32DETAILED ACTION
Non-Final Rejection
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
2. The present application claims the benefit of U.S. Provisional patent application 63/065,993 filed August 14, 2020.
Status of Claims
3. Claims 1-32 filed on 02/08/2023 are pending.
Claim Rejections - 35 USC § 112 (b)
4. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. The claims 10-12 and dependent claims 13-26 (filed on 02/08/2023) are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claims 10-12 recite beads with different diameter (1.3 pm to 1.9 pm in claim 10), (1.6 pm in claim 11) and (2.7 pm in claim 12). The dependent claims 13-26 inherit the limitations on bead diameter.
The specification para [0043] recites beads of about 2.7 µm, from about 1.3 to about 1.9 µm, 1.6 µm. The Example 1 para [0060] recite beads of 1.6 µm, from about 1.3 to about 1.9 µm, 1.6 µm. Example 2, para [0062] recite beads 1.6 µm; Example 5, para [0070] Table 3 recite beads 1.6 µm, 2.7 µm. The claimed diameter of beads in pm does not correspond to specification reciting bead diameter in µm. The art indicates that bead diameter in pm the claims 10-12 recite beads with different diameter (1.3 pm to 1.9 pm in claim 10), (1.6 pm in claim 11) and (2.7 pm in claim 12). 1.0 pm diameter = 1.3-6 µm, is very small measurement (a picometer is one-trillionth of a meter) and is not a practical size for beads used in visual agglutination, as they would be far too small to see with the naked eye.
Claim 11 is directed to a range of diameter of bead from 1.6 pm but does not recite the upper range of the bead diameter and thus the claim is indefinite.
Applicant may review the claims and specification and may amend the claims without introducing a new matter.
6. Claim 25 contains the trademark/trade name “FICOLL”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name “FICOLL” is used to identify/describe hydrophilic polysaccharide or polysucrose and, accordingly, the identification/description is indefinite.
The use of the term “FICOLL”, which is a trade name, or a trademark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term. Although the use of trade names and trademarks are used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. The applicant is encouraged to appropriately cite trade name appropriately with the name of the vendor or company from which “FICOLL” was obtained.
Claim Rejections - 35 USC § 112
7. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 10-12 and dependent claims 13-26 (filed on 02/08/2023) are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the claimed magnetic bead-based assay to detect SARS CoV-2 viral antigen in a sample, does not reasonably provide enablement for the size of beads that have diameter in picometer (pm) size as claimed in claims 10-12. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected to specification para [0008] that recites the size of beads that have diameter in 1.3 to 1.9 µm (micrometer) the specification the invention commensurate in scope with these claims. Beads with a diameter in the picometer (pm) range are not used for agglutination assays, as this size range is smaller than an atom. Agglutination assays typically use beads that are much larger, in the micrometer (µm) to nanometer (nm) range, which is necessary to form visible clumps (See PDF printouts for size of beads, Agilent Technologies, Inc (published 11/15/2016), Bangs Lab 2013 (published 20 March 2013).
Claims 10-12 and dependent claims 13-26 (filed on 02/08/2023) are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The specification para [0043] recites beads of about 2.7 µm, from about 1.3 to about 1.9 µm, 1.6 µm. The Example 1 para [0060] recite beads of 1.6 µm, from about 1.3 to about 1.9 µm, 1.6 µm. Example 2, para [0062] recite beads 1.6 µm; Example 5, para [0070] Table 3 recite beads 1.6 µm, 2.7 µm. The claimed diameter of beads in pm does not correspond to specification reciting bead diameter in µm.
Claims 13-14 and dependent claims 15-26 (filed on 02/08/2023) are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The specification para [0044] recites coating of beads with antibody quantity in range of 10-50 or 25-35 or 30 µg/mg of beads. The instant claims 13-14 recites coating of beads with antibody quantity in range of 25-35 pg/mg of beads (claim 13) and 3 pg/mg of beads.
The claimed quantity of coating antibody in pg/mg of beads does not correspond to specification para [0045] and elsewhere in the specification.
Claim Rejections - 35 USC § 103
8. 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.
9. Claims 1-4, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Cheung et al 2006 (US20060188519A1, published 08/24/2006), and further in view of Chen et al 2020 (Cellular & Molecular Immunology, 17:647 – 649, published 20 April 2020) and Azzi et al 2020 (J Infect. 2020 Sep;81(3): e75-e78).
Claims 1-4 and 27: Cheung et al 2006 (US20060188519A1) is in the art and teaches a method of detecting SARS and SARS-like coronavirus infections in one or more individuals comprising: a) individually combining anti-SARS-CoV surface antigen, such as spike protein peptide SARS-AgS5 (SEQ ID NO: 6) (see para [0039] and [0056]; Figure 11), antibody-coated carboxylated microspheres (Luminex) (See para [0130]) with a saliva sample (see para [0045]) from each of said one or more individuals to form an admixture; b) mixing the beads and saliva sample of each individual's admixture; c) incubating the admixture(s); and d) detecting whether agglutination (see para [0112]) has occurred in each individual's admixture. Cheung et al teaches a saliva sample is comprised in an oral rinse fluid (saliva ...swabbed sample from a mucus membrane ... a buccal surface, (See, para [0045]).
Cheung et al 2006 does not teach SARS CoV-2 and beads coated with anti-SARS CoV-2 antibody.
Chen et al 2020 is in the art and teaches human monoclonal antibodies that bind to SARS-CoV-2 spike protein with the specificity of mAbs (311mab–31B5, −32D4 and −31B9 clones) to SARS-CoV-2 RBD protein by ELISA (See, Fig. 1 f and legend).
Cheung et al 2006 teaches (See, para [0010]) to the fact that said method can be used for detecting not only SARS but also other SARS-like coronaviruses.
Azzi et al 2020 is in the art and comments on and emphasizes rapid salivary test suitable for a mass screening program to detect SARS-CoV-2: A diagnostic accuracy study (See, entire article).
The instant claims 1 and 27 are similar in scope and the combined prior art teachings as recited supra teaches the limitations and renders obvious the claims 1 and 27.
It would have been obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to modify the prior art teachings of Cheung et al 2006 with the teachings of Chen et al 2020 on anti-SARS CoV-2 RBD binding monoclonal antibodies (mAbs binding to spike protein of SARS CoV-2 virus) and coat the beads with the antibodies disclosed by Chen et al 2020 and an opinion on suitability by Azzi et al 2020 to arrive at the invention of claims 1-4 and 27. One of the ordinary skills in the art would have been motivated to develop a bead-based agglutination assay to detect SARS CoV-2 virus in a sample including saliva for simplicity of the assay for diagnosis of SARS-CoV-2 infection and improving the sensitive and/or specific diagnostic assays that can detect, and in particular, that can detect SARS-CoV-2 virus in a manner that reduces the level of false positive results (See, para [0007]-[0008]) in one or more individual and for commercial success. Azzi et al 2020 teaches rapid salivary test suitable for a mass screening program to detect SARS-CoV-2 and indicates that saliva is one of the preferable samples (See, abstract, entire article). There would be a reasonable expectation of success given the applied prior art teachings in the art as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 1-4 and 27. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A, C-E).
10. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Cheung et al 2006 (US20060188519A1, published 08/24/2006), and Chen et al 2020 (Cellular & Molecular Immunology, 17:647 – 649, published 20 April 2020), Azzi et al 2020 (J Infect. 2020 Sep;81(3): e75-e78) as applied to claims 1-4 above and further in view of Franzmann et al 2009 (US20090325201A1, published 12/31/2009).
Claim 5: The combined teachings of Cheung et al 2006, Chen et al 2020, Azzi et al 2020 teaches claim 4 as recited supra, however, does not explicitly teach added limitation of claim 4.
Franzmann et al 2009 is in the field of biomarkers and methods for diagnostics (abstract) and teaches an oral rinse fluid is obtained by having each of the one or more individuals swish and gargle a saline solution in their oral cavity and then expectorate into a collection vessel, whereby the oral rinse fluid is obtained ([t]he subject sample may be selected, for example, from the group consisting of oral rinse, saliva, (See, para [0017]); collection of oral rinse: Samples are collected from patients at the clinic or screening site. For collection, five milliliters of normal saline is placed in the subject's mouths. Patients are asked to, swish for five seconds, gargle for five seconds and then spit into a specimen cup (See, para [0075]).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the combined prior art teachings of Cheung et al 2006, Chen et al 2020, Azzi et al 2020 with the teaching of Franzmann et al for the purpose of ensuring saliva samples have contact with all mucosal surfaces of interest (para [0076]) and would be obvious to the ordinary skills to use the approach recover the viral sample to enhance the detection and sensitivity limit of the assay for commercial success. There would be a reasonable expectation of success given the applied prior art teachings in the art as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claim 5. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A, C-G).
11. Claims 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Cheung et al 2006 (US20060188519A1, published 08/24/2006), and Chen et al 2020 (Cellular & Molecular Immunology, 17:647 – 649, published 20 April 2020), Azzi et al 2020 (J Infect. 2020 Sep;81(3): e75-e78) and Franzmann et al 2009 (US20090325201A1, published 12/31/2009) as applied to claims 5 above, and further in view of Agilent Technologies, Inc (published 11/15/2016), Bangs Lab 2013 (published 20 March 2013), and Castro et al 2018 (Genes, 2018, 9, 281).
Claims 6-9: The combined teachings of Cheung et al 2006, Chen et al 2020, Azzi et al 2020 and Franzmann et al 2009 teaches claim 5 as recited supra, however, does not teach added limitation of claims 6-9.
Agilent Technologies 2016 is in the bead agglutination art for analytes and teaches intensely colored and dark shade latex beads (intensely colored HiDye particles) that can be used for developing bead agglutination assay to detect analyte (See, page 1-3, PDF printout).
Bangs Lab 2013 is in the papilloma virus agglutination assay and teaches magnetic microspheres (beads) (See, page 9 col 1-2, section X Microsphere), colored microspheres (beads) (See, page 2 col 2 section 5 Mixed colors) streptavidin-coated magnetic particles are also used as a solid support in IGEN’s human papilloma virus assay (See, page 9 col 1 last para; entire PDF printout).
Castro et al 2018 teaches high-throughput incubation and quantification of agglutination assays in a microfluidic system that comprise biotin-streptavidin, a specific protein-protein interaction, as a model agglutination assay, consisting of streptavidin microbeads and biotinylated bovine serum albumin (BSA) (See, abstract, page 6, section 2.2 assay protocol).
It would have been obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to modify the combined prior art teachings of Cheung et al 2006, Chen et al 2020, Azzi et al 2020 and Franzmann et al 2009 with the additional teachings of Agilent Technologies 2016, Bangs Lab 2013 and Cstro et al 2018 to arrive at the invention of claims 6-9. One of the ordinary skills in the art would have been motivated to develop colored bead based assay for color coding of different SARS CoV-2 surface antigen epitope targeted mAbs for different epitope target and magnetic colored beads with streptavidin-linked antibodies to enable the rapid (high through-put semi-automated assays), efficient capture, separation, and machine visualization of target antigen and readout by a machine. There would be a reasonable expectation of success given the applied prior art teachings in the art as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 6-9. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A, C-E).
12. Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Cheung et al 2006 (US20060188519A1, published 08/24/2006), Chen et al 2020 (Cellular & Molecular Immunology, 17:647 – 649, published 20 April 2020), Azzi et al 2020 (J Infect. 2020 Sep;81(3): e75-e78) and Franzmann et al 2009 (US20090325201A1, published 12/31/2009), Agilent Technologies, Inc (published 11/15/2016), Bangs Lab 2013 (published 20 March 2013), and Castro et al 2018 (Genes, 2018, 9, 281) as applied to claim 9 above, and further in view of Lee et al 2014 (US20140227679A1, published 08/14/2014).
Claims 10-12: The combined teachings of prior arts as applied above teaches the claim 9 as recited supra, however, does not teach added limitation of claims 10-12 on bead diameter size.
The claims are examined in view of the support in specification para [0043] and elsewhere for bead diameter size in µm (micrometer).
Lee et al 2014 (US20140227679A1) is directed magnetic bead aggregation assay system, provided are a method and system for detecting analytes (can be read on SARS CoV-2 viral antigen in view of combined prior arts as applied to claims 10-12) in a sample by characterizing the magnetic bead aggregates on an aggregate-by-aggregate basis by measuring physical properties of the aggregates (See, abstract). The magnetic beads are selected from beads having a size range of the order of 10 nm to 10,000 nm diameter. The beads are preferably in the range of 0.1 to 5 micron size in diameter (micrometer or µm), most preferably 0.2 to 2 microns. The aggregation of magnetic beads to form aggregates is controllable by controlling magnetic bead size. The rate of aggregation of the magnetic beads increases with a decrease in magnetic particle size (See, para [0020]. The beads of a first type or second type are preferably uniform in physical properties, i.e., magnetization, color and size (See, para [0012], claim 169, entire prior art).
It would have been obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to modify the combined prior art teachings of Cheung et al 2006, Chen et al 2020, Azzi et al 2020 and Franzmann et al 2009, Agilent Technologies 2016, Bangs Lab 2013 and Cstro et al 2018 with the additional teachings of Lee et al 2014 to arrive at the invention of claims 10-12. One of the ordinary skills in the art would have been motivated to develop colored magnetic bead of the claimed diameter size for improved aggregation and sensitivity for detection of SARS CoV-2 surface antigen (See, Lee et al 2014 para [0012], [0020]). There would be a reasonable expectation of success given the applied prior art teachings in the art as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 10-12. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A, C-E).
13. Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Cheung et al 2006 (US20060188519A1, published 08/24/2006), Chen et al 2020 (Cellular & Molecular Immunology, 17:647 – 649, published 20 April 2020), Azzi et al 2020 (J Infect. 2020 Sep;81(3): e75-e78) and Franzmann et al 2009 (US20090325201A1, published 12/31/2009), Agilent Technologies, Inc (published 11/15/2016), Bangs Lab 2013 (published 20 March 2013), and Castro et al 2018 (Genes, 2018, 9, 281), Lee et al 2014 (US20140227679A1, published 08/14/2014) as applied to claim 12 above, and further in view of Buffin et al 2018 (J Virol Methods. 2018 Jan;251: 46-53).
Claims 13-14: The combined teachings of prior arts as applied and recited above teaches claim 12, however, does not teach added limitation of claims 13-14 on quantity of anti-SARS CoV-2 S antibody per mg of beads.
Buffin et al 2018 is in the virial antigen detection latex agglutination assay to quantify the amount of hemagglutinin protein in adjuvanted low-dose influenza monovalent vaccines (See, abstract). Buffin et al 2018 teaches coating of beads with antibody, two amounts of antibodies were tested: 20 and 40 mg per gram of beads that corresponds to (20 µg and 40 µg/mg of beads). This optimization was carried out using beads-coated with three reference epidemic strain serums. The best result was obtained with 40 mg (40 ug/mg of beads) of purified anti-serum per gram of beads (See, page 49, col 2, results section 3.1.).
Furthermore, as applicable to instant claims 13-14, according to section 2144.05 of the MPEP, differences in concentration (antibody coating concentration/mg of beads) or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages”).
It would have been obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to modify the combined prior art teachings of Cheung et al 2006, Chen et al 2020, Azzi et al 2020 and Franzmann et al 2009, Agilent Technologies 2016, Bangs Lab 2013, Cstro et al 2018, Lee et al 2014 with the additional teachings of Buffin et al 2018 to arrive at the invention of claims 13-14. One of the ordinary skills in the art would have been motivated to develop colored magnetic bead agglutination assay of sensitivity for detection of SARS CoV-2 surface antigen and therefore optimization of antibody quantity coating on the beads is a routine as per the bead size used (See, Lee et al 2014 para [0012], [0020]). There would be a reasonable expectation of success given the applied prior art teachings in the art as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 13-14. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A, C-E).
14. Claims 15-26, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Cheung et al 2006 (US20060188519A1, published 08/24/2006), Chen et al 2020 (Cellular & Molecular Immunology, 17:647 – 649, published 20 April 2020), Azzi et al 2020 (J Infect. 2020 Sep;81(3): e75-e78) and Franzmann et al 2009 (US20090325201A1, published 12/31/2009), Agilent Technologies, Inc (published 11/15/2016), Bangs Lab 2013 (published 20 March 2013), Castro et al 2018 (Genes, 2018, 9, 281), and Lee et al 2014 (US20140227679A1, published 08/14/2014), Buffin et al 2018 (J Virol Methods. 2018 Jan;251: 46-53) as applied to claim 14 above, and further in view of Bhaskar et al 2003 (FEMS Immunology and Medical Microbiology 39 (2003) 235-239), Schaff et al 2016 (US9244065B1, 01/26/2016).
Claims 15-26, and 28-30: The combined teachings of prior arts as applied and recited above teaches claim 14. The added limitations of claims 15-26, 28 are taught by the prior arts as recited below:
Claims 15-18, and 28-30: Cheung et al 2006 (US20060188519A1) teaches incubation step (See, para [0113], [0115].
Bhaskar et al 2003 is in the art of latex bead agglutination test and teaches mixing by a stick and incubation of antibody coated latex beads with serum from Mycobacterium tuberculosis at room temperature on a black slide for 2 minutes under field conditions and obtaining positive or negative agglutination result in 2 minutes of incubation (See, Bhaskar et al 2003, abstract, page 236, col 2, section 2.4 Test Procedure). Bhaskar et al 2003 disclosed a simple, inexpensive, sensitive and visually detectable slide agglutination test
which takes just 2 min for diagnosis of pulmonary as well as extrapulmonary TB (See, page 235, col 2 last para).
Incubation of a sample comprising a viral antigen and antibody coated beads or beads coated with viral antigen and a sample comprising an antibody e.g. serum/plasma for diagnostics assays at a room temperature or 370C is known in the art and it is within the routine laboratory practice for bead agglutination assay method optimization skills of the ordinary skills and does not involve inventive concepts. See MPEP 2144.05.
Claim 19: Batistoni et al 2013 (US8417002B2) is in the art of agglutination assay to detect viral infection disease and teaches added limitation of claim 19, wherein the detecting comprises use of a camera (See, US8417002B2, col 7 lines 17-19, col 5 lines 14-15, col 2 lines 40-45).
Claim 20: Moulds et al 2004 (US20040166551A1, published 08/26/2004) is in the art and teaches added limitation of instant claim 20, wherein the detecting comprises use of an optical density meter by disclosing detection may then be performed via methods such as magnetic detection, capacitive measurements, optical density measurements, optical imaging, spectrophotometric, the structure and design of the present invention allows for these alternatives (See, para [0051], [0012]-[0014], [0037], [0001], entire prior art publication).
Claim 21-22: Makino 2001 (Annals of Clinical & Laboratory Science, vol. 31, no. 2, 2001) is in the art and teaches added limitation of claim 22-23, wherein the detecting comprises use of a microplate reader by disclosing use of microtiter plates for latex agglutination immunoassay, an adaptation of the latex agglutination immunoassay, in conjunction with polystyrene microtiter plates and a microtiter plate reader, for the analysis of serum AMG concentrations, and mixing of a sample and antibody coated beads (See, page 205 col 2 para 1, page 207 col 1, Results, reaction time - mixing). The instant claim 21 method comprising the step comprising transferring an aliquot from each individual's admixture to a well of a multi-well plate after the mixing or incubating step and detecting whether agglutination has occurred for each individual's admixture is a design choice and does not contribute to the inventive concept and it is within the routine laboratory practice for bead agglutination assay method optimization skills for performing method for quantification of an analyte (analyte reads on amount of virions) of the ordinary skills and does not involve inventive concepts. See MPEP 2144.05.
Claim 23: Zaiko et al 2008 (Clinical Lab 2008, 54 (7- 8;) p. 273 – 279) is in the art and teaches added limitation of instant claim 23, wherein the detecting comprises use of a microarray digital reader by disclosing A microarray analytical system for performing tests of latex agglutination reaction in microformat with digital image registration was developed. The system allows the application of latex microdrops to the surface of the carrier in the form of a regular microarray and mixing of the latex droplets with the individual samples in each droplet of the microarray. The reaction is performed in a total mixture volume of about 1 microl for each of 30 samples simultaneously with video registration and interpretation of the results using a scanning device and specially developed software. The results of the semi-quantitative determination of C-Reactive Protein, Rheumatoid Factor and Anti-Streptolysin O concentrations by traditional macro- and proposed micro-array agglutination method were compared with the immunoturbidimetric measurements used as reference method. It was concluded that the suggested method for performing latex agglutination reactions on the basis of a microarray approach with digital image evaluation of results can provide a high throughput and reliable results and also offers significant advantages to the traditional latex agglutination tests with visual interpretation. Comprehensive documentation and objectification of readouts show a siginificant improvement to the present methodology (See, Zaiko et al 2008, abstract).
Claims 24-25: Schaff et al 2016 (US9244065B1, published 01/26/2016) is in the art of systems, devices, and methods for agglutination assays and teaches the added limitations of claims 23-24, further comprising adding a viscosifying agent to the admixture after the incubating step but before the transferring step (instant claim 24); and, wherein the viscosifying agent is FICOLL (instant claim 25) by disclosing Percoll as a viscosifying agent, an example of a suitable density media is Percoll™, available from GE Lifesciences. Particular densities may be achieved by adjusting a percentage of Percoll™ in a salt solution (See, US9244065B1 page 12, col 1 lines 44-64, abstract, entire prior art).
Claim 26: Buffin et al 2018 is in the art and teaches a latex agglutination assay to quantify the amount of hemagglutinin protein in adjuvanted low-dose influenza monovalent vaccines (See, abstract, page 47-48 method, Fig 3-5, entire research paper).
Additionally, Batistoni et al 2013 (US8417002B2) teaches a method of an agglutination assay to generate a quantitative result value representative of the degree of agglutination of the sample. The method includes computing the actual concentration of the sample and computing a quantitative result for each sample in the assay (See, abstract, claims 1-9, Fig. 1-11, entire prior art US8417002B2). The instant claim 26 step (d) is an assay method design choice and does not contribute to the inventive concept and it is within the routine laboratory practice for bead agglutination assay method optimization skills for performing method for quantification of an analyte (analyte reads on amount of virions) of the ordinary skills and does not involve inventive concepts. See MPEP 2144.05.
It would have been obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to modify the combined prior art teachings of Cheung et al 2006, Chen et al 2020, Azzi et al 2020 and Franzmann et al 2009, Agilent Technologies 2016, Bangs Lab 2013, Cstro et al 2018, Lee et al 2014 Buffin et al 2018, with the additional teachings of Bhaskar et al 2003, Schaff et al 2016 to arrive at the invention of claims 15-26, and 28-30.
One of the ordinary skills in the art would have been motivated to develop inventions of claims 15-26, and 28-30 comprising bead agglutination assay for sensitivity and point-of-care use or field use for detection of SARS CoV-2 surface antigen in a saliva or other patients sample from suspected COVID-19 disease or suspected SARS-CoV-2 virus infected subjects. There would be a reasonable expectation of success given the applied prior art teachings in the art as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 15-26, and 28-30. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A, C-E).
15. Claims 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over combined teachings of Cheung et al 2006 (US20060188519A1, published 08/24/2006), Chen et al 2020 (Cellular & Molecular Immunology, 17:647 – 649, published 20 April 2020), Azzi et al 2020 (J Infect. 2020 Sep;81(3): e75-e78) and Franzmann et al 2009 (US20090325201A1, published 12/31/2009), Agilent Technologies, Inc (published 11/15/2016), Bangs Lab 2013 (published 20 March 2013), Castro et al 2018 (Genes, 2018, 9, 281), Lee et al 2014 (US20140227679A1, published 08/14/2014), Buffin et al 2018 (J Virol Methods. 2018 Jan;251: 46-53) Bhaskar et al 2003 (FEMS Immunology and Medical Microbiology 39 (2003) 235-239), Schaff et al 2016 (US9244065B1, 01/26/2016) as applied to claim 30 above, and further in view of Hanke et al 2020 (bioRxiv preprint doi: https://doi.org/10.1101/2020.06.02.130161; version posted June 2, 2020).
Claims 31-32: Hanke et al 2020 is in the art and teaches added limitations of instant claims 31, wherein the anti-SARS-CoV-2 surface antigen antibody is an alpaca-derived nanobody (instant claim 31); and added limitations of instant claims 32, wherein the nanobody is Ty1 (instant claim 32) by disclosing the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike. Ty1 binds the RBD with high affinity to an epitope on the RBD accessible in both the ‘up’ and ‘down’ conformations, sterically hindering RBD and ACE2 receptor interaction/binding. Ty1 extremely potent and shows high level of specificity as Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody. Ty can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Therefore, Ty1 is an excellent candidate as an intervention against COVID-19 and can be used for SARS-CoV-2 viral antigen diagnostics assay development (See, abstract).
It would have been obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to modify the combined prior art teachings of Cheung et al 2006, Chen et al 2020, Azzi et al 2020 and Franzmann et al 2009, Agilent Technologies 2016, Bangs Lab 2013, Cstro et al 2018, Lee et al 2014 Buffin et al 2018, Bhaskar et al 2003, Schaff et al 2016 with the additional teachings of Hanke et al 2020 to arrive at the invention of claims 131-32. One of the ordinary skills in the art would have been motivated to develop inventions of claims 30-31 bead agglutination assay comprising beads coated with alpaca-derived Ty1 nanobody for higher sensitivity and point-of-care use or field use for detection of SARS CoV-2 surface antigen in a saliva or other patients sample from suspected COVID-19 disease or suspected SARS-CoV-2 virus infected subjects. There would be a reasonable expectation of success given the applied prior art teachings in the art as recited supra. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 30-31. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A, C-E).
Conclusion
16. No Claim is allowed.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Quality Assurance Specialist, Art Unit 1600