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 .
Applicant’s reply to the February 10, 2026 Office Action, filed April 30, 2026, is acknowledged. Claims 1-19 are currently pending and under examination.
Any objection or rejection of record in the previous Office Action which is not addressed in this action has been withdrawn in light of Applicant’s amendments and/or arguments. This action is FINAL.
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.
Claim 16 is 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 16, is considered vague and indefinite for the following reasons:
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 16 recites the broad recitation “probes are identified by amplification”, and the claim also recites “preferably, by quantitative PCR.”, which is the narrower statement of the range/limitation. This claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Rejections - 35 USC § 102
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.
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.
Claims 1-17 and 19 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Regev et al. (U.S. Patent Application Publication US 2019/0085324 A1, published March 21, 2019).
Regarding claim 1, Regev teaches a method of detecting a nucleic acid (Page 26, [0289] and Page 27, [0299]). Regev teaches providing a nucleic acid-containing compartment (Page 34, [0356], Pages 36-37, [0375] and Page 45, [0453]). Regev teaches hybridizing a plurality of single-stranded DNA oligonucleotide probes to nucleic acid molecules within said compartment (Page 7, [0080], Page 41, [0408], Page 42, [0413] and Page 50, [0503]-[0504]). Regev teaches removing single-stranded DNA oligonucleotide probes from the compartment that have not specifically hybridized to any nucleic acid within the compartment ( Page 41, [0408], Page 42, [0413] and Page 102, [001030]). Regev teaches identifying single-stranded DNA-oligonucleotide probes specifically hybridized to nucleic acid molecules within said compartment by probe sequencing or probe amplification and thus determining nucleic acids corresponding to the probe present in said compartment (Page 3, [0025], Page 7, [0080], Page 41, [0408], Page 42, [0413]-[0414] and Page 50, [0503]-[0504]). Regev teaches the method does not comprise sequential probe hybridization as a means to amplify nucleic acid detection and the method does not comprise a step during which two or more probes are ligated to each other or during which one or more probes are ligated to other types of probes to facilitate probe amplification and gene detection (Page 6, [0066] and Pages 41, [0408]).
Regarding claim 2, Regev teaches the method does not comprise an RNA isolation step (i.e., RNA interacting with proteins; Page 5, [0047]).
Regarding claim 3, Regev teaches the method does not comprise a cDNA generation step (Page 57, [0570]).
Regarding claim 4, Regev teaches the nucleic acid is RNA and/or mRNA (Page 33, [0356]).
Regarding claim 5, Regev teaches the nucleic acid is ssDNA or dsDNA, optionally, ssDNA (Page 13, [0140] and Page 37, [0380]).
Regarding claim 6, Regev teaches the nucleic acid-containing compartment is a eukaryotic cell, a nucleus of a eukaryotic cell, cytoplasm of a eukaryotic cell, a mitochondrion, a chloroplast, an exosome, a prokaryotic cell, a group of cells in a tissue, or a virus (Pages 4, [0042] and Page 60, [0696]).
Regarding claim 7, Regev teaches the nucleic acid -containing compartment is sectioned before step (b) (Page 36-37, [0375]).
Regarding claim 8, Regev teaches the nucleic acid-containing compartment or cell are biochemically separated before step (b) (Page 36-37, [0375]).
Regarding claim 9, Regev teaches step (b) is preceded by fixation of the nucleic acid-containing compartment (Pages 4, [0035] and Page 39, [0398]).
Regarding claim 10, Regev teaches the nucleic acid-containing compartment is not fixated (Page 48, [0481]).
Regarding claim 11, Regev teaches the single-stranded DNA oligonucleotide probes comprise a target region complementary to a nucleotide sequence of a target nucleic acid flanked by a pair of universal primer regions (Page 4, [0035], Page 5, [0045], Page 34, [0360], Page 37, [0378], Page 41, [0408], Page 42, [0413]-[0414], Page 43, [0427]). Regev teaches the single-stranded DNA oligonucleotide probes further comprise a unique molecular identifier (Page 3, [0025], Page 7, [0079] and Page 41, [0408]).
Regarding claim 12, Regev teaches the single-stranded DNA oligonucleotide probes specifically hybridize to a plurality of target nucleic acids present in the compartment (Page 3, [0025], Page 7, [0080], Page 41, [0408], Page 42, [0413]-[0414] and Page 50, [0503]-[0504]).
Regarding claim 13, Regev teaches the single-stranded DNA oligonucleotide probes form a library that covers at least 99% of the RNA present in the compartment (Page 5, [0044], Page 27, [0299] and Page 28, [0310]).
Regarding claim 14, Regev teaches between step (c) and (d), an amplification of bound single-stranded DNA oligonucleotide probes is carried out (Page 7, [0079] and Page 59, [0686]).
Regarding claim 15, Regev teaches the bound single-stranded DNA oligonucleotide probes are identified by sequencing (Page 37, [0376]).
Regarding claim 16, Regev teaches the bound single-stranded DNA oligonucleotide probes are identified by amplification, preferably by quantitative PCR (Page 56, [0557], Page 57, [0568] and Page 59, [0686]).
Regarding claim 17, Regev teaches spatially mapping detected nucleic acids in said compartment (Page 24, [0266], Page 36, [0368], Page 48, [0473], Pages 59-60, [0688], Page 65, [0752] and Pages 79-80, [0840]). Regev teaches sectioning the compartment prior to step (b) to obtain a collection of fractions and thus separating nucleic acid molecules from each other depending on their localization (Page 10, [0117], Page 12, [0141]-[0142], Page 24, [0266], Page 36, [0368], Page 36-37, [0375], Page 45, [0446], Page 53, [0535] and Pages 59-60, [0688]). Regev teaches identifying the single-stranded DNA-oligonucleotide probes specifically hybridized to nucleic acid molecules within each fraction in step (d) and thus determining the presence or absence of RNA corresponding to the probe in each fraction as well as mapping nucleic acids within the compartment (Page 3, [0025], Page 36, [0368], Page , 59-60, [0688], Page 67, [0768] and Page 68, [0775]).
Regarding claim 18, Regev teaches detection of RNA is combined with the detection of at least one DNA locus within said compartment (Page 44, [0437], Page 47-48, [0470], Page 48, [0475], Page 60, [0689] and [0695] and Examples 1-2). Regev teaches determining the presence or absence of at least one DNA locus in each fraction (Page 44, [0437], Page 47-48, [0470], Page 48, [0475], Page 60, [0689] and [0695] and Examples 1-2). Regev teaches determining co-segregation of said at least one DNA locus and the single-stranded DNA oligonucleotide probe(s) specifically hybridized to RNA (Page 44, [0194]-[0196], Page 27, [0299] and Pages 33-34, [0356]).
Regarding claim 19, Regev teaches determining gene expression in single cells, groups of cells or intracellular compartments (Pages 33-34, [0356], Page 5, [0054], Page 11, [0139], Page 12, [0142] and Page 33, [0350]). Regev teaches identifying isoforms and allele-specific variants of RNAs within a compartment (Page 11, [0138], Page 30, [0324], Pages 33-34, [0356], Page 44, [0441], Page 47, [0464], Page 90, [0909]). Regev teaches quantifying transcription of genes (Page 48, [0475], Page 59, [0684], Pages 26-27, [0299], Page 33, [0351], Page 34, [0358] and Page 59, [0684]). Regev teaches identifying cell types of complex heterogenous tissue (Pages 68-69, [0780], Page 71, [0801], Page 39, [0395]). Regev teaches identifying endogenous and exogenous dsDNA and ssDNA within a compartment (Page 50, [0497], Page 51, [0510], Page 55, [0548] and Page 59, [0685]). Regev teaches mapping RNA location in the compartment, mapping RNA and nucleic acid loci location in the compartment, mapping RNA and protein location in the compartment as well as, mapping RNA, protein and nucleic acid loci location in the compartment (Page 3, [0029], Page 24, [0266], Page 36, [0368], Page 48, [0473], Pages 59-60, [0688], Page 65, [0752] and Pages 79-80, [0840]).
Regev teaches each and every limitation of claims 1-19 and therefore Regev anticipates claims 1-19.
Response to Arguments
Applicant’s arguments and amendments filed April 30, 2026, with respect to the
rejections under U.S.C. § 112(b), 102 and 103 have been fully considered and are persuasive. Therefore, these rejections have been withdrawn.
However, upon further consideration, new rejections under 35 U.S.C. § 112(b) and 102
are made in view of applicant’s amendments.
As discussed above, newly cited Regev discloses a method that does not comprise a step during which two or more probes are ligated to each other or during which one or more probes are ligated to other types of probes to facilitate probe amplification and gene detection, in that Regev discloses use of a single probe.
Therefore, for all these reasons and those listed above, Regev is deemed to render the instant invention anticipated.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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