CTNF 18/473,064 CTNF 88602 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 Priority Acknowledgement is made of Applicant’s claimed domestic priority under 35 U.S.C. § 119(e), of U.S. Provisional Application Serial Nos. 63/513,390, filed July 13, 2023 and 63/376,828, filed September 23, 2022. Status of the Claims The amendment dated 12/04/2023 is acknowledged. Claims 1-6, 8-10, 12-14, 16, 19-22, 27 and 30-31 are pending and under examination. Information Disclosure Statement The information disclosure statement (IDS) submitted on 01/31/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner. Drawings The drawing filed on 09/22/2023 are acknowledged and accepted by the Examiner. 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. Claim 16 is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claim 16 recites “substantially”. The term “substantially” is not clear in that it is a relative term. Further, the specification does not define the term “substantially” does not provide a standard for ascertaining the requisite degree, thus a skilled artisan would not be apprised to the metes and bounds of the recitations. Thus, the claims are rendered indefinite. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-12-aia AIA (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. 07-15 AIA Claim s 1, 4-6, 8-10, 12-14, 16, 19, 22, 27 and 31 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Crowe et al. “Crowe” (WO2018/075621, IDS of record dated 01/31/2024) . The claims are directed to a kit for detecting one or more antibody biomarkers of interest in a sample, the kit comprising, in one or more vials, containers, or compartments: a. a surface comprising a panel of antigens immobilized on one or more binding domains, wherein each binding domain comprises an antigen of the panel of antigens immobilized thereon, wherein the panel of antigens comprises a monkeypox virus (MPXV) protein, a vaccinia virus (VACV) protein, or combination thereof; and b. one or more detection reagents, wherein each detection reagent comprises a detection antibody, a detection antigen, or a detection competitor. Regarding claims 1, 13-14, 16, 19 and 27, Crowe discloses an orthopoxvirus protein array for the detection of antibodies against antigens after poxvirus infection, whereby secondary antibodies are used to detect the presence of bound antibodies (claims 1-5 of Crowe). Crowe discloses a “Panel of Poxvirus- Specific Human MAbs. A panel of 89 human mAbs was generated based on reactivity to VACV-infected cell lysate or to VACV protein antigens. Individual mAbs were assessed for cross reactivity using CPXV, MPXV, and VARV-infected cell lysates or antigens. (FIG.1A) Antigen specificity of purified mAbs. Reactivity of Abs of unknown antigen specificity that bound to inactivated VACV-infected cell lysate only is designated as “VACV lysate only”. (FIG.1B) Representation of mAbs in the panel from FIG. 1A that bound only to VACV-infected cell lysate, recombinant VACV proteins, or both, VACV infected cell lysate and recombinant VACV proteins. Binding of individual mAbs is listed in Table S3 and S4. (FIG. 1C) Cross-reactivity of mAbs that bound to VACV lysates from FIG.1B to VACV-, CPXV-, MPXV- or VARV-infected cell lysates” (Figures 1A-1D). Crowe also discloses “the present disclosure concerns immunodetection kits for use with the immunodetection methods described above. As the antibodies may be used to detect Poxvirus or Poxvirus antigens, the antibodies may be included in the kit. The immunodetection kits will thus comprise, in suitable container means, a first antibody that binds to Poxvirus or Poxvirus antigen, and optionally an immunodetection reagent (page 43 third full para and last para). Moreover, Crowe discloses “antibodies of the present disclosure may be linked to at least one agent to form an antibody conjugate. In order to increase the efficacy of antibody molecules as diagnostic or therapeutic agents, it is conventional to link or covalently bind or complex at least one desired molecule or moiety (page 33 last para) (instant claims 1, 13-14, 16 and 19). Regarding claims 4-6, 8 and 22, Crowe discloses the antibody biomarker is IgG (claim 21 of Crowe); and the detection antibody comprises an anti-IgG antibody conjugated with alkaline phosphatase or HRP; and detected with absorbance (page 46 first para and page 47 last para). Regarding claim 9, Crowe discloses embodiments whereby the surface may comprise an electrode (page 36 last full para). Regarding claims 10 and 27, Crowe discloses the surface comprising a well of a mult-well plate comprising one to ten binding domains (Section A. ELISAS page 39). Regarding claim 12, Crowe discloses a buffer, diluent and collection device (page 40 second and fourth para (buffer), page 32 first para (diluent). Regarding claim 31, Crowe discloses the sample comprises a biological fluid, including blood and serum, or a secretion, such as feces or urine (page 37 second para). Therefore, the cited prior art anticipates the claimed invention . Claim Rejections - 35 USC § 103 07-20 AIA The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made. 07-20-02 AIA This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a). 07-21 AIA Claim s 2-3, 20-21 and 30 are rejected under 35 U.S.C. 103(a) as being unpatentable over Crowe et al. “Crowe” (WO2018/075621, IDS of record dated 01/31/2024) as applied to claims 1, 13 and 19 above, in view of Hooper et al. “Hooper” (US PGUB 2011/081368, IDS of record dated 01/31/2024). The teachings of Crowe are outlined above and incorporated herein . The claims are directed to the kit of claim 1, wherein the MPXV protein comprises M1R, A29L, A35R, B6R, E8L, A30L, or combination thereof, and wherein the VACV protein comprises L1R, A27L, A33R, B5R, D8L, A28L, or combination thereof; and wherein the panel of antigens comprises (i) the MPXV proteins M1R, E8L, B6R, A35R, and A29L; and (ii) the VACV proteins A27L, A33R, B5R, D8L, and L1R. Regarding claims 2-3 and 20-21, Crowe discloses a “Panel of Poxvirus-Specific Human MAbs. A panel of 89 human mAbs was generated based on reactivity to VACV-infected cell lysate or to VACV protein antigens. Individual mAbs were assessed for cross reactivity using CPXV, MPXV, and VARV- infected cell lysates or antigens. (FIG.1A). Crowe discloses “the present invention also provides kits which help facilitate using the present vaccines and methods. The kits comprise a first container containing the above-described monkeypox ortholog protein vaccine, or another embodiment of the protein vaccine” (para [0130]). Crowe does not explicitly teach the recombinant proteins of MPXV and VACV. Hooper, however, discloses the use of an ELISA assay for detecting antibody response against subunit recombinant vaccine against monkeypox. The ELISA is conducted with purified monkeypox proteins (A27L, A33R, B5R, and L1R). The monkeypox orthologs of the VACV A27L, A33R, B5R, and L1R genes are A29L, A35R, B6R, and M1R, respectively (para [0140]). Accordingly, it would have been obvious to one of ordinary skill in the art to generate a kit and methods of detecting one or more antibody biomarkers of interest in a sample to MPXV and VACV protein antigens as disclosed by Crowe, whereby the MPXV and VACV antigen proteins are A27L, A33R, B5R, L1R, A29L, A35R, B6R, and M1R as disclosed by Hooper. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success given the fact that Hooper demonstrates the “use of an ELISA assay for detecting antibody response against subunit recombinant vaccine against monkeypox. The ELISA is conducted with purified monkeypox proteins (A27L, A33R, B5R, and L1R). The monkeypox orthologs of the VACV A27L, A33R, B5R, and L1R genes are A29L, A35R, B6R, and M1R, respectively” (para [0140]). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. Regarding claim 30, a method wherein the detection reagent comprises an electrochemiluminescence (ECL) label, an electrode and detecting by voltage an ECL signal, it is not inventive and considered routine and obvious to one of ordinary skill in the art to utilize a well-known antibody detection technique. Crowe lists non-limiting examples of methods including “immunodetection methods (e.g. ELISA, radioimmunoassay, immunoradiometric assay, fluoroimmunoassay, chemiluminescent assay, bioluminescent assay, and Western blot to mention a few” (page 36 last full para). One of ordinary skill in the art would be motivated to do so with a reasonable expectation of success given the fact that antibody detection utilizing a multitude of techniques such as ECL, light scattering, optical absorbance, fluorescence, luminescence, chemiluminescence, bioluminescence, radioactivity, and magnetic field are within the purview of one of ordinary skill in the art and considered conventional and routine for antibody detection of poxviruses. Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. 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. /BARRY A CHESTNUT/Primary Examiner, Art Unit 1672 Application/Control Number: 18/473,064 Page 2 Art Unit: 1672 Application/Control Number: 18/473,064 Page 3 Art Unit: 1672 Application/Control Number: 18/473,064 Page 4 Art Unit: 1672 Application/Control Number: 18/473,064 Page 5 Art Unit: 1672 Application/Control Number: 18/473,064 Page 6 Art Unit: 1672