DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Disposition of Claims
Claims 1-18 and 20-21 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2023/0251259 A1, Published 10 August 2023. Applicant’s amended Specifications as presented on 24 April 2023 and 21 November 2022 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
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.
The information disclosure statement (IDS) submitted on 21 November 2022 has been considered, as a whole, by the examiner. Any individual references with strikethroughs, however have not been considered.
Specification
The disclosure is objected to because of the following informalities: throughout the Specification, the reference strain is referred to by only its Accession Number, MT066156, instead of providing either the GI number or the Accession.Version Number.
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 1-2, 7-10, 12-16, and 18 are objected to because of the following informalities: In Claims 1-2, 7, and 12-16, all instances of the phrase “SARS-CoV-2 virus” should be replaced with “SARS-CoV-2”. The inclusion of the word “virus” is redundant.
In Claim 1, it is suggested that it say “one or more anti-SARS-CoV-2 specific antibodies” instead of “one or more anti-SARS-CoV-2 specific antibody”.
In Claims 8-9, it is suggested that they say “The method according to claim X, wherein”. The commas are missing before their respective wherein clauses.
In Claim 10, it is suggested that it say “spike glycoprotein” instead of “virus spike glycoprotein”.
In Claim 18, it is suggested that it say “or a natural or recombinant derivative thereof” instead of “or natural or recombinant derivative thereof”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
Claim 5, and dependent claims 6-9 and 21 thereof, is 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.
Regarding Claim 5, the use of the word “preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the word are part of the claimed invention. See MPEP § 2173.05(d). It is suggested that the claim be amended by removing said language or reciting the limitations following said word as an additional dependent claim which further limits the parent claim, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 5 is rejected on the grounds of being indefinite. Claims 6-9 and 21 are also rejected because they depend upon Claim 5, but do not remedy the deficiencies of Claim 5.
Claim 9 is 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.
Regarding Claim 9, the use of “e.g.” (“e.g.” means “exempli gratia” which translates to “for example”) renders the claim indefinite because it is unclear whether the limitation(s) following the term are part of the claimed invention. See MPEP § 2173.05(d). It is suggested that the claim be amended by removing said language or reciting the limitations following said word as an additional dependent claim which further limits the parent claim, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 9 is rejected on the grounds of being indefinite.
Claim 10 is 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.
Regarding Claim 10, it recites the limitation “wherein said inactivated purified SARS-CoV-2 whole virus particles comprise at least one of the following proteins of SARS-CoV-2: virus spike glycoprotein, nucleocapsid protein, membrane protein, an envelope protein or an immunogenic fragment thereof”. The use of the phrase “an envelope protein or an immunogenic fragment thereof” renders the claim indefinite because, as currently written, the limitation “an immunogenic fragment thereof” appears to be only in relation to the envelope protein, and not any of the other proteins recited in the claim. If this limitation is meant to be with regard to all the recited proteins, which is believed to be the intention of the claim language, it is suggested that the claim be amended to recite “an envelope protein, or an immunogenic fragment thereof”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 10 is rejected on the grounds of being indefinite.
Claims 11-13 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.
Claims 11-13 recites the limitation "the subject" in Lines 3, 2, and 1, respectively. There is insufficient antecedent basis for this limitation in the claims. All three claims depend upon Claim 1, but Claim 1 does not introduce the limitation of “a subject”. It is suggested that the claims be amended to properly introduce the limitation of “a subject”, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 11-13 are rejected on the grounds of being indefinite.
Claim 16 is 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.
Regarding Claim 16, the use of the phrase “such as” renders the claim indefinite because it is unclear whether the limitation(s) following the word are part of the claimed invention. See MPEP § 2173.05(d). It is suggested that the claim be amended by removing said language or reciting the limitations following said phrase as an additional dependent claim which further limits the parent claim, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 16 is rejected on the grounds of being indefinite.
Claim 16 is 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.
Regarding Claim 16, it recites the limitation “which is for the detection in a sample of antibodies against a variant of SARS-CoV-2 virus, such as English, South African or Brazilian variant”. The use of the phrase “a sample” renders the claim indefinite because it is unclear if this sample is different from the “biological sample” introduced in Claim 1, which Claim 16 depends upon. “A/An” is an indefinite article, while “the” is a definite article. “The” refers back to a specific sample from Claim 1, while “A” can refer back to any non-specific sample and is not clear that it is only referencing the sample of Claim 1. It is suggested that the claim be amended by replacing “a sample” with “the sample”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 16 is rejected on the grounds of being indefinite.
Claim 17 is 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.
Regarding Claim 17, it recites the limitation “a labelled antibody anti-SARS-CoV-2 antigen”. It is unclear exactly what this phrase is referring to or claiming as it appears to be reciting two different types of molecules, namely an antibody and an antigen. Additionally, it is also unclear what an “anti-SARS-CoV-2 antigen” is. This lack of clarity renders the claim indefinite. It is suggested that the claim be amended by clarifying what exactly is being claimed, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 17 is rejected on the grounds of being indefinite.
Claim 18 is 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.
Regarding Claim 18, it recites the limitation “wherein said inactivated purified SARS-CoV-2 whole virus particles are particles of the SARS-CoV-2 strain 2019-nCoV/Italy-INMII (GenBank: SARS-CoV-2/INMII-Isolate/2020/Italy: MT066156) or natural or recombinant derivative thereof”. The use of the Accession Number only, MT066156, as opposed to either the GI number or the Accession.Version number, renders the claim indefinite as it constitutes an improper incorporation by reference. It is suggested that the claim be amended by instead referring to the GI number or the Accession.Version number instead of only the Accession number, as long as said amendment is supported by the originally-filed application, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 18 is rejected on the grounds of being indefinite.
Claim Interpretation
In light of the issues raised above, the claims are being interpreted as reading upon the following:
Claim 1 is drawn to a method of detecting one or more anti-SARS-CoV-2 specific antibody in a biological sample, the method comprising: a) incubating the biological sample with inactivated purified SARS-CoV-2 whole virus particles under suitable conditions to obtain a SARS-CoV-2 virus/antibody complex; b) optionally washing to remove unbound material; c) detecting said SARS-CoV-2 virus/antibody complex.
Further limitations on the method according to Claim 1 are:
2. The method of claim 1, wherein the anti-SARS-CoV-2 antibody is an IgG and/or IgM and/or an IgA antibody.
3. The method of claim 1, wherein said inactivated purified SARS-CoV-2 whole virus particles are pre-immobilized to a solid support.
4. The method of claim 3, wherein the solid support is a chip, column matrix material, a culture plate, a tube, a dish, a flask, a microtiter plate, a bead, microsphere, reactor vessel, wells, a polystyrene paramagnetic particle (PMP) or a latex magnetic particle (LMP) or a combination thereof.
5. The method of claim 1, wherein the detecting step is performed by means of a labelled secondary antibody.
6. The method according to claim 5, wherein the secondary antibody is labeled with a radioactive isotope, or an enzyme.
7. The method of claim 6, wherein the detecting step comprises measuring a signal from the label and comparing the signal to a control signal from a control biological sample known to be negative for SARS-CoV-2 antibodies.
8. The method according to claim 5, wherein said secondary antibody is an antibody against human antibodies or an antibody against a SARS-CoV-2 antigen.
9. The method according to claim 8, wherein said antibody against a SARS-CoV-2 antigen is an antibody directed to the Spike protein of SARS-CoV-2 and/or said antibody has a neutralizing activity.
10. The method of claim 1, wherein said inactivated purified SARS-CoV-2 whole virus particles comprise at least one of the following proteins of SARS-CoV-2: spike glycoprotein, nucleocapsid protein, membrane protein, an envelope protein, or an immunogenic fragment thereof.
11. The method of claim 1, wherein the biological sample is selected from the group consisting of blood, serum, plasma, body fluid, saliva and other secretions from the subject or tissue or cell extracts.
12. The method of claim 1, wherein the biological sample is obtained from the subject at least 3 days for IgM and IgA and at least 10 days for IgG after onset of symptoms of SARS-CoV-2 infection or after a risk of exposure to SARS-CoV-2, or after the subject has recovered from SARS-CoV-2 infection.
13. The method of claim 1, wherein the subject has received a vaccine against SARS-CoV-2 virus and the biological sample is optionally obtained after administration of a vaccine dose.
14. The method of claim 1, further comprising a quantification of amount of specific SARS-CoV-2 virus antibodies in the biological sample.
15. The method of claim 14, wherein the amount of the SARS-CoV-2 antibody in the biological sample is proportional to the amount of the complex detected.
16. The method of claim 1, which is for the detection in the sample of antibodies against a variant of SARS-CoV-2 virus.
17. A kit for working the method according to claim 1, comprising: a) a solid support coated with inactivated purified SARS-CoV-2 whole virus particles, b) at least one labeled secondary antibody able to bind to human IgG and/or IgM and/or IgA; c) a negative control; d) a positive control; e) a cut-off control or calibrator; f) a sample diluent; g ) a substrate solution; h) a washing solution; and i) optionally a stop solution.
18. The method of claim 1, wherein said inactivated purified SARS-CoV-2 whole virus particles are particles of the SARS- CoV-2 strain 2019-nCoV/Italy-INMII (GenBank: SARS-CoV-2/INMII-Isolate/2020/Italy: MT066156.1) or a natural or recombinant derivative thereof.
20. The method of claim 4, wherein the solid support is a microtiter plate.
21. The method of claim 6, wherein the enzyme is peroxidase, alkaline phosphatase, p Galactosidase or acetylcholinesterase.
Claim Rejections - 35 USC § 102
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 1-2, 10-11, 13-14, 16, and 18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Meinke et al. (US 2023/0038284 A1)
Meinke et al. teach detection of anti-SARS-CoV-2 antibodies in patient serum samples as well as determining the concentration of said antibodies, such as IgG antibodies against the spike protein, using an inactivated and purified SARS-CoV-2 vaccine comprising whole virus particles, wherein said virus particles comprise at least a spike protein, a nucleocapsid protein, and a membrane protein, and detection of the complexes formed between the antibodies and the particles (see Paragraphs 0005, 0011, 0041, 0062, 0126; Figure 1), which reads on instant Claims 1-2, 10-11, 13-14. Meinke et al. also teach wherein said inactivated and purified SARS-CoV-2 vaccine comprising whole virus particles can be derived from any known strain or variants thereof, including the South African, Brazilian, and/or UK variants (see Paragraphs 0093-0097), and a strain such as SARS-CoV-2/INMI1-Isolate/2020/Italy, GenBank Accession Number: MT066156) (see Paragraphs 0146, 0367-0368, 0370, 0372), which reads on instant Claims 16 and 18.
For at least these reasons, Meinke et al. teach the limitations of instant Claims 1-2, 10-11, 13-14, 16, and 18 and anticipate the invention encompassed by said claims.
Claim Rejections - 35 USC § 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, 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.
Claims 3-9, 12, 15, 17, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Meinke et al. (US 2023/0038284 A1) as applied to claims 1-2, 10-11, 13-14, 16, and 18 above, and further in view of Wohlstadter et al. (US 2021/0349104 A1)
While Meinke et al. teach the limitations of a number of the instant claims, as noted above, Meinke et al. does not teach a method wherein said inactivated purified SARS-CoV-2 virus particles are pre-immobilized to a solid support; and a method wherein the sample is obtained from the subject after at least three days for IgM and IgA and at least 10 days for IgG. Meinke et al. also does not teach a method wherein the amount of antibody detected is proportional to the amount of the complex detected or a kit for carrying out said method.
Wohlstadter et al. teach a method for detecting and/or quantifying antibody biomarkers against a viral antigen (see Abstract; Paragraph 0014; Figure 1), wherein said antibody biomarkers are IgG, IgM, and IgA and wherein said antibody biomarkers present in a sample are tested for after 10 days for IgG and after 6 days for IgA and IgM after a subject is exposed to the virus and/or infected with the virus (see Paragraphs 0269 and 0272), which reads on instant Claim 12. Wohlstadter et al. also teach a method wherein SARS-CoV-2 antigens are immobilized on distinct binding domains in a well of a 384-well assay plate for measuring IgG and IgM antibody levels, wherein the amount of antibody present in said samples is proportional to the intensity of the detection signal produced when the labelled secondary antibodies bind to the antigen-specific antibodies (see Paragraphs 0026-0027, 0770), which reads on instant Claims 3-5 and 15. Additionally, Wohlstadter et al. also teach a method wherein the detection of the antibodies is compared to a control biological sample that is negative for anti-SARS-CoV-2 antibodies (see Paragraphs 0027, 0036-0037; Figures 11, 16-17), which reads on instant Claim 7.
Furthermore, Wohlstadter et al. teach kits for detecting and/or quantifying antibody biomarkers (see Abstract; Paragraph 0003), wherein said kits comprise a viral antigen that specifically binds an antibody biomarker, a detection reagent that specifically binds the biomarker, and a surface or solid support (see Paragraphs 0011-0012), wherein said detection reagent is an antibody or an antigen-binding fragment thereof (see Paragraphs 0584 and 0586), and wherein said surface is a plate, a multi-well plate, or a particle (see Paragraph 0637), which reads on instant Claim 17. Wohlstadter et al. also teach said kits further comprising a calibration reagent (see Paragraph 0638), which can also serve as a positive control reagent (see Paragraph 0641) or a negative control (see Paragraph 0338), a diluent, a wash buffer (see Paragraph 0645), which also read on instant Claim 17.
The previous teachings of Meinke et al. have been summarized above.
Meinke et al. also teach a method wherein anti-S protein antibodies in a serum sample bind to a Spike protein antigen immobilized on a solid support, wherein said solid support for said detection method can be a microtiter plate (see Paragraphs 0171, 0347-0348), which reads on instant Claims 3-4 and 20. Meinke et al. teach a method wherein detection was performed using a secondary antibody conjugated with an enzyme, specifically Horseradish peroxidase (HRP) conjugate (see Paragraphs 0171 and 0189), which reads on instant Claims 5-6 and 21. Additionally, Meinke et al. also teach a method wherein the labelled secondary antibody is specific for human antibodies or a SARS-CoV-2 antigen, specifically the S1 subunit (see Paragraph 0190; Figure 4A), which reads on instant Claims 8-9. Finally, Meinke et al. teach a method for detecting antibodies against SARS-CoV-2 wherein said comprises the use of a substrate solution and a stop solution (see Paragraphs 0171, 0279), which reads on instant Claim 17.
A person having ordinary skill in the art would have been motivated to modify the teachings of Meinke et al. with those of Wohlstadter et al. in order to develop a method for using inactivated and purified SARS-CoV-2 whole virus particles for detecting antibodies against said virus. While Meinke et al. does not explicitly teach SARS-CoV-2 whole virus particles being immobilized to a solid support, they do contemplate whole virus particles being used to detect antibodies in a sample as well as SARS-CoV-2 antigens being immobilized to a solid support. As such, it would have been obvious for a skilled artisan to try or to substitute the individual antigens for whole virus particles, which would have had a reasonable expectation of success. The teachings of Wohlstadter et al. would have enabled a person having ordinary skill in the art to choose the appropriate time frame in which to detect IgG, IgM, and IgA antibodies, which would make the serological assay of Meinke et al. more effective. While the kits taught by Wohlstadter et al. do not comprise either a substrate solution or a stop solution, Meinke et al. teach their method for detecting anti-SARS-CoV-2 antibodies using a substrate solution and a stop solution. As such, it would have been obvious for a skilled artisan to include such solutions in the kits disclosed by Wohlstadter et al. This would have generated kits with all the materials necessary to carry out the combined methods disclosed by both Meinke et al. and Wohlstadter et al., making them more efficient and cost-effective.
Such modifications, combining prior art elements according to known methods to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the claimed invention. For at least these reasons, instant Claims 3-9, 12, 15, 17, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Cady (US 2022/0026428 A1)
Cady teaches a method for detecting the amount and/or type of one or more antibody biomarkers in a sample. This reference has not been utilized, as rejection would have been redundant to those set forth above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAREY A STUART whose telephone number is (703)756-4668. The examiner can normally be reached Monday - Friday, 7:30 AM - 4:30 PM EST.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671
/JANET L ANDRES/Supervisory Patent Examiner, Art Unit 1671