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 .
Response to Amendment
Applicant amendments filed 11/21/2025 have been entered. Applicant amendments overcomes the previous claim objection set forth in the Office Action mailed 08/22/2025, the previous claim objection is withdrawn.
Status of Claims
Claims 1, 4, 26, 32 remain pending in the application.
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, 4, 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lipskier (US-5910286-A) in view of Sun (US-2019/0313944-A1).
Regarding claim 1, Lipskier teaches a molecularly imprinted polymer (MIP)-coated piezoelectric sensor for detection of volatile organic compounds (VOCs) in exhaled breath comprising:
(i) a polymer film (fingerprint material L) molecularly imprinted with a target molecule (species G) (column 1 lines 55-67 and column 2 lines 1-7, column 2 lines 14-26, column 4 lines 31-32, Figure 2A); and
(ii) a piezoelectric crystal (piezoelectric material) coated with said polymer film (L), wherein the frequency of the piezoelectric crystal (piezoelectric material) changes upon binding with the target molecule (G) (column 4 lines 9-11 where the piezoelectric material seen in Figure 1 can be a plate made of quartz where it is understood that the piezoelectric material seen in Figure 2a may similarly be quartz, column 4 lines 28-45 see when conditions of propagation of the surface acoustic waves are modified between the two series of electrodes the phase variation induced is no longer the same and the oscillating circuit no longer resonates at the same frequency, column 4 lines 48-52 see analysis of the variation in frequency makes it possible to monitor the capture of molecules by the sensitive layer with the reason for this is that capture is reflected by a variation in mass which gives rise to a modification of the propagation of the surface acoustic waves, Figure 2a);
wherein the polymer film (L) is directly formed on the piezoelectric crystal (piezoelectric material) (column 4 lines 28-32, Figure 2a).
Lipskier does teach where the molecule G that serves as a gauge may typically be an ion, an organic molecule of biological or synthetic origin, a polypeptide, a polynucleotide, a polysaccharide or any other chemical species which may be of value in detecting selectively (Lipskier; column 6 lines 17-21), Lipskier does not teach a volatile organic compound target molecule.
In the analogous art of molecularly imprinted polymers, Sun teaches detection of one or more analytes in a sample such as a breath sample (Sun; abstract, [0005]).
Specifically, Sun teaches where molecular imprinting is a technique to polymerize around a template molecule and remove the template after polymerization that leaves cavities with the exact size and shape of the template in the polymer matrix, where elements include: the target molecule (or template) that corresponds to the analyte to be sensed, the functional monomer, and the cross-linking agent (Sun; [0145]). [0084] of Sun describes where one or more analytes are associated with a disease or condition, where devices with MIPs selective for one or more disease can be used as a diagnostic device to detect analytes associated with the particular disease or condition, where a potential source of analytes includes the breath. [0082] of Sun describes where one or more analytes include volatile organic compounds that includes ethanol, and [0097] of Sun describes where the disease is diabetes and an analyte is ethanol.
It is noted that while not required, Sun describes toluene ([0089], [0094]), pentanal ([0089]), octanal ([0089]), hexanal ([0080], [0089], [0096]), nonanal ([0089], heptanal ([0089]), acetone ([0089], [0097]), as possible analytes for various diseases/conditions.
Lipskier is silent with regards to molecule G, therefore, it would have been necessary and thus obvious to look to the prior art for conventional target analytes. Sun provides this conventional teaching showing that it is known in the art for ethanol to be a target analyte related to diabetes used with a MIP. Therefore, it would have been obvious to one having ordinary skill in the art to make the target analyte be ethanol because Sun teaches that ethanol is an effective template used in MIPs and that it is desirable to detect ethanol for detection of diabetes (Sun; [0097]).
Note the limitation “for detection of volatile organic compounds (VOCs) in exhaled breath” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Lipskier and the apparatus of modified Lipskier is capable of detecting VOCs in exhaled breath. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Lipskier (see MPEP §2114).
Regarding claim 1, the method of the polymer film/nanoparticles is directly formed on the piezoelectric crystal is a product-by-process limitation. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process and is therefore taught by modified Lipskier (MPEP § 2113). The burden is on applicants to show product differences in product-by-process claims.
Regarding claim 4, modified Lipskier teaches the sensor according to claim 1. Lipskier further teaches wherein the piezoelectric crystal is a quartz crystal microbalance (QCM) sensor (Lipskier; column 4 lines 9-11 where the piezoelectric material seen in Figure 1 can be a plate made of quartz where it is understood that the piezoelectric material seen in Figure 2a may similarly be quartz, column 4 lines 28-52 which describes analysis of variation in frequency allows monitoring of capture molecules due to variation in mass that gives rise to a modification of the propagation of the surface acoustic waves).
Regarding claim 26, modified Lipskier teaches the sensor of claim 1. Lipskier further teaches wherein the polymer film (L) comprise at least one monomer and a crosslinker (Lipskier; column 1 lines 61-65 see G serves as a gauge in the presence of polymerizable monomers and crosslinking agents, column 6 lines 22-34 see functional monomers, column 6 lines 35-44 see crosslinking agents).
Claim(s) 1, 4, 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dickert et al., "QCM and SAW Transducers Allow Analyte Detection From nanometer to micrometer dimensions using imprinting techniques", herein Dickert, in view of Sun (US-2019/0313944-A1).
Regarding claim 1, Dickert teaches a molecularly imprinted polymer (MIP)-coated piezoelectric sensor for detection of volatile organic compounds (VOCs) in exhaled breath comprising:
(i) a polymer film (molecular imprinted polymer (MIP)) molecularly imprinted with a target molecule (desired analyte) (page 528 column 2 sensitive coatings section see MIPs are produced by polymerization of carefully selected monomers around a template, the desired analyte, see Figure 2); and
(ii) a piezoelectric crystal (piezoelectrical substrate) coated with said polymer film (MIP), wherein the frequency of the piezoelectric crystal (piezoelectric substrate) changes upon binding with the target molecule (desired analyte) (page 528 column 1 mass-sensitive transducers section see quartz and see the frequency of the vibrations corresponds to mass loading, see Figures 1 and 3);
wherein the polymer film (MIP) is directly formed on the piezoelectric crystal (piezoelectric substrate) (Figure 3).
While Dickert does teach possible template materials to include whole cells or small organic molecules (Dickert; page 529, Dickert does not teach a volatile organic compound target molecule.
In the analogous art of molecularly imprinted polymers, Sun teaches detection of one or more analytes in a sample such as a breath sample (Sun; abstract, [0005]).
Specifically, Sun teaches where molecular imprinting is a technique to polymerize around a template molecule and remove the template after polymerization that leaves cavities with the exact size and shape of the template in the polymer matrix, where elements include: the target molecule (or template) that corresponds to the analyte to be sensed, the functional monomer, and the cross-linking agent (Sun; [0145]). [0084] of Sun describes where one or more analytes are associated with a disease or condition, where devices with MIPs selective for one or more disease can be used as a diagnostic device to detect analytes associated with the particular disease or condition, where a potential source of analytes includes the breath. [0082] of Sun describes where one or more analytes include volatile organic compounds that includes ethanol, and [0097] of Sun describes where the disease is diabetes and an analyte is ethanol.
It is noted that while not required, Sun describes toluene ([0089], [0094]), pentanal ([0089]), octanal ([0089]), hexanal ([0080], [0089], [0096]), nonanal ([0089], heptanal ([0089]), acetone ([0089], [0097]), as possible analytes for various diseases/conditions.
It would have been obvious to one skilled in the art to modify the MIP of Dickert such that it is imprinted with ethanol as taught by Sun because Sun teaches that ethanol is an effective template used in MIPs and that it is desirable to detect ethanol for detection of diabetes (Sun; [0097]).
Note the limitation “for detection of volatile organic compounds (VOCs) in exhaled breath” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Dickert and the apparatus of modified Dickert is capable of detecting VOCs in exhaled breath. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Dickert (see MPEP §2114).
Regarding claim 1 the method of the polymer film/nanoparticles is directly formed on the piezoelectric crystal is a product-by-process limitation. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process and is therefore taught by modified Dickert (MPEP § 2113). The burden is on applicants to show product differences in product-by-process claims.
Regarding claim 4, modified Dickert teaches the sensor according to claim 1. Dickert further teaches wherein the piezoelectric crystal is a quartz crystal microbalance (QCM) sensor (Dickert; see Figure 3 which shows a QCM with imprinted polymer).
Regarding claim 26, modified Dickert teaches the sensor of claim 1. Dickert further teaches where MIPs are produced by polymerization of carefully selected monomers around a template (Dickert; page 528 column 2).
While page 529 column 2 of Dickert does describe that the stability of the sensor is guaranteed using highly-crosslinked polymers, it is unclear if Dickert teaches a crosslinker.
In the analogous art of molecularly imprinted polymers, Sun teaches that the three elements in molecular imprinting technique are: the target molecule, the functional monomer (compound having chemical and shape complementary to the template and will help the polymerization to form the polymer matrix) and the cross-linking agent (multifunctional molecule containing two or more reactive split ends able to interact via chemical bond) (Sun; [0145]).
It would have been obvious to one skilled in the art to modify the MIP of Dickert such that there is also a cross-linking agent in addition to the monomer and template because it is taught by Sun that a template, monomer, and cross-linking agent are three elements that are effective for producing MIPs.
Claim(s) 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lipskier (US-5910286-A) and Sun (US-2019/0313944-A1), and in further view of Zhang (US-2015/0299366-A1).
Regarding claim 32, modified Lipskier teaches the sensor of claim 1. Lipskier does not teach wherein said polymer nanoparticles have a particle size ranging from 100 to 500 nm.
In the same problem solving area as recognition of small organic molecules in biological samples, Zhang teaches molecularly imprinted polymer nanoparticles (Zhang; [0002]).
Specifically, Zhang teaches MIP nanoparticles that are compatible with biological samples, in particular pure biological samples, where a template molecule includes small pathological and disease biomarkers (Zhang; [0008], [0027]). The size of the nanoparticles is preferably 10-250 nm (Zhang; [0023]).
It would have been obvious to one skilled in the art to modify the fingerprint material of Lipskier such that it is instead MIP nanoparticles as taught by Zhang because Zhang teaches that MIP nanoparticles show specific template binding capability in aqueous samples an biological samples, in particular pure biological samples, as good as what they show in organic solvent, further the MIP nanoparticles are not interfered by the existence of components rich in biological samples such as proteins (Zhang; [0123]).
Examiner further finds that the prior art contained a device/method/product (i.e., a chemical sensor) which differed from the claimed device by the substitution of component(s) (i.e., fingerprint material) with other component(s) (i.e., polymer nanoparticles), and the substituted components and their functions were known in the art as above set forth. An ordinarily skilled artisan could have substituted one known element with another (i.e., fingerprint material for MIP nanoparticles), and the results of the substitution (i.e., detection of a target analyte) would have been predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to substitute the layer of fingerprint material of Lipskier with the MIP nanoparticles of reference Zhang, since the result would have been predictable.
Response to Arguments
Applicant's arguments filed 11/21/2025 have been fully considered but they are not persuasive.
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., frequency change arises from mass loading on a QCM, where VOC binding to the MIP layer directly increasing the crystal’s mass causing a measurable shift in resonance frequency) 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).
Claim 1 does not require a QCM (this limitation is in claim 4, however Lipskier teaches a QCM), does not describe mass loading, and only recites that the frequency of the piezoelectric crystal changes, not the resonant frequency.
Additionally, please see column 4 lines 48-52 of Lipskier, cited in the previous Office Action mailed 08/22/2025 on page 5, that the variation in frequency makes it possible to monitor the capture of molecules, and the reason for this is that capture is reflected by a variation in mass which gives rise to a modification of the propagation of the surface acoustic waves. Therefore, a mass change will lead to a change in the frequency.
In response to applicant's argument that Sun teaches an electrochemical sensor that works by using a chemical reaction to generate an electrical signal which differs from the piezoelectric sensor of Lipskier, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Further, please note that the teaching of Sun being relied on is related to the molecularly imprinted polymer and the analytes that may be detected.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the prior art did not teach a specific target molecule, therefore there would be motivation to look to the prior art for conventional target molecules. Sun teaches a molecularly imprinted polymer imprinted with a variety of molecules.
Applicant argues on page 5 that the claim requires that no pre-formed film/nanoparticle structure is utilized because the structure must be formed on the piezoelectric crystal and that contact between the film/nanoparticle and piezoelectric crystal is direct. Further, that the claims do not simply say that the film/nanoparticle is on the piezoelectric crystal, it instead specifies that the film/nanoparticle is structured so that it can be formed on the piezoelectric crystal with no additional material.
This is not found persuasive because applicants have not shown product differences between the claimed invention and the current prior art of record.
Applicant argues on page 6 that Dickert fails to specify the analyte or how the sensor is configured, and fails to specify a particular application for health monitoring in exhaled breath.
Please see page 9 of the Office Action mailed 08/22/2025 which states that the limitation “for detection of volatile organic compounds (VOCs) in exhaled breath” is directed to the function of the apparatus and/or the manner of operating the apparatus, and that all structural limitations has been disclosed by modified Dickert.
With regards to arguments directed to Sun, please see above.
Applicant argues on page 6 that Zhang teaches an MIP sensor for detection of biological samples and that the present claims relate to VOC detection from exhaled breath samples, and therefore Zhang does not contemplate or suggest the use of MIP nanoparticles for gas-phase sensing or VOC biomarkers in breath samples.
It is again noted that the limitations regarding a MIP coated piezoelectric sensor for detection of VOCs in exhaled breath is directed to the function of the apparatus and/or the manner of operating the apparatus, and that all of the structural limitations have been taught by modified Lipskier. Additionally, Zhang is being used to modify the fingerprint material of Lipskier (which has also been modified by Sun to have been imprinted with specific target molecules) such that it is the MIP nanoparticles. Therefore, the nanoparticles would be capable of detecting VOCs in exhaled breath.
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 SOPHIA LYLE whose telephone number is (571)272-9856. The examiner can normally be reached 8:30-5:00 M-Th.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Elizabeth Robinson can be reached at (571) 272-7129. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.Y.L./Examiner, Art Unit 1796
/MATTHEW D KRCHA/Primary Examiner, Art Unit 1796
Prosecution Insights