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 1-20 are currently pending and under examination.
Priority
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-
(d) prior to declaration of an interference, a certified English translation of the foreign
application must be submitted in reply to this action. See MPEP 234.01 (c), 37 CFR 41.154(b)
and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the
non-English application.
It is acknowledged that the certified copy for CN 2020116282 was received, however there is no certified English translation.
Information Disclosure Statement
The Information Disclosure Statement filed July 14, 2023 has 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/PatentLegalFramework), 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 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d) (see Figs. 4B, 4C, 5B and 5C). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings (see Figs. 4B, 4C, 5B and 5C).
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 7 and 8 are objected to because of the following informalities:
In claim 7, lines 2-3, “the primer comprises the sequence selected from the sequences shown as Seq ID Nos:” should read “the primer comprises a sequence selected from SEQ ID NOs:”.
In claim 8, lines 5-6, “the sequencing adaptor comprises the sequence selected from the sequences shown as Seq ID Nos:” should read “the sequencing adaptor comprises a sequence selected from SEQ ID NOs:”.
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 1-20 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 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 multiplex PCR product" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
Claims 2-6 and 11-20 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, line 3, the term “and the like”, in line is unclear. It is unclear as to what “and the like” is meant to encompass, therefore the metes and bounds of the claim are unclear.
Claims 11-12, 14 and 17 depend from claim 2 and are therefore included in this rejection.
Claim 9 is considered vague and indefinite for the following reasons:
Claim 9 recites the limitation "the 5’ sticky end" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the 3’ sticky end" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 depends from claim 9 and is therefore included in this rejection.
Claim 10 is considered vague and indefinite for the following reasons:
In claim 10, line 3, the term “and the like”, in line is unclear. It is unclear as to what “and the like” is meant to encompass, therefore the metes and bounds of the claim are unclear.
Claim 10 recites the limitation "the 5’ sticky end" in lines 6-7. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "the 3’ sticky end" in lines 6-7. There is insufficient antecedent basis for this limitation in the claim.
Additionally, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “one or more of a modified nucleotide”, and the claim also recites “preferably, the modified nucleotide comprises one or more of dUTP, dITP and an RNA base.” which is the narrower statement of the range/limitation. Additionally claim 5, recites the broad recitation “the MoCODE barcode has a length of 2-20 nt”, and the claim also recites “preferably, the MoCODE barcode decoding sequence is complementary to a MoCODE barcode sequence, having a length of 2-20 nt” which is the narrower statement of the range/limitation. Additionally, claim 6, recites the broad recitation “the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment”, and the claim also recites “preferably, each sequencing adaptor may be a single adaptor and a bidirectional adaptor” as well as “preferably, enrichment in each specific segment may be decoded by virtue of the single adaptor, the bidirectional adaptor or automatic cyclization”, which is a narrower statement of the range/limitation. Additionally, claim 7, recites the broad recitation “the primer comprises a MoCODE barcode generating sequence”, and the claim also recites “preferably, the primer comprises the sequence selected from sequences shown as Seq ID Nos: 1-22, 27-52, 53, 55, 57-104, 109 and 111”, which is the narrower statement of the range/limitation. Additionally claim 8, recites the broad recitation “the sequencing adaptor comprises a MoCODE barcode decoding sequence” and the claim also recites “preferably, the sequencing adaptor further comprises one or more of a sequencing adaptor of a sequencing platform and an index label” and “preferably, the sequencing adaptor comprises a universal sequence for high-throughput sequencing, an index label and a MoCODE barcode decoding sequence” as well as “preferably, the sequencing adaptor comprises the sequence selected from sequences shown as Seq ID Nos: 23-26, 54, 56, 105-108, 110 and 112”, which is a narrower statement of the range/limitation. Additionally claim 9, recites the broad recitation “each primer, participating to the multiplex PCR reaction, comprising a specific MoCODE barcode generating sequence”, and the claim also recites “ preferably, the primer further comprising a gene-specific sequence”, which is a narrower statement of the range/limitation. Additionally claim 10, recites the broad recitation “a generation mode of the MoCODE barcode comprises one or more of a modified nucleotide”, and the claim also recites “preferably, the modified nucleotide comprises one or more of dUTP, dITP and an RNA base” and “more preferably, the generation mode of the MoCODE barcodes is to use a specific endonuclease for digestion” and “preferably, in step 4), one MoCODE barcode is generated at each of the 5' sticky end and the 3' sticky end, wherein the MoCODE barcodes at the 5' sticky end and the 3' sticky end may be same or different” as well as “preferably, in step 6), each sequencing adaptor may be a single adaptor, a bidirectional adaptor or a cyclization adaptor”, which is the narrower statement of the range/limitation. Additionally claim 14, recites the broad recitation “the MoCODE barcode has a length of 2-20 nt”, and the claim also recites “the MoCODE barcode has a length of 2-20 nt, and preferably, the MoCODE barcode decoding sequence is complementary to a MoCODE barcode sequence, having a length of 2-20 nt” which is the narrower statement of the range/limitation. Additionally claim 15, recites the broad recitation “the MoCODE barcode has a length of 2-20 nt”, and the claim also recites “the MoCODE barcode has a length of 2-20 nt, and preferably, the MoCODE barcode decoding sequence is complementary to a MoCODE barcode sequence, having a length of 2-20 nt” which is the narrower statement of the range/limitation. Additionally claim 16, recites the broad recitation “the MoCODE barcode has a length of 2-20 nt”, and the claim also recites “the MoCODE barcode has a length of 2-20 nt, and preferably, the MoCODE barcode decoding sequence is complementary to a MoCODE barcode sequence, having a length of 2-20 nt” which is the narrower statement of the range/limitation. Additionally claim 17, recites the broad recitation “the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment”, and the claim also recites “preferably, each sequencing adaptor may be a single adaptor and a bidirectional adaptor” as well as “preferably, enrichment in each specific segment may be decoded by virtue of the single adaptor, the bidirectional adaptor or automatic cyclization”, which is a narrower statement of the range/limitation. Additionally claim 18, recites the broad recitation “the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment”, and the claim also recites “preferably, each sequencing adaptor may be a single adaptor and a bidirectional adaptor” as well as “preferably, enrichment in each specific segment may be decoded by virtue of the single adaptor, the bidirectional adaptor or automatic cyclization”, which is a narrower statement of the range/limitation. Additionally claim 19, recites the broad recitation “the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment”, and the claim also recites “preferably, each sequencing adaptor may be a single adaptor and a bidirectional adaptor” as well as “preferably, enrichment in each specific segment may be decoded by virtue of the single adaptor, the bidirectional adaptor or automatic cyclization”, which is a narrower statement of the range/limitation. Additionally claim 20, recites the broad recitation “the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment”, and the claim also recites “preferably, each sequencing adaptor may be a single adaptor and a bidirectional adaptor” as well as “preferably, enrichment in each specific segment may be decoded by virtue of the single adaptor, the bidirectional adaptor or automatic cyclization”, which is a narrower statement of the range/limitation.
These claims are considered indefinite because there is a question or doubt as to
whether the feature introduced by such narrower language is (a) merely exemplary of the
remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 11-12, 14 and 17 depend from claim 2 and are therefore included in this rejection. Claim 20 depends from claim 5 and is therefore included in this rejection. Claim 10 depends from claim 9 and is therefore included in this rejection.
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 1-20 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Stapleton et al. (U.S. Patent Application Publication US 2019/0276884 A1, published September 12, 2019.
Regarding claim 1, Stapleton teaches a method for constructing a multiplex PCR library for high-throughput targeted sequencing (Abstract, Page 1, [0007], Page 5, [0068], Page 29, [0277]-[0278] and [0280] and Example 9). Stapleton teaches by adding polybasic MoCODE barcodes to a specific amplification product, and using the MoCODE barcodes to efficiently ligating the amplification product to sequencing adaptors comprising MoCODE barcode decoding sequences (Page 1, [0007], Pages 1-2, [0010], Page 2, [0013]-[0014], Page 3, [0027], Page 6, [0073] and Page 12, [0117]. Stapleton teaches the MoCODE barcodes refer to overhanging single-stranded nucleotide sequences constituting two sticky ends of an obtained PCR product after the multiplex PCR product is digested with a specific endonuclease (Page 13, [0125], Page 16, [0148], Pages 19-20, [0191], Page 21, [0205], Page 29, [0277], Page 2 , [0013]-[0014], Page 6, [0074], Page 8, [0091], Page 10, [0104]-[0105] and Page 12, [0117]-[0118]). Stapleton teaches the MoCODE barcode decoding sequences are nucleotide sequences complementary to the MoCODE barcodes (Page 2, [0013]-[0014] and Page 6, [0073]).
Regarding claim 2, Stapleton teaches a generation mode of the MoCODE barcodes comprises one or more of: a modified nucleotide, a nicking enzyme, an endonuclease, chemical modification, base photodegradation (Page 6, [0073]-[0074], Page 10, [0105], Page 24, [0230] and Page 33, [0308]).
Regarding claim 3, Stapleton teaches the MoCODE barcodes may be the same or different within molecules (Page 1, [0009], Page 2, [0026], Page 5, [0059] and [0070], Page 9, [0095], Pages 9-10, [0100], Page 10, [0102], [0104] and [0106] and Page 11, [0109]).
Regarding claim 4, Stapleton teaches the MoCODE barcodes are non-random specific barcodes (Pages 9-10, [0100] and Page 18, [0184]).
Regarding claim 5, Stapleton teaches the MoCODE barcode has a length of 2-20 nt (Pages 9-10, [0100]).
Regarding claim 6, Stapleton teaches the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment (Page 3, [0027], Page 5, [0072], Page 8, [0091], page 10, [0101], Pages 10-11, [0108], Page 13, [0129], Page 16, [0148] and Page 19, [0187]).
Regarding claim 7, Stapleton teaches a primer for multiplex PCR for high-throughput targeted sequencing (Abstract, Page 1, [0007], Page 5, [0068], Page 10, [0101], Page , [0112], Page 29, [0277]-[0278] and [0280] and Example 9). Stapleton teaches the primer comprises a MoCODE barcode generating sequence (Pages 1-2, [0010]-[0011], Page 6, [0075], Pages 16-17, [0149] and Page 24, [0230]).
Regarding claim 8, Stapleton teaches a sequencing adaptor for multiplex PCR for high-throughput targeted sequencing (Abstract, Page 1, [0007], Page 5, [0068], Page 5, [0071], Page 10, [0101], Page , [0112], Page 29, [0277]-[0278] and [0280] and Example 9). Stapleton teaches the sequencing adaptor comprises a MoCODE barcode decoding sequence (Page 13, [0125], Page 16, [0148], Pages 19-20, [0191], Page 21, [0205], Page 29, [0277], Page 2 , [0013]-[0014], Page 6, [0074], Page 8, [0091], Page 10, [0104]-[0105] and Page 12, [0117]-[0118]).
Regarding claim 9, Stapleton a method for constructing a multiplex PCR library for high-throughput targeted sequencing (Abstract, Page 1, [0007], Page 5, [0068], Page 29, [0277]-[0278] and [0280] and Example 9). Stapleton teaches extracting DNA from a to-be-tested specimen (Page 25, [0240]). Stapleton teaches performing a multiplex PCR reaction, each primer, participating to the multiplex PCR reaction, comprising a specific MoCODE barcode generating sequence (Pages 1-2, [0010]-[0011], Page 2, [0014], Page 10, [0101], Page 13, [0125], Page 16, [0148], Pages 19-20, [0191], Page 21, [0205], Page 29, [0277]-[0278]). Stapleton teaches purifying a PCR product with magnetic beads (Page 15, [0145]-[0146], Page 19, [0189], Page 28, [0269]-[0272], Pages 28-29, [0274], Page 29, [0278] and Page 33, [0305]). Stapleton teaches generating a 5' sticky end and a 3' sticky end, and generating MoCODE barcodes at the 5' sticky end and the 3' sticky end respectively (Page 2, [0013], Page 10, [0104], Page 13, [0125], Page 16, [0148], Pages 19-20, [0191], Page 20, [0194], Pages 20-21, [0202]-[0205], Page 29, [0277], Page 2, [0013]-[0014], Page 6, [0074], Page 8, [0091], Page 10, [0104]-[0105], Page 12, [0117]-[0118] and Page 34, [0311]). Stapleton teaches purifying the PCR product comprising the MoCODE barcodes with the magnetic beads (Page 15, [0145]-[0146], Page 19, [0189], Page 28, [0269]-[0272], Pages 28-29, [0274], Page 29, [0278] and Page 33, [0305]). Stapleton teaches ligating the PCR product, comprising the MoCODE barcodes, to the sequencing adaptors, the sequencing adaptor comprising MoCODE barcode decoding sequences complementary to the MoCODE barcodes ((Page 13, [0125], Page 16, [0148], Pages 19-20, [0191], Page 21, [0205], Page 29, [0277], Page 2 , [0013]-[0014], Page 6, [0074], Page 8, [0091], Page 10, [0104]-[0105], Page 12, [0117]-[0118], Page 2, [0013]-[0014] and Page 6, [0073]). Stapleton teaches purifying a ligation product with the magnetic beads, and completing construction of the multiplex PCR library for high-throughput targeted sequencing (Page 15, [0145]-[0146], Page 19, [0189], Page 28, [0269]-[0272], Pages 28-29, [0274], Page 29, [0278] and [0280], Pages 30-31, [0285] and Page 33, [0305]).
Regarding claim 10, Stapleton a generation mode of the MoCODE barcode comprises: one or more of a modified nucleotide, a nicking enzyme, an endonuclease, chemical modification, base photodegradation (Page 6, [0073]-[0074], Page 10, [0105], Page 24, [0230] and Page 33, [0308]).
Regarding claim 11, Stapleton teaches the MoCODE barcodes may be the same or different within molecules (Page 1, [0009], Page 2, [0026], Page 5, [0059] and [0070], Page 9, [0095], Pages 9-10, [0100], Page 10, [0102], [0104] and [0106] and Page 11, [0109]).
Regarding claim 12, Stapleton teaches the MoCODE barcodes are non-random specific barcodes (Pages 9-10, [0100] and Page 18, [0184]).
Regarding claim 13, Stapleton teaches the MoCODE barcodes are non-random specific barcodes (Pages 9-10, [0100] and Page 18, [0184]).
Regarding claim 14, Stapleton teaches the MoCODE barcode has a length of 2-20 nt (Pages 9-10, [0100]).
Regarding claim 15, Stapleton teaches the MoCODE barcode has a length of 2-20 nt (Pages 9-10, [0100]).
Regarding claim 16, Stapleton teaches the MoCODE barcode has a length of 2-20 nt (Pages 9-10, [0100]).
Regarding claim 17, Stapleton teaches the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment (Page 3, [0027], Page 5, [0072], Page 8, [0091], page 10, [0101], Pages 10-11, [0108], Page 13, [0129], Page 16, [0148] and Page 19, [0187]).
Regarding claim 18, Stapleton teaches the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment (Page 3, [0027], Page 5, [0072], Page 8, [0091], page 10, [0101], Pages 10-11, [0108], Page 13, [0129], Page 16, [0148] and Page 19, [0187]).
Regarding claim 19, Stapleton teaches the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment (Page 3, [0027], Page 5, [0072], Page 8, [0091], page 10, [0101], Pages 10-11, [0108], Page 13, [0129], Page 16, [0148] and Page 19, [0187]).
Regarding claim 20, Stapleton teaches the sequencing adaptor may be artificially designed and synthesized or matched with an own fragment sequence of a target segment (Page 3, [0027], Page 5, [0072], Page 8, [0091], page 10, [0101], Pages 10-11, [0108], Page 13, [0129], Page 16, [0148] and Page 19, [0187]).
Stapleton teaches each and every limitation of claims 1-20, therefore Stapleton anticipates claims 1-20.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
Prosecution Insights