Seahorse Bioscience

Patent Trials and Appeals Board

Apr 30, 2020

15082658 - (D) (P.T.A.B. Apr. 30, 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.
15/082,658 03/28/2016 David A. Ferrick 20160018-02
(027644.8150)
9007
22878 7590 04/30/2020
Agilent Technologies, Inc.
Global IP Operations
5301 Stevens Creek Blvd
Santa Clara, CA 95051
EXAMINER
BERKE-SCHLESSEL, DAVID W
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
04/30/2020 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 DAVID A. FERRICK and BRIAN DRANKA

Appeal 2019-004928
Application 15/082,658
Technology Center 1600
Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
JAMIE T. WISZ, Administrative Patent Judges.

WISZ, Administrative Patent Judge.

DECISION ON APPEAL

Appeal 2019-004928
Application 15/082,658

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STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–15. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.
CLAIMED SUBJECT MATTER
The Specification describes “[e]mbodiments of the invention [that]
enable the stimulation of both major metabolic/energetic pathways acutely
with a single injection, as well as the determination of the metabolic
potential of these major pathways, i.e., mitochondrial respiration and
glycolysis, based on that single injection.” Spec. 1:27–29. Claim 1, the only
independent claim, is illustrative of the claimed subject matter and is
reproduced below:
1. A method of determining a metabolic potential of a cell
sample, the method comprising the steps of:
measuring an initial oxygen consumption rate and an
initial extracellular acidification rate of the cell sample;
thereafter, simultaneously administering to the cell
sample a mitochondrial uncoupling agent and an ATP
synthase inhibitor;
thereafter, simultaneously measuring a subsequent
oxygen consumption rate and a subsequent extracellular
acidification rate of the cell sample; and
determining the metabolic potential of the cell sample.
Appeal Br. 11 (Claim Appendix).

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies the real party in interest as Agilent
Technologies, Inc. Appeal Br. 2.
Appeal 2019-004928
Application 15/082,658

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REJECTIONS
The Examiner rejected claims 1–15 under 35 U.S.C. § 103 as obvious
over Nicholls,2 as evidenced by Neilson.3
ISSUES AND ANALYSIS
The Examiner finds that Nicholls teaches methods of determining the
metabolic potential of a cell sample by initially measuring the oxygen
consumption rate and extracellular acidification in order to establish a
baseline; sequentially administering a mitochondrial uncoupling agent
(FCCP) and an ATP synthase inhibitor (oligomycin); measuring
simultaneously the oxygen consumption rate (OCR) and extracellular
acidification rate (ECAR); and finally, determining the metabolic potential
of the cell sample. Final Act. 11 (citing Nicholls, 1–2).
The Examiner finds that “[t]he only difference between the cited art,
and the claim, is that the claims require that the mitochondrial uncoupling
agent and the ATP synthase inhibitor are administered simultaneously,
whereas Nicholls provides a method of sequential addition.” Id. at 11–12.
However, the Examiner finds that:
based upon Nicholls, and the fact that the behavior of the
mitochondrial uncoupling agent and the ATP synthase inhibitor,
upon a cell metabolism is predictable (see Figure 2), the
simultaneous administration of the compounds would not
provide for additional variables that the ordinary artisan would
not be able to account for.

2 David G. Nicholls et al., Bioenergetic Profile Experiment using C2C12
Myoblast Cells, Journal of Visualized Experiments, 46, e2511 (2010)
(“Nicholls”).
3 Neilson et al., US 2007/0087401 A1, published Apr. 19, 2007 (“Neilson”).
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Id. at 12.
The Examiner further finds that obviousness is supported by Neilson,
“who measures cellular metabolism in a similar fashion as Nicholls” and
“indicates that the co-administration of compounds to cells is one of many
tools the artisan possesses as a means of understanding the metabolic
pathways.” Id. (citing Neilson ¶ 118).
Appellant asserts that the Examiner “has not established a prima face
case of obviousness, since it has not identified a sufficient reason or
motivation to change Nicholls’ method.” Appeal Br. 4. Furthermore,
Appellant asserts that, without the sequential administration of the ATP
synthase inhibitor and mitochondrial uncoupling agent as described in
Nicholls, one would not be able to measure the percent of O2 consumption
devoted to ATP production nor the amount devoted to maintaining the proton
gradient (due to H+ leak) as shown in the 40–65 minute time period in Figure
4 of Nicholls. Id. at 5–7. According to Appellant, changing the method
disclosed in Nicholls to one of simultaneous administration would change
Nicholl’s principle of operation because a skilled person would lose this
“valuable information.” Id. at 6–7.
Appellant further asserts that Nicholls teaches away from the claimed
invention because it “provides detailed methods related to the sequential
administration and measurement schedule while never even considering,
disclosing or suggesting simultaneous administration/measurement.” Reply
8. According to Appellant, Nicholls also teaches away because it “teaches
garnering important experimental data that can only be collected when the
sequential administration/measurement schedule is followed.” Id.
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The Examiner responds that one of skill in the art would be motivated
to change from a sequential to a simultaneous administration because such
simultaneous administration would remove time points 39 through 65 (on
Figure 4 of Nicholls), which would predictably shorten the duration of the
test. Ans. 6. The Examiner finds that “there is always motivation to make a
process faster, especially when this improvement yields predictable results.”
Id. (citing MPEP §§ 2143 (G), 2144(II)).
The Examiner further finds:
Nicholls shows C2C12 myoblast that are exposed to a
mitochondrial uncoupling agent and an ATP synthase agent
simultaneously. While the method certainly does teach a
sequential administration, the data shows time-points wherein
the cells are exposed to a mitochondrial uncoupling agent and
an ATP synthase agent simultaneously.
Id. at 7. According to the Examiner, if the sequential parts of the method are
known and predictable, then their simultaneous administration would also
lead to predictable results as demonstrated by the fact that Nicholls presents
data wherein the cells are simultaneously exposed to a mitochondrial
uncoupling agent and an ATP synthase inhibitor. Id.
Furthermore, the Examiner finds that there is no disclosure in Nicholls
which indicates that the ATP turnover/proton leak data gathered at time
points 40–65 of Figure 4 of Nicholls is necessary to calculate the respiratory
capacity/metabolic capacity of the cells in question. Id. at 7–8. According
to the Examiner, the Specification appears to determine the “metabolic
potential” of a cell by comparing the oxygen consumption and acidification,
both before and after the administration of a mitochondrial agent and an ATP
synthase agent. Id. at 9. The Examiner concludes:
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Since both of these have highly predictable outcomes on
cellular metabolism, and since Nicholls shows both of them
being exposed to cells simultaneously would suggest to the
ordinary artisan that their simultaneous administration would
result in similar and highly predictable results. Based upon the
claim limitations, when compared to Nicholls, the instant
claims have essentially combined a step to yield predictable
results. As stated previously, the Appellant has never presented
evidence that the simultaneous administration results in
improved data, or some other unexpected feature.
Id.
Having considered Appellant’s arguments in support of claim 1, we
are not persuaded of any reversible error in the Examiner’s rejection of
claim 1. As found by the Examiner, Nicholls shows cells that are
simultaneously exposed to a mitochondrial uncoupling agent and an ATP
synthase agent (e.g., minutes 65–90 in Figure 4); therefore, this data
suggests to one of ordinary skill in the art that simultaneous administration
of these substances would result in similar and predictable results. See
Nicholls, Figure 4.
We are not persuaded by Appellant’s assertion that the Examiner
“does not set forth any motivation or reason to change Nicholls’ method”
and find that, contrary to Appellant’s assertions, the Examiner has
established a prima facie case of obviousness. Reply Br. 3. Specifically, the
Examiner found that one of skill in the art would have been motivated to
change from a sequential to a simultaneous administration because this
“would predictably shorten the duration of the test” and “there is always
motivation to make a process faster, especially when this improvement
yields predictable results.” Ans. 6 (citing §§ MPEP 2143 (G), 2144(II)).
The Examiner also found that the data that would potentially be lost by such
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simultaneous administration (i.e., ATP turnover and H+ leak shown in Figure
4 of Nicholls), is not important to determining the respiratory
capacity/metabolic potential of a cell. Therefore, if one of skill in the art
wanted to determine such metabolic potential, they could simply remove the
time period in between the administration of oligomycin and FCCP (e.g.,
minutes 39–65), in order to more quickly obtain the desired data relating to
metabolic potential.
Because the Examiner presented a prima facie case of obviousness,
the burden then shifts to Appellant. “[T]he examiner bears the initial
burden, on review of the prior art or on any other ground, of presenting a
prima facie case of unpatentability. If that burden is met, the burden of
coming forward with evidence or argument shifts to the applicant.” In re
Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). Appellant has not presented
any persuasive evidence that simultaneous administration provides results
that are better or different than simultaneous exposure as disclosed in
Nicholls. Therefore, we find that one of ordinary skill in the art would have
been motivated to simultaneously administer an ATP synthase inhibitor and a
mitochondrial uncoupling agent to cells in order to determine their metabolic
potential and would have done so with a reasonable expectation of success
because Nicholls shows the results of cells that are simultaneously exposed
to these substances.
We are also not persuaded by Appellant’s argument that Nicholls
teaches away from simultaneously administering the ATP synthase inhibitor
and mitochondrial uncoupling agent. 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) (“The prior
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art’s mere disclosure of more than one alternative does not constitute
a teaching away from any of these alternatives because such disclosure does
not criticize, discredit, or otherwise discourage the solution claimed”).
Appellant has not identified any teaching in Nicholls that expressly or
implicitly discourages simultaneous administration. Appellant has also not
shown that Nicholls teaches that sequential administration is required to
determine the metabolic potential of a cell nor that ATP turnover or H+ leak
values would be needed for such a determination.
With regard to claim 11, which recites the step of mixing the
mitochondrial uncoupling agent and the ATP synthase inhibitor prior to
administering to the cell sample, the Examiner finds that “[t]here is no
evidence of record to suggest that the mitochondrial uncoupling agent and
the ATP synthase inhibitor will react with each other prior to their
simultaneous injection as a pre-mixed reactant.” Ans. 10. Therefore,
according to the Examiner, “if compounds are to be provided
simultaneously, it would be obvious to pre-mix the compounds, as this
would provide no expected changes to the system.” Id. at 10–11.
Appellant asserts that the Examiner “overlooks the interaction shown
in Figures 2 to 4 of Nicholls, where a dramatic change in OCR occurs after
FCCP is administered.” Appeal Br. 7. Appellant further asserts that the
Examiner’s findings rely on the incorrect assumption that the two
compounds were meant to be administered simultaneously while Nicholls
teaching sequential administration. Id.
We are not persuaded by Appellant’s arguments. As discussed
above, we find that it would have been obvious to one of ordinary skill in the
art to simultaneously administer the mitochondrial uncoupling agent and
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ATP synthase inhibitor. Therefore, it also would have been obvious to mix
together these two compounds prior to administering them to the cell
sample. As discussed above, one of skill in the art would have been
motivated to do so in order to simplify and potentially speed up the assay.
One of skill in the art would have done so with a reasonable expectation of
success because the prior art provided no evidence that pre-mixing these two
substances would impede the assay. Furthermore, in response to Appellant’s
arguments, one of skill in the art would measure the OCR after the
simultaneous administration of the oligomycin and FCCP, just as shown in
Nicholls wherein the cells are simultaneously exposed to oligomycin and
FCCP.
With regard to claim 15, which recites that the initial oxygen
consumption rate and initial extracellular acidification rate of the cell sample
are measured simultaneously, the Examiner finds that “although it is unclear
if Nicholls measures the oxygen consumption and the acidification rate
simultaneously, there is nothing non-obvious or unpredictable with
simultaneous measurements, as this allows for multiple measurements in one
time-point.” Final Act. 13. The Examiner further finds that Neilson
suggests that simultaneous measurements are preferable. Id. (citing Neilson
¶ 13).
Appellant asserts that Nicholls does not conduct the measurements of
OCR and ECAR simultaneously because Figure 2 of Nicholls shows
measurement of OCR in which oligomycin is added prior to 24 minutes
while Figure 3 shows measurement of ECAR in which oligomycin was
added at a time closer to 30 minutes. Appeal Br. 8.
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The Examiner responds that Nicholls uses an identical testing
apparatus as that disclosed in Neilson (i.e., Seahorse XF instrument), and
Neilson states that the apparatus is capable of simultaneous measurements.
Ans. 6 (citing Nicholls, 2, 5; Neilson ¶¶ 13, 64, 84, 92, 136, 165, 167). The
Examiner also finds that “just because Nicholls presents multiple graphs of
separate OCR and EGAR measurements, it does not mean that these
variables cannot be measured simultaneously.” Id. at 12–13. The Examiner
further finds that “Appellant has provided no evidence or data to suggest
why it would be non-obvious to measure these variables simultaneously”
and “there is nothing in Nicholls that would teach the ordinary artisan away
from a method that involves simultaneous detection.” Id. at 13.
We are not persuaded by Appellant’s arguments. We agree with the
Examiner that, as evidenced by Neilson, the instrument used in Nicholls
provides for simultaneous measurement of OCR and ECAR (see, e.g.,
Neilson ¶¶ 13, 84) and one of skill in the art would have been motivated to
perform such a simultaneous measurement in order to simplify the assay.
Furthermore, one would have done so with a reasonable expectation of
success based on the capability of the instrument.
For the reasons described herein and those already of record, we
sustain the Examiner’s rejection of independent claim 1 and dependent
claims 11 and 15 under 35 U.S.C. § 103 as being obvious over Nicholls as
evidenced by Neilson. Claims 2–10 and 12–14 are not argued separately,
and, therefore, fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(iv).
CONCLUSION
For the reasons described herein and those already of record, we
affirm the Examiner’s rejection of claims 1–15.
Appeal 2019-004928
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–15 103 Nicholls, Neilson 1–15

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