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
.
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 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/21/2026 has been entered.
Response to Arguments
Applicant's arguments filed 04/21/2026 have been fully considered.
Regarding the objection(s) to claim(s) 14 pertaining to an/the, Applicant argued that the amendment overcame said objection(s); the Examiner is in agreement, therefore said objection(s) has/have been withdrawn.
Regarding the objection(s) to the Abstract pertaining to separate page and phrases which can be implied, Applicant argued that the amendment overcame said objection(s); the Examiner is in agreement, therefore said objection(s) has/have been withdrawn.
Regarding the objection(s) to the Specification pertaining to a typo, Applicant argued that the amendment overcame said objection(s); the Examiner is in agreement, therefore said objection(s) has/have been withdrawn.
Regarding the objection(s) to the Drawings pertaining to claimed subject matter not shown, Applicant argued that the amendment to the claim overcame said objection(s); the Examiner is in agreement, therefore said objection(s) has/have been withdrawn.
Regarding the 112(b)/2nd indefinite rejection(s) of claim(s) 9 & 20 pertaining to multiple plausible claim interpretations, Applicant argued that the amendment overcame said rejection(s); the Examiner is in agreement, therefore said rejection(s) have been withdrawn.
Regarding the 103 prior art obviousness rejection of independent claim 1 and similarly for independent claim 18, Applicant argued that the amendment to add “wherein the crystal microbalance is exposed to a blocking agent to prevent non-specific binding of non-specific material other than the specific pathogen to the pair of metal electrodes” (claim 18 deleted the “optionally” from a similar feature) overcame the prior art rejections in that none of the cited prior art references disclose this language. However this argument is merely an assertion and lacks the necessary supporting evidence. MPEP § 2145(I) states:
Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
In the event that Applicant is trying to argue that Zeng’s blocking agent is inoperable, the Examiner’s assessment of the prior art is still based upon MPEP § 2121(I) and MPEP § 716.07:
2121(I)
When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to provide facts rebutting the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07.”
716.07 (omissions of paragraphs for brevity)
Affidavits or declarations attacking the operability of a patent cited as a reference must rebut the presumption of operability by a preponderance of the evidence. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980)…
Where the affidavit or declaration presented asserts inoperability in features of the reference which are not relied upon, the reference is still effective as to other features which are operative. In re Shepherd, 172 F.2d 560, 80 USPQ 495 (CCPA 1949.
Where the affidavit or declaration presented asserts that the reference relied upon is inoperative, the claims represented by applicant must distinguish from the alleged inoperative reference disclosure. In re Crosby, 157 F.2d 198, 71 USPQ 73 (CCPA 1946). See also In re Epstein, 32 F.3d 1559, 31 USPQ2d 1817 (Fed. Cir. 1994)…
In the present case, primary reference Zeng explicitly and repeatedly teaches such a blocking agent likewise utilized on Zeng’s QCM ([0030], [0036], [0044], [0050], [0055], [0061], [0170] “binding of the analyte is blocked by a blocking agent”; [0170] “blocking agent such as oligo(ethylene glycol)”’; [0199] “plate is blocked with a BSA solution”; [0211] “the binding site is blocked by a blocking agent, such as oligo(ethylene glycol) group”;. [0234] “blocking reagent such as 0.1% Bovine Serum Albumin (BSA) (catalog # A-9418 Sigma, St. Louis, Mo.) in PBS was applied to the scFv modified electrode for 30 min. to absorb onto any of the Au surface not bound with scFv”; [0237] “0.1% BSA blocking reagent”; [0251] “BSA blocking reagent”; [0253] “Blocking with BSA”; [0269] “BSA blocking reagent”; [0238] “0.1% BSA 5% BSA), see present rejections for details. As Applicant has not sufficiently provided facts rebutting the presumption of operability, nor has Applicant explained how either the claimed blocking agent differs in composition and/or use from Zeng, the Examiner retains the prior art rejection. See also In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974) (“Attorney’s argument in a brief cannot take the place of evidence").
Further regarding the 103 prior art obviousness rejection of independent claim 1, Applicant further argued that along with guiding a specific pathogen, the combination of prior art would likely result in additional non-specific material gathered along with the specific pathogen. However, in response to Applicant's argument that the references fail to show certain feature(s) of the invention, it is noted that the feature(s) upon which Applicant relies (i.e., that other non-specific pathogens would not be guided) is/are not recited in the rejected claim(s). Although the claim(s) is/are interpreted in light of the specification, limitations from the specification are not read into the claim(s). See MPEP § 2145(VI) and In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Further regarding the prior art obviousness rejection of independent apparatus claim 1 and method claim 18, Applicant argued that Priyamvada does not teach an electrostatic precipitator configured to exert an electrostatic force to guide specific pathogens for bioaerosol monitoring. While Applicant’s arguments of inoperability of Priyamvada for a specific pathogen (e.g., Covid 19) have been considered, the Examiner’s assessment of the prior art is based upon MPEP § 2121(I) and MPEP § 716.07: 2121(I) When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to provide facts rebutting the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07 (omissions of paragraphs for brevity) Affidavits or declarations attacking the operability of a patent cited as a reference must rebut the presumption of operability by a preponderance of the evidence. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980)… Where the affidavit or declaration presented asserts inoperability in features of the reference which are not relied upon, the reference is still effective as to other features which are operative. In re Shepherd, 172 F.2d 560, 80 USPQ 495 (CCPA 1949. Where the affidavit or declaration presented asserts that the reference relied upon is inoperative, the claims represented by applicant must distinguish from the alleged inoperative reference disclosure. In re Crosby, 157 F.2d 198, 71 USPQ 73 (CCPA 1946). See also In re Epstein, 32 F.3d 1559, 31 USPQ2d 1817 (Fed. Cir. 1994)… In the present case, Priyamvada teaches an electrostatic precipitator configured to exert an electrostatic force to guide specific pathogens for bioaerosol monitoring (Title “Design and evaluation of a new electrostatic precipitation-based portable low-cost sampler for bioaerosol monitoring”; Abstract “The importance of bioaerosols to human and ecosystem health is evident as we tackle the on-going coronavirus pandemic. Understanding the airborne migration of pathogens and the consequent transmission of diseases such as COVID-19” and” improve the collection efficiency of the sampled particles”; Introduction top of page 25 “Many HAI pathogens, e.g., Mycobacterium tuberculosis and many viruses such as influenza virus, norovirus, and the recent corona virus (SARS-CoV-1 and SARS-CoV-2), are predominantly transmitted through air and cause outbreaks in hospitals and other built environments”; Introduction last paragraph “electrostatic precipitation. computational fluid dynamics (CFD) simulations were performed to understand the particle flow and collection behavior with respect to design aspects such as the ionizer orientation and length of the precipitator region. Various experiments were performed with the spores and cells of Bacillus thuringiensis var. kurstaki (Btk) and Arizona road dust to determine the collection efficiency of the device as a function of high voltage, particle ionization, particle concentration, and ionizer’s orientation”; see also section 3.4 CFD modeling, section 5 Conclusion), and the Examiner retains that Priyamvada electrostatic precipitator is so operable for a specific pathogen (e.g., Covid-19). As Applicant has not sufficiently provided facts rebutting the presumption of operability, the Examiner retains the same position as put forth in the preceding Office Actions.
Moreover, as previously noted above, primary reference Zeng is already teaching specific binding & capturing of specific pathogen (e.g., specific virus particle) ([0172] “binding of a single specific antigen, toxin, or virus particle”; [0183] “antigen-binding event is detected by the QCM, which is able to detect binding of a single specific toxin or virus particle”; [0227] “Fv-SAMs can be used for detection of a toxin (e.g., botulism toxin tainted food), a virus (e.g., HIV contaminated blood), a bacterium (e.g., E. coli), and a protozoan (e.g., Cryptosporidium parvum contaminated water)”; [0168] “detecting anthrax” and “detecting salmonella”; [0184] “one QCM could detect anthrax, another salmonella, another botulism toxin, etc.”) as well as preventing other non-specific binding of non-specific material other than the specific pathogen ([0030], [0036], [0044], [0050], [0055], [0061], [0170] “binding of the analyte is blocked by a blocking agent”; [0170] “blocking agent such as oligo(ethylene glycol)”’; [0199] “plate is blocked with a BSA solution”; [0211] “the binding site is blocked by a blocking agent, such as oligo(ethylene glycol) group”; [0234] “blocking reagent such as 0.1% Bovine Serum Albumin (BSA) (catalog # A-9418 Sigma, St. Louis, Mo.) in PBS was applied to the scFv modified electrode for 30 min. to absorb onto any of the Au surface not bound with scFv”; [0237] “0.1% BSA blocking reagent”; [0251] “BSA blocking reagent”; [0253] “Blocking with BSA”; [0269] “BSA blocking reagent”; [0238] “0.1% BSA 5% BSA”). The Examiner notes that “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at 421, 82 USPQ2d at 1397. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 418, 82 USPQ2d at 1396. See also In re Sovish, 769 F.2d 738, 743 (Fed. Cir. 1985) (skill is presumed on the part of one of ordinary skill in the art) and In re Bozek, 416 F.2d 1385, 1390 (CCPA 1969). It is the Examiner's position that in the combination, Zeng’s QCM would still be for specific capturing & binding of specific particulates and also utilizing the aforementioned blocking agent against other particulates, and that only ordinary creativity is required to combine an electrostatic precipitator for directing charged particulates to a QCM with a QCM that measures charged particulates—even when those charged particulates are specifically viruses—especially when there is factually supporting evidence that electrostatic precipitators are known to be used for directing viruses to QCM. The Examiner again notes that further prior art was previously cited to the PTO-892 which factually supports the known common use of electrostatic precipitators for specific pathogens, see previously Final Rejection response to arguments for details including brief identification of those prior art.
Regarding the 103 prior art obviousness rejection(s) of claim(s) 9 and 20, Applicant argued that the amendment to delete one of the listing of alternative capturing materials leaving only the other two alternatives overcame said rejection(s). The Examiner is in agreement, noting that the previous secondary prior art Gluckman was directed to the deleted MIP. However, claim 9 is now rejected instead over newly cited secondary reference Godwin et al (NPL Metal Organic Frameworks as Biosensing Materials for COVID-19; hereafter “Godwin”), see present rejections for details. See also newly cited prior art which are pertinent to the level of ordinary skill in the art for combination of QCM and MOF.
Regarding the 103 prior art obviousness rejection(s) of claim(s) 10, Applicant argued at the top of page 17 that the amendment overcame said rejection; the Examiner is in agreement, noting in particular that while primary reference Zeng is configured to detect a mass change on the QCM due to a plurality of particles of a specific pathogen (e.g., a specific virus) binding to the specific capture probe (and otherwise blocking via a substantially similar blocking agent), Zeng does not teach dividing the determine mass change by a mass of each particle of the specific pathogen nor does this seem to be a necessary modification as Zeng can already indicate the total number of particles (quantity) directly to the degree of change in resonance frequency ([0180] “the degree of change in resonant frequency indicates the quantity”; [0172] “The sensitivity is such as to be able to detect binding of a single specific antigen, toxin, or virus particle”; [0183] “antigen-binding event is detected by the QCM, which is able to detect binding of a single specific toxin or virus particle”; [0227] “can be used for detection of a toxin (e.g., botulism toxin tainted food), a virus (e.g., HIV contaminated blood), a bacterium (e.g., E. coli), and a protozoan (e.g., Cryptosporidium parvum contaminated water)”); [0266] “can be used for detection the of a toxin (e.g., botulism toxin tainted food), a virus (e.g., HIV contaminated blood), a bacterium (e.g., E. coli), and a protozoan (e.g., Cryptosporidium parvum contaminated water)”; [0168] “For example, the apparatus can include one piezoelectric sensor for detecting anthrax, a second for detecting salmonella, a third for detecting botulism toxin, and so on”).
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over previously cited Zeng et al (US 20050003560 A1; hereafter “Zeng”) in view of previously cited Biemmi et al (NPL Direct growth of Cu3(BTC)2(H2O)3 xH2O thin films on modified QCM-gold electrodes – Water sorption isotherms; hereafter “Biemmi”) and in further view of previously cited commercial product SEMTECH®-PPMD Portable Particulate Measurement Device as evidenced by at least* Rubino et al (NPL Portable Emission Measurement Systems (PEMS) for Heavy-duty Diesel Vehicles PM Measurements: the SEMTECH Portable Particulate Measuring Device (PPMD) and the EU PEMS Program Experience; hereafter “Semtech PPPD”) with previously cited Priyamvada et al (NPL Design and evaluation of a new electrostatic precipitation-based portable low-cost sampler for bioaerosol monitoring; hereafter “Priyamvada”).
*Examiner notes additional information on said commercial device can be found in additionally cited NPL of record.
Regarding independent claim 1,
Zeng teaches an apparatus (fig. 1, apparatus 10) (Title “Piezoimmunosensor”; Abstract “Binding of antigen to the recombinant antibodies results in a change in mass on the receptor surface which is detected as a change in resonant frequency”) comprising:
a crystal microbalance (fig. 1, device 11) ([0034] “the piezoelectric mass sensor is a quartz crystal microbalance”) comprising
an acentric, piezoelectric crystal material (fig. 1, piezoelectric crystal wafer 12) ([0147] “cut quartz crystal”; [0239] “cut quartz crystal”) and directly deposited (silent to evaporation) onto a first side (first side of device 11) and a second opposite side (second side of device 11),
a pair of metal electrodes (fig. 1, electrode coatings 14) ([0147] “crystal with an electrode coating 14 deposited on each side of the crystal 12 using a suitable method”) and
a specific capture probe (receptor of receptor surface 15) fixed directly or indirectly to the metal electrode (fig. 1, electrode coating 14) on the first side (first side of device 11) of the crystal microbalance (fig. 1, device 11) (Abstract “receptor layer is a precious metal such as gold which facilitates self-assembly”),
wherein the specific capture probe (receptor of receptor surface 15) specifically binds to and captures a specific pathogen (e.g., specific virus particle) ([0172] “binding of a single specific antigen, toxin, or virus particle”; [0183] “antigen-binding event is detected by the QCM, which is able to detect binding of a single specific toxin or virus particle”; [0227] “Fv-SAMs can be used for detection of a toxin (e.g., botulism toxin tainted food), a virus (e.g., HIV contaminated blood), a bacterium (e.g., E. coli), and a protozoan (e.g., Cryptosporidium parvum contaminated water)”; [0168] “detecting anthrax” and “detecting salmonella”; [0184] “one QCM could detect anthrax, another salmonella, another botulism toxin, etc.”),
wherein capture of the specific pathogen (e.g., specific virus particle) causes a change in mass to the crystal microbalance (fig. 1, device 11), and
wherein the change in mass of the crystal microbalance (fig. 1, device 11) causes a shift in a resonant frequency of the crystal microbalance (fig. 1, device 11) (Abstract “change in mass on the receptor surface which is detected as a change in resonant frequency”; [0211] “QCM sensors detect mass changes in liquid or gas phase by monitoring the frequency”; [0207] “relationship between frequency shift and the amount of mass loaded on the sensor” and “the measured frequency shift is proportional to the mass”; [0180] “For use, the resonant frequency of the sensor is determined and the sensor then incubated with the sample either by dipping in a liquid sample, by application of the liquid sample to the surface of the sensor, or in a liquid, vapor, or gas sample under continuous flow conditions. Afterward a sufficient period of time has elapsed, the resonant frequency of the sensor is measured. A change in resonant frequency indicates that the sample contains the analyte and the degree of change in resonant frequency indicates the quantity of analyte captured by the recombinant scFv polypeptides”); and
wherein the crystal microbalance (fig. 1, device 11) is exposed to a blocking agent (blocking agent) to prevent non-specific binding of non-specific material other than the specific pathogen to the pair of metal electrodes (fig. 1, electrode coatings 14) ([0030], [0036], [0044], [0050], [0055], [0061], [0170] “binding of the analyte is blocked by a blocking agent”; [0170] “blocking agent such as oligo(ethylene glycol)”’; [0199] “plate is blocked with a BSA solution”; [0211] “the binding site is blocked by a blocking agent, such as oligo(ethylene glycol) group”;. [0234] “blocking reagent such as 0.1% Bovine Serum Albumin (BSA) (catalog # A-9418 Sigma, St. Louis, Mo.) in PBS was applied to the scFv modified electrode for 30 min. to absorb onto any of the Au surface not bound with scFv”; [0237] “0.1% BSA blocking reagent”; [0251] “BSA blocking reagent”; [0253] “Blocking with BSA”; [0269] “BSA blocking reagent”; [0238] “0.1% BSA 5% BSA”).
The Examiner notes with respect to the above teachings being shown in different figures and/or taught in different sections, that while the reference does not expressly show all of the above claimed features clearly in a single depicted embodiment as a single figure discussed in a single section only, either one of ordinary skill in the art would at once envisaged the
combination from the generic teachings thereof and/or specific possible choices of the structural components
thereof, or, in the alternative, it at least would have been obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to nevertheless so combine the above features for the
purpose and combinations as proposed by said reference and as analyzed by the Examiner
including the citations and/or Examiner comments provided above in reference to the claimed features.
Pertinently, the Examiner further notes that "Combining two embodiments disclosed adjacent to each other in a prior art patent does not require a leap of inventiveness", see Boston Scientific Scimed, Inc. v. Cordis Corp., 554 F.3d 982, 991 (Fed. Cir. 2009). More particularly, it is Examiner’s position that it would have been obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to combine Zeng’s different embodiments of particular QCM devices with Zeng’s use of generic plurality of QCMs ([0035], [0049], [0060] “plurality of piezoelectric mass sensors”) for the benefits of each as put forth by Zeng, the Examiner noting that the combination provides Zeng’s plurality which increases versatility and marketability of Zeng’s apparatus.
While Zeng generically teaches utilizing a suitable method for directly depositing the pair of metal electrodes (fig. 1, electrode coatings 14) ([0147] “crystal with an electrode coating 14 deposited on each side of the crystal 12 using a suitable method”), Zeng is silent to item 1): the suitable method of evaporating. Zeng does not teach item 2): a concentrator comprising an electrostatic precipitator configured to exert an electrostatic force to guide a specific pathogen to the crystal microbalance.
Regarding item 1):
The Examiner previously took Official Notice that evaporating metal for electrodes is a conventional practice and that an ordinary artisan would at once envisaged evaporating metal electrodes onto the piezoelectric material as a suitable method. As the Applicant had not adequately traversed this assertion, this is considered admitted prior art in accordance with MPEP § 2144.03(C).
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Furthermore, and as supporting factual evidence of the aforementioned assertion, Biemmi teaches an apparatus comprising a crystal microbalance (QCM) comprising an acentric, piezoelectric crystal material (cut quartz) and directly evaporated onto a first side and a second opposite side, a pair of metal electrodes (gold electrodes) (last paragraph of section 1. “A quartz crystal microbalance (QCM) is a well-known sensitive mass sensor that is suitable for the investigation of sorption properties of small amounts (few lg) of porous materials in the form of thin films [25–28]. A QCM typically consists of a thin disk of AT-cut quartz with key-hole electrodes patterned on both sides. The gold electrodes are thermally evaporated onto each face of the crystal”).
In view of the above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the conventionally known suitable method of direct evaporation of gold as electrodes for a QCM—as factually supported by Biemmi’s teaching of the same—for the expected purpose of a suitable attachment at low cost/complexity, low impurity, and/or excellent uniformity, the Examiner additionally noting with respect to directly, that direct evaporative deposition of the gold—such as without using epoxies—makes it solvent resistant and permits the fabrication of thin QCM electrodes without affecting the multiple-harmonics response to mass adsorption or inducing spurious responses caused by thick electrodes.
Regarding item 2):
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Solving a similar problem in a similar QCM (generic) particulate measurement endeavor, Semtech PPPD teaches a housing (housing of PPPD) to mount the quartz crystal microbalance (QCM), said housing (housing of PPPD) including an inlet (air flow inlet) configured to direct the medium (airflow) into the housing (housing of PPPD) and an outlet (air flow outlet) configured to direct the medium (airflow) out of the housing (housing of PPPD), wherein the housing (housing of PPPD) comprises a concentrator comprising an electrostatic precipitator configured to exert an electrostatic force to guide aerosol particles (Examiner notes silent to specific pathogens, though capable thereof) to the quartz crystal microbalance (QCM) (section SEMTECH-PPMD & SET-UP “The QCM technique employs a piezoelectric crystal as a sensitive microbalance. Electrostatic precipitation collects aerosol particles on the surface of the piezoelectric crystal, the crystal is excited in its natural frequency, which decreases with increasing mass load on its surface; the crystal frequency to mass relationship is defined by the Sauerbrey fundamental equation”). The Examiner emphasizes that Semtech’s PPPD teaches a housed electrostatic precipitator for a QCM. The Examiner further notes that aerosol particles is at once envisaged by an ordinary artisan as generically inclusive of pathogens, notably including infectious pathogens that are aerosolized, for example from sneezing, coughing, etc. that cause transmission through air).
It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art, see MPEP § 2144.05 and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In the present case, it is the Examiner’s position that only ordinary skill in the art is required to optimize the configuration of an electrostatic precipitator for specific pathogens.
Factually supporting the aforementioned assertion by solving a similar problem of configuring electrostatic precipitator for specific bioaerosol pathogen concentration, Priyamvada teaches an electrostatic precipitator configured to exert an electrostatic force to guide specific pathogens for bioaerosol monitoring (Title “Design and evaluation of a new electrostatic precipitation-based portable low-cost sampler for bioaerosol monitoring”; Abstract “The importance of bioaerosols to human and ecosystem health is evident as we tackle the on-going coronavirus pandemic. Understanding the airborne migration of pathogens and the consequent transmission of diseases such as COVID-19” and” improve the collection efficiency of the sampled particles”; Introduction top of page 25 “Many HAI pathogens, e.g., Mycobacterium tuberculosis and many viruses such as influenza virus, norovirus, and the recent corona virus (SARS-CoV-1 and SARS-CoV-2), are predominantly transmitted through air and cause outbreaks in hospitals and other built environments”; Introduction last paragraph “electrostatic precipitation. computational fluid dynamics (CFD) simulations were performed to understand the particle flow and collection behavior with respect to design aspects such as the ionizer orientation and length of the precipitator region. Various experiments were performed with the spores and cells of Bacillus thuringiensis var. kurstaki (Btk) and Arizona road dust to determine the collection efficiency of the device as a function of high voltage, particle ionization, particle concentration, and ionizer’s orientation”; see also section 3.4 CFD modeling, section 5 Conclusion). Examiner emphasizes that Priyamvada teaches that an electrostatic precipitator can be optimized for controlling the guidance of specific bioaerosol pathogens (e.g., Covid-19) be monitored by a sensor.
In view of the above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine SEMTECH’s PPMD housed electrostatic precipitator for a QCM with Zeng’s QCM thereby concentrating more particles to the measurement portion of Zeng’s QCM and enabling increased sensitivity, accuracy, and/or precision as well as providing compactness, portability, convenience of packaging, and/or for setting proper distances/orientation of the electrostatic precipitator relative to the QCM. It further would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize said electrostatic precipitator for specific pathogens—as factually supported by Priyamvada’s electrostatic precipitator design aspect understanding of particle flow and collection behavior (e.g., specific to Covid-19)—thereby providing the additional advantages of increased efficiency for pathogens of specific interest (e.g., pertaining to human health) while retaining low-cost and/or low power.
Regarding claim 2, which depends on claim 1,
Zeng teaches wherein the acentric piezoelectric crystal material (fig. 1, piezoelectric crystal wafer 12) is a cut quartz crystal ([0147] “cut quartz crystal”; [0239] “cut quartz crystal”).
The Examiner additionally notes that it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice, see MPEP § 2144.07 and In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960). In the present case it is the Examiner’s position that cut quartz crystal is a conventionally utilized material for QCM, and has known advantage(s) including suitability for room temperature measurements and/or stable/proportional mass to frequency response.
Regarding claim 3, which depends on claim 1,
Zeng teaches wherein the metal is gold or a gold alloy (Abstract, [0004] “precious metal such as gold which facilitates self-assembly”; [0079] “gold”).
The Examiner additionally notes that it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice, see MPEP § 2144.07 and In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960). In the present case it is the Examiner’s position that gold is a conventionally utilized material for the electrode of QCM, and has known advantage(s) including high compatibility with SAMs, nonreactivity to other exposures, and/or high electrical conductivity. The Examiner notes with respect to alloy versus pure, that gold is an expensive precious metal and utilizing other materials in combination would have been alternatively obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to reduce costs with the tradeoffs of reduction of the aforementioned suitability.
Claim(s) 4-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over previously cited Zeng in view of previously cited Biemmi, previously cited commercial product Semtech PPPD with previously cited Priyamvada, and in further view of previously cited Wang et al (US 20080204043 A1; hereafter “Wang”).
Regarding claim 4, which depends on claim 1,
Zeng teaches wherein the specific capture probe (receptor of receptor surface 15) is selected from the group consisting of an ssDNA, a peptide, an aptamer, and a monoclonal antibody (Abstract “polypeptides”; [0097] “Peptide”; [0262] “monoclonal antibody immobilized on the QCM surface”).
Zeng is silent to ssDNA and aptamer.
However:
It has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice, see MPEP § 2144.07 and In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960). In the present case, it is the Examiner’s position that only ordinary skill in the art is required to choose probe material, including of ssDNA, peptide, aptamer, or antibody (e.g., monoclonal) for the intended corresponding use as exemplary suitable to capture genes/nucleic sequences, enzymes, cancer/viruses/metal-ions, and/or antigens.
Wang teaches wherein the specific capture probe is selected from the group consisting of an ssDNA, a peptide, an aptamer, and a monoclonal antibody (Title “Real-Time Assessment Of Biomarkers For Disease”; Abstract “quartz crystal microbalance”; [0121] “quartz crystal is typically a circular "AT-cut" with metal electrodes on opposing faces” and “gold” and “change in resonant frequency, .DELTA.F, of, for example, an AT-cut quartz crystal of area (A) vibrating in air at fundamental frequency, F, when the mass of the crystal is changed”; [0124] “one or both electrodes of the sensor are coated with material which is capable of binding with a target”; [0165] “QCM is typically a disc of crystalline quartz with gold electrodes on the top and lower surfaces”; [0134] “Detection agents, for example, antibodies, whole or fragments, single chain, recombinant forms, aptamers, etc) can be immobilized on the sensor chip (such as a metal, organic, or inorganic monolayer coated quartz crystal microbalance (QCM) for binding (detection of individual biomarkers)”; [0084] “monoclonal antibodies”; [0163] “capture probe may comprise nucleic acid molecules. Single stranded-DNA (ssDNA)”; [0158] “QCM surface comprises surface bound capture probes such as, for example, antibodies”; [0158]-[0161] “peptides”; [0164] “Thus, a QCM may comprise large macromolecules such as, without limitation, antibodies, proteins, polysaccharides, peptides, or receptors as the immobilized capture probe”; [0221] “In a preferred embodiment, the protein-capture agents of the array are monoclonal antibodies”; [0222] “may be monoclonal antibodies, even commercially available antibodies”).
In view of the above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further/alternatively combine the entirety/each of options of the group consisting of an ssDNA, a peptide, an aptamer, and a monoclonal antibody—as factually supported by Wang’s QCM having capturing probe comprising the same group—with Zeng’s apparatus for the expected advantages of increased versatility (e.g., the aforementioned capture of capture genes/nucleic sequences, enzymes, cancer/viruses/metal-ions, and/or antigens) and/or increased marketability. Complementary, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Zeng’s plurality of QCM’s with Wang’s specific capturing probes, thereby providing a plurality of QCM’s for increased range of analytes able to be measured.
Regarding claim 5, which depends on claim 4,
Zeng as previously modified suggests wherein the specific capture probe (receptor of receptor surface 15) is a monoclonal antibody (see obviousness analysis provided for claim 4, especially as pertaining to obvious design choice & Wang [0221]-[0222] “monoclonal antibodies”). The Examiner exemplary notes that monoclonal antibodies have known advantages for selective detection and minimizing false positives, and the Examiner notes that monoclonal antibodies are well known to be used in specific circumstance when necessary for affording homogeneous binding characteristics despite potential expensive costs (Zeng [0025]), and had become commercially available by the time of Wang (Wang [0222] “commercially available”) and preferable for certain situations (Wang, [0221] “preferred”), the Examiner noting particular situations pertaining to disease (Wang Title).
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over previously cited Zeng in view of previously cited Biemmi, previously cited commercial product Semtech PPPD with previously cited Priyamvada, and in further view of previously cited Gluckman (US 20230103369 A1; hereafter “Gluckman”).
Regarding claim 6, which depends on claim 1,
Zeng teaches specific capture probes (receptors of receptor surface 15).
Zeng is silent to further comprising a capture membrane on top of the metal electrode and wherein the specific capture probes are attached on the capture membrane.
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Gluckman teaches further comprising a capture membrane (Molecularly Imprinted Polymer “MIP” array as membrane) on top of the metal electrode (AU electrode) and wherein the specific capture probes (complexing cavities/MIPs of array) ([0006] “Materials comprising a molecularly imprinted polymer of the present disclosure (e.g., macroreticular MIP beads, MIP films, and/or MIP nanoparticles) is/are designed to have a high affinity for all, or part of a target virus, and/or other biomarkers associated with the target virus”; [0011]-[0028]; [0081] pertains to details of MIPs; [0131] “the molecularly imprinted polymer can be in a non-bead form, such as nanowires, thin films or membranes”; [0251] “sensor for detecting a virus, coated with a MIP or MIP array of the present disclosure. In some embodiments, the sensor is selected from a quartz crystal electrode”; [0061] “coronavirus (COVID 2019, MERS 2012, and SARS 2003), influenza viruses (Bird flu H7N9 2013, and Swine flu H1N1 2009), and filoviruses (Zika 2015 and Ebola 2013)”; [0071]-[0077] additional virus types & details; [0078] “molecularly imprinted polymers capable of specifically binding to one or more selected polypeptides and/or portions thereof, wherein each selected polypeptide has an amino acid sequence unique to a specific protein that is uniquely expressed by a specific target virus/or uniquely associated with one or more specific traits of the target virus”; [0267] “quartz crystal microbalance electrode”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Gluckman’s membrane with (at least one of) Zeng’s QCM for the benefits of combining high performance with relatively low cost, and for the expected additional benefit(s) of withstanding harsh conditions without degradation thereby increasing versatility and thus marketability, reducing unwanted binding which improves signal-to-noise ratio, and/or reusability. Complementary, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Zeng’s plurality of QCM’s with Gluckman’s specific MIP array QCM thereby providing a plurality of QCM’s for increased range of analytes able to be measured.
Claim(s) 9 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over previously cited Zeng in view of previously cited Biemmi, previously cited commercial product Semtech PPPD with previously cited Priyamvada, and in further view of newly cited Godwin et al (NPL Metal Organic Frameworks as Biosensing Materials for COVID-19; hereafter “Godwin”).
Regarding claim 9, which depends on claim 1,
Zeng teaches specific capture probes (receptors of receptor surface 15) on the first side (first side of device 11) of the crystal microbalance (fig. 1, device 11), and
wherein the specific capture probe (receptor of receptor surface 15) is fixed to the metal electrode (fig. 1, electrode coating 14) on the first side (first side of device 11) of the crystal microbalance (fig. 1, device 11) ([0159] “A SAM is formed by the spontaneous association of molecules under equilibrium conditions. This spontaneous association yields a stable, structurally well-defined two-dimensional aggregate on the surface”).
Zeng is silent to further comprising a capture membrane situated adjacent to and in contact with the metal electrode on the first side of the crystal microbalance, and wherein the specific capture probe is absorbed or attached to a surface of the capture membrane, and wherein the capture membrane comprises a two dimensional material including a covalent organic framework or a metal-organic framework.
However:
Biemmi teaches a capture membrane situated adjacent to and in contact with the metal electrode (gold electrode) on a first side (first side of QCM) of the crystal microbalance (QCM), and wherein the specific capture probe is absorbed or attached to a surface of the capture membrane, and wherein the capture membrane comprises a two dimensional material including a covalent organic framework (silent) or a metal-organic framework (MOF) (Abstract “preparation of a thin film of the metal–organic framework Cu3(BTC)2(H2O)3 _ xH2O (HKUST-1) on the gold electrode of a quartz-crystal microbalance (QCM) was achieved by direct growth on a 11-mercaptoundecanol self-assembled monolayer (SAM)”; Introduction “well-defined accessible microporosity, large pore volume, and adjustable chemical functionality”). The Examiner acknowledges that while Biemmi teaches MOF structure on a QCM, Biemmi is silent to the specific pathogen captured by the MOF, see Godwin below.
Godwin teaches that MOFs can specifically capture a specific pathogen (e.g., COVID-19) (Title “Metal Organic Frameworks as Biosensing Materials for COVID-19”; Abstract “metal organic frameworks (MOFs) as a biosensor”; page 546 right column “Besides, there are proven cases where MOFs have been used in detection of viruses (HIV, Ebola, Zika, Dengue, etc.) and infectious diseases.58,92,121,130 The high specificity and selectivity of MOFs towards the detection of other viruses and diseases as presented in Section 4”; see also properties in fig. 3). The Examiner acknowledges that Godwin is silent to how to combine a MOF onto QCM, however, see Biemmi above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Godwin’s MOF for specific pathogen capture with (at least one of) Zeng’s QCM (in the manner factually supported by Biemmi which also uses SAM on QCM) for the expected advantages of being able to increase the binding capacity and tunably size for selectivity so as to better exclude all except the specific pathogen, as well as large specific surface area, high porosity, thermal stability, uniformity, and/or biocompatibility.
Regarding independent claim 20,
Zeng teaches an apparatus (fig. 1, apparatus 10) (Title “Piezoimmunosensor”; Abstract “Binding of antigen to the recombinant antibodies results in a change in mass on the receptor surface which is detected as a change in resonant frequency”) comprising:
a crystal microbalance (fig. 1, device 11) ([0034] “the piezoelectric mass sensor is a quartz crystal microbalance”) comprising
an acentric, piezoelectric crystal material (fig. 1, piezoelectric crystal wafer 12) ([0147] “cut quartz crystal”; [0239] “cut quartz crystal”) and directly deposited (silent to evaporation) onto a first side (first side of device 11) and a second opposite side (second side of device 11),
a pair of metal electrodes (fig. 1, electrode coatings 14) ([0147] “crystal with an electrode coating 14 deposited on each side of the crystal 12 using a suitable method”)
a specific capture probe (receptor of receptor surface 15) with a first region (region by electrode coating 14) that is adjacent to and in contact with the metal electrode (fig. 1, electrode coating 14) on the first side (first side of device 11) of the crystal microbalance (fig. 1, device 11) (Abstract “receptor layer is a precious metal such as gold which facilitates self-assembly”),
wherein the specific capture probe (receptor of receptor surface 15) further includes a second region (region away from electrode coating 14) specifically binds to and captures a specific pathogen (e.g., specific virus particle) ([0172] “binding of a single specific antigen, toxin, or virus particle”; [0183] “antigen-binding event is detected by the QCM, which is able to detect binding of a single specific toxin or virus particle”; [0227] “Fv-SAMs can be used for detection of a toxin (e.g., botulism toxin tainted food), a virus (e.g., HIV contaminated blood), a bacterium (e.g., E. coli), and a protozoan (e.g., Cryptosporidium parvum contaminated water)”; [0168] “detecting anthrax” and “detecting salmonella”; [0184] “one QCM could detect anthrax, another salmonella, another botulism toxin, etc.”),
wherein capture of the pathogen (e.g., specific virus particle) causes a change in mass to the crystal microbalance (fig. 1, device 11), and
wherein the change in mass of the crystal microbalance (fig. 1, device 11) causes a shift in a resonant frequency of the crystal microbalance (fig. 1, device 11) (Abstract “change in mass on the receptor surface which is detected as a change in resonant frequency”; [0211] “QCM sensors detect mass changes in liquid or gas phase by monitoring the frequency”; [0207] “relationship between frequency shift and the amount of mass loaded on the sensor” and “the measured frequency shift is proportional to the mass”; [0180] “For use, the resonant frequency of the sensor is determined and the sensor then incubated with the sample either by dipping in a liquid sample, by application of the liquid sample to the surface of the sensor, or in a liquid, vapor, or gas sample under continuous flow conditions. Afterward a sufficient period of time has elapsed, the resonant frequency of the sensor is measured. A change in resonant frequency indicates that the sample contains the analyte and the degree of change in resonant frequency indicates the quantity of analyte captured by the recombinant scFv polypeptides”).
The Examiner notes with respect to the above teachings being shown in different figures and/or taught in different sections, that while the reference does not expressly show all of the above claimed features clearly in a single depicted embodiment as a single figure discussed in a single section only, either one of ordinary skill in the art would at once envisaged the combination from the generic teachings thereof and/or specific possible choices of the structural components thereof, or, in the alternative, it at least would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to nevertheless so combine the above features for the purpose and combinations as proposed by said reference and as analyzed by the Examiner including the citations and/or Examiner comments provided above in reference to the claimed features. Pertinently, the Examiner further notes that "Combining two embodiments disclosed adjacent to each other in a prior art patent does not require a leap of inventiveness", see Boston Scientific Scimed, Inc. v. Cordis Corp., 554 F.3d 982, 991 (Fed. Cir. 2009). More particularly, it is Examiner’s position that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Zeng’s different embodiments of particular QCM devices with Zeng’s use of generic plurality of QCMs ([0035], [0049], [0060] “plurality of piezoelectric mass sensors”) for the benefits of each as put forth by Zeng, the Examiner noting that the combination provides Zeng’s plurality which increases versatility and marketability of Zeng’s apparatus.
While Zeng generically teaches utilizing a suitable method for directly depositing the pair of metal electrodes (fig. 1, electrode coatings 14) ([0147] “crystal with an electrode coating 14 deposited on each side of the crystal 12 using a suitable method”), Zeng is silent to item 1): the suitable method of evaporating. Zeng does not teach item 2): a capture membrane, wherein the specific capture probe first region is absorbed or attached to said capture membrane that is adjacent to and in contact with the metal electrode on the first side of the crystal microbalance, wherein the capture membrane comprises a two dimensional material including a covalent organic framework or a metal-organic framework, wherein the capture membrane improves a specificity of the specific capture probe to specifically bind to the specific pathogen.
Regarding item 1):
The Examiner previously took Official Notice that evaporating metal for electrodes is a conventional practice and that an ordinary artisan would at once envisaged evaporating metal electrodes onto the piezoelectric material as a suitable method. As the Applicant had not adequately traversed this assertion, this is considered admitted prior art in accordance with MPEP § 2144.03(C).
Furthermore, and as supporting factual evidence of the aforementioned assertion, Biemmi teaches an apparatus comprising a crystal microbalance (QCM) comprising an acentric, piezoelectric crystal material (cut quartz) and directly evaporated onto a first side and a second opposite side, a pair of metal electrodes (gold electrodes) (last paragraph of section 1. “A quartz crystal microbalance (QCM) is a well-known sensitive mass sensor that is suitable for the investigation of sorption properties of small amounts (few lg) of porous materials in the form of thin films [25–28]. A QCM typically consists of a thin disk of AT-cut quartz with key-hole electrodes patterned on both sides. The gold electrodes are thermally evaporated onto each face of the crystal”).
In view of the above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the conventionally known suitable method of direct evaporation of gold as electrodes for a QCM—as factually supported by Biemmi’s teaching of the same—for the expected purpose of a suitable attachment at low cost/complexity, low impurity, and/or excellent uniformity, the Examiner additionally noting with respect to directly, that direct evaporative deposition of the gold—such as without using epoxies—makes it solvent resistant and permits the fabrication of thin QCM electrodes without affecting the multiple-harmonics response to mass adsorption or inducing spurious responses caused by thick electrodes.
Regarding item 2):
Biemmi teaches a capture membrane situated adjacent to and in contact with the metal electrode (gold electrode) on a first side (first side of QCM) of the crystal microbalance (QCM), and wherein the specific capture probe is absorbed or attached to a surface of the capture membrane, and wherein the capture membrane comprises a two dimensional material including a covalent organic framework (silent) or a metal-organic framework (MOF) (Abstract “preparation of a thin film of the metal–organic framework Cu3(BTC)2(H2O)3 _ xH2O (HKUST-1) on the gold electrode of a quartz-crystal microbalance (QCM) was achieved by direct growth on a 11-mercaptoundecanol self-assembled monolayer (SAM)”; Introduction “well-defined accessible microporosity, large pore volume, and adjustable chemical functionality”). The Examiner acknowledges that while Biemmi teaches MOF structure on a QCM, Biemmi is silent to the specific pathogen captured by the MOF, see Godwin below.
Godwin teaches that MOFs can specifically capture a specific pathogen with improved specificity (e.g., COVID-19) (Title “Metal Organic Frameworks as Biosensing Materials for COVID-19”; Abstract “metal organic frameworks (MOFs) as a biosensor”; page 546 right column “Besides, there are proven cases where MOFs have been used in detection of viruses (HIV, Ebola, Zika, Dengue, etc.) and infectious diseases.58,92,121,130 The high specificity and selectivity of MOFs towards the detection of other viruses and diseases as presented in Section 4”; see also properties in fig. 3). The Examiner acknowledges that Godwin is silent to how to combine a MOF onto QCM, however, see Biemmi above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Godwin’s MOF for specific pathogen capture with (at least one of) Zeng’s QCM (in the manner factually supported by Biemmi which also uses SAM on QCM) for the expected advantages of being able to increase the binding capacity and tunably size for selectivity so as to better exclude all except the specific pathogen, as well as large specific surface area, high porosity, thermal stability, uniformity, and/or biocompatibility
Claim(s) 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over previously cited Zeng in view of previously cited Biemmi, previously cited commercial product Semtech PPPD with previously cited Priyamvada, and in further view of previously cited Pandey (NPL Design of engineered surfaces for prospective detection of SARS-CoV-2 using quartz crystal microbalance-based techniques; hereafter “Pandey”).
Regarding claim 7 and claim 8, where claim 7 depends on claim 1 and where claim 8 depends on claim 1,
Zeng teaches capturing generic pathogens and reasonably teaches wherein the specific pathogen (e.g., specific virus particle) is selected from the group (language of broader claim 7) consisting of SARS-CoV-2 (silent to this specific virus; additional obviousness analysis provided), influenza A (silent to this specific virus; additional obviousness analysis provided), Bacillus anthracis (at once envisaged from anthrax), and Salmonella typhimurium (at once envisaged from Salmonella) ([0172] “binding of a single specific antigen, toxin, or virus particle”; [0183] “antigen-binding event is detected by the QCM, which is able to detect binding of a single specific toxin or virus particle”; [00227] “Fv-SAMs can be used for detection of a toxin (e.g., botulism toxin tainted food), a virus (e.g., HIV contaminated blood), a bacterium (e.g., E. coli), and a protozoan (e.g., Cryptosporidium parvum contaminated water)”; [0168] “detecting anthrax” and “detecting salmonella”; [0184] “one QCM could detect anthrax, another salmonella, another botulism toxin, etc.”),
While Zeng generically teaches capturing viruses, Zeng does not explicitly teach capturing SARS-CoV-2 or Influenza A (alternatives in claim 7), nor does Zeng teach (claim 8) wherein the specific pathogen captured is SARS-CoV-2.
However:
It has been held that a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus satisfying the claimed structural limitations, Ex parte Masham, 2 USPQ2d - 164 7 (1987). See MPEP 2144(II). In the present case, it is the Examiner’s position that actually capturing SARS-CoV-2 (claim 8), influenza A, Bacillus anthracis, and/or Salmonella typhimurium (all as selected group in claim 7) is intended use, and one of ordinary skill in the art would reasonably expect that Zeng’s apparatus is capable to at least a reasonable proficiency to said use thereof.
Additionally, it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice, see MPEP § 2144.07 and In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960). In the present case it is the Examiner’s position that only ordinary skill in the art is required to select a specific material to capture a specific virus from Zeng’s generic teachings.
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As supporting factual evidence of the aforementioned assertion, Pandey teaches wherein the specific pathogen is selected from the group consisting of SARS-CoV-2 (Examiner notes this as focus of Pandey) and influenza A (Examiner notes that Pandey teaches that this as already known and has citational support thereof) (Title “Design of engineered surfaces for prospective detection of SARS-CoV-2 using quartz crystal microbalance-based techniques”; Abstract “SAMs”; page 428 “The adsorbed proteins on SAMs are desorbed by changing the ionic strength or applying a surfactant [25]. In another study, QCM-based immunosensor was developed for the rapid and sensitive detection of influenza A and B viruses [15]” and “Owen et al. developed a QCM sensor using SAMs and influenza H3N2 polyclonal IgG antibodies [44]. The limit of detection was found to be four influenza A viral particles per mL.”)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Pandey’s SARS-CoV-2 QCM capture specificity as well as Pandey’s referenced knowledge of Influenza-A QCM capture specificity with Zeng’s plurality of QCMs, thereby further increasing versatility and marketability of Zeng’s apparatus, notably enabling Zeng’s apparatus to detect said common viruses and thus providing easy to use & fast, precise identification of Influenza-A/Flu (claim 7) & SARS-CoV-2/Covid-19 (claim 7 & 8) in near real time.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over previously cited Zeng in view of previously cited Biemmi, previously cited commercial product Semtech PPPD with previously cited Priyamvada, previously cited Greenwood et al (US 20220113291 A1; hereafter “Greenwood”), previously cited Wang, and in further view of previously cited Hwang et al (US 20020081587 A1; hereafter “Hwang”).
Regarding claim 18, which depends on claim 1,
Zeng teaches a method of detecting a specific pathogen (e.g., specific virus particle) in the ambient air (Title “Piezoimmunosensor”; Abstract “Binding of antigen to the recombinant antibodies results in a change in mass on the receptor surface which is detected as a change in resonant frequency”) of an enclosed space (so capable of being used in a building, room, or other enclosed spaces; additional obviousness analysis provided) ([0150] “useful for a wide variety of immunoassays including bioterrorism defense, environmental pollutant monitoring, forensic analysis, biological research, and routine clinical tests in laboratory medicine”; [0213] “applications as underground monitoring”; [0228] “system can be used for bioterrorism defense, environmental pollutant monitoring, forensic analysis, biological research, and routine clinical tests in laboratory medicine. With parallel developments in microbiology for better biorecognition reagents, a wide spectrum of piezobiosensors for gas, liquid, and solid detection could be produced” and “the advantages implicit in combining the highly sensitive microbalance with highly selective immunochemical reactions can be realized”; [0219] “in clinical diagnostic, forensic medicine, and environmental monitoring”; [0221] “stability of the SAM in a dirty environment”; [0232] “ability to detect such a small molecule in a dirty solution”; [0152] “portable” and “no sample preparation by the user is required; and, and no secondary label is needed to establish identification”), comprising:
placing the crystal microbalance (fig. 1, device 11) of claim 1 (Title; Abstract; [0172]; [0227]; [0168]; [0184]; [0211]; [0207]; [0180]; see analysis of independent claim 1 for full details) into a sensor configuration (configuration comprising apparatus 10) (silent to chip),
calibrating a resonant frequency of the crystal microbalance (fig. 1, device 11) of claim 1 to a mass on the crystal microbalance (fig. 1, device 11) ([0210] “standard calibration curve”; [0213] “calibrate the sensor frequently to determine its long term stability and reliability. In this context, "long term" is the time period until which the calibration curve shows deterioration of linearity and sensitivity. Our goal is to develop our sensor to be robust and reliable for long-term use. This is important for such applications as underground monitoring. In flow injection analysis, calibration can be performed at any time or at any defined rate, thus the calibration process could be automated”; [0254] “standard calibration data”; Abstract, [0027] “change in mass on the receptor surface which is detected as a change in resonant frequency”);
conjugating the capture probe (receptor of receptor surface 15) to the crystal microbalance (fig. 1, device 11) ([0188] “appropriate conjugates to form the SAMs”; [0191] “conjugation”; [0199], [0247], [0263], [0268] “conjugated”; [0263] “conjugates”) and
blocking non-specific binding by exposing the conjugated surface to a blocking solution (blocking agent) ([0030], [0036], [0044], [0050], [0055], [0061], [0170] “binding of the analyte is blocked by a blocking agent”; [0170] “blocking agent such as oligo(ethylene glycol)”’; [0199] “plate is blocked with a BSA solution”; [0211] “the binding site is blocked by a blocking agent, such as oligo(ethylene glycol) group”; [0234] “blocking reagent such as 0.1% Bovine Serum Albumin (BSA) (catalog # A-9418 Sigma, St. Louis, Mo.) in PBS was applied to the scFv modified electrode for 30 min. to absorb onto any of the Au surface not bound with scFv”; [0237] “0.1% BSA blocking reagent”; [0251] “BSA blocking reagent”; [0253] “Blocking with BSA”; [0269] “BSA blocking reagent”; [0238] “0.1% BSA 5% BSA”);
installing the sensor configuration (configuration comprising apparatus 10) in a flow system (not shown; flow injection system) and directing the ambient air (gas sample, which can be dirty; see citations for preamble; see also additional obviousness analysis) or a sample of the ambient air at the sensor configuration ([0015] “detect antigens in or from the gas phase”; [0172] “sensors can be easily automated or combined with flow injection systems”; [0180] “liquid, vapor, or gas sample under continuous flow conditions”; [0213] “liquid, vapor, or gas sample under continuous flow conditions”; [0228] “wide spectrum of piezobiosensors for gas”);
measuring a resonant frequency of the crystal microbalance (fig. 1, device 11) at predetermined (automated; additional obviousness analysis provided) time intervals and
determining a mass change based on the measured resonant frequency at each predetermined time interval ([0150] “apparatus can be easily automate”; [0227] “devices can be easily automated or combined with flow injection systems”; Abstract, [0027] “change in mass on the receptor surface which is detected as a change in resonant frequency”; [0149] “change in resonant frequency is a result of the increase in mass on the surface of the piezoelectric material caused by the binding”; [0180] “resonant frequency of the sensor is determined and the sensor then incubated with the sample either by dipping in a liquid sample, by application of the liquid sample to the surface of the sensor, or in a liquid, vapor, or gas sample under continuous flow conditions. Afterward a sufficient period of time has elapsed, the resonant frequency of the sensor is measured. A change in resonant frequency indicates that the sample contains the analyte and the degree of change in resonant frequency indicates the quantity of analyte captured”);
relating the mass change to a pathogen (e.g., specific virus particle) load in the ambient air ([0180] “the degree of change in resonant frequency indicates the quantity”; [0172] “The sensitivity is such as to be able to detect binding of a single specific antigen, toxin, or virus particle”; [0183] “antigen-binding event is detected by the QCM, which is able to detect binding of a single specific toxin or virus particle”; [0227] “can be used for detection of a toxin (e.g., botulism toxin tainted food), a virus (e.g., HIV contaminated blood), a bacterium (e.g., E. coli), and a protozoan (e.g., Cryptosporidium parvum contaminated water)”); [0266] “can be used for detection the of a toxin (e.g., botulism toxin tainted food), a virus (e.g., HIV contaminated blood), a bacterium (e.g., E. coli), and a protozoan (e.g., Cryptosporidium parvum contaminated water)”; [0168] “For example, the apparatus can include one piezoelectric sensor for detecting anthrax, a second for detecting salmonella, a third for detecting botulism toxin, and so on”);
determining the pathogen (e.g., specific virus particle) load from the ambient air (silent to excessive load); and
outputting a notification indicating load in the ambient air based on determining that the pathogen (e.g., specific virus particle) exists (silent to excessive load notification) ([0213] “robust (stable) and reliable (few false positive and false negative detections”; [0150], [0172], [0227] “on-line display of the results”; [0152] “displays that information”).
Zeng does not explicitly state item 1) the preamble of detecting ambient air of an enclosed space; and 2) measuring a resonant frequency and mass change at predetermined time intervals. Zeng does not teach items: 3) placing the crystal microbalance into a sensor chip; 4) then installing in a housing; 5) determining whether the pathogen load exceeds a high load threshold; and 6) outputting a notification indicating an excessive load of pathogen.
Regarding items 1), 4), 5), and 6), Greenwood teaches a method of detecting a pathogen in the ambient air of an enclosed space (Title “METHOD AND SYSTEM FOR PATHOGEN DETECTION AND REMEDIATION”; Abstract “pathogen identification and remediation system and method, pathogens are identified by capturing samples in an air stream, identifying the pathogens and neutralizing them, with the option of assessing risk levels and issuing alarms when certain risk levels are exceeded”; [0002] “pathogens such as the flu virus and, more recently, Covid-19”; [0004] “system for capturing air samples in an environment, e.g., an apartment or house or a room in a house. This may include an air re-circulation system or the use of one or more fans that suck air into a remediation housing or duct. The housing or duct may include detectors for identifying pathogens”; [0026] “for detecting viral concentration of SARS-CoV-2 (Covid-19 virus)”), comprising: installing a quartz crystal microbalance sensor (fig. 2, sensor 100) in a housing (housing of sensor unit, or duct as the housing) and directing the ambient air or a sample of the ambient air at the sensor ([0028] “type of biosensor is the piezoelectric biosensor, comprising a quartz crystal microbalance biosensor, which measures any mass change” and “recording frequency and damping change of a quartz crystal resonator”; [0017] “monitoring air samples”; [0040] “Each unit may include a separate housing with one or more chambers, as discussed above, or the duct may define the airflow housing); measuring frequency of the crystal microbalance sensor (fig. 2, sensor 100) and determining a mass change based on the measured frequency; relating the mass change to a pathogen load in the ambient air; determining whether the pathogen load in the ambient air exceeds a high load threshold; and outputting a notification indicating an excessive load in the ambient air based on determining that the pathogen load exceeds the high load threshold (Abstract “issuing alarms when certain risk levels are exceeded”; [0012] “algorithm may define logic for comparing pathogen data received from the at least one biosensor with previously stored information”; [0016] “algorithm may include logic to identify a risk level based on one or more of geographic spread of a particular pathogen, speed of proliferation, density of pathogen, and known risk to humans or other animals posed by the pathogen based on previously captured information, and issuing at least one warning based on the risk level”; [0017] “assessing the risk posed by the at least one type of the pathogens to define a risk level, and notifying one or more persons based on the risk level posed by the at least one type of pathogen. Risk may be based on concentration of the pathogen, the nature of the pathogen (e.g. airborne as opposed to direct contact transmission), virulence, effectiveness in neutralizing the pathogen, etc.”; [0018] “creating heat maps of regions exceeding a predefined risk level and the associated pathogen, or creating contour maps of the various pathogens detected at various risk levels across a geographic area”; [0044] “alerts to be generated based on the nature of the threat posed by the pathogen”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Greenwood’s system comprising sensor housing & alarm with Zeng’s QCM apparatus for the expected purpose of providing useful application in building’s housing/ducts for detecting and alerting occupants/authorities of harmful pathogens and allowing for remediation/neutralization of said pathogens and therefore improving the health & safety of people. Complementarily, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Zeng’s QCM apparatus with Greenwood’s system for the expected purpose(s) of increased range of analytes able to be measured, high sensitivity to small mass changes which allows for the detection of ultrasmall masses with real-time, label-free, in-situ monitoring of molecular events, robustness, and/or reusability.
Regarding item 2):
The Examiner previously took Official Notice that taking measurements at predetermined time intervals is a conventional measurement practice, especially when automating. As the Applicant had not adequately traversed this assertion, this is considered admitted prior art in accordance with MPEP § 2144.03(C).
It has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art, In re Venner, 262 F.2d 91, 95, 120 USPQ 193, 194 (CCPA 1958). See MPEP 2144.04(III). In the present case, Zeng already teaches that the apparatus and sensors can be easily automated ([0150] “apparatus can be easily automated”; [0172] “sensors can be easily automated”; [0213] “calibration process could be automated”; [0227] “The devices can be easily automate”) and it is the Examiner’s position that only ordinary skill in the art would be required to automate the configured steps of Zeng’s invention with predetermined times, including measuring the resonant frequency of Zeng’s QCM and corresponding calculated mass change at predetermined time intervals.
Furthermore, and as additional supporting factual evidence of the Examiner’s position that only ordinary skill in the art is required to automate measurements with predetermined times, Wang teaches measuring a resonant frequency and mass change at predetermined time intervals (desired time intervals based on anticipated need) (Title “Real-Time Assessment Of Biomarkers For Disease”; [0119], [0184] “The sample can be processed by the QCM at time intervals desired by the operator. For example, if the injury appears to be life-threatening, then samples are taken at shorter time intervals to maximize the information, for example, to diagnose whether there has been severe damage, the type of damage, the location of the damage and the progression of the injury. This will provide a medical practitioner to make split-second decisions as to the medical procedures that need to be made to avoid further injury and to stabilize the patients condition. If, however, the patient is stabilized the time interval between different samples monitored may be longer”; [0120] “deposition of small quantities of material onto the crystal changes its resonant frequency and allows the determination of the mass of material deposited”).
In view of the above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine conventional time interval measurements with QCM’s—as factually supported by Wang’s desired time interval QCM measurements of resonance to determine mass changes—with Zeng’s QCM mass determining resonance measurements via Zeng’s alleged “easy” automation, thereby providing the expected benefit(s) of reduced human labor, reduced human mistake(s), more reliable measurements for monitoring changes over time, and/or to meet safety requirements of adequate determinations.
Regarding item 3), Hwang teaches placing a crystal microbalance into a sensor chip (Title “placing the crystal microbalance of claim 1 into a sensor chip”; Abstract “A biological microbalance array module chip, comprising a piezoelectric crystal array, probes, and a plurality of electrodes”; [0011] “The biological chip of the present invention, comprises a test site formed on a piezoelectric substrate; a plurality of electrodes associated with said test site, said test site having at least two electrodes attached thereto, and at least one surface of said electrodes on said test site being optionally immobilized with a plurality of probes which specifically bind to a target molecular structure; and circuitry which couples to said electrodes of said test site to output frequency variance generated from said test site”; [0024] “Piezoelectric materials such as quartz”; [0030]; [0034] “This increase of the mass further causes a variation of the oscillation frequency”.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Hwang’s sensor chip placement of a QCM with Zeng’s QCM thereby providing a convenient location for grouping together QCM(s) and associated circuitry, increased portability/installment (in this case a biological microbalance array sensor chip would be easier to place, including into a housing), decreased hardware costs (through sharing of circuitry), compactness, and/or associated reduced costs.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over previously cited Zeng in view of previously cited Biemmi, previously cited commercial product Semtech PPPD with previously cited Priyamvada, previously cited Greenwood, previously cited Wang, previously cited Hwang, and in further view of previously cited Pandey.
Regarding claim 19, which depends on claim 18,
Zeng as modified by Greenwood suggests wherein the specific pathogen (e.g., specific virus particle) is SARS-CoV-2 virus particles (Greenwood; [0002] “pathogens such as the flu virus and, more recently, Covid-19”; [0026] “for detecting viral concentration of SARS-CoV-2 (Covid-19 virus)”).
For compact prosecution and narrower interpretation:
While it is the Examiner’s position that actually capturing SARS-CoV-2 with Zeng’s apparatus can be reasonably expected with at least some reasonable amount of proficiency, the Examiner acknowledges Zeng as modified by Greenwood does not explicitly teach the specific details for the means of measuring SARS-CoV-2 with QCMs.
Additionally, it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice, see MPEP § 2144.07 and In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960). In the present case it is the Examiner’s position that only ordinary skill in the art is required to select a specific material to capture a specific virus from Zeng’s generic teachings.
As supporting factual evidence of the aforementioned assertion, Pandey teaches wherein the specific pathogen captured is SARS-CoV-2 (Title “Design of engineered surfaces for prospective detection of SARS-CoV-2 using quartz crystal microbalance-based techniques”; Abstract “SAMs”)
In view of the above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Pandey’s SARS-CoV-2 QCM capture specificity with Zeng’s plurality of QCMs, thereby further increasing versatility and marketability of Zeng’s apparatus, notably enabling Zeng’s apparatus to detect said common virus and thus providing easy to use & fast, precise identification of SARS-CoV-2/Covid-19 in near real time.
Allowable Subject Matter
Claim(s) 10-17 is/are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
When this application is finally acted upon and allowed (i.e., the Notice of Allowance), the Examiner will determine, at the same time, whether the reasons why the application is being allowed are sufficiently evident from the record; see MPEP § 1302.14(I).
Conclusion
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure. Applicant is invited to review PTO form 892 accompanying this Office Action listing Prior Art relevant to the instant invention cited by the Examiner. The Examiner notes that each of the newly cited prior art pertain to QCM with MOF, and are considered pertinent to the level of ordinary skill thereof.
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/DAVID L SINGER/Primary Examiner, Art Unit 2855 23JUN2026
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