DETAILED ACTION
Response to Amendment
This is a final office action in response to a communication filed on December 19, 2025. Applicant’s confirmation of the election of Group I, claims 1-16 in the reply is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Currently, claims 1-16 are pending in the application.
Status of Objections and Rejections
All objections from the previous office action are withdrawn in view of Applicant’s amendment.
The rejection of claim 3 is obviated by Applicant’s cancellation.
Some rejections under 35 U.S.C. §112 from the previous office action are withdrawn in view of Applicant’s amendment and some rejections are maintained.
All rejections under 35 U.S.C. §102 and 103 are withdrawn. New grounds of rejection are necessitated by the amendments.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 5 is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 5 recites the limitation "the sample baseline measurement” in last line. It is unclear which sample of this sample baseline measurement and suggested to be “a second sample baseline measurement.”
Claim 5 recites the limitation "the sample” in line 7. It is unclear which sample of this sample and suggested to be “the second sample.”
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.
Claim(s) 1-2, 4, 6-14, and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Paik (US 2017/0356904).
Regarding claim 1, Paik teaches a method for determining a property of an analyte in a sample (¶4: detecting a presence of a target analyte and/or binding energy), the sample comprising the analyte (¶4: target analyte), non-analyte species (¶4: non-target analyte) and a sample matrix in which the analyte and non-analyte species are contained (¶17: a solution containing the target analyte and non-target analyte), the method comprising:
providing a sensor assembly (Fig. 5; ¶77), the sensor assembly comprising a sensing element (Fig. 5; ¶77: sensing location 507 or 514) comprising a capture species (Fig. 5; ¶77: antibody 505 or 519) configured to specifically bind with the analyte (Fig. 5; ¶77: a first target antigen 504 binds to the first antibody 505 (e.g., capture probe)), the sensing element providing a measurement signal indicative of the interaction of the sensing element with the sample (¶4: detecting a signal of the target analyte on the one or more surfaces);
providing the sample to the sensing element (¶4: bringing the one or more surfaces in contact with a solution), wherein at least a portion of analyte in the sample non-specifically bind to the sensing element and wherein least a portion of analyte specifically-binds to the sensing element (Fig. 6A; ¶79);
obtaining a sample baseline measurement based on the measurement signal (Fig. 11A-B; ¶96: signal plateau 1106);
removing at least a portion of the non-specifically-bound analyte from the sensing element by applying an electric field to the sample matrix (Fig. 6C), the electric field configured to remove non-specifically-bound analyte from at least a portion of the sensing element but having a strength less than that required to detach specifically-bound analyte from the sensing element (¶81); and
determining the property of the analyte in the sample based on the measurement signal after the step of removing at least a portion of the non-specifically-bound analyte from the sensing element (¶82: to determine the binding force between the target antigen and the capture probe);
determining an adjustment factor based on the measurement signal during the step of removing at least a portion of the non-specifically-bound analyte from the sensing element and after the sample baseline measurement (Fig. 11B: the signal dropping 1114 along with increasing voltage), and
adjusting at least one parameter of the step of removing at least a portion of the non-specifically-bound analyte from the sensing element based on the adjustment factor (Fig. 11B: along with the dropping signal, the voltage keeps increasing; here the adjustment factor is the slope of the dropping signal, i.e., the increasing rate of the voltage; the parameter is the voltage which is adjustable based on the increasing rate of the voltage; also see Fig. 8A; ¶ 87: there is a difference in sensor voltage signal between the first orifice and the second orifice; thus the increasing rate of voltage at the two confinement locations are different).
Regarding claim 2, Paik teaches wherein the sample baseline measurement is used to determine at least one parameter of the step of removing at least a portion of the non-specifically-bound analyte and/or non-analyte species from the sensing element (Fig. 11B; ¶96: The binding energy voltage can be defined as the voltage (1/2*ΔV) where half of the target analytes are released from the surface 1118).
Regarding claim 4, Paik teaches wherein the adjustment factor is based on the rate of change in the measurement signal during the step of removing at least a portion of the non-specifically-bound analyte from the sensing element (Fig. 11B: the signal dropping 1114 along with increasing voltage; here the adjustment factor is the slope of the dropping signal).
Regarding claim 6, Paik teaches wherein the sample baseline measurement is obtained at least during the step of removing at least a portion of the non-specifically-bound analyte from the sensing element (Fig. 13B: two inflection points of the voltage signal; Examiner notes here the signal before the second inflection point is deemed to be the baseline measurement, which is partially during the step of removing), and the sample baseline measurement comprises the rate of change in the measurement signal (Fig. 13B: the signal before the second inflection point shows a rate of change in the dropping signal).
Regarding claim 7, Paik teaches wherein the strength of the electric field is varied during the step of removing at least a portion of the non-specifically-bound analyte from the sensing element (Fig. 11B: the increasing voltage, corresponding to an increasing of the electric field strength).
Regarding claim 8, Paik teaches the method further comprising manipulating at least a portion of the specifically-bound analyte after the step of removing at least a portion of the non-specifically-bound analyte from the sensing element (Fig. 6D), wherein manipulating specifically-bound analyte comprises applying a force (due to the electric field) to the sample matrix sufficient to move specifically-bound analyte on the sensing element (¶82: at a third voltage, some specifically bound analytes detach as well); and
wherein determining the property of the analyte in the sample is based on the measurement signal during and/or after the step of manipulating specifically-bound analyte (Fig. 11B: the signal dropping during the manipulating step; ¶96: the binding energy voltage can be defined as the voltage where half of the target analytes are released from the surface 1118).
Regarding claim 9, Paik teaches wherein determining the property of the analyte is based on the rate of change in the measurement signal during the step of manipulating specifically-bound analyte (Fig. 11B; ¶96: the binding energy voltage 1118 is defined as the voltage where half of the target analytes are released from the surface, which is based on the rate of change in the measurement signal, i.e., the signal dropping curve).
Regarding claim 10, Paik teaches the method further comprising detaching at least a portion of the specifically-bound analyte (Fig. 6D: a portion of the specifically-bound analyte are detached) after the step of removing at least a portion of the non-specifically-bound analyte from the sensing element, wherein detaching specifically-bound analyte comprises applying a force to the sample matrix sufficient to detach specifically-bound analyte from the sensing element (due to the increased electric field with increasing voltage); and
wherein determining the property of the analyte in the sample is based on the measurement signal during and/or after the step of detaching the specifically-bound analyte (Fig. 13B; ¶98: two binding energy voltages, 1316 and 1318; here the second binding energy voltage is determined during or after the step of detaching the specifically-bound analyte).
Regarding claim 11, Paik teaches wherein determining the property of the analyte is based on the rate of change in the measurement signal during the step of detaching the specifically-bound analyte (Fig. 11B; ¶96: the binding energy voltage 1118 is defined as the voltage where half of the target analytes are released from the surface; Fig. 13B; ¶98: two binding energy voltages, 1316 and 1318; both are determined based on the rate of change in the measurement signal, i.e., the signal dropping curve).
Regarding claim 12, Paik teaches wherein the force is provided by at least one of an electric field (Fig. 11B; ¶96: application of a linearly increasing applied voltage creates an electric field and an applied force on the charged analytes).
Regarding claim 13, Paik teaches
wherein the method further comprises providing a detection species (Fig. 8B; ¶85: a charge label) to the sample matrix, the detection species specifically-binding to the analyte (Fig. 8B; ¶85: the analyte is not charged but becomes charged by associating with a charge label); and
wherein strength of the electric field configured to remove non-specifically-bound analyte from at least a portion of the sensing element is less than that required to detach specifically-bound detection species from the analyte (Fig. 6A-E; Fig. 11B; since the increasingly applied voltage detaches the non-specifically-bound analyte followed by detaching the specifically-bound detection species (e.g., the analyte with the charged label), the required strength of the electric field for removing non-specifically-bound analyte must be less than that required to detach specifically-bound detection species).
Regarding claim 14, Paik teaches wherein the sensing element comprises a sensing layer (Fig. 7; ¶83: sensing electrode 705 or 709), the sensing layer having a plurality of structures formed therein (Fig. 1: sensing electrodes 705 and 709 constitute a plurality of structures); and wherein the measurement signal is dependent on the location of the analyte relative to the plurality of structures in the sensing layer (¶83: the binding of charged analytes in proximity to the first field confinement feature can be monitored by a first voltage output 703; the binding of charged analytes in proximity to the second field confinement feature can be monitored by a second voltage output 710).
Regarding claim 16, Paik teaches wherein the step of providing the sample matrix to the sensing element comprises:
applying an electric field to the sample matrix on the sensing element, the electric field being configured so as to cause movement of the analyte towards the capture species (Fig. 6B; ¶80: a first voltage where initial binding occurs).
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.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Paik.
Regarding claim 5, Paik discloses all limitations of claim 1. Paik does not disclose the method further comprising: subsequently providing a second sample to the sensor assembly, the sample comprising the analyte, the non-analyte species and the sample matrix in which the analyte and non-analyte species are contained; and determining the property of the analyte in the second sample based on the measurement signal for the second sample and a signal compensation factor, wherein the signal compensation factor is based on the sample baseline measurement and the measurement signal for the sample.
However, Paik teaches along with increasing voltage, the electrokinetic force on the hybridized nucleic acid may increase until nucleic acid is pulled off (¶78). This pull-off voltage is related to the binding energy of the target analyte to the capture probe and can be used to discriminate between the a target that may be a correct complementary match and a target that has a single or plurality of mutations and is not completely complementary to the capture probe (¶78). Thus, Paik teaches use a measured binding energy with fully complementary binding (i.e., a first sample) to determine whether the subsequent sample (i.e., a second sample) is a fully complementary binding or not due to a single or plurality of mutations for example, due to the target detaching at a lower voltage.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Paik by subsequently providing a second sample to the apparatus to determine if the subsequent sample is identical to the first sample based on the binding energy, for example, a lower binding energy voltage corresponding to mutation presences, because this method would provide a means to identify mixed mutation samples (¶78), i.e., between similar molecular analytes. Here, applying a known technique to a known method ready for improvement to yield predictable results is prima facie obvious. MPEP 2141(III)(D).
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Paik in view of Lu (J. Lu, Plasmonic-Based Electrochemical Impedance Spectroscopy: Application to Molecular Binding, Analytical Chemistry, 2012(84), pp. 327-333).
Regarding claim 15, Paik teaches all limitations of claim 14, but fails to teach wherein the measurement signal is indicative of an impedimetric property of the sensing layer and the configuration of the sensing layer and the capture species is such that analyte that is specifically bound to the capture species is able to modify an impedimetric property of the sensing layer.
However, Lu teaches P-EIS is to investigate molecular binding on surfaces ([Abstract]). Impedance spectrum is obtained by measuring impedance vs frequency with P-EIS (bridging para. of pp. 327-328) for molecular binding studies, e.g., human IgG and anti-human IgG interaction (p. 327, col. 1, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Paik by employing impedimetric signal of the sensing surface to investigation the molecular binding as taught by Lu because impedance is a property useful for studying the molecular binding. Applying a known technique to a known method ready for improvement to yield predictable results is prima facie obvious. MPEP 2141(III)(D).
Response to Arguments
Applicant’s arguments have been considered but are unpersuasive.
Applicant argues Paik’s rate of voltage increase is linear, and thus Paik does not disclose or suggest any adjustment of its rate of voltage increase (p. 8, last para.). This argument is unpersuasive because the adjustment factor is the increasing rate (i.e., the slope), which is not necessarily varying as recited, and the parameter is the voltage, which is adjustable based on the increasing rate at different times. Further, Examiner notes that Fig. 8A of Paik indicates that the sensor voltages at different confinement locations increases at different rate, which suggests that the increasing rate of the voltage is variable.
Applicant asserts that it does not admit the interpretation of Paik as described in the previous Office action (p. 8, last para.), but does not provide any interpretation. Since the limitations “an adjustment factor” and “at least one parameter” are broad, Examiner requests Applicant to clarify what these limitations are and provide evidentiary support in the original disclosure of the instant application.
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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 CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795
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