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 .
Office Action: Notice
Any objection or rejection of record in the previous Office Action, mailed 9/26/2025,
which is not addressed in this action has been withdrawn in light of Applicants' amendments
and/or arguments. This action is FINAL
Claim Status
Applicant has amended claims 1, 2, 5, 9-11 and 19 (1/23/2026). No new matter was added. Claims 1-19 are under examination (1/23/2026).
Priority
Claims 1-19 receive a priority date of 5/28/2015, the effective filing date of US Provisional Patent 62/167,463.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The Information Disclosure Statement filed 12/15/2025 has been considered.
Objections Withdrawn
Specification:
The objections to the specification due to the use of a trademark or tradenames are withdrawn in view of Applicant’s amendments.
Claims:
The minor formality objection to claim 19 is withdrawn in view of Applicant’s amendments.
Rejections Withdrawn
Claim Rejections - 35 USC § 112(b)
The rejections of claims 1-2 and 7-18 under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, 2nd paragraph, are withdrawn in view of Applicant’s amendments of claims 1 and 2.
Rejections Maintained
Claim Rejections - 35 USC § 112(b)
Claim 3 is further rejected. Claim 3 recites the limitation "the nucleic acid" in line 2. There is insufficient antecedent basis for this limitation in the claim, since both double-stranded nucleic acid and single-stranded nucleic acid are applied in previous independent claim 1.
Claims 4-6 are included in this rejection due to their dependency on claim 3.
Applicant’s Response: The Applicant did not address the 112(b) rejection of claim 3 in their remarks.
Examiner’s Response to Traversal: There was no argument set forth by the Applicant to consider. There is insufficient antecedent basis for the limitation, “the nucleic acid” in the instant claim, since both double-stranded nucleic acid and single-stranded nucleic acid are applied in previous independent claim 1. As of note, claim 2 was amended for proper antecedent basis; however, claim 3 relies on claim 1, not claim 2, so this does not address the lack of antecedent basis in instant claim 3 for the same terminology.
Claim Rejections - 35 USC § 102
Claims 1-19 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Li et al., (WO 2012/044847 A1, published 4/5/2012).
Regarding claim 1, Li teaches compositions, systems, methods, and kits for joining together the ends of one or more polynucleotides using at least one pair of blocking oligonucleotide adaptors, where blocking oligonucleotide adaptors can be used to reduce the formation of adaptor dimers or trimers (or higher-order concatemers) which can improve the yield of desirable polynucleotide-adaptor products in any recombinant nucleic acid workflow (Abstract). Additionally, Li teaches that one or more polynucleotides of interest can be fragmented using mechanical stress, including without limitation: shearing forces, fluid shear, hydrodynamic shear, or pulsatile shear, where mechanical stress can be applied to a polynucleotide of interest by: sonication, nebulization, or cavitation (Paragraph 180, lines 1-5). Further, Li teaches that mechanical stress can randomly fragment nucleic acids, where a polynucleotide of interest can be fragmented with enzymatic reactions, such as: any type I, type II, type Iis, type IIB, type III or type IV restriction endonucleases; any nicking endonuclease restriction enzymes; endonuclease (i.e., DNase I); and/or exonuclease enzymes, as well as a transposase and transposable element, for example Nextera™ technology from Epicentre (Paragraph 180, lines 5-10).
Li also teaches that blocking oligonucleotide adapters can each comprise: (i) a first and second single- stranded oligonucleotide that are annealed together to form a nucleic acid duplex with an overhang portion; and (ii) a third single-stranded oligonucleotide (blocking oligonucleotide) that is annealed to the overhang portion (Paragraph 63, lines 1-5). Specifically, Li teaches that mate-pair library can generally include: (a) providing a linear polynucleotide of interest (i.e., a double- stranded polynucleotide) having a first and second end; (b) joining the first end of the linear polynucleotide of interest to a first oligonucleotide adaptor and joining the second end of the linear polynucleotide of interest to a second oligonucleotide adaptor so as to generate an adaptor-polynucleotide-adaptor product; and (c) circularizing the adaptor-polynucleotide- adaptor product, where a circularizing step (c) can include removing the third single-stranded oligonucleotide (blocking oligonucleotide) from the overhang portions of the first and second oligonucleotide adaptors so as to expose the overhang portions of the adaptor-joining ends (Paragraph 63, lines 5-10). Further Li teaches that the exposed overhang ends can be annealed together, thereby circularizing the adaptor- polynucleotide-adaptor product and exposed overhang ends can hybridize to each other so as to leave a gap or nick on one or both strands at the junction between the adaptor-joining ends of the first and second adaptors (Paragraph 63, lines 5-10). Li teaches that a strand opposite the new position of the nick can be cleaved with a single-strand specific endonuclease enzyme to release a linear mate pair construct having a pair of blocking oligonucleotide adaptors (minus the blocking oligonucleotide) flanked by two portions of the polynucleotide of interest (i.e., tags) where lengths of the tags or tagmentation can be modulated by increasing or decreasing the length of time of the nick translation reaction (Paragraph 63, lines 20-25). Li further teaches that immobilized oligonucleotide capture primers can anneal to an immobilization adaptor that is joined to a released mate pair construct, and a primer extension reaction can be conducted to generate a complimentary copy of the released mate pair construct attached to a surface where, a bridge amplification reaction can be conducted by joining a released mate pair construct to different adaptors at each end (where the adaptors are complementary to different oligonucleotide capture primers that are attached to a surface) and conducting multiple primer extension reactions (Paragraph 88, lines 5-10).
Further, Li teaches that fragmented polynucleotides of interest can be subjected to any size-selection procedure to obtain any desired size range, where, nucleic acid size selection method includes without limitation: solid phase adherence or immobilization; electrophoresis, such as gel electrophoresis; and chromatography, such as HPLC and size exclusion chromatography (Paragraph 79, lines 1-5).
Regarding claim 2, Li teaches that the previously described method for transposase-mediated sequences directed towards a polymerase that requires the terminal 3 ' OH of a nucleic acid primer to initiate nucleotide polymerization where, a linker nucleic acid provides a terminal 3' OH for the polymerase to polymerize the nucleotides (Paragraph 217, lines 1-5).
Regarding claims 3-6, Li teaches that the previously described method for transposase-mediated sequences includes a fragmenting step that can generate first ends, second ends, or internal portions, having undesirable features, such as nicks, overhang ends, ends lacking a phosphorylated end, ends having a phosphorylated end, or nucleic acid fragments having apurinic or apyrimidinic residues, where polynucleotide fragments can be repaired at one or both ends, and/or repaired at an internal region (i.e., enzymatic reactions can be conducted to convert overhang ends to blunt ends, or to phosphorylate or de- phosphorylate the 5' end of a strand, or to close nicks, or to repair oxidized guanines or pyrimidines) (Paragraph 184, lines 1-10). Further, Li teaches that the previously described phosphorylation method includes repairing or end-repairing nucleic acid fragments includes contacting nucleic acid fragments, or contacting a plurality of first ends and/or second ends with: an enzyme to close single- stranded nicks in duplex DNA (i.e., T4 DNA ligase); an enzyme to phosphorylate the 5' end of at least one strand of a duplex DNA (i.e., T4 polynucleotide kinase or terminal transferase); an enzyme to remove a 5' phosphate (Paragraph 185, lines 1-5). Also, Li teaches that a DNA polymerase can be used to add one or more non- template nucleotides to a terminal 3' end of a nucleic acid strand where a non-proofreading DNA polymerase can be used to add a single non- template A-residue to a 3' end a of a nucleic acid strand (Paragraph 188, lines 5-10). Specifically, Li teaches that a DNA polymerase can be a Taq DNA polymerase (or a derivative thereof) where DNA polymerases having proofreading activity can be used to add a single non-template 3' A-tail (Paragraph 188, lines 5-10).
Regarding claim 7, Li teaches that the previously described method for transposase-mediated sequences includes a preemptive step of preparing mate pair constructs and mate pair libraries which can comprise a nucleic acid denaturation or an annealing step where nucleic acids can be denatured or hybridized by adjusting the: temperature, pH, sodium concentration, and/or formamide concentration and can be denatured into two single strands (Paragraph 215, lines 1-3).
Regarding claims 8-9, Li teaches that immobilized oligonucleotide capture primers can anneal to an immobilization adaptor that is joined to a released mate pair construct, and a primer extension reaction can be conducted to generate a complimentary copy of the released mate pair construct attached to a surface where, a bridge amplification reaction can be conducted by joining a released mate pair construct to different adaptors at each end (where the adaptors are complementary to different oligonucleotide capture primers that are attached to a surface) and conducting multiple primer extension reactions (Paragraph 88, lines 5-10).
Regarding claims 10-11, Li teaches that fragmented polynucleotides of interest can be subjected to any size-selection procedure to obtain any desired size range, where, nucleic acid size selection method includes without limitation: solid phase adherence or immobilization; electrophoresis, such as gel electrophoresis; and chromatography, such as HPLC and size exclusion chromatography (Paragraph 79, lines 1-5). Specifically, Li teaches that such templates can be attached as clonal populations to a solid support, such as a particle, bead, or the like, and said clonal populations are loaded into reaction chambers (Paragraph 248, lines 5-6).
Li teaches that immobilized oligonucleotide capture primers can anneal to an immobilization adaptor that is joined to a released mate pair construct, and a primer extension reaction can be conducted to generate a complimentary copy of the released mate pair construct attached to a surface where, a bridge amplification reaction can be conducted by joining a released mate pair construct to different adaptors at each end (where the adaptors are complementary to different oligonucleotide capture primers that are attached to a surface) and conducting multiple primer extension reactions (Paragraph 88, lines 5-10).
Regarding claim 12, Li teaches that the previously described method for transposase-mediated sequences applies to a polynucleotide of interest that can be isolated from any source including: an organism; normal or diseased cells or tissues; fresh or archived (i.e., formalin and/or paraffin) cell or tissue samples; chromosomal, genomic, organellar, methylated, cloned, amplified, DNA, cDNA, RNA, RNA/DNA or synthesized (Paragraph 77, lines 1-3).
Regarding claims 13-16, Li teaches that mate-pair library can generally include: (a) providing a linear polynucleotide of interest (i.e., a double- stranded polynucleotide) having a first and second end; (b) joining the first end of the linear polynucleotide of interest to a first oligonucleotide adaptor and joining the second end of the linear polynucleotide of interest to a second oligonucleotide adaptor so as to generate an adaptor-polynucleotide-adaptor product; and (c) circularizing the adaptor-polynucleotide- adaptor product, where a circularizing step (c) can include removing the third single-stranded oligonucleotide (blocking oligonucleotide) from the overhang portions of the first and second oligonucleotide adaptors so as to expose the overhang portions of the adaptor-joining ends (Paragraph 63, lines 5-10).
Further, Li teaches that typically, hydrogen ions are released as byproducts of nucleotide incorporations occurring during template-dependent nucleic acid synthesis by a polymerase, where the Ion Torrent PGM™ sequencer detects the nucleotide incorporations by detecting the hydrogen ion byproducts of the nucleotide incorporations and the Ion Torrent PGM™ sequencer can include a plurality of nucleic acid templates to be sequenced, each template disposed within a respective sequencing reaction well in an array (Paragraph 246, lines 1-10).
Li further teaches that immobilized oligonucleotide capture primers can anneal to an immobilization adaptor that is joined to a released mate pair construct, and a primer extension reaction can be conducted to generate a complimentary copy of the released mate pair construct attached to a surface where, a bridge amplification reaction can be conducted by joining a released mate pair construct to different adaptors at each end (where the adaptors are complementary to different oligonucleotide capture primers that are attached to a surface) and conducting multiple primer extension reactions (Paragraph 88, lines 5-10).
Regarding claims 17-18, Li teaches that kits or compositions of parts can include any combination of: one or more types of blocking oligonucleotide adaptors (with or without biotin) (Figures 1A and B- 7); reagents for fragmenting a polynucleotide of interest; reagents for end-repairing the ends of the fragments of a polynucleotide of interest; reagents for size-selecting nucleic acids; reagents for joining one or both ends of a fragment of a polynucleotide of interest to one or more types of adaptors (i.e., blocking oligonucleotide adaptors or additional types of adaptors); reagents for circularizing a linear polynucleotide of interest joined to one or more blocking oligonucleotide adaptors; reagents for performing a nick translation reaction or exonuclease digestion reaction or strand extension reaction; reagents for releasing a linear mate pair construct; reagents to perform a tailing reaction; reagents for purifying a polynucleotide of interest (i.e., as a mate pair construct); reagents for quantifying nucleic acids; reagents for amplifying nucleic acids and/or reagents for sequencing nucleic acids (Paragraph 255, lines 5-10). Further, Li taches that the kits can include any combination of: various enzymes to conduct reactions such as ligating, end-repairing, size-selecting, adaptor-joining, circularizing, nick- translating, degrading linear nucleic acids; releasing a mate-pair, tailing, and amplifying; beads for nucleic acid capture; reagents for washing; reagents for PCR amplification; adaptors (e.g., PI, P2, A, blocking oligonucleotide adaptors); PCR primers; nucleic acid purification columns; and/or components for nucleic acid gel or bead-free extraction (Paragraph 255, lines 10-15).
Regarding claim 19, Li teaches that a surface can be planar, convex, concave, or any combination thereof and can comprise an inorganic material, natural polymers, synthetic polymers, or non-polymeric material (Paragraph 91, lines 1-2). Further, Li teaches that a surface includes a flow cell or device, well, groove, channel, reservoir, filter, gel or inner walls of a capillary and a mate pair construct can be immobilized to an acrylamide compound coating on a surface (Paragraph 91, lines 1-5). Further, Li teaches accompanying methods to the surface device including methods for preparing mate pair constructs and mate pair libraries which can comprise a purifying step including separating polynucleotides fragments from non-desirable components (i.e., buffers, salts, enzymes, primer-dimers, or excess adaptors or primers) (Paragraph 214, lines 1-5). Li also teaches that in some embodiments, a purification procedure can be conducted at least once at any stage in a workflow (i.e., bead purification, column purification, gel electrophoresis, dialysis, alcohol, precipitation, size-selective PEG precipitation and the like) (Paragraph 214, lines 1-5).
Additionally, Li teaches that the previously described flow cell device can be applied to nucleic acid manipulations that involve joining together the ends of two or more different polynucleotides, or joining together two ends of one polynucleotide for circularization, where for example, nucleic acid sample preparation or library preparation workflows can include at least one joining step mediated by one or more nucleic acid adaptors and the resulting constructs can be sequenced in a next-generation sequencing process, in which large numbers of relatively small nucleic acid fragments can be sequenced at the same time in parallel (Paragraph 4, lines 1-5).
Li teaches each and every limitation of claims 1-19, and therefore Li anticipates claims 1-19.
Applicant’s Response: The Applicant argues that Li does not anticipate independent claims 1 and 19 because Li fails to teach each and every recited limitation. With respect to amended claim 1, the Applicant contents that Li does not teach applying a single stranded nucleic acid to a solid support comprising an immobilized capture sequence under conditions permitting hybridization, but instead teaches double-stranded constructs with overhangs and circularization via blocking oligonucleotides. Regarding amended claim 19, the Applicant asserts that Li does not teach a solid support that permits sample migration via capillary action from a sample deposition region to a tagmentation region, and that reference to capillary walls or surfaces in Li do not satisfy the functional limitation.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully and fully considered but are not found persuasive, as discussed below.
Under MPEP 2131, a claim is anticipated when a single prior art reference discloses each and every element of the claimed invention, either expressly or inherently. The reference need not use identical terminology so long as the claimed subject matter is described in sufficient detail to establish possession of the claimed invention. See also MPEP 2111 (claims given their broadest reasonable interpretation).
In regards to independent claim 1, the Applicant argues that Li fails to teach applying a single stranded nucleic acid to a solid support comprising an immobilized capture sequence under conditions whereby the single stranded nucleic acid hybridizes to the capture sequence, asserting that Li teaches only double stranded constructs with overhangs. This argument is not persuasive because Li teaches that immobilized oligonucleotide capture primers are attached to a surface and that released constructs anneal to such capture sequences, followed by primer extension (Paragraph 88, lines 5-10). Li further teaches denaturation of nucleic acids into single strands (Paragraph 215, lines 1-3) and fragmentation and enzymatic processing that generate single stranded regions (Paragraph 63, lines 1-10; Paragraph 180, lines 5-10). Under the BRI, applying a nucleic acid (including a denatured or partially single stranded construct) to a surface bearing immobilized capture sequences such that annealing occurs reads on the claimed applying a single stranded nucleic acid…under conditions whereby it hybridizes. The claims do not exclude constructs having prior double stranded origin or transient duplex formation.
Li also teaches extension reactions and subsequent enzymatic steps (Paragraphs 184-188), which reasonably correspond to extending the immobilized capture sequence to form double stranded nucleic acid prior to further processing. Accordingly, Li discloses each limitation of amended claim 1.
In regards to independent claim 19, the Applicant argues that Li does not teach a solid support that permits sample migration via capillary action from the sample deposition region to the tagmentation region, arguing that references to capillary walls are insufficient. The argument is also unpersuasive. Li teaches that the surface may include a flow cell, well, groove, channel, reservoir, filter, gel or inner walls of a capillary (Paragraph 91, lines 1-5). Such structures inherently permit fluid migration via capillary forces. Under MPEP 2112 (inherency), when a prior art structure is capable of performing the claimed function, and the function is a natural result of the structure, the limitation is met. Channels, capillaries, and porous materials (i.e., filters, gels) are well known to support capillary driven flow.
Li further teaches immobilization of constructs on such surfaces and nucleic acid manipulation workflows, performed in these devices (Paragraphs 4, 214, 246), including transposase-mediated fragmentation (Paragraph 180). Thus, Li teaches a surface device comprising regions for sample processing and enzymatic manipulation, and the recited capillary migration is an inherent property of the disclosed capillary/channel structures.
Therefore, Li teaches or inherently discloses each and every limitation of independent claims 1 and 19. Dependent claims fall with their respective independent claims. Accordingly, the rejection of claims 1-19 under 35 USC 102(a)(1) and (a)(2) is maintained.
Conclusions
No claim is allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ROSE LAFAVE whose telephone number is (703)756-4747. The examiner can normally be reached Compressed Bi-Week: M-F 7:30-4:30.
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/ELIZABETH ROSE LAFAVE/ Examiner, Art Unit 1684
/HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684