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 .
Status of the Application
The Amendment and the Request for Continued Examination, each filed November 3, 2025, are acknowledged.
Claims 1-8, 10-14, 19-20 and 24-26 were pending. Claims 1, 6-8, 19-20 and 24-26 are being examined on the merits. Claims 2-5 and 10-14 are canceled.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 3, 2025 has been entered.
Response to Arguments
Applicant’s arguments filed November 3, 2025 have been fully considered.
The following objections and rejections are WITHDRAWN in view of Applicant’s arguments and amendments to the claims:
Objections to the Specification – Sequence Listing
Prior Art rejections
The following rejections are MODIFIED in view of Applicant’s arguments and amendments to the claims:
Double patenting rejections
Response to arguments regarding prior art rejections
Applicant argues that the prior art rejections should be withdrawn because the cited art does not teach or suggest all of the limitations of instantly amended claim 1 (Remarks, pp. 7-15).
The Examiner agrees that the cited art does not teach, at least, the combination of the instant amendments to claim 1.
New prior art rejections appear below.
Response to arguments regarding double patenting rejections
Applicant argues that instantly amended claim 1 of the instant application is patentably distinct from claim 1 of the reference application, which does not teach or suggest all of the limitations of amended claim 1 (Remarks, p. 16).
The rejection is modified below to account for the instant claim amendments and to reflect that the reference application has now issued into a patent.
Claim Rejections - 35 USC § 103
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.
Claims 1, 7, 19-20 and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac (WO 2014/145820 A2) in view of Tang (WO 2016/077313 A1).
Regarding independent claim 1 and dependent claims 7, 19-20 and 24, Drmanac teaches …
A multimer configured to allow sequencing and sequence analysis of at least one nucleic
acid segment, the multimer comprising multiple units, wherein each unit comprises: (a) a segment comprising a target nucleic acid sequence to be sequenced and analyzed (Fig. 2B, top pane; paras. 140-141: individual segments between barcode sequences 22a-22d);
(b) an introducer comprising a nucleic acid sequence that is configured to mark a 5’-end of the unit; a closure comprising a nucleic acid sequence that is configured to mark a 3’-end of the unit, wherein the introducer and the closure are further configured to serve as target sequences for the annealing of primers of a PCR (Fig. 2B; paras. 140-141, 145: primer binding site, 23, marks the 5’ and 3’ end of each segment, as also shown in Fig. 2B middle pane);
and (d) an identifier (1) that is unique for every copy of said nucleic acid segment; (2) that identifies copies of the same target nucleic acid sequence in said nucleic acid segment and (3) whose presence distinguishes errors occurring during at least a second amplification and/or sequencing of said multimer and mutations in said target sequence (Fig. 2B; paras. 79, 86-87, 93, 128, 140-141, 145: unique tag sequence, 22a-22d).
Further, regarding the identifier, Drmanac teaches that the barcode sequences (Fig. 2B; paras. 140-141, 145: unique tag sequence, 22a-22d) are unique for each copy of the segment. As can also be seen in Fig. 2B (middle pane), identifiers 22a and 22b are both attached to the first segment (one at each end), while 22b and 22c are attached to the second segment, and so on. Since each barcode sequence is unique, then the combination of 22a and 22b is also unique as to the first segment, as is the combination of 22b and 22c as to the second segment, and so on. Thus, each of 22a-22d can be considered a partial identifier, and collectively they can be considered multiple partial identifiers, wherein one partial identifier is attached to one side of the segment and the other partial identifier is attached to the other side of the segment. Finally, Drmanac teaches that each barcode sequence is any length sufficient to provide a population of different tags, including 10-20 nucleotides (para. 124-125). Finally, these unique sequences, e.g., 22a plus 22b, are capable of identifying copies of the same target nucleic acid sequence in said nucleic acid segment, and whose presence can be used distinguish errors occurring during at least a second amplification and/or sequencing of said multimer and mutations in said target sequence.
Finally, regarding the index, Drmanac generally teaches adding an index sequence to each target segment (e.g., para. 145 and Fig. 3: barcode (22) serves as an identifier for each segment of the target nucleic acid, thus could be used as a sample index), but does not teach an embodiment where an index sequence is attached to each unit of a monomer in a concatemer. However, Tang teaches an index comprising a nucleic acid sequence that is unique to an origin of the segment in a concatemer and identifies the source of the sequence of the segment (para. 53).
Prior to the effective filing date of the instant invention, it would have been prima facie
obvious to modify the Drmanac multimer with the Tang index sequences. Drmanac teaches that associating an index sequence with each target segment is useful for downstream sequence assembly, while Tang teaches attaching an index sequence to each monomer in a concatemer. The ordinary artisan would have been motivated to include the index sequence with each monomer of the Drmanac concatemer with the expectation that doing so would result in the advantage of a concatemer which, when used in, e.g., long read sequencing, would result in sequencing data that is readily aligned and analyzed. There would also have been an expectation that such a concatemer would increase the throughput and efficiency of sequencing, as samples from different sources could be pooled and analyzed at once, while still generating data that can be matched to the original sample source. The ordinary artisan would have had an expectation of success as the modification of nucleic acids by adding indices, identifiers, or other barcodes is well-known in the art, and because Drmanac teaches the use of such index sequences in other embodiments.
Regarding dependent claims 25-26, Drmanac additionally teaches that at least some of the units differ in the sequence of their segments (Figs. 2A-B; paras. 20-21: e.g., the segments are from adjacent regions of the same target nucleic acid), while Tang teaches that at least some of the units have identical sequences (paras. 53-55).
Claims 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac (WO 2014/145820 A2) in view of Tang (WO 2016/077313 A1) as applied to claim 1 above, and further in view of Fu1 (US Patent App. Pub. No. 2016/0289740).
Fu teaches combinatorial coding of nucleic acids to increase sequencing throughput.
Regarding dependent claims 6 and 8, as noted above, Drmanac teaches that various
barcodes can be split into multiple partial barcodes (e.g., Fig. 2B: 22a-22d). Drmanac also teaches that splitting barcodes into multiple partial barcodes is advantageous because such combinatorial barcoding “provides a larger repertoire of possible barcodes while reducing the number of full-size barcodes that need to be generated” (para. 126). Tang specifically teaches a sample index that is unique to the origin of the segment. Further, Fu also teaches that identifiers/indices/barcodes can be split into multiple, partial identifiers/indices/barcodes and that each partial sequence can be attached on either side of the segment, or on both sides (paras. 11, 13, 99). Fu also teaches that combinatorial coding of nucleic acids increases sequencing throughput (paras. 3, 6). Further, regarding claim 6, Fu teaches that the identifier/index/barcode can have varying lengths from 1 nucleotide to 300 nucleotides (para. 64). Fu does not teach any particular length for the partial identifiers/indices/barcodes however the ordinary artisan would be able to optimize to arrive at the length of at least 6 nucleotides.
Prior to the effective filing date of the instant invention, it would have been prima facie
obvious to further modify the modified Drmanac multimer, discussed above, to optimize the length of the barcodes/indices/identifiers. The ordinary artisan would have been motivated to optimize the length of the partial barcodes/indices/identifiers through routine experimentation in order to customize the assay as needed. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. MPEP 2144.05 (II)(A). The ordinary artisan would have had an expectation of success as the modification of nucleic acids by adding indices, identifiers, or other barcodes is well-known in the art, and because Fu provides direction on how to do so.
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, 6-8, 19-20 and 24-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 12,410,471 (hereinafter, the ‘471 patent).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1 and 5 of the ‘471 patent teaches or suggests all of the limitations of instant claims 1, 6-8, 19-20 and 24-26, although in different embodiments. Further, the specific limitations of the instant claims, including incorporating various numbers and types of indices and identifiers into various positions relative to the target nucleic acid, can all be arrived at through routine optimization, and thus are obvious based on the limitations of claims 1 and 5 of the ‘471 patent. In addition, the ordinary artisan would have had an expectation of success in making these modifications as optimizing nucleic acid design prior to sequencing is well-known in the art.
Conclusion
Claims 1, 6-8, 19-20 and 24-26 are being examined, and are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 Fu was cited in the Information Disclosure Statement submitted May 12, 2021.