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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/05/2026 has been entered.
Claim Interpretation
Regarding limitations recited in claims 1-30 which are directed to a manner of operating the disclosed protein characterization systems, it is noted that neither the manner of operating a disclosed device nor material or article worked upon further limit an apparatus claim. Said limitations do not differentiate apparatus claims from prior art. See MPEP § 2114 and 2115.
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 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.
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.
Claim(s) 1-15 and 17-30 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by Yu et al. (Multiplexed Nucleic Acid Programmable Protein Arrays, cited in IDS filed 07/14/2025) or, in the alternative, under 35 U.S.C. 103 as obvious over Yu et al. (Multiplexed Nucleic Acid Programmable Protein Arrays, cited in IDS filed 07/14/2025), in view of Cohen et al. (Single-Molecule Arrays for Protein and Nucleic Acid Analysis).
Regarding claim 1, Yu discloses a protein characterizing system (pg. 4062-4064/Performing functional assays using M-NAPPA arrays), comprising:
(a) a solid support having a plurality of attached proteins from a sample, wherein individual proteins in the plurality of attached proteins have a unique spatial address on the solid support and are spatially separated from each other (see: viral M-NAPPA protein microarrays comprising a plurality of display proteins from serum samples, wherein the display proteins are arranged in a multiplexed grid configuration);
(b) a set of different affinity reagents configured to bind with at least one of the plurality of attached proteins, wherein the set of different affinity reagents comprises individual affinity reagents which differ from one another (see: arrays were probed with a Rb1 query protein fused to HaloTag and interactions were detected using an anti-HaloTag antibody, and subsequently additional interactions were analyzed using HaloTagged-Jun, -Fos, and -LidA);
(c) a detector configured to measure binding of the individual affinity reagents with the individual proteins, thereby generating empirical measurement outcomes for each of the individual proteins of the plurality of attached proteins at their unique spatial address (pg. 4059/Detection of protein expression on M-NAPPA, see: the arrays were scanned by a Tecan scanner); and
(d) a computing system (pg. 4059-4060/Detection of protein-protein interactions on M-NAPPA, see: the protein binding signal was quantified using Array-Pro Analyzer (Media Cybernetics) software) configured to:
(i) receive binding probabilities for each of the individual affinity reagents to one or more candidate proteins of the sample (see: 30 possible candidate target proteins; pg. 4060/Data visualization, see: Cytoscape software),
(ii) receive the empirical measurement outcomes (pg. 4060/Detection of serological antibodies on M-NAPPA, see: fluorescence signal intensity using Array-Pro Analyzer software), and
(iii) characterize the plurality of attached proteins based on the binding probabilities and the empirical measurement outcomes (Table S2, Table S3, see: identified proteins considered to be potential antigens had a ratio higher than 2 and a ring score higher than 1).
Regarding limitations directed towards the attached proteins arranged on the solid support being positioned so that individual proteins are detectably separated from each other, it is the position of the Examiner that the proteins in the arrays disclosed by Yu are fully capable of being analyzed individually, not only by a plurality of microscopy techniques well known in the art, but Yu explicitly discloses validating the arrays using ELISA techniques, which Cohen teaches are capable of single-molecule array protein analysis (pg. 351-352/3.2. Digital ELISA).
Alternatively, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to arrange the proteins in the array disclosed by Yu, in single molecule microarrays and utilize digital ELISA techniques for analysis, as taught by Cohen, in order to provide for an increase in sensitivity, specificity, and the other advantages disclosed by Cohen (Cohen: pg. 358-359/6. CONCLUSION AND FUTURE DIRECTIONS).
Regarding claim 2, Yu further discloses the plurality of attached proteins includes an unknown protein, and wherein characterizing the plurality of attached proteins includes identifying the unknown protein as one of the one or more candidate proteins of the sample (Table S2, Table S3, see: identified proteins considered to be potential antigens).
Claims 3-12 are entirely directed towards the manner in which the instantly claimed protein characterization system is intended to be used. A recitation directed to the manner in which a claimed apparatus is intended to be used does not distinguish the claimed apparatus from the prior art, if the prior art has the capability to so perform. The recitation of a new intended use for an old product does not make a claim to that old product patentable. In re Schreiber, 44 USPQ2d 1429 (Fed. Cir. 1997).
Regarding claim 13, Yu further discloses the individual proteins on the solid support are optically resolvable from each other (Figure 5, see: M-NAPPA array).
Regarding claim 14, Yu further discloses the individual proteins on the solid support are spatially separated from each other in a grid of predetermined unique addresses (Figure 5, see: M-NAPPA array).
Regarding claim 15, Yu further discloses the spatially separated individual proteins are each in individual wells or chambers (Figure 6, see: nano-well array; pg. 4064-4067/ High throughput identification of immune-dominant antigens using M-NAPPA tuberculosis proteome microarrays).
Claims 17-18 are entirely directed towards the manner in which the instantly claimed protein characterization system is intended to be used. A recitation directed to the manner in which a claimed apparatus is intended to be used does not distinguish the claimed apparatus from the prior art, if the prior art has the capability to so perform. The recitation of a new intended use for an old product does not make a claim to that old product patentable. In re Schreiber, 44 USPQ2d 1429 (Fed. Cir. 1997).
Regarding claim 19, Yu further discloses the plurality of attached proteins comprise full-length proteins (pg. 4059/Detection of protein expression on M-NAPPA, see: GST-tagged proteins).
Claims 20-23 are entirely directed towards the manner in which the instantly claimed protein characterization system is intended to be used. A recitation directed to the manner in which a claimed apparatus is intended to be used does not distinguish the claimed apparatus from the prior art, if the prior art has the capability to so perform. The recitation of a new intended use for an old product does not make a claim to that old product patentable. In re Schreiber, 44 USPQ2d 1429 (Fed. Cir. 1997).
Regarding claim 24, Yu further discloses the one or more candidate proteins include a first candidate protein, and the first candidate protein represents a canonical form of the first candidate protein and isoforms of the canonical form of the first candidate protein (pg. 4060/Data visualization, see: Cytoscape software).
Claims 25 is entirely directed towards the manner in which the instantly claimed protein characterization system is intended to be used. A recitation directed to the manner in which a claimed apparatus is intended to be used does not distinguish the claimed apparatus from the prior art, if the prior art has the capability to so perform. The recitation of a new intended use for an old product does not make a claim to that old product patentable. In re Schreiber, 44 USPQ2d 1429 (Fed. Cir. 1997).
Regarding claim 26, Yu further discloses the individual affinity reagents include antibodies (pg. 4062-4064/Performing functional assays using M-NAPPA arrays, see: interactions were detected using an anti-HaloTag antibody).
Regarding claim 27, Yu further discloses individual affinity reagents in the set of different affinity reagents recognize target epitopes present in multiple different proteins of the plurality of attached proteins (pg. 4062-4064/Performing functional assays using M-NAPPA arrays, see: interactions were detected using an anti-HaloTag antibody).
Regarding claim 28, Yu further discloses the detector is configured to measure the binding of the set of different affinity reagents applied to the plurality of attached proteins in series with binding measurements for each of the individual affinity reagents made individually from another individual affinity reagent (pg. 4059/Detection of protein expression on M-NAPPA, see: the arrays were scanned by a Tecan scanner).
Regarding claim 29, Yu further discloses the detector is configured to measure the binding of the set of different affinity reagents applied to the plurality of attached proteins in a mixture of the set of different affinity reagents, and wherein characterizing the attached proteins includes identifying post-translational modifications (PTMs) of the plurality of attached proteins (pg. 4059/Detection of protein expression on M-NAPPA, see: the arrays were scanned by a Tecan scanner; pg. 4067/Discussion, see: NAPPA has been widely applied in post-translational modifications (PTMs)).
Regarding claim 30, Yu discloses a protein characterizing system (pg. 4062-4064/Performing functional assays using M-NAPPA arrays), comprising:
(a) a solid support having a plurality of attached proteins, wherein individual proteins in the plurality of attached proteins are spatially separated from each other (see: viral M-NAPPA protein microarrays);
(b) a detector configured to measure binding of a set of different affinity reagents with the attached proteins, thereby generating empirical measurement outcomes for the individual proteins of the plurality of attached proteins (pg. 4059/Detection of protein expression on M-NAPPA, see: the arrays were scanned by a Tecan scanner), wherein the set of different affinity reagents comprises individual affinity reagents which differ from one another (see: arrays were probed with a Rb1 query protein fused to HaloTag and interactions were detected using an anti-HaloTag antibody, and subsequently additional interactions were analyzed using HaloTagged-Jun, -Fos, and -LidA); and
(c) a computing system (pg. 4059-4060/Detection of protein-protein interactions on M-NAPPA, see: the protein binding signal was quantified using Array-Pro Analyzer (Media Cybernetics) software) configured to:
(i) receive binding probabilities for each of the individual affinity reagents to candidate proteins of the sample (see: 30 possible candidate target proteins; pg. 4060/Data visualization, see: Cytoscape software),
(ii) receive the empirical measurement outcomes (pg. 4060/Detection of serological antibodies on M-NAPPA, see: fluorescence signal intensity using Array-Pro Analyzer software), and
(iii) characterize the plurality of attached proteins based on the binding probabilities and the empirical measurement outcomes (Table S2, Table S3, see: identified proteins considered to be potential antigens had a ratio higher than 2 and a ring score higher than 1).
Regarding limitations directed towards the attached proteins arranged on the solid support being positioned so that individual proteins are detectably separated from each other, it is the position of the Examiner that the proteins in the arrays disclosed by Yu are fully capable of being analyzed individually, not only by a plurality of microscopy techniques well known in the art, but Yu explicitly discloses validating the arrays using ELISA techniques, which Cohen teaches are capable of single-molecule array protein analysis (pg. 351-352/3.2. Digital ELISA).
Alternatively, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to arrange the proteins in the array disclosed by Yu, in single molecule microarrays and utilize digital ELISA techniques for analysis, as taught by Cohen, in order to provide for an increase in sensitivity, specificity, and the other advantages disclosed by Cohen (Cohen: pg. 358-359/6. CONCLUSION AND FUTURE DIRECTIONS).
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (Multiplexed Nucleic Acid Programmable Protein Arrays, cited in IDS filed 07/14/2025), in view of Yu et al. (Multiplexed Nucleic Acid Programmable Protein Arrays, cited in IDS filed 07/14/2025), in view of Cohen et al. (Single-Molecule Arrays for Protein and Nucleic Acid Analysis).
Regarding claim 16, Yu does not explicitly disclose each of the individual proteins are attached to separate beads, and each of the separate beads are in a separate well from another bead.
Cohen teaches an analogous method of digital ELISA, wherein the solid phase is configured as functionalized beads disposed in a plurality of microwells (Figure 4). It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention to configure the array of wells in the device disclosed by Yu, with beads as taught by Cohen, in order to provide for an increase in sensitivity, specificity, and the other advantages disclosed by Cohen (Cohen: pg. 358-359/6. CONCLUSION AND FUTURE DIRECTIONS).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8-14 of copending Application No. 18/916,443 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the narrower scope of the analogous system for characterizing proteins in a sample would be fully encompassed by the instantly claimed protein characterization system.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-30 have been considered but are moot because the new ground of rejection does not rely on any reference combination applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J EOM whose telephone number is (571)270-7075. The examiner can normally be reached Monday-Friday (9:00AM-5:00PM).
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/ROBERT J EOM/ Primary Examiner, Art Unit 1797
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