Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 25 November, 2025. Claims 1-6, 18-21, and 23 are pending in the instant application. Applicants’ election of Group I (claims 1-6) without traverse for examination on the merits is noted. Accordingly, claims 18-21 and 23 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention.
37 C.F.R. § 1.98
The information disclosure statements filed 27 February, 2025 (03), 17 March, 2025, 24 July, 2025, and 24 November, 2025, have been placed in the application file and the information referred to therein has been considered.
37 C.F.R. § 1.84
The drawings filed 12 January, 2023, have been reviewed and are acceptable.
Claim Objections
Claims 1-6 are objected to because of the following informalities: the abbreviation “SARS-CoV2” (claims 1-4) should read “SARS-CoV-2” (see Abdelrahman et al., 2020). Claim 3 is objected to because of the following informalities: the SARS-CoV-2 S mutant “R683A R685” should read “R683A, R685A”. Appropriate correction is required.
Effective Filing Date
For the purpose of applying prior art, the filing date of the claimed invention is 03 June, 2021. The earlier filed applications do not support the claim invention.
Joint Inventors, Common Ownership Presumed
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 at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed 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.
35 U.S.C. § 103
The following is a quotation of 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, 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.
Graham v. Deere
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 U.S.P.Q. 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 2, and 6 are rejected under 35 U.S.C. § 103 as being unpatentable over Huang et al. (U.S. Patent No. 11,249,083 B1, issued 15 February, 2022, and claiming priority to Prov. Appl. No. 63/125,087, filed 14 December, 2020; hereinafter referred to as “Huang et al. (2022)”). Claim 1 is directed toward method of detecting presence or absence of antibodies that target the severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) virus in a patient sample, the method comprising the following:
-incubating a solution of the patient sample with a recombinant SARS-CoV-2 S protein, peptide, or variant thereof to form a SARS-CoV-2 S treated sample solution;
-immobilizing a recombinant human angiotensin-converting enzyme 2 (rhACE2) protein, peptide, or variant thereof on a detection surface to form an ACE2-bound detection surface;
-incubating the SARS-CoV-2 S treated sample solution with the ACE2-bound detection surface to form a sample treated ACE2-bound detection surface in solution;
-removing the solution from the sample treated ACE2-bound detection surface to remove any SARS-CoV-2 S protein, peptide, or variant thereof not bound to the ACE2-bound detection surface;
-adding a labeled probe that binds to the SARS-CoV-2 S protein, peptide, or variant thereof when bound to the immobilized rhACE2 protein, peptide, or variant thereof on the detection surface;
-and, identifying or quantifying the labeled probe on the sample treated ACE2-bound detection surface,
wherein detecting the labeled probe on the sample treated ACE2-bound detection surface indicates an absence or decrease in the patient sample of anti-SARS-CoV-2 S antibodies. Claim 2 subjects the washed sample to another round of detection. Claim 6 simply specifies a patient sample (e.g., sera) be analyzed.
Huang et al. (2022) provide a method of detecting the presence or absence of antibodies capable of binding to SARS-CoV-2 S in a sample comprising the following steps:
-immobilizing a recombinant human angiotensin-converting enzyme 2 (rhACE2) protein, peptide, or variant thereof on a detection surface to form an ACE2-bound detection surface;
-incubating a solution of the patient sample with a recombinant SARS-CoV2 S protein, peptide, or variant thereof to form a SARS-CoV2 S treated sample solution;
-incubating the SARS-CoV2 S treated sample solution with the ACE2-bound detection surface to form a sample treated ACE2-bound detection surface in solution;
-removing the solution from the sample treated ACE2-bound detection surface to remove any SARS-CoV2 S protein, peptide, or variant thereof not bound to the ACE2- bound detection surface;
-adding a labeled probe that binds to the SARS-CoV2 S protein, peptide, or variant thereof when bound to the immobilized rhACE2 protein, peptide, or variant thereof on the detection surface;
-and, identifying or quantifying the labeled probe on the sample treated ACE2-bound detection surface,
wherein detecting the labeled probe on the sample treated ACE2-bound detection surface indicates an absence or decrease in the patient sample of anti-SARS-CoV2 S antibodies (see Fig. 2; col. 2; Examples 1-4). In particular, ACE2 was immobilized/coated on the well surfaces of a microtiter plate. A sample was admixed with a modified S RBD protein comprising an Fc tag. The sample was added to the well to allow ACE2-RBD binding followed by a rinsing step to remove unbound RBD. A detection reagent was added (HRP-conjugated anti-Fc antibody) and ACE2-RBD binding determined upon substrate (TMB) addition. In the absence of inhibitory antibodies, a strong signal is obtained. In the presence of neutralizing antibodies, the signal strength is reduced depending upon the concentration of antibody present. This teaching did not specifically disclose the testing of a patient sample (e.g., sera).
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize patient sera to detect anti-SARS-CoV-2 S neutralizing antibodies. Claim 9 specifically notes that biological samples obtained from SARS-CoV-2 patients may be utilized to look for neutralizing antibodies. One of ordinary skill in the art would have also been motivated to subject the wash to an additional test to determine if any residual unbound antibody is present.
Claim 3 is rejected under 35 U.S.C. § 103 as being unpatentable over Huang et al. (2022)), as applied supra to claim 1, and further in view of Andreano et al. (2021). The claim further requires the utilization of an S protein comprising an N501Y mutation in the assay. Andreano et al. (2021) identify potent neutralizing antibodies from patient convalescent sera that bind to an emerging SARS-CoV-2 S variant comprising the N501Y substitution. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize an emerging variant S protein including the N501Y mutation to provide adequate coverage and detection of new isolates.
Claims 4 and 5 are rejected under 35 U.S.C. § 103 as being unpatentable over Huang et al. (2022)), as applied supra to claim 1, and further in view of Lee et al. (U.S. Pub. No. 2023/0146256 A1, published 11 May, 2023, and claiming priority to Prov. Appl. No. 63/011,761, filed 17 April, 2020; hereinafter referred to as Lee et al. (2023)). The claims further require the utilization of an S protein comprising a detection label (e.g., His tag). Lee et al. (2023) discloses the expression, isolation, and characterization of a SARS-CoV-2 S RBD protein comprising a His tag (see Figs. 1A and 2A). The authors note that said modified S protein is particularly useful for immunoassays and can be detected using an anti-His antibody (see ¶s [0134-0140]; Example 1, pp. 23-24). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the S His tag recombinant protein of Lee et al. (2023) in the ACE2-RBD detection method of Huang et al. (2022). One of ordinary skill in the art would have been motivated to utilize this reagent because of its facile nature. The recombinant protein can be expressed and purified in large quantities making it particularly useful for large-scale immunoassays.
Additional Prior Art
The following additional prior art is noted:
- RayBio® COVI-19 Spike-ACE2 binding assay kit II, For COVID-19 drug and antibody screening, User Manual Version 1.5, published 17 November, 2020.
35 U.S.C. § 112(a)
The following is a quotation 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.
Written Description
Claims 1-6 are rejected under 35 U.S.C. § 112(a), 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, at the time the application was filed, had possession of the claimed invention. Amgen, Inc. v. Sanofi, 872 F.3d 1367, 124 U.S.P.Q.2d 1354 (Fed. Cir. 2017). AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 111 U.S.P.Q.2d 1780 (Fed. Cir. 2014). Univ. of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 920, 69 U.S.P.Q.2d 1886, (Fed. Cir. 2004). Enzo Biochem, Inc. v. Gen-Probe, Inc., 296 F.3d 1316, 63 U.S.P.Q.2d 1609, (Fed. Cir. 2002). Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 U.S.P.Q.2d 1398, (Fed. Cir. 1997). Fiers v. Revel Co., 984 F.2d 1164, 25 U.S.P.Q.2d 1601, (Fed. Cir. 1993). Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016, (Fed. Cir. 1991). In re Rasmussen, 650 F.2d 1212, 211 U.S.P.Q. 323 (C.C.P.A. 1981). In re Wertheim, 541 F.2d 257, 191 U.S.P.Q. 90 (C.C.P.A. 1976).
The crux of the statutory requirement governing written description is whether one skilled in the art, familiar with the practice of the art at the time of the filing date, could reasonably have found the later claimed invention in the specification as filed. In re Kaslow, 707 F.2d 1366, 1375, 217 U.S.P.Q. 1089, 1096 (Fed. Cir. 1983). In re Wilder, 736 F.2d 1516, 1520 222 U.S.P.Q. 349, 372 (Fed. Cir. 1984, cert. denied, 469 U.S. 1209 (1985). Texas Instruments, Inc. v. International Trade Comm’n, 871 F.2d 1054, 1063, 10 U.S.P.Q.2d 1257, 1263 (Fed. Cir. 1989). Moreover, the courts have stated that the evaluation of written description is highly fact-specific, and that broadly articulated rules are inappropriate. In re Wertheim, 541 F.2d 257, 263, 191 U.S.P.Q. 90, 97 (C.C.P.A. 1976). In re Driscoll, 562 F.2d 1245, 1250, 195 U.S.P.Q. 434, 438 (C.C.P.A. 1977). It is also important to remember that the true issue in question is not whether the specification enables one of ordinary skill in the art to make the later claimed invention, but whether or not the disclosure is sufficiently clear that those skilled in the art will conclude that the applicant made the invention having the specific claim limitations. Martin v. Mayer, 823 F2d 500, 505, 3 U.S.P.Q.2d 1333, 1337 (Fed. Cir. 1987).
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor has possession of the claimed invention. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 U.S.P.Q.2d 1961, 1966 (Fed. Cir. 1997). The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 U.S.P.Q.2d 1895, 1905 (Fed. Cir. 1996).
Determination of adequate written description requires the Examiner to read and analyze the specification for compliance with 35 U.S.C. § 112(a). In particular, each claim should be analyzed to determine its broadest reasonable interpretation consistent with written description. Each claim should be evaluated to determine if sufficient structures, acts, or functions are recited to make clear the scope and meaning of the claim, including the weight to be given the preamble. The entire application should be reviewed including the specific embodiments, figures, and sequence listings, to understand how applicant provides support for the various features of the claimed invention. The analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated that the inventor was in possession of the claimed invention. Such a review is conducted from the standpoint of one of ordinary skill in the art at the time the application was filed (see, e.g., Wang Labs., Inc. v. Toshiba Corp., 993 F.2d 858, 865, 26 USPQ2d 1767, 1774 (Fed. Cir. 1993)) and should include a determination of the field of the invention and the level of skill and knowledge in the art. Finally, the Examiner should determine whether there is sufficient written description to inform a skilled artisan that the inventor was in possession of the claimed invention as a whole at the time of filing.
Claim 1 is directed toward method of detecting presence or absence of antibodies that target the severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) virus in a patient sample, the method comprising the following:
-incubating a solution of the patient sample with a recombinant SARS-CoV-2 S protein, peptide, or variant thereof to form a SARS-CoV-2 S treated sample solution;
-immobilizing a recombinant human angiotensin-converting enzyme 2 (rhACE2) protein, peptide, or variant thereof on a detection surface to form an ACE2-bound detection surface;
-incubating the SARS-CoV-2 S treated sample solution with the ACE2-bound detection surface to form a sample treated ACE2-bound detection surface in solution;
-removing the solution from the sample treated ACE2-bound detection surface to remove any SARS-CoV-2 S protein, peptide, or variant thereof not bound to the ACE2-bound detection surface;
-adding a labeled probe that binds to the SARS-CoV-2 S protein, peptide, or variant thereof when bound to the immobilized rhACE2 protein, peptide, or variant thereof on the detection surface;
-and, identifying or quantifying the labeled probe on the sample treated ACE2-bound detection surface,
wherein detecting the labeled probe on the sample treated ACE2-bound detection surface indicates an absence or decrease in the patient sample of anti-SARS-CoV-2 S antibodies.
The claims encompass a large genus of severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) spike (S) and angiotensin-converting enzyme 2 (ACE2) variants. The SARS-CoV-2 spike protein is 1,273 amino acids in length and comprises the following amino acid sequence:
MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT (GenBank: QOH25833.1, Spike protein [Cloning Vector pCDNA3.1.2S]).
The human ACE2 protein is 805 amino acids in length and comprises the following amino acid sequence:
MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSGENPYASIDISKGENNPGFQNTDDVQTSF (GenBank: AAF99721.1; ACE-related carboxypeptidase ACE2 [Homo sapiens]).
The term variant encompasses proteins with single or multiple amino acid substitutions, insertions, or deletions. It has been well-documented that even single amino acid substitutions can abrogate antigen-antibody binding interactions. Moreover, the disclosure fails to identify suitable variants that will function in the recited assay. There is no discussion about the molecular determinants that are sine qua non for antigen-antibody binding interactions and which amino acids should be targeted for modification to produce a variant S or ACE2 protein.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that Applicant was not in possession of a sufficient number of S or ACE2 variants to support the claim breadth currently sought.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the Examiner are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 07 January, 2026