CTNF 18/352,722 CTNF 77364 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’s preliminary amendment filed 7/14/2023 is acknowledged. Claims 1-59 have been canceled. Claims 60-79 have been added and are pending. Priority This application is a DIV of 17/844,498 filed 06/20/2022, now US PAT 11,746,389 which is a CON of 17/002,559 filed 08/25/2020, now ABN which is a CON of 15/325,225 filed 01/10/2017, now US PAT 10,793,917 which is a 371 of PCT/GB2015/052006 filed 07/10/2015. Information Disclosure Statement 06-52 The information disclosure statement (IDS) submitted on 10/20/2023 and 10/18/2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Drawings 06-37 AIA The drawings were received on 7/14/2023 . These drawings are found acceptable by the examiner . Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA 8. Claim (s) 60-79 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nikiforov et al {Nikiforov, used interchangeably herein} (WO 9416090, July 1994) in view of Zweitzig et al (Zweitzig, used interchangeably herein) Nucleic acid Research, 40 (14): e109, 1-12, April 2012, citation made of record on IDS) . Regarding claims 60, Nikiforov teaches an article of manufacture, a kit being specifically adapted to contain in close compartmentalization a first container which contains an oligonucleotide comprising a plurality of phosphorothioate nucleotide derivatives {nuclease resistant molecules) (about 4) and a second container which contains a second oligonucleotide without phosphorothioate, such that the two oligonucleotides can be used to amplify a predetermined nucleic acid sequence (page 16, lines 1-7; page 17, lines 23-25; page 20, lines 16-24; claims 24-25) wherein the amplification of the predetermined nucleic acid sequence occurs in the presence of a polymerase activity of microorganism such as a virus, bacterium, yeast, fungus or lower eukaryote (see “Summary of the Invention” at pages 12-16 and page 17, lines 11-25) resulting in a partially double stranded molecule (e.g., pages 12-16 and page 27 at lines 35-26). With regards to the presence of uracil in the complementary strand when used in an extension reaction, Nikiforov teaches wherein dATP, dCTP, dGTP, dTTP, ATP, CTP, GTP or UTP (uracil triphosphate) may be provided in a reaction mixture (see page 21, lines 10-13). Nikiforov teaches wherein the kit may additionally contain buffers, enzymes, instructional brochures and the like (see page 29, lines 16-24). Regarding claim 61-62, Nikiforov teaches the nuclease resistant nucleic acid molecule may comprise of a synthetic nucleotide (phosphorothioate nucleotide) or a methylated nucleotide (e.g., page 18, lines 4-15). Regarding claims 63-64, Nikiforov teaches wherein the modification by the nuclease resistant nucleotide(s) comprises a modification at the 3-end to prevent extension (see page 8 which teaches that the phosphorothioate nucleotides are used to modify the 3’ hydroxyl terminus, thereby producing a strand that is resistant to exonuclease attack (page 8, lines 5-9). Regarding claim 64 and 65, Nikiforov teaches wherein the incorporation of non-extendible nucleotide is within the scope of the instant invention, wherein the non- extendible nucleotides are 2’3’ dideoxy derivatives of either an A, T, C or G nucleotide triphosphate (page 10, lines 16-18; page 14, lines 31-33). With regards to claims 66-79, While Nikiforov teaches that the kit may additionally comprise of added buffers, reagents and instructional brochures and the like, Nikiforov does not teach expressly teach wherein the kit comprise of at least one internal positive control (IPC) which comprises identical primer binding sites to the nuclease resistant nucleic aid molecules that that there is competition for primer binding in a nucleic acid amplification reaction or wherein the IPC molecule is modified so as to protect it from the nuclease activity. Likewise, the reference does not teach pH lowering or pH increasing buffering agents. However, such buffering reagents such as NAOH or Tris-HCL are well-known and commonly used in the technical field and would only require routine optimization of known parameters and conditions. Regarding claim 60-79, Zweitzig teaches a teach method and reagents involving DNA polymerase activity assay enabling sensitive, quantitative and universal detection of viable microbes, wherein the method comprises the use of reagents and buffers comprising a nuclease resistant molecule comprising a synthetic nucleotide, competitive internal positive control, DNA polymerase, a high pH reagent, oligo comprising dideoxycytidine at the 3’ end of the oligo, dNTPs, detection probe comprising a fluorescent label, wherein the probe is specific for the competitive internal control DNA, pH buffering agents and stock solutions (see pages 2-4; see also Figures and legends). It would have been obvious to one of ordinary skill in the art at the time of the claimed invention to incorporate multiple reagents and components such as taught by Zweitzig into the kit of Nikiforov et al for the obvious benefit of detecting desired sequences as suggested by Nikiforov et al (see e.g., background beginning at page 3) and for the benefit of detection of potentially any microorganism as suggested by Zweitzig (see abstract). With regards to pH lowering and pH increasing agents, these claims recite well-known agents as well as routine optimization of known reaction components, concentration and paraments. Such modifications and optimization do not contribute towards patentability. Thus, one of ordinary skill in the art would have been motivated to modify the primary references in the manner of the claims to achieve the expected benefits, optimizations and/or expanded applications. Conclusion 9. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA B WILDER whose telephone number is (571)272-0791. The examiner can normally be reached Flexible. 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, GARY BENZION can be reached at 571-272-0782. 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. /CYNTHIA B WILDER/Primary Examiner, Art Unit 1681 Application/Control Number: 18/352,722 Page 2 Art Unit: 1681 Application/Control Number: 18/352,722 Page 3 Art Unit: 1681 Application/Control Number: 18/352,722 Page 4 Art Unit: 1681 Application/Control Number: 18/352,722 Page 5 Art Unit: 1681 Application/Control Number: 18/352,722 Page 6 Art Unit: 1681 Application/Control Number: 18/352,722 Page 7 Art Unit: 1681