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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-28 and 49 in the reply filed on 01/02/2026 is acknowledged. Further, election of S235F for the C-terminal domain nucleocapsid, K417N for the RBD in claim 1, the use of a C-terminal domain nucleocapsid for claims 8, 9, 11, and 14, and the immunoassay species for claims 15 and 23 is acknowledged.
Claims 6, 9, 24, 61, 76, and 88 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected groups and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/02/2026.
Status of the Claims
Claims 6, 9, 61, 76, and 88 are withdrawn. Claims 1-5, 7-8, 10-23, 25-28, and 49 are pending and examined herein.
Priority
This application, filed 10/12/2022, is a CON of PCT/US21/26149, filed 04/07/2021, which claims benefit of 63/170,259, filed 04/02/2021, and 63/165,567, filed 03/24/2021, and 63/163,908, filed 03/21/2021, and 63/160,615, filed 03/12/2021, and 63/157,393, filed 03/05/2021, and 63/154,505, filed 02/26/2021, and 63/153,239, filed 02/24/2021, and 63/149,694, filed 02/16/2021, and 63/146,854, filed 02/08/2021, and 63/143,591, filed 01/29/2021, and 63/136,007, filed 01/11/2021, and 63/132,143, filed 12/30/2020, and 63/132,138, filed 12/30/2020, and 63/123,673, filed 12/10/2020, and 63/093,735, filed 10/19/2020, and 63/079,906, filed 09/17/2020, and 63/021,313, filed 05/07/2020, and 63/019,088, filed 05/01/2020, and 63/015,408, filed 04/24/2020, and 63/009,981, filed 04/14/2020, and 63/009,079, filed 04/13/2020.
Claims 1, 3-5, 7-8, 10-13, 15-23, and 49 are considered to have a priority date of 04/24/2020 for the specific disclosure of the RBD of a spike protein.
Claims 2 and 14 are considered to have a priority date of 01/11/2021 for the specific disclosure of the S235F mutation.
Claim 25 is considered to have a priority date of 05/07/2020 for the disclosure of using the sample for convalescent therapy.
Claims 26 and 27 are considered to have a priority date of 02/26/2021 for the disclosure of the BAU/mL unit.
Claim 28 is considered to have a priority date of 03/21/2021 for the disclosure of the ACE2 binding inhibition assay.
Information Disclosure Statement
The Information Disclosure Statements filed 01/09/2025, 01/10/2025, 03/26/2025, and 01/02/2026 are acknowledged and have been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that Claim 22 recites “a control reagent comprising a sequence of monoclonal antibody CR3018 or CR3022”, but there is no SEQ ID or disclosed sequence for CR3018 or CR3022. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112
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.
Claims 1-5, 7-8, 10-23, 25-28, and 49 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.
Claim 1 recites “or variant thereof”. Claim 2 recites “binds to a variant” and, similarly, “the nucleocapsid protein having one or more substitutions, deletions…comprising”. Claim 8 recites “nucleocapsid protein or variant thereof”. Claim 11 recites “nucleocapsid protein or variant thereof” and “a spike protein or variant thereof”. Claim 14 recites “comprises a variant” and “the nucleocapsid protein having one or more substitutions, deletions…comprising” and “the RBD of a spike protein having one or more substitutions, deletions…comprising”. Claim 49 recites “isolated polypeptide or variant thereof”. The use of “variant thereof” and/or the description of unspecified substitutions and deletions, including an undefined number of substitutions and deletions, fails to define the metes and bounds of the variety of proteins that could be used in the claimed invention. Claims 3-5, 7, 10, 12, 13, and 15-28 are rejected for being dependent on a rejected claim.
Claim 15 recites the limitation "wherein the SARS-CoV-2 is detected" in line 2. There is insufficient antecedent basis for this limitation in the claim. In this case, SARS-CoV-2 is not detected in the preceding claims 1, 4, and 12.
Claim 22 recites “comprising a sequence of monoclonal antibody CR3018 or CR3022.” It is unclear what “a sequence of” defines in this context. For example, given its broadest reasonable interpretation, “a sequence of” could comprise as few as 1, 2, or 3 amino acids from the full-length sequence of either antibody, which results in a vast number of potential reagents.
The terms “high qualitative agreement”, “high titer levels”, and “high probability” in claim 28 are relative terms which renders the claim indefinite. The term terms “high qualitative agreement”, “high titer levels”, and “high probability” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 26 and 27 recite the unit “BAU/mL”; however, the abbreviation “BAU” is not defined. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 25-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to§ 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is "directed to," we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a
fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical
application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an "'inventive concept' sufficient to 'transform"' the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not "wellunderstood,
routine, conventional" in the field (see MPEP § 2106.0S(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception. See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Claim 25 recites “wherein the method further comprises identifying a subject…as a candidate subject to provide a biological sample”.
The step of “identifying a subject” is categorized as an abstract idea, namely it is a mental process performed in the human mind. For example, “identifying a subject” encompasses a practitioner simply observing the results of an assay, thinking about the levels of antibodies detection from a patient sample, comparing the levels to a threshold, and making an evaluation (See MPEP 2106.04(a)(2) regarding groupings of abstract ideas). The claim, under broadest reasonable interpretation, cover the performance of these steps solely within the human mind.
Dependent claims 26 and 27 recites levels of SARS-CoV-2 IgG or IgM antibodies that would be used as threshold values to determine whether a subject should be identified. A threshold value itself is also an abstract idea, in that a threshold value is a mathematical concept. The threshold value itself merely narrows the abstract idea (the comparison of the measured value to the threshold), which does not make the comparison step less abstract and is not sufficient to provide eligibility on its own.
Step 2A, Prong 2
The above-discussed steps of “identifying” and the disclosure of threshold values are insufficient to integrate into a practical application. Specifically, steps corresponding to mental activity, which could be performed in a practitioner’s head, and mathematical concepts, are themselves judicial exceptions and not a practical application thereof.
Regarding additional recited steps, claim 1 recites a method of contacting a biological sample with a first and second specific binder and assessing a signal wherein the signal indicates the presence or amount of the target antibody. These are steps necessarily performed in order to determine the levels of the target antibodies, i.e., mere data gathering steps performed so that the antibody levels can be determined. The purpose of these limitations is merely to obtain the data. Further, such steps do not go beyond insignificant extra-solution activity in that these are mere data gathering steps necessary in order to use the abstract idea.
ELIGIBILITY OF STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN “INVENTIVE CONCEPT”
Further, the additional elements of the claims (the active method steps/limitations recited in addition to the judicial exceptions themselves) do not add significantly more to the judicial exception(s); the additional recited claim elements are recited at a high level of generality, and are not, for example, limited to any particular testing technique or platform as claimed.
As taught by US 2023/0184765 A1, “DETECTION ASSAYS FOR CORONAVIRUS NEUTRALIZING ANTIBODIES” (priority to 04/17/2020, referred to herein as Russell), the detection of anti-SARS-CoV-2 antibodies is important for selecting the best donors for convalescent plasma therapy (para. 0132, lines 1-13).
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well-understood, conventional or routine in the field of antibody detection and patient serum evaluation.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3- 5, 8, 10-13, 17, 19-21, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cai et al., “A peptide-based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Corona Virus Disease 2019 (COVID-19)” medRxiv (published 02/25/2020, IDS dated 01/09/2025, referred to herein as Cai).
Regarding claim 1, 4, 5, 10, and 23, Cai teaches an immunoassay method for detecting an anti-SARS-CoV-2 antibody in a subject (lines 122-123) comprising contacting a biological sample with a nucleocapsid protein and a second binding partner with a detectable label, i.e. an enzyme-conjugated antibody, resulting in an immunocomplex (lines 122-130). Cai teaches that the signal from the complex is assessed and indicates the presence of an anti-coronavirus IgG and IgM antibodies (lines 94-97).
Regarding claims 3 and 16, Cai teaches that the biological samples are patient sera (lines 100-104).
Regarding claims 8 and 11, the claimed SEQ ID NO: 1 is the C-terminal domain of the SARS-CoV-2 nucleocapsid protein. Cai teaches using the SARS-CoV-2 nucleocapsid protein as the first specific binding partner in the assay (lines 122-126), which has the sequence of SEQ ID NO: 1. Cai teaches detecting IgG and IgM antibodies in a single sample using the method (lines 170-171).
Regarding claim 12, Cai teaches all of the components and steps of claim 4 and, therefore, would be considered to be capable of detecting the same amount of anti-SARS-CoV-2 IgG antibodies as the claimed method, such as about 91% or about 99%.
Regarding claim 13, Cai teaches detecting SARS-CoV-2 from the biological samples with real time RT-PCR (lines 103-104).
Regarding claim 17, Cai teaches detecting positive results for IgM and IgG antibodies in a single sample that is positive for infection, which is an acute phase of infection (lines 190-192).
Regarding claim 19, Cai teaches immobilizing the peptide to a solid support bead (lines 126-127).
Regarding claim 20, Cai teaches doing the method in about 10 minutes (lines 128-130).
Regarding claim 21, Cai teaches using sera from people infected with other viruses, which is considered to be a control reagent (lines 152-153).
Claim 7 is rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Cai.
Regarding claim 7, Cai teaches the use of an “antibody conjugate” (lines 129-130) to specifically detect IgG and IgM antibodies captured by the target peptide (lines 94-97). An artisan would recognize that the antibody conjugates used by Cai are anti-human-IgG IgG and anti-human-IgM IgG. In the alternative interpretation where the antibody conjugate used by Cai is not interpreted to be these antibodies, it would have been obvious for an artisan to substitute the antibody conjugates used by Cai with anti-human-IgG IgG and anti-human-IgM IgG as is routine in the art of antibody detection.
Claims 1, 3-5, 7, 8, 10, 12, 13, 15, 16, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Okba et al., “SARS-CoV-2 specific antibody responses in COVID-19 patients” medRxiv (published 03/20/2020, IDS dated 01/09/2025, referred to herein as Okba).
Regarding claim 1, Okba teaches a method for detecting the presence of an anti-SARS-CoV-2 antibody in a subject (Abstract, lines 4-5). Okba teaches contacting a biological sample with the RBD of a spike protein and the nucleocapsid protein, which includes the C-terminal domain (p. 2, para. 2, lines 8-12). Okba teaches contacting the sample with a second specific binding partner with an HRP-label (p. 5, para. 4, lines 5-6), forming a complex. Okba teaches assessing the signal to detect the tarter antibody (p. 5, para. 5, line 6 – p. 6, para. 1, line 1).
Regarding claim 3, Okba teaches that the biological samples are serum (p. 3, para. 2, line 1 and para. 3, line 1).
Regarding claim 4, Okba teaches detection of an IgG antibody (p. 5, para. 4, lines 5-6).
Regarding claims 5, 7, and 10, Okba teaches the use of the nucleocapsid protein to detect anti-coronavirus IgG antibody with rabbit anti-human IgG (p. 5, para. 4, lines 1-6).
Regarding claim 8, the claimed SEQ ID NO: 1 is the C-terminal domain of the SARS-CoV-2 nucleocapsid protein. Okba teaches using the SARS-CoV-2 nucleocapsid protein as the first specific binding partner in the assay (p. 2, para. 2, lines 8-12).
Regarding claim 12, Okba teaches all of the components and steps of claim 4 and, therefore, would be considered to be capable of detecting the same amount of anti-SARS-CoV-2 IgG antibodies as the claimed method, such as about 91% or about 99%.
Regarding claims 13 and 15, Okba teaches using PCR and spike protein immunofluorescence to detect SARS-CoV-2 in the sample (p. 3, para. 3, lines 1-3).
Regarding claim 16, Okba teaches that the samples are obtained at different times (p. 3, paras. 2 and 3).
Regarding claim 28, Okba teaches further detecting neutralizing antibodies (p. 4, para. 2, lines 1-4).
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.
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.
Claims 2 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Okba in view of Haynes et al., “Impact of B.1.1.7 variant mutations on antibody recognition of linear SARS-CoV-2 epitopes” medRxiv (published 01/08/2021, referred to herein as Haynes).
Regarding claims 2 and 14, Okba teaches using a nucleocapsid protein (p. 2, para. 2, lines 8-11).
However, Okba does not teach the use of a nucleocapsid peptide with the S235F mutation.
Haynes teaches that the S235F mutation is present in the nucleoprotein B.1.1.7 strain of SARS-CoV-2 (p. 1, col. 2, para. 3, lines 1-2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the nucleocapsid protein taught by Okba by including the S235F mutation taught by Haynes. An artisan would have had an expectation of success and be motivated to make this change in order to study the antibodies generated in patients by the B.1.1.7 strain by this naturally occurring protein.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Cai in view of Okba et al., “SARS-CoV-2 specific antibody responses in COVID-19 patients” medRxiv (published 03/20/2020, referred to herein as Okba).
Regarding claim 15, Cai teaches detecting SARS-CoV-2 in patient samples by its viral RNA (lines 103-104).
However, Cai does not teach detecting SARS-CoV-2 in patient samples by its viral antigen.
Okba teaches that when using samples for detecting the presence of anti-SARS-CoV-2 antibodies (Abstract, lines 4-5), presence of the virus can be detected with PCR and/or antigen-based immunoassay (p. 3, para. 3, lines 1-3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Cai by substituting the PCR-based detection of SARS-CoV-2 with the antigen-based immunoassay taught by Okba. Doing so would have been readily apparent and deemed to be a mere simple substitution of one known element for another to obtain predictable results (See MPEP 2141(III): Exemplary Rationales that support a conclusion of obviousness). One skilled in the art would have had a reasonable expectation of success in making this substitution because as taught by Okba, SARS-CoV-2 detection in patient samples can be done by PCR or antigen-based immunoassay.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Cai in view of Martins et al., “An Evaluation of the Effectiveness of Three Immunoglobulin G (IgG) Removal Procedures for Routine IgM Serological Testing” Clinical and Diagnostic Laboratory Immunology (published 01/1995, referred to herein as Martins).
Regarding claim 18, Cai teaches the detection of IgM using an ELISA (lines 141-143).
However, Cai does not teach a pre-treatment step comprising anti-human IgM and/or IgG.
Martins teaches a method of detecting IgM in a sample comprising pre-treatment with anti-human IgG (p. 98, col. 2, para. 1, lines 1-14 and p. 100, col. 2, para. 2, lines 1-4). Martins teaches that pre-treatment with anti-human IgG removes false-negative reactions during IgM detection via viral antigen by removing interfering IgG antibodies (p. 101, col. 1, para. 2, lines 1-10).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the IgM detection method taught by Cai by adding the pre-treatment step with anti-human IgG taught by Martins. An artisan would have been motivated and had a reasonable expectation of success in making this change because, as taught by Martins, this step is useful for the removal of false-negative results when detecting IgM levels using viral antigens, such as in the method taught by Cai.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Cai in view of Martins and further in view of van den Brink et al., “Molecular and Biological Characterization of Human Monoclonal Antibodies Binding to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome Coronavirus” Journal of Virology (published 02/2005, IDS dated 01/09/2025, referred to herein as Brink).
Regarding claim 22, Cai teaches a method of detecting anti-SARS-CoV-2 nucleocapsid IgG antibodies (lines 141-145).
However, Cai doesn’t teach using a control reagent comprising a sequence of monoclonal antibody CR3018 or CR3022.
Martins teaches a method of detecting antibodies in a sample comprising the use of a positive control (Table 5, “ELISA controls, Positive”). Martins teaches that the positive control comprises a control antibody (p. 101, col. 1, para. 2, lines 1-5). Martins teaches that the use of a positive control is useful in order to establish “cutoff” values (p. 101, col. 2, para. 2, lines 23-33).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the IgG detection method taught by Cai to include a positive control, as taught by Martins. An artisan would have been motivated to make this change and have a reasonable expectation of success because, as taught by Martins, the use of a positive control antibody is useful for determining cutoff control and the functionality of the assay, which is routine in the art of biochemical antibody-based detection methods.
However, Cai in view of Martins does not teach the specific use of a reagent comprising a sequence of CR3018 or CR3022.
Brink teaches that the CR3018 antibody binds to the nucleocapsid protein of SARS coronavirus (Figure 4A, p. 1637, col. 2, para. 2, lines 8-12).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of IgG detection with a positive control, as taught by the combination of Cai in view of Martins, by using the CR3018 antibody taught by Brink as the positive control. An artisan would have been motivated to make this change in order to have a specific control for binding to the nucleocapsid protein used by Cai for the detection of IgG. An artisan would have had a reasonable expectation of success because, as taught by Brink, the CR3018 antibody binds to the RSAPRITFG residues of the SARS-CoV nucleocapsid protein, which are highly conserved in the SARS-CoV-2 nucleocapsid protein.
Claims 25 is rejected under 35 U.S.C. 103 as being unpatentable over Cai in view of US 2023/0184765 A1 “DETECTION ASSAYS FOR CORONAVIRUS NEUTRALIZING ANTIBODIES” (priority date 04/17/2020, referred to herein as Russell).
Regarding claim 25, Cai teaches a method of detecting anti-SARS-CoV2 IgG and IgM antibodies in patient serum samples (lines 57-60).
However, Cai does not teach identifying a subject having IgM or IgG antibodies as a candidate subject to provide a biological sample for use in convalescent therapy against SARS-CoV-2.
Russell teaches a method of detecting SARS-CoV-2 neutralizing antibodies in a sample (Abstract, lines 3-11). Russell teaches that methods detecting seropositivity in patient samples, such as detecting the production of IgG and IgM in patient samples, is useful “for selecting best donors for convalescent plasma therapy” (para. 0132, lines 1-13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of antibody detection taught by Cai in order to identify donors for convalescent therapy as taught by Russell. An artisan would have been motivated to use the assay to make this selection because the identification of convalescent therapy donors is an important step in producing useful therapeutics against SARS-CoV-2 infection. An artisan would have had a reasonable expectation of success in identifying donors by using the method taught by Cai because the method taught by Cai identifies subjects that produce antibodies that bind to the major SARS-CoV-2 antigen nucleocapsid and spike proteins. As taught by Russell, antibodies against the nucleocapsid and spike proteins are effective at neutralizing the virus.
Claims 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Cai in view of Russell as applied to claim 25 above, and further in view of “Establishment of the WHO International Standard and Reference Panel for anti-SARS-CoV-2 antibody” World Health Organization (published 12/10/2020, referred to herein as WHO).
Regarding claims 26 and 27, Cai in view of Russell teach a method of detecting anti-SARS-CoV-2 antibodies and identifying subjects as potential donors for convalescent therapy.
However, Cai in view of Russell does not teach a specific threshold value for identifying subjects as donors.
WHO teaches that serum with 250 IU/ampule is the standard for neutralizing and binding antibody activity (p. 16, para. 5, lines 3-7). WHO teaches that each ampule has 0.25 mL, which results in a binding activity of 1000 IU/mL concentration (p. 16, para. 5, line 7). The IU/mL unit described by WHO is considered to be equal to the claimed BAU/mL unit, as both are arbitrary units that describe the binding of anti-SARS-CoV-2 antibodies to antigens. The concentration of 1000 IU/mL is at least 100 BAU/mL as in claim 26 and at least 500 BAU/mL as in claim 27. WHO teaches that this sample can be used as a standard for selecting convalescent plasma samples from patients (p. 16, para. 5, line 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to identify subjects as being donors for convalescent therapy as taught by Cai in view of Russell by using the threshold IU/mL value taught by WHO. An artisan would have been motivated and had a reasonable expectation of success in using this threshold because, as taught by WHO, this standard concentration describes anti-SARS-CoV-2 antibody binding and should be used as a Standard for comparison when evaluating potential convalescent plasma samples (p. 16, para. 5, line 1).
Claim 49 is rejected under 35 U.S.C. 103 as being unpatentable over Okba in view of Zuk et al. (US 4,208,479, published 06/17/1980).
Regarding claim 49, Okba teaches doing as immunoassay comprising a SARS-CoV-2 polypeptide as a specific binding partner and a second specific binding partner with a detectable label (p. 5, para. 4, lines 1-6).
However, Okba does not specifically teach including these components in a kit.
Zuk teaches that in performing assays, it is convenient and to combine the necessary reagents together in a kit (column 22, lines 20-68 in particular). Zuk further teaches that this may improve assay accuracy.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to package together the reagents of Okba in the form of a kit for convenience, improvement in accuracy, and/or for the purpose of commercial sale.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 19-21, and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 13-16 of copending Application No. 17/934,810 (reference application, referred to herein as ‘810). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application claims a genus of the species claimed in ‘810.
Regarding claim 1 of the instant application, ‘810 discloses a method of detecting the presence or amount of an anti-SATS-CoV-2 antibody in a subject comprising contacting the sample with a first specific binding partner comprising a spike protein polypeptide, and a second specific binding partner with a detectable label, then assessing a signal from the complex wherein it indicates the presence or amount of the target antibody (claim 1).
Regarding claim 4 of the instant application, ‘810 discloses detecting an IgG or IgM antibody (claims 2 and 3).
Regarding claim 19 of the instant application, ‘810 discloses immobilizing the polypeptide on a solid support (claim 13).
Regarding claim 20 of the instant application, ‘810 discloses performing the method in about 5 to 20 minutes (claim 14).
Regarding claim 21 of the instant application, ‘810 discloses using a calibrator or control reagent (claim 15).
Regarding claim 23 of the instant application, ‘810 discloses the method is an immunoassay or clinical chemistry assay (claim 16).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowable.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 April 4, 2026