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
The present application was filed 04/02/2023. The priority information to provisional application No. 63/004,221, filed on 04/02/2020 is acknowledged.
Claim Status
Claims 1-2, 4-13, 15-16, and 21 are pending. Claims 1-2, 12, and 15-16 are amended. Claims 3, 14, and 17-20 are cancelled. Claim 21 is new. Claims 1-2, 4-13, 15-16, and 21 are examined below.
Withdrawn Rejections
The rejection under 35 U.S.C. 112(b) has been withdrawn due to the amendment of claim 1.
Regarding the rejection under 35 U.S.C. 112(d), applicant’s arguments have been fully considered and are persuasive. The rejection of claim 2 under 35 U.S.C. 112(d) has been withdrawn.
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, 5-11 are rejected under 35 U.S.C. 103 as being unpatentable over Bell et al. USPGPUB 20190023984, filed 08/07/2018 (see PTO-892, 08/01/2023) in view of Kim et al. A two-colour multiplexed lateral flow immunoassay system to differentially detect human malaria species on a single test line. Malaria journal. 2019 Sep 18;18(1):313 (PTO-892, 10/01/2025) and Fujimoto, US20110217207A1, 09/08/2011 (PTO-892, 05/31/2024).
Regarding claim 1, Bell teaches a lateral flow device (Bell, page 1, paragraph [0004], line 11), comprising a nitrocellulose membrane on an adhesive backing (substrate), a sample pad on the proximal portion of the substrate, an absorbent pad located distally from the substrate pad, and a test line on the substrate pad configured to bind an analyte (Bell, sheet 7, Fig. 7A). Bell further teaches a detectable phosphor label (rare earth particle), conjugated to a capture molecule specific for an analyte (capable of conjugating to an analyte; Bell, page 3, paragraph [0033], lines 1-4). Bell further teaches rare earth crystalline phosphors that are monodisperse (pure), morphologically and size uniform (three dimensional size and polyhedral uniform) including phosphor compositions comprising a crystal lattice (Bell, page 3, see paragraph [0037]). Still further, Bell teaches that the rare earth crystals can be hexagonal or diamond shaped (polyhedral; Bell, page 3, paragraph [0036], lines 8-11). Bell further teaches detecting one or more analytes in a sample by contacting the sample with two or more types of phosphor particles, wherein each type of phosphor is conjugated to a specific capture molecule to separately label each analyte of interest and then detecting each labelled analyte by the unique optical lifetime signature of the corresponding phosphor (Bell, page 1, see paragraph [0009]). Bell further teaches that the detecting step can be performed in a single readout (Bell, page 1, paragraph [0010], lines 1-3). Bell further teaches two or more types of phosphor particles conjugated to capture molecules specific for each analyte and the phosphor particles conjugated to each type of capture molecules have unique and uniform morphology, size, and/or composition (Bell, page 4, paragraph [0050], lines 3-7). Bell further teaches detecting one or more analytes in a sample by capturing one or more analytes on an analyte specific capture molecule attached to a substrate, which comprises the test line, followed by detecting the sample with two or more types of phosphor particles (Bell, page 1, paragraph [0010], lines 4-7).
Bell does not clearly teach one test line comprising a single test line capable of binding two or more analytes. Bell further does not teach a conjugate release pad nor does Bell teach a separate information portion to encode information about the test strip. .
Kim teaches a quantitative multiplexing lateral flow immunoassay with one test line and one control line, the test line containing a mixture of antibodies specific for two different proteins, PfHRP2 and (pan)pLDH, respectively, and a control line comprising anti-mouse IgG antibody (Kim, page 2, 2nd column, 2nd paragraph, lines 1-9, and page 3, Fig. 1).
Kim, Fig. 1:
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Kim further teaches that the sample liquid is dispensed on a sample pad and flows to the conjugate pad, where blue and red latex particles capture pLDH and PfHRP2 antigens, respectively, and that the antigens bound to the latex particles are subsequently transported through the strip, and are detected at the test line where a mixture of detection antibodies to (pan)pLDH and PfHRP2 are functionalized (Kim, page 4, ‘Results’, lines 1-9). Kim further teaches that multiplexing in traditional lateral flow assays usually brings more test lines, which is confined to the spatial and physical limitation of the strip and this is further complicated by the uncertainty of changes when passing through multiple lines and that it is anticipated that the next generation of rapid diagnostic tests should have a multiplexing potential for detecting multiple biomarkers simultaneously, to provide patients with more health data (Kim, page 2, 2nd column, lines 5-12). Kim further teaches that this assay overcomes the physical limitations of traditional lateral flow assays (Kim, page 9, ‘Conclusion’, lines 14-17).
Fujimoto teaches an analysis tool having a reagent portion to be used for an analysis process and a separate identifying marker portion formed by using an invisible substance (Fujimoto, page 1, see paragraph [0008] and Figure 1, (103)). Fujimoto further teaches that the identifying marker portion is formed by using an invisible substance on the front surface. Fujimoto further teaches that the invisible substance is, for example a fluorescent ink, which may be an inorganic dye such as one based on rare earth (Fujimoto, page 5, see paragraph [0049]). Fujimoto further teaches that identification information about the analysis tool may be recorded on the identifying marker portion (Fujimoto, page 1, paragraph [0013], lines 1-3). Fujimoto further teaches that the analysis tool can be a test paper, a test strip or the like used to analyze urine, blood, or the like (Fujimoto, page 1, paragraph [0003]). Fujimoto further teaches an analysis apparatus comprising a light emitter emitting light and a light receiver receiving light emitted by the identifying marker portion (Fujimoto, page 3, paragraph [0024], lines 9-12). Fujimoto further teaches that it is not easy for a user to distinguish the regular analysis tool from any imitation or copy which is produced to have an appearance similar to that of the regular product, which can lower the reliability and miss the illness or disease of an examinee (Fujimoto, page 1, paragraph [0005], lines 6-20). Fujimoto further teaches that the analysis tool having an identifying marker portion makes it possible to easily judge whether or not an analysis tool is authentic (Fujimoto, page 1, see paragraph [0006]).
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 device of Bell, such that the test line is a singular test line that binds the two or more targets as taught by Kim in order to detect multiple biomarkers simultaneously to provide patients with more health data as taught by Kim. One of ordinary skill in the art would have been motivated to do so because Kim teaches that this modification overcomes disadvantages in traditional multiplexing in lateral flow assays where multiple test lines are confined to the spatial and physical limitation of the strip thus causing uncertainty of changes when sample passes through multiple lines, whereas the single test line assay overcomes these physical limitations.
The ordinary artisan would have a reasonable expectation of success, because both Bell and Kim teach a lateral flow device with all of the necessary reagents for performing an immunoassay. Adding antibodies specific for multiple analytes instead of a single analyte to the test line to capture multiple analytes would not change the principal of the assay taught by Bell comprising capturing analytes bound by labeled capture molecules on a test line.
It would have further 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 device of Bell to add a conjugate release pad such as taught by Kim, to Bell’s device (rather than providing conjugate solution separately, to be contacted with sample prior to addition to a test strip). One of ordinary skill in the art would be motivated to modify as such for the advantage of a simple, convenient, one-step assay to detect analytes with reasonable sensitivity.
The ordinary artisan would have a reasonable expectation of success in modifying the device of Bell to include all necessary pads including a conjugate pad and a single test line as taught by Kim because both Bell and Kim teach a lateral flow device with various zones for detection of analytes.
It would have further been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device taught by Bell and the prior art with the identifying marker portion of Fujimoto (namely to include the rare-earth particles providing information about the test strip), because of the teaching of Fujimoto that the identifying marker makes it possible to judge whether or not an analysis tool is authentic and therefore reliable.
The ordinary artisan would have a reasonable expectation of success, because Bell teaches a nitrocellulose (paper) test strip with a sample pad and Fujimoto similarly teaches that the device labeled with the identifying marker can be a test paper or strip comprising a sample pad for examining liquid samples.
Regarding claims 5 and 6, Bell and the cited art above teach a rapid diagnostic test strip substantially as claimed.
Bell further teaches rare earth crystalline phosphors , comprising nanocrystals that phosphor particles, in particular upconverting phosphor particles can be formed into materials with an infinite amount of distinct signatures, such as absorption and emission (Bell, page 3, paragraph [0036], lines 1-6) and further teaches using two or more types of phosphor particles to detect an analyte, wherein each type of phosphor is conjugated to a capture molecule (Bell, page 1, paragraph [0009], lines 3-6). As such, the device as taught by Bell comprises at least two conjugated materials that can absorb at least one different wavelength from at least one other conjugate.
Regarding claim 7, Bell teaches a lateral flow device with a control line distant from the test line (Bell et al., sheet 7, figure 7A).
Regarding claim 8, Bell teaches a rapid diagnostic test strip substantially as claimed.
Bell teaches a device comprising a sample pad, followed by a substrate, comprising the test and control line on top of the substrate, and further followed by an absorbent pad (Bell, sheet 7, Figure 7A).
Bell does not teach a conjugate release pad.
As discussed previously in detail above, Kim teaches a lateral flow assay comprising a conjugate release pad where the sample liquid is dispensed on a sample pad and flows to the conjugate pad and antigens bound to the latex particles deposited in the conjugate pad are subsequently transported through the strip, and are detected at the test line where a mixture of detection antibodies are functionalized (Kim, page 4, ‘Results’, lines 1-9).
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 device of Bell with the conjugate release pad of Kim for the same reasons as applied to claim 1, the same reason also applies to claim 8.
It would have further been prima facie obvious to locate the test line between the conjugate release pad and the absorbent pad as taught by Kim to the device of Bell because it allows the analyte to be bound by the labeled capture molecules before the labeled analyte complex is bound by the analyte specific antibodies at the test line, in order to visualize if analyte is present in the sample.
Regarding claim 9, Bell and the cited art above teaches a device substantially as claimed.
Bell teaches that one can combine known emission wavelengths, intensity amplitudes and lifetimes for detectable labels which may be used in a multiplexed assay to detect a single sample or substrate (Bell, page 4, paragraph [0042].
Bell fails to teach rare-earth particles attached to the top of the diagnostic pad relating emission profiles to information about the test strip.
Fujimoto teaches an analysis tool having a reagent portion to be used for an analysis process and an identifying marker portion formed by using an invisible substance (Fujimoto, page 1, see paragraph [0008]). Fujimoto further teaches that the identifying marker portion is formed by using an invisible substance on the front surface. Fujimoto further teaches that the invisible substance is, for example a fluorescent ink, which may be an inorganic dye such as one based on rare earth. Fujimoto further teaches that the fluorescent dye may be a known single fluorescent dye or a mixture of two or more types of fluorescent dyes (Fujimoto, page 5, see paragraph [0049] and Figure 1, (103)). Fujimoto further teaches that identification information about the analysis tool may be recorded on the identifying marker portion (Fujimoto, page 1, paragraph [0013], lines 1-3). Fujimoto further teaches that the analysis tool can be a test paper, a test strip or the like used to analyze urine, blood, or the like (Fujimoto, page 1, paragraph [0003]) and that method performed on the analysis tool such that color development is brought about when a reagent portion (reagent pad or the like) containing a reagent to cause a reaction with the sample is impregnated with the sample and optically observed (Fujimoto, page 1, paragraph [0004]). Fujimoto further teaches an analysis apparatus comprising a light emitter emitting light and a light receiver receiving light emitted by the identifying marker portion (Fujimoto, page 3, paragraph [0024], lines 9-12). Fujimoto further teaches that it is not easy for a user to distinguish the regular analysis tool from any imitation or copy which is produced to have an appearance similar to that of the regular product, which can lower the reliability and miss the illness or disease of an examinee (Fujimoto, page 1, paragraph [0005], lines 6-20). Fujimoto further teaches that the analysis tool having an identifying marker portion makes it possible to easily judge whether or not an analysis tool is authentic (Fujimoto, page 1, see paragraph [0006]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device taught by Bell with the identifying marker portion of Fujimoto (namely to include the rare-earth particles attached to the top of the diagnostic pad relating emission profiles to information about the test strip), because of the teaching of Fujimoto that the identifying marker makes it possible to judge whether or not an analysis tool is authentic and therefore reliable.
The ordinary artisan would have a reasonable expectation of success, because Bell teaches a nitrocellulose (paper) test strip with a sample pad and Fujimoto similarly teaches that the device labeled with the identifying marker can be a test paper or strip comprising a sample pad for examining liquid samples.
Regarding claim 10, Bell teaches that the phosphor particles have unique and uniform morphology, size, and/or composition and produce a unique optical lifetime signature (Bell, page 4, paragraph [0044], lines 12-15).
Regarding claim 11, Bell and the cited art above teaches a device substantially as claimed.
Bell fails to teach information about the test strip comprising the type of analytes, a date, or a combination thereof.
Fujimoto teaches that the information about the analysis tool is used to identify the tool to be used for an analysis apparatus. Fujimoto further teaches that the information may include product specification information such as the type of measuring component (analyte; Fujimoto, page 1, see paragraph [0013]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device taught by Bell with the identifying marker portion of Fujimoto, comprising information about the type of measuring component (i.e., about what analytes the device is configured to assay) in order for the analysis apparatus to be able to identify the analysis tool and provide information about the type of analyte that is measured.
The ordinary artisan has a reasonable expectation of success, for the same reasons as discussed in claim 9, the same reasoning applies here.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Bell, in view of Kim and Fujimoto et al. as applied to claim 1 above, and further in view of Bobosha et al. (2014) “Field-Evaluation of a New Lateral Flow Assay for Detection of Cellular and Humoral Immunity against Mycobacterium leprae”, PLOS Neglected Tropical Diseases, 8, 5, pages 1-12 (see PTO-892, 08/01/2023).
Regarding claim 2, Bell and the cited art above teach a rapid diagnostic test strip substantially as claimed. Bell further teaches that a capture molecule such as an antibody or a protein specific for the analyte is conjugated to the detectable phosphor labels and can be detected in various assay formats (Bell, page 3, paragraph [0033], lines 1-3).
Bell differs from the claimed invention in that, even though Bell teaches capturing and detecting analytes, comprising proteins and viruses (Bell, page 1, paragraph [0003], lines 3-4), for example using phosphor labeled protein-A as the capture agent to detect human antibodies using a lateral flow device (Bell, page 5, paragraph [0065], lines 5-8), the device is not configured to specifically detect coronavirus or influenza antigen, antibody subtypes, or cytokines.
Bobosha teaches a multiplex lateral flow assay for simultaneous detection of IP-10 and anti-PGL-1 antibodies using reporter technology comprising phosphor (Bobosha, page 1, Abstract, see methods). Bobosha further teaches using anti-IP10, anti-IL-10 anti-IFNγ antibody, as well as anti-human IgM or IgG/IgM/IgA antibody phosphor-conjugates. Bobosha further teaches that leprosy is a curable infectious disease that the WHO considers one of the six diseases that are a major threat to developing countries (Bobosha, page 1, ‘Introduction’, lines 1-4) and that in leprosy the innate and adaptive immune response to M.leprae matches the clinical manifestations, therefore field-applicable tests should allow simultaneously detection of biomarkers for humoral as well as cellular immunity (Bobosha, page 2, see 2nd paragraph).
It would have been prima facie obvious to one having ordinary skill at the time the claimed invention was effectively filed to have modified the device of Bell with the cytokine and/or antibody subtype specific antibodies of Bobosha, to detect cytokines and/or antibody subtypes. The ordinary artisan would have been motivated to do so, because of the teaching of Bobosha, namely to detect biomarkers for humoral as well as cellular immune response. Specifically, it would be obvious to modify the device of Bell, in order to include the cytokine specific antibodies, as an obvious matter of a simple substitution of one capture agent over another. One of ordinary skill in the art would have found it obvious to substitute one for the other, in order to specifically capture and detect cytokines and antibody subtypes, to detect biomarker for humoral and cellular immune response.
The ordinarily skilled artisan would have a reasonable expectation of success, because both Bell and Bobosha teach a diagnostic test strip using reporter technology comprising phosphor.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Bell, in view of Kim and Fujimoto et al. as applied to claim 1 above, and further in view of Pawlak et al., US5766961A, 06/16/1998 (see PTO-892, 08/01/2023).
Regarding claim 4, Bell and the cited art above teach a rapid diagnostic test strip substantially as claimed. The combined art further teaches a conjugate release pad, where the analyte binds to the capture agent. While Bell does teach a flow control line comprising Protein A, Bell and the cited art above does not specifically teach a test strip comprising a control material that is disposed in the conjugate release pad.
Pawlak discloses a one-step lateral flow assay comprising a sample receiving zone, a labelling zone, a capture zone and a control zone. Pawlak teaches an assay label comprising visible moieties which are coupled to specific binding reagent for analyte. Pawlak further teaches that the visible moieties to which analytes are bound are captured in the capture zone. Control label comprising visible moieties, distinguishable from those of the assay label, may also be included in the labeling zone (i.e. conjugate area) and captured in a separate control portion of the capture zone to verify that the flow of liquid is as expected (See Abstract). Pawlak further teaches that the visible moieties can be dyes, dyed latex beads, metallic, organic, inorganic, or dye sols and the like (Pawlak, column 4, lines 44-49).
It would have been prima facie obvious to one having ordinary skill at the time the claimed invention was effectively filed, to have modified the device of Bell to include a control label as taught by Pawlak because of the teaching of Pawlak that it is advantageous to have a separate control material to verity that the flow of liquid is as expected.
The ordinarily skilled artisan would have a reasonable expectation of success having modified the assay of Bell with control label as taught by Pawlak because Bell teaches the use of two or more types of phosphor articles in a lateral flow assay and Pawlak teaches a similar lateral flow assay and one would therefore expect success using one of the one or more phosphor articles as a control as taught by Pawlak.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Bell, in view of Kim and Fujimoto et al. as applied to claim 1 above, and further in view of Xie et al., US11397181B2.
Regarding claim 12, Bell and the cited art above teaches a lateral flow strip comprising an information portion substantially as claimed and a lateral flow strip reader (Bell et al., page 2, paragraph [0029], lines 2-3, and Figure 12).
Bell fails to teach a reader configured to illuminate the information portion of the test strip, compare the response to a database and determine assay validity based on that information.
Xie teaches a lateral flow assay reader device having a barcode scanning input device that reduces errors compared to manual data entry (Xie, Abstract, lines 1-6). Xie further teaches an assay reader device that is simple and reliable by including a module for simple barcode scan input of any needed additional information and by minimizing the number of steps required for the user between sample application and result notification. Xie teaches an assay reader device that includes a module providing network connectivity capabilities for providing test results to one or more centralized databases. Xie further teaches that the barcode scan input can provide a high level of traceability and compliance by allowing laboratories to implement custom test result documentation standards and that communications between the reader and a database can be used to ascertain whether transmitted test data complies with such standards (Xie, column 1, line 52- column 2, line 9). Xie further teaches circuitry for reading information from an information element of an inserted module and transferring that information to a processor for analysis or validation (Xie, column 17, lines 57-60).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the lateral flow assay system comprising a lateral flow assay comprising an information portion as taught by Bell and the cited art above as well as a reader device, with the lateral flow assay reader device of Xie comprising a module for simple input of an information element including a module for communicating with a database to ascertain that test data complies with standards and for validation because of the teaching of Xie that this minimizes the number of steps required and makes the assay reader simple and reliable. One of ordinary skill in the art would have been motivated to do so because of the teaching of Xie that the barcode (information portion) and connectivity to a database allows for test result documentation standards to be implemented and can be used to ascertain whether test data complies with such standards.
One of ordinary skill in the art would have a reasonable expectation of success because Bell teaches a lateral flow device comprising detectable rare earth particles and a reader capable of detecting said particles, Fujimoto teaches an information portion on a lateral flow device comprising information about the lateral flow device, and Xie similarly teaches a reader for a lateral flow device that comprises an information portion, i.e. a barcode. As such, one of ordinary skill in the art would have a reasonable expectation of success in modifying the lateral flow assay reader device of Bell to also read a rare earth particle labeled information portion of the lateral flow device and communicate with a database in order to validate the assay as taught by Xie.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Bell, in view of Kim, Fujimoto, and Xie as applied to claim 12 above, and further in view of Mokkapati (see PTO-892, 08/01/2023).
Regarding claim 13, Bell et al. and the cited art above teach a device substantially as claimed.
Bell teaches a modified Fluoro-Count Packard benchtop reader for scanning LF strips (Bell, page 5, paragraph[0063], lines 18-21). Bell further teaches that in the multiplex assay, the phosphor particles conjugated to each type of capture molecule have unique and uniform morphology, size, and/or composition producing a unique optical lifetime signature (Bell, page 4, paragraph [0044], lines 11-15). Bell further teaches rare earth crystalline phosphors comprising nanocrystals, phosphor particles, in particular upconverting phosphor particles that can be formed into materials with an infinite number of distinct signatures, such as absorption and emission (Bell, page 3, paragraph [0036], lines 1-6). Bell further teaches that the lifetimes of the phosphor particles can be precisely tuned for each emitted wavelength of the particle determined by the particle morphology and composition, for example in Figure 1 a spherical and a hexagonal particle possess identical compositions, but have different morphologies yielding a unique lifetime signature (Bell, page 4, see entire paragraph [0042]). Put another way, the unique lifetime signature (temporal response) can be used to distinguish between different morphologies (shape) of the particles.
Bell does not teach a reader containing a processor configured to cause the reader to emit at least one wavelength of light that a rare earth particle is capable of absorbing, detect an emission profile of the rare-earth particle in response to the at least one wavelength of light after at least one wavelength of light no longer being emitted, determine if a parameter of the emission profile is above a predetermined threshold, determine a temporal response of the rare earth particle based on the emission profile and provide a test result based on the temporal response.
Mokkapati describes a portable reader with a built-in infrared laser and disposable cassettes containing lateral flow strips with phosphor technology. Mokkapati further teaches that the reader scans the strips and displays the results such that subjective interpretation is eliminated Mokkapati, page 477, 3rd paragraph, lines 8-12). Mokkapati further teaches that the analyzer is a reader with integrated software (reader contains a processor; Mokkapati, page 478, ‘Uplink Platform-Detection of UPT Reporters’, lines 6-7). Mokkapati further teaches the IR laser interrogates UPT-deposited lateral flow strips (emit at least one wavelength that […] a rare-earth particle […] is capable of absorbing (Mokkapati, page 478, ‘Uplink Platform-Detection of UPT Reporters’, lines 3-4). Mokkapati further teaches an emission profile (allow the reader to detect an emission profile) and teaches a display that shows a negative control, a positive result, and a negative result (Mokkapati, page 479, Figure 1 D). Mokkapati further teaches that all specimen signals above a predetermined cut-off value were considered positive (Mokkapati, page 480, lines 9-11). Mokkapati further teaches that the reader is fully automated, inexpensive and portable developed for on-site and POC testing (Mokkapati, page 483, ‘Discussion’, lines 5-7).
Mokkapati does not teach a processor configured to allow the reader to detect an emission profile […] after at least one wavelength of light is no longer being emitted, nor does it teach determining a temporal response. However, Mokkapati teaches a device with software programmed to scan the strips and measure fluorescence (see above) and as such, would be capable to be programmed to determine a temporal response.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the system as taught by Bell to replace the reader of Bell with the reader as taught by Mokkapati, because the reader is fully automated, inexpensive, and portable and eliminates subjective interpretation. It would have further been obvious to program the reader to detect an emission profile after at least one wavelength of light is no longer being emitted and to determine the temporal response, because of the teaching of Bell that the unique optical lifetime signature of each rare earth particle is used for multiplexing.
The ordinary artisan would have a reasonable expectation of success because Mokkapati teaches success using a reader device to read a lateral flow assay using phosphor labeling and Bell also teaches success using a reader to read a lateral flow assay using phosphor labeling.
Claims 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Bell, in view of Kim, Fujimoto, and Xie as applied to claim 12 above and further in view of Bobosha.
Regarding claims 15 and 16, Bell and the cited art above teach a rapid diagnostic test strip substantially as claimed. Bell further teaches that a capture molecule such as an antibody or a protein specific for the analyte is conjugated to the detectable phosphor labels and can be detected in various assay formats (Bell et al., page 3, paragraph [0033], lines 1-3).
Bell differs from the claimed invention in that, even though Bell teaches capturing and detecting analytes, comprising proteins and viruses (Bell, page 1, paragraph [0003], lines 3-4), for example using phosphor labeled protein-A as the capture agent to detect human antibodies using a lateral flow device (Bell, page 5, paragraph [0065], lines 5-8), the device is not configured to specifically detect antibody subtypes, or cytokines.
As discussed previously in detail above (see rejection of claim 2), Bobosha teaches a multiplex lateral flow assay for simultaneous detection of IP-10 and anti-PGL-1 antibodies using reporter technology comprising phosphor (Bobosha, page 1, Abstract, see methods). Bobosha further teaches using anti-cytokine antibody, as well as anti-human IgM or IgG/IgM/IgA antibody phosphor-conjugates (Bobosha, page 3, ‘Upconverting phosphor (UCP) conjugates and LF strips’, lines 1-16). Bobosha further teaches field-applicable tests should allow simultaneously detection of biomarkers for humoral as well as cellular immunity (Bobosha, page 2, see 2nd paragraph).
It would have been prima facie obvious to one having ordinary skill in the art at the time the claimed invention was effectively filed, to have modified the device of Bell with the cytokine and/or antibody subtype specific antibodies of Bobosha, to detect cytokines and/or antibody subtypes. The ordinary artisan would have been motivated to do so, because of the teaching of Bobosha, namely to detect biomarkers for humoral as well as cellular immune response.
Specifically, it would be obvious to have modified the device of Bell, in order to include the cytokine specific antibodies, as an obvious matter of a simple substitution of one capture agent over another. One of ordinary skill in the art would have found it obvious to substitute one for the other, in order to specifically capture and detect cytokines and antibody subtypes, to detect biomarker for humoral and cellular immune response.
The ordinarily skilled artisan would have a reasonable expectation of success, because both Bell and Bobosha teach a diagnostic test strip using reporter technology comprising phosphor.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Bell, in view of Kim and Fujimoto as applied to claim 1 above, and further in view of Zorner et al., US20200102602A1.
Regarding claim 21, Bell and the cited art above teach a rapid diagnostic test strip substantially as claimed.
Bell further teaches that the lifetimes of phosphor particles can be precisely tuned for each emitted wavelength of the particle determined by the particle morphology and composition yielding a unique lifetime signature (Bell, page 4, see entire paragraph [0042]).
Bell does not teach that the temporal variable comprises rise time and/or decay time.
Zorner teaches a lateral flow assay format where nanocrystals in the detectable label may be an upconverting phosphor particle and a detection device detecting the up-converting phosphor wavelength or the phosphor lifetime signature assay for multiplexed detection of analytes using nanocrystals (Zorner, page 2, see paragraph [0026]). Zorner further teaches that optical lifetime signatures comprise the rise and decay times (Zorner, page 2, paragraph [0016], line 6). Zorner further teaches that monodisperse particles are varied in composition and/or shape give different decay lifetimes and having different decay lifetimes allows unique phosphor particles to be differentiated from one another. Zorner further teaches that the ability to have monodisperse particles of the same composition but different morphologies permits the use of one composition (especially in regulated industries such as pharmaceuticals or medical devices) but to distinguish its morphologies through their unique optical properties (Zorner, page 6, see entire paragraph [0085]).
It would have been prima facie obvious to one having ordinary skill in the art at the time the claimed invention was effectively filed, to have applied the device of Bell to measure a temporal emission profile comprising the decay lifetime of the monodisperse particles because of the teaching of Zorner that this allows the use of one composition with multiple morphologies especially in regulated industries such as the pharmaceutical and medical device industries.
One of ordinary skill in the art would have a reasonable expectation of success because Bell teaches a system capable of measuring a phosphor lifetime signature the same measurement as used in the lateral flow assay system used by Zorner.
Response to Arguments
Applicant’s arguments, see page 8, line 5- page 9, line 3, filed 01/30/2026, with respect to amended claim 1 have been fully considered and are persuasive. The rejection of claim 1 has been withdrawn.
See new rejection under 35 U.S.C. §103 above.
Applicant argues, starting on page 9, that the cited references do not teach or suggest a validation mechanism that relies on a separate encoded phosphor region and reader logic/database comparison to confirm validity as claimed in claim 12.
This argument is not persuasive.
The combination of the prior art (as applied to the amended claims) does teach a separate information portion on a lateral flow device (comprising information about the analysis tool) that can be printed using ink based on rare earth materials, as taught by Fujimoto. Xie teaches a lateral flow assay system that uses information printed on the test strip to compare to data in a centralized database that can be used to ascertain whether transmitted test data complies with certain standards. As such the combination of the art teaches a system comprising an information portion on the strip that comprises rare earth materials and can be used to validate the lateral flow test strip.
Applicant further argues (page 9) that the limitations of new claim 21, comprising identification and analysis based on temporal variables in emission profiled, including rise time and decay times and comparison of those variables against a database reinforces that the invention is not merely “fluorescent labeling” but rather a database-driven, time-resolved multiplexing platform.
This argument is not persuasive.
As explained in detail previously above, the combination of the prior art teaches a database driven, time-resolved multiplexing platform.
Further, claim 21 depends on claim 1 which is not limited to a system comprising the comparison of the response to a database and therefore the argument is not commensurate with the claim.
For all the reasons above the arguments are not persuasive.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Communication
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/STEFANIE J. KIRWIN/Examiner, Art Unit 1677
/Soren Harward/Primary Examiner, TC 1600
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