ETAILED ACTION
Non-Final Rejection
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/20/2026 has been entered.
Election/Restrictions
3. Applicant’s election without traverse of inventions of Group I, claims 1-8 in the reply filed on 02/19/2025 is acknowledged.
For the elected Group I, applicant has elected a species viral pathogen including a coronavirus, SARS-CoV-2, without traverse.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election is made final.
Status of claims
4. Claims 1-3, and 6-20 as amended on 01/20/2026 are pending.
5. Claims 9-20 are withdrawn in response to restriction/election.
6. Claims 1-3, and 6-8 as amended on 01/20/2026 are under examination.
Information Disclosure Statement
7. The information disclosure statements (IDS) submitted on 04/13/2022, 09/30/2024, 05/30/2025, and 01/20/2026 is in-compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Rejection under 35 USC § 112(a)
8. Withdrawn rejection of claims 1-8 under 35 USC § 112(a).
Claim Interpretation
9. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
The instant claim 1 is directed to a method for detecting viral or bacteriological pathogens comprising: collecting a potentially pathogenic sample via a collector;
binding a first portion of the potentially pathogenic sample (e.g. a pathogenic virus, bacteria, parasite antigen) to a magnetic particle via a first coating on the magnetic particle, wherein the first coating is an antibody that binds to a first epitope of the pathogen;
binding a second portion of the potentially pathogenic sample comprising a second epitope different from the first epitope to an antibody in a second coating on a fluorescently labeled particle to create aggregates comprising the potentially pathogenic sample, magnetic particle, and the fluorescently labeled particle;
separating the aggregates magnetically via a gradient-based microfluidic magnetic separator according to their magnetic dipole moments;
detecting a fluorescence of the separated aggregates; and
estimating an amount of the pathogen based on the detected fluorescence and based on a spatial distribution of the detected fluorescence resulting from the separating.
The instant Claim 2 is interpreted to be directed to the method of claim 1, wherein at least one of:
the collector is a breathalyzer;
the collecting comprises obtaining the potentially pathogenic sample from a patient's breath via the breathalyzer;
the pathogen is a coronavirus;
the coronavirus is SARS-CoV-2;
the first epitope and the second epitope are on a SARS-CoV-2 spike protein;
the second coating comprises angiotensin converting enzyme 2 (ACE2); and the separating comprises separating the aggregates via a microfluidic magnetic separator according to their magnetic dipole moments.
The inventions of claims 1-3 and 6-8 are interpreted to be based on the inventive concept detection and quantification a pathogen in a sample (e.g. a pathogenic viral, bacterial or parasite antigen) that is bound to two different specific antibodies on two different epitopes of the pathogen (e.g. a pathogenic virus). One of the two pathogen (e.g. virus) epitopes specific antibody being attached or coated to a magnetic particle (e.g. magnetic sphere/bead), and second epitope specific antibody attached or coated to a fluorescently labeled particle (e.g. non-magnetic sphere) forms antigen-antibody interacted complex aggregate that comprise a complex, “the magnetic particle-a pathogen epitope 1 bound to epitope 1 specific antibody 1-a pathogen epitope 2-epitope 2 specific antibody 2 bound to a fluorescent particle”.
The pathogen antigen-antibody complex comprising the viral pathogen sandwiched by binding to the two different epitope specific antibodies that are attached or coated on the magnetic particle and a fluorescent particle that forms aggregates with magnetic properties are detected and quantified by physical aggregates, spatial distribution of fluorescence and electromagnetic dipole moments.
The claims 2-3 are interpreted to be directed to a method of detection of SARS-CoV-2, in particular the target is epitopes on spike protein, with a first coating of an antibody is directed to first epitope on the Spike protein and the second coating comprises ACE2 protein that binds to an epitope on the S protein (e.g. RBD domain).
Claim Rejections - 35 USC § 103 (Modified)
10. 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
11. Claims 1, and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Moriwaki et al 2019 (WO2019138865A1, published 18 July 2019, English Google Machine translated PDF printout), and further in view of Elshabrawy et al 2012 (PloS one, 7(11), e50366), Fleischman et al 2003 (US6623984B1, 09/23/2003), Aojula et al 2016 (US20160209406A1, 07/21/2016), Zborowski et al 1999 (US5968820A, 10/19/1999), Ingber et al 2009 (US20090220932A1, 09/03/2009), McCash et al 2008 (US7384793B2 published 10 June 2008), Kim et al 2017 (published in Lab Chip, 2017, 17, 2095-2103), Leong et al 2016 (Interface Focus 6: 20160048), Wu et al 2020 (ACS Appl. Nano Mater. 2020, 3, 9560−9580).
Claim 1. A method for detecting viral or bacteriological pathogens comprising:
collecting a potentially pathogenic sample via a collector; binding a first portion of the potentially pathogenic sample to a magnetic particle via a first coating on the magnetic particle, wherein the first coating is an antibody that binds to a first epitope of the pathogen;
binding a second portion of the potentially pathogenic sample comprising a second epitope different from the first epitope to an antibody in a second coating on a fluorescently labeled particle to create aggregates comprising the potentially pathogenic sample, magnetic particle, and the fluorescently labeled particle;
separating the aggregates magnetically via a gradient-based microfluidic magnetic separator according to their magnetic dipole moments;
detecting a fluorescence of the separated aggregates; and
estimating an amount of the pathogen based on the detected fluorescence and based on a spatial distribution of the detected fluorescence resulting from the separating.
Claims 1, and 6-8: Moriwaki et al 2019 (WO2019138865A1) teaches a method for detection of a target substance (a virus) in a test specimen comprising target substance (a virus) combined with a magnetic particle coated with a specific antibody against a virus and a fluorescent particle coated with different specific antibody against the same virus (the target substance such as a virus) is detected at a high sensitivity. The antigen-antibody reaction utilizes specific binding with a target substance (a virus), and therefore has the advantage that the anti-virus antibody coated magnetic particles, and the anti-virus antibody fluorescent particles can be selectively bound to the virus antigen (a target substance) (See, WO2019138865A1, Abstract, page number 6/18 of the pdf printout, para 5-7, see all pages). The target substance is an antigen such as a virus, it is necessary to bind in advance an antibody against the virus (as the target substance) to the magnetic particle and / or the fluorescent particle. The binding between the target substance and the particle is a specific binding with the target substance, such as an antigen-antibody reaction forms a complex of the magnetic particle-viral antigen- fluorescent particle that emits fluorescence upon irradiation with excitation light (See, WO2019138865A1, page number 6/18 pdf printout, para 5-7, see all pages). The detection device comprises a cell that houses a liquid containing a test specimen (comprising a virus). The antibody coated magnetic particles that bind to the target substance (a virus) in the liquid test specimen are mixed with magnetic bead-virus antigen complex that further specifically bind to the anti-virus antibody fluorescent particles. A magnetic field generating unit is used for moving the magnetic beads- the virus-fluorescent particle complex sample (moving mechanism of the magnet) in a direction having an angle with respect to the optical axis of the imaging unit and an excitation light irradiating part irradiating the antigen antibody complex with excitation light so as to generate fluorescence the target substance such as a virus can be detected at a high sensitivity (See, WO2019138865A1, abstract). A variety of sample in which the target substance (a virus) is detected are body fluids such as blood and lymph, saliva, sweat, runny nose, tears, etc. These samples may be collected by known methods according to the samples including swabs (a sample collector). Moriwaki et al 2019 teaches even if the amount of the target substance in the sample is small, the target substance can be detected, and the presence or absence of the target substance in the sample can be detected (See, page 12, pdf printout, para 4). Moriwaki et al 2019, recites that “according to the present invention, it is possible to detect a target substance with high sensitivity at a high S / N ratio by removing noise due to fluorescent particles etc. which are nonspecifically adsorbed to a cell or the like for detecting a target substance is there (See, page 5, para 1).
Moriwaki et al 2019 (WO2019138865A1) does not explicitly teach added limitations of the amended claim 1
different epitope (epitope 1 and epitope 2) specific binding antibody of a pathogen,
magnetic dipole moments,
spatial distribution of the detected fluorescence resulting from the separating.
Elshabrawy et al 2012 is in the anti-SARS CoV monoclonal antibody art and teaches human monoclonal antibodies that bind to different epitopes of Spike protein of SARS CoV (See, abstract, Table 1), notably 2D6 bind to HR2 of Spike, 6H2 binds to HR1 of spike and 4G10 binds to S-ectodomain (See, page 7, Table 1), and these human monoclonal antibodies directed to different epitopes of the SARS CoV Spike protein satisfy the antibodies required that are directed to the different epitopes (a pathogen / virus epitope 1 and epitope 2) of a virus.
Fleischman et al 2003 (US6623984B1) is in the art and is directed to a MEMS-based integrated magnetic particle identification system having a substrate, a magnetic structure, and a bioferrograph (See, abstract). Fleischman et al 2003 teaches a MEMS-based integrated particle identification system employing an antibody cocktail. Particles suitable for separation by the present invention include organic and non-organic particles. Organic particles preferably include, for example, cells, viruses, organelles, and DNA. Non-organic particles preferably include magnetic and paramagnetic particles such as, for example, metallic and non-metallic particles and molecules. Therefore, the antibody and virus particles would be expected to bind specifically for the identification and separation. Fleischman et al 2003 is based on the magnetic particle properties and teaches the concept of dipole moment (See, col 1 line 50-51). The magnetic structure is in physical communication with the topside and backside portions of the substrate and has at least two pole pieces. A plurality of pole piece embodiments are provided for generating a magnetic field that acts on magnetically susceptible particles in the flow stream. The bioferrograph has at least one sensor for identifying the presence and quantity of magnetically susceptible particles. A plurality of sensor embodiment are provided (See, abstract, claims 1-21, see entire prior art).
Aojula et al 2016 (US20160209406A1) is in the art and is directed to an apparatus for detecting an analyte using a fluid having magnetic particles with a binding ligand for binding the analyte. The analyte may be a virus (See, para [0046], claim 56). The binding ligand may be, for example, an antibody (See, para [0043], [0106]-[0107]). Analytes are collected using binding agents such as antibodies immobilized on the magnetic particles, the magnetic particles may then be subjected to a variety of analytical and assay methods (See, para [0002]), by binding fluorescent labels to analytes bound to particles and fluorescence spectroscopy is performed (See, para [0003]). Imaging from a dark background in order to maximize the contrast of the light scattered by the mobile particles, light sources such as LEDs (See, para [0052]).
Zborowski et al 1999 (US5968820A) is in the art and is directed to a method for magnetically separating cells into fractionated flow streams. The method provides a flow through dipole fractional cell sorting process that is based on the application of a magnetic force to cells having a range of magnetic labeling densities (See, abstract). The magnetically-labeled cells cross streamlines as they travel towards the source of the magnetic energy gradient. Therefore, one may expect that the magnetic cells travel at different velocities towards the magnet: those cells that bind the largest amount of the magnetic label will travel the fastest across the streamlines (reads on the instant claims magnetic particle aggregates formed by specific binding of the pathogen to the antibodies coated on magnetic particle and fluorescent particle), while those cells that bind a small amount of magnetic label will travel more slowly (See, US5968820A, col 12 last para lines 52-67, col 13 lines 1-5). The sorting methods and apparatuses of the present invention may also be applied to other particles than cells, such as cell organelles and viruses (See, col 19 last para line 61-63).
Ingber et al 2009 (US20090220932A1) is in the art and teaches concept of microfabricated high-gradient magnetic field concentrator (HGMC) integrated with a microfluidic channel, a miniaturized, integrated, microfluidic device pulls materials bound to magnetic particles from one laminar flow path to another by applying a local magnetic field gradient, and teaches the method of separating target material (reads on virus), wherein the separated magnetically susceptible target material includes at least one of bacterial, viral, or fungal pathogens (See, abstract, claim 60).
Hess et al 2006 is in the art and teaches a new method for fluorescence imaging has been developed that can obtain spatial distributions of large numbers of fluorescent molecules on length scales shorter than the classical diffraction limit (See, abstract, entire article).
McCash et al 2008 teaches a method of detecting a pathogen ( a virus) in a sample using viral antigen specific antibodies, separation of fluorescent magnetic particles coated with specific antibody to which the virus is bound, the method, inter alia, uses only one type of spheres or particles that are fluorophores conjugated fluorescent latex coated magnetic spheres, (See, abstract, claim 11), the method is adopted for detecting one or more pathogens including a virus (See, col 8, lines 7-9). A sample collector incorporating a venturi and a partial negative pressure (a sample collector) may be applied to assist to obtain said one or more sample (See, col 8, lines 27-28). Spatial concentration of the sample is capable of enhancing the measurement sensitivity of the system (See, claims 1-2, 11). The detection of the pathogens is performed using a fluorescently labeled assay, using evanescent-wave spectroscopy preferably by using a single-reflective technique (See, abstract); marking means for optically labeling the components present in the concentrated sample to produce labeled components; and interrogating means for optically interrogating said labeled components and thereby generating a measure of the concentration of components present in the sample (see McCash et al 2018 -claim 11), (instant claim 8 limitation). McCash et al 2018 teaches estimating pathogen amount based on fluorescence by disclosing a spatial concentrated sample which is transferred to a region within said vessel where the concentrated sample is optically interrogated (optical detection/estimation of fluorescent labeled component) (See, abstract, claims 1, 2, 4-5 and 11, see entire US7384793B2).
Kim et al 2017 is in the virology art and teaches bead aggregation for microfluidic immunodetection assay for rapid, label-free, and sub-picomolar influenza virus antigen (protein) detection. The binding occurs between 1 μm magnetic (MG) beads and 2.8 μm polystyrene (PS) beads coated with specific antibodies for a target antigen (influenza virus antigen). Detection of such aggregation is achieved by optical monitoring of AIBs in a flow under an external magnetic field. The detection ranges from 54 pg mL−1 to 54 ng mL−1 is demonstrated for the influenza type A H1N1 nucleoprotein. This immunosensing system is simple, highly sensitive, and capable of quantitative detection of antigens in a single test without fluorescent or enzyme labeling, hence is useful for the rapid detection of biomarkers in clinical and biomedical applications (See, abstract). Kim teaches aggregated beads are attracted to the upper surface of the microchannel by a magnetic field and made to slide along the surface by a flow drag force. Kim et al 2017 teaches that since only aggregates are selectively and magnetically picked up (separated), the structure and testing steps can be further simplified (See, Page 2102, col 2, para 1). Kim et al 2017 teaches magnetic beads coated with influenza virus antigen specific antibodies, however, the polystyrene (PS) beads although are coated with specific antibodies for a target antigen the polystyrene beads are non-fluorescent, provides a suggestion that in addition, it may require color beads or fluorescence labeling for optical clearness (See, introduction, col 2, first para, last 2 lines).
Leong et al 2016 is in the art and reviewed application of gradient magnetic separation, an external magnetic field is applied to drive the separation of target entity (e.g. bacteria, viruses, parasites and cancer cells) from a complex raw sample in order to ease the subsequent task(s) for disease diagnosis. It is noteworthy that effectiveness of the magnetic separation process not only determines the outcome of a diagnosis but also directly influences its accuracy as well as sensing time involved (See, abstract and entire article).
Wu et al 2020 is in the art and is directed to a method and device of magnetic-nano sensor-based virus and pathogen detection strategies before and during COVID-19. Wu et al 2020 teaches (See, Figure 9B) the steps of NMR-based immunoassay with MNP−pathogen interaction, magnetic separation, and filtration. As mentioned in section 3.3, for volume-based biosensing platforms, the filtration step could effectively reduce the interference of unbound MNPs. The magnetic separation and filtration are not necessary but are favored for high-sensitivity immunoassays (See, p. 9571, col 2, para 2, abstract, entire article).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art teachings of Moriwaki et al 2019 on detection of a viral pathogen using specific antibodies coated on magnetic particle and fluorescent particles as recited supra with the teachings of Elshabrawy et al 2012 on two different epitope specific antibodies on a pathogen, on the Spike protein of a SARS-CoV, and the claim limitations requiring the claimed electromagnetic (dipole moment), physical aggregation comprising a pathogen, a virus-specific first epitope binding antibody labelled magnetic particle and fluorescent particle labelled with a second epitope binding specific antibody and optical fluorescence measurement (spatial measurement of fluorescence), detection and quantification of a pathogen concentration (a virus or viral antigen concentration) taught by combined prior art teachings of Moriwaki et al 2019, Elshabrawy et al 2012, Fleischman et al 2003, Aojula et al 2016, Zborowski et al 1999, Ingber et al 2009, McCash et al 2008, Kim et al 2017, Leong et al 2016, and Wu et al 2020, as recited supra, to arrive at the invention of instant claims 1, 6-8. One of ordinary skills in the art would have been motivated to develop a sensitive method for detection and quantification of viral or a pathogen infection based on the magnetic beads coated with virus specific antibody to concentrate a low titer virus in a sample bound to a magnetic bead antibody complex and specificity offered by use of two types of beads and specific antibodies and increased fluorescence detection and quantification sensitivity due to the formed aggregates of the particles based on antigen-antibody interaction and magnetic beads, separating the formed aggregates magnetically, detecting and quantifying the fluorescence of the separated aggregates for quantitative estimation of the pathogen (See, Hess et al 2006, McCash et al 2008, Moriwaki et al 2019 abstract, Kim et al 2017, abstract) and for commercial advantage and success. One of the ordinary skills would have been apprised of a reasonable expectation of success to arrive at the invention of claims 1, 6-8 given the combined prior art teachings as applied to claims 1, and 6-8 as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 1, and 6-8. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
12. Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Moriwaki et al 2019 (WO2019138865A1, published 18 July 2019, English Google Machine translated PDF printout), and further in view of Elshabrawy et al 2012 (PloS one, 7(11), e50366), Fleischman et al 2003 (US6623984B1, 09/23/2003), Aojula et al 2016 (US20160209406A1, 07/21/2016), Zborowski et al 1999 (US5968820A, 10/19/1999), Ingber et al 2009 (US20090220932A1, 09/03/2009), McCash et al 2008 (US7384793B2 published 10 June 2008), Kim et al 2017 (published in Lab Chip, 2017, 17, 2095-2103), Leong et al 2016 (Interface Focus 6: 20160048), Wu et al 2020 (ACS Appl. Nano Mater. 2020, 3, 9560−9580) as applied to claims 1, and 6-8 above and further in view of Shan et al 2017 (published in ACS Nano 2020, 14, 12125−12132), Chi et al 2020 (published in- Science, 7 August 2020, 7;369 (6504): 650-655), Yang et al 2020 (published in Nat Commun, 2020, 11, 4541), Lu et al 2005 (published in Chinese. 2005, Sep; 19(3):260-3, PMID: 16261211), and Zhou et al 2021 (WO-2021226249-A1 published 11 November 2021 with an earlier priority date based on US filing US63020952 filed on 6 May 2020, US63085037 filed on 29 September 2020).
The combined teachings of Moriwaki et al, and other prior arts as teaches a method of claim 1 as recited supra and the teachings are incorporated here in entirety.
The combined teachings as applied to claim 1, however, does not teach added limitations of the instant claim 2-3 on (i) a breathalyzer, (ii) detection of SARS-CoV-2 virus.
Shan et al 2017 is in the art and teaches detection of SARS-CoV-2 associated with COVID-19 in exhaled breath sample. Shan teaches the collector is a breathalyzer by disclosing a hand-held breathalyzer system, inter alia, teaches a clinical trial involving breathalyzer for sample collection from a COVID-19 infected (SARS CoV-2 coronavirus infection) and control patient (See, abstract, figure 1-2 and legends, see entire article).
Chi et al 2020 teaches a human monoclonal antibody 4A8 (4A8 mAb) that binds to an epitope in the N-terminal domain of the S protein of SARS-CoV-2 virus (See, abstract and entire research paper).
Zhou et al (WO-2021226249-A1, priority date 6 May 2020) teaches neutralizing antibodies that bind the SARS-CoV-2 Spike protein and a method for detecting the presence of a coronavirus in a sample, inter alia, wherein the antibody-antigen complex is detected using a magnetic or fluorescence mode of detection and a method for diagnosing a subject suspected of having a coronavirus infection by detecting the SARS-CoV-2 Spike protein (See, claims 48-52; para [0026], [00145], [00256]).
Yang et al 2020 teaches SARS-CoV-2 coronavirus entry into host cells is mediated by the angiotensin-converting enzyme 2 (ACE2) a cellular receptor interaction with the viral spike glycoprotein (S-glycoprotein). The attachment of SARS-CoV-2 to cells involves specific binding between the viral S glycoprotein and the cellular receptor, ACE2. Structural studies have previously obtained a complex between the receptor-binding domain (RBD, a subunit of the S glycoprotein) and the angiotensin-converting enzyme 2 (ACE2) receptor (See, abstract and figure 1 and associated legends).
Lu et al 2005 teaches cloning and expression of functional ACE-2 receptor for the SARS coronavirus and its expression in eukaryotic cells (See, abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art combined teachings as applied to render obvious the claim 1 as recited supra, with additional teachings of Shan et al on a breathalyzer to collect the samples from a suspected COVID-19 patient, Zhou et al on a monoclonal antibody that bind the SARS-CoV-2 Spike protein (replace SARS-CoV mAbs of Elshabrawy et al 2012) and a method for detecting the presence of the SARS-CoV-2 in a sample wherein the antibody-antigen complex is detected using a magnetic or fluorescence mode of detection to diagnosing a subject suspected of having a SARS-CoV-2 infection, Chi et al on a human mAb 4A8 that binds to SARS CoV-2 Spike protein to an epitope in NTD which is different than epitopes on RBD domain of S protein and use mAb 4A8 to perform first coating on a magnetic particle, teachings of Yang et al and Lu et al to express and purify ACE-2 receptor protein and perform second coating on fluorescent particles to arrive at the invention of claim 2. One of ordinary skills in the art would have been motivated to develop a rapid method for detection of SARS CoV-2 infection due to teachings of Zhou et al on SARS-CoV-2 Spike protein detection assay involving using a monoclonal antibody that bind to SARS-CoV-2 Spike protein NTD and teachings on use of magnetic or fluorescence mode of detection to diagnose a subject suspected of having a SARS-CoV-2 infection. One of ordinary skills in the art would have been motivated to develop a sensitive method for detection and quantification of SARS-CoV-2 viral antigen or the virus based on the magnetic beads coated with virus specific antibody to concentrate a low titer virus in a sample bound to a magnetic bead antibody complex and specificity offered by use of two types of beads and a specific antibody to epitopes on SARS CoV-2 S protein, and epitope in RBD that binds to ACE-2 protein coated on a fluorescent particle, and increased fluorescence detection and quantification sensitivity due to formed aggregates of the particles based on antigen-antibody interaction and magnetic beads (See, Hess et al 2006, McCash et al 2008, Moriwaki et al 2019 abstract, Kim et al 2017, abstract; Zhou et al WO2021226249A1, claims 48-52; para [0026], [00145], [00256]). One of the ordinary skills would have been apprised of a reasonable expectation of success to arrive at the invention of claim 2 given the combined prior art teachings as applied to instant claim 2 as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claim 2. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
Claim 3: Moriwaki et al 2019 further teaches added limitation of the instant claim 3, wherein separating of the aggregates in a magnetic field generating part moving the test specimen in a cell housing a liquid (microfluidic) in a direction having an angle to the optical axis of the imaging part (See, abstract, claim 1-9 and 11, see entire WO2019138865A1).
Zborowski et al 1999 (US5968820A) is in the art and is directed to a method for magnetically separating cells into fractionated flow streams. The method provides a flow through dipole fractional cell sorting process that is based on the application of a magnetic force to cells having a range of magnetic labeling densities (See, abstract). The magnetically-labeled cells cross streamlines as they travel towards the source of the magnetic energy gradient. Therefore, one may expect that the magnetic cells travel at different velocities towards the magnet: those cells that bind the largest amount of the magnetic label will travel the fastest across the streamlines (reads on the instant claims magnetic particle aggregates formed by specific binding of the pathogen to the antibodies coated on magnetic particle and fluorescent particle), while those cells that bind a small amount of magnetic label will travel more slowly (See, US5968820A, col 12 last para lines 52-67, col 13 lines 1-5). The sorting methods and apparatuses of the present invention may also be applied to other particles than cells, such as cell organelles and viruses (See, col 19 last para line 61-63).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the prior art combined teachings as applied to claim 2 by incorporating additional teachings of Moriwaki et al, Zborowski et al 1999 and McCash et al on taking measurement of the “magnetic particle-viral antigen-fluorescent particle complex” utilizing the magnetic properties, aggregate size and time required to travel the distance (spatial parameter) for the immunomagnetic fluorescent complex and fluorescence reading. Estimation of amount of a pathogen is routine in the art of diagnostic assay based on the designed readout, in this case, a fluorescence readout. One of ordinary skills in the art would have been motivated to develop a sensitive method for detection of SARS CoV-2 infection due to teachings of Zhou et al on antibodies that bind the SARS-CoV-2 Spike protein and a method for detecting the presence of the SARS-CoV-2 in a sample wherein the antibody-antigen complex is detected using a magnetic or fluorescence mode of detection to diagnose a subject suspected of having a SARS-CoV-2 infection, and teachings of Chi et al on SARS CoV-2 S protein specific 4A8 mAb and Lu et al on ACE-2 protein to arrive at the invention of claim 3 a rapid test for detection of SARS CoV-2 for commercial advantage and success. One of the ordinary skills would have been apprised of a reasonable expectation of success to arrive at the invention of claims 3 given the combined teachings as applied and as recited supra including entire patent publications of the applied prior arts. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 3. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
Response to Arguments
13. Applicant’s arguments with respect to the amended claims 1-3 and 6-8 filed on 01/20/2026 have been considered but are moot because the new ground of rejection does not only rely on the reference that were applied in the prior rejection of record. The office action as recited supra includes additional new prior art references as recited supra for any teaching or matter specifically challenged in the arguments.
The modified 35 U.S.C. 103 rejection as recited supra in the office action has addressed the applicant’s arguments and rendered obvious the amended claims that has introduced new limitations or new elements.
Applicant’s arguments are moot in view of the modified 35 U.S.C. 103 rejection as recited supra.
Conclusion
14. No claim is allowed.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner, Art Unit 1600