ACEA Biosciences, Inc.

Patent Trials and Appeals Board

Apr 26, 2021

2020003634 (P.T.A.B. Apr. 26, 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.
15/478,041 04/03/2017 Nan Li 10101-101390 5308
22878 7590 04/26/2021
Agilent Technologies, Inc.
Global IP Operations
5301 Stevens Creek Blvd
Santa Clara, CA 95051
EXAMINER
QIAN, CELINE X
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
04/26/2021 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):
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 NAN LI, XIAOBO WANG, YAMA A. ABASSI, BIAO XI,
WEN FU ZHANG, and XIAO XU
Appeal 2020-003634
Application 15/478,041
Technology Center 1600
Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims directed to a method of determining a
beating parameter of cells that undergo excitation contraction coupling for
obviousness and obviousness-type double patenting. We have jurisdiction
under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the term “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as ACEA
BIOSCIENCES, INC. (Appeal Br. 3.)
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Application 15/478,041

2
STATEMENT OF THE CASE
Appellant’s Specification states “[c]ardiac safety pharmacology is the
study of the potential undesirable pharmacodynamic effects of a substance
on heart function in relation to exposure to the substance in the therapeutic
range and above.” (Spec. 1.) Cardiomyocytes, specialized muscle cells of
the myocardium, are commonly used in biomedical research to assess the
cardiotoxicity of potential drugs or treatments. (Id. at 3.) Cardiomyocytes
are capable of excitation-contraction coupling, a physiological process of
converting an electrical stimulus to a mechanical response, which is
fundamental to muscle physiology. (Id. at 2–3.)
Appellant’s invention is directed to a method of determining a beating
parameter of a cell that undergoes excitation contraction coupling. (Id. at 1.)

Claim 1, reproduced below, is illustrative of the claimed subject
matter:
1. A method of determining a beating parameter of cells that
undergo excitation contraction coupling, the method comprising:
a) providing a cell analysis device comprising a substrate and a
sensor that measures cell adhesion and morphology on the
substrate in millisecond time resolution;
b) adding excitable cells capable of undergoing excitation
contraction coupling to the substrate;
c) monitoring cell adhesion to the substrate and morphology of
the excitable cells on the substrate in millisecond time resolution;
and
d) calculating one or more beating parameters from the
monitored adhesion and morphology.
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REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Wang et al. US 2004/0152067 A1 Aug. 5, 2004
Berdondini High-density electrode
array for imaging in
vitro
electrophysiological
activity, 21 Biosensors
and Bioelectronics 167–
74
2005

REJECTIONS
The following rejections by the Examiner are before us on review:
Claims 1–39 are rejected under 35 U.S.C. § 103 as being unpatentable
over Wang and Berdondini.
Claims 1–39 are rejected on the ground of nonstatutory double
patenting as being unpatentable over the claims2 of U.S. Patent 10,539,523.
DISCUSSION
I. Non-Obviousness
The Examiner finds that Wang teaches methods of using a sensor that
measures cell adhesion and morphology through impedance measurements.
(Final Action 3.) The Examiner explains that cardiomyocytes are cells used
in assays for determining cytotoxic effect of substrates. (Id. (citing, inter

2 The Examiner only identifies claims 1–4 of the patent. However, we
determine that to have been an inadvertent error since the patent as issued
includes 5 claims, and there is no reason to exclude claim 5 of the patent
from the nonstatutory double patenting analysis
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alia, Wang ¶ 163).) The Examiner also notes that the “physiological status”
of the cells can be monitored by impedance or resistance between electrodes
and that the electrodes/sensors “can also have geometries suitable for
measuring extracellular recording of excitable cells.” (Ans. 10 (citing Wang
¶¶ 163, 164).)
The Examiner acknowledges that Wang does not teach taking
measurements “in millisecond time resolution.” (Final Action 3.) The
Examiner, however, concludes that doing so would have been obvious from
the teachings of Berdondini. (Id.) In particular, the Examiner finds that
Berdondini teaches using MEA (microelectrode arrays) sensors to take
electrophysiological measurements of cardiomyocytes, such as beat rate, in
millisecond resolution. (Id. at 3–4.) The Examiner concludes that it would
have been obvious to one having ordinary skill in the art “to recognize that
using the device taught by Wang et al. for determining effects of a potential
cytotoxic compound to cardiomyocytes would have to use millisecond time
resolution because the electrophysiology of cardiomyocytes requires the
resolution to be in millisecond for determining a beat parameter as
demonstrated by Berdondini et al.” (Id. at 4.) The Examiner finds that
“[t]he ordinary skilled [person] in the art would be motivated to use such
time resolution based on the characteristic of cells that undergo excitation
contraction such as cardiomyocytes.” (Id.)
We do not agree with the Examiner’s conclusion of obviousness. In
particular, Berdondini’s sensors measure changes of voltage near an
electrode due to the beating of a cell (i.e., contractile activity), i.e.,
extracellular electrophysiological signals in terms of change in voltage are
measured. (Appeal Br. 11, 14–15; Berdondini 171–173.) As Appellant
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explains, Berdondini monitors the influx or outflow of current, i.e., the
difference in charge between two points (in micro-volts). This is not a
measurement of cell-adhesion and morphology as required by the claims.
And there is no indication in Berdondini how the charge difference that is
measured would be indicative of, or could be correlated to, cell adhesion and
morphology.
Wang explains that its sensor is measuring the migration of a cell.
(Wang Abstr.) The electrode of Wang measures a change in impedance
because of the contact of cells (adhesion) with the electrodes. (Wang Abstr.,
id. ¶¶ 19, 31, 89 (“Preferred electrode structure units of the present invention
can measure impedance changes due to cell attachment to an electrode
surface.”).) As Appellant explains, Wang teaches that the physiological
status of cells, such as attachment or viability, can be determined by
monitoring impedance changes of an electrode. (Appeal Br. 14; Wang ¶ 70
(“The disclosed apparatuses and systems can provide kinetic information as
for the cell number, cell biological status (including their attachment status,
status, viability, etc.).”), id. ¶ 160 (explaining the use of microelectronic
sensors to detect cells that “tightly contact” a sensor through “cell-substrate
impedance measurement”), id. ¶ 163 (“The cell physiological status is
monitored or measured by monitoring the impedance or resistance between
the electrodes fabricated in the multiple-well plate.”).)
Although it is true, as the Examiner notes (Ans. 10), that Wang
teaches sensors can be designed so as to measure “extracellular recording of
excitable cells,” Wang describes such a sensor as sensing/monitoring “the
metabolic molecules” that may be toxic or non-toxic after a drug candidate
is metabolized by measuring type and or concentration of those molecules.
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(Wang ¶ 164.) Wang indicates known biosensors such as genetically
engineered cell-based biosensors can be used for “specific agent
classification.” (Id.) In other words, this teaching of Wang does not suggest
sensors used for impedance measurements can be used to measure a beating
parameter of a cell.
In other words, there is nothing in Berdondini to suggest a new use for
its electric potential measuring sensors, which measure changes in voltage
near the sensor at millisecond intervals to assess electrophysiological
changes associated with the beating of a cell, to instead assess impedance
changes of the sensor, much less at millisecond intervals, to measure the
beating or beating parameter of a cell. Nor is there anything in Wang that
would suggest a new use for its impedance measuring sensors which take
measurements of the binding of cells to sensors such that they could be used
to assess a cell beating parameter.
Consequently, we find that the Examiner fails to adequately explain
why one of ordinary skill in the art would have found it obvious to operate
the sensor of Wang in the millisecond time resolution based on Berdondini’s
sensor measurements measuring a different parameter. Thus, we do not
sustain the Examiner’s rejection of claims 1–39 as being obvious from Wang
and Berdondini.
II. Non-Statutory Double Patenting
The Examiner finds that the claims of the ’523 patent are directed to
“a method for monitoring excitable cells by using a device that measures
impedance in millisecond resolution and determining beating cycle of the
cells based on the measured impedance (claims 3 and 4).” (Ans. 7.) In
addition, the Examiner finds claims 1 and 2 of the ’523 are drawn to “a
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method that determines a compound’s effect on the beating cycle by using
impedance measurement method (claims 1 and 2).” (Id.)
The Examiner concludes that “it would have been obvious to an
ordinary skilled [person] in the art that the impedance measurement device
recited in the ’523 patent claims can be used to determine impedance in
millisecond resolution as claimed in the instant application.” (Id.)
We agree with the Examiner that the claims on appeal are obvious
variants of the claims in the ’523 patent.
Claims 1 and 3 of the ’523 patent include adding cardiomyocytes to a
well that has a nonconductive substrate with a surface suitable for
attachment of excitable cells, monitoring impedance at 10 millisecond time
resolution and assessing the effect of a compound on cell beating. An effect
on cell beating is further elucidated to include a beating cycle in claim 2 of
the ’523 patent. We find cell beating to be a measurable factor, i.e.,
parameter, of beating.
Moreover, claim 3 of the ’523 patent includes an additional step of
extracellular recording of the electro-stimulated cells in the process of
assessing the effect of a compound on cell beating and claim 5 of the ’523
patent states that the beating cycle “is resolved using the monitored
impedance.”
We find that in combination, therefore the claims of the ’523 patent,
indicate that determining a cell beating parameter, such as a beating cycle,
occurs after impedance monitoring, among other measurements such as
extracellular recording of the electro-stimulated cells over time, and that a
beating parameter is resolved using the monitored impedance, a
measurement that the prior art teaches is a measure of cell adhesion (see,
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e.g., Wang). Thus, it is clear from the claims of the ’523 patent that a
beating parameter is being “resolved,” i.e., calculated, at least in part based
on from the impedance monitoring, and consequently, claim 1 is at least
obvious from the claims of the ’523 patent. ,
In view of the foregoing, Appellant’s argument that the ’523 patent
does not claim a beating parameter (Reply Br. 17), is not persuasive of error
in the Examiner’s rejection of claim 1 or 12. Moreover, Appellant’s
argument that the ’523 patent does not claim cardiomyocytes (id.) is
demonstrably false. (See ’523 patent claim 1 (“b) adding a sample of
cardiomyocyte . . . cells to the device”).)
Furthermore, that the claims of the ’523 patent do not describe where
the added cardiomyocytes come from does not persuade us the Examiner
erred in rejecting claims 4, 5, and 23 for non-statutory double patenting.
That is because one of ordinary skill in the art would have found it obvious
to use any source of cardiomyocytes known in the art. As for the
specifically claimed beating parameters recited in claims 33, 34, and 35
(Reply Br. 17), we find too that those would have been obvious from the
claims of the ’523 patent and the prior art, in light of the fact that there is no
evidence that such parameters are not known to be monitored parameters of
excitable cells when assessing the effect of a compound administered to a
beating cell, which is the purpose of the method of the ’523 patent claims.
Finally, we also do not find persuasive Appellant’s argument that
claim 11 requires determining 5 beating parameters, which is not taught or
suggested by the claims of the ’523 patent (Reply Br. 17). In particular, the
claims of the ’523 patent are not in any way restricted to only one effect on
cell beating being measured. “[W]here the general conditions of a claim are
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disclosed in the prior art, it is not inventive to discover the optimum or
workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456
(CCPA 1955). Furthermore, “[t]he law is replete with cases in which the
difference between the claimed invention and the prior art is some range or
other variable within the claims. These cases have consistently held that in
such a situation, the applicant must show that the particular range is critical,
generally by showing that the claimed range achieves unexpected results
relative to the prior art range.” In re Woodruff, 919 F. 2d 1575, 1578, 16
USPQ2d 1934, 1936 (Fed. Cir. 1990) (citations omitted, emphasis in
original). Appellant has not established that determination of five beating
parameters achieves an unexpected result relative to the teaching of the
claims of the ’523 patent.
For the foregoing reasons, we affirm the Examiner’s rejection of
claims 1–39 for non-statutory double patenting over the claims of the ’523
patent.
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DECISION SUMMARY
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–39 103 Wang, Berdondini, 1–39
1–39 Non-statutory
Double Patenting
1–39
Overall
Outcome
1–39

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