DETAILED ACTION
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 .
Response to Arguments
2. Response to the Applicant's arguments filed on 01/20/2026 (in response to the first Non-Final Rejection office action mailed on 03/21/2025), and the arguments filed on 07/07/2026 in response to the second Non-Final Rejection office action mailed on 03/09/2026 is presented as item 13 below in this office action.
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 Claims 9-20 are withdrawn in response to restriction/election.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 statement (IDS) submitted on 07/07/2026 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Withdrawn Rejection under 35 USC § 112(a)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 Withdrawn rejection of claims 1-8 under 35 USC § 112(a).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 (Maintained)
10. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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. 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 Applicant’s Arguments
13. Applicant's arguments filed on 01/20/2026 in response to the first Non-Final Rejection office action mailed on 03/21/2025, and arguments filed on 07/07/2026 in response to the second Non-Final Rejection office action mailed on 03/09/2026 have been fully considered but they are not persuasive.
(A). Applicant’s Argued (see, Remarks filed on 01/20/2026) against 35 U.S.C. 103 obviousness rejection filed in response to the First Non-Final Rejection office action on 03/21/2025.
In summary, applicant argued that the prior art teachings alone or in combination do not teach and do not render obvious the claims 1 and 6-8. In particular, applicant argued that the prior art Leong, Ingber, and Wu did not teach claim 1 limitation "separating the aggregates magnetically via a gradient-based microfluidic magnetic separator according to their magnetic dipole moments" 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." For example, Leong notes that microfluidic devices have been used to separate malaria-infected red blood cells based on intrinsic magnetic susceptibility differences (Leong Section 2, p. 2). It describes "continuous MS" of magnetically labeled cancer cells in a microfluidic separator (id.). However, neither disclosure involves pathogen-dependent aggregates whose magnetic dipole moments increase with pathogen loading, as required by the claimed separation step. Although Leong discusses aggregation effects in the context of magnetophoretic kinetics, specifically that magnetic particles tend to collapse to form larger clusters with stronger magnetic response (Leong Section 3.2, p. 5), this discussion is limited to magnetic particle aggregation and cooperative magnetophoresis. Leong does not disclose or suggest forming aggregates comprising a pathogen, a magnetic particle, and a fluorescently labeled particle.
The eleven-reference combination further evidences impermissible hindsight.
For the above reasons, the cited references, alone or in combination, fail to teach or suggest the features of newly amended claim 1 or its dependent claims. Moreover, the proposed combinations lack motivation and rely on hindsight. For these reasons, Applicant respectfully requests that the § 103 rejections of claims 1-8 be withdrawn.
In Response:
The applicant presented amended claims on 01/20/2026. Instead of a Final Rejection office action, the examiner has issued a second non-final office action and rendered obvious the amended claims by incorporating additional prior art to render obvious the amended claims so that the applicant has an opportunity to review the second non-final rejection office action.
The applicant raised arguments over multiple combination references and hindsight. In this context, the multiple prior art can be used to render obvious the claims in contrast to anticipation rejection.
In response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991).
In response to applicant's argument that, “Leong notes that microfluidic devices have been used to separate malaria-infected red blood cells” is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, malaria parasite is a pathogen.
Leong et al 2016 is in the art and has reviewed the working principle of 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. Leong has disclosed viral and bacterial pathogens, antibody coated magnetic and superparamagnetic green fluorescent bead , fluorescent–magnetic bifunctional nanoparticles, and thus it is obvious to use non-magnetic fluorescent beads. Particle aggregation, magnetic dipole movement. In addition to particle size, the separation kinetic of MS is also strongly dependent on the concentration of the magnetic particles. This phenomenon is attributed to the cooperative nature of the magnetic particle system in which magnetic particles tend to aggregate and move collectively towards the magnetic source upon exposure to an external magnetic field. (See, entire article). The combined prior art teachings render obvious the claims as recited in the office action.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
ARGUMENT DOES NOT REPLACE EVIDENCE WHERE EVIDENCE IS NECESSARY
An argument by the applicant 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. Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); 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 applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration. See, MPEP 2145.
(B). Applicant’s Argued (see, Remarks filed on 07/07/2026) against 35 U.S.C. 103 obviousness rejection filed in response to the Second Non-Final Rejection office action on 03/09/2026.
Rejections under 35 U.S.C. 103
Claims 1 and 6-8 are rejected under 35 U.S.C. § 103 as unpatentable over Moriwaki (W02019138865A1) in view of Elshabrawy, "Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein are More Broadly Neutralizing"; Fleischman (US 6,623,984); Aojula (US 2016/0209406); Zborowski (US 5,968,820); Ingber (US 2009/0220932); Hess, "Ultra-High Resolution Imaging by Fluorescence Photoactivation Localization Microscopy"; McCash (US 7,384,793); Kim (Lab Chip, 2017, 17, 2095-2103); Leong, "Working principle and application of magnetic separation for biomedical diagnostic at high- and low-field gradients"; and Wu, "Magnetic-Nanosensor-Based Virus and Pathogen Detection Strategies before and during Covid-19". (Office Action at page 7).
Claims 2-3 are rejected under § 103 over the same combination, further in view of five (5) additional references: Shan (ACS Nano, 2020, 14, 12125-12132), Chi (Science, 2020, 369, 650- 655), Yang (Nat. Commun., 2020, 11, 4541), Lu (Zhonghua, 2005, 19, 260-3), and Zhou (WO2021226249A1).
Applicant respectfully disputes these rejections and respectfully submits that the Office has failed to present a prima facie case of obviousness.
The Examiner Has Failed to Present a Prima Facie Case of Obviousness
In the instant Office Action, the Examiner has failed to respond to or consider Applicant's prior rebuttal argument/evidence against the applied references. The MPEP is clear that the Office must consider and respond to Applicant's rebuttal evidence and failure to do so is against USPTO procedures. See MPEP § 2145. However, the Response to Arguments Section of the instant Office Action dismisses Applicant's prior arguments as moot because "the new ground of rejection does not rely only on the reference [sic] that were applied in the prior rejection of record." According to the Examiner, application of new references renders prior arguments against current references moot. This is improper and firmly against the guidance of the MPEP.
Here, Applicant previously provided detailed arguments and evidence against current references: Moriwaki, McCash, Ingber, Leong, Wu, Shan, Chi, Yang, Lu, and Zhou. See Office Action response of 1/20/26. Although the Office intimates in the Response to Arguments section that these arguments are considered/addressed in the body of the Office Action, Applicant cannot identify any such discussion. Rather, it appears that the Examiner has newly applied various parts/pieces of Elshabrawy, Fleishman, and Aojula and assumes that Applicant will fill in the blanks of the rejection. Again, this is improper.
(Applicant notes that Mathewson (J. Gen. Virol., 2008, 89, 2741-2745) is cited in the Notice of References cited but is not mentioned in the Office Action and Hess is not listed in the captions but is discussed in the body of the rejections).
Applicant's previous responses detailed why Moriwaki, McCash, Ingber, Leong, Wu, Shan, Chi, Yang, Lu, and Zhou fail to disclose or suggest, alone or in combination, various features of claim 1. The Office Action does not dispute these contentions. Instead, it appears to rely solely on newly cited references (i.e., Elshabrawy, Fleishman, and Aojula) to fill in the gaps in teachings of the prior 13 references. There is little to no guidance in the Office Action to how the reference teachings are to be combined. Various underlining appears random at points and, even if this were the intention, fails to make the Examiner's rationale explicit or clear, as required by the MPEP. Rather, the lack of context for each reference appears to indicate the Examiner has merely performed a key word search to identity references and set the pieces together without any express framework. There is no direction as to whether certain parts are meant to replace portions of the primary reference, modify it, or provide background to interpret it. The Examiner has merely quoted various portions and failed to explain how the references should be interpreted together. The MPEP and long-standing case law require that the reasoning supporting any rejection must be explicit. See MPEP § 2143.
Nevertheless, as Applicant's prior arguments against the proposed combinations of Moriwaki, McCash, Ingber, Leong, Wu, Shan, Chi, Yang, Lu, and Zhou were not rebutted, Applicant will not reiterate the earlier arguments here but hereby incorporates those arguments herein. Applicant respectfully maintains that the combined teachings of the references, alone or in combination, fail to properly disclose or otherwise suggest the claimed features as discussed previously. Further, as the Office Action fails to present a prima facie case of obviousness, Applicant submits that Elshabrawy, Fleishman, and Aojula do not remedy the deficiencies of the prior combinations. Accordingly, Applicant requests the rejections be withdrawn.
The Examiner has Failed to Present a Proper Motivation to Combine the References to
Achieve the Claims
MPEP § 2141(III) sets forth the basic requirements for a proper obviousness rejection: "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious." The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "'[R]ejections on obviousness cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness."' KSR, 550 U.S. at 418, 82 USPQ2d at 1396. See also Adapt Pharma Operations Ltd. v. Teva Pharms. USA, Inc., 25 F.4th 1354, 1365, 2022 USPQ2d 144 (Fed. Cir. 2022) (stating that a determination of obviousness "requires 'identify[ing] a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does"' (quoting KSR, 550 U.S. at 418, 82 USPQ2d at 1395) (emphasis added).
When explaining the reasoning/motivation for combining the references, the MPEP requires: "Office personnel must articulate findings of fact that support the rationale relied upon in an obviousness rejection." MPEP § 2141(V). Further, the Office Action should "clearly communicate the Office's findings and conclusions, articulating how the conclusions are supported by the findings." (emphasis added).
MPEP § 2143 provides further clarity in that "the analysis that "should be made explicit" refers not to the teachings in the prior art of a motivation to combine, but to the [examiner's] analysis. . .. Ball Aerosol, 555 F.3d at 993, 89 USPQ2d at 1877. The Federal Circuit's directive in Ball Aerosol was addressed to a lower court, but it applies to Office personnel as well. When setting forth a rejection, Office personnel are to continue to make appropriate findings of fact as explained in MPEP § 2141 and § 2143 and must provide a reasoned explanation as to why the invention as claimed would have been obvious to a person of ordinary skill in the art at the relevant time.
The Supreme Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness." See MPEP § 2141, subsection III.
It is respectfully submitted that the Examiner has failed to present/explain a proper motivation based on an articulated reasoning supported by facts on the record. For example, on page 15 of the instant Office Action, the Examiner presented their proposed motivation to combine/modify the references, Applicant has reproduced the relevant section below for ease of reference:
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.
Review of this proposed "motivation" shows that it is mostly a recitation of various features of Applicant's independent claim and ending with "for commercial advantage and success." Reading this in the light most favorable to the Examiner, it appears that they are asserting an ordinary artisan would have been motivated to modify the teachings of Moriwaki with Elshabrawy; Fleischman; Aojula; Zborowski; Ingber; Hess; McCash; Kim; Leong; and Wu, because of "commercial advantage and success." However, there are no facts presented in the Office Action that could be said to relate to "commercial advantage and success" of this modified/combined device/method. If the Examiner is proposing that Moriwaki would have been more commercially advantageous and successful when modified, then facts must be presented to establish this concept. See MPEP § 2141(V) - the Office Action should clearly communicate the Office's findings and conclusions, articulating how the conclusions are supported by the findings (emphasis added). No such explanation is presented in the Office Action. Commercial advantage and success is so generic and all-encompassing a "motivation" that it would likely apply to nearly all proposed combinations, especially when it is no tethered to any specific findings. This is a prime example of unsupported, dismissive handwaving and to fails to meet the standards set forth in the MPEP for a proper rejection.
A strikingly similar motivation is presented on page 20 with respect to the rejection of claims 2-3. In that rejection, the "motivation" to achieve the claims was "for commercial success and advantage." Again, no facts are presented to support this proposed motivation to combine. Accordingly, Applicant submits that the Examiner has failed to present any factual underpinnings that would support a motivation to combine/modify the references in a rejection based on obviousness. This is especially glaring inasmuch as the rejection relies on the teachings of no fewer than sixteen individual references, each of which must be integrated into the Examiner's proposed combination and would require some fact-based reason to do so. Unless and until the Examiner can provide persuasive facts supporting the proposed motivation, the rejection is improper and must be withdrawn.
The Examiner Has Failed to Establish a Reasonable Expectation of Success
A proper obviousness rejection requires not only a motivation to combine, but the Examiner must also establish a PHOSITA would have a reasonable expectation of success in combining the references. See MPEP § 2143.02. In a similar fashion to the lack of proper motivation to combine, here the Examiner has also failed to establish a reasonable expectation of success in combining the references to achieve the instant claims. For example, on page 15 the Examiner makes the following statement:
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.
A similar statement is presented on page 20 with respect to claims 2-3. MPEP § 2143.02 in combination with 2141 requires the Examiner to substantiate their reasonable expectation of success with reasoning based on facts from the record. No facts are presented here. At best it is a circular line without any support other than "take a look, it's in the references somewhere." This is insufficient to establish a reasonable expectation of success and against the directives of the MPEP. Unless and until the Examiner can provide facts from the record supporting some reasonable expectation of success, there is no prima facie case of obviousness and the rejection is improper. Accordingly, Applicant requests the rejection be withdrawn.
In Response:
Inventive Concept of the Claimed Invention:
Instant claim 1 is directed to a method for detecting viral or bacteriological pathogens. A magnetic particle is coated with the first antibody to which a first epitope of a pathogenic virus in a sample bind. Second epitope (that is different than first epitope) of the virus binds to the second antibody coated on a fluorescently labeled particle. The antigen-antibody binding create aggregates comprising the virus, magnetic particles, and the fluorescently labeled particle. A gradient-based microfluidic magnetic separator separating the aggregates magnetically via magnetic dipole moments. Estimating the amount of the virus is based on detecting the fluorescence of the separated aggregates and spatial distribution of the detected fluorescence. Thus, the virus is sandwiched between specific antibodies for epitope 1 and 2, and the antibodies are coated on magnetic beads and fluorescent beads. It is sandwich antigen assay using two antibodies that are directed to two different epitopes on the antigen. The magnetic beads provide characteristics for separation (microfluidic magnetic gradient separation using a Gradient Magnetic Separation (HGMS) configuration, refer to paragraph 20 of specification) of the antigen-antibody complex, and the fluorescent beads provide a reporter for reading out of the assay. The quantity is determined by the size of the aggregates and frequency of aggregates in a area of separation (spatial distribution). Magnetic field (dipole movement) is generated as the method uses a device and magnet. In addition, dipole movement is an inherent phenomena to the magnetic particle due to the Magnetic field in the claimed method.
Applicant's arguments filed on 07/07/2026 have been fully considered but they are not persuasive. The applied prior art combination has rendered obvious the amended claims 1, and 6-8 with a reasonable expectation of success with a motivation 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 as recited supra in this office action.
All components, elements or limitations of the amended claim 1 and dependent claims are taught by the combined teachings of the applied prior arts. Applicant did not point if any element or limitation is missing from the applied prior art that rendered obvious the amended claim 1 and dependent claims.
In response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In response to applicant's argument that, “Leong notes that microfluidic devices have been used to separate malaria-infected red blood cells” is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, malaria parasite is a pathogen.
Leong et al 2016 is in the art and has reviewed the working principle of 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. Leong has disclosed viral and bacterial pathogens, antibody coated magnetic and superparamagnetic green fluorescent bead , fluorescent–magnetic bifunctional nanoparticles, and thus it is obvious to use non-magnetic fluorescent beads. Particle aggregation, magnetic dipole movement. In addition to particle size, the separation kinetic of MS is also strongly dependent on the concentration of the magnetic particles. This phenomenon is attributed to the cooperative nature of the magnetic particle system in which magnetic particles tend to aggregate and move collectively towards the magnetic source upon exposure to an external magnetic field. (See, entire article). The combined prior art teachings render obvious the claims as recited in the office action. The method is highly predictable in view of the applicant’s claimed inventive concept and applied combined prior art teachings and obviousness analysis because the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). See, MPEP 2143. Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) 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 claimed invention.
ARGUMENT DOES NOT REPLACE EVIDENCE WHERE EVIDENCE IS NECESSARY:
An argument by the applicant 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. Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); 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 applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration. See, MPEP 2145.
No secondary considerations or unexpected or surprising findings:
The Applicant has not filed any secondary considerations showing unexpected results or surprising findings or results obtained from the claimed invention. See, MPEP 2145.
The rejections are maintained in this office action as recited supra.
Conclusion
14. No claim is allowed.
15. THIS ACTION IS MADE FINAL. Applicants are reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
16. 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
