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 .
Election/Restrictions
Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claim 1-5 and 10-14, drawn to a nanoscale molecularly imprinted polymer thin film, classified in B01J20/268.
II. Claim 6-9, drawn to a method of manufacturing a nanoscale molecularly imprinted polymer thin film for small molecules, classified in G01N33/5438.
The inventions are independent or distinct, each from the other because:
Inventions II and I are related as process of making and product made. The inventions are distinct if either or both of the following can be shown: (1) that the process as claimed can be used to make another and materially different product or (2) that the product as claimed can be made by another and materially different process (MPEP § 806.05(f)). In the instant case the product as claimed can be made by another and materially different process.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries);
(d) the prior art applicable to one invention would not likely be applicable to another invention; and
(e) the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
During a telephone conversation with Sandra Katz on 08/31/2026 a provisional election was made without traverse to prosecute the invention of group I, claim 1-5 and 10-14. Affirmation of this election must be made by applicant in replying to this Office action. Claim 6-9 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-5 and 10-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yin et al. (WO 2022/170361) (Yin) in view of Lee et al. (Korean Society of Analytical Sciences, 68th Spring Conference, 2022) (Lee) and Suda et al. (Royal Society Open Science, 2017) (Suda).
Regarding claim 1, Yin discloses a molecularly imprinted polymer thin film, which is a molecularly imprinted polymer thin film for small molecule detection (par [0093]), in which a plurality of specific recognition spaces for small molecules of 1000 Da or less (cortisol) are formed (par [0157]),
wherein a receptor polymer is present at one end of the specific recognition spaces (par [0160]), and Prussian blue, ferrocene or polymethylene blue as a redox probe (par [0157]), and
the small molecule is a steroid hormone (par [0155]).
Yin does not expressly teach that the redox probe is “present in a wire form.”
Lee teaches a cortisol-detecting MIP incorporating a conductive polymethylene-blue redox probe. Specifically, Lee teaches “the measurement of polymer conductance with MIP incorporating redox probe prepared from co-electropolymerization of β-cyclodextrin and Methylene Blue,” wherein “[t]he β-cyclodextrin polymer provides the cavity to which cortisol binds as an MIP, and the poly methylene blue film is redox probe to create a faradaically-active site of the film” (p. 129). Lee further teaches that cortisol binding causes “decreases of polymer conductance” (p. 129). Thus, Lee teaches the use of polymethylene blue in a conductive polymer-film form as the redox-probe pathway and suggests the claimed redox probe present in a wire form.
Lee teaches polymethylene blue present in a wire form as a redox probe because Lee teaches an electrode-coupled conductive PMB film formed by co-electropolymerization of methylene blue, wherein the PMB film serves as the redox probe having faradaically-active sites and conducts electrons with the electrode, with cortisol binding decreasing the polymer conductance (p. 129). This corresponds to the claimed “wire form” because Applicant's Specification defines PMB serving as a “wire” as a polymer chain connecting a redox site to an electrode such that electron transfer occurs through the PMB (Spec. par [0033]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the cortisol MIP sensor of Yin to employ the polymethylene-blue conductive redox-probe film taught by Lee. Yin expressly identifies methylene blue as a suitable redox signal indicator, and Lee teaches that co-electropolymerizing methylene blue in a cortisol MIP forms a polymethylene-blue redox-probe film whose conductance changes upon cortisol binding. One of ordinary skill in the art would therefore have been motivated to use Lee's polymethylene-blue conductive redox-probe arrangement in Yin's MIP sensor to provide an internal redox-active conductive pathway for detecting cortisol binding.
Yin and Lee do not expressly teach that the molecularly imprinted polymer thin film is “nanoscale.”
Suda teaches a cortisol-specific MIP thin layer and teaches that “SI-AGET ATRP ... is employed to form a homogeneous polymer matrix around the imprinted cavities, resulting in MIP thin layers with the desired thickness and low non-specific binding properties” (p. 3, par 0). Suda further teaches that “[a]fter 30 min of polymerization, the thickness is estimated to be approximately 3 nm” (p. 3, par 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the cortisol MIP thin film of Yin as modified by Lee to have the approximately 3 nm thickness taught by Suda, thereby providing a nanoscale MIP thin film, because Suda teaches forming cortisol-recognition MIP thin layers at that thickness with low non-specific binding properties and for highly sensitive cortisol detection. The resulting modified cortisol MIP sensor would therefore comprise a nanoscale molecularly imprinted polymer thin film having cortisol-recognition spaces, a receptor polymer, and a polymethylene-blue redox probe present in a conductive wire form, as claimed.
Regarding claim 2, Lee teaches that wherein the molecularly imprinted polymer thin film is manufactured by electrochemically copolymerizing a small molecule, β-cyclodextrin, and methylene blue (p. 129).
Yin teaches “and then removing the small molecule” (par [0175]).
Therefore, Lee teaches electrochemically copolymerizing the claimed cortisol, β-cyclodextrin, and methylene blue components, while Yin teaches removing the cortisol template after formation of the MIP, as claimed.
Regarding claim 3, Yin teaches wherein the small molecule is cortisol or melatonin (par [0157]).
Regarding claim 4, Suda teaches wherein the nanoscale molecularly imprinted polymer thin film has a thickness of 5 nm or less (p. 3).
Regarding claim 5, Lee teaches wherein the receptor polymer is formed from β-cyclodextrin, pyrrole, or phenylenediamine monomer (p. 129).
Regarding claim 10, Yin in view of Lee and Suda teaches “a method of detecting small molecules” using the molecularly imprinted polymer thin film of claim 1 for the reasons discussed above.
Yin teaches bringing a biological sample into contact with a quantum electrochemical detection device including the molecularly imprinted polymer thin film of claim 1 (par [0162] [0171]);
applying voltage to the quantum electrochemical detection device (par [0160]).
Yin does not explicitly teach monitoring changes in resonant quantum conductance from the device when a target small molecule binds to a specific recognition space inside the molecularly imprinted polymer thin film.
However, Lee teaches that traditional EIS does not report “resonant conductance/resistance” because such measurement requires the density of states (DOS) exchanging electrons with the electrode and teaches that electrochemical capacitance is directly correlated with the conductance arising from embedded faradaically-active sites. Lee further teaches detecting cortisol “based on the measurement of polymer conductance with MIP incorporating redox probe,” wherein β-cyclodextrin provides the cavity to which cortisol binds and polymethylene blue provides the redox probe, and expressly detects cortisol based on “decreases of polymer conductance due to cortisol binding to MIP” (p. 129).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yin's cortisol MIP detection method to monitor the resonant conductance taught by Lee because Lee teaches that measurement of polymer conductance resulting from cortisol binding provides a highly sensitive conductance bioassay for cortisol.
Regarding claim 11, Suda teaches “wherein the biological sample is selected from the group consisting of plasma, serum, saliva, urine, mucus, and tears,” wherein Suda expressly teaches that “detection of cortisol in saliva samples was demonstrated as a feasibility study.” (abstract). Thus, Suda teaches the claimed biological sample comprising saliva.
Regarding claim 12, Lee teaches wherein the quantum electrochemical detection device is a device that measures resonant quantum conductance using quantum electrochemical impedance spectroscopy (EIS).
Specifically, Lee teaches that “[t]raditional electrochemical impedance spectroscopy (EIS) does not report on resonant conductance/resistance because this requires that the density of state (DOS) exchanging electrons with the electrode is rather electronically and mechanically coupled to it, not in solution.” Lee further teaches that electrochemical capacitance spectroscopy monitors changes in the charging state of the interface, that “[e]lectrochemical capacitance is given by the diameter of a capacitive Nyquist semicircle,” and that “[t]his conductance is directly correlated to the electrochemical or redox capacitance of the film that arises from its embedded faradaically-active sites.” (p. 129).
Lee further applies this measurement to the claimed type of MIP sensor by detecting cortisol “based on the measurement of polymer conductance with MIP incorporating redox probe,” with cortisol binding causing decreases in polymer conductance. (p. 129). Thus, Lee teaches determining resonant conductance from electrochemical capacitive/impedance measurements of an electrode-coupled redox film in response to target binding, corresponding to the claimed quantum electrochemical impedance spectroscopy.
Regarding claim 13, Lee teaches “wherein the small molecule is detected at a concentration of 1.0 × 10⁻¹³ to 1.0 × 10⁻⁶,” wherein Lee teaches a cortisol conductance bioassay having “a linear dynamic range of 1.00 × 10⁻¹² M - 1.00 × 10⁻⁶ M and a detection limit of 3.93 × 10⁻¹³ M (S/N = 3).” (p. 129).
Thus, Lee's disclosed detection range and detection limit fall within the claimed concentration range.
Regarding claim 14, Yin teaches “an electrochemical biosensor for small molecule detection”, wherein Yin states that “[t]his patent document relates to electrochemical sensors” (par [0002]) and discloses a cortisol sensor having “a molecular imprinted polymer (MIP) layer containing a signal indicator and cavity for cortisol detection” (par [0093]).
Regarding “including the molecularly imprinted polymer thin film of claim 1,” Yin teaches that “electropolymerized polypyrrole (PPy) MIP electrodes are synthesized in the presence of cortisol as the template, along with Prussian blue (PB) as the embedded redox probe,” and that removal of cortisol produces “surface recognition cavities that are complementary to the shape and size of the target cortisol molecule” (par [00157]). The molecularly imprinted polymer thin film of claim 1 is taught or suggested by Yin in view of Lee and Suda for the reasons set forth above with respect to claim 1.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to XIAOYUN R XU, Ph. D. whose telephone number is (571)270-5560. The examiner can normally be reached M-F 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at 571-272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797
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