Ikeda Food Research Co., Ltd. et al.

Patent Trials and Appeals BoardAug 9, 2021

2021002022 (P.T.A.B. Aug. 9, 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. 16/278,030 02/15/2019 Hironori Omura 43111/0006 2263 1912 7590 08/09/2021 AMSTER, ROTHSTEIN & EBENSTEIN LLP 90 PARK AVENUE NEW YORK, NY 10016 EXAMINER LIU, SAMUEL W ART UNIT PAPER NUMBER 1656 MAIL DATE DELIVERY MODE 08/09/2021 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte HIRONORI OMURA, HIROKAZU SANADA, TAKAKO YADA, TETSUNARI MORITA, MIKA KUYAMA, TOKUJI IKEDA, KENJI KANO, and SEIYA TSUJIMURA Appeal 2021-002022 Application 16/278,030 Technology Center 1600 Before TAWEN CHANG, RACHEL H. TOWNSEND, and DAVID COTTA, Administrative Patent Judges. CHANG, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 23 and 24. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real parties in interest as Ikeda Food Research Co., Ltd. and PHC Corporation. Appeal Br. 3. Appeal 2021-002022 Application 16/278,030 2 STATEMENT OF THE CASE “Glucose is present in blood and utilized as an important marker for diabetes. A method for measuring a glucose has conventionally been a chemical method or an enzymatic method, and an enzymatic method is regarded generally to be excellent in view of the specificity and the safety.” Spec. 1:28–2:2. According to the Specification, however, certain prior art enzymatic methods for measuring glucose are lacking because, e.g., they: “employ a plural[ity] of enzymes” and/or require “adding a coenzyme NAD(P) to the reaction systems,” id. at 2:5–10; use an enzyme (glucose oxidase) that is “highly suspected to give a measured value involving an error due to level of the residual oxygen,” id. at 2:27–3:2; and/or “exhibit[] a poor selectivity for glucose,” id. at 3:24–4:3. Further according to the Specification, “an objective of the invention is to provide a novel glucose dehydrogenase which exhibits an excellent substrate-recognizing ability toward glucose and which has low activity on maltose,” as the latter is “employed widely as an infusion component” and thus present at a high level in the blood of an infused patient. Spec. 3:29– 4:1, 4:5–8. Other objectives of the invention described in the Specification include providing “a method for producing [the novel glucose dehydrogenase] and a microorganism having an ability of producing the same,” as well as providing a “glucose measuring method, measuring reagent and biosensor which employ the novel glucose dehydrogenase and which are capable of quantifying glucose rapidly and conveniently at a high accuracy.” Id. at 4:8–15. Appeal 2021-002022 Application 16/278,030 3 CLAIMED SUBJECT MATTER The claims are directed to a biosensor for measuring glucose in a sample liquid. Claim 23 is illustrative: 23. A biosensor for measuring glucose in a sample liquid, comprising: an electrode system comprising an action electrode and a counter electrode; and an enzymatic reaction layer in contact with the action electrode and/or the counter electrode, the enzymatic reaction layer comprising an electron acceptor and a soluble flavin adenine dinucleotide-binding glucose dehydrogenase (FAD- GDH) obtained from Aspergillus wherein the flavin adenine dinucleotide-binding glucose dehydrogenase is secreted from an Aspergillus fungal body and has enzymatic activity to glucose comprising catalyzing a reaction for oxidizing glucose in the presence of the electron acceptor, wherein enzymatic activity of the FAD-GDH to maltose is 5% or less relative to the enzymatic activity of the FAD- GDH to glucose, and wherein enzymatic activity of the FAD-GDH to D- fructose is not more than enzymatic activity of the FAD-GDH to D-mannose, and wherein the biosensor is capable of quantifying glucose concentrations ranging from 4.5 mM to 30 mM. Appeal Br. 28 (Claims App.). Appeal 2021-002022 Application 16/278,030 4 REJECTIONS A. Claims 23 and 24 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Senior,2 Yugawa ’702,3 and Yugawa ’946,4 as evidenced by Sekisui.5 Ans. 4. B. Claims 23 and 24 are provisionally rejected under 35 U.S.C. § 101 as claiming the same invention as that of claims 23 and 24 of copending Application No. 16/278,019 (’019 application). Ans. 8. OPINION A. Obviousness rejection over Senior, Yugawa ’702, and Yugawa ’946, as evidenced by Sekisui Diagnostics (claims 23 and 24) 1. Issue The Examiner finds that Senior teaches almost all of the limitations of the claims, as evidenced by Sekisui, except that Senior does not “expressly teach that [its] electrode system (or glucose biosensor) comprises . . . an enzymatic layer having GDH . . . wherein said glucose sensor can measure/quantify[] glucose concentration of 4.5-30 mM.” Ans. 4–6. However, the Examiner finds that Yugawa ’702 teaches “a glucose biosensor . . . for measuring glucose concentration comprising . . . a reaction layer,” wherein “the ‘reaction layer’ comprises the ‘glucose dehydrogenase’ (GDH) and ‘ferricyanide,’” which is an electron acceptor. Id. at 6. The 2 Senior et al., EP 0 094 161 A1, published Nov. 16, 1983. 3 Yugawa et al., US 6,656,702 B1, issued Dec. 2, 2003. 4 Yugawa et al., US 6,059,946, issued May 9, 2000. 5 Sekisui Diagnostics, ENZYMES: GLUCOSE DEHYDROGENASE FAD DEPENDENT (2017). Appeal 2021-002022 Application 16/278,030 5 Examiner further cites to Yugawa ’946, which the Examiner finds “discloses substantially same subject matters as Yugawa [’702].” Id. The Examiner concludes that, at the time of the invention, it would have been obvious to a skilled artisan to incorporate into Senior’s glucose biosensor the “reaction layer” in the biosensors of the Yugawa references. Ans. 6. In particular, the Examiner finds that Yugawa references teach that their biosensors are advantageous in (1) providing high enzyme stability, (2) being low-cost, compact, and disposable, and (3) reducing the amount of enzyme needed per biosensor, and further teach that their biosensor may be used with “different enzymes such as glucose dehydrogenase (GDH) . . . to make ‘glucose biosensor’ . . . which is the common subject matter of Senior.” Id. at 7–8. The Examiner finds that it would have been obvious to use the particular GDH enzyme disclosed in Senior (EC 1.1.99.10) because, among other things, this enzyme is “particularly preferred when the glucose to be measured is from blood serum sample . . . due to its . . . relatively higher Km value.” Id. Appellant contends that “[t]he cited art combination does not teach or suggest a biosensor comprising an FAD-GDH wherein the ‘enzymatic activity of the FAD-GDH to D-fructose is not more than enzymatic activity of the FAD-GDH to D-mannose,’ as recited in independent claim 23.” Appeal Br. 11. The issue with respect to this rejection is whether a preponderance of evidence supports the Examiner’s finding that Senior teaches an FAD-GDH wherein the “enzymatic activity of the FAD-GDH to D-fructose is not more than enzymatic activity of the FAD-GDH to D-mannose,” as recited in claim 23. Appeal 2021-002022 Application 16/278,030 6 2. Analysis We agree with Appellant that a preponderance of evidence does not support a finding that Senior teaches a FAD-GDH wherein the “enzymatic activity of the FAD-GDH to D-fructose is not more than enzymatic activity of the FAD-GDH to D-mannose,” as recited in claim 23. The Examiner asserts that Senior teaches “an electrode sensor system to measure glucose concentration in a sample,” comprising glucose dehydrogenase (GDH) preferably obtained from Aspergillus oryzae and having the enzyme classification number EC 1.1.99.10, which denotes a Flavin-dependent enzyme (FAD-GDH). Ans. 4. The Examiner asserts that GDHs having the enzyme classification number EC6 1.1.99.10 inherently have the substrate specificity with respect to glucose and D-mannose recited in claim 23 (i.e., wherein “enzymatic activity of the FAD-GDH to maltose is 5% or less relative to the enzymatic activity of the FAD-GDH to glucose” and “enzymatic activity of the FAD-GDH to D-fructose is not more than enzymatic activity of the FAD-GDH to D-mannose”). Id.; see also id. at 11. We agree with the Examiner that Senior teaches a method for determining the glucose content in a sample by contacting the sample with “an assay mixture comprising . . . a flavin-dependent glucose dehydrogenase enzyme EC No. 1.1.99.10,” which “contains the prosthetic group flavin adenine dinucleotide (FAD).” See, e.g., Senior 1:2–6, 1:20–2:2, 5:1–3. Senior further teaches that “[t]he glucose dehydrogenase enzymes may be obtained from any microorganism containing these enzymes,” that 6 “The E.C. . . . Nos. . . . are enzyme numbers assigned to enzymes in the Enzyme Nomenclature of the Nomenclature Committee of the International Union of Biochemistry (NC-IUB).” Senior 2:10–13. Appeal 2021-002022 Application 16/278,030 7 “[m]icroorganisms containing these enzymes and which can usefully be used as sources for them include . . . Aspergillus as sources of E.C. 1.1.99.10,” and that “[p]referred sources of E.C. 1.1.99.10 include Aspergillus oryzae strain ATCC 9102.” Id. at 3:35–4:13, 5:1–3. However, “[i]nherency may not be established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient to establish inherency.” Scaltech Inc. v. Retec/Tetra L.L.C., 178 F.3d 1378, 1384 (Fed. Cir. 1999). In support of his inherency finding, the Examiner cites to Table 1 of the Specification. Ans. 5, 6. The Examiner further asserts that Sekisui provides “factual evidence that the FAD-GDH enzyme from Aspergillus species with EC 1.1.99.10 (Senior) has the [claimed] ‘substrate specificity’ [in] that the enzymatic activity to D-fructose [is] not more than the activity to D-mannose (claim 23)” and that “the enzymatic activity to maltose is 5% or less (claim 23) or 3% or less (claim 24) relative to the enzymatic activity to glucose.” Id. at 4, 5, 6, 10–12, 12–13, 16. We are not persuaded. Table 1 of the Specification sets forth the substrate specificity, including secondary substrate specificity, and relative activity of one enzyme within the EC 1.1.99.10 classification, i.e., the coenzyme-binding glucose dehydrogenase derived from the Aspergillus Terreus microorganism designated “97508” and deposited under FERM BP- 08578. Spec. 27:8–29, 31:3–15, 39:1–2, 39:24–41:24, 42:1–4, 44:2–4. Similarly, Sekisui sets forth the substrate specificity and relative activity of Appeal 2021-002022 Application 16/278,030 8 one FAD-GDH enzyme derived from an unidentified Aspergillus species and having the EC 1.1.99.10 classification. Sekisui 1–2.7 Although both of these enzymes have the same EC classification and the claimed substrate specificity for glucose and similar relative activities for other sugars that meet the claim requirements, this does not establish that the enzyme described in Senior also has the claimed specificities. Appellant has submitted evidence, including in the form of the Kotera Declaration,8 that the EC Number classification scheme for enzymes is “based on the primary chemical reaction that an enzyme catalyzes” and “provides no information about the enzyme’s possible specificity for any secondary substrate and no information about the enzyme’s activity level on any possible secondary substrates.” Kotera Decl. ¶¶ 6, 11. Thus, the fact that two enzymes having the EC 1.1.99.10 classification also have the claimed secondary substrate specificity and relative activity does not indicate that the FAD-GDH enzymes taught in Senior necessarily (i.e., inherently) have the claimed secondary substrate specificity and relative activity as the Examiner asserts.9 The Examiner asserts: 7 Sekisui is not paginated. Therefore, we refer to page numbers as if the document was numbered consecutively starting with the first page. 8 Declaration of Masaaki Kotera under 37 C.F.R. § 1.132 (Oct. 9, 2019) (“Kotera Decl.”). 9 We note that the Examiner has not asserted: that the particular enzymes disclosed in Table 1 of the Specification or Sekisui are identical to the enzymes taught in Senior, except in so far as they are classified under the same EC number and may be derived from the same genus of microorganisms; that they were known in the prior art; or that it would have been obvious to use them in the methods suggested by the combination of cited prior art. Appeal 2021-002022 Application 16/278,030 9 As far as the argument “ . . . FAD-GDH enzyme of Sekisui is from an Aspergillus species which is not defined in the reference . . . [”] is concerned, instant claim 23 is directed to a biosensor comprising an electrode system that comprises enzymatic reaction layer containing FAD-GDH enzyme obtained from Aspergillus (genus) and the specification enables using the FAD- GDH from the species of Aspergillus; and thus, the appellants’ argument does not support the appellants’ position. Ans. 11–12. We are not persuaded. The Examiner has not cited Sekisui as prior art. Thus, the pertinent issue is whether a preponderance of the evidence of record, including Sekisui, supports the Examiner’s finding that enzymes disclosed in the prior art reference Senior inherently possess the secondary substrate specificity and relative activity recited in the claims. We find that it does not for the reasons discussed herein. The Examiner asserts that “Appellants have not provided any factual indicia/evidence showing that, if two FAD-GDH enzymes from an Aspergillus species have identical EC number, (i.e., EC 1.1.99.10), said two enzymes will not have ‘identical enzyme activity’ nor have the ‘same substrate specificity.’” Ans. 12. The Examiner asserts that the Kotera Declaration is not persuasive because In re Ikeda Food Res. Co., Ltd., 758 F. App’x. 952 (Fed. Cir. 2019), held that Senior inherently discloses the claimed FAD-GDH substrate specificity. Id. at 12–13. We are not persuaded. Appellant has provided persuasive evidence that not all Aspergillus-derived FAD-GDH will inherently have the claimed secondary substrate specificity and relative activity even if categorized as EC 1.1.99.10. Indeed, Appellant has provided evidence that not all FAD- Appeal 2021-002022 Application 16/278,030 10 GDH derived from a particular species, Aspergillus oryzae, will inherently have the claimed secondary substrate specificity and relative activity. In particular, Appellant cites to Bak III.10 Table I of Bak III shows that, for at least one FAD-GDH11 derived from Aspergillus oryzae, the activity of the enzyme to D-fructose was higher than the activity to D-mannose, contrary to the requirement of the claims. Bak III 320, Table I. The Kotera Declaration also points to the Amano Application12 as evidence that the classification itself in EC 1.1.99.10 of seven different enzymes, all of which were obtained from A. oryzae strains, “provides no information about the enzyme’s activity level on any secondary substrates.” Kotera Decl. ¶ 13. The Examiner asserts that Appellant’s arguments based on Bak III is not persuasive because the GDH enzymes disclosed therein has not been indicated to be associated with EC 1.1.99.10. Ans, 15, 16. The Examiner also asserts that Table 4 of the Amano Application does not support Appellant’s position because Amano application neither mentions ‘secondary substrate’ nor provides factual evidence that the FAD-GDH from Aspergillus species having EC 1.1.99.10 does not possess the substrate specificity toward maltose which is 5% or less relative to the enzymatic activity toward glucose, and substrate specificity that the activity for D- fructose is not more than the activity for D-mannose. 10 Tchan-Gi Bak, Studies on Glucose Dehydrogenase of Aspergillus Oryzae: III. General Enzymatic Properties, 146 BIOCHIMICA ET BIOPHYSICA ACTA, 317 (1967). 11 Appellant asserts, and the Examiner has not disputed, that the glycose hydrogenase enzyme described in Bak III is a FAD-GDH. Appeal Br. 15– 17; see also Bak III 317 (stating that “the purified enzyme is a glycoflavoprotein containing 1 mole of FAD per mole of enzyme”). 12 Tanaka et al., US 2009/0181408 A1, published July 16, 2009. Appeal 2021-002022 Application 16/278,030 11 Final Act. 8–9. We are not persuaded. Regardless of whether Bak III itself indicates the EC number of its glucose dehydrogenase to be EC 1.1.99.10, Appellant has provided evidence that the glucose dehydrogenase described in Bak III is properly classified under EC 1.1.99.10, and the Examiner has not provided persuasive evidence to the contrary. See, e.g., Appeal Br. 15–17; see also Decl. ¶¶ 6, 8.13 We are similarly unpersuaded by the Examiner’s assertions regarding the Amano Application. Amano describes Table 4 as a “[c]omparison of [the enzymes’] relative activity to each substrate” when “the activity with respect to D-glucose . . . was assumed to be 100%.” Amano Application ¶¶ 142–143. That Amano Application does not use the term “secondary substrate” does not change the probative value of the data set forth in Table 4 with regard to whether enzymes derived from Aspergillus oryzae and classified under EC 1.1.99.10 would inherently have the same secondary substrate specificity or relative activity. 13 The Kotera Declaration states that EC number “is a numerical classification scheme for enzymes[] based on the primary chemical reaction that an enzyme catalyzes” and that, “[i]n the case of EC 1.1.99.10 the reaction being catalyzed is D-Glucose + acceptor  D-Glucono-1,5-lactone + reduced acceptor.” Kotera Decl. ¶¶ 6, 8. Although Bak III states that the reaction catalyzed by its enzyme is D-Glucose + acceptor  D-gluconate + reduced acceptor, Bak III 317–318, we understand that D-Glucono-1,5- lactone is the cyclic ester of D-gluconate and that the two molecules are in equilibrium in aqueous solution at neutral pH. Neither has the Examiner asserted that the primary reaction catalyzed by the Bak III enzyme differs from that catalyzed by the other enzymes classified under EC 1.1.99.10. Appeal 2021-002022 Application 16/278,030 12 As to the Examiner’s point that Table 4 of the Amano Application does not provide “factual evidence that the FAD-GDH from Aspergillus species having EC 1.1.99.10 does not possess the [claimed] substrate specificity,” we are not persuaded to the extent the Examiner’s assertion is based on the lack of explicit disclosure in the Amano Application regarding the EC Number of enzymes disclosed therein, for the same reason discussed above with respect to Bak III. To the extent the Examiner’s point is that the substrate specificities of each of the enzymes analyzed in Table 4 of the Amano Application in fact fall within the relevant limitations of the claims on appeal, we agree with that factual finding but disagree that the Amano Application therefore does not support Appellant’s argument. Although each of the enzymes in Table 4 meets the relevant limitations in the claims regarding substrate specificity and relative activity, Table 4 shows differences in the specificity and relative activity to various secondary substrates among the seven enzymes, and these specificities and relative activities also appear to differ from those of the FAD-GDH derived from the Aspergillus oryzae disclosed in Bak III. Thus, Table 4 of the Amano Application supports Appellant’s argument that Aspergillus-derived enzymes classified under EC 1.1.99.10 do not necessarily and inevitably (i.e., inherently) possess identical secondary substrate specificity or relative activity.14 14 As with the enzymes disclosed in Table 1 of the Specification and/or Sekisui, the Examiner has not asserted: that the enzymes disclosed in Table 4 of the Amano Application are identical to the enzymes taught in Senior, except in so far as they are classified under the same EC number and may be derived from the same species of microorganisms; that they were known in the prior art; or that it would have been obvious to use them in the methods Appeal 2021-002022 Application 16/278,030 13 Finally, we are unpersuaded by the Examiner’s reliance on In re Ikeda Food Res. Co., Ltd., 758 F. App’x 952 (2019). Ans. 12. The Federal Circuit noted in its opinion that “Ikeda’s counsel does not dispute that enzymes with the same E.C. number have the same substrate specificity ‘for purpose of [that] appeal.’” Ikeda, 758 F. App’x at 957. Thus, the disputed issue of fact at the center of the instant appeal was not an issue in front of, and not decided by, the Ikeda court. Accordingly, for the reasons discussed above, we reverse the Examiner’s rejection of claims 23 and 24 as obvious over Senior, Yugawa ’702, and Yugawa ’946, as evidenced by Sekisui. B. Statutory double patenting rejection over ’019 application The Examiner provisionally rejected claims 23 and 24 under 35 U.S.C. § 101 as claiming the same invention as claims 23 and 24 of co- pending ’019 application. Ans. 8. In light of the Board’s precedential decision in Ex Parte Moncla, 95 USPQ 2d 1884 (BPAI 2010), concluding it premature to address a provisional, albeit non-statutory, double patenting rejection when all other remaining rejections are reversed, we decline to address the merits of this rejection at this time. suggested by the combination of cited prior art. We also note that the Amano Application itself states that “the substrate specificities of FAD- GDH derived from Aspergillus oryzae BB-56, IAM2603, IAM2628, IAM2683, IAM2736, IAM2706, or NBRC30113 are the same as each other.” Amano Application ¶ 142. Nevertheless, the actual data set forth in Table 4 of the Amano Application does suggest differences in secondary substrate specificities and relative activities among the seven enzymes and, as discussed above, between the seven enzymes and the enzyme disclosed in Bak III. Id. ¶ 143, Table 4; Bak III 320, Table I. Appeal 2021-002022 Application 16/278,030 14 CONCLUSION In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 23, 24 103(a) Senior, Yugawa ’702, Yugawa ’946, Sekisui 23, 24 23, 24 101 Provisional Statutory Double Patenting, 16,278,01915 Overall Outcome 23, 24 REVERSED 15 As indicated above, we decline to address the merits of this rejection at this time.