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
Pursuant to a preliminary amendment, claims 1, 3, 5, 14, 15, 18, 23 29, 36-41, 45, 48, 52, 56, 57 and 59 are currently pending in the instant application, filed July 20, 2026.
Response to Election/Restriction
Applicant's election of Group I with traverse, claims 1, 3, 5, 14, 15, 18, 23, 29, 36-41, 45, 48 and 52 directed to a method of generating clusters of amplicons for a nucleic acid library; and Applicant’s election of Species with traverse as follows:
Species (A): wherein the 5’ region of the forward primer is a poly-A strand and the 5’ region of the reverse primer is a poly-T strand (claim 14);
Species (B): further comprising, after step (c): (d) incubating the solid surface with an exonuclease for a period of time (claim 45);
Species (C): wherein step (c) comprises a super-surface PCR during which 3’ end of the immobilized DNA strand extended from the forward primer hybridizes (claim 41); and
Species (D): wherein step (e) comprises a super-surface PCR (claim 48), in the reply filed July 20, 2026 is acknowledged.
Response to Traversals:
The traversal of is on the grounds that: (a) Groups I, II and III are closely related subject matter and could be searched and examined simultaneously without placing a serious burden on the Examiner (Applicant Remarks, pg. 8, fourth full paragraph); (b) in Species (A), claims 5, 14 and 15 define different aspects of the forward primer and/or the reverse primer (Applicant Remarks, pg. 9, last full paragraph); (c) in Species (B), claims 29, 37, or 45 define different additional steps that can be included in the claimed method (Applicant Remarks, pg. 9, last partial paragraph); (d) in Species (C), claims 39 and 41 define different types of PCR that both can occur during step (c) (Applicant Remarks, pg. 10, first full paragraph); and (e) in Species (D), claims 48 and 52 define different aspects of PCR (Applicant Remarks, pg. 10, second full paragraph).
Regarding (a), please see the Requirement for Election/Restriction mailed May 20, 2026 regarding how each of Groups I-IV is distinct. Because the inventions of Groups I, II, and III are distinct, a search for the invention of Group I and Groups II or III will not be coextensive because a search indicating the process is novel or unobvious would not extend to a holding that the other processes are novel or unobvious. Each of Groups I-III recite different process steps, such that a search for prior art and consideration of patentability of all claims of Group I, II and III together do not necessary overlap with one another, thereby generating an undue burden in the examiner. The restriction is proper.
Regarding (b)-(e), with regard to Species (A)-(D), Applicant’s arguments are exactly the reason that each Species election is required. Each of the claims recites a different species including different primer structures, methods further comprising different process steps, a different PCR steps that are carried out, the use of different types of PCR, and/or the different primer structures are unique a priori (e.g., synthesized using different starting materials, reaction conditions, analysis techniques, having different structural/functional features, activities, binding affinities, etc.), such that the different species require (at least) different fields of search (e.g., searching different classes and/or subclasses or electronic resources, or employing different search queries); the prior art applicable to one species would not likely be applicable to another species; the species are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph, etc. The requirement for restriction/election is proper.
Claims 56, 57 and 59 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 5, 15, 18, 23, 29, 37, 39, 40 and 52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on July 20, 2026.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 3, 14, 36, 38, 41, 45 and 48 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed November 1, 2023, and claims the benefit of the US Provisional Patent Application 63421693, filed November 2, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 20, 2026 has been considered. An initialed copy of the IDS accompanies this Office Action.
Claim Objections/Rejections
Claim Objections
Claims 3 and 14 are objected to because of the following informalities: Claims 3 and 14 recite the terms “fmol/mm2,” “poly-A,” and “poly-T,” where an abbreviation should be spelled out in the first encounter of the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1, 3, 14, 36, 38, 41, 45 and 48 are rejected 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 1 is indefinite for the recitation of the term “providing a solid surface immobilized with a plurality of forward primers” such as recited in claim 1, line 3 because the phrase is confusing and unclear. It is unclear whether the solid surface is immobilized to something or somewhere using forward primers, or whether forward primers are immobilized on a solid support and, thus, the metes and bounds of the claim cannot be determined.
Claims 1, 14, 41 and 48 are indefinite for the recitation of the terms “each forward primer”, “each reverse primer”, “the forward primer”, and “the reverse primer” such as recited in claim 1, lines 3-6 and 11-13. There is insufficient antecedent basis for the terms “each forward primer”, “each reverse primer”, “the forward primer”, and “the reverse primer” in the claim because claim 1, lines 3-4 recites the term “a plurality of forward primers” and “a plurality of reverse primers.”
Claims 1 and 38 are indefinite for the recitation of the term “the library” such as recited in claim 1, line 9. There is insufficient antecedent basis for the term “the library” in the claim because claim 1, line 1 recites the term “a nucleic acid library.”
Claim 1 is indefinite for the recitation of the term “corresponds to” such as recited in claim 1, lines 10 and 12 because it is unclear how the sequences “correspond to” one another. It is unclear the whether the first adapter sequence and a sequence in the 3’ region of forward primer (or the 3’ sequence of a reverse primer) are both complementary to the same nucleic acid sequence; whether they each have different nucleic acid sequences; whether they are complementary to each other; or whether the term refers to some other way that the sequences correspond to one another and, thus, the metes and bounds of the claim cannot be determined.
Claim 3 is indefinite for the recitation of the term “the forward and/or reverse primers” such as recited in claim 3, line 1. There is insufficient antecedent basis for the terms “the forward and/or reverse primers” in the claim because claim 1, lines 3-4 recites the term “a plurality of forward primers” and “a plurality of reverse primers.” The Examiner suggests that Applicant amend the claim to recite, for example, wherein the plurality of forward primers and the plurality of reverse primers are immobilized.”
Claim 3 is indefinite for the recitation of the term “immobilized to the solid surface” such as recited in claim 3, line 2 because claim 3 depends from instant claim 1, wherein claim 1, lines 3-4 recites the term “a solid surface is immobilized with a plurality of forward primers and a plurality of reverse primers” (e.g., the solid surface is immobilized) and, thus, the metes and bounds of the claim cannot be determined.
Claim 3 is indefinite for the recitation of the term “optionally” such as recited in claim 3, line 3 because it is unclear whether the “optional” density occurs, such that the claim does not particularly point out and distinctly claim the subject matter that Applicant regards as the invention and, thus, the metes and bounds of the claim cannot be determined.
Claim 3 is indefinite for the recitation of a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Instant claim 3, lines 2-4 recites a broad range of a density of about 1 to 1000 fmol/mm2, while also reciting a density of about 200 fmol/mm2, which is a narrow range or limitation and, thus, the metes and bounds of the claim cannot be determined.
Claims 38, 41, 45 and 48 are indefinite for the recitation of the term “step” such as recited in claim 38, line 1 because claims 38, 41 and 45 depend from instant claim 1; and claim 48 depends from claim 1 and 45, wherein claim 1 recites (a), (b) and (c) and, thus, the metes and bounds of the claim cannot be determined.
Claim 38 is indefinite for the recitation of the terms “the immobilized forward or reverse primers” and “the forward or reverse primers” such as recited in claim 38, lines 2 and 4. There is insufficient antecedent basis for the terms “immobilized forward or reverse primers” and “the forward or reverse primers” in the claim because claim 1, lines 3-4 recites the term “a plurality of forward primers” and “a plurality of reverse primers.”
Claim 38 is indefinite for the recitation of the term “wherein step (c) comprises” such as recited in claim 38, line 1 because claim 38 depends from instant claim 1, wherein claim 1(c) already comprises “performing an amplification process” such that dependent claim 38 cannot recite that independent claim 1(c) comprises something entirely different and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend the claim to recite, for example, “wherein the amplification process comprises: (i) annealing…” Or, “wherein (c) further comprises.”
Claim 41 is indefinite for the recitation of the term “wherein step (c) comprises” such as recited in claim 38, line 1 because claim 38 depends from instant claim 1, wherein claim 1(c) already comprises “performing an amplification process” such that dependent claim 38 cannot recite that independent claim 1(c) comprises something entirely different and, thus, the metes and bounds of the claim cannot be determined.
Claim 41 is indefinite for the recitation of the terms “3’ end of the immobilized DNA strand”; “DNA strands”; “other immobilized DNA strand”; and “template” such as recited in claim 41, lines 2-5 because claim 41 depends from claim 1, wherein claim 1 does not recite the presence of immobilized DNA strands, DNA strands, other immobilized DNA strands; and/or templates and, thus, the metes and bounds of the claim cannot be determined.
Claim 41 is indefinite for the recitation of the terms “supersurface PCR” such as recited in claim 41, lines 1-2 because the term is not commonly used in the art and the as-filed Specification does not define the term, such that the specific method steps, techniques, and/or components of “supersurface PCR” are unclear. Moreover, it is unclear whether the term is meant to refer to a known PCR method such as bridge PCR and, thus, the metes and bounds of the claim cannot be determined.
Claims 41 and 48 are indefinite for the recitation of the terms “the other immobilized DNA strand” such as recited in claim 41, line 4. There is insufficient antecedent basis for the terms “the other immobilized DNA strand” in the claim.
Claim 48 is indefinite for the recitation of the term “wherein step (e) comprises” such as recited in claim 45, line 1 because claim 48 depends from instant claims 1 and 45, wherein claim 45(e) already comprises “conducting a second phase of PCR to generate the clusters of amplicons” such that dependent claim 48 cannot recite that claim 45(e) comprises something entirely different and, thus, the metes and bounds of the claim cannot be determined.
Claim 48 is indefinite for the recitation of the terms “3’ end of the immobilized DNA strand”; “DNA strands”; “other immobilized DNA strand”; and “template” such as recited in claim 48, lines 2-5 because claim 48 depends from claims 1 and 45, wherein claims 1 and 45 do not recite the presence of immobilized DNA strands, DNA strands, other immobilized DNA strands; and/or templates and, thus, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3, 38, 41, 45 and 48 are rejected 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.
Claim 3 recites (in part): “wherein the forward and/or reverse primers are immobilized to the solid surface” in lines 1-2 because the claim 3 depends from instant claim 1, wherein claim 1 recites that the solid surface is immobilized with a plurality of forward primers and a plurality of reverse primers. Thus, claim 3 is an improper dependent claim 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.
Claims 38, 41, 45 and 48 recite (in part): “step” in line 1 because the claims 38, 41 and 48 depends from instant claim 1; and claim 48 depends from 1 and 45, wherein claim 1 does not recite a “step”. Thus, claims 38, 41, 45 and 48 are improper dependent claims 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.
Claim 41 and 45 recite (in part): “a supersurface PCR during which 3’ end…the other immobilized DNA strand as a template” such as recited in claim 41, lines 2-5 because claims 41 depends from claim 1, and claim 48 depends from claims 1 and 45, wherein claims 1 and 45 do not recite the presence of immobilized DNA strands, DNA strands, other immobilized DNA strands; and/or templates. Thus, claims 41 and 45 are improper dependent claims 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.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 14, 36, 38, 41, 45 and 48 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Kersey et al. (hereinafter “Kersey”) (US Patent No. 9758825, issued September 12, 2017) as evidenced by Wang et al. (hereinafter “Wang”) (International Application WO2018186930, published October 11, 2018)
Regarding claim 1, Kersey teaches improved compositions, methods, apparatus, and kits for high-throughput nucleic acid amplification, detection and sequencing are disclosed, wherein a nucleic acid cluster having an identifiable center is produced by generating on a solid support an immobilized nucleic acid complement from a template, one of which comprises a detectable label; and amplifying the complement and the template to obtain a nucleic acid cluster on the support, the cluster having a substantially central location marked by the detectable label and a surrounding region comprising immobilized copies; as well as, nucleotide sequence determination in nucleic acid clusters so produced, center position annotation in the clusters, assignment of sequence information to overlapping clusters, and related compositions and methods (interpreted as providing a solid surface comprising immobilized primers; contacting the nucleic acids with the primers; and performing an amplification to generate clusters, claim 1) (Abstract). Kersey teaches "solid-phase amplification", which refers to a nucleic acid amplification conducted on or in association with a solid support, which can comprise only one species of oligonucleotide primer immobilized to a solid support; or alternatively, the solid support can comprise a plurality of first and second different immobilized oligonucleotide primer species, such that solid-phase amplification refers to any nucleic acid amplification reaction carried out on or in association with a solid support, such that all or a portion of the amplified nucleic acids remain immobilized on the solid support as they are formed; where in particular, the term encompasses solid phase amplification reactions analogous to standard solution phase primer extension or PCR except that one or both of the forward and reverse amplification primers is/are immobilized on the solid support as they are formed (interpreted as immobilizing forward and/or reverse primers to a solid surface; performing an amplification process; and encompassing supersurface PCR, claim 1a and 1c) (col 19, lines 23-31; and col 39, lines 6-22). Kersey teaches that oligonucleotide sequences can be adapters that are ligated to the 5' and/or 3' ends of a nucleic acid, wherein oligonucleotide sequences can already be present in the nucleic acid to be used as a template (interpreted as contacting the immobilized primers with a nucleic acid molecule comprising adapters on both the 3’ end and the 5’ end of the template sequence, claim 1b) (col 16, lines 24-28). Kersey teaches that solid-phase nucleic acid amplification reactions can generally comprise at least one of two different types of nucleic acid amplification: (1) interfacial amplification and (2) surface (or bridge) amplification, such that in interfacial amplification the solid support comprises a nucleic acid template that is indirectly immobilized to the solid support by hybridization to an immobilized colony primer X as described herein, wherein the immobilized colony primer can be extended in the course of a polymerase-catalyzed, template-directed elongation reaction (e.g., primer extension) to generate an immobilized complementary nucleic acid that remains attached to the solid support, such that after the extension phase, the nucleic acids (e.g., template and its complementary product) can be denatured such that the template nucleic acid is released into solution and made available for hybridization to another colony primer X (interpreted as performing an amplification process, claim 1c) (col 39, lines 23-38). Kersey teaches that surface or bridge amplification occurs when, on a solid support, an immobilized nucleic acid template or nucleic acid complement hybridizes to an immobilized colony primer X, wherein the 3' end of the immobilized nucleic acid template or immobilized nucleic acid complement provides the template for a polymerase-catalyzed, template-directed elongation reaction (e.g., primer extension) extending from the complementary and immobilized colony primer X, such that the resulting double-stranded product "bridges" the two colony primers, and both strands are covalently attached to the support; and in the next cycle, following denaturation that yields a pair of single strands (the immobilized template and the extended-primer product) immobilized to the solid support, both immobilized strands can serve as templates for new primer extension, thereby providing a mechanism for nucleic acid cluster formation (interpreted as performing an amplification process; and generating clonal clusters, claim 1c) (col 39, lines 42-58).
Regarding claim 3, Kersey teaches that the distance between the individual colony primers and/or the individual nucleic acid templates (and hence the density of the colony primers and/or nucleic acid templates) can be controlled by altering the concentration of colony primers and nucleic acid templates that are directly immobilized to the support including a density of at least 1 fmol/mm2, at least 10 fmol/mm2, and between 30 to 60 fmol/mm2, such that the density of nucleic acid templates for use in the method of the invention is typically 10,000/mm2 to 100,000/mm2, wherein higher densities are also achievable, for example, 100,000/mm2 to 1,000,000/mm2 and 1,000,000/mm2 to 10,000,000/mm2 (interpreted as encompassing a density of 1 fmol/mm2 to about 1000 fmol/mm2, claim 3) (col 36, lines 12-23).
Regarding claim 14, Kersey teaches that the primer 1 and primer 2 sequences can be complementary to a nucleic acid sample with known ends, for example, ends that have been attached to the sample by ligation of a universal adapter sequence (interpreting primers to comprise a poly-T or poly-A sequence, claim 14) (col 3, lines 21-24). Kersey teaches that for the generation of an immobilized nucleic acid complement, an immobilized primer can be extended by a primer extension reaction using a nucleotide mix comprising unlabeled dATP, dTTP, and dGTP and detectably labeled dCTP (interpreted as primers comprising a poly-A strand or a poly-T strand, claim 14) (col 18, lines 27-31). Kersey teaches that typically the nucleic acid to be used as a template is first obtained in double-stranded form, such that when the nucleic acid is provided in single-stranded form, as mRNA for example, it can be first made into a double-stranded form by means well-known and documented in the art, for example, by synthesizing a cDNA using oligo-dT primers, reverse transcriptase, and DNA polymerase (interpreted as primers comprising a poly-T strand, claim 14) (col 37, lines 3-9).
Regarding claim 36, Kersey teaches nucleic acid complements can be immobilized to a solid support at their 5' ends, copies of the immobilized nucleic acid complements can be generated by performing nucleic acid amplification, such as primer extension, thermal polymerase chain reaction (thermal PCR), isothermal polymerase chain reaction (isothermal PCR), or other nucleic acid amplification methodologies (interpreting the amplification process to comprise PCR, claim 36) (col 18, lines 2-8).
Regarding claim 38, Kersey teaches that nucleic acid amplification of one or a plurality of copies of an immobilized nucleic acid template and/or of an immobilized nucleic acid complement of a template, such as at a substantially central location within a nucleic acid cluster as provided herein, can be performed using one or more oligonucleotide primers having their 5' ends immobilized to a solid support, such that each amplification cycle comprises a melting, annealing, and polymerase-driven, template-directed (or complement-directed) extension step usually carried out at differing temperatures in the presence of a thermostable polynucleotide polymerase, nucleotide precursors to be incorporated by extension, and co-factors and ancillary reagents as will be familiar to those skilled in the art (interpreted as annealing, and generating immobilized strands by extending primers, claim 38) (col 18, lines 2-8). Kersey teaches that the attachment is typically of sufficient strength that it cannot be removed by washing with water or aqueous buffer under DNA-denaturing conditions (interpreted as denaturing, and washing, claim 38) (col 30, lines 30-32). Kersey teaches that after completion of the attachment process, the strands can desirably be separated, for example, by heating to 94 °C. or by using a suitable chemical denaturant (e.g., about 0.1 to about 0.5N NaOH), before washing the released strands away (interpreted as denaturing, and washing, claim 38) (col 35, lines 38-42).
Regarding claims 41 and 48, Kersey teaches that surface or bridge amplification occurs when, on a solid support, an immobilized nucleic acid template or nucleic acid complement hybridizes to an immobilized colony primer X, wherein the 3' end of the immobilized nucleic acid template or immobilized nucleic acid complement provides the template for a polymerase-catalyzed, template-directed elongation reaction (e.g., primer extension) extending from the complementary and immobilized colony primer X, such that the resulting double-stranded product "bridges" the two colony primers, and both strands are covalently attached to the support; and in the next cycle, following denaturation that yields a pair of single strands (the immobilized template and the extended-primer product) immobilized to the solid support, both immobilized strands can serve as templates for new primer extension, thereby providing a mechanism for nucleic acid cluster formation (interpreted as performing surface or bridge amplification, claims 41 and 48) (col 39, lines 42-58).
Regarding claim 45, Kersey teaches that primer extension comprises the 5' to 3' extension of an oligonucleotide primer hybridized to a target nucleic acid, wherein primer extension can be performed using, but does not require, thermocycling (e.g., temperature fluctuations that permit alternating periods of temperatures conducive to nucleic acid hybridization, and temperatures conducive to denaturation of nucleic acid duplexes, typically in the presence of a thermostable polynucleotide polymerase) and can also be conducted at static (e.g., substantially invariant or isothermal) temperature, for example, when using a DNA dependent polymerase such as Taq DNA polymerase for primer extension including at a temperature of 72oC (interpreting Taq DNA polymerase to have exonuclease activity; incubating; and interpreting thermocycling as multiple phases of PCR to generate clusters, claim 45) (col 40, lines 35-46), where it is known that Taq DNA polymerase is useful in PCR due to its 5’-3’ exonuclease activity as evidenced by Wang (paragraph [0162]).
Kersey meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Claim Rejections - 35 USC § 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.
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.
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.
Claims 1, 3, 14, 36, 38, 41, 45 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Kersey et al. (hereinafter “Kersey”) (US Patent No. 9758825, issued September 12, 2017) in view of Stapleton et al. (hereinafter “Stapleton”) (US Patent Application Publication 20190276884, published September 12, 2019) as evidenced by Wang et al. (hereinafter “Wang”) (International Application WO2018186930, published October 11, 2018).
The teachings of Kersey as applied to claims 1, 3, 14, 36, 38, 41, 45 and 48 are described supra.
Kersey does not specifically exemplify the use of an exonuclease enzyme (claim 45, in part).
Regarding claim 45 (in part), Stapleton teaches methods for obtaining nucleic acid sequence information by constructing a nucleic acid library and reconstructing longer nucleic acid sequences by assembling a series of shorter nucleic acid sequences (Abstract). Stapleton teaches that asymmetric adapters are ligated to each end of the molecules, such that limited-cycle PCR is performed with a first primer complementary to the asymmetric adapter and the second primary complementary to the internal annealing sequence from the tripartite adapter, wherein the primers add the full sequencing adapter sequences to the PCR product, wherein only molecules containing internal annealing sequences and barcodes are exponentially amplified in the PCR (interpreted as amplification; and PCR) (paragraph [0071]). Stapleton teaches that the asymmetric adapter comprises two oligonucleotides, one of which is longer than the other, wherein the shorter oligonucleotide is complementary to the longer oligonucleotide and, upon annealing, creates a ligation-competent adapter with a 3' dT-tail suitable for specific ligation to the A-tailed fragment; and the adapter sequence is complementary to a PCR primer that adds a second sequencing primer sequence (e.g., Illumina) by overlap-extension PCR, but only the longer of the two oligonucleotides is long enough to productively anneal to this primer during PCR such that as a result, following ligation of an asymmetric adapter to both ends of a fragment each of the two strands of the fragment has an annealing-competent sequence at only one end (interpreted as comprising a poly-T sequence; and ligating adaptors to both ends of the nucleic acid fragment) (paragraph [0098]). Stapleton teaches that an adapter is attached to the nucleic acid following end-repair and any of dT-tailing, dA-tailing, dG-tailing, or dC-tailing (interpreted as adaptors comprising a poly-T or a poly-A tail, claim 14) (paragraph [0108], lines 5-7). Stapleton teaches that the adapters were ligated at both ends of the DNA, wherein a single adapter is ligated to each end of the nucleic acid by including an overhang on the 3' strand of the non-ligating end, thus blocking concatamerization on the end of the adapter, such that library molecules that failed to ligate to an adapter at both ends were removed by incubation with 10 units of exonuclease III and 20 units of exonuclease I (NEB) in NEBuffer 1 for 45 minutes at 37° C., followed by 20 minutes at 80° C (interpreted as incubating with an exonuclease, claim 45) (paragraph [0266]). Stapleton teaches that DNA at a final concentration of 1 ng/µL was mixed with 3000 units of T4 DNA ligase and T4 DNA ligase buffer to IX, and incubated at 16° C. for 16 hours; and linear DNA was digested by the addition of 10 units of T5 exonuclease and incubation at 37o C for 1 hour (interpreted as incubating with an exonuclease, claim 45) (paragraph [0271]). Stapleton teaches that DNA fragments created by linear or exponential amplification contain known end sequences that are reverse complements of each other and contain one or more deoxyuracil bases in the 5' ends, such that a combination of uracil-DNA glycosylase (UDG) and exonuclease VIII can then be used to remove the 5' ends, leaving long single-stranded complimentary sequences that can anneal to increase the efficiency of intramolecular circularization, wherein treatment with UDG and exonuclease VIII is preceded by treatment with Klenow fragment or a similar enzyme to remove non-templated deoxyadenosine bases added to the 3' ends during extension (interpreted as incubating with an exonuclease, claim 45) (paragraph [0306]).
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 removing unused primers from PCR reaction products as exemplified by Stapleton, it would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to modify the high-throughput method for nucleic acid amplification, detection, and sequencing including a solid-phase amplification method such as bridge amplification as disclosed by Kersey to include the method of incubating PCR products with an exonuclease such as exonuclease I, T5 exonuclease, and/or exonuclease VIII as taught by Stapleton with a reasonable expectation of success in amplifying nucleic acids and generating nucleic acid clusters on a support, wherein the clusters have a substantially central location marked by a detectable label; in preparing DNA fragments for NGS sequencing by removing library molecules that fail to ligate to an adaptor at both ends; and/or in blocking concatamererization on the end of an adaptor to ensure accurate clonal amplification.
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.
Conclusion
Claims 1, 3, 14, 36, 38, 41, 45 and 48 are rejected.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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