DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
The amendment filed 8/26/2025 has been entered. Claims 1, 4, and 10 have been amended. Claims 1-2 and 4-10 are currently pending and examined herein.
Status of the Rejection
Applicant’s amendments to the claims have overcome various objections and rejections previously set forth in the Non-Final Rejection filed 5/30/2025.
All 35 U.S.C. § 102 and 103 rejections from the previous office action are withdrawn in view of the Applicant’s amendment.
New grounds of rejection under 35 U.S.C. § 103 are necessitated by the amendments as outlined below.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 4-6, 8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Lacey et al. (“Amperometric enzyme electrode for NADP+ based on a ferrodoxin-NADP+ reductase and viologen-modified glassy carbon electrode,” 1995, Journal of Electroanalytical Chemistry, vol. 390, pgs. 69-76) in view of Elgrishi et al. (“A Practical Beginner’s Guide to Cyclic Voltammetry,” 2018, J. Chem. Educ., vol. 95, pgs. 197-206 and pgs. 1-28 of Supporting Information).
Regarding claim 1, Lacey teaches a target molecule redox method (method for detecting NADP+ based on reduction of NADP+ at a modified electrode [pg. 1, Abstract; pg. 72, col. 1, para. 2]) comprising:
a first process of bringing a liquid containing a target molecule to a non-flowing state (cyclic voltammetry is used to induce the reduction of NADP+ in solution in Fig. 2(A) [pg. 70, col. 2, para. 4; pg. 71, col. 1, para. 1; pg. 72, col. 1, para. 2]. As evidenced by Elgrishi, cyclic voltammetry is performed in the absence of convection [pg. 201, col. 1, para. 4; pg. 2 of Supporting Information, para. 2]), an electron carrier immobilized on an electrode (methyl aminohexyl viologen [MAHV] acts as a redox mediator [pg. 69, col. 2, para. 1; pg. 70, col. 1, paras. 3-4]), the electrode being connected to an external power supply outside the liquid (potentiostat [pg. 70, col. 2, para. 4]).
Lacey is silent to the following limitations: (1) a second process of bringing the liquid to a flowing state, wherein the first process and the second process are sequentially repeated, including performing at least the first process, the second process after the first process, and the first process after the second process; and (2) a duration of the first process is longer than a duration of the second process.
Elgrishi teaches a target molecule redox method (methods for cyclic voltammetry [pg. 197, Abstract]), wherein the method comprises a first process of bringing a liquid containing a target molecule to a non-flowing state (cyclic voltammetry is performed in the absence of convection [pg. 201, col. 1, para. 4; pg. 2 of Supporting Information, para. 2]), and a second process of bringing the liquid to a flowing state (sample solutions are stirred between measurements [pg. 2 of Supporting Information, para. 2]), wherein the first process and the second process are sequentially repeated, including performing at least the first process, the second process after the first process, and the first process after the second process (repeating the cyclic voltammetry measurement would result in performing the first process, the second process, and the first process again to obtain two cyclic voltammograms). Elgrishi teaches that the second process renews the layer of solution near the surface of the electrode for an accurate second cyclic voltammetry measurement [pg. 2 of Supporting Information, para. 2]. Additionally, the duration of the first process affects the extent of diffusion of analyte to the electrode surface [pg. 201, col. 1, para. 4], and the duration of the second process affects the extent of convection of analyte away from the electrode surface [pg. 201, col. 1, para. 4; pg. 2 of Supporting Information, para. 2].
Lacey and Elgrishi are both considered analogous to the claimed invention because they are in the same field of target molecule redox methods. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in Lacey by adding a second process of bringing the liquid to a flowing state, wherein the first process and the second process are sequentially repeated, including performing at least the first process, the second process after the first process, and the first process after the second process, as taught in Elgrishi, since this would renew the layer of solution near the surface of the electrode for an accurate second cyclic voltammetry measurement [pg. 2 of Supporting Information, para. 2 in Elgrishi]. Furthermore, Elgrishi teaches the claimed improvement as a known technique that is applicable to the base device in Lacey. One skilled in the art could have applied the second process and subsequent repetition in Elgrishi in the same way to the base device in Lacey, yielding predictable results (MPEP 2143(I)(D)).
As the diffusion of analyte to the electrode surface and the convection of analyte away from the electrode surface are variables that can be modified, among others, by adjusting the durations of the first and second processes, the precise durations of the first and second processes would have been considered result effective variables by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed relationship between the durations of the first and second processes cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the durations of the first and second processes in modified Lacey to be such that the duration of the first process is longer than the second process in order to obtain the desired analyte diffusion and convection, as taught by Elgrishi. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II).
The limitation “causing electron transfer between an electron carrier immobilized on an electrode and the target molecule to oxidize or reduce the target molecule” is an intended result of a positively recited step. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). MPEP 2111.04(I).
Regarding claim 2, modified Lacey teaches the target molecule redox method according to claim 1, and further teaches wherein in the second process, the liquid is agitated or shaken to bring the liquid to the flowing state (the sample is agitated via stirring to induce convective flow [pg. 2 of Supporting Information, para. 2 in Elgrishi]).
Regarding claim 4, modified Lacey teaches the target molecule redox method according to claim 1, but is silent to the limitation wherein a ratio of the duration of the first process to the duration of the second process is between 10:1 and 100:1, inclusive.
As the diffusion of analyte to the electrode surface and the convection of analyte away from the electrode surface are variables that can be modified, among others, by adjusting the durations of the first and second processes, the precise durations of the first and second processes would have been considered result effective variables by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed relationship between the durations of the first and second processes cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, a ratio of the duration of the first process to the duration of the second process in modified Lacey to be between 10:1 and 100:1 in order to obtain the desired analyte diffusion and convection, as taught by Elgrishi. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II).
Regarding claim 5, modified Lacey teaches the target molecule redox method according to claim 4, but is silent to the limitation wherein the duration of the first process is between 30 minutes and 90 minutes, inclusive, and the duration of the second process is between 1 minute and 2 minutes, inclusive.
As the diffusion of analyte to the electrode surface is a variable that can be modified, among others, by adjusting the duration of the first process, the precise duration of the first process would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed duration of the first process cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the duration of the first process in modified Lacey to be between 30 and 90 minutes in order to obtain the desired analyte diffusion, as taught by Elgrishi. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II).
As the convection of analyte away from the electrode surface is a variable that can be modified, among others, by adjusting the duration of the second process, the precise duration of the second process would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed duration of the second process cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the duration of the second process in modified Lacey to be between 1 and 2 minutes in order to obtain the desired analyte convection, as taught by Elgrishi. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II).
Regarding claim 6, modified Lacey teaches the target molecule redox method according to claim 1, and Lacey further teaches wherein the target molecule is NADP+ (method for detecting NADP+ based on reduction of NADP+ at a modified electrode [pg. 1, Abstract; pg. 72, col. 1, para. 2]).
Regarding claim 8, modified Lacey teaches the target molecule redox method according to claim 1, and Lacey further teaches wherein the electron carrier is a 4,4'-bipyridinium derivative (viologens such as MAHV are derivatives of 4,4’-bipyridyl [pg. 69, col. 2, para. 1; pg. 70, col. 1, para. 3]).
Regarding claim 10, modified Lacey teaches the target molecule redox method according to claim 1, and Lacey further teaches wherein a voltage is applied via the external power supply in the first process (the potentiostat applies voltage during cyclic voltammetry in Fig. 2(A) when the solution is not flowing [pg. 70, col. 2, para. 4]).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Lacey in view of Elgrishi, as applied to claim 8 above, and further in view of Passon et al. (“Redox behaviour of some asymmetrically substituted viologens and an alkyl bridged bis-viologen in non-aqueous solvents: a voltammetric and spectroscopic investigation,” 2015, J. Solid State Electrochem., vol. 19, pgs. 85-101).
Regarding claim 9, modified Lacey teaches the target molecule redox method according to claim 8, but is silent to the limitation wherein the electron carrier is 1-methyl-1'-hexyl-4,4'-bipyridinium.
Passon teaches a 1-methyl-1'-hexyl-4,4'-bipyridinium electron carrier (viologen 3 in Scheme 1 is 1-hexyl-1’-methyl-4,4’-bipyridinium, which is structurally equivalent to the claimed compound [pg. 85, col. 2, para. 2; pg. 88, col. 1, para. 4]). Passon further teaches that using this viologen offers controllable redox properties [pg. 100, col. 1, para. 3].
Modified Lacey and Passon are both considered analogous to the claimed invention because they are in the same field of viologen electron carriers. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the viologen electron carrier in modified Lacey with 1-methyl-1'-hexyl-4,4'-bipyridinium, as taught in Passon, because the substitution would offer controllable redox properties [pg. 100, col. 1, para. 3 in Passon]. Furthermore, the claimed method differs from modified Lacey by the substitution of some components (the immobilized viologen MAHV in modified Lacey) with other components (1-methyl-1'-hexyl-4,4'-bipyridinium in Passon) whose functions were known in the prior art. One of ordinary skill in the art could substitute one known element for another to yield predictable results (MPEP 2143(I)(B)).
Furthermore, the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07.
Claims 1 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Madoz-Gurpide et al. (“Modulation of Electroenzymatic NADPH Oxidation through Oriented Immobilization of Ferredoxin:NADP+ Reductase onto Modified Gold Electrodes,” 2000, J. Am. Chem. Soc., vol. 122, pgs. 9808-9817, referred to herein as Madoz) in view of Elgrishi.
Regarding claim 1, Madoz teaches a target molecule redox method (a method for oxidizing NADPH [Title]) comprising:
a first process of bringing a liquid containing a target molecule to a non-flowing state (cyclic voltammetry is used to induce the oxidation of NADPH in solution in Figs. 2 and 3 [pg. 9811, col. 1, para. 5; pg. 9811, col. 2, para. 2]). As evidenced by Elgrishi, cyclic voltammetry is performed in the absence of convection [pg. 201, col. 1, para. 4; pg. 2 of Supporting Information, para. 2]), an electron carrier immobilized on an electrode (redox mediators covalently attached to an electrode in Figs. 2 and 4 [pg. 9808, Abstract; pg. 9810, col. 2, para. 4]), the electrode being connected to an external power supply outside the liquid (as evidenced by Elgrishi, an external power source is required to apply voltage to the electrode for cyclic voltammetry [pg. 197, col. 2, para. 3]); wherein the first process is repeated (8 cyclic voltammetry measurements were performed for each experimental condition in Table 1 [pg. 9811, col. 2, para. 3; pg. 9812, col. 1, para. 1]).
Madoz is silent to the following limitations: (1) a second process of bringing the liquid to a flowing state, wherein the first process and the second process are sequentially repeated, including performing at least the first process, the second process after the first process, and the first process after the second process; and (2) a duration of the first process is longer than a duration of the second process.
Elgrishi teaches a target molecule redox method (methods for cyclic voltammetry [pg. 197, Abstract]), wherein the method comprises a first process of bringing a liquid containing a target molecule to a non-flowing state (cyclic voltammetry is performed in the absence of convection [pg. 201, col. 1, para. 4; pg. 2 of Supporting Information, para. 2]), and a second process of bringing the liquid to a flowing state (sample solutions are stirred between measurements [pg. 2 of Supporting Information, para. 2]), wherein the first process and the second process are sequentially repeated, including performing at least the first process, the second process after the first process, and the first process after the second process (repeating the cyclic voltammetry measurement would result in performing the first process, the second process, and the first process again to obtain the 8 cyclic voltammogram experiments). Elgrishi teaches that the second process renews the layer of solution near the surface of the electrode for accurate repeated cyclic voltammetry measurements [pg. 2 of Supporting Information, para. 2]. Additionally, the duration of the first process affects the extent of diffusion of analyte to the electrode surface [pg. 201, col. 1, para. 4], and the duration of the second process affects the extent of convection of analyte away from the electrode surface [pg. 201, col. 1, para. 4; pg. 2 of Supporting Information, para. 2].
Madoz and Elgrishi are both considered analogous to the claimed invention because they are in the same field of target molecule redox methods. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in Madoz by adding a second process of bringing the liquid to a flowing state, wherein the first process and the second process are sequentially repeated, including performing at least the first process, the second process after the first process, and the first process after the second process, as taught in Elgrishi, since this would renew the layer of solution near the surface of the electrode for accurate repeated cyclic voltammetry measurements [pg. 2 of Supporting Information, para. 2 in Elgrishi]. Furthermore, Elgrishi teaches the claimed improvement as a known technique that is applicable to the base device in Madoz. One skilled in the art could have applied the second process and subsequent repetition in Elgrishi in the same way to the base device in Madoz, yielding predictable results (MPEP 2143(I)(D)).
As the diffusion of analyte to the electrode surface and the convection of analyte away from the electrode surface are variables that can be modified, among others, by adjusting the durations of the first and second processes, the precise durations of the first and second processes would have been considered result effective variables by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed relationship between the durations of the first and second processes cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the durations of the first and second processes in modified Madoz to be such that the duration of the first process is longer than the second process in order to obtain the desired analyte diffusion and convection, as taught by Elgrishi. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II).
The limitation “causing electron transfer between an electron carrier immobilized on an electrode and the target molecule to oxidize or reduce the target molecule” is an intended result of a positively recited step. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). MPEP 2111.04(I).
Regarding claim 7, modified Madoz teaches the target molecule redox method according to claim 1, and Madoz further teaches wherein the electrode includes a substrate including gold (the electrode is a gold electrode [pg. 9811, col. 2, para. 2]).
Response to Arguments
Applicant’s arguments, see Remarks pgs. 4-7, filed 8/26/2025, with respect to the 35 U.S.C. § 102 and 103 rejections have been fully considered. All 35 U.S.C. § 102 and 103 rejections from the previous office action are withdrawn in view of the Applicant’s amendment. However, applicant’s arguments are moot in view of the new grounds of rejection.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/K.T./Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795