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 .
Claims 1-19 are currently pending and under examination.
Information Disclosure Statement
The Information Disclosure Statements filed November 21, 2023; March 11, 2025; and April 01, 2026 have been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1),
1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response – Applicant must:
Amend the Sequence Listing Incorporation by Reference paragraph at page 1 of the
specification. It is noted the Sequence Listing Incorporation by Reference paragraph lists the size of the ASCII text file as 2 kilobytes, whereas the ASCII text file itself lists the size as 1,591 bytes.
Specification
The use of the terms USER®, NEBNext®, MiSeq™ (see, Page15, Line 2, Page 20, Line 30, Page 20, Lines 3 and 4), which are trade names or a marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1, 6, 8 and 12 are objected to because of the following informalities:
In claim 1, line 7, “the end of the products” should read “an end of the products”.
In claim 6, lines 1-2, “the sequences of multiple fragments”, should read “the sequences of fragments”.
In claim 8, line 4, “or an amplification product thereof” should read “or amplification products thereof”.
In claim 12, lines 8-9, “the two molecules”, should read “the two identical molecules”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-13 and 16-19 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is considered vague and indefinite for the following reasons:
Claim 1 recites the limitation "the support" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the products" in line 7. There is insufficient antecedent basis for this limitation in the claim.
Claims 2-11 depend from claim 1 and are therefore included in this rejection.
Claim 2 is considered vague and indefinite for the following reasons:
In claim 2, the terms “cleaving the ends off the products”, in lines 3-6, is unclear and confusing. It is unclear as to which ends are being cleaved off the products; is this both/all/any ends or a specific end?
Claim 2 recites the limitation "the products" in lines 3-6. There is insufficient antecedent basis for this limitation in the claim.
Claim 2 recites the limitation "the stranded amplification products" in lines 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 3 is considered vague and indefinite for the following reasons:
Claim 3 recites the limitation "the support" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 4-6 depend from claim 3 and are therefore included in this rejection.
Claim 4 is considered vague and indefinite for the following reasons:
Claim 4 recites the limitation "the released transposomes" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 5-6 depend from claim 4 and are therefore included in this rejection.
Claim 5 is considered vague and indefinite for the following reasons:
Claim 5 recites the limitation "the tagmentation products" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 depends from claim 5 and is therefore included in this rejection.
Claim 8 is considered vague and indefinite for the following reasons:
Claim 8 recites the limitation "the support" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the tagmentation products" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claims 9-11 depend from claim 8 and are therefore included in this rejection.
Claim 9 is considered vague and indefinite for the following reasons:
Claim 9 recites the limitation "the support" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claims 10-11 depend from claim 9 and are therefore included in this rejection.
Claim 10 is considered vague and indefinite for the following reasons:
Claim 10 recites the limitation "the support" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 depends from claim 10 and is therefore included in this rejection.
Claim 12 is considered vague and indefinite for the following reasons:
Claim 12 recites the limitation "the support" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claims 13, 16-19 depend from claim 12 and are therefore included in this rejection.
Claim 19 is considered vague and indefinite for the following reasons:
Claim 19 recites the limitation "the assembled sequence" in line 1. There is insufficient antecedent basis for this limitation in the claim.
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 (i.e., changing from AIA to pre-AIA ) 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 1-19 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Shendure et al. (U.S. Patent Application Publication US 2013/0203605 A1, published August 08, 2013), cited on the IDS filed April 01, 2026.
Regarding claim 1, Shendure teaches method for producing a population of symmetrically barcoded transposomes (Page 2, [0016], Page 5, [0065], Page 10, [0113]-[0115] and Page 11, [0121]-[0123]). Shendure teaches amplifying a template that contains a randomized sequence and a transposon end sequence on a solid support by bridge polymerase chain reaction (PCR) to produce uniquely barcoded clusters of single-stranded amplification products that are tethered to the support (Pages 1-2, [0008]-[0013], Page 2, [0016] and [0020]-[0021], Page 4, [0051] and [0055], Page 5, [0061]-[0063], Pages 6-7, [0077]-[0079], Page 9, [0103], Page 10, [0114]-[0117], Page 11, [0122], Pages 11-12, [0132], Page 13, [0160], Page 14, [0165]-[0172], Page 16, [0196], Page 21, [0250]-[0254] and [0257] and Fig. 8). Shendure teaches processing the single-stranded amplification products so that the transposon end sequence is double-stranded and at the end of the products (Page 7, [0081], Page 11, [0122], Page 14, [0166] and Figs. 9-10). Shendure teaches adding transposase to the support under conditions by which the transposase binds to the double-stranded transposon end sequences, to produce the population of symmetrically barcoded transposomes (Page 2, [0016], Page 5, [0065], Page 10, [0113]-[0115], Page 11, [0121]-[0123] and Page 14, [0165]-[0172]).
Regarding claim 2, Shendure teaches extending a primer using the single stranded amplification products as a template to produce double stranded products and then cleaving the ends off the products using a restriction enzyme (Page 9, [0095]-[0096], Page 11, [0122], Page 12, [0144], Page 15, [0183]-[0184] and Fig. 19).
Regarding claim 3, Shendure teaches releasing the population of symmetrically barcoded transposomes from the support after step (c) (Pag 11, [0123], Page 15, [0181]-[0184], and Page 20, [0239]).
Regarding claim 4, Shendure teaches performing a tagmentation reaction using the released transposomes (Page 3, [0048], Page 8, [0093], Page 11, [0126] and Page 21-22, [0256]-[0257]).
Regarding claim 5, Shendure teaches sequencing the tagmentation products to produce sequence reads, wherein the sequence reads comprise sequences of fragments that comprise a barcode derived from the randomized sequence (Page 2, [0021], Page 4, [0058], Page 6, [0077]-[0078] and Page 11, [0122]).
Regarding claim 6, Shendure teaches assembling the sequences of multiple fragments into a longer sequence using the barcodes (Page 11, [0126], Page 3, [0039], Page 5, [0065] and [0069] and Page 6, [0077]).
Regarding claim 7, Shendure teaches sequencing the unique barcodes of each of the clusters between steps (a) and (c) (Page 5, [0063] and Page 6, [0077]-[0079]).
Regarding claim 8, Shendure teaches the sequencing provides a spatial coordinate for each the sequenced barcodes (Page 2, [0009]-[0010], Page 4, [0058] and Page 5, [0062]-[0063]). Shendure teaches the method further comprises performing a tagmentation reaction on a planar biological sample that is placed on the support (Page 1, [0008], Page 3, [0048], Page 8, [0093], Page 11, [0126], Page 14, [0166], Page 21-22, [0256]-[0257] and Page 24, [0287]). Shendure teaches releasing the barcoded transposomes from the support, and then sequencing the tagmentation products, or an amplification product thereof (Pag 11, [0123], Page 15, [0181]-[0184], Page 20, [0239], Page 2, [0009]-[0010], Page 4, [0058] and Page 5, [0062]-[0063]).
Regarding claim 9, Shendure teaches tagmentation products are tethered to the support, and the method comprises amplifying the tagmentation products, collecting the amplification products, and sequencing the amplification products (Page 12, [0154], Page 13, [0158] and Page 15, [0179]).
Regarding claim 10, Shendure teaches mapping a sequence to a site on the support using the barcode associated with the sequence and the spatial coordinates for that barcode (Page 2, [0009]-[0010], Page 4, [0058] and Page 5, [0062]-[0063])..
Regarding claim 11, Shendure teaches constructing an image of the sample (Page 2, [0025]-[0026] and Page 3, [0047]).
Regarding claim 12, Shendure teaches a substrate comprising clusters of transposomes (Page 6, [0075], Page 14, [0169]-[0170] and [0175], Page 15, [0183]-[0184] and Page 16, [0192]). Shendure teaches two identical molecules of amplification product that each have a proximal end that is tethered to the support, a barcode sequence, and a distal end that comprises a double-stranded transposon end sequence (Page 1, [0007]-[0011], Page 2, [0016] and [0020], Page 2, [0030], Page 10, [0115]-[0116], Page 11, [0122], Page 13, [0160], Page 8, [0094], Fig. 3 and Example 2). Shendure teaches the barcode sequence is the same for the transposomes within a cluster but different for transposomes in different clusters (Page 1, [0007]-[0011], Page 2, [0016] and [0020], Page 2, [0030], Page 10, [0114]-[0117], Page 11, [0122], Page 13, [0160], Page 8, [0094], Fig. 3 and Example 2). Shendure teaches a transposase, wherein the transposase is bound to the transposon end sequences of the two molecules of amplification product of (a) (Pages 9-10, [0110] and Page 10, [0114]-[0117]).
Regarding claim 13, Shendure teaches the substrate comprises at least 1M of said clusters (Page 24, [0289]).
Shendure teaches each and every limitation of claims 1-13 and therefore Shendure anticipates claims 1-13.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 14-19 are rejected under 35 U.S.C. as being unpatentable over Shendure et al. (U.S. Patent Application Publication US 2013/0203605 A1, published August 08, 2013), cited on the IDS filed April 01, 2026, as applied to claims 1-13 above, in view of Gormley et al. (U.S. Patent Application Publication US 2015/0284714 A1, published October 08, 2015), cited on the IDS filed November 21, 2023.
Regarding claims 14 and 15, Shendure teaches a population of symmetrically barcoded transposomes (Page 2, [0016], Page 5, [0065], Page 10, [0113]-[0115] and Page 11, [0121]-[0123]). Shendure teaches each transposome comprises a transposase and two identical molecules of nucleic acid that each comprise a barcode sequence and a double- stranded transposon end sequence (Page 1, [0007]-[0011], Page 2, [0016] and [0030], Page 5, [0065], Page 10, [0113]-[0116] and Page 11, [0121]-[0123]). Shendure teaches the population comprises different barcode sequences (Page 15, [0182], Page 12, [0151]-[0152]).
Regarding claim 16, Shendure teaches a method comprising tagmenting a nucleic acid sample (Page 3, [0048], Page 8, [0093], Page 11, [0126], Page 21-22, [0256]-[0257], Page 2, [0016], Page 5, [0065], Page 10, [0113]-[0115] and Page 11, [0121]-[0123]). Shendure teaches the nucleic acid sample with the substrate of claim 12 as discussed above.
Regarding claim 17, Shendure teaches comprising sequencing the tagmentation products to produce sequences of fragments appended to a barcode (Page 2, [0021], Page 4, [0058], Page 6, [0077]-[0078] and Page 11, [0122]).
Regarding claim 18, Shendure teaches assembling multiple fragment sequences into a longer sequence using the barcodes (Page 11, [0126], Page 3, [0039], Page 5, [0065] and [0069] and Page 6, [0077]).
Regarding claim 19, Shendure teaches the assembled sequence is a circular molecule (Page 12, [0149], Page 21, [0245] and Page 11, [0131]-[0132]).
Shendure does not explicitly teach or suggest the population comprises at least 1,000 different barcode sequences or at least 1 million different barcode sequences. Shendure does not teach or suggest a divalent cation to produce a reaction mix and incubating the reaction mix to tagment the nucleic acid sample.
Gormley teaches symmetrically barcoded transposomes (Page 13, [0114]). Gormley teaches a transposon end sequence bound to a solid support (Page 12, [0105] and [0110]). Gormley teaches the transposase is bound to the transposon end sequence (Abstract and Page 1, [0004]-[0008]). Gormley teaches amplifying the template as well as using bridge amplification to create clusters (Page 2, [0018] and Page 6, [0062]). Gormley teaches at least 1,000 different barcode sequences or at least 1 million different barcode sequences (Page 14, [0123]). Gormley teaches a divalent cation to produce a reaction mix and incubating the reaction mix to tagment the nucleic acid sample (Page 3, [0041], Page 15, [0139] and Claim 37). Gormley teaches using these methods provides several advantages over other solution based tagmentation methods such as intact DNA template can be loaded directly onto a flowcell for generation of clusters, without prior sample preparation, as well as the contiguity of sequence information in the original intact DNA can be physically preserved by the juxtaposition of tagmented fragments on the surface of the flowcell which further allows for providing rapid and efficient detection of polynucleotide targets as well as generating physical maps of immobilized polynucleotides which can be exploited to identify clusters (Page 3, [0035], Page 8, [0073] and Page 11, [0095]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Shendure with the teachings of Gormley to use at least 1 million different barcodes and a divalent cation to produce a reaction mix and incubating the reaction mix to tag the nucleic acid sample. Using these methods would allow for several advantages over other solution based tagmentation methods such as intact DNA template can be loaded directly onto a flowcell for generation of clusters, without prior sample preparation, as well as the contiguity of sequence information in the original intact DNA can be physically preserved by the juxtaposition of tagmented fragments on the surface of the flowcell which further allows for providing rapid and efficient detection of polynucleotide targets as well as generating physical maps of immobilized polynucleotides which can be exploited to identify clusters as taught by Gormley (Page 3, [0035], Page 8, [0073] and Page 11, [0095]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JESSICA D PARISI/ Examiner, Art Unit 1684
/HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684
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