DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This application has been transferred from Examiner B. Sisson to Examiner D. Johannsen. The application remains assigned to Art Unit 1682.
This action is responsive to the Amendment and Response filed 26 February 2026. Independent claims 1 and 10 have been amended. Claims 1-20 remain under consideration. Applicant’s amendments and arguments have been thoroughly reviewed, and upon further consideration, the following rejections set forth in the Office action mailed 27 October 2025 are withdrawn:
The rejection of dependent claims 5-9 and 11-15 under 35 USC 102(a)(1) as being anticipated by Santos-Cancel et al (ACS Sensors 3(6):1203-1209 [2018]; cited in IDS) (although it is noted that claims 1-4 and 10 remain rejected for the reasons given below);
The rejection of claims 1-20 under 35 USC 103 as being unpatentable over Santos-Cancel et al (Analytical Chem. 89:5598 [2017]; previously cited) in view of Piermarini et al (Biosensors and Bioelectronics 22:1434 [2006]; previously cited); and
The rejections of claims under 35 USC 101 and 112 (related to alleged lack of utility and enablement).
The claims remain rejected on the grounds set forth below. Any rejections and/or objections note reiterated in this action have been withdrawn. This action is NON-FINAL.
Priority
This application is the national stage of PCT/US20/16475, filed 04 February 2020, claiming priority to US provisional application 62/800,696, filed 04 February 2019. As the noted provisional application does not disclose methods/systems having all of the recited limitations of instant independent claims 1, 10, and 16, the effective filing date of the claims now under consideration (for purposes of comparing the claims to the prior art) is that of the PCT application, 04 February 2020. It is noted that the International Search Report and Written Opinion issued in the PCT application have been received and reviewed.
Claim Interpretation
With regard to the recitation in the claims of the limitation “media solution” (see, e.g., independent claims 1, 10, and 16), it is noted that the application as filed refers throughout to the practice of methods of the claims in a “media”/”medium” (see, e.g., the Background and Summary at paragraphs 3-8 and the Detailed Description at paragraphs 40, 42 and 102-108 of corresponding published application US2022095961, noting the numerous references to determination of “a concentration of a target in a media” including activities such as “dispensing target in the media”); the application also discloses to the practice of methods of the invention in a “solution”, which term is employed in a manner that makes clear that the term solution is also being used (in these contexts) to reference a medium/media in which the recited dispensing, sensing, determination of concentration, etc., occur (see, e.g., paragraphs 42, 44-45, 74, 78, 90 of corresponding published application US2022095961). It is also noted that the term “media” used alone in the claims was previously rejected as indefinite, with the claims subsequently being amended to recite a ”media solution”; Applicant’s arguments of the date of that amendment (14 October 2024) discuss the support for use of the terms “media”, “medium”, and “solution”, stating the term ”media” is “also referenced as a medium and solution” in the application (Reply of 14 October 2024 at pages 14-15). The term “media solution” was subsequently also rejected as indefinite (Office action of 24 February 2025); however, the rejection was not repeated in a Non-Final Office action mailed 27 October 2025. Based on the use of these terms in the application as filed as well as the prior prosecution history, the term “media solution” as presently used has been interpreted as equivalent to a “media”, “medium”, and/or “solution” as discussed above (i.e., the use of the full term “media solution” does not add new matter, but rather makes clear that the “media” of the invention is also a “solution” [as opposed to, e.g., some type of solid medium/media).
With regard to independent claim 1 and claims dependent therefrom (claims 2-9), as well as independent claim 10 and claims dependent therefrom (claims 11-15), it is noted that while the steps/actions of “applying”’ an IPA waveform and “determining the concentration of the target molecule in the media solution” must occur following the “dispensing the target molecule in the media solution”, given the use of the open transitional language “comprising’ the activity of “determining a reference point of the target molecule-binding aptasensor to set a baseline level corresponding to the reference point” need only have occurred prior to the final activity of “determining the concentration….based on the baseline level of the reference point” (as the claims recite the open transitional language “comprising”, and there is no reference in the “determining a reference point” to the activities of the prior two steps that necessitates a particular order of steps).
Also regarding independent claim 1 and claims dependent therefrom, while the independent claim requires both an “applying” that is sufficient to “sense the target molecule”, and a “determining the concentration of the target molecule in the media solution”, the claim as written does not require any particular relationship between these two steps/activities.
Claim Rejections - 35 USC § 112(b)/second paragraph
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 1-20 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding independent claim 1 and claims dependent therefrom, claim 1 recites – following the recitation of a method “of using a target molecule-binding aptasensor to determine a concentration of a target molecule in a media solution” and an action/step of “dispensing the target molecule in the media solution” – the limitation “applying an intermittent pulse amperometry (“IPA”) waveform to the target molecule-binding aptasensor in the media solution to sense the target molecule”. This language is confusing, because clear antecedent basis is lacking for “the target molecule-binding aptasensor in the media solution”, as the claim does not previously reference or otherwise clearly require a “target molecule-binding aptasensor in the media solution”. It is unclear whether the claimed methods require that the aptasensor be present in the “media solution” prior to the “dispensing” (which seems to be suggested by reference to “the….aptasensor in the media solution”), or whether the claims embrace, e.g., addition of the aptasensor following the “dispensing” (as is suggested by the use of the open transitional language “comprising”, and the lack of an explicitly reference to a media solution that includes the aptasensor). As there are multiple reasonable interpretations of the claim language that impart different boundaries on what is being claimed, clarification is required.
Regarding independent claim 10 and claims dependent therefrom, claim 10 recites – following the recitation of a method “of using a target molecule-binding aptasensor to determine a concentration of a target molecule in a media solution” and an action/step of “dispensing the target molecule in the media solution” – the limitation “applying an intermittent pulse amperometry (“IPA”) waveform to the target molecule-binding aptasensor in the media solution to sense the target molecule”. This language is confusing, because clear antecedent basis is lacking for “the target molecule-binding aptasensor in the media solution”, as the claim does not previously reference or otherwise clearly require a “target molecule-binding aptasensor in the media solution”. It is unclear whether the claimed methods require that the aptasensor be present in the “media solution” prior to the “dispensing” (which seems to be suggested by reference to “the….aptasensor in the media solution”), or whether the claims embrace, e.g., addition of the aptasensor following the “dispensing” (as is suggested by the use of the open transitional language “comprising”, and the lack of an explicitly reference to a media solution that includes the aptasensor). As there are multiple reasonable interpretations of the claim language that impart different boundaries on what is being claimed, clarification is required.
Claims 10-15 are also indefinite over the recitation in independent claim 10 of the limitation “determining the concentration of the target molecule in the media solution based on the baseline level of the reference point, wherein the concentration of the target molecule is determined based on a temporal resolution of 2 milliseconds of the applied IPA waveform”. This language states that concentration is “based on” two different criteria that are not clearly linked together by the present claim language (either in the final “determining” itself, or via some type of other previously recited requirement that would necessarily relate/link these two activities to one another). The recitation of determining concentration “based on” a baseline level of a reference point, and as also “based on” a temporal resolution of 2 milliseconds of the applied IPA waveform, is vague, appearing to reference alternative possible ways in which the final activity of the claim may be performed (as opposed to clearly relating these two activities to one another so as to apprise one of ordinary skill in the art how concentration is to be determined). Further clarification is therefore needed.
Claims 16-20 are indefinite over the recitation in independent claim 16 of the limitation “determining the concentration of the target molecule in the media solution based on the baseline level of the reference point, wherein the concentration of the target molecule is determined based on a temporal resolution of 2 milliseconds of the applied IPA waveform”. This language states that concentration is “based on” two different criteria that are not clearly linked together by the present claim language (either in this “determining” itself, or via some type of other previously recited requirement that would necessarily relate/link these two activities to one another). The recitation of determining concentration “based on” a baseline level of a reference point, and as also “based on” a temporal resolution of 2 milliseconds of the applied IPA waveform, is vague, appearing to reference alternative possible ways in which the final activity of the claim may be performed (as opposed to clearly relating these two activities to one another so as to apprise one of ordinary skill in the art how concentration is to be determined). Further clarification is therefore needed.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-4 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Santos-Cancel et al (ACS Sens. 3:1203-1209 [2018]; cited in IDS).
Santos-Cancel et al teach the use of intermittent pulse amperometry (IPA) in interrogation of electrochemical aptamer-based sensors (i.e., aptasensors) to achieve rapid quantitative detection of target analytes, teaching that changes in sensor current “are quantitatively related to target analyte concentration” (see the entire reference, particularly the Abstract and the section “IPA Enables Rapid and Quantitative Measure of E-AB Sensor Performance” at page 1205, right column-1207, noting the statement that these results “demonstrate the applicability of IPA for a quantitative measure of target analyte concentration” [page 1205, right column]). Thus, the methods disclosed by Santos-Cancel et al meet the claim requirement of “using a target molecule-binding aptasensor to determine a concentration of a target molecule in a media solution”. With regard to the particular steps of independent claims 1 and 10, Santos-Cancel et al teach:
Addition of target molecules into media solution containing a target-molecule binding (tobramycin or ATP) aptasensor (see, e.g., page 1205, left column, first full paragraph; page 1207, right column and Figure 6);
Applying IPA waveforms to sense the target molecule (see, e.g., page 1205, left column, first paragraph; page 1205, left column under “Results and Discussion” [describing IPA]; page 1207, right column-page 1208 including Figures 6-7);
Determining a type of reference point of aptasensors “to set a baseline level corresponding to” a reference point (see, e.g., comparisons of current-time traces with and without target and comparisons of current response in the presence and absence of target at page 1206 and Figures 2-4, which establish and depict a type of baseline “reference point”); and
Quantitative determination of target analyte concentration in a manner that takes into account the knowledge of responses in the absence of target, which meets the requirement of a determining “based on the baseline level of the reference point” (see, e.g., page 1206, right column-page 1207 including Figures 3-7).
With further regard to dependent claims 2-3 as well as independent claim 10, Santos-Cancel et al disclose determination of concentration “based on a temporal resolution of” an applied IPA wave form, where the temporal resolution is 2 milliseconds; see, e.g., page 1207, right column (particularly at the first and last full paragraphs) and Figure 6). Regarding dependent claim 4 as well as independent claim 10, Santos-Cancel et al disclose applying an IPA waveform as recited in the claim (see, e.g., page 1207, right column, second full paragraph). With further regard to independent claim 10, it is reiterated that the final “determining” of the claim is indefinite (as discussed above); the methods disclosed by Santos-Cancel et al meet all requirements of the claim to the extent that it is presently understood.
The Reply of 26 February 2026 traverses the prior rejection of claims under 35 USC 102(a)(1) based on the Santos-Cancel et al reference on the following grounds.
The Reply summarizes the requirements of the claims (Reply page 6-7) as well as the teachings of the specification, focusing on Figures 1-5 (Reply pages 7-10). Applicant then argues that the Santos-Cancel reference “does not describe any calibration free detecting of a target in a media”, urging that Santos-Cancel et al describe “resetting a sensor baseline of a sensor modified with methylene blue (MB), wherein resetting occurs with the working electrode held at 0.0V”, noting further than Santos-Cancel et al teach that “magnitude and polarity of a change in current with and without a target is a function of when current is sampled after application of a pulse, where to quantify E-AB sensor response, a percent signal change is traditionally used and defined as a difference between a current response of a sensor with and without target in solution over the current response of a sensor without target in solution multiplied by 100” (Reply page 10). Applicant further states that Santos-Cancel et al “focuses on quantitative change observations in both portions of a current-time trace upon target addition”, and urges that thus Santos-Cancel et al “is not directed to a calibration free determination of a target analyte concentration” (Reply page 10 bridging to page 11). The Reply further argues that Santos-Cancel et al “does not describe determining a reference point to set a corresponding baseline level to permit, for example, a calibration free determination of a target analyte concentration in the media solution” (Reply page 11). Applicant also argues that Santos-Cancel et al “is silent as to any crossing point of current decay curves of target-free and target-bonded aptasensors let alone a crossing point identified as a reference point…” (Reply page 11). Applicant thus argues that Santos-Cancel et al do not teach a method including all limitations required by the claims (summarized at page 11 in the second full paragraph).
These arguments have been thoroughly considered, and it is noted that those claims to methods requiring a reference that is a reset point (claims 5-7 and 11-13) or a reference that is a crossing point (claims 8-9 and 14-15) are not rejected herein. However, Applicant’s arguments are not found persuasive with regard to claims 1-4 and 10. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “calibration free” determination of a target analyte) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As set forth in the rejection above, Santos-Cancel et al teach methods meeting all requirements of the claims as written; the present wording of the claims does not limit them to a method that is “calibration-free”; it is also noted that the claims recite applying IPA waveforms and determining concentration following dispensing of the target in the media solution, with the “determining a reference point….to set a baseline level” (as discussed above) having been performed at any time prior to “determining the concentration”. Again, as discussed in the above rejection, the requirement for “determining a reference point” as actually set forth in the claims is met by the teachings of Santos-Cancel et al. Thus, these arguments are non-persuasive with regard to the present rejection of claims 1-4 and 10.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Independent claim 1 and claims dependent therefrom (claims 2-9) are directed to a method “of using a target molecule-binding aptasensor to determine a concentration of a target molecule in a media solution”, with independent claim 1 concluding with the recitations “determining a reference point….to set a baseline level corresponding to the reference point” and “determining the concentration of the target molecule in the media solution based on the baseline level of the reference point”. Independent claim 10 and claims dependent therefrom (claims 11-15) are similarly drawn to a method “of using a target molecule-binding aptasensor to determine a concentration of a target molecule in a media solution”, with independent claim 10 concluding with the recitations “determining a reference point….to set a baseline level corresponding to the reference point” and “determining the concentration of the target molecule in the media solution based on the baseline level of the reference point, wherein the concentration of the target molecule is determined based on a temporal resolution of 2 milliseconds of the applied IPA waveform”. The activities of “determining a reference point” and “determining the concentration” as written in the claims (with the final step of independent claim 10 being indefinite as noted above) correspond to activities such as observing and thinking about reference/baseline levels and forming conclusions regarding target concentrations based on such comparisons, i.e., activities that may be performed entirely in the human mind; thus, the claims as presently written are directed to abstract ideas. This judicial exception is not integrated into a practical application because the active steps of the claims of dispensing a target and applying IPA waveforms to sense those targets are data gathering steps required to sense target molecules in order to “determine the concentration…”, and thus do not add a meaningful limitation as they are insignificant extra-solution activity (i.e., there is no further action following the “determining” that constitutes an application/implementation of the judicial exception). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these actions, whether considered alone or as an ordered combination, constituted well-understood, routine, and conventional activity as of Applicant’s effective filing date (as evidenced by, e.g., the teachings of Santos-Cancel et al discussed above in the rejection under 35 USC 102). With further regard to the more particular applied IPA waveforms of claims 2-4 (and recited in independent claim 10), these correspond to well-understood, routine, and conventional activities as established by Santos-Cancel et al (and again relate to the manner of gathering of data, rather than any type of application/implementation of a judicial exception [JE]). Regarding dependent claims 5-9 and 11-14, these claims as presently written are further limiting of (or further) abstract ideas, rather than any kind of application/ implementation of a JE, or something adding “more” to a JE. An inventive concept cannot be furnished by a judicial exception (i.e., a law of nature/natural phenomenon/abstract idea) itself (see MPEP 2106.05(I)). Furthermore, regard to the application of a negative potential of -0.4V (see dependent claims 6 and 12), this is also taught by Santos-Cancel et al as an element of their method noted above (page 1207, right column), and thus is considered well-understood, routine, and conventional activity. Thus, none of claims 1-15 is directed to patent eligible subject matter.
(With regard to claim 16 and claims dependent therefrom, it is noted that while claim 16 recites activities such as those in independent claims 1 and 10 discussed above, those activities are in the form of stored executable instructions in a system also including a media solution, a target molecule dispensed in the media solution, a target molecule-binding aptasensor “configured to determine a concentration of the target molecule dispensed in the media solution”, and a processor “communicatively coupled to the target molecule-binding aptasensor” [which processor performs the recited stored instructions]). Thus, these claims require a particular machine that applies the judicial exceptions [see MPEP 2106.05(b)], and are directed to patent eligible subject matter.)
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Plaxco et al (US2020/0182820 [11 June 2020; PCT filed 1 June 2018]; cited herein) disclose “Calibration-Free Measurement with Electrochemical Biosensors”, encompassing embodiments practiced with and without pre-calibration steps, and employing aptamer sensors and pulsed voltammetry/square wave voltammetry (see entire reference); a similar disclosure is provided in Li et al (JACS 139:11207 [2017]; cited herein). Plaxco (WO 2019/089465 A1 [09 May 2019]; cited herein) discloses “Calibration-Free in vivo Measurement of Analytes using Electrochemical Sensors” in which chronoamperometry is employed with aptamer sensors; a similar disclosure is provided in Arroyo-Curras et al (ACS Sens. 3:360 [2018]; cited herein). Pellitero et al (Journal of the Electrochemical Society 167:037529, 14 pages [19 Dec 2019]; cited herein) provide an overview of “the specific advantages of the electroanalytical methods most commonly used for the interrogation of DNA-based sensors”, including discussing the use of amperometry (see Abstract and in particular page 4, right column-page 5, left column); it is noted that Pellitero et al reference the use of intermittent-pulse amperometry (IPA) by Santos-Cancel and colleagues, as well as the use of chronoamperometry by Arroyo-Curras and colleagues (see page 5, left column). Sharma et al (Chemosensors 5:1 [2017]; cited herein) provide an overview of “Recent Advances in Electrochemical-Based Platforms for Aflatoxins Detection”, including discussing the use of IPA with immunosensors and amperometry (generally) with aptasensors (sections 3 and 4 including Tables 2 and 4).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DIANA B JOHANNSEN whose telephone number is (571)272-0744. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm EST.
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682
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