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 .
Response to Amendment
The amendment filed March 13th, 2026 is acknowledged. Regarding the Office Action mailed November 28th, 2025:
The objections to the specification are withdrawn in view of the amendments.
The rejection set forth under 35 U.S.C. 112(b) is withdrawn in view of the amendments.
Maintained, modified, or new rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 1, 9, and 10 have been amended. Claims 12-21 have been canceled. Claims 22 and 23 have been added. Claims 1-11 and 22-23 are pending. Claims 1-11 and 22-23 are under examination and discussed in this Office action.
Claim Objections - New - Necessitated by Amendment
Claim 23 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
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.
Modified - Necessitated by Amendment
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Raine (US 20190194649 A1; previously cited), in view of Schweyen (Detection and Removal of PCR Duplicates in Population Genomic ddRAD Studies by Addition of a Degenerate Base Region (DBR) in Sequencing Adapters, The Biological Bulletin, October 2014, 227, 146-160; previously cited) and Smith (Unique Molecular Identifiers – the problem, the solution and the proof [online]. CGAT Oxford, [2015] [retrieved on May 9th, 2026]. Retrieved from: https://cgatoxford.wordpress.com/2015/08/14/unique-molecular-identifiers-the-problem-the-solution-and-the-proof/).
Regarding instant claim 1, Raine teaches a method of producing a nucleic acid library, comprising: combining (i) a nucleic acid composition comprising single-stranded nucleic acid (ssNA), (ii) a plurality of first oligonucleotide species, and (iii) a plurality of first scaffold polynucleotide species (FIG. 1 SPLAT diagram, reference 180; Page 8, paragraph [0104]), wherein: (a) each polynucleotide in the plurality of first scaffold polynucleotide species comprises an ssNA hybridization region and a first oligonucleotide hybridization region (Page 8, paragraph [0104]: random overhang and short double-stranded region); and (d) the nucleic acid composition, the plurality of first oligonucleotide species, and the plurality of first scaffold polynucleotide species are combined under conditions in which a molecule of the first scaffold polynucleotide species is hybridized to (i) a first ssNA terminal region and (ii) a molecule of the first oligonucleotide species, thereby forming hybridization products in which an end of the molecule of the first oligonucleotide is adjacent to an end of the first ssNA terminal region (FIG. 1 SPLAT diagram, reference 180; Page 8, paragraph [0104]).
Raine does not teach (b) each oligonucleotide in the plurality of first oligonucleotide species comprises a first unique molecular identifier (UMI) flanked by a first flank region and a second flank region, wherein the UMI comprises a random sequence; (c) the first oligonucleotide hybridization region comprises (i) a polynucleotide complementary to the first flank region, and (ii) a polynucleotide complementary to the second flank region.
Schweyen, in the same field of endeavor, teaches that a first oligonucleotide can comprise a UMI flanked by a first flank region and a second flank region (Figure 3, P5 end: barcode is equivalent to UMI, flanked by the “Ins” first flank and Flow cell binding and Read primer second flank). Schweyen further teaches that an oligonucleotide complementary to the first oligonucleotide can comprise a polynucleotide complementary to the first flank region and a polynucleotide complementary to the second flank region (Figure 3, P5 end).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the composition of Raine with the oligonucleotide components of Schweyen. Since both Raine and Schweyen are in the same field of endeavor (e.g. adapters for next generation sequencing), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because barcodes (e.g. UMIs) facilitate assignment of reads to individuals (Schweyen, Page 151, column 1, paragraph 2). The first flank region (e.g. “Ins”) helps generate a high diversity of nucleotides to preserve sequencing lasers (Schweyen, Page 149, column 2, paragraph 2; Figure 3, caption). The second flank is necessary for sequencing of the intended target (Schweyen, Figure 3). In addition, it would have been obvious to one of ordinary skill in the art that the known methods of the cited references could have been combined with predictable results because the known techniques in the cited methods both predictably result in the ligation of an adapter to a nucleic acid target. Both of techniques include aspects that would successfully interact with a single-stranded nucleic acid. The components of the adapters are also known in the methods and can be combined with predictable results (see MPEP 2141(III)).
Neither reference as presented teaches that the UMI comprises a random sequence.
Smith, in a reasonably pertinent field, teaches that UMIs may comprise random sequences (Page 2, paragraph 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Raine and Schweyen with the random UMIs of Smith. Since Smith teaches on nucleic acid libraries, which is reasonably pertinent to the method of Raine and Schweyen, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because random UMIs aid in the identification of PCR duplicates (Smith, Page 2, paragraph 2).
Regarding instant claim 2, Raine, in view of Schweyen and Smith, teaches the method of claim 1. Schweyen further teaches wherein the first oligonucleotide hybridization region comprises (iii) a region that corresponds to the first UMI (Figure 3, P5 end).
Regarding instant claim 3, Raine, in view of Schweyen and Smith, teaches the method of claim 1. Schweyen further teaches wherein the first flank region of each of the first oligonucleotide species comprises a nonrandom sequence species from a pool of nonrandom sequence species (Page 158, Figure A1: P5 fragments). It is noted by the Examiner that the first flank region is equivalent to the “Ins” sequence of listed fragments, of which there are three nonrandom sequences, necessarily representing a pool of sequence species.
Regarding instant claim 4, Raine, in view of Schweyen and Smith, teaches the method of claim 1. Schweyen further teaches wherein the second flank region of each of the first oligonucleotide species comprises a first primer binding domain (Figure 3, P5 end: read primer).
Regarding instant claim 5, Raine, in view of Schweyen and Smith, teaches the method of claim 1. Raine further teaches the method which further comprises combining the nucleic acid composition with (iv) a second oligonucleotide, and (v) a plurality of second scaffold polynucleotide species (FIG. 1 SPLAT diagram, reference 184; Page 8, paragraph [0104]), wherein: (e) each polynucleotide in the plurality of second scaffold polynucleotide species comprises an ssNA hybridization region and a second oligonucleotide hybridization region (Page 8, paragraph [0104]: random overhang and short double-stranded region); and (f) the nucleic acid composition, the second oligonucleotide, and the plurality of second scaffold polynucleotide species are combined under conditions in which a molecule of the second scaffold polynucleotide species is hybridized to (i) a second ssNA terminal region and (ii) a molecule of the second oligonucleotide, thereby forming hybridization products in which an end of the molecule of the second oligonucleotide is adjacent to an end of the second ssNA terminal region (FIG. 1 SPLAT diagram, reference 184; Page 8, paragraph [0104]).
Claims 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Raine (US 20190194649 A1; previously cited), in view of Schweyen (Detection and Removal of PCR Duplicates in Population Genomic ddRAD Studies by Addition of a Degenerate Base Region (DBR) in Sequencing Adapters, The Biological Bulletin, October 2014, 227, 146-160; previously cited) and Smith (Unique Molecular Identifiers – the problem, the solution and the proof [online]. CGAT Oxford, [2015] [retrieved on May 9th, 2026]. Retrieved from: https://cgatoxford.wordpress.com/2015/08/14/unique-molecular-identifiers-the-problem-the-solution-and-the-proof/), as applied to claims 1-5 above, and further in view of Peterson (Double Digest RADseq: An Inexpensive Method for De Novo SNP Discovery and Genotyping in Model and Non-Model Species, PLOS One, May 2012, 7, 1-11; previously cited).
Regarding instant claim 6, Raine, in view of Schweyen and Smith, teaches the method of claim 1. Raine further teaches the method which further comprises combining the nucleic acid composition with (iv) a plurality of second oligonucleotide species, and (v) a plurality of second scaffold polynucleotide species (FIG. 1 SPLAT diagram, reference 184; Page 8, paragraph [0104]), wherein: (e) each polynucleotide in the plurality of second scaffold polynucleotide species comprises an ssNA hybridization region and a second oligonucleotide hybridization region (Page 8, paragraph [0104]: random overhang and short double-stranded region); and (h) the nucleic acid composition, the plurality of second oligonucleotide species, and the plurality of second scaffold polynucleotide species are combined under conditions in which a molecule of the second scaffold polynucleotide species is hybridized to (i) a second ssNA terminal region and (ii) a molecule of the second oligonucleotide species, thereby forming hybridization products in which an end of the molecule of the second oligonucleotide is adjacent to an end of the second ssNA terminal region (FIG. 1 SPLAT diagram, reference 184; Page 8, paragraph [0104]).
Raine does not teach (f) each oligonucleotide in the plurality of second oligonucleotide species comprises a second unique molecular identifier (UMI) flanked by a third flank region and a fourth flank region; (g) the second oligonucleotide hybridization region comprises (i) a polynucleotide complementary to the third flank region, and (ii) a polynucleotide complementary to the fourth flank region.
Schweyen, in the same field of endeavor, teaches that a second oligonucleotide can comprise a UMI flanked by a third flank region and a fourth flank region (Figure 3, P7 end: barcode is equivalent to UMI, flanked by the “Ins” and Read primer third flank and Flow cell binding fourth flank). Schweyen further teaches that an oligonucleotide complementary to the second oligonucleotide can comprise a polynucleotide complementary to the third flank region and a polynucleotide complementary to the fourth flank region (Figure 3, P7 end).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the composition of Raine with the oligonucleotide components of Schweyen. Since both Raine and Schweyen are in the same field of endeavor (e.g. adapters for next generation sequencing), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because barcodes (e.g. UMIs) facilitate assignment of reads to individuals (Schweyen, Page 151, column 1, paragraph 2). The third flank region (e.g. “Ins” and “Read primer”) helps generate a high diversity of nucleotides to preserve sequencing lasers and is necessary for sequencing of the intended target (Schweyen, Page 149, column 2, paragraph 2; Figure 3, caption). The fourth flank is necessary for sequencing of the intended target (Schweyen, Figure 3). In addition, it would have been obvious to one of ordinary skill in the art that the known methods of the cited references could have been combined with predictable results because the known techniques in the cited methods both predictably result in the ligation of an adapter to a nucleic acid target. Both of techniques include aspects that would successfully interact with a single-stranded nucleic acid. The components of the adapters are also known in the methods and can be combined with predictable results (see MPEP 2141(III)).
Schweyen’s adapters are modified from Peterson, which is also in the same field of endeavor (e.g. adapters for next generation sequencing). Peterson teaches on a two-tier indexing system that introduces two barcodes (e.g. barcode and index) in the full sequencing library, increasing the uniquely identifiable samples while avoiding extra oligonucleotide synthesis and sequencing costs with longer unique barcodes (Page 4, column 1, paragraph 3 to column 2, paragraph 1). This serves to provide further motivation for having the second UMI taught by Schweyen.
Regarding instant claim 7, Raine, in view of Schweyen, Smith, and Peterson, teaches the method of claim 6. Schweyen further teaches wherein the second oligonucleotide hybridization region comprises (iii) a region that corresponds to the second UMI (Figure 3, P7 end).
Regarding instant claim 8, Raine, in view of Schweyen, Smith, and Peterson, teaches the method claim 6. Schweyen further teaches wherein the third flank region of each of the second oligonucleotide species comprises a nonrandom sequence species from a pool of nonrandom sequence species (Page 158, Figure A1: P7 fragments). It is noted by the Examiner that the third flank region is equivalent to the “Ins” and “Read primer” sequence of listed fragments, of which there are four nonrandom sequences, necessarily representing a pool of sequence species.
Regarding instant claim 9, Raine, in view of Schweyen, Smith, and Peterson, teaches the method of claim 6. Raine further teaches wherein the fourth flank region of each of the second oligonucleotide species comprises a nonrandom sequence (Figure 3, P7 end: flow cell binding).
Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Raine (US 20190194649 A1; previously cited), in view of Schweyen (Detection and Removal of PCR Duplicates in Population Genomic ddRAD Studies by Addition of a Degenerate Base Region (DBR) in Sequencing Adapters, The Biological Bulletin, October 2014, 227, 146-160; previously cited) and Smith (Unique Molecular Identifiers – the problem, the solution and the proof [online]. CGAT Oxford, [2015] [retrieved on May 9th, 2026]. Retrieved from: https://cgatoxford.wordpress.com/2015/08/14/unique-molecular-identifiers-the-problem-the-solution-and-the-proof/), as applied to claims 1-5 above, and further in view of Gansauge (Single-stranded DNA library preparation from highly degraded DNA using T4 DNA ligase, Nucleic Acids Research, January 2017, 45, 1-10; previously cited).
Regarding instant claim 10, Raine, in view of Schweyen and Smith, teaches the method of claim 1.
None of these references teach wherein the ssNA is not modified prior to the combining.
Gansauge, in the same field of endeavor, teaches a similar method of single-stranded library preparation (FIG. 1, ssDNA2.0), wherein the target nucleic acids are only dephosphorylated and denatured before library preparation begins (FIG. 1 caption). It is noted that the Applicant's specification states that adding a phosphate group to one or both ends of a nucleic acid, and denaturing a nucleic acid, are generally not considered modifying the nucleic acid (Page 71 of the instant specification, lines 11-24). For the purpose of examination, removing a phosphate group as described by Gansauge is being considered as an “equivalent” manipulation (i.e., not modifying) as the addition of a phosphate group as discussed by the Applicant.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Raine, in view of Schweyen and Smith, with the non-modified ssNA of Gansauge. Since both Raine and Gansauge are in the same field of endeavor (e.g. adapters for next generation sequencing), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because Gansauge teaches that single-stranded library preparation has significant advantages for certain sample types (Page 3, column 1, paragraph 2). In addition, it would have been obvious to one of ordinary skill in the art that the known methods of the cited references could have been combined with predictable results because the known techniques in the cited methods both predictably result in the ligation of an adapter to a nucleic acid target. Both of techniques include aspects that would successfully interact with a single-stranded nucleic acid (see MPEP 2141(III)).
Regarding instant claim 11, Raine, in view of Schweyen and Smith, teaches the method of claim 1.
Neither reference teaches wherein the ssNA is from cell-free nucleic acid.
Gansauge, in the same field of endeavor, teaches that single-stranded library preparation can be used for cell-free DNA (Page 3, column 1, paragraph 3; Page 7, column 1, paragraph 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the ssNA of Raine, in view of Schweyen and Smith, with the cell-free nucleic acid of Gansauge. Since both Raine and Gansauge are in the same field of endeavor (e.g. adapters for next generation sequencing), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because single-stranded libraries provide a higher level of resolution in sequence data generated from cell-free nucleic acids (Gansauge, Page 3, column 1, paragraph 3).
Response to Arguments
Applicant's arguments filed March 13th, 2026 have been fully considered but they are not persuasive.
The Applicant first provides a summary of the Examiner’s previous rejection (Pages 7 and 8 of the Remarks filed March 13th, 2026). The Applicant reproduces claim 1 as amended, noting that claims 2-11, 22 and 23 depend from claim 1 and incorporate its features (Page 8 of the Remarks filed March 13th, 2026). The Applicant provides a summary of pertinent information from the instant specification (Pages 8-9 of the Remarks filed March 13th, 2026). The Applicant argues that the barcode of Schweyen is not equivalent to a UMI as claimed because the Schweyen barcode is shared among sequences obtained from a specific sample or source (Page 9 of the Remarks filed March 13th, 2026). The Applicant argues that the claimed UMI uniquely marks molecules of interest and thus is different for each molecule being sequenced (Page 9 of the Remarks filed March 13th, 2026). The Applicant argues that, given that the UMI uniquely marks molecules of interest, the UMI as claimed and the Schweyen barcode are clearly for different purposes (Page 9 of the Remarks filed March 13th, 2026). The Applicant further argues that as now claimed, the UMI comprises a random nucleotide sequence, while the Schweyen barcode is predefined and not random (Page 9 of the Remarks filed March 13th, 2026).
In response to the Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which the Applicant relies (i.e., the UMI uniquely marks molecules of interest and thus is different for each molecule being sequenced) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). There is no recitation in the claims related to different molecules having different UMIs, this is only addressed in the specification. With no specific language indicating that this is a required feature of the invention in the claims, it is not being considered for the above rejection. Furthermore, as described in the specification (see Page 17 of the most recently filed specification), there is no limiting definition of what comprises a UMI. The specification describes that a UMI may be referred to as a barcode, as it has been referred to in Schweyen. Therefore, these arguments are not found persuasive.
In response to the argument regarding the UMI being random, as covered by the newly introduced reference of Smith, it is taught that UMIs can comprise random sequences. Therefore, this argument is not found persuasive.
New - Necessitated by Amendment
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Raine (US 20190194649 A1; previously cited), in view of Schweyen (Detection and Removal of PCR Duplicates in Population Genomic ddRAD Studies by Addition of a Degenerate Base Region (DBR) in Sequencing Adapters, The Biological Bulletin, October 2014, 227, 146-160; previously cited) and Smith (Unique Molecular Identifiers – the problem, the solution and the proof [online]. CGAT Oxford, [2015] [retrieved on May 9th, 2026]. Retrieved from: https://cgatoxford.wordpress.com/2015/08/14/unique-molecular-identifiers-the-problem-the-solution-and-the-proof/).
Regarding instant claim 22, Raine, in view of Schweyen and Smith, teaches the method of claim 1. Raine teaches one or both native ends of the ssNA are present when the ssNA is combined with the plurality of first oligonucleotide species and the plurality of first scaffold polynucleotide species (FIG. 1 SPLAT diagram, reference 180; Page 8, paragraph [0104]).
Double Patenting - Modified - Necessitated by Amendment
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 1-11 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-10, 15, 17, 21, 27-29, and 39-42 of copending Application No. 17440386 in view of Raine (US 20190194649 A1; previously cited), Schweyen (Detection and Removal of PCR Duplicates in Population Genomic ddRAD Studies by Addition of a Degenerate Base Region (DBR) in Sequencing Adapters, The Biological Bulletin, October 2014, 227, 146-160; previously cited), Smith (Unique Molecular Identifiers – the problem, the solution and the proof [online]. CGAT Oxford, [2015] [retrieved on May 9th, 2026]. Retrieved from: https://cgatoxford.wordpress.com/2015/08/14/unique-molecular-identifiers-the-problem-the-solution-and-the-proof/), Peterson (Double Digest RADseq: An Inexpensive Method for De Novo SNP Discovery and Genotyping in Model and Non-Model Species, PLOS One, May 2012, 7, 1-11; previously cited), and Gansauge (Single-stranded DNA library preparation from highly degraded DNA using T4 DNA ligase, Nucleic Acids Research, January 2017, 45, 1-10; previously cited).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ’386 application and the instant application claim a method of producing a nucleic acid library, comprising: combining a nucleic acid composition comprising single-stranded nucleic acid (ssNA), (ii) a first oligonucleotide, and (iii) a plurality of first scaffold polynucleotide species, (iv) a second oligonucleotide, and (v) a plurality of second scaffold polynucleotide species, wherein:(a) each polynucleotide in the plurality of first scaffold polynucleotide species comprises an ssNA hybridization region and a first oligonucleotide hybridization region; (b) the nucleic acid composition, the first oligonucleotide, and the plurality of first scaffold polynucleotide species are combined under conditions in which a molecule of the first scaffold polynucleotide species is hybridized to (i) a first ssNA terminal region and (ii) a molecule of the first oligonucleotide, thereby forming hybridization products in which an end of the molecule of the first oligonucleotide is adjacent to an end of the first ssNA terminal region; and (c) each polynucleotide in the plurality of second scaffold polynucleotide species comprises an ssNA hybridization region and a second oligonucleotide hybridization region; (d) the nucleic acid composition, the second oligonucleotide, and the plurality of second scaffold polynucleotide species are combined under conditions in which a molecule of the second scaffold polynucleotide species is hybridized to (i) a second ssNA terminal region and (ii) a molecule of the second oligonucleotide, thereby forming hybridization products in which an end of the molecule of the second oligonucleotide is adjacent to an end of the second ssNA terminal region. Both applications also claim that the ssNA is not modified prior to combining, one or both native ends of the ssNA are present when the ssNA is combined with the first oligonucleotide and the plurality of first scaffold polynucleotide species, and the ssNA is from cell-free nucleic acid.
The ‘386 application claims do not require the aspects of the UMI or flank regions that are claimed in the instant application. However, Raine, in view of Schweyen, Peterson, and Gansauge, teaches the claimed limitations as discussed in the above 103 rejections, obviating these variations to the claims of the ‘386 application. Any additional limitations of the claims of copending Application No. 17440386 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1-11 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 19106916 in view of Raine (US 20190194649 A1; previously cited), Schweyen (Detection and Removal of PCR Duplicates in Population Genomic ddRAD Studies by Addition of a Degenerate Base Region (DBR) in Sequencing Adapters, The Biological Bulletin, October 2014, 227, 146-160; previously cited), Smith (Unique Molecular Identifiers – the problem, the solution and the proof [online]. CGAT Oxford, [2015] [retrieved on May 9th, 2026]. Retrieved from: https://cgatoxford.wordpress.com/2015/08/14/unique-molecular-identifiers-the-problem-the-solution-and-the-proof/), Peterson (Double Digest RADseq: An Inexpensive Method for De Novo SNP Discovery and Genotyping in Model and Non-Model Species, PLOS One, May 2012, 7, 1-11; previously cited), and Gansauge (Single-stranded DNA library preparation from highly degraded DNA using T4 DNA ligase, Nucleic Acids Research, January 2017, 45, 1-10; previously cited).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ’916 application and the instant application claim a method of producing a nucleic acid library, comprising: combining a nucleic acid composition comprising single-stranded nucleic acid (ssNA), (ii) a first oligonucleotide, and (iii) a plurality of first scaffold polynucleotide species, (iv) a second oligonucleotide, and (v) a plurality of second scaffold polynucleotide species, wherein:(a) each polynucleotide in the plurality of first scaffold polynucleotide species comprises an ssNA hybridization region and a first oligonucleotide hybridization region; (b) the nucleic acid composition, the first oligonucleotide, and the plurality of first scaffold polynucleotide species are combined under conditions in which a molecule of the first scaffold polynucleotide species is hybridized to (i) a first ssNA terminal region and (ii) a molecule of the first oligonucleotide, thereby forming hybridization products in which an end of the molecule of the first oligonucleotide is adjacent to an end of the first ssNA terminal region; and (c) each polynucleotide in the plurality of second scaffold polynucleotide species comprises an ssNA hybridization region and a second oligonucleotide hybridization region; (d) the nucleic acid composition, the second oligonucleotide, and the plurality of second scaffold polynucleotide species are combined under conditions in which a molecule of the second scaffold polynucleotide species is hybridized to (i) a second ssNA terminal region and (ii) a molecule of the second oligonucleotide, thereby forming hybridization products in which an end of the molecule of the second oligonucleotide is adjacent to an end of the second ssNA terminal region.
The ‘916 application claims do not require the aspects of the UMI or flank regions that are claimed in the instant application. However, Raine, in view of Schweyen, Smith, Peterson, and Gansauge, teaches the claimed limitations as discussed in the above 103 rejections, obviating these variations to the claims of the ‘916 application. Any additional limitations of the claims of copending Application No. 19106916 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed March 13th, 2026 have been fully considered but they are not persuasive.
Applicant’s arguments related to the double patenting rejections rely on alleged deficiencies previously addressed for the 103 rejections, which are unpersuasive for the reasons discussed above. Therefore, the claims remain rejected based on the prior art citations and analysis presented in the above rejection.
Conclusion
Claims 1-11 and 22 are rejected. Claim 23 is objected to as depending from a rejected claim.
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 Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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, Anne Gussow can be reached at (571) 272-6047. 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.
/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
Prosecution Insights