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 .
Response to Amendment
The Amendment filed 01/23/2026 has been entered. Claims 1-19 remain pending in the application. Claims 9-19 are withdrawn. Applicant’s amendments to the claims have overcome each and every objection and 112(b) rejections previously set forth in the Non-Final Office Action mailed 10/23/2025.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 1, 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (LI Z. et al., "Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis," J. Med Virol., 92(9): 1518-1524 (2020); cited in the IDS filed 11/02/2022) in view of Skraba et al. (US 20200241010 A1; filed 04/13/2020).
Regarding claim 1, Li teaches a diagnostic device (Figs. 1-2; abstract) for detecting a first member of a reporter-analyte pair or a first member of each of a plurality of reporter-analyte pairs (abstract teaches a lateral flow immunoassay that can detect IgM and IgG via SARS-CoV-2 antigen labeled gold colorimetric reagent, i.e. first member of a reporter-analyte pair) comprising:
an inlet for receiving a liquid, biological sample (Fig. 2 shows an inlet, i.e. bottom ports, for receiving a liquid biological sample); and
a porous membrane element (Fig. 1, nitrocellulose membrane) comprising a detection portion (Fig. 1, interpreted as the portion comprising the M and G lines), the detection portion being in liquid communication with the inlet (Figs. 1-2) and a second member of the or each reporter-analyte pair being immobilisable on the detection portion (Fig. 1, IgM and IgG antibodies immobilisable on the M and G lines respectively),
wherein one of the first or second member of the reporter-analyte pair or each of the plurality of the reporter-analyte pairs comprises a biological antigen (Fig. 1, covid-19 antigen of the gold covid-19 antigen conjugate, i.e. first member) and the other of the first or second member of the reporter-analyte pair or each of the reporter-analyte pairs comprises an antibody specific for the biological antigen (Fig. 1, shows antibodies for covid-19 IgM and IgG, i.e. second member), and wherein
i) the biological antigen comprises:
(a) a COVID-19 S1 spike protein or a fragment thereof (section 2.1 teaches a recombinant antigen that is a receptor binding domain of SARS-CoV-2 Spike protein is used); and/or
(b) a first biological antigen from a first reporter-analyte pair comprising a COVID-19 S1 spike protein or a fragment thereof (section 2.1 teaches a recombinant antigen that is a receptor binding domain of SARS-CoV-2 Spike protein is used), or
ii) the biological antigen comprises a COVID-19 S1 spike protein or a fragment thereof (section 2.1 teaches a recombinant antigen that is a receptor binding domain of SARS-CoV-2 Spike protein is used).
Li fails to teach:
i) the biological antigen comprises:
(a) a COVID-19 S1 spike protein comprising the sequence of SEQ ID NO: 4 or a sequence having at least 99% or 100% sequence identity to the sequence of SEQ ID NO: 4; and/or
(b) the first biological antigen from the first reporter-analyte pair comprising a COVID-19 S1 spike protein or a fragment thereof, and a second biological antigen from a second reporter-analyte pair comprising a COVID-19 S2 spike protein or a fragment thereof,
and wherein the device is for independent detection of a spike protein, or a fragment thereof, or of an antibody specific for a spike protein, or a fragment thereof, in the biological sample, or
ii) the biological antigen comprises a COVID-19 S1 spike protein or a fragment thereof comprising a sequence in which one or more amino acids are substituted in a sequence consisting of the N-terminal 100, 200, 300, 400, 500 or 600 amino acids of the sequence of SEQ ID NO: 4, and wherein the device is for independent detection of the COVID-19 S1 spike protein, or the fragment thereof, in which one or more amino acids has been substituted, or of an antibody specific for the COVID-19 S1 spike protein, or the fragment thereof, in which one or more amino acids has been substituted, in the biological sample.
Skraba teaches methods and kits for sampling mucous to determine if a sample includes bacterial types and viruses (abstract), such as for SARS-CoV-2 (paragraph [0008]). Skraba teaches the assays can include any antigen binding agents that bind antigens specific to each type of bacteria and viruses (paragraph [0191]), and pairs or pools of antibodies may be chosen to have low cross-reactivity, while allowing comparable detection of the bacterium/bacteria and/or virus(es); and a pair or pool of antibodies specific to one or more antigen binding agents can be relatively specific or characteristic of a bacteria or virus (paragraph [0191]). Skraba teaches the binding agent includes a binding agent for SARS-CoV-2 that may bind with Spike antigen binding site, such as S1, S2 subunits (paragraph [0191]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biological antigen of Li to incorporate the teachings of assays to detect viruses using binding agents for SARS-CoV-2, such as binding agents for S1 and S2 spike proteins (paragraph [0191]) to provide: i) the biological antigen comprises: (b) the first biological antigen from the first reporter-analyte pair comprising a COVID-19 S1 spike protein or a fragment thereof, and a second biological antigen from a second reporter-analyte pair comprising a COVID-19 S2 spike protein or a fragment thereof, and wherein the device is for independent detection of a spike protein, or a fragment thereof, or of an antibody specific for a spike protein, or a fragment thereof, in the biological sample. Doing so would have a reasonable expectation of successfully improving detection of viruses, i.e. COVID-19, and binding sites of desired viruses, such as the S1 and S2 subunits of SARS-CoV-2.
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the first biological antigen from the first reporter-analyte pair comprising a COVID-19 S1 spike protein or a fragment thereof, and a second biological antigen from a second reporter-analyte pair comprising a COVID-19 S2 spike protein or a fragment thereof) by known methods with no change in their respective functions (i.e. detection of COVID-19 S1 and S2 spike proteins), and the combinations yielded nothing more than predictable results (i.e. providing the claimed first and second biological antigens would yield nothing more than the obvious and predictable result of enabling improved detection of COVID-19 proteins). See MPEP 2143(A).
Regarding claim 6, modified Li fails to teach wherein the biological antigen further comprises a third biological antigen from a third reporter-analyte pair and wherein the third biological antigen comprises a COVID-19 nucleoprotein or a fragment thereof.
Skraba teaches a cartridge may comprise a plurality (e.g., 3) of solid phase substrates, wherein each solid phase substrate holds one of the first bacterial-binding agent, the second bacterial-binding agent or the third bacterial-binding agent (paragraph [0018]). Skraba teaches testing for the presence of two types of viruses and three different types of bacteria in parallel (paragraph [0193]). Skraba teaches the assays can include any antigen binding agents that bind antigens specific to each type of bacteria and viruses (paragraph [0191]), and pairs or pools of antibodies may be chosen to have low cross-reactivity, while allowing comparable detection of the bacterium/bacteria and/or virus(es); and a pair or pool of antibodies specific to one or more antigen binding agents can be relatively specific or characteristic of a bacteria or virus (paragraph [0191]). Skraba teaches the binding agent includes a binding agent for SARS-CoV-2 that may bind with a nucleoprotein and/or Spike (S1, S2, or RBD subunits) antigen binding site of coronavirus (e.g. SARS-CoV, MERS-CoV, or SARS-CoV-2) (paragraph [0191]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the biological antigen of modified Li to incorporate the teachings of detecting multiple antigens, such as a nucleoprotein and Spike subunits of SARS-CoV-2 of Skraba (paragraphs [0018],[0191],[0193]) to provide: wherein the biological antigen further comprises a third biological antigen from a third reporter-analyte pair and wherein the third biological antigen comprises a COVID-19 nucleoprotein or a fragment thereof. Doing so would have a reasonable expectation of successfully improving detection of components of desired viruses, such as the nucleoprotein of SARS-CoV-2.
Regarding claim 8, modified Li fails to teach wherein the second member of the reporter-analyte pair or each of the reporter-analyte pairs is immobilised on the detection portion.
Li teaches antigens of reporter-analyte pairs are immobilized on the detection portions (Fig. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second member of the or each reporter-analyte pair of modified Li to incorporate the teachings of immobilizing antigens of Li (Fig. 1) to provide: wherein the second member of the reporter-analyte pair or each of the reporter-analyte pairs is immobilised on the detection portion. Doing so would have a reasonable expectation of successfully improving positioning of the second member to allow for detection of the analyte in relation to the second member.
Claims 2 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Skraba as applied to claim 1 above, and further in view of Ji (US 20230168245 A1; effectively filed 04/24/2020).
Regarding claim 2, while Li teaches a recombinant antigen that is a receptor binding domain of SARS-CoV-2 Spike protein is used (section 2.1), modified Li fails to teach: wherein the first biological antigen comprising the COVID-19 S1 spike protein or the fragment thereof is a polypeptide comprising a sequence of at least 8, 10, 12, 14, 16, 18, 20, 30, 100, 200 or 300 amino acids from an amino acid sequence having at least 70%, 80%, 90%, 95%, 99% or 100% sequence identity to the sequence of SEQ ID NO: 4, optionally wherein the COVID-19 S1 spike protein or the fragment thereof comprises the COVID-19 S1 spike protein receptor binding domain having the sequence of SEQ ID NO: 3.
Ji teaches a lateral flow device for detecting COVID-19 (abstract), such as detecting the presence of IgG anti-S1 spike antibodies, IgM anti-S1 antibodies, and neutralizing antibodies (e.g., both IgM and IgG) that block binding between ACE2 antigen and S1 spike protein (paragraph [0003]). Ji teaches the lateral flow device or kit, wherein the coronavirus S1 spike polypeptide in the plurality of detectably labeled coronavirus S1 spike polypeptide conjugates comprises S1 spike polypeptide from SARS-CoV-2 and having the amino acid sequence of SEQ ID NO: 3-4 (paragraph [0010] and Fig. 10 teaches SEQ ID NO: 2, which comprises the instant application’s SEQ ID NO: 3 and 4). Ji teaches in one embodiment, the immobilized ACE2 receptor capture polypeptide binds the receptor binding domain (RBD) on an S1 spike polypeptide from a SARS-CoV-2 virus, where the S1 spike polypeptide comprises the amino acid sequence of SEQ ID Nos: 3-4 (paragraph [0164] and Fig. 10 teaches SEQ ID NO: 2, which comprises the instant application’s SEQ ID NO: 3 and 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first biological antigen of modified Li to incorporate the teachings of known sequences of SARS-Cov-2 spike S1 subunits of Ji (Fig. 10; paragraphs [0010],[0164]) to provide: wherein the first biological antigen comprising the COVID-19 S1 spike protein or the fragment thereof is a polypeptide comprising a sequence of at least 8, 10, 12, 14, 16, 18, 20, 30, 100, 200 or 300 amino acids from an amino acid sequence having at least 70%, 80%, 90%, 95%, 99% or 100% sequence identity to the sequence of SEQ ID NO: 4, optionally wherein the COVID-19 S1 spike protein or the fragment thereof comprises the COVID-19 S1 spike protein receptor binding domain having the sequence of SEQ ID NO: 3. Doing so would have a reasonable expectation of successfully improving specificity of antigen-antibody detection of a sequence of the desired COVID-19 S1 spike protein.
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the first biological antigen comprising the claimed SEQ ID: 3 or 4) by known methods with no change in their respective functions (i.e. detection of COVID-19 components), and the combinations yielded nothing more than predictable results (i.e. providing the first biological antigen comprising the claimed SEQ ID: 3 or 4 would yield nothing more than the obvious and predictable result of enabling improved detection of COVID-19 proteins). See MPEP 2143(A).
Regarding claim 5, modified Li fails to teach wherein the COVID- 19 S1 spike protein or the fragment thereof and the COVID-19 S2 spike protein or the fragment thereof are comprised within a single polypeptide chain, the single polypeptide chain being immobilisable on the detection portion.
Ji teaches a lateral flow device for detecting COVID-19 (abstract), such as detecting the presence of IgG anti-S1 spike antibodies, IgM anti-S1 antibodies, and neutralizing antibodies (e.g., both IgM and IgG) that block binding between ACE2 antigen and S1 spike protein (paragraph [0003]). Ji teaches the lateral flow device or kit, wherein the coronavirus S1 spike polypeptide in the plurality of detectably labeled coronavirus S1 spike polypeptide conjugates comprises S1 spike polypeptide from SARS-CoV-2 and having the amino acid sequence of SEQ ID NO: 3-4 (paragraph [0010], SEQ ID NO:2 also shown in Fig. 10 is equivalent to the instant application’s SEQ ID NO: 3 and 4). Ji teaches in one embodiment, the immobilized ACE2 receptor capture polypeptide binds the receptor binding domain (RBD) on an S1 spike polypeptide from a SARS-CoV-2 virus, where the S1 spike polypeptide comprises the amino acid sequence of SEQ ID Nos: 3-4 (paragraph [0164], SEQ ID NO:2 also shown in Fig. 10 is equivalent to the instant application’s SEQ ID NO: 3 and 4). Ji teaches a synthetic antigen binding protein can comprise antibody fragments, 1-6 or more polypeptide chains, asymmetrical assemblies of polypeptides, or other synthetic molecules (paragraph [0082]). Ji teaches single-chain antibodies and single chain fragments (paragraphs [0086]-[0087]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the COVID- 19 S1 spike protein or the fragment thereof and the COVID-19 S2 spike protein or the fragment thereof of modified Li to incorporate the teachings of a lateral flow device for COVID-19 and single polypeptide chains or single chain antibodies or fragments of Ji (paragraphs [0082],[0086],[0087]) to provide: the COVID- 19 S1 spike protein or the fragment thereof and the COVID-19 S2 spike protein or the fragment thereof are comprised within a single polypeptide chain, the single polypeptide chain being immobilisable on the detection portion. Doing so would have a reasonable expectation of successfully improving antigen-antibody detection of a sequence of the desired COVID-19 S1 and S2 spike protein.
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the S1 and S2 spike protein being a single polypeptide chain) by known methods with no change in their respective functions (i.e. detection of COVID-19 S1 and S2 spike proteins), and the combinations yielded nothing more than predictable results (i.e. providing the claimed S1 and S2 spike proteins as a single polypeptide chain would yield nothing more than the obvious and predictable result of enabling improved detection of COVID-19 proteins). See MPEP 2143(A).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Skraba as applied to claim 1 above, and further in view of Wang et al. (US 20210302434 A1; effectively filed 03/25/2020).
Regarding claim 3, modified Li fails to teach wherein the second biological antigen comprising the COVID-19 S2 spike protein or the fragment thereof is a polypeptide comprising a sequence of at least 8, 10, 12, 14, 16, 18, 20, 30, 100, 200 or 300 amino acids from an amino acid sequence having at least 70%, 80%, 90%, 95%, 99% or 100% sequence identity to the sequence of SEQ ID NO: 5 or SEQ ID NO: 6.
Wang teaches a kit for detection of antibodies for diagnosis of SARSr-COV infection (abstract). Wang teaches the invention uses an antigen coating and binding of antigen-specific antibody (paragraph [0083]). Wang teaches the kit comprises (i) a spike protein or a fragment thereof encoded by a SARSr-CoV, and (ii) an ACE2 protein or a fragment thereof which binds specifically to the spike protein or fragment of (i) (paragraph [0012]). Wang teaches SARSr-CoV spike protein comprises S1 and S2 subunits (paragraph [0115]). Wang teaches the spike protein of SARS-CoV-2 may have the amino acid sequence shown in SEQ ID NO: 5 (paragraph [0110] teaches SEQ ID NO: 5, which comprises the SEQ ID NO: 5 of the instant application). Wang teaches a polypeptide encoded by a SARS-CoV-2 may comprise or consist of the amino acid sequence of SEQ ID NO: 5 (paragraph [0112] teaches SEQ ID NO: 5, which comprises the SEQ ID NO: 5 of the instant application).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second biological antigen comprising the COVID-19 S2 spike protein or the fragment thereof of modified Li to incorporate the teachings of known sequences of SARS-Cov-2 of Wang (paragraphs [0110],[0112) to provide: wherein the second biological antigen comprising the COVID-19 S2 spike protein or the fragment thereof is a polypeptide comprising a sequence of at least 8, 10, 12, 14, 16, 18, 20, 30, 100, 200 or 300 amino acids from an amino acid sequence having at least 70%, 80%, 90%, 95%, 99% or 100% sequence identity to the sequence of SEQ ID NO: 5. Doing so would have a reasonable expectation of successfully improving specificity of antigen-antibody detection of a sequence of the desired COVID-19 protein.
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the second biological antigen comprising the claimed SEQ ID: 5) by known methods with no change in their respective functions (i.e. detection of COVID-19 components), and the combinations yielded nothing more than predictable results (i.e. providing the second biological antigen comprising the claimed SEQ ID: 5 would yield nothing more than the obvious and predictable result of enabling improved detection of COVID-19 proteins). See MPEP 2143(A).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Skraba as applied to claim 1 above, and further in view of Wang et al. (US 20210302434 A1; effectively filed 03/25/2020) and Baumkoetter et al. (US 20230120988 A1; effectively filed 04/23/2020).
Regarding claim 4, modified Li fails to teach wherein the COVID- 19 S2 spike protein or the fragment thereof comprises a sequence in which the C- terminal six or 62 amino acids are deleted from the sequence of SEQ ID NO: 5 or SEQ ID NO: 6.
Wang teaches a kit for detection of antibodies for diagnosis of SARSr-COV infection (abstract). Wang teaches the invention uses an antigen coating and binding of antigen-specific antibody (paragraph [0083]). Wang teaches the kit comprises (i) a spike protein or a fragment thereof encoded by a SARSr-CoV, and (ii) an ACE2 protein or a fragment thereof which binds specifically to the spike protein or fragment of (i) (paragraph [0012]). Wang teaches SARSr-CoV spike protein comprises S1 and S2 subunits (paragraph [0115]). Wang teaches The spike protein of SARS-CoV-2 may have the amino acid sequence shown in SEQ ID NO: 5 (paragraph [0110] teaches SEQ ID NO: 5, which comprises the SEQ ID NO: 5 of the instant application). Wang teaches a polypeptide encoded by a SARS-CoV-2 may comprise or consist of the amino acid sequence of SEQ ID NO: 5 (paragraph [0112] teaches SEQ ID NO: 5, which comprises the SEQ ID NO: 5 of the instant application).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the second biological antigen comprising the COVID-19 S2 spike protein or the fragment thereof of modified Li to incorporate the teachings of known sequences of SARS-Cov-2 of Wang (paragraphs [0110],[0112) to provide: wherein the COVID- 19 S2 spike protein or the fragment thereof comprises a sequence from the sequence of SEQ ID NO: 5. Doing so would have a reasonable expectation of successfully improving specificity of antigen-antibody detection of a sequence of the desired COVID-19 protein.
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the second biological antigen comprising the claimed SEQ ID: 5) by known methods with no change in their respective functions (i.e. detection of COVID-19 components), and the combinations yielded nothing more than predictable results (i.e. providing the second biological antigen comprising the claimed SEQ ID: 5 would yield nothing more than the obvious and predictable result of enabling improved detection of COVID-19 proteins). See MPEP 2143(A).
Modified Li fails to teach: wherein the COVID- 19 S2 spike protein or the fragment thereof comprises a sequence in which the C- terminal six or 62 amino acids are deleted from the sequence of SEQ ID NO: 5 or SEQ ID NO: 6.
Skraba teaches in some variations, the assay is capable of detecting biomarkers that may be biologically active variants of the naturally occurring molecule of interest (paragraph [0155]).
Baumkoetter teaches methods of detecting anti-coronavirus antibodies in a sample using a corona antigen (abstract). Baumkoetter teaches the inventors could show that by using the nucleocapsid protein of SARS CoV-2 as an antigen, both a high sensitivity and a high specificity of the resulting immunological test could be achieved allowing for the development of the urgently needed and eagerly awaited automated high-throughput Corona antibody assay (paragraph [0009]). Baumkoetter teaches variants of a corona sequence are easily created by a person skilled in the art (paragraph [0137]) and the variant exhibits modifications to its amino acid sequence, in particular selected from the group consisting of amino acid exchanges, deletions or insertions compared to the amino acid sequence embodiments (paragraph [0138]). Baumkoetter teaches where amino acid are C- or N-terminal deleted or inserted at one end or at both ends by 1 to 10 amino acids (paragraph [0139]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the COVID- 19 S2 spike protein or the fragment thereof that includes the sequence of SEQ ID NO: 5 of modified Li to incorporate the teachings of detecting biologically active variants of Skraba (paragraph [0155]) and the teachings of variant sequences including amino acid C-terminal deletions by 1-10 amino acids (paragraphs [0137]-[0139]) to provide: wherein the COVID- 19 S2 spike protein or the fragment thereof comprises a sequence in which the C- terminal six amino acids are deleted from the sequence of SEQ ID NO: 5. Doing so would have a reasonable expectation of successfully improving analysis and detection of variants of COVID 19 proteins.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Skraba as applied to claim 1 above, and further in view of Kouvonen et al. (US 5965458 A).
Regarding claim 7, modified Li fails to teach wherein the porous membrane element further comprises a reference element for indicating a level of the first member of the or each reporter-analyte pair in the liquid, biological sample.
Kouvonen teaches a test strip for rapid immunoassay containing specific reagent zones (abstract). Kouvonen teaches the strip comprises multiple membranes or zones, and the strip contains several different concentrations of the same reagent or label in order to determine different analyte concentrations semiquantitatively (column 4, lines 1-9). Kouvonen teaches the same membrane may contain several reagents for detecting different concentrations of the same analyte (column 5, lines 55-58).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the porous membrane element of modified Li to incorporate the teachings of test strips with multiple zones with different concentrations of a reagent or label for determining analyte concentration of Kouvonen (column 4, lines 1-9; column 5, lines 55-58) to provide: wherein the porous membrane element further comprises a reference element for indicating a level of the first member of the or each reporter-analyte pair in the liquid, biological sample. Doing so would have a reasonable expectation of successfully improving semiquantitative analysis of a desired analyte as discussed by Kouvonen (column 4, lines 1-9; column 5, lines 55-58).
Response to Arguments
Applicant’s arguments, see page 1, filed 01/23/2026, with respect to claim objections and rejections under 35 U.S.C. 112(b) have been fully considered and are persuasive. The claim objections and rejections under 35 U.S.C. 112(b) of 10/23/2025 have been withdrawn.
Applicant's arguments, see pages 2-8, filed 01/23/2026, with respect to the rejections under 35 U.S.C. 103, specifically regarding claim 1, have been fully considered but they are not persuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine Li and Skraba since the prior art does not teach or suggest selecting S1 protein from multiple antigens and at the priority date there was prejudice towards using RBD and not S1 protein (Remarks, pages 2-8), 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 this case, Skraba provides teachings and suggestions of determining if a sample includes SARS-CoV-2 (paragraph [0008]) and assays including any antigen binding agents that antigens specific to the desired virus (paragraph [0191]). Specifically, Skraba teaches “the binding agent/indicator for coronavirus (e.g. SARS-CoV, MERS-CoV, or SARS-CoV-2) may bind with specificity to a nucleoprotein and/or Spike (S1, S2, or RBD subunits) antigen binding site of coronavirus (e.g. SARS-CoV, MERS-CoV, or SARS-CoV-2)” (paragraph [0191]).
It would have been obvious to one of ordinary skill in the art to have modified the biological antigen of Li to incorporate the teachings of assays to detect viruses using binding agents for SARS-CoV-2, such as binding agents for S1 and S2 spike proteins (paragraph [0191]) to provide: i) the biological antigen comprises: (b) the first biological antigen from the first reporter-analyte pair comprising a COVID-19 S1 spike protein or a fragment thereof, and a second biological antigen from a second reporter-analyte pair comprising a COVID-19 S2 spike protein or a fragment thereof, and wherein the device is for independent detection of a spike protein, or a fragment thereof, or of an antibody specific for a spike protein, or a fragment thereof, in the biological sample. Doing so would have a reasonable expectation of successfully improving detection of viruses, i.e. COVID-19, and binding sites of desired viruses, such as the S1 and S2 subunits of SARS-CoV-2.
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the first biological antigen from the first reporter-analyte pair comprising a COVID-19 S1 spike protein or a fragment thereof, and a second biological antigen from a second reporter-analyte pair comprising a COVID-19 S2 spike protein or a fragment thereof) by known methods with no change in their respective functions (i.e. detection of COVID-19 S1 and S2 spike proteins), and the combinations yielded nothing more than predictable results (i.e. providing the claimed first and second biological antigens would yield nothing more than the obvious and predictable result of enabling improved detection of COVID-19 proteins). See MPEP 2143(A).
Furthermore, since Skraba teaches a need or desire to determine if a sample includes SARS-CoV-2 (paragraph [0008],[0191]) and Skraba teaches a finite number of identified, predictable potential solutions to detect SARS-CoV-2 (paragraph [0191], e.g. S1 and S2 spike proteins), it would have been obvious to have modified the biological antigen of Li to provide: i) the biological antigen comprises: (b) the first biological antigen from the first reporter-analyte pair comprising a COVID-19 S1 spike protein or a fragment thereof, and a second biological antigen from a second reporter-analyte pair comprising a COVID-19 S2 spike protein or a fragment thereof, and wherein the device is for independent detection of a spike protein, or a fragment thereof, or of an antibody specific for a spike protein, or a fragment thereof, in the biological sample. I.e., it would have been obvious to try the COVID-19 S1 spike protein and COVID-19 S2 spike protein to improve detection of viruses, i.e. COVID-19, and binding sites of desired viruses, such as the S1 and S2 subunits of SARS-CoV-2. MPEP 2143(I)(E).
Therefore, 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 to have arrived at the claimed invention. Additionally, Li in view of Skraba provides teachings and suggestions to arrive at the claimed invention as discussed above and does not teach away from the use of COVID-19 S1 and S2 spike proteins; wherein the teachings of Li in view of Skraba outweighs the teachings of Annex A and Annex B provided by the applicant (Remarks, pages 2-3), which have not been used in the current prior art rejection.
In regards to applicant’s arguments regarding dependent claims 2-7, the examiner disagrees for the same reasons above regarding claim 1 with respect to the claimed “COVID-19 S1 spike protein” and “COVID-19 S2 spike protein”.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Hall et al. (US 20210278358 A1; effectively filed 03/07/2020) teaches a method and device to detect an analyte (abstract). Hall teaches a sensor for detection of COVID-19 and a receptor that interacts and binds with spike proteins on the surface of SARS-COV-2 virus (paragraph [0087]).
Wang et al. (US 20210263023 A1; effectively filed 09/13/2018) teaches systems for detection of SARS-Cov-2 (abstract). Wang teaches the analyte being a coronavirus nucleocapsid or a coronavirus spike (paragraph [0020]).
McDevitt et al. (US 20210311055 A1; effectively filed 03/25/2020) teaches assays for diagnosing and assessing pathogen-mediated diseases and infections (abstract). McDevitt teaches in the context of SARS CoV-2, the first panel of biomarkers comprises a biomarker of SARS CoV-2, including any viral protein or viral nucleic acid, such as SARS CoV-2 spike protein (e.g., spike antigen), the S1 or S2 subunits of the SARS CoV-2 spike protein, or the SARS CoV-2 nucleocapsid protein (N-protein) (paragraph [0059]).
Laderman et al. (US 20230204581 A1; effectively filed 03/03/2020) teaches methods and devices for detection of SARS-CoV-2 (abstract). Laderman teaches In one embodiment, the SARS-CoV-2 antigen is selected from the group consisting of a spike protein (S), a receptor-binding (RBD) protein, a S1 protein, a S2 protein, a whole protein (S1+S2), and a nucleocapsid protein (NP); in a specific embodiment, the SARS-CoV-2 antigen is a nucleocapsid protein; and in another specific embodiment, the SARS-CoV-2 antigen is a spike protein (paragraph [0009]).
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758