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 .
Status of the Claims
Claim 7 has been cancelled by Applicant. Claims 1-6 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.
Withdrawn Rejections/Objections
The rejection of claims 1-10, 12-16, and 19 under 35 U.S.C. 102 is withdrawn in response to Applicant’s amendments.
The rejection of claim 11 under 35 U.S.C. 103 is withdrawn in response to Applicant’s amendments.
The rejection of claims 17 and 18 under 35 U.S.C. 103 is withdrawn in response to Applicant’s amendments.
New 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 1-4 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 claim 1, 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).
Regarding claim 3, Zhang teaches the target, PCV2, is a virus (p. 1, para. 1, lines 1-3).
Regarding claim 4, 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).
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).
Regarding claims 1 and 4, as described above, Zhang in view of Liu teaches a detection method comprising a capture antibody, an antigen, and a reporter complex comprising a detection antibody linked to a reporter.
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 with respect to claims 1-19 have been considered but are moot because the claims have been rejected under new grounds in response to Applicant’s amendments.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 May 27, 2026
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