James Nial. Hynes et al.

Patent Trials and Appeals Board

May 28, 2020

2019000485 (P.T.A.B. May. 28, 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.
14/233,602 01/17/2014 James Nial Hynes LUXCL005USPT01 6117
22878 7590 05/28/2020
Agilent Technologies, Inc.
Global IP Operations
5301 Stevens Creek Blvd
Santa Clara, CA 95051
EXAMINER
PATURY, SRIKANTH
ART UNIT PAPER NUMBER
1657
NOTIFICATION DATE DELIVERY MODE
05/28/2020 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):
Agilentdocketing@cpaglobal.com
ipopsadmin@agilent.foundationip.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JAMES NIAL HYNES and DMITRI BORIS PAPKOVSKY

Appeal 2019-000485
Application 14/233,602
Technology Center 1600
____________

Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
ULRIKE W. JENKS, Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 files this appeal from
Examiner’s decision to reject the claims as obvious. We have jurisdiction
under 35 U.S.C. § 6(b).
We AFFIRM.

1 Appellant identifies the real party in interest as Luxcel Biosciences, Ltd.
Appeal Br. 2. We use the word “Appellant” to refer to “applicant” as defined
in 37 C.F.R. § 1.42(a).
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STATEMENT OF THE CASE
Claims 1–4, 6–9, 11, 14, 15 and 19 are on appeal, and can be found in
the Claims Appendix of the Appeal Brief. Claim 1 is representative of the
claims on appeal, and reads as follows:
1. A method of detecting the presence of thermoduric
microorganisms in a product, comprising the steps of:
(a) placing an aliquot of the product into a vessel
equipped with an optical probe sensitive to a thermoduric
microorganism metabolite, wherein the thermoduric
microorganism metabolite is oxygen, and wherein the optical
probe is an oxygen sensitive photoluminescent dye,
(b) hermetically sealing the aliquot and the optical probe
within the vessel,
(c) pasteurizing the hermetically sealed aliquot within the
vessel,
(d) incubating the pasteurized and hermetically sealed
aliquot within the vessel for an incubation period, and
(e) periodically interrogating the probe during the
incubation period, wherein the interrogations measure changes
in the probe reflective of changes in concentration of a
thermoduric microorganism metabolite within the aliquot, with
such changes in concentration indicative of the presence of
viable thermoduric microorganisms in the aliquot, having
survived pasteurization of the hermetically sealed aliquot.
Appeal Br., Claims Appendix.
REFERENCES
The prior art relied upon by Examiner is:
Name Reference Date
Kleinerman US 6,607,300 B1 Aug. 19, 2003
Belhumeur et al.
(“Belhumeur”)
US 7,851,178 B1 Dec. 14, 2010
Papkovsky et al.
(“Papkovsky”)
US 2006/0002822 A1 Jan. 5, 2006
G.L. Pettipher & Ubaldina M. Rodrigues, Rapid Enumeration of Bacteria
in Heat-treated Milk and Milk Products Using a Membrane Filtration-
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Name Reference Date
Epifluorescent Microscopy Technique, 50 J. Applied Bacteriology 157–66
(1981) (“Pettipher”)
Milk Facts, Heat Treatments and Pasteurization,
http://milkfacts.info/Milk%20Processing/Heat%20Treatments%20and%20
Pasteurization.htm, last accessed March 2, 2017 (“Milk Facts”)
REJECTION
Claims 1–4, 6–9, 11, 14, 15, and 19 are rejected under pre-AIA
35 U.S.C. §103(a) as being unpatentable over Papkovsky in view of
Pettipher, Belhumeur, and Milk Facts as further evidenced by Kleinerman.
OBVIOUSNESS
The issue is whether the preponderance of evidence of record supports
Examiner’s conclusion that the method of detecting the presence of
thermoduric microorganisms is obvious.
A. Findings of Fact (FF)
FF1. Pettipher teaches that “[q]uality control in the dairy industry would
benefit from the use of a rapid, inexpensive, sensitive, direct method
for enumerating bacteria in milk and milk products.” Pettipher 157.
Pettipher teaches using “[a] rapid direct epifluorescent filter technique
(DEFT) . . . to enumerate bacteria in heat-treated milk and milk
products.” Id., Abstract. Pettipher teaches collecting samples from
collection tankers and pasteurizing the sample in the laboratory at
63°C for 30 minutes, storing the sample in the refrigerator, and
examining the product daily over a 5 day period. Id. at 157.
FF2. Milk Facts teaches that the commercial implementation of
pasteurization eliminated the common milkborne illnesses such as
“typhoid fever, scarlet fever, septic sore throat, diptheria, and
diarrheal diseases.” Milk Facts 3. Milk Facts teaches that
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“pasteurization conditions of 145°F (62.8°C) for 30 minutes for a
batch process, or 161°F (71.7°C) for 15 sec for a continuous process,
were adopted in order to inactivate Coxiella burnetii, and these
conditions are still in use today.” Id.
FF3. Papkovsky teaches that “solid-state luminescent oxygen probes and
systems based thereon have been used in various assays and
applications in particular in blood gas analysis, monitoring biological
activity, presence of microorganisms, cellular respiration, . . . or
sterility for example.” Papkovsky ¶ 5. Papkovsky teaches using an
improved oxygen sensitive probe to monitor
oxygen uptake by chemical or biological samples
comprising the step of adding an oxygen sensitive probe
to a test sample and measuring changes in the probe
emission which reflect changes in the dissolved oxygen
concentration, [] wherein the probe comprises a
monofunctional derivative of an oxygen-sensitive
photoluminescent dye covalently attached to a water-
soluble hydrophilic macromolecular carrier.
Id. ¶ 34.
FF4. The biological test samples contemplated by Papkovsky include
“microorganisms, subcellular organell[e]s, animal tissue or aquatic
animals.” Id. ¶ 35.
FF5. Papkovsky teaches:
Monofunctional derivatives of water-soluble Pt-
coproporphyrins are preferred dyes[, because they are
easily conjugated to macromolecules]. . . . [These
o]xygen probes based on Pt-coproporphyrins have
emission at about 650 nm and they are suitable for time-
resolved fluorescence measurements and lifetime-based
oxygen sensing with relatively simple instrumentation.
. . . [T]he probes can be used in trace amounts even in
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complex biological samples with high scattering and
autofluorescence.
Id. ¶ 65. Papkovsky teaches conjugating the oxygen-sensitive
luminescent dyes to hydrophilic macromolecular carriers. Id. ¶ 67.
The preferred conjugates are:
Pt-porphyrins with poly(ethyleneglycols), (PEGs), such
as PEG-5,000, PEG-10,000 and PEG-20,000 (numbers
correspond to different molecular weights). PEG
molecules normally contain terminal OH-group(s), and
no other reactive functionality within the chain. These
terminal OH-groups are suitable for chemical
modification and/or for site-directed conjugation with the
oxygen-sensitive dyes.
Id. ¶ 68.
FF6. Papkovsky teaches a method of monitoring cellular respiration using a
cell viability assay. Id. ¶¶ 112–114, see Fig. 3. The steps include
adding “PtCP-BSA 2:1 or PtCP-PEG-20, 000 (1:1) conjugate . . . at a
concentration 10.6 to 10-9 M” to a well containing 150 µl of cells at a
concentration range of 105-107 cells/ml. Id. ¶ 112. To this cell:dye
mixture the method adds “100 ul of heavy mineral oil . . . on top of
each sample to reduce the effect of atmospheric oxygen and
phosphorescence intensity readings were taken at regular time
intervals (1-3 minutes) for a for a period of 30-120 min.” Id. ¶ 112,
see also id. ¶ 47 (“Mineral oil reduces diffusion of ambient air oxygen
into the sample thus acting as a seal.”). In addition, Papkovsky teaches
that the dye can be either added directly to the sample or it can be pre-
coated onto the walls of the sample well before adding the sample. Id.
¶ 114.
FF7. Belhumeur teaches a method of evaluating the efficiency of a
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sterilization process. Belhumeur 2:18–20. The method includes
subjecting a prion protein degradation indicator in a container to a
sterilization process followed by determining the degradation of the
indicator. Id. at 2:21–24. “The indicator may be a biological indicator,
biochemical indicator, or chemical indicator.” Id. at 2:36–37.
FF8. Kleinerman teaches photoluminescent material such as platinum(I)
porphyrin among others. Kleinerman 4:13–16. Kleinerman teaches
that it is only “[i]n the high temperature region (above 500°C.) within
which the luminescence decay time τ decreases appreciably,”
resulting in a decrease of luminescent efficiency. Id. at 6:18–20.
FF9. The Specification describes hermetically sealing as any “sealing
techniques capable of withstanding the thermal treatment, including
specifically but not exclusively a screw cap 20, a heat or adhesive
sealing foil (not shown), layer of mineral oil (not shown), etc.” Spec.
¶ 40.
B. Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
C. Analysis
Examiner finds that Papkovsky teaches a method for measuring
oxygen concentration/uptake in biological samples comprising
microorganisms using photoluminescent dyes. Final Act. 3; see also Ans. 6
(Papkovsky “teaches the use of porphyrin based photo luminescent oxygen
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probes (the same dyes used in the instant application) to monitor
microorganism levels in samples.”); FF3–FF6. Examiner finds that
Papkovsky’s method “can measure/monitor any microorganism based on
oxygen consumption/levels in its methods.” Ans. 6. Examiner finds that
Papkovsky correlates the oxygen concentration to cell number. Final Act. 3;
FF6. Examiner acknowledges that Papkovsky “does not teach pasteurization
of the biological sample to be a food sample and monitoring thermoduric
microorganisms in the sample.” Final Act. 4. Examiner relies on Pettipher
and Milk Facts for teaching that pasteurization conditions for milk product
are optimizable. Ans. 6; FF1, FF2. Examiner relies on Pettipher for teaching
a method of monitoring thermoduric bacteria in pasteurized milk. Ans. 6;
FF1. Examiner finds that Kleinerman teaches that “that the porphyrin
oxygen probes can withstand high temperatures.” Ans. 7; FF8. Belhumeur
teaches measuring the sufficiency of a sterilization process using an
indicator. FF7. Examiner cites Belhumeur “to teach that sterilization
(autoclaving) of probes to monitor contamination was known in the art.”
Ans. 7.
Based on these disclosures, Examiner concludes that it would have
been obvious to one of ordinary skill at the time the invention was made to
substitute one known biological sample having the potential for containing
viable bacteria for another. Ans. 5; FF1, FF6. Examiner further concludes
that it would have been obvious to add an oxygen sensitive probe into a
sample before pasteurizing the sample in order to prevent contamination of
the sample after pasteurization. Ans. 5.
Appellant contends that none of the references teach all the limitations
of the present claims. Appeal Br. 5–6. Appellant contends that Pettipher
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“says nothing about use of the technique to specifically measure only
thermoduric bacteria in the milk and milk products.” Appeal Br. 6 (emphasis
added). Appellant contends that Belhumeur “does not disclose a probe to
monitor contamination” because it only measures degradation of the
indicator. Reply Br. 2; see Appeal Br. 6–7.
We have reviewed Appellant’s contentions in light of Examiner’s
cited art and find that the preponderance of the evidence supports
Examiner’s conclusion that the claims are obvious. We address Appellant’s
contentions below.
We are not persuaded by Appellant’s contention that the references do
not disclose all the claimed elements. We note that Appellant’s arguments
attacking the Papkovsky, Pettipher, Belhumeur, Milk Facts, and Kleinerman
references individually (see, e.g., Appeal Br. 5–6), where the rejection is
based on their combination, is improper. “Non-obviousness cannot be
established by attacking references individually where the rejection is based
upon the teachings of a combination of references. . . . [The reference] must
be read, not in isolation, but for what it fairly teaches in combination with
the prior art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir.
1986).
Papkovsky teaches that oxygen sensitive probes were known to be
used to test for sterility. FF3. Papkovsky teaches using oxygen sensitive
probes for monitoring cellular respiration using a cell viability assay. FF6.
The assay takes cells and exposes them to an oxygen-sensitive luminescent
dye before taking phosphorescence intensity readings at intervals over a
two-hour period. FF6. Papkovsky teaches that oxygen-sensitive luminescent
dye and test sample are mixed and then sealed with mineral oil in order to
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reduce the diffusion of ambient oxygen into the test sample. FF6, see FF9
(hermetically sealing encompasses using a layer of mineral oil). Thus, as
acknowledged by Examiner, Papkovsky teaches all the steps but for the
pasteurizing step. See Final Act. 4.
Examiner relies on Pettipher and Milk Facts for teaching
pasteurization of milk to make it safe for consumption, and for teaching that
the process can be optimized. Ans. 6; FF1, FF2. Pettipher teaches that there
is a need for better “[q]uality control in the dairy industry” and that the
industry “would benefit from the use of a rapid, inexpensive, sensitive,
direct method for enumerating bacteria in milk and milk products.” FF1.
Thus, Pettipher teaches that milk even after pasteurization needs to be
checked for the presence of viable bacteria to ensure that the pasteurization
process was effective. Examiner finds that “[t]he artisan would be motivated
to add the oxygen probe in the sample wells with the sample before
pasteurizing so as to not contaminate the samples after pasteurizing.” Ans. 5.
We find no error with Examiner’s conclusion that it would have been
obvious to include an oxygen sensitive probe before sealing and pasteurizing
the sample.
We are not persuaded by Appellant’s contention that Pettipher “says
nothing about use of the technique to specifically measure only thermoduric
bacteria in the milk and milk products.” Appeal Br. 6 (emphasis added). One
of skill in the art would understand that thermoduric bacteria are bacteria
that can survive, to varying extents, the pasteurization process. FF1, FF2; see
Spec. ¶ 3 (“The standard test for detecting and enumerating thermoduric
bacteria is the Laboratory Pasteurization Count (LPC), which serves as an
indicator of the effectiveness of farm sanitation and hygiene procedures.”).
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Thermoduric bacteria does not pertain to a particular strain of bacteria but is
generally understood as any bacteria that survives the pasteurization process.
Pettipher teaches the need for improved quality control in the dairy industry
to ensure the efficacy of the pasteurization process in order to make sure the
milk product is safe for consumption. FF1. Because Pettipher detects
bacteria after pasteurization, we agree with Examiner that pasteurized milk
has the potential to contain thermoduric bacteria. See Ans. 6 (“[I]t would be
obvious to an artisan to use the pasteurized milk comprising thermoduric
bacteria.”).
We are not persuaded by Appellant’s contention that Belhumeur
“does not disclose a probe to monitor contamination.” Reply Br. 2; see
Appeal Br. 7. Belhumeur teaches adding an indicator before applying a
sterilization process. FF8. We agree with Examiner that Belhumeur teaches
using an indicator for determining that the sterilization condition applied to a
sample was sufficient to decontaminate the sample. See Ans. 7 (Examiner
explains that “Bellhumeur was cited to teach that sterilization (autoclaving)
of probes to monitor contamination was known in the art.”). Papkovsky
teaches that oxygen probes were known to be used to test sample sterility.
FF1. Papkovsky’s oxygen sensitive probe can measure viable bacteria and
the probe can be added either before or after applying a pasteurization
process. Picking one of a finite number of known solutions to a known
problem is obvious. KSR, 550 U.S. at 421:
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this leads
to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
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instance the fact that a combination was obvious to try might
show that it was obvious under § 103.
Here, Examiner finds that “[t]he artisan would be motivated to add the
oxygen probe in the sample wells with the sample before pasteurizing and
seal the samples during the testing so as to not contaminate the samples after
pasteurizing.” Ans. 7. We find no error with Examiner’s conclusion that
based on the combination of references one of ordinary skill in the art would
have been motivated to use an oxygen sensitive probe to measure the
efficiency of the pasteurization process. See FF1–FF6. We agree with
Examiner’s rationale that the choice of adding the probe to the sample
before the pasteurization process ensures that any viable bacteria in the
sample is not a product of post-pasteurization contamination but instead is a
product of insufficient pasteurization.
D. Conclusion
We conclude, considering the totality of the cited evidence and
arguments, that the preponderance of the evidence supports Examiner’s
conclusion of obviousness with respect to claim 1, and Appellant has not
provided sufficient rebuttal evidence or evidence of secondary
considerations that outweighs the evidence supporting Examiner’s
conclusion. As Appellant does not argue the claims separately, claims 2–4,
6–9, 11, 14, 15 and 19 fall with claim 1. 37 C.F.R. § 41.37 (c)(1)(iv).

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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–4, 6–9,
11, 14, 15,
19
103(a) Papkovsky,
Pettipher,
Belhumeur, Milk
Facts, Kleinerman
1–4, 6–9,
11, 14, 15,
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).

AFFIRMED