ACEA Biosciences, Inc.Download PDFPatent Trials and Appeals BoardApr 26, 20212020003634 (P.T.A.B. Apr. 26, 2021) Copy Citation 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.) Appeal 2020-003634 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. Appeal 2020-003634 Application 15/478,041 3 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 Appeal 2020-003634 Application 15/478,041 4 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 Appeal 2020-003634 Application 15/478,041 5 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. Appeal 2020-003634 Application 15/478,041 6 (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 Appeal 2020-003634 Application 15/478,041 7 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, Appeal 2020-003634 Application 15/478,041 8 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 Appeal 2020-003634 Application 15/478,041 9 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. Appeal 2020-003634 Application 15/478,041 10 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 Copy with citationCopy as parenthetical citation