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 .
Applicant cancels claims 16, 19-45 and 49-141. Claims 1-15, 17-18 and 46-48 are currently pending and under examination.
Information Disclosure Statement
The Information Disclosure Statement filed November 26, 2025 has been considered.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: In Figure 2, reference 208 is missing from the specification . Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see Page 11, [064]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term NEBNext® (Page 20, [0135], Page 22, [0146] and [0148], Page 51, [0305], Page 52, [0312], Page 53, [0316], Page 65, [0383] and [0386], and Examples 5 and 7). , which is a trade name or a mark 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
Claim 1 is objected to because of the following informalities:
In claim 1, lines 15 and 16, the terms “the 5’ and 3’ end” should read “5’ and 3’ ends”. Appropriate correction is required.
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, 3-6, 8, 10-15, 17 and 46-47 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Langmore et al. (U.S. Patent Application Publication US 2006/0068394 A1, published March 30, 2006), cited on the IDS filed November 26, 2025.
Regarding claim 1, Langmore teaches a method of preparing a library of nucleic acids (Title, Page 1, [0004] and [0010] and Page 3, [0031]). Langmore teaches providing a sample of nucleic acids comprising at least one sequence of interest (i.e., target; Page 20, [0280], Page 30, [0364] and Pages 7-8, [0082]-[0086]). Langmore teaches blocking 3' ends of the nucleic acids, thereby preventing polymerase extension of the 3' ends (Page 1, [0013]-[0014], Page 6, [0059], Page 8, [0084] and Page 15, [0159]-[0160]). Langmore teaches contacting the sample of nucleic acids with a plurality of first polymerase chain reaction (PCR) primers, and a first polymerase under conditions that allow PCR to occur, thereby generating a plurality of first single-sided PCR products (Pages 1-2, [0013]-[0017], Page 4, [0037], Page 5, [0052], Page 13, [0143], Page 18, [0217]-[0219], Page 27, [0327], Page 35, [0426] and Page 41, [0558]-[0559]). Langmore teaches contacting the plurality of first single-sided PCR products with a terminal transferase and dNTPs under conditions sufficient to transfer dNTPs to the 3' ends of the plurality of first single-sided PCR products, thereby generating a plurality of PCR products comprising 3' tails (Pages 1-2, [0013]-[0017], Page 4, [0037], Page 5, [0052], Page 13, [0143], Page 15, [0156], Page 18, [0217]-[0219], Page 27, [0327], Page 35, [0426], Page 41, [0558]-[0559], Page 48, [0686], Page 49, [0703], Page 57, [0845]-[0847] and Examples 8-13, 21, 24 and 28). Langmore teaches contacting the plurality of PCR products comprising 3' tails with a plurality of second PCR primers and the first polymerase under conditions that allow PCR to occur (Page 2, [0016]-[0017], Page 8, [0089], Page 11, [0122], Page 16, [0163]-[0164], Page 45, [0646], Page 48, [0689], Langmore teaches generating a library of nucleic acids with adapters at the 5' and 3' ends (Title, Page 1, [0004] and [0010], Page 3, [0031]Page 9, [0097], Page 12, [0138], Page 13, [0142], Page 33, [0393], Pag 35, [0419], Page 36, [0471], Page 42, [0577], Page 47, [0682] and Page 52, [0758]).
Regarding claim 3, Langmore teaches the plurality of first PCR primers comprises a sequence complementary to a sequence adjacent to or overlapping the at least one sequence of interest, and a first adapter sequence (Pages 7-8, [0083], Page 16, [0164], Page 20, [0281], Page 77, [1028] and Page 10, [0107]).
Regarding claim 4, Langmore teaches the first adapter sequence is 5' of the sequence complementary to the sequence adjacent to or overlapping the at least one sequence of interest (Page 16, [0164], Page 20, [0281], Page 77, [1028] and Page 10, [0107]).
Regarding claim 5, Langmore teaches the 3' tail is a polyA tail, a polyG tail, a polyC tail or a polyT tail (Page 20, [0285], Page 57, [0847], Page 71, [0994] and Example 30).
Regarding claim 6, Langmore teaches the sequence complementary to a sequence adjacent to or overlapping the at least one sequence of interest is a random sequence (Page 7, [0073]).
Regarding claim 8, Langmore teaches the plurality of first PCR primers comprises at least one base-pair comprising a phosphorothioate linkage (Page 1, [0014], Page 19, [0274] and Page 34, [0405]).
Regarding claim 10, Langmore teaches isothermal amplification reactions (Page 7, [0082] and Page 26, [0315]-[0318]).
Regarding claim 11, Langmore teaches the first polymerase is Phi29, Klenow exo- or Bsu DNA Polymerase, Large Fragment (Page 25, Table 2 and [0299]-[0300]).
Regarding claim 12, Langmore teaches the plurality of second PCR primers comprises a sequence complementary to the 3' tails and a second adapter sequence (Page 2, [0016]-[0017], Page 77, [1028], Page 11, [0124] and Page 12, [0138]).
Regarding claim 13, Langmore teaches the second adapter sequence is 5' of the sequence complementary to the 3' tail (Page 2, [0016]-[0017], Page 10, [0107], Page 16, [0164], Page 20, [0281],Page 77, [1028], Page 11, [0124] and Page 12, [0138]).
Regarding claim 14, Langmore teaches the 3' tails comprise polyG tails, and wherein the sequence complementary to the 3' tail comprises polyC (Page 2, [0017] and Page 15, [0156]).
Regarding claim 15, Langmore teaches the plurality of second PCR primers comprises at least one base-pair comprising a phosphorothioate linkage (Page 1, [0014], Page 2, [0017], Page 8, [0089], Page 11, [0122], Page 19, [0274] and Page 34, [0405]).
Regarding claim 17, Langmore teaches is using an emulsion (Page 28, [0343]).
Regarding claim 46, Langmore teaches the sequence adjacent to the sequence of interest is within 1-25 nucleotides of the sequence of interest (Pages 7-8, [0083], Page 9, [0091], Page 26, [0306]-[0307], Page 30, [0359]).
Regarding claim 47, Langmore teaches the sequence of interest comprises a single nucleotide polymorphism (SNP), a miniSTR (mini short tandem repeat), a mitochondrial marker, a Y chromosome marker, a taxonomic marker, or a disease trait marker (Page 2, [0024], Page 7, [0079], Page 30, [0362], Page 46, [0650], Page 58, [0865]).
Langmore teaches every limitation of claims 1, 3-6, 8, 10-15, 17 and 46-47, therefore Langmore anticipates claims 1, 3-6, 8, 10-15, 17 and 46-47.
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 2, 7, 9, 18 and 48 are rejected under 35 U.S.C. as being unpatentable over Langmore et al. (U.S. Patent Application Publication US 2006/0068394 A1, published March 30, 2006), cited on the IDS filed November 26, 2025, as applied to claims 1, 3-6, 8, 10-15, 17 and 46-47 above, in view of Zhao et al. (U.S. Patent Application Publication US 2019/0085384 A1, published October 08, 2015), cited on the IDS filed November 21, 2023.
Regarding claim 2, Langmore teaches contacting the library of nucleic acids with a first and second primers under conditions that allow PCR to occur as discussed above. Langmore teaches a second polymerase (Page 2, [0018] and [0020], Page 9, [0096], Page 26, [0309] and Pages 24-25, [0297]-[0300]).
Regarding claim 7, Langmore teaches the random sequence as discussed above.
Regarding claim 9, Langmore teaches phosphorothioate linkages as discussed above.
Regarding claim 18, Langmore teaches a first and second primer as discussed above.
Regarding claim 48, Langmore teaches a disease trait marker as discussed above.
Langmore does not teach or suggest a plurality of first indexing primers, a plurality of second indexing primers and a second polymerase under conditions that allow PCR to occur. Langmore does not teach or suggest the random sequence is specifically a random 9mer. Langmore does not teach the plurality of first PCR primers comprises two 3' and two 5' base pairs comprising phosphorothioate linkages. Langmore does not teach or suggest first indexing primers comprise a sequence complementary to the first adapter and a first unique molecular identifier sequence (UMI). Langmore does not teach or suggest the disease trait marker comprises a marker for specifically for pathogenicity, virulence, resistance or strain identification.
Zhao teaches generating a library of nucleic acids (Page 1, [0002]-[0004], Page 12, [0145]-[0146] and Page 15, [0172]). Zhao teaches a blocking moiety on the 3’end that prevents polymerase extension (Page 27, [0315]). Zhao teaches a first indexing primers, a plurality of second indexing primers and a second polymerase under conditions that allow PCR to occur (Page 12, [0147], Page 16, [0185], Page 35, [0383]-[0384], Example 3 and Figs. 1B, 1G, 2A). Langmore does not teach or suggest the random sequence is specifically a random 9mer (i.e., the random sequence may be any selected number n of nucleotides; Page 4, [0073], Page 25, [0293] and Page 28, [0322]-[0324]). Zhao teaches Zhao teaches the plurality of first PCR primers comprises two 3' and two 5' base pairs comprising phosphorothioate linkages (Page 27, [0315]-[0316]). Zhao teaches first indexing primers comprise a sequence complementary to the first adapter and a first unique molecular identifier sequence (UMI) (Page 14, [0159]-[0160], Page 16, [0188], Pages 25-26, [0297] and Page 35, [0380]-[0381]). Zhao teaches a disease trait marker comprises a marker for specifically for virulence and/or strain identification (Page 32, [0360] and Page 32, [0352]). Zhao teaches using these methods and indexed primers allows for multiplexing of multiple samples on a sequencing platform in a single sequencing and decreasing cycle time providing faster sequencing reads to determine long fragments of low allele frequencies (Page 24, [0288], Page 32, [0351]-[0354] and Page 33, [0364]).
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