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 .
Claims Status
Claims 1-5 & 7-10 filed on 03/10/2026 are pending. Claims 11-16 are withdrawn from consideration as being drawn to a non-elected invention. The cancellation of claim 6 is acknowledged. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant application. Response to Applicant’s argument follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 102
Claim(s) 1-5 & 7-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Makino (Makino et al; Journal of the American Chemical Society, Vol. 144, pages 1572-1579, January 20th, 2022), as cited on the IDS dated 04/11/2023.
Regarding amended claim 1, Makino teaches a color-changing fluorescent barcode (CCFB) comprising target oligonucleotides such as strands F2 and F4 (at least one first oligonucleotide) attached to polystyrene beads (support structure) (a least one first oligonucleotide connected to the support structure) and oligonucleotides attached with a fluorophore (label) and a quencher such as strands F1, F3, and F5 (at least a second oligonucleotide with at least one label connected) that hybridizes to target oligonucleotides such as strands F2 and F4 (at least one first oligonucleotide) (at least a second oligonucleotide partially complementary to a part of the first oligonucleotide) (abstract lines 9-17; pg. 1574-1575 paragraph bridging pg. 1574 & 1575 lines 1-12; Figure 1; Figure 2). Makino also teaches the that emission color of the fluorophore label can be varied in the predetermined sequence (predetermined sequence is unique to at least one label) and that the color sequence of this CCFB complex from the different fluorophore labels can be detected (a sequence of part of the first oligonucleotide and part of the second oligonucleotide that is complementary is predetermined and is unique to at least one label) (abstract lines 12-14; pg. 1574-1575 paragraph bridging pg. 1574 & 1575 lines 1-12; Figure 1; Figure 2).
Regarding amended claim 2, Makino teaches the label comprises at least a first fluorophore (pg. 1574-1575 paragraph bridging pg. 1574 & 1575 lines 1-12; Figure 1; Figure 2).
Regarding amended claim 3, Makino teaches the target oligonucleotides such as strands F2 and F4 (at least one first oligonucleotide) are attached to polystyrene beads (support structure is a microbead) (abstract lines 9-17; supporting information pg. 3 3rd full paragraph lines 1-6).
Regarding amended claims 4 & 5, Makino teaches the oligonucleotides attached with a fluorophore (label) and a quencher such as strands F1, F3, and F5 comprise different fluorophores of Cy5, Cy3, and FAM to create a unique color sequence (the label comprises at least a second fluorophore wherein the first fluorophore and the second fluorophore differ in their optical properties) (pg. 1573-1574 paragraph bridging pg. 1573 & 1574 lines 1-17; pg. 1574-1575 paragraph bridging pg. 1574 & 1575 lines 1-12; Figure 1; Figure 2).
Regarding amended claim 7, Makino teaches the fluorophore label is connected to the ends of the oligonucleotides attached with a fluorophore (label) and a quencher (at least a second oligonucleotide) (first fluorophore and/or second fluorophore are connected to distinct parts of the second oligonucleotide) (pg. 1574-1575 paragraph bridging pg. 1574 & 1575 lines 1-12; Figure 1; Figure 2).
Regarding amended claim 8, Makino teaches the removal of the F1 strand (at least one first oligonucleotide) from the complex through strand displacement (the part of the first oligonucleotide partially complementary to the second oligonucleotide is cleavable from the second oligonucleotide) (pg. 1575 paragraph bridging columns 1 & 2 lines 8-10).
Regarding amended claim 9, Makino teaches the oligonucleotides attached with a fluorophore (label) and a quencher such as strands F1, F3, and F5 (at least a second oligonucleotide) are tethered to a fluorophore and a quencher at each terminus by complementary oligomers (first fluorophore is connected to the second oligonucleotide by a third oligonucleotide partially complementary to a part of the second oligonucleotide) (pg. 1573-1574 paragraph bridging pg. 1573 & 1574 lines 25-31; Figure 1 description).
Regarding amended claim 10, Makino teaches the oligonucleotides attached with a fluorophore (label) and a quencher such as strands F1, F3, and F5 (at least a second oligonucleotide) are tethered to a fluorophore and a quencher at each terminus by complementary oligomers (second fluorophore is connected to the second oligonucleotide by a fourth oligonucleotide partially complementary to a part of the second oligonucleotide) (pg. 1573-1574 paragraph bridging pg. 1573 & 1574 lines 25-31; Figure 1 description).
Response to Arguments
The response traverses the rejection. The response asserts that as discussed in the specification and illustrated in FIG. 1 that the part 108 of the first oligonucleotide 104 and the part 110 of the second oligonucleotide 106 comprise a predetermined nucleotide sequence that is unique to a particular combination of fluorophores and/or their particular fluorescent properties of the label 112. Further, the response asserts that Makino discloses a color-changing fluorescent barcode (CCFB) approach in which the emission of CCFB can vary in the predetermined sequence so that multiple targets can be detected simultaneously and therefore, multiple targets can be identified by decoding the color sequence from acquired images. Further, the response asserts that, for example, as various can be decoded by the same Q strands, complicated nanostructure designs and a large number of oligonucleotides are not necessary for the CCFB labeling system. Further, the response asserts that to verify the multiplexed capability of the CCFB approach, a mixture of beads barcoded with different sequences was prepared and that each bead exhibited a different color change in which the sequential addition of Q strands could induce stranded displacement in each bead and since all barcodes are composed of strands with same sequences, completion of strand exchange of the barcode with no color change can be judged from the color change of other barcodes. Specifically, the response asserts that in the CCFB approach of Makino, all the barcodes are composed of strands with same sequences and different color-changing sequences are used to identify multiple target molecules and therefore, Makino does not disclose wherein a sequence of the part of the first oligonucleotide and the part of the second oligonucleotide is predetermined and unique to at least one label as recited in amended claim 1. This argument has been thoroughly reviewed but was not found persuasive. First, Makino teaches the that emission color of the fluorophore label can be varied in the predetermined sequence (predetermined nucleotide sequence that is unique to a particular combination of fluorophores and/or their particular fluorescent properties of the label) and that the color sequence of this CCFB complex from the different fluorophore labels can be detected (a sequence of part of the first oligonucleotide and part of the second oligonucleotide that is complementary is predetermined and is unique to at least one label) (abstract lines 12-14; pg. 1574-1575 paragraph bridging pg. 1574 & 1575 lines 1-12; Figure 1; Figure 2). Second, the claim is a comprising claim which is “open” and does not exclude the use of multiple labels for the detection of multiple targets. In addition, the disclosure of Makino that all barcodes are composed of strands with same sequences does not require that the entire sequence is the same and further, as discussed above, Makino teaches the that emission color of the fluorophore label can be varied in the predetermined sequence (predetermined sequence is unique to at least one label) and therefore, Makino teaches a sequence of the part of the first oligonucleotide and the part of the second oligonucleotide is predetermined and unique to at least one label as recited in claim 1 as currently amended.
The response also asserts that because Makino fails to disclose at least the above-recited features of amended independent claim 1, Makino cannot anticipate claim 1 or its dependent claims 2-5 and 7-10. This argument has been thoroughly reviewed but was not found persuasive for the reasons set forth above.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Double Patenting
Claims 1, 2, 4, 5, & 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 6, 8, 11, 16, & 17 of copending Application No. 19/209,831 (reference application) and over claims 1, 3, 8, & 12 of copending Application No. 19/353,632 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because each patent application provides a marker comprising a label, at least a first and second oligonucleotides, and a support structure.
Regarding claim 1, the instant application claims a constituent part of a marker comprising a support structure, at least one first oligonucleotide connected to the support structure, at least a second oligonucleotide at least partially complementary to a part of the first oligonucleotide, and at least one label connected to the second oligonucleotide. Copending Application No. 19/209,831 claims a marker for analyzing a biological sample comprising a first label comprising a first nucleic acid backbone, a second label comprising a second nucleic acid backbone, wherein the first nucleic acid backbone and the second nucleic acid backbone hybridize at least partially to each other, and at least one first and second labelling moiety attached to either the first or second nucleic acid backbone (at least one label connected to the second oligonucleotide), and an anchor to anchor the marker to a solid support (first oligonucleotide connected to the support structure) (see claims 1, 8, 16, & 17).
Regarding claims 2, 4, & 5, the instant application claims that the label comprises at least a first and a second fluorophore that differ in their optical properties. Copending Application No. 19/209,831 claims the at least one first and second labelling moiety are optically detectable first and second fluorescent dyes that have different characteristics (see claims 5 & 6).
Regarding claim 7, the instant application claims the first and/or second fluorophore are each connected to distinct parts of the second oligonucleotide. Copending Application No. 19/209,831 claims each the plurality of first and/or second labelling moieties are equally spaced from each other (connected to distinct parts) (see claim 11).
Regarding claim 1, the instant application claims a constituent part of a marker comprising a support structure, at least one first oligonucleotide connected to the support structure, at least a second oligonucleotide at least partially complementary to a part of the first oligonucleotide, and at least one label connected to the second oligonucleotide. Copending Application No. 19/353,632 claims a marker for analyzing a biological sample comprising a first label part comprising at least one first nucleic acid strand, a second label part comprising a second nucleic acid strand, and a third label part comprising a third nucleic acid strand, wherein the at least one first strand is at least partially complementary to the hybridized second and third nucleic acid strand, wherein the first label part comprising a first nucleic acid strand comprises at least on labelling moiety (a second strand at least partially complementary to the first oligonucleotide that comprises at least one label), and wherein the at least one first nucleic acid strand is immobilized on a solid support (see claims 1, 3, 8, & 12).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
The response traverses the rejection. The response asserts that since each of the reference applications were in fact filed after the present application, they cannot be reference application to this earlier filed application and therefore a double patenting rejection would only be appropriate, if at all, in the later filed applications and moreover the claims of the cited reference applications have not been patented. This argument has been thoroughly reviewed but was not found persuasive as MPEP §804(1)(b)(i) states that an application under examination that have an earlier term filing date in which the provisional nonstatutory double patenting rejection should be withdrawn if it is the only rejection remaining in an application having the earlier patent term filing date, however claims 1-5 & 7-10 have 102 rejections that have been maintained and applied to the newly amended claims and therefore, as there are other rejections remaining in the instant application MPEP §804(1)(b)(i) does not apply.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Conclusion
Claims 1-5 & 7-10 are rejected.
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 BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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