DETAILED ACTION
Applicant’s response filed 05/08/2026 has been fully considered. The following rejections and/or objections are either reiterated or newly applied.
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 .
Claim Status
Claims 19, 24 and 30 are cancelled by Applicant.
Claims 1-18, 20-23, 25-29 and 31 are currently pending.
Claims 26-27 and 29 are withdrawn as discussed in the Election of Species section in the Office action mailed 09/09/2024.
Claims 1-18, 20-23, 25, 28 and 31 are herein under examination.
Claims 1-12 and 16-18, 20-23, 25, 28 and 31 are rejected.
Claims 13-16 are identified as allowable subject matter.
Priority
The instant application claims domestic benefit as a continuation of U.S. Application No. PCT/US2022/037785 filed 07/21/2022, which claims domestic benefit to U.S. Provisional Application No. 63/346,307 filed 05/26/2022, U.S. Provisional Application No. 63/345,866 filed 05/25/2022, U.S. Provisional Application No. 63/332,245 filed 04/18/2022, U.S. Provisional Application No. 63/329,781 filed 04/11/2022, and International Application No. PCT/US2021/060647 filed on 11/23/2021. The claims to the benefit of domestic priority for claims 1-18, 20-23, 25, 28 and 31 are acknowledged. As such, the effective filing date for claims 1-18, 20-23, 25, 28 and 31 is 11/23/2021.
Drawings
The objection to the drawings filed 12/04/2024 is withdrawn in view of amended drawings filed 05/08/2026. The drawings filed 12/04/2024 are accepted.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. Figure 16B reference character 1545 contains a nucleotide sequence with 12 specifically defined nucleotides which is not present in the Sequence Listing or the CRF. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Response to Arguments under Sequence Listing
Applicant’s remarks filed 05/08/2026 have been fully considered but they are not persuasive.
Applicant argues that the nucleotide sequence in Figure 16B reference character 1545 does not fall in the scope of 37 CFR 1.831 because at most it contains 5 specifically defined nucleotides (pg. 8, para. 2-4). Applicant’s argument is not persuasive because:
In Figure 16B sequence 1531 is flanked by sequence 1545 on both sides which generates the following nucleotide sequence with 12 specifically defined nucleotides: 5’-NNNNN GAATTC … NNNNN GAATTC NNNNN-5’. Defined sequences “GAATTC” and “GAATTC” are part of a linear region of a branched sequence, even though undefined nucleotides connect them. As such, sequence 1545 requires a Sequence Listing.
Withdrawn Rejections
35 USC 112(b)
The rejection of claims 3-6, 15 and 28 under 35 USC 112(b) is withdrawn in view of claim amendments.
35 USC 103
The rejection of claims 1-5, 7-13, 15, 18, 20, 22-23 and 25 under 35 U.S.C. 103 as being unpatentable over Church et al. in view of Kühnemund et al. and Galanti et al. is withdrawn in view of claim amendment.
The rejection of claims 14, 16-17 and 28 under 35 U.S.C. 103 as being unpatentable over Church et al. in view of Kühnemund et al., and Galanti et al., as evidenced by Margeridon et al., and in further view of Lizardi et al., Pourjahed et al., and Clausson et al. is withdrawn in view of claim amendment.
The rejection of claims 6, 21 and 31 under 35 U.S.C. 103 as being unpatentable over Church et al. in view of Kühnemund et al., and Galanti et al., as evidenced by Margeridon et al., and in further view of Kühnemund et al. is withdrawn in view of claim amendment.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-12, 18, 20-23, 25 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Kühnemund et al. (“Kühnemund 2017”; Nucleic Acids Research 45, no. 8 (2017): e59-e59; previously cited on PTO892 mailed 09/09/2024) in view of Kühnemund et al. (“Kühnemund 2021”; WO 2023/283442 A1; effective filing date 09/07/2021; newly cited) and Church et al. (“Church”; ref. 33 on IDS filed 01/26/2024; US 2008/0269068 A1; previously cited).
This rejection is newly recited as necessitated by claim amendment.
The bold and italicized text below are the limitations of the instant claims, and the italicized text serves to map the prior art onto the instant claims.
Claim 1:
A method of conducting an assay for a set of DNA targets, the method comprising:
Kühnemund 2017 discloses a sensitive and inexpensive digital DNA analysis by microfluidic enrichment of rolling circle amplified single-molecules (abstract).
(a) subjecting the set of DNA targets extracted from a biological sample to a recognition event, in which each DNA target of the set of DNA targets is uniquely recognized by and bound to at least one coded recognition element from a set of coded recognition elements,
Kühnemund 2017 extracted bacterial genomic DNA from cultured bacterial strains (set of DNA targets), wherein the DNA was targeted by barcoded target-specific padlock probes (coded recognition element) (recognition event) (pg. 4, col. 2, para. 1) (Figure A 1-1.5).
each coded recognition element comprising a target-specific binding site and a code from a set of codes, wherein the target-specific binding site is complementary to a known 3’ region and a know 5’ region of a DNA target of the set of DNA targets, wherein each code of the set of codes comprises at least one segment encoding one or more symbols, to yield a set of coded DNA targets, wherein each coded DNA target of the set of coded DNA targets comprises a DNA target of the set of DNA targets bound to a coded recognition element of the set of coded recognition elements;
Kühnemund 2017 recites “Padlock probes were designed to detect species-specific DNA sequences from three bacterial pathogens: Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, and 2 antibiotic resistance markers: OXA-48 and mecA, for carbapanem and methicillin resistance, respectively” (pg. 4, col. 1, last para.) Table S3 shows that the padlock probes contain target complementary regions shown as bolded and detection oligonucleotides marked in green. The DNA sequences marked in green read on the claimed one or more symbols. Figure 1A 1.2 shows the DNA ligated to the barcoded target-specific padlock probes.
wherein the set of DNA targets comprises unamplified nucleic acids extracted from the biological sample;
Kühnemund 2017 does not amplify the extracted genomic DNA prior to ligation with the padlock probes (pg. 4, col. 1, last para. – col. 2, para. 1). Amplification only occurs during RCA (Figure 1).
(b) subjecting the set of coded recognition elements bound to the set of coded DNA targets to a molecular transformation event to yield a set of circularized coded recognition elements; (c) introducing an exonuclease to the set of circularized coded recognition elements to reduce one or more recognition elements of the set of coded recognition elements that were not uniquely recognized by and bound to a DNA target of the set of DNA targets;
Kühnemund 2017 shows in Figure 1A 1.2 the padlock probes ligated with the extracted DNA, yielding circularized templates (pg. 2, col. 2, para. 3)
However, Kühnemund 2017 does not introduce an exonuclease to the circularized templates to reduce padlock probes or target DNA that was not ligated.
Church discloses multiplex decoding of sequence tags in barcodes (abstract). Circularizing probes, such as padlock probes used in RCA, are desirable because non-circularized probes/oligonucleotides are digested with single stranded exonucleases in order to greatly reduce background noise due to spurious amplification and the like [42] [50].
It would have been prima facie obvious to have modified the RCA procedure of Kühnemund 2017 by introducing an exonuclease to digest non-circularized probes/oligonucleotides before performing RCA as taught by Church because it greatly reduces background noise due to spurious amplification. See Church at [42]. There would have been a reasonable expectation of success because Church states that this technique is used in RCA with barcoded padlock probes [27-28] [50]. Kühnemund 2017 also uses barcoded padlock probes in combination with RCA (Figure 1).
(d) performing rolling circle amplification of the set of circularized coded recognition elements to produce amplified circularized coded recognition elements; and
Kühnemund 2017 performs RCA on circularized templates to produce RCA products (RCP) (Figure 1A. 1.3).
(e) detecting the set of DNA targets associated with the amplified circularized coded recognition elements by decoding amplified codes of the amplified circularized coded recognition elements, wherein the decoding comprises performing soft decision decoding.
Kühnemund 2017 teaches that RCPs were fluorescently labelled by hybridization of short fluorescent tagged complementary detection probes that bind to the barcode of each padlock probe and were imaged using fluorescent microscopy (pg. 2, col. 2, para. 4) (Table S3) (Figures 1 and 3). However, Kühnemund 2017 does not perform soft decision decoding of the barcodes.
Kühnemund 2021 detects analytes using sparse labelling which includes decoding of hybridization probes (abstract) [206]. The instant specification at para. [104] defines “soft decision decoding” as calculating a probability that a particular nucleic acid is present. Kühnemund 2021 teaches that RCPs with barcodes are detected using decoding methods that include assigning probabilities to each barcode to determine which barcode/nucleic acid is being detected [227-229] [327] [231] [325] (Table 1).
It would have been prima facie obvious to have detected the RCPs in Kühnemund 2017 by using the sparse labeling technique of Kühnemund 2021. Kühnemund 2021 recites motivation for the combination by teaching that decoding allows identification of very closely localized RCPs and more accurate quantification [80] [217] [229] as well as higher resolution and increased dynamic range [371].
There would have been a reasonable expectation of success because the decoding method of Kühnemund 2021 is dependent on optical images associated with a padlock barcode taken with fluorescent microscopy after RCA [8] [231] and is compatible with multiplexed barcoded experiments [78] [217]. One of ordinary skill would recognize that such a method is applicable to Kühnemund 2017 who also uses barcoded padlock probes used in RCA where fluorescent images are taken (Figure 1).
There would have also been a reasonable expectation of success because Kühnemund 2021 states that sparse labeling is compatible with immobilized targets [316], wherein Kühnemund 2017 discloses that RCPs are immobilized on a microfluidic device then subsequently imaged (Figure 1).
Claim 2:
Kühnemund 2017 shows in Table S3 five barcoded padlock probes. However, Kühnemund 2017 does not teach at least 10 barcoded padlock probes.
Kühnemund 2021 teaches that there may be at least 10 barcodes [184] and that sequential hybridization can be used [186]. It would have been prima facie obvious to have used at least 10 barcoded padlock probes in Kühnemund 2017 as taught by Kühnemund 2021. Motivation for doing so is that Kühnemund 2017 teaches that their microfluidic chip opens the door for sequential hybridization and NGS chemistry for highly multiplexed and targeted nucleic acid sequencing analysis (pg. 9, col. 2, para. 1). There would have been a reasonable expectation of success to use at least 10 barcoded padlock probes because Kühnemund 2017 teaches that sequential hybridization can be used to have more than 5 barcodes (caption of Table 2).
Claims 3-5:
Regarding claims 3 and 5, Kühnemund 2017 teaches that RCPs were fluorescently labelled by hybridization with short fluorescent tagged complementary detection probes that bind to the barcode of each padlock probe and were imaged (nucleic acid hybridization) (pg. 2, col. 2, para. 4) (Table S3) (Figures 1 and 3). Regarding claim 4, this claim is contingent upon the optional limitation in claim 3 of interrogating using sequencing. As such, claim 4 is rejected for its dependency on rejected claim 3 that does not require sequencing.
Claims 6, 21 and 31:
Kühnemund 2017 teaches barcoded padlock probes (codes recognition elements), wherein each barcode is unique and contains 20 nucleotides (at least 16 symbols) (Figure 1) (Table S3). Each barcode of the padlock probes is hybridized with a fluorescently tagged complementary detection probe to produce a detectable signal (nucleic acid hybridization with a plurality of hybridization probes) (Figure 3) (Figure 1A 1.4) (Table S3). Table S3 shows that detection probes each have a distinct fluorophore (a label that is distinct from the other hybridization probes). However, Kühnemund 2017 does not teach that each barcode contains a plurality of segments, 3 or more segments, 4 or more segments.
Kühnemund 2021 teaches that each barcode can include two or more sub-barcodes that function together as a single barcode [185]. MPEP 2144.05.I recites “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists” and also recites “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” As such, two or more sub-barcodes reads on claims 6, 21 and 31 of “a plurality of segments”, “3 or more segments”, and “4 or more segments”.
It would have been prima facie obvious to have modified the barcodes of Kühnemund 2017 by dividing each barcode into two or more sub-barcodes as taught by Kühnemund 2021. Motivation for doing so is taught by Kühnemund 2021 who recites that the sub-barcodes “provide a platform for targeting functionalities, such as oligonucleotides, oligonucleotide-antibody conjugates, oligonucleotide-streptavidin conjugates, modified oligonucleotides, affinity purification, detectable moieties, enzymes, enzymes for detection assays or other functionalities, and/or for detection and identification of the polynucleotide” [185]. There would have been a reasonable expectation of success because Kühnemund 2021 uses these barcodes in padlock probes in RCA, wherein Kühnemund 2017 also uses barcoded padlock probes in RCA.
Claims 7-9 and 11:
Kühnemund 2017 shows in Figure 1A that padlock probes are ligated, by T4 ligase, to the target DNA to yield circularized templates (pg. 5, col. 1, last para.) Each padlock probe contains a unique barcode (sample index) (Figure 1).
Claim 10:
Kühnemund 2017 shows in Table S3 padlock probes with 3’ and ‘5 probe arms that bind to the complementary 5’ and 3’ regions of the target DNA sequence (Figure 1).
Claim 12:
Claim 12 is contingent upon optional limitation (ii) in claim 11. As such, claim 12 is rejected for its dependency on rejected claim 11 that does not require (ii).
Claim 18:
Claim 18 is being interpreted as a product by process as indicated by “are error corrected” because there is no active step of error correcting. MPEP 2113.I recites “[e]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” As such, the barcodes of the padlock probes in Kühnemund 2017 read on error corrected codes, even if the barcodes were produced by a different method.
Claims 20 and 22:
Kühnemund 2017 shows in Table S3 the barcodes of the padlock probes contain 20 nucleotides.
Claim 23:
Kühnemund 2017 teaches that ~300 genomic copies were detected (pg. 7, col. 1, para. 1).
Claim 25:
Kühnemund 2017 detects point mutations in KRAS (pg. 5, col. 1, para. 3).
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kühnemund et al. (“Kühnemund 2017”; Nucleic Acids Research 45, no. 8 (2017): e59-e59; previously cited on PTO892 mailed 09/09/2024) in view of Kühnemund et al. (“Kühnemund 2021”; WO 2023/283442 A1; effective filing date 09/07/2021; newly cited) and Church et al. (“Church”; ref. 33 on IDS filed 01/26/2024; US 2008/0269068 A1; previously cited), as applied to claim 1 above, and in further view of Lizardi et al. (“Lizardi”; Nature genetics 19, no. 3 (1998): 225-232; previously cited on PTO892 mailed 09/09/2024) and Clausson et al. (“Clausson”; Scientific reports 5, no. 1 (2015): 12317; previously cited on PTO892 mailed 09/09/2024).
This rejection is newly recited as necessitated by claim amendment.
The limitations of claim 1 have been taught in the rejection above by Kühnemund 2017, Church and Kühnemund 2021.
Claims 16-17:
Kühnemund 2017 discloses circularized templates derived from ligating barcoded padlock probes to extracted genomic DNA (Figure 1). However, Kühnemund 2017 does not condense the circularized templates by using multivalent oligonucleotide sequences nor circularized templates with one or more modified nucleotides that participate in crosslinking with the multivalent oligo sequences.
Lizardi states that DNA generated by RCA is labelled with fluorescent DNP-oligonucleotide tags that hybridize at multiple sites in the tandem DNA sequence (one or more modified nucleotides). The labeled DNA is then condensed into small objects by cross-linking with a multivalent anti-DNA IgM (pg. 227, col. 2, para. 2 – pg. 228, col. 1). Figure 6 shows the process.
It would have been prima facie obvious to have modified the RCA procedure of Kühnemund 2017 by condensing the DNA generated by RCA as taught by Lizardi. Motivation is taught by Clausson who teaches that reducing the size of fluorophore-labeled RCA products increases the local concentration of fluorophores and as a result increases signal intensity and signal-to-noise ratio (abstract). There would have been a reasonable expectation of success because these references use barcoded padlock probes in detection of DNA/RNA in RCA.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Kühnemund et al. (“Kühnemund 2017”; Nucleic Acids Research 45, no. 8 (2017): e59-e59; previously cited on PTO892 mailed 09/09/2024) in view of Kühnemund et al. (“Kühnemund 2021”; WO 2023/283442 A1; effective filing date 09/07/2021; newly cited) and Church et al. (“Church”; ref. 33 on IDS filed 01/26/2024; US 2008/0269068 A1; previously cited), as applied to claim 1 above, and in further view of Lizardi et al. (“Lizardi”; Nature genetics 19, no. 3 (1998): 225-232; previously cited on PTO892 mailed 09/09/2024).
This rejection is newly recited as necessitated by claim amendment.
The limitations of claim 1 have been taught in the rejection above by Kühnemund 2017, Church and Kühnemund 2021.
Claim 28:
Kühnemund 2017 uses extracted genomic DNA (pg. 6, col. 2, last para.). However, Kühnemund 2017 does not teach an initial DNA concentration of 10 pM to 100 pM.
Lizardi states that target concentration was in the 0.1—0.2 nM range in padlock probe RCA (abstract) (pg. 231, col. 2, para. 3). MPEP 2144.05.I recites “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.” Therefore, it would have been prima facie obvious to use an initial DNA concentration 0.1—0.2 nM range because it overlaps with the claimed range.
Response to Arguments under 35 USC 103
Applicant's arguments filed 05/08/2026 have been fully considered but they are not persuasive.
Applicant’s remarks in sections I.A and II.A–II.D are noted but are not persuasive because they pertain to a combination of references no longer relied upon, and pertain to portions of previously applied references that are not relied upon for any teaching or matter specifically challenged in the argument in the new ground of rejection necessitated by claim amendment.
Applicant’s remarks in section I.A regarding a larger number of references are not persuasive because MPEP 2145.V recites “[r]eliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention.”
Applicant’s remarks in section I.B regarding compact prosecution are noted.
Applicant’s remarks in section I.C regarding Pourjahed are noted but are not persuasive because Pourjahed is no longer relied upon in view of the new ground of rejection necessitated by claim amendment.
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.
Double Patenting Rejection over 18/253,803
Claims 1, 7-8, 11-12, 18, 20, 23 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 14, 23, 40 and 161 of copending Application No. 18/253,803 (Application ‘803) in view of Gataric et al. (“Gataric”; bioRxiv (2021): 2021-10; published 10/14/2021; previously cited on PTO892 mailed 09/09/2024) and Kühnemund et al. (“Kühnemund 2017”; Nucleic Acids Research 45, no. 8 (2017): e59-e59; previously cited on PTO892 mailed 09/09/2024).
Any newly recited portions herein are necessitated by claim amendment.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the claims in Application ‘803.
Application ‘803 claims 1-2, 5 and 10 read on instant claims 1 and 20. Application ‘803 claim 23 reads on instant claims 7-8. Application ‘803 claim 14 reads on instant claims 11-12. Application ‘803 claim 161 reads on instant claim 23. Application ‘803 claim 40 reads on instant claim 25.
Application ‘803 claim 1 differs from instant claim 1 in that it does not use soft decision decoding to decode coded recognition elements.
Kühnemund 2017 in Figure 1 uses bacterial genomic DNA extracted from cultured strains which were not amplified before ligation with the padlock probes (DNA targets extracted from a biological sample) (pg. 4, col. 2, para. 1; pg. 6, col. 2, last para.). Table 1 shows the padlock probes contain sequences that are complementary to the target DNA sequence (wherein the target-specific binding site is complementary to a known 3’ region and a known 5’ region of a DNA target of the set of DNA targets). It would have been prima facie obvious to one of ordinary skill in the art to have modified Application ‘803 by extracting genomic unamplified DNA from a biological sample as taught by Kuhnemund 2017 because extracted genomic DNA detects pathogenic genomic DNA in samples containing different pathogenic species (pg. 7, col. 2, para. 2). One of ordinary skill in the art would have had a reasonable expectation of success for extracting DNA to perform RCA because Kuhnemund uses padlock probes with RCA on extracted DNA.
Gataric discloses PoSTcode, a probabilistic image-based spatial transcriptomics decoder that can decode hundreds of thousands of fluorescent signals each derived from single molecules of mRNA (abstract). Figure 1C demonstrates how PoSTcode performs the decoding, which includes computing posterior probabilities to decode barcodes. Gataric also states that PoSTcode improves decoding results due to a novel probabilistic model used to assign barcodes to image values extracted at detected locations of an RNA signal (by decoding the amplified codes of the amplified circularized coded recognition elements, wherein the decoding comprises performing soft decision decoding).
Double Patenting Rejection over 18/670,329
Claims 1, 3-7, 11-12 and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-9, 11, 13-14 and 16-17 of copending Application No. 18/670,329 (Application ‘329) in view of Church et al. (“Church”; ref. 033 on IDS filed 01/26/2024; US 2008/0269068 A1; previously cited on PTO892 mailed 07/14/2025).
Any newly recited portions herein are necessitated by claim amendment.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the claims in Application ‘329.
Application ‘329 claims 1, 4, 8-9 and 11 read on instant claim 1. Application ‘329 claims 4-5 read on instant claims 3-6. Application ‘329 claims 16-17 read on instant claim 7. Application ‘329 claims 6, 7, 13 and 14 read on instant claims 11, 12, 21 and 22, respectively.
Application ‘329 claim 1 differs to instant claim 1 because it does not teach “wherein the target-specific binding site is complementary to a known 3' region and a known 5' region of a DNA target of the set of DNA targets”.
Church discloses a method for RCA using MIP and padlock probes (abstract). Church discloses that the MIPs contains one or more guide sequences that are complementary to specific position on a template target, such as a bead-bound oligonucleotide, and thus hybridize with this sequence (target-specific binding site) [2]. Figure 2A shows two guide sequences “ACT” and “TCG” that are complementary to known 3’ and 5’ positions in the template target. The known positions are TGA and AGC (wherein the target-specific binding site is complementary to a known 3’ region and a know 5’ region of a DNA target of the set of DNA targets).
It would have been prima facie obvious to one of ordinary skill in the art to have modified the target specific binding sites in Application ‘364 by making them complementary to known sequences of a target sequence as taught by Church in order to target a desired sequence. One of ordinary skill in the art would have had a reasonable expectation of success because the probes of Application ‘364 already have a target specific binding site, wherein the modification of Church would have further specified it to be complementary to a known target sequence, which is what Church achieves in their method.
This is a provisional nonstatutory double patenting rejection.
Double Patenting Rejection over 18/670,364
Claims 1, 3-6 and 21-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-7, 13 and 15-17 of copending Application No. 18/670,364 (Application ‘364) in view of Church et al. (“Church”; ref. 033 on IDS filed 01/26/2024; US 2008/0269068 A1; previously cited on PTO892 mailed 07/14/2025).
Any newly recited portions herein are necessitated by claim amendment.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the claims in Application ‘364.
Application ‘364 claims 1 and 15-17 read on instant claims 3 and 5-6. Application ‘364 claims 1 and 6 read on instant claims 3-6. Application ‘364 claim 2 reads on instant claim 4. Application ‘364 claim 13 reads on instant claim 23. Application ‘364 claim 7 reads on instant claims 21-22.
Application ‘364 claim 1 differs from instant claim 1 because it does not teach step (C) or a target specific binding side with known 5’ and 3’ regions.
Church discloses a method for RCA using MIP and padlock probes (abstract). Church discloses that the MIPs contains one or more guide sequences that are complementary to specific position on a template target, such as a bead-bound oligonucleotide, and thus hybridize with this sequence (target-specific binding site) [2]. Figure 2A shows two guide sequences “ACT” and “TCG” that are complementary to known 3’ and 5’ positions in the template target. The known positions are TGA and AGC (wherein the target-specific binding site is complementary to a known 3’ region and a know 5’ region of a DNA target of the set of DNA targets). Church discloses “Such probes are desirable because non-circularized probes can be digested with single stranded exonucleases thereby greatly reducing background noise due to spurious amplifications, and the like.” [42]. Church discloses “performing rolling circle amplification such that the barcode sequence of one molecular inversion probe is transferred to one immobilized query oligonucleotide sequence” [7].
It would have been prima facie obvious to one of ordinary skill in the art to have modified the method Application ‘364 by using RCA as the amplification event for probes and by using an exonuclease as taught by Church. The motivation for doing so is that using RCA and exonuclease for MIP or padlock probes reduces background noise as taught by Church [42]. One of ordinary skill in the art would have had a reasonable expectation of success for the combination because Church provides specific techniques to perform an amplification event described in Application ‘364 (i.e., RCA, exonuclease, MIPs and padlock probes).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments under Double Patenting
Applicant argues that claim 1 amendments make the application patentably distinct from the co-pending application (pg. 16 of Applicant’s remarks). Applicant’s argument is not persuasive because the Double Patenting rejections have been updated to reflect the new limitation in claim 1. It is noted that none of the co-pending applications amplify any of their nucleic acid analytes prior to a recognition event or molecular transformation, which under their BRI include them being unamplified.
Conclusion
No claims are allowed.
Claims 13-15 are not rejected under 35 USC 103 because there is a lack of motivation to modify the rolling circle amplification (RCA) of Kühnemund et al. (“Kühnemund 2017”; Nucleic Acids Research 45, no. 8 (2017): e59-e59; previously cited on PTO892 mailed 09/09/2024) by adding a solid support to perform the RCA. Performing RCA on solid surfaces is known such as in Church et al. (“Church”; ref. 033 on IDS filed 01/26/2024; US 2008/0269068 A1) in Figures 3A-3B and para. [34]-[36]. However, there is no motivation to modify Kühnemund 2017 to perform RCA on a solid support. This is because after RCA in Kühnemund 2017, the resultant RCPs are flowed through a microfluidic chip for imaging analysis. Thus, it’s unclear why one of ordinary skill would want to perform RCA on a solid support then transfer the RCPs to a microfluidic chip.
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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/N.A.A./Examiner, Art Unit 1687
/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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