DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Acknowledgement is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/US2019/021696, filed 03/11/2019, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/640,628, filed 03/09/2018.
Status of the Claims
Claims 1-2, 7, 14-15, and 38-41 are pending and examined below. Claim 1 is amended and claim 41 is new. Claims 3-6, 8-13, and 16-37 are cancelled.
Withdrawn Rejection
The rejection of claims 1-2, 4, 7-8, 10, 14-15, and 38-40 under § 103 are withdrawn due to the amendment of claim 1 and the cancellation of claims 4 and 8.
See new grounds of rejection below.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-2, 7, 14, and 38-40 are rejected under 35 U.S.C. 103 as being unpatentable over Pris et al., US20100129787A1, 05/27/2010 (see PTO-892, 05/01/2025), in view of Damon et al. (2016) “Direct Biofluid Analysis Using Hydrophobic Paper Spray Mass Spectrometry”, Analytical Chemistry, 88, pages 1878-1884 (see PTO-892, 01/30/2025), Cao et al. Gold nanoparticle-based signal amplification for biosensing. Analytical biochemistry. 2011 Oct 1;417(1):1-6 (see PTO-892, 05/01/2025), Jia et al. Nano-ELISA for highly sensitive protein detection. Biosensors and Bioelectronics. 2009 May 15;24(9):2836-41, Chen et al. (2016) Mass spectrometry for paper-based immunoassays: toward on-demand diagnosis. Journal of the American Chemical Society. May 25;138(20):6356-9; see PTO-892, 01/30/2025), and Hari et al. Synthetic applications of eosin Y in photoredox catalysis. Chemical Communications. 2014;50(51):6688-99 (see PTO-892, 04/07/2026).
Regarding claim 1, Pris teaches a method of detecting the presence of a target in a test sample (detecting at least one antigen in a sample) comprising: (a) providing a test sample and a target present in the test sample, (b) providing a capture agent capable of selectively binding to the target, wherein the capture agent is adhered to a solid support, (c) providing a binder capable of selectively binding to the target, wherein the binder is coupled to a catalyst, (d) contacting the test sample with the capture agent and the binder in an assay solution, wherein a captured target complex containing the capture agent, the target, and the binder is formed when the capture agent and the binder combine with the target (e) separating the captured target complex from non-complexed assay components, (f) combining a substrate reactive with the catalyst, wherein the catalyst converts the substrate to a catalysis product and (g) performing analysis of the solution of step (f) for an analyte selected from the substrate or the catalysis product (Pris, page 1, see entire paragraph [0005]). Pris further teaches that examples of catalysts include inorganic, organic, or biological catalysts that allow for redox, electronic or enzymatic conversion and that the catalyst may be selected according to the chemical reaction in which a selected substrate is converted into a catalysis product (Pris, page 4, paragraph [0040], lines 7-11). Pris further teaches that the sample tested in the provided assay may be for example a biological sample (Pris, page 4, paragraph [0035, lines 1-2). Pris further teaches that the target can for example be an antigen (Pris, page 5, paragraph [0045], lines 6-7). Pris further teaches that the target is adhered to a solid support, which may be any surface comprised of a porous or on-porous water-insoluble material and that the surface can be hydrophilic or capable of being rendered hydrophilic and includes materials such as those derived from cellulose, for example fiber containing papers (Pris, page 4, paragraph [0037], lines 1-11). Pris further teaches that the capture agent can for example be an antibody and that a suitable binder is for example an antibody (Pris, page 4, paragraph [0036], lines 2-13). Pris further teaches that step (e), separating the captured target complex from non-complexed assay components, is achieved by washing the solid support (Pris, page 1, paragraph [0007], 2nd column, lines 9-11). Pris further teaches that the sample is exposed to the catalyst associated binder as well as to a solid support associated target capture agent either sequentially or simultaneously (Pris, page 2, paragraph [0021], lines 4-6). Pris further teaches that the detection method may be used for mass spectrometry (Pris, page 3, paragraph [0029], lines 4-5). Pris further teaches that the catalysts include those that allow for redox conversion (Pris, page 4, paragraph [0040], lines 7-9) and specifically exemplified non-limited examples of catalysts including inorganic, organic, or biological catalysts that effect redox, electronic or enzymatic conversation (Pris, page 2, paragraph [0013]). Pris further teaches that the analyte can be 3,3’,5,5’-tetramethylbenzide (TMB), 8-hydroxyquinoline, or ammonia. As such, Pris teaches an analyte that is an electron donor. Pris teaches detecting ammonia and pyridoxamine, primary amines, as catalysis products, i.e. reporter compounds. See page 4, Table 2.
Pris fails to teach that the cellulose substrate is hydrophobic and further fails to teach that the substrate the reporter antibody is bound to is a gold nanoparticle.
Pris further fails to teach that the reporter of the reporter antibody is a photoredox catalyst comprising Rose Bengal, Eosin Y, TPP+, Mes-Acr+, or a combination thereof which is also conjugated to the gold nanoparticle.
Pris further fails to teach generating the reporter compound by reacting a sacrificial electron donor in the presence of light and oxygen.
Damon teaches biofluid analysis using hydrophobic paper spray mass spectrometry (Damon, page 1878, see title). Damon further teaches that the underlying principle when using hydrophobic surfaces is to prevent wetting so that the aqueous based samples can be organized as spherical droplets for enhanced sampling (Damon, page 1878, 2nd column, 3rd paragraph, lines 1-6). Damon further teaches that the technique greatly facilitates sample loading and extraction from paper and potentially increase in the sensitivity of PS ionization and further that it is compatible with raw blood, serum, and whole urine (Damon, page 1882, ‘Conclusion’, lines 4-8).
Cao teaches that colloidal gold particles (AuNPs) have been widely used as labels for analytical signal amplification (Cao, page 1, 2nd paragraph, lines 1-2). Cao further teaches that because of their narrow size distribution, good biocompatibility, and ease of modification, AuNPs could serve as carriers for the immobilization of captured probes and that the application includes immobilization of more biorecognition elements or a large number of tags on AuNPs, which prove more binding sites or amplification of the analytical signal in a single recognition reaction (Cao, page 2, ‘AuNPs as carriers’, lines 1-7). Cao further teaches capture probes immobilized on a solid substrate and AuNPs carrying detecting probes modified with signal inducers, resulting in signal amplification (Cao, page 2, Figure legend 1(B)). Cao further teaches a sandwich assay for protein detection that uses two affinity aptamers for increasing specificity and AuNPs for signal amplification and inductively coupled plasma mass spectrometry (ICP-MS) for highly sensitive detection. The first aptamer was conjugated to AuNPs and the second aptamer was coupled conjugated to magnetic beads. Both first and second aptamer bind to the target molecule and after removal of magnetic beads the AuNPs in the solution are analyzed by ICP-MS. Cao further teaches that the detection limit was as low as 0.5 fmol and the dynamic range covered approximately 3 orders of magnitude (Cao, page 13, ‘Inductive coupled plasma mass spectrometry’, see entire first paragraph). Chen teaches a method comprising immobilization of the capture antibody, capture of antigen, complexation of detection antibody conjugated with a cleavable charge-tag followed by mass spectrometry (Chen, page 6356, Figure 1 (a) and figure legend).
Jia teaches an enzyme linked immunosorbent assay comprising gold nanoparticles modified with a monoclonal detector antibody as well as horseradish peroxidase immobilized on AuNP probes (Jia, page 2836, ‘Abstract, lines 1-4 and Scheme 1. A). Jia further teaches that the gold nanoparticles are used as amplifiers (Jia, page 2841, 2nd column, line 1). Jia teaches an earlier method in which gold nanoparticles comprising anti-human-IgG-HRP-conjugated antibody significantly improved the detection limit and further teaches that HRP can oxidize various chromogenic substrates (redox catalyst). However, one major drawback of that method is that the detector antibody needs to be conjugated with HRP and the process of creating HRP-linked antibodies is very complex and expensive which limits its application widely (Jia, page 2836, see entire 3rd paragraph).
Hari teaches that Eosin Y is widely used as an organo-photocatalyst in synthetic transformations and that the long known dye molecule finds application in cell staining , as a pH indicator, and as a dye pigment. Hari further teaches that organic dyes such as Eosin Y have been used as an attractive alternative to transition metal complexes in photoredox catalysis because they are typically less expensive and less toxic, easy to handle and even outperform organometallic and inorganic catalysts in some cases. Hari teaches applications of Eosin Y as a visible light photocatalyst (Hari, page 6688, see entire 2nd paragraph). Hari further teaches that upon excitation by visible light, Eosin Y undergoes rapid intersystem crossing to the lowest energy triplet state (Hari, page 6689, lines 1-3). Hari further teaches a visible light mediated method using Eosin Y as a photoredox catalyst under visible light using molecular oxygen from air as the terminal oxidant (Hari, page 6690, ‘4.1. Oxidative iminium ion formation’, see entire 1st paragraph). Hari further teaches that in the reduction of nitrobenzene Eosin Y was used as a photocatalyst and triethanolamine was used as a sacrificial reducing agent for the efficient photocatalytic reduction of nitrobenzene in a reaction that is chemoselective and tolerates the presence of other functional groups (Hari, page 6689, ‘3.2. Reduction of nitrobenzene’, lines 1-6). Hari further teaches that adducts comprising trapped radical intermediates of photocatalytic direct C-H arylation reaction comprising Eosin Y can be confirmed by mass spectrometry (Hari, page 6694, see entire 2nd paragraph).
Pris teaches a binder (antibody) which is coupled to a catalyst (Pris, page 1, paragraph [0005], lines 6-7) and Pris in view of Hari teaches that the catalyst is a photocatalyst (see above). As such the combination of the art teaches a probe, which is conjugated to a gold nanoparticle, is conjugated to a photoredox catalyst.
It would have been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention, to have modified the method of Pris to use, as the cellulose substrate, a hydrophobic paper (cellulose) substrate as in Damon, because of the teaching of Damon that a hydrophobic surfaces allows for the samples to be organized as spherical droplets which facilitates sample loading and extraction from paper and can increase the sensitivity of the paper spray ionization.
One of ordinary skill in the art would have a reasonable expectation of success in using a hydrophobic surface as taught by Damon in the method of Pris, because both Pris and Damon use a method of detecting a target in a sample by mass spectrometry and paper as the substrate.
It would have further been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention, to have modified the method of Pris by immobilizing the detection probe with the signal inducer on a gold nanoparticle because of the teaching of Cao that gold nanoparticles can be used for the amplification of signal and because of the teaching of success of Chen of using a probe-conjugated detection antibody in paper-based mass spectrometry immunoassay. It would have further been obvious to use the immobilized probes in a sandwich assay in which the method of detection is mass spectrometry because of the teaching of Cao that the assay is very sensitive and has a dynamic range of approximately 3 orders of magnitude.
One of ordinary skill in the art would have a reasonable expectation of success using a labeled detection/capture probe immobilized to a gold particle because Pris teaches a sandwich assay with a capture and a detection antibody and Cao teaches success using a gold particle to immobilize a labeled detection probe in a sandwich assay. The ordinary artisan would further have a reasonable expectation of success using a probe immobilized to a gold particle in mass spectrometry because of the teaching of Cao that mass spectrometry using gold particles is a very sensitive assay with a large dynamic range.
It would have further been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention, to have modified the invention of Pris and conjugated the redox enzyme to the gold nanoparticle instead of the antibody attached to the nanoparticle because of the teaching of Jia that creating enzyme linked antibodies is very complex and expensive and limits its application.
One of ordinary skill in the art would have a reasonable expectation of success using a gold nanoparticle with the catalyst attached to the gold nanoparticle as taught by Jia rather than the antibody as taught by Pris because the prior art teaches detecting an analyte bound to a probe comprising a gold nanoparticle bound to an antibody, bound to a catalyst and Jia teaches success amplifying the signal of an immunoassay using a gold nanoparticle and a catalyst in an immunoassay whether the catalyst is attached to the gold nanoparticle directly or through the antibody. As such one of ordinary skill in the art would also expect success in an antibody based assay that uses the gold nanoparticle and a catalyst to amplify the signal.
It would have further been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention, to have used Eosin Y as the photoredox catalyst in the method of Pris because of the teaching of Hari that organic dyes such as Eosin Y, which achieves photoredox catalysis under visible light and using molecular oxygen from air, are an attractive alternative to other photoredox catalysts because they are typically less expensive and less toxic, easy to handle and even outperform organometallic and inorganic catalysts in some cases. It would have further been obvious to use triethanolamine as a sacrificial reducing agent because it results in an efficient photocatalytic reduction that tolerates the presence of other functional groups.
One of ordinary skill in the art would have a reasonable expectation of success using Eosin Y as the photoredox catalyst and triethanolamine as a sacrificial reducing agent in the method of Pris because Hari teaches that organic dyes such as Eosin Y outperform organometallic and inorganic catalysts in some cases and further that using triethanolamine as a reducing agent results in an efficient photocatalytic reduction. Hari further teaches success detecting adducts comprising trapped radical intermediates of a photocatalytic reaction comprising eosin Y can be confirmed by mass spectrometry and as such teaches success detecting catalysis products by mass spectrometry.
Regarding claims 2 and 40, Pris and the cited art above teach a method of detecting an antigen by reacting a reporter antibody, comprising a photoredox catalyst, to generate a reporter compound detected by mass spectrometry, substantially as claimed.
Pris teaches combining a substrate reactive with the catalyst, wherein the catalyst converts the substrate to a catalysis product and performing analysis of the solution for an analyte selected from the substrate or the catalysis product (Pris, page 1, paragraph [0005], lines 13-18). Pris further teaches that the detection method may be used for mass spectrometry (Pris, page 3, paragraph [0029], lines 4-5).
Pris does not teach that the reporter compound comprises a quaternary amine or a secondary amine (claim 2), nor does Pris teach that the reporter compound comprises diethanolamine (claim 40).
Hari teaches utilizing eosin Y as a photocatalyst and triethanolamine as a sacrificial reducing agent for an efficient photocatalytic reduction (Hari, page 6689, ‘3.2. Reduction of nitrobenzene’) and further teaches that the reaction in the presence of water gives glycolaldehyde, diethanolamine (a secondary amine) and further reduced intermediates (Hari, page 6689, ‘3.2. Reduction of Nitrobenzene’, 2nd paragraph, lines 6-9).
It would have been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention, to have modified the method of Pris by using Eosin Y as the catalyst and triethanolamine as the sacrificial electron donor for the reasons explained previously above and it would have further been obvious to have detected the secondary amine diethanolamine in the method of Pris because Pris teaches a method of detecting an analyte in a sample by reacting a substrate with a catalyst and performing analysis of the sample for the substrate of the catalysis product and further teaches that mass spectrometry can be used to detect the product. Applying the method of Pris, namely detecting the analysis product by mass spectrometry would have necessarily resulted in the detection of diethanolamine (claim 40), a secondary amine (claim 2).
One of ordinary skill in the art would have a reasonable expectation of success using Eosin Y as the photoredox catalyst and triethanolamine as a sacrificial reducing agent for the same reasons as applied to claim 1 and because using Eosin Y as a catalyst and triethanolamine as the sacrificial electron donor results in the production of diethanolamine one would have necessarily detected diethanolamine if modifying the method of Pris with the method of Hari.
Regarding claim 7, Pris and the cited art above as applied to claim 1, also applies to claim 7.
Hari teaches triethanolamine as a sacrificial reducing agent (Hari, page 6689, ‘3.2. Reduction of nitrobenzene’, lines 1-6).Triethanolamine is a tertiary amine.
Regarding claim 14, Pris and the cited art above teach a method of detecting an analyte in a sample substantially as claimed.
Pris and the prior art do not teach that the hydrophobic cellulose substrate has a base and first and second edges (a triangle) where the sum of angles at which the first and second edges intersect is greater than 135 degrees.
Damon teaches a method of detecting an analyte using a hydrophobic cellulose substrate with a base width of 9.5 mm and a height of 16.6 mm (Damon, page 1879, ‘Hydrophobic Paper Preparation’, lines 8-9). As such, Damon teaches a triangle with a sum of the angles at which the first and second edges intersect the base which is 150 degrees and therefore greater than 135 degrees, which results in a narrow angle of 30 degrees at the tip of the triangle. Damon further teaches that the required sample volume is dependent on the paper geometry and the position of the loaded sample with respect to the paper tip. Damon further teaches that in the current experiment the signal generated from < 1 μl is adequate for analyte characterization and will provide a method of analysis for samples of small volumes taken by minimally invasive methods (Damon, page 1881, lines 13-21).
It would have been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention to have modified the method of Pris by using a triangularly shaped paper substrate with the sum of the angles at the base is greater than 135 degrees, because of the teaching of Damon that the required sample volume is dependent on the paper shape and that the substrate as taught by Damon requires a sample of less than 1 μl, which can be obtained by minimally invasive measures.
One of ordinary skill in the art would have a reasonable expectation of success in using a hydrophobic surface where the sum of angles at which the first and second edges intersect is greater than 135 degrees as taught by Damon in the method of Pris, because both Pris and Damon teach a method of detecting a target in a sample by mass spectrometry wherein the capture antibody is immobilized on a cellulose substrate and Damon teaches success with the sum of angles greater than 135 degrees.
Regarding claim 38, Pris and the cited art above as applied to claim 1 also applies to claim 38.
Hari teaches applications of eosin Y as a visible light photocatalyst (Hari, page 6688, 2nd paragraph, lines 8-9).
Regarding claim 39, Pris and the cited art above as applied to claim 1, also applies to claim 39.
Hari teaches that triethanolamine was used as a sacrificial reducing agent for the efficient photocatalytic reduction of nitrobenzene (Hari, page 6689, ‘3.2. Reduction of nitrobenzene’, lines 1-6).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Pris et al., in view of Damon et al., Cao et al., Jia et al., Chen et al., and Hari et al. as applied to claim 14 above, and further in view of Murray et al. Improving the analytical performance and versatility of paper spray mass spectrometry via paper microfluidics; 2016 Analyst, 141 pages 4065-4073 (see PTO-892, 01/30/2024).
Regarding claim 15, Pris and the cited art above teach a method of detecting an analyte in a sample substantially as claimed.
Pris fails to teach a fluid-impermeable barrier permeating the thickness of the substrate defining a boundary of a reservoir region and a boundary of a channel region , which are in fluid communication with each other, where the channel region extends between second ends of the first and second edges and the reservoir, opposite of the first ends.
Chen teaches a wax printed paper substrate with matching hydrophilic channels (Chen, page 6358, lines 1-2).
Murray teaches paper spray mass spectrometry comprising patterning paper into regions of hydrophilic channels as defined by hydrophobic barriers, which allows precise fluid control via capillary action from sample loading to subsequent detection. Murray further teaches that this concentrates the analyte on paper which is essential for detection of low abundant analytes or analysis of volume limited samples (Murray, page 4065, 2nd column, lines 8-14). Murray further teaches that the optimal method for hydrophobic barrier fabrication for mass spectrometric detection is wax patterning which is relatively inexpensive using a commercially available wax printer and the capability to restrict radial dispersion of both the analyte deposition solvent and spray solvent significantly increases the sensitivity and detection time of the analyte (Murray, page 4066, see 3rd paragraph). Murray further teaches heating the was before creating barriers in order to spread the wax vertically to the opposite side (permeating a thickness of the substrate; Murray, page 4069, ‘Solvent containment and organic swell determination’, lines 3-6). Murray further teaches a sample loading circle (reservoir region) and an emitter channel (channel region; Murray, page 4067, ‘Concentration effect’, 2nd paragraph, lines 2-3). Murray further teaches that the reservoir and channel regions are in fluid communication and that the channel region extends between the second ends of the first and second edges and the reservoir (Murray; page 4070, see Figure 4B).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method of Pris and the cited art above by adding barriers to the paper spray substrate that permeate the thickness of the substrate and define the boundary of a reservoir and a channel region in fluid communication with each other and where the channel region extends between second ends of the first and second edges of the reservoir, opposite the first ends because of the teaching of Murray that the barriers restrict radial dispersion of the analyte deposition solvent and spray solvent, channels allow precise fluid control, concentrate the analyte on paper, and increases the sensitivity and detection time of the assay.
One of ordinary skill in the art would have a reasonable expectation of success, because both Chen and Murray teach the use of paper spray mass spectrometry to detect analytes in a sample.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Pris et al., in view of Damon et al., Cao et al., Jia et al., Chen et al., and Hari et al. as applied to claim 1 above, and further in view of Safazadeh et al. Photopatterning of stable, low-density, self-assembled monolayers on gold. Langmuir. 2015 Mar 10;31(9):2689-96.
Regarding claim 41, Pris and the cited art above teach a method of detecting an analyte in a sample substantially as claimed.
Pris fails to teach that the photoredox catalyst is conjugated to the gold nanoparticle via self-assembly chemistry.
Safazadeh teaches that self-assembled monolayers are organic assemblies formed by the adsorption of molecular species from solution onto the surface of solids and that the that the high affinity of alkanethiolates for gold surfaces, the inert properties of gold, the versatility of thiol chemistry make it possible to construct well-defined surfaces of numerous chemical functionalities. (Safazadeh, page 2689, see entire 1st paragraph). Safazadeh further teaches that patterned self-assembled monolayers provide well-characterized supports for physicochemical and biochemical processes. (Safazadeh, page 2695, lines 2-4). Safazadeh further teaches a system based on thiol-yne click chemistry that enables adsorbates of many functional groups (Safazadeh, page 2689, 3rd paragraph, lines 15-18). Safazadeh teaches preparing solid-phase low-density monolayers comprising gold substrates and eosin Y (Safazadeh, page 2690, ‘Monolayer Preparation, see entire paragraph). Safazadeh further teaches that the resulting monolayer provides high stability (Safazadeh, page 2690, 2nd paragraph, lines 1-8).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method of Pris and the cited art above by conjugating the photoredox catalyst to the gold nanoparticle via self-assembly chemistry as taught by Safazadeh because of the teaching of Safazadeh that the resulting self-assembled monolayer provides high stability.
One of ordinary skill in the art would have a reasonable expectation of success in doing so because of the teaching of success of Safazadeh of conjugating eosin Y to a gold nanoparticle by self-assembly chemistry.
Response to Arguments
Applicant's arguments filed 07/07/2026 have been fully considered but they are not persuasive.
Applicant argues, starting on page 4, that the amended claim 1 comprises the subject matter of claims 8 and 10 which were not rejected under 35 U.S.C. 103 over Pris, Damon, and Hari, and are therefore patentable.
The rejection of the claims under 35 U.S.C. 103 over Pris, Damon, and Hari has been withdrawn. See new grounds of rejection above.
Applicant further argues, starting on page 6, that the specification recites that many current blood tests are not sensitive enough for accurate diagnosis and that paper substrates can be deployed to detect the presence of an antigen using reporter antibodies which can generate or release a reporter compound that is easily detected. Applicant further argues that the present invention permits the detection of a small molecule of defined mass on portable mass spectrometers. Further, applicant argues, that the specification recites that because the sandwich immunoassay is analyzed using small molecule mass spectrometry, antigens can be detected at extremely low concentrations. Applicant further argues on page 7, reciting the specification, that redox chemistry can be employed for to amplify the signal by introducing a compound known to react when irradiated in the presence of the photocatalyst.
Applicant further recites from the specification that the paper surface can become a bioactive sensing device and that the claimed methods involve a three component photocatalytic system for mass spectrometry signal amplification, where the signal is amplified by both the gold nanoparticle and the catalytic effect of the photoredox catalyst.
In response to applicant's argument above, it is noted that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The combination of the prior teaches the limitations of the claims.
Applicant argues, page 7, that the tandem amplification strategy provides improved results for disease detection, which would have been unexpected even in view of Pris, Damon, Hari, Chen and Cao.
This argument is not persuasive.
The arguments of counsel cannot take the place of factually supported objective evidence. Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results.
In the instant case, the arguments of counsel do not constitute sufficient evidence of unexpected results, and Applicant has not provided factual evidence in which the claimed invention is compared with the closest prior art.
Furthermore, Applicant has not substantiated, through appropriate documentary evidence, that the improved results would have been unexpected by the ordinary artisan.
Applicant further argues on page 8 that the office is not considering the claimed invention as a whole and instead is considering each portion of the claim separately.
Applicant argue that the office relies on Pris, Damon, and Chen for their general description of paper substrates and sandwich assays and Hari for its description of Eosin Y as a photocatalyst. Applicant argues that nothing in Pris Damon, or Hari would suggest that such a combination would lead to an improved result by amplification in the mass spectrometry signal described by the applicant.
An improved result by amplification of the mass spectrometry signal is not a limitation of the claims and as such the argument is not commensurate with the claim.
Applicant further argues on page 8 that the office turns to Cao for the description of gold nanoparticles for signal amplification but that the combination fails to disclose or suggest the claimed methods involving a three component photocatalytic system for mass spectrometry signal amplification where the signal is amplified by both the gold nanoparticle and the catalytic effect of the photoredox catalyst and provides improved results for disease detection.
This argument is not persuasive.
The combination of the art does teach the claimed method of a mass spectrometry method comprising a gold nanoparticle conjugated to a photoredox particle and an antibody for the detection of an antigen in a sample as claimed.
As discussed previously above, an improved result by amplification of the mass spectrometry signal is not a limitation of the claims and as such the argument is not commensurate with the claim.
Applicant further argues that claim 15 is allowable because claims 1 and 14 are allowable over Pris, Damon, and Hari. However the rejection of claims 1 and 14 has been withdrawn, see new rejection of claim 15 over Pris et al., Damon et al., Cao et al., Jia et al., Chen et al., Hari et al. and Murray et al.
Communication
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/STEFANIE J. KIRWIN/Examiner, Art Unit 1677
/Soren Harward/Primary Examiner, TC 1600
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