS GISLER,
ALFRED MOERTLSEDER, and SASCHA ROEHRIG1
Appeal 2020-005524
Application 13/714,243
Technology Center 1600
Before DEBORAH KATZ, JOHN G. NEW, and
ROBERT A. POLLOCK, Administrative Patent Judges.
POLLOCK, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a method of
simultaneous analyzing batches of nucleic acids having different
amplification temperature profiles. Appellant seeks our review of the
Examiner’s decision to reject claims 1–6, 8, and 16–19 as obvious over the
prior art.2 We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a). Appellant identifies the real party in interest as Roche Molecular
Systems, Inc. Appeal Br. 3.
2 The Examiner withdrew the rejection of claims 1–6, 8, and 16–19 as patent
ineligible. Ans. 3.
Appeal 2020-005524
Application 13/714,243
2
Statement of the Case
According to the Specification, standard procedures for assaying
nucleic acids include amplification of the nucleic acids by applying specific
temperature cycles under optimal conditions. Spec. p. 4. The Specification
discloses that “known instruments for amplification” are limited to batch-
wise testing of nucleic acids in a micro-well plate, subjected to the same
temperature cycles. Id. “If not enough samples are available which have to
be tested for the same [nucleic acid],” the test is delayed until the multi-well
plate is filled or the test is run with empty wells. Id. “Both options therefore
reduce testing efficiency.” Id. However, these disadvantages “can be
mitigated by a method and system which allows to run the analysis for
different nucleic acids (i.e. different assays) within the same batch.” Id. at 5.
Accordingly, the Specification describes a segmented thermal unit having
segments which can run different thermal profiles. Id. at 19. Figure 4, for
example, “shows a segmented thermal unit having two areas (211c’, 211c’’
which can be temperature regulated independently from each other. Id. at
22, Fig. 4. In one embodiment, one segment may run cycles at 40 to 70 °C,
and another segment of the thermal unit cycles at 45 to 80 °C.
This means some microwells of the same microwell plate are
subjected to a first thermal profile while others are subjected to
a second thermal profile. In case of a segmented thermal unit all
sample aliquots located in wells which are heated by a
particular segment belong to the same test class while overall
the microwell plate may contain sample aliquots belonging to
different test classes.
Id.
Claims 1–6, 8, and 16–19 are on appeal, of which claims 1 and 17 are
independent. Appellant argues the elements of claims 1 and 17 collectively,
Appeal 2020-005524
Application 13/714,243
3
and sets forth no additional arguments with respect to the dependent claims.
See Appeal Br. 21–28. Claim 1 is representative:
1. A method for nucleic acid analysis in a nucleic acid
analysis system, the method comprising the steps of
receiving, in a sample reception unit of the system,
sample tubes each containing a sample,
receiving, in a data management unit of the system, a test
request for each sample, said test request specifying one or
more assays to be conducted for said sample,
obtaining, using one or more pipettors of the system, one
or more sample aliquots of each sample depending on the one
or more assays are to be conducted, wherein the one or more
pipettors are operably connected to a control unit programmed
to receive the test request from the data management unit,
assigning, by the data management unit, each of the
sample aliquots of each sample to one or more test classes, each
sample aliquot being assigned to a test class according to the
assay which is to be conducted for that sample aliquot, wherein
the test class to which a particular sample aliquot is assigned is
chosen at least according to a thermal profile and a set of
sample treatment conditions to be employed for the assay to be
conducted,
combining, using the one or more pipettors of the system,
sample aliquots belonging to a first test class into a first batch
in a first multiwell plate, said first batch comprising a first
sample aliquot for which a first assay is to be conducted and a
second sample aliquot for which a second different assay is to
be conducted, wherein the first assay and the second different
assay employ a first thermal profile and a first set of sample
treatment conditions,
combining, using the one or more pipettors of the system,
one or more additional sample aliquots belonging to a second
test class into a second batch in a second multiwell plate, said
second batch comprising at least one additional sample
aliquot for which one or more additional assays are to be
Appeal 2020-005524
Application 13/714,243
4
conducted, wherein the one or more additional assays employ a
second thermal profile and a second set of sample treatment
conditions and the first thermal profile differs from the second
thermal profile and the first and second sets of sample
processing treatment are different,
subjecting, by one or more sample treatment subsystems
of the system, the first and second batches to the first and
second sets of sample treatment conditions, respectively,
simultaneously subjecting, by a thermal unit of the system, said
first and second batches to the first and second thermal profiles,
respectively, and thereby simultaneously amplifying nucleic
acids contained in said first and second batches, and
conducting, by one or more of a detection unit and
evaluation unit of the system, an analysis of the sample aliquots
to determine the presence and/or concentration of nucleic acids
in said sample aliquots.
Id. at 30–31.
Issue
The Examiner rejects claims 1–6, 8, and 16–19 under 35 U.S.C.
§ 103(a) as obvious in view of Arciniegas,3 Cohen,4 Applied Biosystems,5
and Aoyagi.6 Final Act. 5–11. The Examiner also rejects claim 16 as
obvious in view of Arciniegas, Cohen, and Crosby.7 Id. at 11–12.
Appellant contends that none of the above combinations teach or
suggest “grouping assays in a batch-wise manner based on common thermal
profiles and sample treatment conditions.” Appeal. Br. 27. We do not find

3 Arciniegas et al., US 2005/0009070 A1, publ. Jan. 13, 2005.
4 Cohen et al., US 2008/0255252 A1, publ. Oct. 16, 2008.
5 Applied Biosystems, Applied Biosystems 7300/7500/7500 Fast Real-Time
PCR System, Relative Quantification Getting Started Guide (2010).
6 Aoyagi, K., PCR, in Molecular Biology Problem Solver: A Laboratory
Guide, 292–329 (Alan S. Gerstein ed., 2001).
7 Crosby et al., US 2007/0264636 A1, publ. Nov. 15, 2007.
Appeal 2020-005524
Application 13/714,243
5
Appellant’s arguments persuasive. For the reasons set forth below, we affirm
the Examiner’s rejection of independent claims 1 and 17. Appellant does not
separately contest any element of dependent claims 2–6, 8, 16, 18, and 19,
such that they fall with the independent claims.
We adopt the Examiner’s findings of fact and reasoning regarding the
content and application of Arciniegas, Cohen, Applied Biosystems, and
Aoyagi.8 We emphasize the following findings of fact relevant to the
contested elements.
Findings of Fact (“FF”)
1. Arciniegas discloses a system for “controlling the temperature
in discrete regions of a spatial array of reaction zones, thereby allowing
different thermal domains to be created and maintained in a single multi-
well plate.” Arciniegas ¶ 8. Arciniegas discloses that “[t]he invention thus
allows two or more individualized PCR experiments to be run in a single
plate,” so that multiple procedures can “be performed simultaneously with
improved uniformity and reliability within each zone, together with
reductions in cost and complexity. Id.
2. Arciniegas discloses that the system “applies to spatial arrays of
reaction zones in which the arrays are either a linear array, a two-
dimensional array, or any fixed physical arrangement of multiple reaction
zones” and “is of particular interest to sample blocks that form planar two-
dimensional arrays of reaction zones, and most notably microplates of
various sizes.” Id. ¶ 23. “The most common microplates are those with 96

8 We need not reach the Examiner’s further argument with respect to
Crosby.
Appeal 2020-005524
Application 13/714,243
6
wells arranged in a standardized planar rectangular array of eight rows of
twelve wells each, with standardized well sizes and spacings.” Id.
3. Cohen discloses testing a sample for the presence of
Propionibacterium acnes. Cohen ¶ 52. The analysis involves extracting
DNA from the test sample and amplifying P. acnes DNA by PCR using
primers specific to P. acnes Groups 1, 2, and 3. Id. ¶ 53. For example, the
“primer may comprise sequences that are common in different groups of P.
acnes, such as Groups 1, 2, and 3, but amplify a DNA sequence specific for
P. acnes Group 1 and/or Group 2 and/or Group 3.” Id. ¶ 115.
4. Cohen discloses various examples of applying different primers
to detect P. acnes from a specific Group. See id. ¶¶ 220–229. For example,
Cohen discloses amplifying nucleotides from only Group 1 with: (a)
primers PR090 and PR108, subject to PCR cycling of “15 mins at 95° C., 35
cycles of 30 seconds at 94° C., 30 seconds at 55° C. and 1 min at 72° C.,
followed by 7 min extension at 72° C.”; and (b) primers PR213 and PR216,
subject to PCR cycling of “15 mins at 95° C., 35 cycles of 30 seconds at 94°
C., 30 seconds at 58° C. and 1 min at 72° C., followed by 7 min extension at
72° C.” Id. ¶¶ 221–222 (emphasis added). Likewise, Cohen discloses
amplifying nucleotides from only Group 2, with: (a) primers PR217 and
PR218, subject to PCR cycling of “15 mins at 95° C., 35 cycles of 30
seconds at 94° C., 30 seconds at 55° C. and 1 min at 72° C., followed by 7
min extension at 72° C” and (d) primers PR256 and PR257 subject to PCR
cycling of “15 mins at 95° C., 35 cycles of 30 seconds at 94 ° C., 30 seconds
at 58° C. and 1 min at 72° C., followed by 7 min extension at 72° C.” Id.
¶¶ 224, 227 (emphasis added).
Appeal 2020-005524
Application 13/714,243
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5. Applied Biosystems discloses using PCR to perform a relative
quantification assay for multiple different genes of interest in a sample.
Applied Biosystems 10. Applied Biosystems discloses designing
“experiments so that several samples are amplified on the same plate.” Id.
6. Aoyagi teaches optimizing various PCR parameters, including
buffer components and cycling conditions as shown in Tables 11.3, 11.4,
and 11.5. Aoyagi 303. For example, Table 11.4 lists several PCR enzymes
along with their differing heat stabilities. Id. at 301.
Analysis
The Examiner finds that Arciniegas “teaches multiple sections of a
single multiwell plate run at different PCR thermal profiles.” Final Act. 7–8
(citing Arciniegas ¶¶ 8, 23). The Examiner finds that it was well known to
use two sample aliquots in different assays on the same multiwell plate, but
using the same thermal profile for each. Id. at 8; see also 9–10 (citing
Applied Biosystems). The Examiner finds that Cohen teaches optimizing
different PCR profiles for different target nucleic acids based on primer
melting/annealing temperatures, e.g., 30 seconds at 55–66° C. Id. at 9 (citing
Cohen ¶¶ 186, 201, 218–220, 224, 226–229, 232–235 (Examples 1–8)). The
Examiner finds that a skilled artisan would have been motivated to group
together nucleic acid targets according to similar thermal profiles for testing
as taught by Arciniegas. See id. 9. The Examiner concludes that:
It would have been prima facie obvious to one having
common sense and ordinary skill in the art at the time of the
invention to simply apply multiple assays (e.g., multiple target
nucleic acids as in COHEN and Applied Biosystems) in a
multiwall plate, for example using familiar segmented thermal
amplification blocks, in order to reduce costs, materials, time
Appeal 2020-005524
Application 13/714,243
8
and complexity (e.g. increase efficiency) with a reasonable
expectation of success.
Id. at 6.
Appellant acknowledges that “Arciniegas discloses a means for
independently controlling the temperature in discrete regions of a spatial
array of reaction zones, such that two or more individual PCR experiments
can be run on a single plate,” but argues that “Arciniegas fails to teach or
suggest combining different assays into the same batch based on a common
thermal profile and sample treatment conditions.” Appeal Br. 21–23.
Appellant argues that Cohen discloses “reactions that can be conducted in
isolation and [] does not suggest performing two assays simultaneously in a
single batch where the two assays share a common thermal profile and
reaction conditions.” Id. at 24. Appellant further argues that Cohen
“explicitly teaches away” from grouping assays based on a common set of
treatment conditions and thermal profile because “Cohen specifies a
different set of reaction conditions that are individually optimized for each
reaction and primer set used to detect the various target sequences.” Id. at
26.
With respect to Applied Biosystems and Aoyagi, Appellant argues
that neither reference teaches or suggests grouping assays in a batch-wise
manner based on common thermal profiles and sample treatment conditions.
Id. at 27. Specifically, Appellant argues that the “Applied Biosystems Guide
arguably discloses is that one can design singleplex and multiplex assays but
there is no suggestion that one can group those assays based on a common
thermal profile and set of sample treatment conditions.” Id. Appellant argues
that Aoyagi is limited to disclosing “optimization of various reagents
components in a PCR assay.” Id.
Appeal 2020-005524
Application 13/714,243
9
We do not find Appellant’s argument persuasive. In determining
obviousness, “the test is what the combined teachings of the references
would have suggested to those of ordinary skill in the art.” In re Keller, 642
F.2d 413, 425 (CCPA 1981). Accordingly, “one cannot show non-
obviousness by attacking references individually where, as here, the
rejections are based on combinations of references.” Id. at 426. We agree
with the Examiner that it was well known to test for multiple genes of
interest on the same multiwell plate using individualized sample treatment
conditions. See FF 5. Cohen confirms that it was known to apply different
thermal profiles for different primers when testing for different nucleic acids
from the same sample. See FF 3, 4 (Group 1 tests (a), (b); Group 2 (tests (a),
(d)); see also FF 6. Arciniegas discloses a system for applying discrete
temperatures zones to known multiwell plates for performing multiple
different tests on a sample, thereby reducing cost and complexity. See FF 1,
2. It would have been obvious, for the reasons given by the Examiner, to
perform Cohen’s tests for P. acnes Groups 1, 2, and 3 on a multi-well plate
and group the tests into discrete temperature zones, e.g., one zone for Group
1 test (a) and Group 2 test (a), and a different zone for Group 1 test (a) and
Group 2 test (d). Accordingly, the combined prior art teaches or suggests all
of the elements of the claims.
We are also not persuaded by Appellant’s argument that Cohen
teaches away from the combination. A teaching away requires a reference to
actually criticize, discredit, or otherwise discourage the claimed solution.
See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). Cohen does not
criticize, discredit, or discourage performing the disclosed assay on a
multiwell plate by disclosing optimized parameters for individual tests.
Appeal 2020-005524
Application 13/714,243
10
Rather, Arciniegas proposes a solution for allowing Cohen’s tests to be
performed on the same multi-well plate, despite having different thermal
profiles.
Appellant has not shown that the Examiner erred in rejecting claims 1
and 17. Accordingly, we affirm the Examiner’s rejection of those claims.
Claims 2–6, 18, 16, 18, and 19, which are not separately argued, fall with
claims 1 and 17. 37 C.F.R. § 41.37(c)(1)(iv).
CONCLUSION
Claims
Rejected
35
U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–6, 8,
16–19
103(a) Arciniegas, Cohen,
Applied
Biosystems,
Aoyagi
1–6, 8,
16–19

16 103(a) Arciniegas, Cohen,
Crosby
16
Overall
Outcome
1–6, 8,
16–19

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED