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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/20/2026 has been entered.
Status of the Claims
Claim 2 has been cancelled by Applicant. Claims 1, 3-6 and 8-19 are pending and examined herein.
Priority
This application, filed 07/12/2023, claims benefit of PRO 63/388,354, filed 07/12/2022. This benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 07/12/2022.
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, 3-6, and 8-19 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 “wherein each…corresponds to a target-specific binding event involving one bound target molecule”. It is unclear how, when using a detection antibody, it can be determined whether one or two binding interactions are occurring per reaction. Antibodies are typically bivalent and a single antibody can bind one or two antigens simultaneously unless they have been altered to be specifically monovalent, but this has not been described in the specification. For the purposes of compact prosecution, any antibody-antigen interaction in the art will be considered to correspond to a target-specific binding event involving one bound target molecule; however, appropriate clarification is required.
Further regarding claim 1, in “a target-specific binding event involving one bound target” it is unclear whether “involving” is open or closed language, i.e. does the limitation require only one bound target or does the limitation require at least one bound target? As stated above, if the limitation requires only one bound target, it is unclear how this was accomplished and determined in the instant application. For the purposes of compact prosecution, “involving” is interpreted as meaning at least one bound target, consistent with the broadest reasonable interpretation of the word “involving”; however, appropriate clarification is required.
Claims 3-6 and 8-19 are rejected for being dependent on rejected claim 1.
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, 3-4, 8-9, and 12-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2004/0265923 A1 “METHOD AND APPARATUS TO DETERMINE THE PERFORMANCE OF PROTEIN ARRAYS” (published 12/30/2004, referred to herein as Gilmore) as evidenced by Wiese et al., “Simultaneous Multianalyte ELISA Performed on a Microarray Platform” Clinical Chemistry (published 08/01/2001, NPL corresponding to Gilmore, referred to herein as Wiese).
Regarding claims 1, 4, 8, and 9, Gilmore teaches a method for detecting a target in a sample (para. 0005, lines 1-3) comprising providing a capture species immobilized on a microplate surface (para. 0016, lines 1-6), exposing the immobilized capture species to a sample to form a bound target molecule (para. 0016, lines 14-16), exposing the bound target to a reporter complex to bind to the bound target wherein the reporter complex comprises a detection antibody bound to a reporter enzyme, alkaline phosphatase (para. 0071, lines 13-20). Gilmore teaches that the reporter enzyme is alkaline phosphatase, which can convert a plurality of enzyme substrates, e.g. Molecule Probes #E-6604 (para. 0071, lines 21-24) which is ELF-97 as evidenced by Wiese (p. 1453, col. 1, para. 1, lines 1-2), into a plurality of water-insoluble reporter molecules that aggregate to form an imageable larger particle that precipitates on the fixed surface. Gilmore teaches imaging the fixed surface (para. 0072, lines 1-2) and using densitometry analysis to calculate the concentration of bound antigen complexes (para. 0072, lines 5-11). Based on its broadest reasonable interpretation, “counting” in claim 1 is interpreted to mean quantitatively determining the number of something. In this case, using image-based quantification of fluorescent signals generated from the imageable particles generated from the ALP-converted ELF-97 substrate to determine the amount of bound antigen, as taught by Gilmore, is considered to be a method of counting the imageable particles. Gilmore teaches that the imageable particles are generated from a target-specific binding event, i.e. an antibody binding a target, which involve a bound target molecule as evidenced by Wiese (Figure 1 “Single Element”).
Regarding claim 3, Gilmore teaches that the target is a protein (para. 0008, lines 1-5).
Regarding claims 12-14, Gilmore teaches imaging using scanning microscopy to image the surface and detect the detection probe, i.e. imaging and counting (para. 0064, lines 1-7 and para. 0072, lines 1-11).
Amended 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 1, 3, 4, and 8-19 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al., “Highly Sensitive Detection of PCV2 Based on Tyramide Signals and GNPL Amplification” Molecules (published 11/29/2019, referred to herein as Zhang) in view of Liu et al., “A whole area scanning–enabled direct-counting strategy for studying blocking efficiency in mitigating protein-solid surface binding” Analytical and Bioanalytical Chemistry (published 01/19/2021, IDS dated 01/18/2024, referred to herein as Liu).
Regarding claims 1 and 4, Zhang teaches a method for detecting a target molecule in a sample (p. 2, para. 3, lines 1-2, Figure 1A TSA Technique) comprising providing a capture antibody, “anti-PCV2 capture antibody”, immobilized on a microwell of a microplate (p. 7, para. 3, lines 3-5), exposing the capture species to a sample to bind the target (p. 7, para. 3, lines 7-8), exposing the bound target to a reporter complex (p. 7, para. 3, lines 8-11). Zhang teaches that the capture species is an antibody (p. 7, para. 3, lines 3-5), the target molecule is a PCV2 antigen, and the reporter complex comprises a detection antibody linked to HRP, which converts TMB substrate to an imageable color (p. 7, para. 3, lines 8-14). Zhang teaches that the reporter system and signal correspond to a target-specific binding event involving one bound target molecule, i.e. an antibody-antigen binding reaction (Figure 1A).
Regarding claim 3, Zhang teaches the target, PCV2, is a virus (p. 1, para. 1, lines 1-3).
Regarding claim 10, Zhang teaches that the detection antibody is conjugated to biotin (Figure 1A).
Regarding claims 15 and 16, Zhang teaches exposing the bound target to a detection antibody linked to HRP and amplifying the signal by exposing the bound detection HRP to peroxide and biotinyl-tyramide (p. 7, para. 3, lines 8-11).
However, Zhang does not teach a method comprising imaging the fixed surface to count the number of an imageable product wherein the imageable product aggregates to form larger particles that precipitate on the fixed surface.
Liu’s general disclosure is directed to developing a “WAS-enabled direct counting strategy”, which is a fluorescent reporter and scanning microscopy-based detection system for the high sensitivity detection of target molecules.
Regarding claim 1, Liu teaches a method for detecting comprising imaging a fixed surface to count the number of imageable products derived from a reporter complex, wherein the imageable product aggregates to form larger particles that precipitate on the fixed surface (p. 1495, col. 1, para. 2, lines 8-19).
Regarding claim 2, Liu teaches that the counted reporter product derived from the complex corresponds to one target (Figure 3, p. 1496, col. 2, para. 2, lines 24-27).
Regarding claim 8, Liu teaches that the aggregate is fluorescent (Figure 3, p. 1496, col. 2, para. 2, lines 24-27).
Regarding claim 9, Liu teaches that the reporter enzyme is alkaline phosphatase (p. 1494, col. 2, para. 2, lines 9-12).
Regarding claims 10 and 17, Liu teaches that the reporter enzyme in the complex is Streptavadin-alkaline phosphatase, i.e. Strep-ALP (p. 1494, col. 2, para. 2, lines 4-5).
Regarding claims 11 and 18, Liu teaches that the substrate is ELFP (p. 1495, col. 1, para. 2, lines 9-10) is exposed to the Strep-ALP reporter.
Regarding claims 12-14, Liu teaches that multiple portions of the well is imaged and signal is counted by scanning microscopy (p. 1495, col. 1, para. 2, lines 14-19).
It would have been obvious to one of ordinary skill in the art to modify the method taught by Zhang by substituting the TSA-plate reader reporter system for the WAS-enabled direct counting strategy taught by Liu. An artisan would have been motivated to make this change because, as taught by Liu, the WAS-enabled direct counting strategy can be used to develop digital biosensors (p. 1496, col. 2, para. 2, lines 32-35), which is a useful technology for the detection of PCV2, as taught by Zhang (p. 1, para. 2, lines 1-3). An artisan would have had a reasonable expectation of success in making this substitution because both assays are directed toward that amplification-based fluorescent detection of reporter systems in the art of biochemical detection. An artisan would readily recognize that components such as the HRP reporter enzyme of Zhang could readily be replaced by ALP as taught by Liu, along with any associated components necessary for its use.
Regarding claim 19, the limit of detection of a method of detection is considered to be an inherent property of the assay. A rejection can be made when the prior art method seems to be identical except that the prior art is silent as to an inherent characteristic (See MPEP 2112(III)). In this case, the combined teachings of Zhang in view of Liu teach an identical method of analyte detection, including amplifying the signal with the signal amplifying complex, i.e. antibody bound to HRP, and amplifying the signal with biotinyl-tyramide as described in claims 1 and 15. Due to the identical method steps and components described to carry out the method of claims 1 and 15, the method described by Zhang in view of Liu is considered to have an identical limit of detection, even if the limit is not explicitly disclosed.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang in view of Liu as applied to claims 1 and 4 above, and further in view of US 2017/0370920, “METHOD FOR DETECTING ANALYTE” (published 12/28/2017, referred to herein as Akama).
The teaching of Zhang in view of Liu regarding claims 1 and 4, as described above in the rejection under 35 U.S.C. 103 are incorporated herein.
However, Zhang in view of Liu does not teach a reporter complex wherein the reporter is an imageable microbead or nanobead or wherein the capture or detection antibody further comprise a magnetic microbead or nanobead.
Regarding claim 5, Akama teaches a digital detection method wherein the reporter complex wherein the detection antibody (Figure 2E) is linked to a fluorescent nanobead (para. 0090, lines 7-9 and para. 0091, lines 4-6).
Regarding claim 6, Akama teaches the use of magnetic microbeads linked to HRP as a reporter detected by microscopy (Example 2, para. 0157).
It would have been obvious to one of skill in the art before the effective filing date to modify the method taught by Zhang in view of Liu by substituting the reporter enzyme linked to the detection antibody for a magnetic fluorescent bead, as taught Akama. Making this modification is considered to be a simple substitution of known method steps to obtain predictable results (See MPEP 2143(I)(B)). In this case, the substitution of known components in the method taught by Zhang in view of Liu for known components in Akama for the detection of biological targets in fluorescence-based digital detection is considered to be the use of known components for their known purpose to achieve predictable results, i.e. the detection of a target using immunoassay methods.
Response to Arguments
Applicant's arguments filed 08/20/2026 have been fully considered but they are not persuasive for the following reasons:
Regarding the remarks on pages 7 and 8 on the rejection of claims 1-4 and 8-19 under 35 U.S.C. 103, Applicant argues that regarding claim 2, Liu does not teach counted precipitates corresponding to a target molecule.
This argument is considered moot for being directed towards a cancelled claim. Further regarding amended claim 1, Liu is not relied upon to teach the amended limitation of a target specific binding even involving one bound target molecule, as described under the amended rejection under 35 U.S.C. 103. Liu is relied upon for the teaching of an enzyme labelling systems useful for detection.
Conclusion
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 September 10, 2026
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