DETAILED 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. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. SG10202009679P, filed on 09/29/2020.
Status of Claims
3. Claims 1, 3-7 and 18-30 filed on 02/15/2023 are pending.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted/filed on 02/15/2023 and 10/15/2024 is in compliance with the provisions of 37 CFR 1.97 and is being considered by the examiner.
5. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 102
6. 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
7. Claims 1, 3-7 and 18-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lapuente et al 2020 (published in medRxiv May 13, 2020).
Claims 1 and 19: Lapuente et al 2020 disclose a method of claims 1 and 19, a method of identifying / characterizing coronavirus infection, SARS-CoV-2 infection (coronavirus infection) in a subject, the flow cytometric method to assess SARS CoV-2 spike-(SARS CoV-2 S protein) specific antibody responses. HEK 293T cells expressing SARS-CoV-2 spike protein in its natural confirmation on the surface were used to detect specific IgG and IgM antibody responses in patient sera by flow cytometry. The method comprised contacting a serum sample from the subject with HEK 293T cells expressing SARS-CoV-2 spike protein and detecting a binding of SARS-CoV-2 specific gG and IgM antibody binding to the SARS-CoV-2 spike protein expressed on the surface of HEK 293T cells. The disclosed method of Lapuente et al 2020 can therefore implicitly and specifically detect antibodies to SARS CoV-2 S protein in a subject having immunity for SARS CoV-2 infection (coronavirus infection) as recited supra (See, p. 1 abstract; p. 3, materials and methods, serum samples).
Claims 3 and 20: Lapuente et al 2020 disclose the added limitation of claims 3 and 20 by disclosing flow cytometric antibody assay, the gating strategy and the respective IgM and IgG mean fluorescence 172 intensity (MFI) signals for three negative controls and three SARS-CoV-2 convalescent sera. (See, abstract’ p.4 methods; p.7 lines 171-179; p. 17 Figure 1 and legends; p.18, figure 2).
Claims 4 and 21: Lapuente et al 2020 disclose the added limitation of claims 4 and 21 by disclosing, the method further comprising contacting / incubating the sample with one or more detection or secondary antibody (See, p. 5 line 119 of lines 112-119; p.7 lines 164-166; p. 17 Figure 1 legend).
Claim 5, 18 and 22-23: Lapuente et al 2020 disclose the added limitation of claims 5 and 22-23 by disclosing, wherein the method is a diagnostic method, a serological diagnostic method by disclosing evaluation of a novel flow cytometric approach to assess spike-specific antibody responses based on the HEK 293T cells expressing SARS-CoV-2 spike protein to detect specific IgG and IgM antibody responses in patient sera by flow cytometry. Analyses of 201 pre-COVID-19 sera proved a high assay specificity in comparison to commercially available CLIA and ELISA systems, while also revealing the highest sensitivity in specimens from PCR-confirmed SARS-CoV-2-infected patients. The external standard allowed robust quantification of antibody responses among different assay platforms. newly established flow cytometric assay allows sensitive and quantitative detection of SARS-CoV-2-specific antibodies, which can be easily adopted in different laboratories and does not rely on external supply of assay kits. The flow cytometric assay also provides a blueprint for rapid development of serological tests to other emerging viral infections (See, abstract, p. 8 lines 180-186, p. 10 lines 243-245, p. 302-304; p.16 Table 1).
Claims 6 and 24: Lapuente et al 2020 disclose the added limitation of claims 6 and 24 by disclosing, the method further comprising performing a further assay such as a polymerase chain reaction (PCR)-based assay to detect/confirm coronavirus infection, SARS-CoV-2 infection (See, p. 4 lines 88-89, p. 8 lines 183; p. 16 table 1 last row; p. 16 table 2).
Claims 7 and 25: Lapuente et al 2020 disclose the added limitation of claims 7 and 25 by disclosing the HEK293 cells expressing SARS CoV-2 S protein-based flow cytometric method for detection antibodies (IgG and IgM) in serum samples obtained from SARS CoV-2 patients as the method is an in-vitro or an ex-vivo method (See, abstract).
Claims 26-28: Lapuente et al 2020 disclose the added limitation of claims 26-28 by disclosing:
a product comprising:
a) a nucleic acid, an isolated and/or recombinant nucleic acid, encoding for the full length spike protein (S protein) of severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), (the nucleotide sequence, the codon-optimized sequence of SARS CoV-2 S protein), encoding SARS CoV-2 S protein is incorporated by reference 12 Hoffman et al 2020 (See, p. 4, lines 94-96), or
c) a host cell, an isolated host cell, HEK293 cells expressing SARS CoV-2 full length S protein, comprising a nucleic acid, an isolated and/or recombinant SARS CoV-2 full length S protein encoding nucleic acid of severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) (See, p. 4 lines 100-106; p.5 107-115, p. 7 lines 164-165).
Claim 29: Lapuente et al 2020 disclose the added limitation of claims 29 by disclosing, wherein the S protein comprises SEQ ID NO: 1. The instant SEQ ID NO: 1 (Qy) has full length 100% amino acid sequence identity with the sequence deposited in the GenBank Sequence ID: YP_009724390.1 (Lapuente et al 2020 disclosed by Hoffmann et al 2020 Cell, 2020, 181, p. 271–280 reference incorporated for the SARS CoV-2 S protein full sequence YP_009724390.1 (See, p.4 lines 95-96, and reference 12 of Hoffmann et al 2020 as reference to p. 14 line 358), the amino acid sequence identity match is shown below.
Query Match 100.0%; Score 6722; DB 1; Length 1273;
Best Local Similarity 100.0%;
Matches 1273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
Qy 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
Qy 121 NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE 180
Qy 181 GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQT 240
Qy 241 LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK 300
Qy 301 CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN 360
Qy 361 CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 420
Qy 421 YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC 480
Qy 481 NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN 540
Qy 541 FNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITP 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 FNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITP 600
Qy 601 GTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSY 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSY 660
Qy 661 ECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTI 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 ECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTI 720
Qy 721 SVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQE 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 SVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQE 780
Qy 781 VFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 VFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC 840
Qy 841 LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM 900
Qy 901 QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALN 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALN 960
Qy 961 TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA 1020
Qy 1021 SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA 1080
Qy 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
Qy 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
Qy 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD 1260
Qy 1261 SEPVLKGVKLHYT 1273
|||||||||||||
Db 1261 SEPVLKGVKLHYT 1273
Claim 30: Lapuente et al 2020 disclose the added limitation of claims 20 by disclosing the host cell is bound to an antibody, an antibody against SARS-CoV-2 shows the flow cytometry results (figure on left, and additional figures in figure 1 and legends) showing HEK293 cells expressing SARS CoV-2 full length S protein bound to SARS CoV-2 specific IgG or IgM antibodies and the binding is detected by a secondary fluorescence marker labelled antibody (See, p. 17 figure 1; methods and results for HEK293 cells expressing SARS CoV-2 S protein and methods for serum samples from SARS CoV-2 patients and positive and negative control sera).
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, 3-7 and 18-30 are rejected under 35 U.S.C. 103 as being unpatentable over Lapuente et al 2020 (published in medRxiv May 13, 2020) and further in view of Hoffmann et al 2020 (Cell, 2020, 181, 271–280), Grzelak et al 2020 (Sci. Transl. Med. 12, eabc3103, p. 1-13), Schwartz et al 2021 (WO2021209824A1 with an earlier priority date 04/17/2020 for US 63/011,368 and 05/05/2020 US 63/020,063), Csiszovszki et al 2021 (Publication of US10973909B1 published 04/13/2021 with earlier priority to GB2004974 filed on 04/03/2020), and Wajnberg et al 2020 (Lancet Microbe. 2020 Nov;1(7):e283-e289).
Claims 1, 3-7 and 18-30: The disclosures of the prior art teachings of Lapuente et al 2020, as recited supra, are incorporated by reference here in entirety to render obvious the claims 1, 3-7 and 18-30.
Lapuente et al 2020 is in the art and teaches instant claims 1, 3-7 and 18-30 as recited supra and is incorporated here in entirety.
Hoffmann et al 2020 is in the art and teaches SARS CoV-2 S protein full length 100% amino acid sequence identity as recited supra (claim 29 limitation).
Grzelak et al 2020 is in the art and teaches a comparison of four serological assays for detecting anti–SARS-CoV-2 antibodies in human serum samples from different populations. One of the four assays is S-Flow assay that recognized (SARS CoV-2 antibodies in patients serum samples) the S protein expressed at the 293T cell surface using flow cytometry, measuring anti–SARS-CoV-2 antibodies in human serum samples with the S-Flow assay, teaches SARS CoV-2 S gene GenBank QHD43416.1 that has 100% amino acid sequence identity with instant SEQ ID NO: 1 (See, abstract, p. 3 col 1-2, p. 5 Fig 1 and associated legends, p.6 Figure 2 and legends, p.10 col 2 S-Flow assay , p.11 col 1).
Schwartz et al 2021 (WO2021209824A1 ) is in the art and teaches eukaryotic cells, such as 293T cells, expressing a SARS-CoV-2 S protein, immune complexes comprising the cells, and methods of using the cells to detect antibodies against a SARS-CoV-2 S protein and methods of using the cells for diagnosing of a SARS-CoV-2 infection in a patient using the method based on flow-cytometry (See, abstract, claims 1-27, para [0008], [0014]-[0027] and entire WO2021209824A1).
Csiszovszki et al 2021 (US10973909B1) teaches coronavirus vaccine, the polypeptides and vaccines comprise T cell and/or B cell epitopes that are immunogenic in a high percentage of individuals in the human population and a method of stimulating an immune response against a SARS-CoV-2 infection in an individual. The SEQ ID NO 122 disclosed by Csiszovszki et al 2021 has 100% amino acid sequence identity match with SARS CoV-2 S protein sequence in SEQ ID NO: 1 of instant claim 29. Csiszovszki et al 2021 teaches subjects having vaccine induced immunity for coronavirus and provides serum or plasma samples from the immune subjects for the method of claim 19 and dependent claims (See, abstract and claims 1-12, entire prior art).
Horndler et al 2020 is in the art and teaches claims 26-28 by disclosing a sensitive and quantitative flow cytometry method using the cytometer-friendly non-adherent Jurkat T-cell line that is stably transfected using a lentiviral vector and the stably transfected cells expresses the full-length native spike "S" protein of SARS-CoV-2 (See, abstract and entire article).
Wajnberg et al 2020 is in the art and teaches instant claims 6, 22, and 24 by disclosing humoral response (antibody) and PCR positivity in patients with COVID-19 (SARS CoV-2 infected patients) and concludes that most patients with confirmed COVID-19 seroconvert (See, abstract and entire article).
It would have been obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior teachings of Lapuente et al 2020 with the additional prior art teachings of Hoffmann et al 2020, Grzelak et al 2020, Schwartz et al 2021, Csiszovszki et al 2021, Horndler et al 2020 and Wajnberg et al 2020, as applied and recited supra, to arrive at the invention of claim 1, 3-7 and 18-30. The motivation would be to develop a SARS COV-2 S protein native confirmation based qualitative and quantitate flow cytometry-based serological (antibody) assay for serological diagnosis in SARS CoV-2 (coronavirus infected subjects) patients for confirmatory serological diagnosis or determining an antibody response in the SARS CoV-2 S protein comprising vaccine composition immunized / vaccinated subjects to assess the antibody immune status of the subjects and for the commercial success. One of the ordinary skills in the art would have a reasonable expectation of success given the disclosures of the prior art teachings as applied to claims 1, 3-7 and 18-30 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, 3-7 and 18-30. 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, G).
Conclusion
10. No claim is allowed.
11. 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; Off every second Friday in bi-weekly PP..
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/SAMADHAN JAISING JADHAO/ Examiner, Art Unit 1671
/JANET L ANDRES/ Supervisory Patent Examiner, Art Unit 1671