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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Apr. 16, 2026. Claims 1-19 are pending and currently examined.
Claim Rejections - 35 USC § 112(b)
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.
(Previous Rejection – Partially Maintained) Claims 1-19 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. This rejection has the following grounds.
The base claim 1 recites the limitations of “at least one type of SARS-CoV-2 antigen or fragment or variant thereof”, and “at least one type of anti-SARS-CoV-2 antibody or fragment or variant thereof”. These limitations are unclear. Neither the claim nor the specification clearly defines the term “variant thereof” for the claimed antigen or antibody. Therefore, it is not clear what structural and/or functional characteristics the “variant thereof” must have.
Applicant argues that the specification clearly defines SARS-CoV-2 antigen and antibody variants. Applicant argues that paragraphs [0121-0124], [0136-0137] and [0145-0149] describe suitable variants for use in the methods of the disclosure.
Applicant’s argument is not persuasive. The specification provides some examples for “variants” of antigens and antibodies. However, it does not describe what structural and/or functional characteristics the “variant thereof” must have to be suitable for use in the claimed method. Since the term “variant” is highly general, it is not clear what it may encompass besides the examples given in the specification.
Claim Rejections - 35 USC § 112 (Enablement)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(Previous Rejection – Withdrawn) Claims 1-19 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
This rejection is withdrawn in view of the amendment filed on Apr. 16, 2026.
Claim Rejections - 35 USC § 102/103
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)(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.
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.
(New Rejection – Necessitated by Amendment) Claims 1, 2 and 8-19 are rejected under 35 U.S.C. 102/103 as being unpatentable over Vashist et al. (US 2022/0163528 A1, published on May 26, 2022; PCT filed on Jul. 29, 2021; claiming priority on foreign application NZ 766621, filed on Jul. 29, 2020).
The base claim 1 is amended to specify that “at least one detection composition comprising (a) at least one first detection reagent comprising at least one detectable label that specifically binds to the at least one type of SARS- CoV-2 antigen or fragment or variant thereof bound to the first microparticle reagent to form a first microparticle reagent-first detection reagent complex; and (b) at least one second detection reagent comprising at least one detectable label that specifically binds to the at least one type of SARS-CoV-2 antibody or fragment or variant thereof bound to the second microparticle reagent to form a second microparticle reagent-second detection reagent complex”.
The claims thus read a method for the detection of both the SARS-CoV-2-specific antibodies and SARS-CoV-2 antigens in a sample by a combination or a multiplexed form of bead-based antibody test and bead-based antigen test, as presented below:
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Vashist teaches an invention on detecting antibodies in response to SARS-CoV-2 infection in multiplex immunoassays. See Abstract.
Vashist teaches that, in one embodiment, the invention provides, a substrate with at least two capture elements specific for SARS-CoV-2 on the substrate, each capture element corresponding to and being able to bind a target analyte. In one aspect, the capture elements bind target analytes, wherein the target analytes are indicative of exposure to SARS-CoV-2 and/or COVID-19; In one aspect, the target analyte is a SARS-CoV-2 antibody, fragment or binding domain thereof; In an additional aspect, the capture element is a virus structural protein or epitope thereof; In an additional aspect, the virus structural protein or epitope thereof is selected from a SARS-CoV-2 Membrane protein (MP), Nucleocapsid protein (NP), Spike protein (SP), fragment thereof or any combination thereof; In one aspect, the substrate is a solid or a porous substrate; In an additional aspect, the solid substrate is a paramagnetic bead, microtiter plate, microparticle, or a magnetic bead. See [0008].
FIGS. 2A-E of Vashist show a COVID-19 MIA protocol design. FIG. 2A. Printing of SARS-CoV-2 structural proteins on the assay surface (substrate surface). FIG. 2B. Blocking of assay surface after protein/Ab printing. FIG. 2C. Detection of target COVID-19 analytes in the patient sample. FIG. 2D. Detection of specifically bound COVID-19 analytes by binding with HRP-labelled detection Ab against the analytes. FIG. 2E. Generation of colorimetric array spots by the addition of HRP substrate (TMB). See [0014].
FIGS. 2A-E of Vashist is shown below.
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Based on the teachings presented above, the solid black circle in figure 2A is considered as representing a SARS-CoV-2 antigen molecule, the Y-shaped feature is considered as representing a SARS-CoV-2-specific antibody molecule, and the horizonal straight line is considered as representing the surface of a solid substrate where the antigen and antibody molecules attach to, and the substrate surface can be that of a paramagnetic bead, microparticle, or a magnetic bead.
Accordingly, Vashist teaches a bead-based multiplex immunoassay for the detection SARS-CoV-2-specific antibodies, that is indistinguishable from the antibody assay as instantly claimed. However, even though it explicitly disclosed an assay design that reads on the antigen assay of the instant claims (see Figures 2 A-E above, the features on the right side of each figure), Vashist does not disclose in text an embodiment for detecting SARS-CoV-2 antigens as analyte. One of skill in the art would have found it obvious make such an assay for the detection of SARS-CoV-2 antigens based on the teachings in Figure 2 A-E of Vashist.
Accordingly, Vashist anticipates or makes obvious claims 1, 2 and 8-19.
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.
(New Rejection – Necessitated by Amendment) Claims 3-7 are rejected under 35 U.S.C. 103 as being unpatentable over Vashist et al. (US 2022/0163528 A1, published on May 26, 2022; PCT filed on Jul. 29, 2021; claiming priority on foreign application NZ 766621, filed on Jul. 29, 2020), as applied above, in view of Wrobel et al. (Nat Commun 11, 5337 (2020)).
These claims specify an anti-SARS-CoV-2 spike RBD antibody or antibody fragment or variant thereof.
Relevance of Vashist is set forth above. However, it is silent on an anti-SARS-CoV-2 spike RBD antibody. Instead, Vashist teaches using antibodies against various SARS-CoV-2 antigens in general. See discussions above.
Wrobel teaches a study on characterization of a neutralizing monoclonal antibody, CR3022, which binds to an epitope in the RBD of the SARS-CoV-2 Spike antigen. See page 2, left column, para 1.
Accordingly, teachings of Wrobel indicate that a SARS-CoV-2 Spike protein RBD binding antibody is known at the time of invention.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to introduce the antibody CR3022 of Wrobel into the study of Vashist, which teaches using antibodies against SARS-CoV-2 Spike protein in general. Such a combination, or a substitution of one element for another known in the field to have the same function, is evidence that the claimed invention may be found obvious. See MPEP 2144.06 and KSR International v. Teleflex Inc., 82 U.S.P.Q.2d 1385, at 1395. Therefore, the instant invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 4-7 specify additional specific binding partners (third, fourth, fifth etc.) that bind to different SARS-CoV-2 antigens and/or antibodies. Based on the teachings of Vashist that various types of SARS-CoV-2 antigens and antibodies can be analytes as well as binding partners in the disclosed multiplex immunoassays, one of skill in the art would have found it obvious to include multiple different binding partners, as claimed, in the multiplex immunoassays disclosed in Vashist for the detection of multiple analytes.
(New Rejection – Necessitated by Amendment) Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Marien et al. (Journal of Virological Methods 288 (2021) 114025; available online Nov. 20, 2020) in view of Lee et al. (Biosensors and Bioelectronics 171 (2021) 112715; available online Oct. 15, 2020).
Marien teaches a study on evaluating SARS-CoV-2 spike and nucleocapsid proteins as targets for antibody detection in severe and mild COVID-19 cases using a Luminex bead-based assay. It teaches that bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies against multiple antigens and against other pathogens. The authors compare the performance of spike (S) and nucleocapsid (NP) antigens for the detection of SARS-CoV-2 specific IgG, IgM and IgA antibodies in a panel of sera that includes recent (up to six weeks after symptom onset, severe n = 44; and mild cases n = 52) and old infections (five months after symptom onset, mild n = 104), using a Luminex-bead based assay and comparison to a virus neutralization test. In conclusion, their data supports the use of RBD and NP for the development of SARS-CoV-2 serological IgG bead-based assays. See Abstract.
The Luminex bead-based immunoassay was described in Methods 2.3. Briefly, recombinant antigens from SARS-CoV-2 were conjugated to microsphere beads from Luminex; antigen-conjugated beads were mixed with serum samples containing IgG, IgA and/or IgM for reaction between the SARS-CoV-2 antigens and SARS-CoV-2 antigen-specific antibodies; reactions were then read after incubation (30 min) with a biotin-labeled anti-human IgG, IgA or IgM secondary antibody and streptavidin-R-phycoerythrin conjugate (10 min) using a Luminex 100/200 analyzer; and results were expressed as median fluorescent intensities (MFI). See page 2, right column, para 2 and 3.
Accordingly, the bead-based assay of Marien is indistinguishable from the antibody assay as instantly claimed, i.e., an assay comprising conjugating a SARS-CoV-2 antigen onto a microparticle for the detection of SARS-CoV-2 antigen-specific antibodies in a sample. However, Marien is silent on combining this bead-based antibody assay with a bead-based antigen assay, as instantly claimed.
Lee teaches a study on rapid detection for SARS-CoV-2 spike 1 antigen using human angiotensin converting enzyme 2 (ACE2). The authors designed and developed a novel rapid detection method for SARS-CoV-2 spike 1 (S1) protein using the SARS-CoV-2 receptor ACE2, which can form matched pairs with commercially available antibodies. ACE2 and S1-mAb were paired with each other for capture and detection in a lateral flow immunoassay (LFIA) that did not cross-react with SARS-CoV Spike 1 or MERS-CoV Spike 1 protein. The SARS-CoV-2 S1 (<5 ng of recombinant proteins/reaction) was detected by the ACE2-based LFIA. The limit of detection of our ACE2-LFIA was 1.86 × 105 copies/mL in the clinical specimen of COVID-19 Patients without no cross-reactivity for nasal swabs from healthy subjects. See Abstract.
Lee teaches preparation of antibody conjugated beads in the section 2.3 of Materials and Methods. A 1% stock solution of red cellulose nanobeads (CNBs) was purchased from Asahi Kasei Fibers Corporation (NanoAct, Cat. No. RE2AA; Miyazaki, Japan); the beads have an average diameter of 345 nm. A CNB conjugation kit, containing conjugation buffer, blocking buffer, and wash buffer, was purchased from DCN Diagnostics (CA, USA). Conjugation of the SARS-CoV-2 spike antigen-specific antibodies (CR3022, F26G19, S1mAb) and binding protein (ACE2) to the surface of CNBs was performed according to the manufacturer’s instructions. See page 2, right column, para 2.
Figure 1 shows a schematic picture for ACE2-based LFIA. See below:
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Fig. 1 shows that a microparticle is conjugated to a SARS-CoV-2 S1-specific antibody, the antibody binds to the SARS-CoV-2 Spike antigen, and the bound Spike antigen binds to the ACE2 probe immobilized on a strip to generate a detection signal.
Accordingly, teachings of Lee indicate that detection of SARS-CoV-2 antigens is desired and can be achieved by a bead-based assay comprising a SARS-CoV-2-specific antibody-conjugated bead.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to introduce the bead-based assay design of Lee, i.e., a design with antibodies as the capture agent, for the antigen detections, into study of Marien, which relies on a bead-based assay for detection of antibodies, i.e., a design with antigens as the capture agent. One would have been motivated to do so to develop a multiplexed bead-based assay system that can detect both the SARS-CoV-2 antigens and antibodies against the SARS-CoV-2 antigens. There is a reasonable expectation that such a combined assay system can be produced based on the teachings of Marien and Lee, as well as knowledge available in the art at the time of invention.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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