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
This application claims the benefit under 35 U.S.C §119(e) of US Provisional Application No. 63/342962, filed on May 17, 2022. All content in this instant application is supported in the provisional application, thus the effective filing date of examined instant claims have an effective filing date of May 17, 2022.
Election/Restrictions
Applicant's election, with traverse, of the invention of Group I, claims 1-15, drawn to a product/device for detecting at least two analytes in a sample, in reply filed on 03/09/2026 is acknowledged.
Claims 16-20, drawn to a method for using a device for detecting at least two analytes in a sample, are withdrawn, by Applicant, with traverse, from further consideration as being drawn to a nonelected invention, in reply filed on 03/09/2026 is acknowledged.
The traversal is on the ground(s) that Examiner's to Group I (claims 1-15).
This is not found persuasive because the distinctness test between Group I (claims 1-15), drawn to a produce/device, and Group II (claims 16-20), drawn a method/process, requires the examiner to show either one or both of the following:
(Requirement 1) the process for using the product as claimed can be practiced with another materially different product or
(Requirement 2) the product as claimed can be used in a materially different process of using that product (See MPEP § 806.05 (h))
The alternative product (microfluidic chip device) used as an example for the distinctness test, under requirement 1 above, with Group II is not applicable to Group I because Group I is drawn to a product/device. The distinctness test does not require a product-to-product analysis. To address Group I, drawn to a product/device, in a distinctness test, requirement 2 above would need to be applied, showing the product/device recited in Group I (claims 1-15) can be used in a process distinct from Group II (claims 16-20). See MPEP § 806.05 (h). This is not the analysis or requirement for distinctness applied by the Examiner, as such, Applicant’s argument regarding applicability of the alternative product (microfluidic chip device) to Group I for a distinctness test is moot.
Further, Applicant does not argue that the alternative product (microfluidic chip device) provided in the Examiner’s example for the distinctness test, under requirement 1 above, with Group II, is improper or that the method/process recited in Group II cannot be practiced with the alternative product (microfluidic chip device). Examiner’s example of a microfluidic chip device as an alternative product, distinct from the product recited in Group I, to satisfy requirement 1 above for the distinctness test with Group II is not traversed by the Applicant. Thus, Examiner shows that Group I and Group II are independent or distinct inventions and thus require a restriction, per MPEP § 806.05 (h).
Applicant further argues that there is no serious burden on the Examiner for examining the claims of Group I and Group II.
This is not persuasive because there would be a serious search and/or examination burden if restriction were not required for the following reasons:
(1) the inventions have acquired a separate status in the art in view of their different classification (eg., Group I is classified in G01N33/54389 and Group II is classified in G01N33/558);
(2) the inventions have acquired a separate status in the art due to their recognized divergent subject matter; and
(3) the inventions require a different field of search (e.g., searching different classes/subclasses or electronic resources, or employing different search strategies or search queries). A search of the invention of Group I is not likely to coextend to each of Group II. For example, the particulars of Group I are not required of Group II, and so upon a search of either one of these groups, it would also be necessary to search/consider the other Group independently, relying on different text-based queries of both the patent and non-patent literature-based databases.
For the reasons discussed herein above, the requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-20 are pending. Claims 16-20 are withdrawn. Claims 1-15 are examined herein below.
Information Disclosure Form
One Information Disclosure Statement (IDS), filed 05/23/2023, is acknowledged and considered.
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.
Claim(s) 1-6, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Chun Wang et al., Lateral flow immunoassay integrated with competitive and sandwich models for the detection of aflatoxin M1 and Escherichia coli O157:H7 in milk, 2018, J. Dairy Sci., 101, 8767-8777), in view of Sakamoto et al., (S. Sakamoto, et al., Enzyme-linked immunosorbent assay for the quantitative/qualitative analysis of plant secondary metabolites, 2018, Journal of Natural Medicines, 72, 32–42), and O’Farrell (B. O’Farrell, Evolution in Lateral Flow-Based Immunoassay Systems, 2009th ed., Eds. Raphael C. Wong and Harley Y. Tse, Lateral Flow Immunoassay, 2008, 1-5 provided, Humana Press), as evidenced by Zhang et al., (Yi Zhang et al., Improvement in Detection Limit for Lateral Flow Assay of Biomacromolecules by Test-Zone Pre-enrichment, 2020,Scientific Reports, 10, 9604, 1-9).
Throughout the article, Wang teaches a lateral flow assay with two detection regions in liquid communication wherein a first molecule is immobilized in the first detection region and a second molecule is immobilized in the second detection region. Wang teaches for a sample with analytes applied to the first and second detection regions, a first analyte bound to the first detection region is detected using a competitive detection mode, wherein the signal detection is inversely proportional to the concentration of the first analyte, specifically no signal is generated in the presence of the first analyte and a signal is generated in the absence of the first analyte. Wang further teaches detection of the second analyte bound to the second immobilized molecule in the second detection region is detected using a sandwich detection mode, wherein the second analyte bound to the second immobilized molecule also binds the detection molecule and this complex generates a signal indicating presence of the second analyte. Wang further teaches first immobilized molecule is immobilized in the second detection region and the second immobilized molecule is immobilized in the first detection region.
Regarding claims 1, Wang teaches an assay system for detecting presence or absence of at least a first analyte and a second analyte in a sample; and an assay device comprising: a first detection region configured to receive the sample in a vertical direction perpendicular to a longitudinal axis of the assay; a second detection region in liquid communication with the first detection region and configured to receive the sample from the first detection region in a horizontal direction parallel to the longitudinal axis a first immobilized molecule immobilized in one of the first and second detection regions and configured to bind to the detection molecule to indicate the absence of the first analyte in the sample; and a second immobilized molecule immobilized in the other one of the first and second detection regions and configured to bind to the second analyte to generate a complex, wherein the detection molecule is also configured to bind to the complex to indicate the presence or the absence of the second analyte in the sample (C. Wang et al., 2018, J. Dairy Sci., 101, pg. 8767, Abstract; pg. 8768, Fig. 1; pg. 8769; pg. 8770 full paras 3-4 and Fig. 2). Wang does not teach the assay system comprising: a label solution comprising a detection molecule or a first immobilized molecule immobilized and configured to bind the first analyte to indicate the presence of the first analyte in the sample.
Throughout the review article, Sakamoto teaches the state of the prior art of various ELISA methods, which is known for having various advantages including simplicity, cost efficiency, and selectivity. Sakamoto teaches advantages and disadvantages already known in the art for different ELISA types. Sakamoto teaches the indirect competitive ELISA method, which among other steps, comprises the preparation of a separate label solution (Sakamoto et al., 2018, Journal of Natural Medicines, 72, pg. 36, Fig. 4). Sakamoto teaches that the label solution is applied after the sample has been applied to the detection regions (wells). Sakamoto further teaches that signal detection decreases with increasing amount of target analyte (Sakamoto et al., 2018, Journal of Natural Medicines, 72, pg. 35, full para 3).
Sakamoto teaches an indirect competitive ELISA and the teachings read on the limitation of claim 1 reciting wherein “the assay system comprising: a label solution comprising a detection molecule” (Sakamoto et al., 2018, Journal of Natural Medicines, 72, pg. 35, “Indirect competitive ELISA”; pg. 36, Fig. 4). Sakamoto does not teach a first immobilized molecule immobilized and configured to bind the first analyte to indicate the presence of the first analyte in the sample.
In the book chapter, O’Farrell teaches the history of lateral flow immunoassay development and urine testing for medical diagnostic purposes was the main driver of the early development of the this rapid-test technology. O’Farrell teaches the conventional configuration and traditional design of LFA. O’Farrell further teaches direct sandwich and competitive immunoassay modes. O’Farrell teaches that in competitive mode, a molecule with affinity for the analyte is immobilized in the detection region (Test Line). O’Farrell teaches, in competitive mode, when the analyte (blue spheres) is present in the sample, the analyte binds the immobilized molecule, blocking binding between the immobilized molecule and the detection molecule, resulting in no signal indication presence of analyte (pg. 4, Fig,. 1.2b, Positive Result). O’Farrell further teaches, in competitive mode, when analyte is absence in the sample, the detection molecule binds the immobilized molecule, generating a signal indicating absence of analyte (pg. 4, Fig,. 1.2b, Negative Result).
O’Farrell teaches the limitation(s) of claim 1 reciting an immobilized molecule configured to bind the first analyte to indicate the presence of the analyte in the sample (pg. 4, Fig. 1.2b).
It would have been prima facie obvious, at the time of filing, to combine the assay system comprising of two detection regions in liquid communication and an immobilized molecule in each region for detecting at least two analytes as taught by Wang with the assay method comprising a separate label solution comprising a detection molecule, as taught by Sakamoto. A skilled artisan would have been motivated to combine these teachings because having a separate label solution offers versatility, in an indirect competitive assay, including enabling the use a polyclonal antibody as part of the detection molecule capable of recognizing more than one region of the target molecule/antigen thus increasing detection sensitivity (see Sakamoto et al., 2018, Journal of Natural Medicines, 72, pg. 36, Fig. 4 and full para 1). At the time of filing, Wang taught detection of at least two analytes using the same assay system comprising two detection regions and, at the time of filing, Sakamoto taught an analyte detection method comprising a label solution comprising a detection molecule. Thus, at the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining elements known in the art, that perform the same function separately as they do when combined, according to known methods would yield expected and predictable results.
It would have been prima facie obvious, at the time of filing, to combine the assay system comprising two detection regions in liquid communication, and each with an immobilized molecule for detecting at least two analytes, as taught by Wang, in view of Sakamoto, with the competitive detection method wherein the immobilized molecule binds either the detection molecule or the analyte to indicate absence or presence of the analyte, as taught by O’Farrell. A skilled artisan would have been motivated to combine these teachings to improve the detection system comprising a detection molecule with affinity for the immobilized molecule and the analyte, as taught by Wang, with the competitive detection assay taught by O’Farrell wherein the analyte does not have affinity for the detection molecule and binds only the immobilized molecule, because the detection rate and signal sensitivity of the analyte would be improved without requiring an extended reaction time between analyte and labeled detection molecule (see Chun Wang et al., 2018, J. Dairy Sci., 101, pg. 8773, full para 1). At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining elements known in the art to improve assay sensitivity and the detection rate of the first detected analyte using a competitive mode wherein the detection molecule has affinity for the immobilized molecule and not the target analyte, amounts to applying a known improvement to a similar method/product to yield expected and predictable results.
Regarding claim 2, Wang, Sakamoto, and O’Farrell teach all the limitations of claim 1. Wang further teaches wherein the first immobilized molecule is immobilized in the first detection region and the second immobilized molecule is immobilized in the second detection region (C. Wang et al., 2018, J. Dairy Sci., 101, pg. 8768, Fig. 1; pg. 8769 and pg. 8770, Fig. 2).
Regarding claim 3, Wang, Sakamoto, and O’Farrell teach all of the limitations of claims 1 and 2. O’Farrell further teaches wherein if the first immobilized molecule remains unbound by the first analyte after the sample is applied to the first detection region, the detection molecule binds to the first immobilized molecule to generate a detectable signal indicating the absence of the first analyte in the sample (pg. 4, Fig,. 1.2b, Negative Result). O’Farrell further teaches the limitation(s) of claim 3 reciting if the first immobilized molecule binds to the first analyte after the sample is applied to the first detection region, the detection molecule does not bind to the first immobilized molecule and generates a null signal indicating the presence of the first analyte in the sample (pg. 4, Fig,. 1.2b, Positive Result and pg. 5, top half).
It would have been prima facie obvious, at the time of filing, to combine the teachings of Wang with the teachings of O’Farrell in order to improve the competitive detection assay of the first analyte in the first detection region. A skilled artisan would have been motivated to combine these teachings and improve the detection system comprising a detection molecule with affinity for the immobilized molecule and the analyte, as taught by Wang, with the competitive detection assay taught by O’Farrell wherein the analyte does not have affinity for the detection molecule and binds only the immobilized molecule, thus improving the detection rate and signal sensitivity without requiring an extended reaction time between analyte and labeled detection molecule (see Chun Wang et al., 2018, J. Dairy Sci., 101, pg. 8773, full para 1). At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining elements known in the art to improve the detection rate and signal sensitivity of the first analyte detected using a competitive mode, amounts to applying a known improvement to a similar method/product to yield expected and predictable results.
Regarding claims 4, and 9, Wang, Sakamoto, and O’Farrell teach all of the limitations of claims 1 and 2. Wang further teaches wherein: if the second immobilized molecule binds to the second analyte to generate the complex after the sample is applied to the second detection region, the detection molecule binds to the complex to generate a detectable signal indicating the presence of the second analyte in the sample (C. Wang et al., 2018, J. Dairy Sci., 101, pg. 8770, Fig. 2, LFI set-up I and paras 3-4), and if the second immobilized molecule remains unbound by the second analyte after the sample is applied to the second detection region, the detection molecule does not bind to any complex and generates a null signal indicating the absence of the second analyte in the sample (C. Wang et al., 2018, J. Dairy Sci., 101, pg. 8770, Fig. 2, LFI set-up I and paras 3-4). Wang further teaches wherein the first immobilized molecule comprises: a protein, an antibody, an antigen-binding fragment of an antibody, an antigen, a peptide, a nucleic acid, or a combination thereof; or any molecule that can bind a protein, an antibody, an antigen-binding fragment of an antibody, an antigen, a peptide, or a nucleic acid (C. Wang et al., 2018, J. Dairy Sci., 101, pg. 8769 and pg. 8770, Fig. 2, LFI set-up I and paras 3-4).
Regarding claim 5, Wang, Sakamoto, and O’Farrell teach all of the limitations of claims 1. Wang further teaches wherein the first immobilized molecule is immobilized in the second detection region and the second immobilized molecule is immobilized in the first detection region (C. Wang et al., 2018, J. Dairy Sci., 101, pg. 8770, Fig. 2 LFI set-up I and LFI set-up II; pg. 8772-8773).
Regarding claim 6, Wang and Sakamoto teach all of the limitations of claim 1. Wang further teaches applying a sample to a first detection region or applying a sample to a second detection region. Sakamoto further teaches applying a sample to a detection region prior to the label solution (signaling unit) being applied/added (Sakamoto et al., 2018, Journal of Natural Medicines, 72, pg. 36, Fig. 4).
It would have been prima facie obvious, at the time of filing, to combine the assay system comprising two detection regions in liquid communication and each with an immobilized molecule for detecting at least two analytes as taught by Wang, with the teachings of Sakamoto in order to improve the immunoassay sensitivity and limit of detection of the assay system. A skilled artisan would have been motivated to combine these teachings in order to improve the immunoassay limit of detection and sensitivity by applying the sample to the detection region prior to the label solution (signaling unit), as taught by Sakamoto, because this would enable the target analytes to interact and bind with the immobilized/capture molecules in each detection region without interference, enriching each detection region with analyte without requiring larger sample volumes, thus lowering the limit of detection up to 100-fold and increasing detection sensitivity (see Zhang et al., 2020, Scientific Reports, 10, 9604, pg.1, Abstract and full paras 1-2; pg. 2, full para 2 and para 3 “Results and discussion, Workflow of sampling method”; pg. 4, “Competitive format I”; pg. 5, Fig. 4a). At the time of filing, Wang taught detection of at least two analytes using the same assay system comprising two detection regions in liquid communication, with a first and second immobilized molecule respectively. Additionally, at the time of filing, Sakamoto taught applying the sample to the detection region prior to the label solution (signaling unit) to enrich the detection region with analyte c. Thus, at the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings known in the art to modify and improve the limit of detection and detection sensitivity by applying the label solution after the sample is applied to each detection region, amounts to applying a known improvement to a similar method/product to yield expected and predictable results.
Regarding claim 11, Wang, Sakamoto, and O’Farrell teach all of the limitations of claim 1. Wang further teaches wherein the detection molecule comprises a binding moiety and a label moiety, wherein the binding moiety is a protein, an antibody, an antigen-binding fragment of an antibody, an antigen, or a peptide (Wang et al., 2018, J. Dairy Sci., 101, pg. 8769, full para 2 and Fig. 1, anti-E. coli O157:H7 mAb-AuNP ).
Claim(s) 7 is rejected under 35 U.S.C. 103 as being unpatentable over unpatentable over Wang et al. (Chun Wang et al., 2018, J. Dairy Sci., 101, 8767-8777), in view of Sakamoto et al., (S. Sakamoto, et al., 2018, Journal of Natural Medicines, 72, 32–42), and O’Farrell (B. O’Farrell, Evolution in Lateral Flow-Based Immunoassay Systems, 2009th ed., Eds. Raphael C. Wong and Harley Y. Tse, Lateral Flow Immunoassay, 2008, 1-5 provided, Humana Press), as applied to claim 1 above, further in view of J.J. Wang et al., ( J.J. Wang et al., Rapid lateral flow tests for the detection of SARS-CoV-2 neutralizing antibodies, 2021, Expert Rev Mol Diagn, 12, 1-8), and as evidenced by Ragnesola et al., (Ragnesola et al., COVID19 antibody detection using lateral f low assay tests in a cohort of convalescent plasma donors, 2020, BMC Res Notes, 13, 372, 1-7).
Regarding claim 7, the teachings of Wang, Sakamoto, and O’Farrell are discussed herein above. Wang, Sakamoto, and O’Farrell teach all of the limitations of claim 1. Wang, Sakamoto, and O’Farrell do not teach than an antibody is the first analyte.
Throughout the review article, J. J. Wang teaches the importance of awareness and monitoring of SARS-CoV-2 neutralizing antibodies (Nabs) for combating the COVID-19 pandemic. J.J. Wang further teaches a comparison of available methods for the detection of SARS-CoV-2 Nabs and teaches the challenges for developing rapid lateral flow tests for the detection of SARS-CoV-2 NAbs. J.J. Wang outlines product formats and applications in research and in disease management, including competitive (inhibition) later flow assays comprising an immobilized protein, protein domain, or peptide that binds SARS-CoV-2 NAbs and capable of binding ACE2.
J. J. Wang teaches the limitation(s) of claim 7 reciting wherein an analyte is an antibody (J.J. Wang et al., 2021, Expert Rev Mol Diagn, 12, pg. 3, full para 3 and pg. 4, Fig. 2, immobilized RBD to detect NAbs).
It would have been prima facie obvious, at the time of filing, to combine the teaching of Wang et al., in view of Sakamoto and O’Farrell, to modify the target analyte for detection of the assay system with the method for detecting an antibody, as taught by J.J. Wang. At the time of filing, combating the COVID-19 pandemic was of paramount priority and one important step in this process required obtaining seroconversion data by using immunoassays to detect COVID-19 specific antibodies to enable monitoring and responding to the pandemic, especially in patients with a previous documented COVID-19 infection (see Ragnesola et al., 2020, BMC Res Notes, 13, 372, pg. 1 Abstract and full paras 1-2). Thus, a skilled artisan would have been motivated to combine the teaching of Wang et al., in view of Sakamoto and O’Farrell, with the teaching of J.J. Wang to modify the assay system for antibody detection because it would enable an assay for detection of COVID-19 antibodies to monitor seroconversion, thus responding to the urgent market and societal need to monitor and respond to the COVID-19 pandemic at the time of filing. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings known in the art to modify the assay system taught by Wang with the method for antibody detection as taught by J.J. Wang, amounts to applying a known improvement to a similar method/product to yield expected and predictable results.
Claim(s) 8 is rejected under 35 U.S.C. 103 as being unpatentable over unpatentable over Wang et al. (Chun Wang et al., 2018, J. Dairy Sci., 101, 8767-8777), in view of Sakamoto et al., (S. Sakamoto, et al., 2018, Journal of Natural Medicines, 72, 32–42), and O’Farrell (B. O’Farrell, Evolution in Lateral Flow-Based Immunoassay Systems, 2009th ed., Eds. Raphael C. Wong and Harley Y. Tse, Lateral Flow Immunoassay, 2008, 1-5 provided, Humana Press), as applied to claim 1, further in view of C. Wang et al., (Chongwen Wang et al., 2021, ACS Appl. Mater. Interfaces, 13, 40342-40353).
Regarding claim 8, the teachings of Wang, Sakamoto, and O’Farrell are discussed herein above. Wang, Sakamoto, and O’Farrell teach all of the limitations of claim 1. C. Wang, Sakamoto, and O’Farrell do not teach the second analyte is a viral particle or an antigenic portion thereof.
Throughout the disclosure, C. Wang teaches a dual-mode lateral flow immunoassay (LFIA) biosensor for dual detection of SARS-CoV-2 spike (S) and nucleocapsid protein (NP) antigens on one test strip. C. Wang teaches this dual-mode LFIA is beneficial for improving the detection accuracy and efficiency of SARS-CoV-2 infection especially for point-of-care devices. C. Wang teaches detecting these target analytes in saliva and nasal swab samples. C. Wang teaches immobilizing a SARS-CoV-2 S1 antibody on the first detection region, T line 1, for detection of SARS-CoV2- Spike protein, an antigenic portion of the SARS-CoV-2 virus.
C. Wang teaches the limitation of claim 8 reciting herein the second analyte is a viral particle or an antigenic portion thereof (Wang et al., 2021, ACS Appl. Mater. Interfaces, 13, pg. 40345, Scheme 1c, T line 1 and T line 2).
It would have been prima facie obvious, at the time of filing, to combine the teachings of and modify the assay system for detecting multiple analytes as taught by Wang with the assay system for detecting SARS-COV-2 antigens, including antigenic portions of the virus, as taught by C. Wang. At the time of filing, with the COVID-19 pandemic, sensitive point-of-care methods for detecting SARS-COV-2 antigens was an urgent global need. Detecting SARS-COV-2 antigens, such as a viral particle or an antigenic portion thereof, enables rapid COVID19 diagnosis during early stages of the infection of up to several days before experiencing clinical symptoms (see C. Wang et al., 2021, ACS Appl. Mater. Interfaces, 13, pg. 40342, Abstract and pg. 40343 top partial para). Thus, at the time of filing, a skilled artisan would have been motivated to combine these teachings and modify the assay system taught by Wang with the method of detecting a viral particle or an antigenic portion of the viral particle, as taught by C. Wang, to detect COVID-19 during the early stages for effective disease management and to stem spread of the disease. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings known in the art to modify the assay system taught by Wang with the method for detecting a viral particle or antigenic portion of the viral particle, as taught by C. Wang, amounts to applying a known improvement/modification to a similar method/product to yield expected and predictable results.
Claim(s) 10 is rejected under 35 U.S.C. 103 as being unpatentable over unpatentable over Wang et al. (Chun Wang et al., 2018, J. Dairy Sci., 101, 8767-8777), in view of Sakamoto et al., (S. Sakamoto, et al., 2018, Journal of Natural Medicines, 72, 32–42), and O’Farrell (B. O’Farrell, 2009th ed., 2008, 1-5 provided, Humana Press), as applied to claim 1 above, and further in view of J.J. Wang et al., (J.J. Wang et al., 2021, Expert Rev Mol Diagn, 12, 1-8), and C. Wang et al., (Chongwen Wang et al., , 2021, ACS Appl. Mater. Interfaces, 13, 40342-40353), and as evidenced by Ragnesola et al., (Ragnesola et al., 2020, BMC Res Notes, 13, 372, 1-7).
Regarding claim 10, the teachings of Wang, Sakamoto, and O’Farrell are discussed herein above. Wang, Sakamoto, and O’Farrell teach all of the limitations of claim 1. Wang, Sakamoto, and O’Farrell do not teach wherein the first immobilized molecule comprises a peptide that binds to an anti-SARS-Cov-2 S-protein neutralizing antibody and an angiotensin converting enzyme 2 (ACE 2) protein, and wherein the second immobilized molecule comprises a recombinant anti-SARS-Cov-2 antibody.
The teachings of J.J. Wang are discussed herein above. J.J. Wang teaches the limitation in claim 10 that recites wherein the first immobilized molecule comprises a peptide (immobilized RBD domain) that binds to an anti-SARS-Cov-2 S-protein neutralizing antibody and an angiotensin converting enzyme 2 (ACE 2) protein (J.J. Wang et al., 2021, Expert Rev Mol Diagn, 12, pgs. 3-4, full para 3-8 and pg. 4, Fig. 2, immobilized RBD to detect neutralizing antibodies). J.J. Wang does not teach the second immobilized molecule comprises a recombinant anti-SARS-Cov-2 antibody.
The teachings of C. Wang are discussed herein above. C. Wang teaches the limitation of claim 10 that recites wherein the second immobilized molecule comprises a recombinant anti-SARS-Cov-2 antibody (Chongwen Wang et al., , 2021, ACS Appl. Mater. Interfaces, 13, pg. 40345, Scheme 1c, T line 1 and T line 2; see C. Wang Supporting Information, pgs. S1-S2, SARS-CoV-2 spike antibodies S1, Catalog S2 #40150-D001 in Sino Biological; and see Sino Biological Datasheet).
It would have been prima facie obvious, at the time of filing, to combine the assay system comprising two detection regions in liquid communication for detecting at least two analytes, as taught by Wang, with the assay system comprising immobilizing a peptide that binds an anti-SARS-Cov-2 S-protein Nab and ACE 2 protein, as taught by J.J. Wang, with the assay system comprising immobilizing a recombinant SARS-COV-2 antibody that is capable if binding SARS-Cov-2 S-protein Nab and ACE 2 protein, as taught by C. Wang. At the time of filing, combating the COVID-19 pandemic was of paramount priority and one important step required in the process was obtaining seroconversion data, which refers to human antibodies produced during the infection and that are detectable in later stages of infection, using immunoassays to detect COVID-19 specific antibodies enabling the monitoring and responding to the pandemic (see Ragnesola et al., 2020, BMC Res Notes, 13, 372, pg. 1 Abstract and full paras 1-2). Further, at the time of filing, with the COVID-19 pandemic, sensitive point-of-care methods for detecting SARS-COV-2 antigens was an urgent global need. Detecting SARS-COV-2 antigens, such as a viral particle or an antigenic portion thereof, enables rapid COVID19 diagnosis up to several days before experiencing clinical symptoms (see C. Wang et al., 2021, ACS Appl. Mater. Interfaces, 13, pg. 40342, Abstract and pg. 40343 top partial para). Thus, at the time of filing, a skilled artisan would have been motivated to combine these teachings because simultaneously detection of neutralizing antibodies, detectable during the latter stage of infection would indicate progression of infection, and detecting an antigenic portion of the virus, which would be detectable during initial or early stages of infection, would increase detection rates (inclusive of symptomatic and asymptomatic patients) and enable efficient disease monitoring for all stages of the infection (ranging from early to late stages of infection). At the time of filing, an assay system comprising two detection regions in liquid communication for detecting at least two analytes, comprising immobilizing a peptide that binds an anti-SARS-Cov-2 S-protein Nab and ACE 2 protein, and immobilizing a recombinant SARS-COV-2 antibody for binding SARS-COV-2 viral antigens or antigenic viral portion thereof, though separately, were already taught in the prior art. Thus, at the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these prior art elements, that perform the same function separately as they do when combined, amounts to combining prior art elements according to known methods to yield expected and predictable results.
Claim(s) 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Chun Wang et al., 2018, J. Dairy Sci., 101, 8767-8777), in view of Sakamoto et al., (S. Sakamoto, et al., 2018, Journal of Natural Medicines, 72, 32–42), and O’Farrell (B. O’Farrell, 2009th ed., 2008, 1-5 provided, Humana Press), as applied to claims 1 and 11 above, further in view of Gribnau et al., (US Patent No. 4,373,932), and Zarubina et al., (Zarubina et al., Physical Chemistry Fibre-Forming Polymers, 2004, Fibre Chemistry, 36, 4, 278-282).
Regarding claims 12, Wang, Sakamoto, and O’Farrell teach all of the limitations of claim 1 and Wang further teaches the limitation(s) of claim 11. Wang, Sakamoto, and O’Farrell do not teach wherein the label moiety comprises a vat dye particle, wherein the vat dye particle comprises isatin, vat red 1, vat red 41, or vat orange 7.
Throughout the disclosure, Gribnau teaches method, reagents and test kits for the qualitative and/or quantitative determination of an immunochemically reactive component, such as a hapten, antigen, antibody, or other macromolecule, in which one or more labelled components are used. The immunochemically reactive component is either directly or indirectly coupled to an aqueous dispersion of a hydrophobic dye or pigment particle. Gribnau teaches (leuco) vat dyes are among one of these dye particles. Gribnau teaches the vat dye particles have a size ranging between 5-500 nm. Gribnau further teaches the dye particle carries a charge and coating the dye particle with polar macromolecules prevents aggregation. Gribnau teaches the quantity of the vat dye can be determined either during the reaction, after an adequate reaction time, or after a separation of the bound and free labelled components. Additionally, Gribnau teaches the immunoassay relies on the specific interaction between immunochemically reactive components.
Gribnau teaches the limitation of claim 11 reciting wherein the label moiety comprises a vat dye particle (US Patent No. 4,373,932: Abstract; col. 2, lines 10-25; col. 3, lines 8-34; col. 16, lines 21-29). Gribnau does not teach wherein the vat dye particle comprises isatin, vat red 1, vat red 41, or vat orange 7.
Throughout the article, Zarubina teaches obtaining quantitative information on the electron adsorption spectra of vat dyes using the diffuse reflection spectrum of dyed textile materials. Zarubina teaches that vat dyes sorbed on polyester fabric aggregate inside the textile material. Zarubina further teaches vat red 1 as a dye used for dyeing textile materials.
Zarubina teaches the limitation of claim 11 reciting a dye particle comprising vat red 1 (Zarubina et al., 2004, Fibre Chemistry, 36, 4, pg. 279).
It would have been prima facie obvious, at the time of filing, to combine the assay system comprising two detection regions in liquid communication for detecting at least two analytes, as taught by Wang, in view of Sakamoto and O’Farrell, with the teachings of a vat dye particle as a label moiety, as taught by Gribnau, and to try vat red 1 dye, as taught by Zarubina. A skilled artisan would have been motivated to combine the teachings of Wang, in view of Sakamoto and O’Farrell, with the teachings of Gribnau to improve the detection method by modifying the label solution taught by Sakamoto with the method of labeling a detection molecule with a vat dye, as taught by Gribnau, because it would enable the qualitative and quantitative determination of each analyte detected. At the time of filing, Gribnau taught vat dye particles as label moieties in a detection molecule for analyte detection in an immunoassay and Zarubina taught quantitative and qualitative information of at least 4 vat dyes, including vat red 1. Thus, a skilled artisan would have been further motivated to try vat red 1 as the dye particle for the label moiety in the detection molecule because the prior teaches it exhibits the same properties as the vat dyes taught by Gribnau and a skilled artisan would be choosing from a finite number of identified and predictable solutions and thus would have a reasonable expectation of success. Additionally, at the time of filing, a person having ordinary skill in the art would have a further reasonable expectation of success because combining the known teachings of Wang, in view of Sakamoto and O’Farrell, with the known teachings of Gribnau to modifying the label solution with a vat dye particle label would amount to combining known prior art elements according to known methods to yield expected and predictable results.
Regarding claims 13-15, Wang, Sakamoto, and O’Farrell teach all of the limitations of claim 1, Wang further teaches the limitation(s) of claim 11, and Gribnau and Zarubina teach the limitations of claim 12. Gribnau further teaches wherein the vat dye particle is below a threshold size (US Patent No. 4,373,932: cols. 25-26 claim 4; col. 4, lines 1-8; col 25, lines 27-40). Additionally, Gribnau teaches wherein: the vat dye particle has a positively charged hydrophilic group and the binding moiety is treated to have a negative charge; or the vat dye particle has a negatively charged hydrophilic group and the binding moiety is treated to have a positive charge (US Patent No. 4,373,932: col. 3, lines 16-22; col. 4, lines 9-16; col. 26, claim 8) and wherein each detection molecule has more than one label moiety attached to one binding moiety (US Patent No. 4,373,932: Gribnau: Abstract and col. 2, lines 10-25).
It would have been prima facie obvious, at the time of filing, to combine the teachings of Wang, in view of Sakamoto and O’Farrell, with the teachings of Gribnau and Zarubina. At the time of filing, a skilled artisan would have been motivated to combine these teachings in order to modify and improve the label moiety taught by Wang with the vat dye particle as the label moiety that is below a size threshold, as taught by Gribnau, because it would ensure the vat dye particle is stable and has a high molar absorptivity for improved signal intensity and detection sensitivity. At the time of filing, a skilled artisan would have been further motivated to combine these teachings in order to modify and improve the label moiety taught by Wang with the vat dye particle as the label moiety that is hydrophilic and bound to a an oppositely-charged binding moiety, as taught by Gribnau, because the hydrophilic, charged (leuco) form of the vat dye ensures the dye is water soluble and dispersible and the charged vat dye bound to an oppositely-charged binding moiety ensures a stable conjugation between the vat dye and the binding moiety via electrostatic or ionic interactions. At the time of filing, a skilled artisan would have been motivated to combine these teachings in order to modify and improve the label moiety taught by Wang with the vat dye particle as the label moiety that is bound to the binding moiety in multiples, as taught by Gribnau, because the presence of multiple labels on the binding moiety of the detection molecule enables increased signal intensity and qualitative and quantitative determination of each analyte. At the time of filing, the prior art taught immunoassay systems for detecting at least two analytes and the use of vat dyes as the label moiety of detection molecules for detecting and quantifying analytes in an immunoassay system. Thus, at the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these known teachings amounts to applying a known method /product for improvement/modification of a known method/product to yield expected and predictable results.
Conclusion
All examined claims (1-15) are rejected. No claims are allowed.
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/MELISSA LIZETTE LIRIANO/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 April 29, 2026
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