DETAILED ACTION
Status of the Claims
Claims 1-2, 4-6, 8-9, 11-14, 16-18, 20, 22-24, and 28-29 are currently pending.
Claims 28 and 29 have been withdrawn as being drawn to non-elected subject matter (see below).
Claims 1-2, 4-6, 8-9, 11-14, 16-18, 20, 22-24, and 28-29 are examined herein.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as "means" and "said," should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because it is currently too long. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Drawings
The drawings are objected to because the “FIG.” labels appear to be misplaced. As an example, page 4 of the Drawings recites “FIG. 4” and “FIG. 5”, however, there is only a single drawing. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 11/21/2023 and 04/11/2025 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
Response to Restriction Requirement
Applicant's election with traverse of Group I (claims 1-2, 4-6, 8-9, 11-14, 16-18, 20, and 22-24) in the reply filed on 08/06/2026 is acknowledged. The traversal is on the ground(s) that “the claims of Groups I, II and III remain linked by common technical subject matter”. This is not found persuasive because the technical feature (e.g., the subject matter of claim 1) linking Groups I-III was previously known in the art (e.g., see the rejection below), and therefore, it does not constitute a special technical feature as defined by PCT Rule 13.2, as it does not define a contribution over the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claims 28 and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected groups, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 08/06/2026.
Claim Rejections - 35 USC § 112(b) -- Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16-18 and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 16 depends from claim 15, which is cancelled. Accordingly, the metes and bounds of the claim are unascertainable. Claims 17-18 and 20 indirectly depend from cancelled claim 15 and are therefore similarly rejected.
As per MPEP 2173: It is of utmost importance that patents issue with definite claims that clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter. Therefore, claims that do not meet this standard must be rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph as indefinite. Further, as per MPEP 2173.02: If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. As currently written, the metes and bounds of the rejected claims are unascertainable for the reasons set forth above, thus the above claim(s) and all dependent claims are rejected under 35 USC 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
Claim Rejections – 35 U.S.C. 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Vermaas et al.
Claims 1-2, 4-6, 8-9, 11-14, 16-18, and 23-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vermaas et al. (WO 2018/200386 A1).
Regarding claim 1, Vermaas discloses a sequencing method (e.g., as per the Abstract), comprising providing a solid substrate (e.g., solid surface 300 as per para 00165 and/or Fig. 4) having a surface connected with a plurality of single-stranded nucleic acids, wherein 5' ends of the single-stranded nucleic acids are connected to the surface (e.g., the copy strand 201 attached to the solid surface 300 as per para 00166 and/or Fig. 4), the single-stranded nucleic acids are polynucleotides comprising an insert and a first sequence being a predetermined sequence comprising a tag specific to the sample under test (e.g., sample-derived nucleic acid is termed ‘template’ by Vermaas and labeled 210 as per para 00164 and/or Fig. 3-4, which has had adaptors 100 attached to each end to form a ‘template polynucleotide’ 200, the adaptors adding primer and sequencing index sites as per para 00159-00163 and/or Fig. 2). Vermaas then discloses providing a first sequencing primer capable of hybridizing with a 5' end of the first site and hybridizing the first sequencing primer with the single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine a part of the sequence of the single-stranded nucleic acid by extending the first sequencing primer, so as to acquire a sequencing result (e.g., as per para 00139-00141, 00147-00150, and/or 00159).
Regarding claim 2, Vermaas discloses the above sequencing method, wherein the sequencing result comprises a read comprising sequence information of the tag and at least a part of the insert (e.g., “[t]he index tag sequence and target sequence may be determined in a single read from a single sequencing primer” as per para 00141).
Regarding claim 4, Vermaas discloses the above sequencing method, wherein the first sequence is a predetermined sequence comprising a second site - the tag - the first site (e.g., corresponding to 144 – 142 – 140 as per para 00158 and/or Fig. 2), and the method further comprises providing a second sequencing primer capable of hybridizing with a 5' end of the second site and hybridizing the second sequencing primer with the single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine at least a part of the sequence of the insert on the single-stranded nucleic acid by extending the second sequencing primer, so as to acquire the sequencing result (e.g., as per para 00159-00161).
Regarding claim 5, Vermaas discloses the above sequencing method, wherein the sequencing result comprises a first read and a second read; the first read comprises sequence information of the tag, and the second read comprises sequence information of at least a part of the insert (e.g., index-tag and insert sequence reads as per para 00141).
Regarding claim 6, Vermaas discloses the above sequencing method, wherein the single-stranded nucleic acid is a polynucleotide comprising a second sequence - the insert - the first sequence, and the second sequence is a predetermined sequence comprising a third site, optionally wherein the single-stranded nucleic acid is covalently attached to the surface of the solid substrate via a 5' end of the second sequence (e.g., a third site originating from the adaptor comprising sequences 130 – 132 - 134 as per para 00158-00162 and Fig. 2).
Regarding claim 8, Vermaas discloses the above sequencing method, wherein the tag is a first tag, the second sequence is a predetermined sequence comprising a second tag - the third site or a predetermined sequence comprising a fourth site - the second tag - the third site, and the second tag is a predetermined sequence with specificity to the sample under test (e.g., the index sequences are specific for the samples from which they originate as per para 0003, 0049, and/or 0079-0083).
Regarding claim 9, Vermaas discloses the above sequencing method, further comprising providing a third sequencing primer capable of hybridizing with a 5' end of the third site; and hybridizing the third sequencing primer with the single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine the sequence of the second tag on the single-stranded nucleic acid by extending the third sequencing primer, so as to acquire the sequencing result, optionally wherein the sequencing result further comprises a third read comprising sequence information of the second tag (e.g., hybridizing a sequencing primer to sequence 134 to sequence the index tag 132 as per para 00160 with sequencing-by-synthesis described in para 00139-00141 and 00147).
Regarding claim 11, Vermaas discloses the above sequencing method, wherein the single-stranded nucleic acid is a first single-stranded nucleic acid; the surface is further connected with a second single- stranded nucleic acid; the second single-stranded nucleic acid is a complementary strand of the first single-stranded nucleic acid; the second single-stranded nucleic acid is connected via a 5' end of a part thereof complementary to the first sequence with the surface (e.g., sequences 201 and 202 are immobilized on the solid substrate wherein sequence 201 is produced by primer extension from an immobilized primer 310 as shown in Fig. 4).
Regarding claim 12, Vermaas discloses the above sequencing method, further comprising providing a fourth sequencing primer capable of hybridizing with a 5' end of a part of the second single-stranded nucleic acid complementary to the third site; and hybridizing the fourth sequencing primer with the second single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine at least a part of the sequence of the insert on the single-stranded nucleic acid by extending the fourth sequencing primer, so as to acquire the sequencing result (e.g., sequencing the opposite end of the fragment after synthesizing a complementary substrate-immobilized strand, removing the original template, and annealing a sequencing primer to the new strand as per para 00152, wherein a primer annealed to the 5’-portion of the complementary strand extends into the complementary insert region, reading on the claimed fourth-primer read).
Regarding claim 13, Vermaas discloses the above sequencing method, wherein the single-stranded nucleic acid is a first single-stranded nucleic acid; the surface is further connected with a second single-stranded nucleic acid; the second single-stranded nucleic acid is a complementary strand of the first single-stranded nucleic acid; the second single-stranded nucleic acid is connected via a 5' end of a part thereof complementary to the first sequence with the surface; the second sequence is a predetermined sequence comprising the fourth site - the second tag - the third site; the method further comprises providing a third sequencing primer capable of hybridizing with a 5' end of a part of the second single-stranded nucleic acid complementary to the third site, providing a fourth sequencing primer capable of hybridizing with a 5' end of a part of the second single-stranded nucleic acid complementary to the fourth site, hybridizing the third sequencing primer with the second single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine at least a part of the sequence of the insert on the single-stranded nucleic acid by extending the third sequencing primer; (e.g., hybridizing a sequencing primer to sequence 134 to sequence the index tag 132 as per para 00160 with sequencing-by-synthesis described in para 00139-00141 and 00147); and hybridizing the fourth sequencing primer with the second single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine the sequence of the second tag on the single-stranded nucleic acid by extending the fourth sequencing primer, so as to acquire the sequencing result (e.g., sequencing the opposite end of the fragment after synthesizing a complementary substrate-immobilized strand, removing the original template, and annealing a sequencing primer to the new strand as per para 00152, wherein a primer annealed to the 5’-portion of the complementary strand extends into the complementary insert region, reading on the claimed fourth-primer read).
Regarding claim 14, Vermaas discloses the above sequencing method, wherein the single-stranded nucleic acid is a first single-stranded nucleic acid; the surface is further connected with a second single-stranded nucleic acid; the second single-stranded nucleic acid is a complementary strand of the first single-stranded nucleic acid (e.g., as depicted in Fig. 4); the second single-stranded nucleic acid is connected via a 5' end of a part thereof complementary to the first sequence with the surface, a library is amplified on the surface to provide the single-stranded nucleic acid, the library comprises a plurality of double-stranded nucleic acid molecules formed from a forward strand and a reverse strand that are complementary; the single-stranded nucleic acid comprises an identical sequence to the reverse strand (e.g., amplification as per para 0052-0054 and 0074-0078).
Regarding claim 16, Vermaas discloses the above sequencing method, wherein the amplification comprises melting the library to give an initial template comprising the forward strand and the reverse strand (e.g., denaturation by melting as per para 0076-0077, 00175, and 00190), providing a plurality of forward amplification primers and reverse amplification primers immobilized to the surface at 5' ends thereof, wherein the forward amplification primer is capable of hybridizing with a 3' end of the forward strand and the reverse amplification primer is capable of hybridizing with a 3' end of the reverse strand (e.g., primers 310 and 320 as per Fig. 4); hybridizing at least a part of the initial template with the forward amplification primer and/or the reverse amplification primer to synthesize a nascent strand complementary to the initial template by extending the forward amplification primer and/or the reverse amplification primer (e.g., strand 200 hybridizes to primer 310 and is extended to form 201 as per para 00165-00166); removing the initial template (e.g., as per para 00166); and
performing bridge amplification by using the nascent strand as a template and the forward amplification primer or the reverse amplification primer as a primer to give a solid substrate having a surface with a plurality of first single-stranded nucleic acids and a plurality of second single-stranded nucleic acids immobilized thereon (e.g., bridge amplification as per Fig. 4 and para 00166-00167).
Regarding claim 17, Vermaas discloses the above sequencing method, further comprising: removing the plurality of second single-stranded nucleic acids immobilized on the surface before the polymerization sequencing (e.g., removal as per para 0004 and/or 00143-00146).
Regarding claim 18, Vermaas discloses the above sequencing method, wherein the reverse amplification primer comprises a cleavage site, and the cleavage site is an enzyme action site, optionally wherein the cleavage site is deoxyuridine (e.g., using uracil DNA glycosylase and endonuclease VIII as per para 00153).
Regarding claim 23, Vermaas discloses the above sequencing method, wherein constructing the library comprises providing a double-stranded insert (e.g., as per Fig. 3), ligating adapters to the two ends of the insert to give an adapter - insert - adapter double-stranded nucleic acid molecule, wherein the adapters are double-stranded nucleic acid molecules with predetermined sequences, the adapters consist of a first strand and a second strand that are partially complementary, and a 3' end of the first strand comprises a modification (e.g., adaptors as per Fig. 2 ligated to the double-strand DNA sample as shown in Fig. 3), providing a first amplification primer and a second amplification primer, wherein a 3' end of the first amplification primer is capable of hybridizing with the 3' end of the first strand of a non-complementary part, a 3' end of the second amplification primer is capable of hybridizing with a 3' end of a complementary strand of the second strand of the non-complementary part, and the second amplification primer comprises the first site and the tag; synthesizing a new strand complementary to the adapter - insert - adapter using the first amplification primer; synthesizing a complementary strand of the new strand using the second amplification primer to give a library template comprising the tag and the first site; and amplifying the library template using the first amplification primer and the second amplification primer to give the library, wherein a forward strand of the library comprises the first strand (e.g., as depicted in Fig. 1).
Regarding claim 24, Vermaas discloses the above sequencing method, wherein constructing the library comprises providing a double-stranded insert (e.g., as per Fig. 3), ligating adapters to the two ends of the insert to give an adapter - insert - adapter double- stranded nucleic acid molecule, wherein the adapters are double-stranded nucleic acid molecules with predetermined sequences, the adapters consist of a first strand and a second strand that are partially complementary, the second strand of a non-complementary part comprises the tag and the first site, and a 3' end of the first strand comprises a modification (e.g., adaptors as per Fig. 2 ligated to the double-strand DNA sample as shown in Fig. 3), providing a first amplification primer and a second amplification primer, wherein the first amplification primer is capable of hybridizing with the 3' end of the first strand of a non- complementary part, and the second amplification primer is capable of hybridizing with a 3' end of a complementary strand of the second strand of the non-complementary part; and amplifying the adapter - insert - adapter using the first amplification primer and the second amplification primer to give the library, wherein a forward strand of the library comprises the first strand (e.g., as per Fig. 1).
Illumina
Claims 1, 4-6, and 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Illumina (Indexed Sequencing Overview Guide, Document #15057455v08, Nov. 2020, cited in IDS of 04/11/2025).
Regarding claim 1, Illumina discloses a sequencing method (e.g., “Dual-Indexed Sequencing Overview” as per page 2+), comprising providing a solid substrate (e.g., the surface of a flow-cell as per para Fig. 3) having a surface connected with a plurality of single-stranded nucleic acids, wherein 5' ends of the single-stranded nucleic acids are connected to the surface (e.g., at their 5’-ends as per Fig. 3), the single-stranded nucleic acids are polynucleotides comprising an insert and a first sequence being a predetermined sequence comprising a tag specific to the sample under test (e.g., sample-derived nucleic acid is termed ‘DNA insert’ by Illumina as per Fig. 3 to which has been added a unique identifier or indexing sequence during library preparation as per page 1). Illumina then discloses providing a first sequencing primer capable of hybridizing with a 5' end of the first site and hybridizing the first sequencing primer with the single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine a part of the sequence of the single-stranded nucleic acid by extending the first sequencing primer, so as to acquire a sequencing result (e.g., the Read1 Primer as per Fig. 3).
Regarding claim 4, Illumina discloses the above sequencing method, wherein the first sequence is a predetermined sequence comprising a second site - the tag - the first site (e.g., the Read2 primer binding site as per Fig. 3), and the method further comprises providing a second sequencing primer capable of hybridizing with a 5' end of the second site and hybridizing the second sequencing primer with the single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine at least a part of the sequence of the insert on the single-stranded nucleic acid by extending the second sequencing primer, so as to acquire the sequencing result (e.g., from extension of the Read2 primer as per Fig. 3).
Regarding claim 5, Illumina discloses the above sequencing method, wherein the sequencing result comprises a first read and a second read; the first read comprises sequence information of the tag, and the second read comprises sequence information of at least a part of the insert (e.g., resulting from the sequencing information from the Read1 and/or Read2 primers as well as the i5 and/or i7 index primers in Fig. 3).
Regarding claim 6, Illumina discloses the above sequencing method, wherein the single-stranded nucleic acid is a polynucleotide comprising a second sequence - the insert - the first sequence, and the second sequence is a predetermined sequence comprising a third site (e.g., the i7 index as per Fig. 3).
Regarding claim 8, Illumina discloses the above sequencing method, wherein the tag is a first tag, the second sequence is a predetermined sequence comprising a second tag - the third site or a predetermined sequence comprising a fourth site - the second tag - the third site, and the second tag is a predetermined sequence with specificity to the sample under test (e.g., resulting from the sequencing information from the Read1 and/or Read2 primers as well as the i5 and/or i7 index primers in Fig. 3).
Regarding claim 9, Illumina discloses the above sequencing method, further comprising providing a third sequencing primer capable of hybridizing with a 5' end of the third site; and hybridizing the third sequencing primer with the single-stranded nucleic acid and placing under a condition suitable for polymerization sequencing to determine the sequence of the second tag on the single-stranded nucleic acid by extending the third sequencing primer, so as to acquire the sequencing result, optionally wherein the sequencing result further comprises a third read comprising sequence information of the second tag (e.g., resulting from the sequencing information from the Read1 and/or Read2 primers as well as the i5 and/or i7 index primers in Fig. 3).
Claim Rejections – 35 U.S.C. 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Vermaas et al. and Wu et al.
Claims 1-2, 4-6, 8-9, 11-14, 16-18, 20, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Vermaas et al. (WO 2018/200386 A1) in view of Wu et al. (WO 2019/222264 A1).
Vermaas is relied on as above, however, the reference is silent as to the reverse amplification primer is an oligonucleotide comprising poly(N)n- the cleavage site - a complementary part of the first site, or,the reverse amplification primer is an oligonucleotide comprising poly(N)n - a complementary part of the first site, the cleavage site is embedded in the complementary part of the first site, N is A, T, C or G, and n is a natural number of not less than 5 and not more than 15, as set forth in claim 20.
Wu discloses a standard P5 surface primer with a poly(T) spacer having such a structure (e.g., as per para 0055 of Wu).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to use the P5 primer with poly(T) spacer as per Wu in the sequencing methods of Vermaas. One of ordinary skill in the art would have been motivated to do so since Vermaas recites in general the need for surface primers that support amplification and selective enzymatic cleavage using their disclosed USER cleavage mechanism (e.g., as per para 00153), and Wu provides a viable option (e.g., with a deoxyuridine cleavage site on the P5 primer as per para 0051).
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since Wu explicitly discloses that their P5 primer retains the required primer hybridization, extension (bridge amplification), and selective release functions as required by Vermaas.
Vermaas et al. and Li et al.
Claims 1-2, 4-6, 8-9, 11-14, 16-18, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Vermaas et al. (WO 2018/200386 A1) in view of Li et al. (U.S. PGPub 2012/0156728 A1).
Vermaas is relied on as above, however, the reference is silent as to the claimed free reverse primer template-walking steps as set forth in claim 22.
Li discloses denaturing the dsDNA library and extending from 5’-attached primers to form complementary sequences (e.g., as per para 00140-00143 of Li), which can be combined with Vermaas removal of the original DNA template following synthesis of the copy (e.g., as per para 00164-00167 and/or Fig. 4 of Vermaas). Li then provides amplification via an immobilized primer and a soluble (free) primer (e.g., as per para 0033-0035, 0054, and 0069 of Li). Template-walking amplification to produce multiple copies of the immobilized first strands is taught by Li (e.g., as per para 0037-0046 and 0053 of Li). Finally, Vermaas discloses synthesizing complementary copies from the second surface primers (e.g., as per para 00142 and 00166-00168 of Vermaas) noting that Li allow for multiple surface-bound primer sequences and complementary 5’-attached products (e.g., as per para 0018 and/or 0097).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to use the localized template-walking amplification in the sequencing methods of Vermaas. One of ordinary skill in the art would have been motivated to do so since Li explicitly identifies sequencing as a use for the amplification products and provides isothermal amplification conditions (e.g., as per para 0034, 0049, and/or 0055).
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since both references similarly use complementary pairing of adaptors and primers with polymerase extension.
Conclusion
No claims are allowed.
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/JEREMY C FLINDERS/
Primary Examiner, Art Unit 1684
