Neil Reginald. Beer

Patent Trials and Appeals Board

Jul 14, 2020

14334462 - (D) (P.T.A.B. Jul. 14, 2020)

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.
14/334,462 07/17/2014 Neil Reginald Beer IL-11764B 1071
24981 7590 07/14/2020
Lawrence Livermore National Security, LLC
LAWRENCE LIVERMORE NATIONAL LABORATORY
PO BOX 808, L-703
LIVERMORE, CA 94551-0808
EXAMINER
CROW, ROBERT THOMAS
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
07/14/2020 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):
llnldocket@llnl.gov
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte NEIL REGINALD BEER1
________________

Appeal 2019–000493
Application 14/334,462
Technology Center 1600
________________

Before: JEFFREY N. FREDMAN, JOHN G. NEW, and
JAMIE T. WISZ, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the word “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant identifies Lawrence Livermore National
Security, LLC and the United States of America, as represented by the
United States Department of Energy (DOE), as the real parties-in-interest.
App. Br. 2.
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SUMMARY
Appellant files this Appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 17 and 30 as unpatentable under 35
U.S.C. § 112(b) as lacking written descriptive support.
Claims 17 and 30 also stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Mathies et al. (US
2005/0287572 A1, December 29, 2005) (“Mathies”), Bruno (US
2006/0257958 A1, November 16, 2006) (“Bruno”) and Pamula et al. (US
2007/0243634 A1, October 18, 2007) (“Pamula”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to a system for fast DNA
sequencing by amplification of genetic material within microreactors,
denaturing, demulsifying, and then sequencing the material, while retaining
it in a PCR/sequencing zone by a magnetic field. Abstr.

REPRESENTATIVE CLAIM
Independent claim 17 is representative of the claims on appeal
and recites:
Claim 17. A method of sequencing nucleic acids in a sample
on a microchip, comprising performing the steps of:

providing a microchannel flow channel in the microchip;
isolating the nucleic acids in the sample;

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combining the nucleic acids in the sample with water
producing nucleic acids in the sample in said water;

providing magnetic nanoparticles;

combining the nucleic acids in the sample in said water
and said magnetic nanoparticles producing nucleic acids in the
sample in said water combined with said magnetic nanoparticles;

hybridizing the nucleic acids in the sample in said water
nucleic acids in the sample in said water hybridized to said
magnetic nanoparticles producing nucleic acids in the sample in
said water hybridized to said magnetic nanoparticles;

providing a droplet maker connected to said microchannel
flow channel wherein said nucleic acids in the sample in said
water hybridized to said magnetic nanoparticles are directed into
said microchannel flow channel;

transferring the nucleic acids in the sample in said water
hybridized to said magnetic nanoparticles to said droplet maker;

using said droplet maker to form microreactors in said
microchannel flow channel, said microreactors containing the
nucleic acids in the sample in said water hybridized to said
magnetic nanoparticles;

providing a magnetic trap in said microchannel flow
channel;

providing a thermal cycler connected to said microchannel
flow channel at the location of said magnetic trap in said
microchannel flow channel;

providing a hydrophobic carrier fluid in said microchannel
flow channel for moving said microreactors containing the
nucleic acids in the sample in said water hybridized to said
magnetic nanoparticles in said microchannel flow channel;
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using said hydrophobic carrier fluid for positioning said
microreactors containing the nucleic acids in the sample in said
water hybridized to said magnetic nanoparticles in said magnetic
trap with said thermal cycler connected to said microchannel
flow channel at the location of said magnetic trap in said
microchannel flow channel, using said thermal cycler to provide
heating and cooling of the nucleic acids in the sample in said
water hybridized to said magnetic nanoparticles;

amplifying the nucleic acids in the sample in said water
hybridized to said magnetic nanoparticles by polymerase chain
reaction heating and cooling of the nucleic acids in the sample in
said water hybridized to said magnetic nanoparticles using said
thermal cycler to produce amplified nucleic acids, wherein said
step of amplifying the nucleic acids is performed with the nucleic
acids in said microchannel flow channel at the location of said
magnetic trap in said microchannel flow channel,

providing a laser that produces a laser beam,

positioning said laser in a position to direct said laser beam
into said magnetic trap and onto said amplified nucleic acids in
said magnetic trap,

sequencing said amplified nucleic acids in said
microchannel flow channel at the location of said magnetic trap
in said microchannel flow channel by directing said laser beam
onto said amplified nucleic acids in said magnetic trap wherein
said amplified nucleic acids are excited by said laser beam into
fluorescence thereby producing
emissions,

providing a complementary metal-oxide-semiconductor
imager,

positioning said complementary metal-oxide-
semiconductor imager in a position to receive emissions from
said magnetic trap, and
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reading said emissions using said complementary metal-
oxide-semiconductor imager while said amplified nucleic acids
are in said magnetic trap.

App. Br. 22–23.

ISSUES AND ANALYSES
We do not agree with and we decline to adopt, the Examiner’s
findings, reasoning, and conclusion that claims 17 and 30 lack written
descriptive support. We agree with the Examiner’s findings, reasoning, and
conclusion that claims 17 and 30 are obvious over the combined cited prior
art. We address the arguments raised sequentially by Appellant below.

A. Rejection of claims 17 and 30 under 35 U.S.C. § 112(b)

Issue
Appellant argues that the Examiner erred in concluding that the
limitations of claims 17 and 30 reciting “positioning said laser in a position
to direct … in said magnetic trap” and “positioning said complementary
metal-oxide-semiconductor imager … from said magnetic trap” are not
provided with adequate written descriptive support in Appellant’s
Specification. App. Br. 9.

Analysis
The Examiner finds that, above, although neither limitation of the
amended claims is necessarily limited to an active method step of
positioning either device, the claims nevertheless encompass active method
steps of positioning the devices. Final Act. 4. The Examiner finds that
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Appellant’s specification provides no disclosure of any active step of
“positioning” of either the laser or the metal-oxide-semiconductor imager
and, therefore, the amended limitations constitute new matter. Id.
Appellant points to paragraphs [0063] and [0070] and to Figure 3 of
the Specification as disclosing the disputed limitations. The relevant portion
of Figure 3 is depicted below:

Figure 3 (detail) of Appellant’s Specification depicts an
embodiment of a system for sequence analysis of a nucleic acid
constructed in accordance with the claimed invention

Appellant argues that a person skilled in the art would understand that
Figure 3 of the Specification shows laser 316 directing a laser beam into the
magnetic and fluidic trap 312 and onto the amplified nucleic acids in the
magnetic trap. App. Br. 10. Similarly, Appellant asserts, a person of
ordinary skill would comprehend that Figure 3 also shows that the laser 316
is positioned to direct its laser beam into the magnetic trap and onto the
amplified nucleic acids in the magnetic. Id. at 12.
We agree with Appellant. The written description requires that the
Specification “clearly allow persons of ordinary skill in the art to recognize
that [the inventor] invented what is claimed.” Vas–Cath Inc. v. Mahurkar,
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935 F.2d 1555, 1563 (Fed. Cir. 1991). Paragraph [0063] of Appellant’s
Specification discloses, in relevant part:
When the droplets pass through the optical enhancement, or
“Capture Zone” 312, the electromagnets 313 strip the passing
droplets of their nanoparticles, accumulating them first near the
walls (close to the magnets) and then further and further into the
free stream of the fluid flow. As the entire channel begins to fill,
optical density reaches a practical maximum, and the
nanoparticles are excited by laser or LED light source 316 into
fluorescence. As they fluoresce, their emission is read by a
photodiode with amplification (such as a Trans-impedance
amplifier), or an imaging system such as a CCD or CMOS array
317. After the measurement is taken, the magnets 313 are de-
energized and the magnetic beads, or nanoparticles 304a, wash
away, clearing the channel 302 for the next assay.

Paragraph [0070] similarly discloses that:
Once the channel 302 has been saturated with the sample 304 and
nanoparticles 304a, the optical density of fluorophores will be
highest, at which time the instrument will be its most sensitive.
Optical excitation by LED, laser, or other means 316 will elicit
the strongest response, and the system will capture this signal at
such sensors as a photodiode with trans-impedance amplifier, or
an imaging array such as a CCD or CMOS imager 317.

These passages, in conjunction with Figure 3 of the Specification,
inform a person of ordinary skill in the art that the laser and the metal-oxide-
semiconductor imager are respectively positioned “to direct said laser beam
into said magnetic trap and onto said amplified nucleic acids” and “to
receive emissions from said magnetic trap.” Indeed, the Examiner concedes
that the limitations are not “necessarily limited to an active method step of
positioning either device,” but finds that “the claims do encompass active
method steps of positioning the devices.” Ans. 3. Nevertheless, we agree
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with Appellant that an artisan of ordinary skill would understand that, upon
comprehending the disclosures of the Specification, for the laser and the
imager to be positioned to “direct said laser beam into said magnetic trap
and onto said amplified nucleic acids” and to “receive emissions from said
magnetic trap,” one must first correspondingly position the laser and imager
to achieve their respective intended purposes. We consequently agree with
Appellant that the disclosures of the Specification “clearly allow persons of
ordinary skill in the art to recognize that [the inventor] invented what is
claimed,” and we reverse the Examiner’s rejection of the claims upon this
ground. See Vas–Cath, 935 F.2d at 1563.

B. Rejection of claims 17 and 30 under 35 U.S.C. § 103

Issue 1
Appellant argues that the Examiner erred in finding that the combined
cited prior art teaches or suggests the limitations of the claims reciting
“positioning said laser in a position to direct said laser beam into said
magnetic trap and onto said amplified nucleic acids in said magnetic trap”
and “positioning said complementary metal-oxide-semiconductor imager in
a position to receive emissions from said magnetic trap.” App. Br. 16, 23.

Analysis
The Examiner finds that Mathies teaches a method of sequencing
nucleic acid comprising providing a microfluidic flow channel in a chip, in
the form of a microfabricated structure comprising thermal cycling
chambers, in which magnetic beads are retained. Final Act. 4 (citing ¶¶ 9,
60). The Examiner finds that Mathies also teaches isolation of nucleic acids
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from a sample, in the form of genomic DNA from whole blood. Id. at 5
(citing ¶ 51). In this method, the Examiner finds, Mathies teaches that
isolated nucleic acids are hybridized to microspheres as sequencing
templates, using magnetic beads as microspheres, and microreactors, in the
form of microemulsions, are formed, which comprise the magnetic particles
having the hybridized PCR amplicons attached. Id. (citing Mathies ¶¶ 47,
58, 59–60).
Specifically, the Examiner finds that Mathies teaches forming
microreactors by combining water, microspheres, PCR reagents (i.e., an
aqueous solution), and DNA template fragments, which are formed using a
hydrophobic carrier solution. Final Act. 5 (citing ¶¶ 93–94). The Examiner
finds that Mathies teaches that the microreactors are formed with a droplet
maker, which is connected directly to the channel. Id. (citing ¶ 46, 100, Fig.
10B).
The Examiner finds that Mathies teaches that PCR amplification,
which occurs in the microsphere solution introduced through the droplet
maker (i.e., the T injector region 1006) is performed while the
microemulsions are magnetically trapped and the nucleic acids are
subsequently sequenced via use of a thermal cycler. Final Act 5–6 (citing
Mathies Abstr., ¶¶ 60, 94). The Examiner further finds that Mathies teaches
using a laser in conjunction with a photodiode for detecting fluorescent
signaling due to amplicon size (paragraph 0054), and detection of
fluorescence in the thermal cycling chamber. Id. at 6 (citing Mathies ¶¶ 54,
77, 95). The Examiner concludes that it would therefore have been obvious
to a skilled artisan to direct the laser to detect the fluorescence of the
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amplified genetic material and to detect the amplified genetic material with
the photodiode. Id.
The Examiner finds that, although Mathies teaches the use of particles
with diameters of 1 micron, Mathies does not teach the use of nanoparticles
nor the use of a complementary metal-oxide-semiconductor imager. Final
Act. 7. However, the Examiner finds that Bruno teaches a method for
detection of nucleic acids oligonucleotides, in which the detection method
utilizes nanoparticles and fluorescence detection. Id. (citing Bruno Abstr.,
¶ 10). The Examiner finds that Bruno teaches that detection is performed
with a complementary metal-oxide-semiconductor device to detect images.
Id. (citing Bruno ¶¶ 10, 23). The Examiner also finds that Bruno teaches
that its method uses a magnetic field to trap the nanoparticles in a detection
window where they are imaged, which has the added advantage of allowing
unwanted material to be left behind. Id. (citing Bruno ¶¶ 10, 22).
Finally, the Examiner finds that although neither Mathies nor Bruno
teach or suggest the positioning of the laser and imager, Pamula teaches a
method of using a lab-on-a-chip, comprising a flow channel connecting
reservoir 312 to waste area 314. Final Act. 7 (citing Pamula ¶ 143, Fig. 3).
The Examiner finds that Pamula teaches magnetic nanoparticles connected
to amplified nucleic acids, which are then sequenced, and a droplet maker, in
the form of a droplet microactuator, which forms droplets (paragraph 0021 ),
and which is connected to a microchannel. Id. at 7–8 (citing Bruno ¶¶ 19,
21, 27, 157, 369, Fig. 16B).
The Examiner also finds that Pamula teaches a PCR and sequencing
zone in the form of imaging area 318, which also comprises thermal cycling
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area 316. Final Act. 8 (citing Pamula ¶ 143, Fig. 3). The Examiner finds
that Pamula teaches the use of lasers for fluorescence excitation (paragraph
0088) and fluorescence detection using photodiodes, and further teaches
positioning the laser (i.e., aligning the light source) for detection in a droplet.
Id. (citing Pamula ¶¶ 88, 558). Similarly, the Examiner finds that Pamula
also teaches positioning the imager (i.e., aligning the sensor) to detect the
signals. Id. (citing ¶¶ 253, 518, 531, 558).
The Examiner concludes that it have been obvious to a person of
ordinary skill in the art to combine the teachings of Mathies, Pamula, and
Bruno to arrive at Appellant’s claimed method with a reasonable expectation
of success. Final Act. 10. The Examiner further concludes that a skilled
artisan would have been motivated to combine the references to obtain the
following added advantages: (1) allowing higher throughput in a faster time
as taught by Pamula (¶ 255); (2) reducing the cost and space requirements of
genome sequencing as taught by Mathies (¶ 8); and (3) permitting unwanted
material to be left behind as well as washing as taught by Bruno (¶ 10). Id.
Appellant argues that none of the references teach the limitations
reciting “positioning said laser in a position to direct said laser beam into
said magnetic trap and onto said amplified nucleic acids in said magnetic
trap” and “positioning said complementary metal-oxide-semiconductor
imager in a position to receive emissions from said magnetic trap.” App. Br.
16. Specifically, Appellant argues that Pamula teaches only a “thermal
cycling area 316” and does not does not teach or suggest the disputed claim
limitations. App. Br. 18.
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We are not persuaded by Appellant’s argument. Pamula, upon which
the Examiner relies (see Final Act. 8) teaches the use of, inter alia, lasers as
preferred light sources for fluorescent detection:
Fluorescence detection is suitable for detection of amplified
nucleic acid. Light emitting diodes (LEDS) and laser diodes are
suitable as excitation sources because of their small physical size,
low power requirements and long life. LEDs are appealing
because of their low cost and laser diodes because of their narrow
spectral width, and the fact that they can be focused to small spot
sizes without discarding a substantial amount of light.

Pamula ¶ 88. Pamula also teaches that:
[W]here a light source is necessary to cause fluorescence of a
molecule in a droplet on the droplet microactuator, the light
source may be mounted to the cartridge or other component of
the droplet microactuator device or system and aligned so that
the light source can reach the droplet to produce the desired
fluorescence.

Id. at ¶ 558 (emphasis added). Similarly, with respect to sensors, the
Examiner finds that Bruno teaches the use of complementary metal-oxide-
semiconductor sensors in fluorescence detection in lab-on-a-chip system:
Finally, results are detected or quantified by fluorometer,
fluorescence intensity, spectrofluorometry features, fluorescence
lifetime analysis, spectrophotometry, spectrofluorometer, time-
resolved fluorometer, photodiode, photodiode array, charge-
couple device (“CCD”) camera, complementary metal oxide
semiconductor (“CMOS”), photomultiplier tube (“PMT”), or
visual assessment of the magnetic bead-target complexes in the
miniature detection window.

Bruno ¶ 10 (emphasis added). Pamula teaches, with respect to such sensors:
Where sensors are exterior to the droplet microactuator, those
sensors may in some embodiments be aligned such that upon
coupling to the droplet microactuator system, the sensing
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elements are appropriately aligned to detect signals from the
droplet microactuator, e.g., the photon sensor is aligned with the
appropriate window and/or with the appropriate location on the
droplet microactuator where the sensing step will be
accomplished in the course of a droplet protocol.

Pamula ¶ 518 (emphasis added). Pamula further teaches that:
[A] sensor may be provided on a cartridge to which the droplet
microactuator is coupled. The coupling is arranged so that when
the droplet microactuator is coupled to the cartridge, suitable
components are aligned to permit detection. Thus, for example,
photon sensor may be aligned with a window or other
transparent substrate so that when the droplet microactuator is
properly mounted on the cartridge, photons emitted from a
droplet on the droplet microactuator may pass through the
window or substrate for detection by the photon sensor.

Id. at ¶ 558 (emphasis added). Pamula thus teaches that both the laser light
source and the CMOS sensor must necessarily be aligned (i.e., positioned)
so that the laser can illuminate the droplet and the sensor can detect the
signal. As we have explained supra, a person of ordinary skill in the art,
realizing that Pamula teaches that the laser and sensor are positioned to
illuminate and detect, would understand how to first position the laser and
sensor to achieve those ends in the context of the devices of Mathies and
Bruno. We conclude that Appellant’s argument is without merit.

Issue 2
Appellant argues that the Examiner erred because a person of ordinary
skill in the art would not have had a reasonable expectation of success in
combining the references. App. Br. 19.

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Analysis
Appellant argues that the systems taught respectively by Mathies,
Bruno, and the Pamula are elaborate systems with many interconnected
components. App. Br. 19. According to Appellant, the proposed
combination of Mathies, Bruno, and the Pamula reference system would not
provide a functioning system, because the proposed combination would be
such an elaborate combined system that many interconnected components
would not function together. Id. Appellant asserts that the Final Office
Action does not explain how the references could be combined into a single
functioning system. Id. Appellant also repeats the argument supra that the
combined references fail to teach or suggest the “positioning laser” and
“positioning imager” limitations recited by Appellant’s claims. Id.
We are not persuaded by Appellant’s arguments. As an initial matter,
we have explained our reasoning with respect to why we conclude that the
combined references teach the disputed “positioning laser” and “positioning
imager” limitations. We find Appellant’s argument upon this subject no
more persuasive upon repetition.
“The test for obviousness is not whether the features of a secondary
reference may be bodily incorporated into the structure of the primary
reference…. Rather, 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 (C.C.P.A. 1981). As we have explained supra,
the Examiner finds, in considerable detail, that Mathies teaches all of the
limitations of Appellant’s claims, with the exception of the use of
nanoparticles and a laser and a CMOS imaging/sensor device positioned to
detect fluorescence images. See Final Act. 4–7. The Examiner relies upon
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Bruno as teaching the use of nanoparticles and CMOS sensors. See Final
Act. 7, 10. The Examiner also relies upon Pamula as teaching the use of
lasers for fluorescence excitation and fluorescence detection using
photodiodes, as well the “positioning laser” and “positioning imager”
limitations, as we have already explained. See Final Act. 8. Additionally,
and as we have explained, the Examiner has also articulated reasons as to
why a person of ordinary skill would have found it obvious to combine the
teachings of the references, and why a skilled artisan would have been
motivated to do so. See Final Act. 10–11.
Furthermore, all of the references are directed to closely-related
inventions. Mathies is directed to a “microfabricated structure including a
microfluidic distribution channel [ ] configured to distribute microreactor
elements having copies of a sequencing template into a plurality of
microfabricated thermal cycling chambers” for genomic analysis, including
via PCR. Mathies, Abstr. ¶¶ 7, 11. Mathies teaches that: “Microspheres are
ideal carriers, providing flexible control over size, surface, fluorescent, and
magnetic properties” and that “[s]econdary PCR amplification can be
performed in an on-chip, dual-use thermal cycling chamber in which
paramagnetic microspheres are routed to individual reactors and
magnetically retained for analysis.” Id. at ¶¶ 55, 60.
Bruno teaches:
[A] small (business card-sized) disposable mesofluidic or
microfluidic plastic cartridge containing several straight
microchannels potentially filled with culture media, solubilizing
reagents (e.g., detergents) nitrocellulose paper strip, gel or other
matrix materials and lyophilized paramagnetic microbeads or
microparticles coated with antibodies, nucleic acid aptamers,
oligonucleotides, or other types of proteins or other receptors for
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capture and concentration of target analytes in environmental,
food, animal, or clinical body fluid samples. Target analytes in
fluids are allowed to wet and interact with the lyophilized capture
reagent-magnetic beads and are then moved to a second position
by means of an external magnetic field.

Bruno ¶ 10.
Pamula is directed to, inter alia:
[M]ethods, devices and systems for amplification of nucleic
acids in droplets on a droplet microactuator. A large number of
copies of one or more nucleic acid molecules can be made in a
single droplet from a small number of copies or even a single
copy present in the droplet. The methods of the invention
generally involve combining the necessary reactants to form an
amplification-ready droplet and thermal cycling the droplet at
temperatures sufficient to result in amplification of a target
nucleic acid, e.g., by the polymerase chain reaction (PCR).

Pamula ¶ 55. Pamula also teaches the use of microbead and nanobead
carriers and that “where magnetically responsive beads are used, they may
be maintained in place using a magnetic field and/or they may be transported
from place-to-place in droplets.” Id. at ¶¶ 19, 182.
In summary, all three references are directed to microchannel “lab-on-
a-card” type analyte detection or sequencing systems that use magnetic
micro- or nanobeads that can be used to immobilize and/or transport the
analyte in, or to and from, a testing chamber. Given the similarities of the
systems in these respects, we agree with the Examiner that an artisan skilled
in this field would have had a reasonable expectation of success in
combining the references. We are consequently not persuaded by
Appellant’s argument.

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Issue 3
Appellant argues that the Examiner erred by failing to provide reasons
for combining the references to produce the proposed combination. App.
Br. 20.

Analysis
Appellant contends that the reasons stated by the Examiner in the
Final Office Action for combining the references, viz.: (1) allowing higher
throughput in a faster time; (2) reducing the cost and space requirements of
genome sequencing; and (3) permitting unwanted material to be left behind
as well as washing, are only lists of added advantages and not an explanation
of how the references would or could be combined. App. Br. 20 (citing
Final Act. 10). Appellant repeats the argument that the references each
teach elaborate systems with many interconnected components, and that the
Examiner does not explain how the systems taught by the several references
could be combined into a single functioning system. Id. at 20–21.
We are not persuaded. The Examiner expressly finds that: “Mathies
et al[.] does not explicitly teach nanoparticles nor the use of a
complementary metal-oxide-semiconductor imager. However, Bruno
teaches a method for detection of nucleic acids (i.e., oligonucleotides),
wherein the detection utilizes nanoparticles and fluorescence detection.”
Final Act. 7 (internal citations omitted). The Examiner also finds that
“Pamula et al[.] teach a method comprising use of a microchip, in the form
of a lab-on-a-chip” and that:
Pamula et al[.] teach using lasers and positioning of the laser (i.e.,
aligning the light source) for detection in a droplet. Pamula et
al[.] further teach positioning the imager (i.e., including aligning
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the sensor) to detect the signals. Thus, positioning the laser to
direct the beam into the magnetic trap and positioning the imager
in a position to receive emissions from the magnetic trap would
be obvious.

Id. at 7, 8 (internal citations omitted). The Examiner thus concludes that
Appellant’s invention would have been obvious over the combined cited
prior art, because it would have been obvious to substitute the nanoparticles
and CMOS emission detector of Bruno for the microbeads and fluorescence
detection taught by Mathies. We determine that this is a reasonable
conclusion by the Examiner, given that both Mathies and Bruno teach very
similar systems, and that Bruno teaches that: “The beads may be any suitable
size, including for example, microbeads, microparticles, nanobeads and
nanoparticles. In some cases, beads are magnetically responsive….” Bruno
¶ 19. This would teach a person of ordinary skill in the art that nanoparticles
could be substituted for the microbeads of the similar system taught by
Mathies. See Mathies ¶¶ 56, 60. Bruno further teaches that:
Finally, results are detected or quantified by fluorometer,
fluorescence intensity, spectrofluorometry features, fluorescence
lifetime analysis, spectrophotometry, spectrofluorometer, time-
resolved fluorometer, photodiode, photodiode array, charge-
couple device (“CCD”) camera, complementary metal oxide
semiconductor (“CMOS”), photomultiplier tube (“PMT”), or
visual assessment of the magnetic bead-target complexes in the
miniature detection window.

Bruno ¶ 19. We agree with the Examiner that it would have thus been
obvious to a skilled artisan that CMOS-based detection could be substituted
for the fluorescence detection taught by Mathies. See, e.g., Mathies ¶¶ 81,
91; see also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (holding
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that: “The combination of familiar elements according to known methods is
likely to be obvious when it does no more than yield predictable results”).
Similarly, the Examiner concludes that it would have been obvious to
use a laser diode as a light source, as taught by Pamula, in the system of
Mathies, and that it would have been obvious to position the laser and
CMOS sensor in such a manner that they could detect the reaction product.
Mathies teaches that: “The microspheres having a DNA sequencing template
are then identified (step 210). The microspheres may be identified by a
fluorescence activated cell sorting (FACS) technique.” Mathies ¶ 47.
Pamula teaches:
Fluorescence detection is suitable for detection of amplified
nucleic acid. Light emitting diodes (LEDS) and laser diodes are
suitable as excitation sources because of their small physical size,
low power requirements and long life. LEDs are appealing
because of their low cost and laser diodes because of their narrow
spectral width, and the fact that they can be focused to small spot
sizes without discarding a substantial amount of light.

Pamula ¶ 88. We agree with the Examiner that it would have been obvious,
for the reasons stated in the passage above, to employ a laser diode for the
fluorescence detection method taught by Mathies. See KSR, 550 U.S. at 416.
Finally, and as we have explained (and Appellant acknowledges
supra), the Examiner has articulated a reason why a person of ordinary skill
in the art would have been motivated to combine the references. See Final
Act. 10; App. Br. 20.
Because we conclude that the Examiner has established a prima facie
case that claims 17 and 30 are obvious over the combined teachings of the
prior art references and, further, that Appellant has failed to overcome the
Examiner’s prima facie case, we affirm the rejection of the claims.
Appeal 2019–000493
Application 14/334,462

20
CONCLUSION
The Examiner’s rejection of claims 17 and 30 under 35 U.S.C.
§ 112(b) is reversed.
The Examiner’s rejection of claims 17 and 30 under 35 U.S.C.
§ 103(a) is 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)(1).

AFFIRMED

Claims
Rejected
35
U.S.C.
§
Reference(s)/Basis Affirmed Reversed
17, 30 112(b) Written Description 17, 30
17, 30 103 Mathies, Bruno,
Pamula
17, 30
Overall
Outcome 
    17, 30