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 September 3, 2026 has been entered. Claims 1-2, 7-11, and 13 have been amended; and claims 12 and 14-20 have been withdrawn. Claims 1-11, and 13 are currently examined herein.
Status of the Rejection
Applicant’s amendments to the Claims have partially overcome the claim objection previously set forth in the Non-Final Office Action mailed June 3, 2026.
New grounds of claim objections are necessitated by the amendment as outlined below.
Applicant’s amendments to the Claims have overcome the claim rejections under 112(b) previously set forth in the Non-Final Office Action mailed June 3, 2026.
New grounds of claim rejection under 35 U.S.C. § 112(a) and 112(b) are necessitated by the amendment as outlined below.
All 35 U.S.C. § 102 rejections from the previous office action are essentially maintained and modified in response to the amendment as outlined below.
The 35 U.S.C. § 103 rejection for claim 8 from the previous office action is withdrawn in view of the amendment.
Claim Objection
Claims 1 and 9-11 are objected to because of the following informalities:
Claim 1: please amend “analyte binding to at least one affinity-based probe” to – the at least one analyte binding to at least one affinity-based probe --.
Claim 9: please amend “the electrode” (two places) to –the at least one electrode--.
Claim 10: please amend “the redox tags of the plurality of redox tags” to -- at least one electrode--.
Claim 11: please amend “the aptamer” to – [[the]] each aptamer--; “the electrode” to –the at least one electrode--.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 8 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 8 recites “wherein each redox tag comprises at least one molecule that is distinct from at least one other redox tag of the plurality of redox tags”, while the amended claim 1 recites “wherein each of the plurality of redox tags are configured such that their redox peaks overlap”, and the specification does not disclose the redox tags must simultaneously satisfy the above two conditions. Therefore, claim 8 is a new matter.
Claim 10 recites “wherein the redox tags of the plurality of redox tags that are contributing to a measured signal each have a redox potential measured by the electrode and the redox potentials are within 0.125 V or less of each other”, while the amended claim 1 recites “wherein each of the plurality of redox tags are configured such that their redox peaks overlap”. The limitation of claim 10 requires that the redox potentials of the redox tags may be different, and their differences are within 0.125 V or less, while claim 1 requires the redox tags having the same redox potential (redox peaks overlap), thus, there is an inconsistence on the redox potentials of the redox tags. Furthermore, the specification does not disclose the redox tags must simultaneously satisfy the two conditions of claims 1 and 10. Therefore, claim 10 is a new matter.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
Claim 8 recites “wherein each redox tag comprises at least one molecule that is distinct from at least one other redox tag of the plurality of redox tags”. Since each redox tag comprises at least one molecule that is distinct from at least one other redox tag of the plurality of redox tags, their redox peaks are different and will not overlap. But the amended claim 1 recites “wherein each of the plurality of redox tags are configured such that their redox peaks overlap”. Therefore, there is an inconsistence on the redox potentials of the redox tags. It is unclear if the plurality of redox tags are the same molecules such that their redox peaks overlap or distinct from each other. Therefore, the scope of claim 8 is indefinite.
Claim 10 recites “wherein the redox tags of the plurality of redox tags that are contributing to a measured signal each have a redox potential measured by the electrode and the redox potentials are within 0.125 V or less of each other”, while the amended claim 1 recites “wherein each of the plurality of redox tags are configured such that their redox peaks overlap”. The limitation of claim 10 requires that the redox potentials of the redox tags may be different, and their differences are within 0.125 V or less, while claim 1 requires the redox tags having the same redox potential (redox peaks overlap), thus, there is an inconsistence on the redox potentials of the redox tags. Therefore, the scope of claim 10 is indefinite.
Claim Rejections - 35 USC § 102
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 1-7, 9-11 and 13 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rozenblum et al. (US20230031265A1). Plaxco et al. (US20190209063A1) is used as an evidence for claim 9.
Regarding claim 1, Rozenblum teaches a device (a biosensor device 100 in Fig.1 [para. 0038]); “for detecting or measuring at least one analyte in a sample fluid” is an intended use limitation [see MPEP 2111.02]. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Rozenblum teaches the biosensor device comprising working electrode 108 functionalized with an aptamer probe 106 that may be designed to bind specifically to a particular target molecule 109 in a sample fluid 104, act as a non-specific binding control, or to perform some other assay function [para. 0038, 0040, 0046, 0059]. Thus, the disclosed biosensor device is configured to perform the intended use of detecting or measuring at least one analyte 109 in a sample fluid 104. The device comprising:
at least one electrode (working electrodes 108 in Fig.1 [para. 0038]);
the sample fluid (a liquid solution such as liquid buffer solution 104 in Fig.1 containing analytes to be detected [para. 0059]); and
a plurality of affinity-based probes (one or more probes 112 in Fig.1 [para. 0038]) capable of binding to the at least one analyte (Each working electrode 108 may be functionalized with an aptamer probe 106 that may be designed to bind specifically to a particular target molecule 109 [para. 0040]), wherein the plurality of affinity-based probes each carry a plurality of redox tags (one or more redox molecules 105 in Fig.1 [para. 0038]; the one or more redox labels comprise Methyl Blue. In some embodiments, the probe comprises at least 3 redox molecules [para. 0011]);
wherein each of the plurality of redox tags are configured such that their redox peaks overlap (a gold working electrode is functionalized with an aptamer probe labelled with a sequence of three Methyl Blue redox molecules [para. 0094]; since the three redox tags have the same molecule of Methyl Blue, their redox peaks overlap); and
wherein the detection or measurement of the at least one analyte is caused by the at least one analyte binding to at least one affinity-based probe of the plurality of affinity-based probes (Each working electrode 108 may be functionalized with an aptamer probe 106 that may be designed to bind specifically to a particular target molecule 109 [para. 0040; claim 6]) which further causes a change in electron transfer from the at least one redox tag of the plurality of redox tags (wherein the one or more electrical current signals is generated by a change in the surface potential of a first working electrode of one or more working electrodes due to a change in distance between the one or more redox molecules of a first probe of the one or more probes and the first working electrode caused by a change in structure of the aptamer upon binding with a target of the one or more targets. Redox molecule denotes a molecule capable of accepting or donating an electron thereby changing its redox state. [claim 11, para. 0009]).
Regarding claim 2, Rozenblum teaches the device of claim 1, wherein the plurality of affinity-based probes are aptamers (each working electrode 108 is functionalized with an aptamer probe 106 and one or more redox molecules 105 [para. 0038]).
Regarding claim 3, Rozenblum teaches the device of claim 1, “wherein the device has a redox signal strength, and the redox signal strength, when compared to a probe with a singular redox tag, is at least 1.5 times greater” is a functional recitation of the device. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Rozenblum teaches the biosensor device 100 configured for amperometric sensing utilizing aptamer probes immobilized onto the working electrodes 108 and labeled with redox molecules 105 for current signal amplification. The probe may contain one or more redox molecules such as Methyl Blue, for example. The number of redox molecules attached to one probe is 3 to 20, 4 to 5, 4 to 10, 4 to 20, 5 to 10, 5 to 20, or 10 to 20 [para. 0038, 0041]. In order to increase the signal upon ligand binding, a branched phosphoramidite can be added during synthesis to increase the number of redox molecules in each probe molecule [para. 0089]. In some embodiments, synthesis of aptamers with enhanced redox reporters to enhance the signal upon target-ligand binding is achieved by adding several redox molecules [para. 0091]. The instant specification discloses: The present invention is capable of 2, 3, 5, or even 10 redox tags, or more, improving redox signal strength compared to a singularly tagged aptamer by at least one of 1.5×, 2×, 3×, 10× [para. 0037 ] in PG-Pub. Therefore, the disclosed biosensor device comprising substantially the same elements or components as that of the instant device wherein each probe is an aptamer carrying a plurality of redox tags for increasing the redox signal strength, it is contended that the biosensor device of the prior art is capable of providing the same redox signal strength as the instant device. Note that the redox signal strength is proportional to the number of redox tags, since the number of redox molecules attached to the disclosed probe is 3 to 20, 4 to 5, 4 to 10, 4 to 20, 5 to 10, 5 to 20, or 10 to 20 [para. 0041], the disclosed device is capable of providing a redox signal strength, when compared to a probe with a singular redox tag, is at least 1.5 times greater.
Regarding claim 4, Rozenblum teaches the device of claim 1, “wherein the device has a redox signal strength, and the redox signal strength, when compared to a probe with a singular redox tag, is at least 2 times greater” is a functional recitation of the device. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Rozenblum teaches the biosensor device 100 configured for amperometric sensing utilizing aptamer probes immobilized onto the working electrodes 108 and labeled with redox molecules 105 for current signal amplification. The probe may contain one or more redox molecules such as Methyl Blue, for example. The number of redox molecules attached to one probe is 3 to 20, 4 to 5, 4 to 10, 4 to 20, 5 to 10, 5 to 20, or 10 to 20 [para. 0038, 0041]. In order to increase the signal upon ligand binding, a branched phosphoramidite can be added during synthesis to increase the number of redox molecules in each probe molecule [para. 0089]. In some embodiments, synthesis of aptamers with enhanced redox reporters to enhance the signal upon target-ligand binding is achieved by adding several redox molecules [para. 0091]. The instant specification discloses: The present invention is capable of 2, 3, 5, or even 10 redox tags, or more, improving redox signal strength compared to a singularly tagged aptamer by at least one of 1.5×, 2×, 3×, 10× [para. 0037 ] in PG-Pub. Therefore, the disclosed biosensor device comprising substantially the same elements or components as that of the instant device wherein each probe is an aptamer carrying a plurality of redox tags for increasing the redox signal strength, it is contended that the biosensor device of the prior art is capable of providing the same redox signal strength as the instant device. Note that the redox signal strength is proportional to the number of redox tags, since the number of redox molecules attached to the disclosed probe is 3 to 20, 4 to 5, 4 to 10, 4 to 20, 5 to 10, 5 to 20, or 10 to 20 [para. 0041], the disclosed device is capable of providing a redox signal strength, when compared to a probe with a singular redox tag, is at least 2 times greater.
Regarding claim 5, Rozenblum teaches the device of claim 1, “wherein the device has a redox signal strength, and the redox signal strength, when compared to a probe with a singular redox tag, is at least 3 times greater” is a functional recitation of the device. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Rozenblum teaches the biosensor device 100 configured for amperometric sensing utilizing aptamer probes immobilized onto the working electrodes 108 and labeled with redox molecules 105 for current signal amplification. The probe may contain one or more redox molecules such as Methyl Blue, for example. The number of redox molecules attached to one probe is 3 to 20, 4 to 5, 4 to 10, 4 to 20, 5 to 10, 5 to 20, or 10 to 20 [para. 0038, 0041]. In order to increase the signal upon ligand binding, a branched phosphoramidite can be added during synthesis to increase the number of redox molecules in each probe molecule [para. 0089]. In some embodiments, synthesis of aptamers with enhanced redox reporters to enhance the signal upon target-ligand binding is achieved by adding several redox molecules [para. 0091]. The instant specification discloses: The present invention is capable of 2, 3, 5, or even 10 redox tags, or more, improving redox signal strength compared to a singularly tagged aptamer by at least one of 1.5×, 2×, 3×, 10× [para. 0037 ] in PG-Pub. Therefore, the disclosed biosensor device comprising substantially the same elements or components as that of the instant device wherein each probe is an aptamer carrying a plurality of redox tags for increasing the redox signal strength, it is contended that the biosensor device of the prior art is capable of providing the same redox signal strength as the instant device. Note that the redox signal strength is proportional to the number of redox tags, since the number of redox molecules attached to the disclosed probe is 3 to 20, 4 to 5, 4 to 10, 4 to 20, 5 to 10, 5 to 20, or 10 to 20 [para. 0041], the disclosed device is capable of providing a redox signal strength, when compared to a probe with a singular redox tag, is at least 3 times greater.
Regarding claim 6, Rozenblum teaches the device of claim 1, “wherein the device has a redox signal strength, and the redox signal strength, when compared to a probe with a singular redox tag, is at least 10 times greater” is a functional recitation of the device. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Rozenblum teaches the biosensor device 100 configured for amperometric sensing utilizing aptamer probes immobilized onto the working electrodes 108 and labeled with redox molecules 105 for current signal amplification. The probe may contain one or more redox molecules such as Methyl Blue, for example. The number of redox molecules attached to one probe is 3 to 20, 4 to 5, 4 to 10, 4 to 20, 5 to 10, 5 to 20, or 10 to 20 [para. 0038, 0041]. In order to increase the signal upon ligand binding, a branched phosphoramidite can be added during synthesis to increase the number of redox molecules in each probe molecule [para. 0089]. In some embodiments, synthesis of aptamers with enhanced redox reporters to enhance the signal upon target-ligand binding is achieved by adding several redox molecules [para. 0091]. The instant specification discloses: The present invention is capable of 2, 3, 5, or even 10 redox tags, or more, improving redox signal strength compared to a singularly tagged aptamer by at least one of 1.5×, 2×, 3×, 10× [para. 0037 ] in PG-Pub. Therefore, the disclosed biosensor device comprising substantially the same elements or components as that of the instant device wherein each probe is an aptamer carrying a plurality of redox tags for increasing the redox signal strength, it is contended that the biosensor device of the prior art is capable of providing the same redox signal strength as the instant device. Note that the redox signal strength is proportional to the number of redox tags, since the number of redox molecules attached to the disclosed probe is 3 to 20, 4 to 5, 4 to 10, 4 to 20, 5 to 10, 5 to 20, or 10 to 20 [para. 0041], the disclosed device is capable of providing a redox signal strength, when compared to a probe with a singular redox tag, is at least 10 times greater.
Regarding claim 7, Rozenblum teaches the device of claim 1, wherein the plurality of redox tags comprise the same molecule (the nucleotide on the opposite end of the linker end, is labeled with a sequence of three Methyl Blue redox molecules [para. 0094]).
Regarding claim 9, Rozenblum teaches the device of claim 1, wherein the plurality of redox tags have an average position relative to the at least one electrode during measurement (Fig.1 shows the redox tags 105 have an average position relative to the electrode 108 during measurement), and
“the plurality of redox tags with further position from the at least one electrode have a redox peak voltage that is less than the redox peak voltage for the plurality of redox tags in closer position to the electrode” is an inherent characteristic of the electrochemical aptamer-based (E-AB) sensor. Since the prior art does disclose E-AB biosensor device comprising substantially the same elements or components as that of the applicant, it is contended that the plurality of redox tags of the prior art with further position from the at least one electrode have a redox peak voltage that is less than the redox peak voltage for the plurality of redox tags in closer position to the at least one electrode. Furthermore, Rozenblum teaches wherein Fig.1 shows the redox tags 105 with a further position from the electrode 108 when the probe is not binding to the target molecule 109 and the redox tags 105 with a closer position to the electrode 108 when the probe is binding to the target molecule 109 (the complimentary probe-target binding, causing the aptamer to change conformation 110, places the redox molecules in closer proximity to the working electrode 108 [para. 0101]). This decrease in distance between the redox molecules and the working electrode causes an increase in the electrical current [para. 0101]. As further evidenced by Plaxco wherein Fig.2A shows the electrical current caused by the redox tag Methylene blue (MB) increases as the aptamer probe binding to the target analyte and the redox peak voltage for the MB redox tag in closer position to the electrode (for 0.1 mM and 1.0 mM target analyte concentrations in Fig.2A) is higher than the redox peak voltage for the MB redox tag in a further position from the electrode (no target in Fig.2A since the redox tag is brought in closer proximity to the working electrode when the aptamer binds to the target) [para. 0010 in Plaxco]. Note that Rozenblum teaches wherein the one or more redox molecules comprise Methyl Blue [para. 0041, 0094], and the redox tags of MB is the same as the MB redox tag of Plaxco. Thus, the disclosed redox tags of Rozenblum with further position from the at least one electrode have a redox peak voltage (corresponding to the redox peak voltage with No target as shown in Fig.2A in Plaxco and the redox tags 105 with further position from the electrode 108 with no target as shown in Fig.1 in Rozenblum) that is less than the redox peak voltage for the redox tags in closer position to the at least one electrode (corresponding to the redox peak voltage with 0.1 mM and 1 mM target as shown in Fig.2A in Plaxco and the redox tags 105 in closer position to the electrode 108 when the aptamer binds to the target 109 as shown in Fig.1 in Rozenblum).
Regarding claim 10, Rozenblum teaches the device of claim 1, wherein the redox tags of the plurality of redox tags that are contributing to a measured signal each have a redox potential measured by the at least one electrode (the one or more redox molecules is Methyl Blue [para. 0041, 0094], each MB redox tag has a redox potential) and the redox potentials are within 0.125 V or less of each other (the nucleotide is labeled with a sequence of three Methyl Blue redox molecules [para. 0094]; since the redox tags are the same, the redox potentials of the redox tags are the same, thus are within 0.125 V or less of each other).
Regarding claim 11, Rozenblum teaches the device of claim 2, wherein the aptamer is bound to a material that itself is directly or indirectly attached to the at least one electrode (a probe composition has the formula: [[A]n[X]m]y-L-S, wherein each A independently comprises a monomer linked to one or more redox molecules, each X independently comprises a monomer, L comprises a linker, S comprises a substrate. In some embodiments, the linker comprises a thiol end group. In some embodiments, the substrate comprises gold [para. 0011]; the nucleotide sequence is attached to the gold surface of the working electrode by the reaction product of the linker 1-0-Dimethoxytrityl-hexyldisulfide,r-[(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite as seen in Fig.7 [para. 0094]; thus the aptamer is bound to a material [a linker] that itself is directly attached to the at least one electrode).
Regarding claim 13, Rozenblum teaches the device of claim 1, wherein the plurality of affinity-based probes each carry at least three redox tags (wherein the probe comprises at least 3 redox molecules [claim 26; para. 0011]; the nucleotide on the opposite end of the linker end, is labeled with a sequence of three Methyl Blue redox molecules [para. 0094]).
Response to Arguments
Applicant's arguments, see Remarks Pgs. 7-9, filed 9/3/2026, with respect to the 35 U.S.C. § 102(a)(1) and 35 U.S.C. § 103 rejections have been fully considered.
Applicant’s Argument #1:
Regarding the 102(a)(1) rejections, Applicant argues at page 10 that the amended claim 1 recites that the device comprises affinity probes carrying a plurality of redox tags, wherein each of the plurality of redox tags are configured such that their redox peaks overlap. Rozemblum fails to teach the above amended feature.
Examiner’s Response #1:
Applicant’s arguments have been fully considered, but are moot in view of the new grounds of rejection for claim 1 above.
Applicant’s Argument #2:
Regarding the 103 rejection for claim 8, Applicant argues at page 11 that the prior art does not teach the amended feature of claim 1.
Examiner’s Response #2:
Applicant’s arguments have been fully considered, and the 103 rejection for claim 8 is withdrawn. Claim 8 is rejected under 112(a) and 112(b) as outlined above.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHIZHI QIAN whose telephone number is (571)272-3487. The examiner can normally be reached Monday-Thursday 8:00 am-5:00 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan V Van can be reached on 571-272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHIZHI QIAN/Primary Examiner, Art Unit 1795
