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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Status of Claims
Claims 16-23 are currently pending. Claims 16-20 have been amended by Applicants’ amendment filed 02-23-2026. No claims have been added or canceled by Applicants’ amendment filed 02-23-2026.
A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Therefore, claims 16-23 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed November 3, 2022 is a CON of US Patent Application 16721533 (now abandoned), which is a CON of 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2018/067246, filed June 27, 2018; which claims the benefit of US Provisional Patent Application 62525595, filed June 27, 2017.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed February 23, 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or
objection not specifically addressed below are herein withdrawn.
Drawing Objection
The objections to the drawings are withdrawn due to Applicant’s amendments to the drawings, filed February 23, 2026.
Claim Rejections - 35 USC § 112(d)
The rejection of claims 17-20 is withdrawn under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends due to Applicant’s amendment of the claims, in the reply filed 02-23-2026.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Maintained Objections/Rejections
Claim Interpretation: the term “variable length punctuation mark” in claim 16 is interpreted to refer to a single nucleotide or a nucleotide sequence of any length that is located at the end of each oligonucleotide adapter.
The term “adapter-target-adapter construct” in claim 16 is interpreted to refer to constructs that are (or are not) annealed and/or hybridized one to the other via the complementary sequences.
The term “common sequence” in claim 16 is interpreted to refer to any sequence including any sequence that is commonly found in nature, is commonly used in the method, is common in a sample or a sample type, is common within a species or common across different species, a sequence having a particular G/C content, etc.
Specification Objections
The objection to the disclosure is maintained because of the following informalities: the as-filed Specification, filed November 3, 2022, does not include the status of US Patent Application No. 16721533
(now abandoned).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 16-23 is maintained under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 16 is indefinite for the recitation of the term “the target” such as recited in claim 16, line 23. There is insufficient antecedent basis for the term “the target” in the claim. The Examiner suggests that Applicant amend the claim to recite, for example, “comprises a target and a pair.”
Claims 16-20 are indefinite for the recitation of the term “a pair of a plurality of oligonucleotide adapters” such as recited in claim 16, line 23 because the term “a pair of a plurality of oligonucleotide adapters” is confusing and unclear. It is unclear whether each adapter-target-adapter construct comprises two pluralities of oligonucleotide adapters (e.g., a pair of a plurality), one plurality oligonucleotide adapters, a pair of oligonucleotide adapters, or whether the term refers to something else and, thus, the metes and bounds of the claim cannot be determined.
Claims 21-23 are indefinite insofar as they ultimately depend from instant claim 16.
Claim Rejections - 35 USC § 102
The rejection of claims 16-23 is maintained under 35 U.S.C. 102(a1)/(a2) as being anticipated by Diehn et al. (hereinafter “Diehn”) (International Application WO2016040901, published March 17, 2016).
Regarding claim 16, Diehn teaches polynucleotide adapter and method of use thereof for identifying and analyzing nucleic acids, including cell-free nucleic acids from a patient sample; as well as, methods of using the adaptors to detect, diagnose, or determine prognosis of cancers (Abstract). Diehn teaches that the invention is a pool of unique adaptors for analyzing nucleic acids in a sample, each adaptor comprising: a double stranded portion at a proximal end and two single stranded portions at a distal end (interpreted as a first and second tail sequence), wherein the double stranded portion comprises a double-stranded barcode of at least two base pairs specific to the adaptor (interpreting the double-stranded portion of the adaptor as a variable length punctuation mark comprising complementary sequences), and wherein the single-stranded portion comprises: a pre-defined single-stranded barcode of at least two nucleotides specific to the sample (interpreted as first and second common sequence); and a random single-stranded barcode of at least two nucleotides specific to the adaptor (interpreted as the first and second unique identifier sequence), wherein the pool of adaptors can have the double-stranded portion further comprising one or more G/C base pairs between the double-stranded barcode of at least two base pairs and the proximal end of the adaptor, such that the pool of adaptors can also a number of G/C base pairs that varies among the adaptors in the pool (interpreting the barcodes/UID comprising G/C base pairs as a first and second variable length punctuation mark that are complementary), wherein the double-stranded barcode can comprise 2-20 base pairs; the pre-defined single-stranded barcode can comprise 4-20 nucleotides; and the random single-stranded barcode can comprise 4-20 nucleotides (interpreted as an adapter-target-adapter construct, claim 16) (paragraph [0005]). Diehn teaches that a method of analyzing a plurality of double-stranded nucleic acids, the method comprising: attaching a pool of adaptors according to claims 1-6 to both ends of the plurality of double-stranded nucleic acids; amplifying both strands of the adaptor-nucleic acids to produce first amplicons and second amplicons, wherein the first amplicons are derived from a first strand of the double-stranded nucleic acids and contain a first strand of the double-stranded barcodes, and the second amplicons are derived from a second strand of the double-stranded nucleic acids and contain a second strand of the double-stranded barcodes; determining the sequence of the first and second amplicons; and identifying mutations in the first and second amplicons, where the amplicons of (c) comprise different random barcodes derived from the random single-stranded barcode of the adaptor (interpreted as attaching one of the oligonucleotide adaptors to each end of the target nucleic acid; and where the unique identifier sequences of the oligonucleotide pairs are different, claims 16 and 17) (paragraph [0007], lines 1-10 and 20-22). Diehn teaches in Figure 1(c) that the Y-shaped adaptor comprised a random barcode and a fixed barcode on its non-hybridizable portion, and a primer sequence on its hybridizable portion (interpreted as a first and second priming sequence comprising a sample identifier sequence, claim 16) (paragraph [0018]; and Figure 1(c)). Diehn teaches in Figure 2b, that Y-shaped adaptors were attached to cfDNA (interpreted as a forked adaptor; and adapter-target-adapter, claims 16 and 20) (paragraph [0019]; and Figure 2b). Figure 2b is shown below:
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Diehn teaches that primers for amplification can be covalently attached to slides in the flow cells and then the flow cells can be exposed to reagents for nucleic acids extension and sequencing (interpreted as forming extension products complementary to each strand, claim 16) (paragraph [00147], lines 8-10). Diehn teaches that cfDNA is commonly obtained from blood or plasma (interpreting cfDNA to comprising common sequences, claim 16) (paragraph [0055]). Diehn teaches that each Y-shaped adaptor can further comprise a primer sequence, which can be a PCR primer sequence or a sequencing primer sequence, wherein the primer sequence can be on the non-hybridizable portion of the Y-shaped adaptor or on the hybridizable portion of the Y-shaped adaptor (interpreted as primer sequences, claim 16) (paragraph [0076]). Diehn teaches the preparation of pre-capture sequencing libraries, wherein cfDNA was input for a cfDNA sample that was 12-plexed in an Illumina HiSeq 2000 High Output lane, while germline or tumor DNA was used as input for a 24-plexed Illumina HiSeq 2000 High Output lane, wherein sequencing library preparation was performed using the KAPA LTP Library Prep Kit (interpreted as preparing a library of nucleic acid molecules, claim 16) (paragraph [0232], lines 1-9). Diehn teaches that DNA was diluted, end repaired, bead cleanup performed, A-tailing performed, ligation was performed using excess adaptors relative to the input DNA samples, such that after ligation, DNA was isolated, PCR was performed with KAPA HiFi and Illumina Universal Primers with an annealing step (interpreted as a first tail and a second tail; annealing first and second primers; and extending the first and second primers to form extension products, claim 16) (paragraph [0232], lines 9-20). Diehn teaches that the barcodes on the two strands are complementary to each other, such as if UID are located in the stem region of the adaptor (interpreting the barcode as unique identifier sequences that are complementary and/or variable length punctuation marks that are complementary, claim 16) (paragraph [0199], lines 4-5). Diehn teaches that pairing the sequences into a double-stranded nucleic acid if the sequences have complementary barcodes (interpreting the barcode as unique identifier sequences that are complementary and/or variable length punctuation marks that are complementary, claim 16) (paragraph [0015]).
Regarding claim 17, Diehn teaches a method of analyzing a plurality of double-stranded nucleic acids, the method comprising: attaching a pool of adaptors according to claims 1-6 to both ends of the plurality of double-stranded nucleic acids; amplifying both strands of the adaptor-nucleic acids to produce first amplicons and second amplicons, wherein the first amplicons are derived from a first strand of the double-stranded nucleic acids and contain a first strand of the double-stranded barcodes, and the second amplicons are derived from a second strand of the double-stranded nucleic acids and contain a second strand of the double-stranded barcodes; determining the sequence of the first and second amplicons; and identifying mutations in the first and second amplicons, where the amplicons of (c) comprise different random barcodes derived from the random single-stranded barcode of the adaptor (interpreted as attaching one of the oligonucleotide adaptors to each end of the target nucleic acid; and where the unique identifier sequences of the oligonucleotide pairs are different, claim 17) (paragraph [0007], lines 1-10 and 20-22).
Regarding claims 18 and 19, Diehn teaches A-tailing, which can comprise performing an A-tailing reaction on the plurality of nucleic acids to produce a plurality of A-tailed nucleic acids, wherein the A-tailing reaction can be conducted prior to attaching the adaptors to the plurality of nucleic acids, prior to amplification of the adaptor-modified nucleic acids, conducted after amplification of the adaptor-modified nucleic acids, conducted prior to or after fragmenting, and/or prior to or after end repair of the plurality of nucleic acids (interpreted as the first tail sequences are the same; and the second tail sequences are the same, claims 18 and 19) (paragraphs [00157]-[00160]).
Regarding claim 20, Diehn teaches in Figure 2b, that Y-shaped adaptors were attached to cfDNA (interpreted as a forked adaptor, claim 20) (paragraph [0019]; and Figure 2b). Figure 2b is shown below:
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Regarding claim 21, Diehn teaches that if the short barcodes are complementary to each other and the genomic coordinates of the insert map to the opposite strands, the reads represent reciprocal strands of a duplex molecule (interpreted as sample identifier sequences have a one-to-one mapping, claim 21) (paragraph [00199], lines 11-13). Diehn teaches that the invention is a method of analyzing nucleic acids that comprises a step of error suppressing using barcodes including a step of mapping the sequence to the reference genome and identifying all single nucleotide variants (SNVs) (i.e., bases different from the reference sequence) (interpreted as sample identifier sequences have a one-to-one mapping, claim 21) (paragraph [00200], lines 1-4).
Regarding claim 22, Diehn teaches that the pool of adaptors can have the double-stranded portion further comprising one or more G/C base pairs between the double-stranded barcode of at least two base pairs and the proximal end of the adaptor, such that the pool of adaptors can also a number of G/C base pairs that varies among the adaptors in the pool (interpreted as a first and second variable length punctuation mark), wherein the double-stranded barcode can comprise 2-20 base pairs; the pre-defined single-stranded barcode can comprise 4-20 nucleotides; and the random single-stranded barcode can comprise 4-20 nucleotides (interpreting the random barcodes as encompassing that the unique identifier sequences have a length of at least 5 nucleotides, claim 22) (paragraph [0005]).
Regarding claim 23, Diehn teaches that to make the index adaptors, standard 8-base barcode Illumina adaptors were used, replacing the 8-base indexes with 4 random bases followed by a 4-base multiplexing barcode, such that 24 different adaptor sequences were designed such that all pairs of multiplexing barcodes had edit distances of at least 2 (interpreted as encompassing a first unique identifier sequence as having a pairwise edit distance of at least 3, claim 23) (paragraph [00235]). Diehn teaches that tandem adaptors were designed with index adaptors as a starting point, wherein 12 index adaptors with pairwise edit distances of at least 3 were used (interpreted as a first unique identifier sequence as having a pairwise edit distance of at least 3, claim 23) (paragraph [00236], lines 1-2).
Diehn meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Response to Arguments
Applicant’s arguments filed February 23, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Diehn does not teach: (i) modular adapters, and methods of use thereof; and/or (ii) adapters comprising, inter alia, a first variable length punctuation and a second variable length punctuation mark which are complementary to each other, as is recited in claim 16 (Applicant Remarks, pg. 14, last partial paragraph through pg 15, first partial paragraph); (b) the as-filed Specification provides that the claimed modular adapter design allows for reduction in production needs and costs, where Diehn teaches Y-shaped adapters that contain both a sample-specific barcode and an adapter-specific barcode in the same adapter, such that Diehn does not teach the claimed generation of modular adapters and uses thereof (pg. 15, first full paragraph through pg. 16, first partial paragraph); and (c) Diehn does not disclose variable length punctuation marks (pg. 16, first full paragraph).
Regarding (a) and (c), 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, 26USPQ2d 1057 (Fed. Cir. 1993). Additionally, MPEP 2112.01(I) states that:
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Applicant’s assertion that Diehn does not teach (i) modular adapters, generating modular adaptors, and methods of use thereof; and/or (ii) adapters comprising a first variable length punctuation and a second variable length punctuation mark including those that are complementary to each other, is not found persuasive. As an initial matter, instant claim 16 does not recite modular adapters, the generation of modular adapters, and/or methods of using modular adapters. Applicant is respectfully reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. Thus, Diehn is not required to teach limitations that are not recited in instant claim 16.
Regarding the variable length punctuation marks, the Examiner has interpreted the term “variable length punctuation mark” in claim 16 to refer to a single nucleotide or a nucleotide sequence of any length that is located at the end of each oligonucleotide adapter (See, claim interpretation supra). Additionally, instant claim 16, recites:
“(2) a second oligonucleotide having a second tail sequence, a second common sequence complementary to the first common sequence, and at least one of: (i) a second unique identifier sequence complementary to the first unique identifier sequence, and (ii) a second variable length punctuation mark complementary to the first variable length punctuation mark” in lines 9-13.
Thus, the Diehn is required to teach: (i) a second unique identifier sequence complementary to the first unique identifier sequence, and/or (ii) a second variable length punctuation mark complementary to the first variable length punctuation mark. Because Applicant has not argued that Diehn does not teach the other option of “a second unique identifier sequence that is complementary to the first unique identifier sequence,” Diehn clearly teaches the limitation recited in claim 16(a)(2). Moreover,
Diehn teaches:
Each adaptor comprises: a double stranded portion at a proximal end and two single stranded portions at a distal end (interpreted as a first and second tail sequence), wherein the double stranded portion comprises a double-stranded barcode of at least two base pairs specific to the adaptor (interpreting the double-stranded portion and double-stranded barcode of the adaptor to comprise unique identifier sequences that are complementary; and variable length punctuation marks comprising complementary sequences).
The pool of adaptors can have the double-stranded portion further comprising one or more G/C base pairs between the double-stranded barcode of at least two base pairs and the proximal end of the adaptor (interpreting the barcodes/UID comprising G/C base pairs as unique identifier sequences that are complementary and/or variable length punctuation marks that are complementary) (paragraph [0005]).
The barcodes on the two strands are complementary to each other, such as if UID are located in the stem region of the adaptor (interpreting the barcode/UID to comprise unique identifier sequences that are complementary and/or variable length punctuation marks that are complementary) (paragraph [0199]).
Pairing the sequences into a double-stranded nucleic acid if the sequences have complementary barcodes (interpreting the barcodes as unique identifier sequences that are complementary and/or variable length punctuation marks that are complementary) (paragraph [0015]).
Diehn teaches all of the limitations as recited in instant claim 16. Thus, the rejection is maintained.
Regarding (b), please see the discussion supra regarding the Examiner’s response to Applicant’s arguments including that instant claim 16 does not recite modular adapters, the generation of modular adapters, and/or methods of using modular adapters. Applicant’s assertion that Diehn does not teach the adapters as recited in claim 16 because Diehn teaches Y-shaped adapters that contain both a sample-specific barcode and an adapter-specific barcode in the same adapter, is not found persuasive. As an initial matter, instant claim 1 uses the term “comprising”, which is open-ended and does not exclude additional, unrecited elements or method steps, including additional barcodes, UMIs, etc. Regarding the adapter shape, instant claim 20 is specifically directed to forked adapters, and the as-filed Specification teaches a pool of forked adapters is prepared with each adapter having a UID (paragraph [053]), where “forked adapters” are also referred to as Y-adapters as evidenced by Costa (col 9, lines 15-18), such that Diehn teaches adapters having the same shape as the adapters of the instant invention. Diehn teaches all of the limitations as recited in instant claim 16. Thus, the rejection is maintained.
Claim Rejections - 35 USC § 103
The rejection of claims 16-23 is maintained under 35 U.S.C. 103 as being unpatentable over Diehn et al. (hereinafter “Diehn”) (International Application WO2016040901, published March 17, 2016) in view of Newman et. al. (hereinafter “Newman”) (Nature Biotechnology, 2016, 34(5), 547-560; and Supplementary Information, 2016, 34(5), 1-22).
The teachings of Diehn as applied to claims 16-23 are described supra.
Diehn does not specifically exemplify the term oligonucleotide pairs (claim 17-20, in part).
Regarding claim 17-20 (all in part), Newman teaches that high-throughput sequencing of circulating tumor DNA (ctDNA) promises to facilitate personalized cancer therapy; wherein low quantities of cell-free DNA (cfDNA) in the blood and sequencing artifacts currently limit analytical sensitivity, such that to overcome these limitations, an approach for integrated digital error suppression (iDES) was introduced, which combines in silico elimination of highly stereotypical background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules, wherein these two methods each improve the sensitivity of cancer personalized profiling by deep sequencing (CAPP-Seq) by about threefold, and synergize when combined to yield ~15-fold improvements, such that iDES-enhanced CAPP-Seq facilitates noninvasive variant detection across hundreds of kilobases; and when applied to non-small cell lung cancer (NSCLC) patients, the method enabled biopsy-free profiling of EGFR kinase domain mutations with 92% sensitivity and >99.99% specificity at the variant level, and with 90% sensitivity and 96% specificity at the patient level, which allowed monitoring of NSCLC ctDNA down to 4 in 105 cfDNA molecules, such that iDES is anticipated aid the noninvasive genotyping and detection of ctDNA in research and clinical settings (Abstract). Newman teach in Supplementary Figure 1(a), a diagram illustrating the design and usage of custom sequencing adaptors that implement two types of molecular barcodes (pg. 1, Supplementary Information, Figure 1a). Supplementary Figure 1(a) is shown below:
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Newman teaches that pairs of single-stranded oligonucleotides harboring individual insert barcodes of predefined sequence were chemically synthesized, wherein these pairs were then annealed individually, before pooling, to generate a diverse mixture with defined composition and desired diversity; and additional advantages of this approach are described in Supplementary Note, such that tandem adapters with 12 different sample multiplexing barcodes (with pairwise edit distances ≥3) were designed (interpreted as oligonucleotide pairs, claim 17-20) (pg. 556, col 2, first full paragraph).
Newman teaches that by matching complementary insert UIDs, this allows for reconstruction of parental double-stranded DNA duplexes as shown in Figure 2a (interpreted complementary UIDs as unique identifier sequences that are complementary and/or variable length punctuation marks that are complementary, claim 16) (pg. 548, 1, last full paragraph; and Figure 2a). Newman teaches that a constant 2-bp sequence (GT) was incorporated at the ligating end of each tandem adapter, immediately adjacent to the insert barcodes, wherein the T was required for ligation, and the G was chosen to maintain the GC ‘clamp’ base pair located at the end of standard Illumina adapters, such that the GT dinu-cleotide additionally served as a punctuation mark, allowing for the assess-ment of proper adapter ligation in sequencing data; and for each of the 12 sample multiplexing barcodes, 16 pairs of oligonucleotides were obtained—one for each two-base insert barcode (interpreted as a variable length punctuation marks, claim 16) (pg. 556, col 2, second full paragraph).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of improving analytical sensitivity as exemplified by Newman, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of identifying and analyzing nucleic acids from a patient’s sample including a patient’s cfDNA sample using indexed and barcoded polynucleotide adaptors to detect, diagnose and/or determine a prognosis of cancer as disclosed by Diehn to include the integrated digital error suppression method and tandem adaptors with 12 different multiplexing barcodes as taught by Newman with a reasonable expectation of success in creating a non-invasive method having improved sensitivity and specificity in personalized cancer profiling through improvements in the analysis of low nucleic acid yields, reducing analytical artifacts and/or reducing sequencing errors; and/or in improving the non-invasive detection of cancer-derived cfDNA in a patient sample including the ability to monitor a patient in clinical settings.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103(a) as obvious over the art.
Response to Arguments
Applicant’s arguments filed February 23, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Diehn and Newman do not teach: (i) modular adapters, and methods of use thereof; and/or (ii) adapters comprising a first variable length punctuation and a second variable length punctuation mark which are complementary to each other (Applicant Remarks, pg. 19, first partial paragraph, lines 4-8); and (b) Diehn and Newman do not teach claims 17-23 because when an independent claim is nonobvious under 35 U.S.C. § 103, then any claim depending therefrom is nonobvious (Applicant Remarks, pg. 19, last partial paragraph, lines 10-12).
Regarding (a) and (b), 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, 26USPQ2d 1057 (Fed. Cir. 1993). Moreover, it is noted that none of the references has to teach each and every claim limitation. If they did, this would have been anticipation and not an obviousness-type rejection. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s assertion that the combined references do not teach modular adapters, and methods of use thereof; and/or adapters comprising a first variable length punctuation and a second variable length punctuation mark which are complementary to each other, is not found persuasive. Please see the discussion supra regarding the Examiner’s interpretation of the claim language, and the Examiner’s response to Applicant’s arguments including that instant claim 16 does not recite modular adapters, the generation of modular adapters, and/or methods of using modular adapters. Thus, the combined references of Diehn and Newman are not required to teach limitations that are not recited in instant claim 16. As discussed supra, instant claim 16 recites an option for the structure of the instant adaptor:
“(2) a second oligonucleotide having a second tail sequence, a second common sequence complementary to the first common sequence, and at least one of: (i) a second unique identifier sequence complementary to the first unique identifier sequence, and (ii) a second variable length punctuation mark complementary to the first variable length punctuation mark” in lines 9-13.
Thus, the combined references of Diehn and Newman must teach at least one of: (i) a second unique identifier sequence complementary to the first unique identifier sequence, and/or (ii) a second variable length punctuation mark complementary to the first variable length punctuation mark. Applicant has not argued that the combined references of Diehn and Newman do not teach a second unique identifier sequence that is complementary to the first unique identifier sequence, such that Diehn clearly teaches the limitations recited in claim 16(a). Moreover, please see the teachings of Diehn supra. Additionally,
Newman teaches:
By matching complementary insert UIDs, this allows for reconstruction of parental double-stranded DNA duplexes (interpreting complementary UIDs as unique identifier sequences that are complementary and/or variable length punctuation marks that are complementary, claim 16) (pg. 548, 1, last full paragraph).
A constant 2-bp sequence (GT) was incorporated at the ligating end of each tandem adapter, immediately adjacent to the insert barcodes, wherein the T was required for ligation, such that the GT dinu-cleotide served as a punctuation mark (interpreting as variable length punctuation marks that are complementary, claim 16) (pg. 556, col 2, second full paragraph).
The combined references of Diehn and Newman teach all of the limitations as recited in instant claim 16. Thus, the rejection is maintained.
Conclusion
Claims 16-23 are rejected.
THIS ACTION IS MADE FINAL. 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 AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684