CTFR 17/794,520 CTFR 86822 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 This Final Office Action is responsive to the communication received 1/29/2026. Claims 1-20 are pending. Claims 1-20 are under examination in this Office Action. Previous Rejections and/or Objections Any objections and/or rejections raised in the previous Office Action but not reiterated below are considered to have been withdrawn. Claim Rejections - 35 USC § 101 - Necessitated by Amendment 07-04-01 AIA 07-04 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to nonstatutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a judicial exception, an abstract idea of mental processes, without significantly more. Claims 1-20 depend directly or indirectly from claim 1. The claim 1 limitations directed to an abstract idea are determining levels of each of the analysis substrate in each sample at a plurality of times; and calculating rate of depletion or enrichment of each of the analysis substrates from each sample which are mental processes. The claim 1 limitations directed to well understood, routine, conventional activity already engaged in by the scientific community are a method providing a plurality of individual discrete samples comprising populations of cells, wherein each population of cells overexpresses both (i) a single genome engineering protein or a variant thereof and (ii) a reporter protein, wherein (i) and (ii) are expressed in a known ratio, in the samples; lysing the cells to release the proteins; normalizing levels of the genome engineering proteins or variants thereof based on levels of the reporter protein; allowing the genome engineering proteins or variants thereof to combine with a guide RNA under conditions sufficient to form ribonucleoprotein complexes in each sample; contacting each sample with a plurality of analysis substrates, under conditions sufficient for the genome engineering protein or variant thereof to act on one or more of the analysis substrates. Zhang et al. (06/07/2018) US Patent Application Publication 2018/0155716 A1 cited in the 4/24/2023 IDS (hereinafter known as "Zhang") teaches a method providing a plurality of individual discrete samples comprising populations of cells, wherein each population of cells overexpresses both (i) a single genome engineering protein or a variant thereof and (ii) a reporter protein, wherein (i) and (ii) are expressed in a known ratio, in the samples; lysing the cells to release the proteins; normalizing levels of the genome engineering proteins or variants thereof based on levels of the reporter protein; allowing the genome engineering proteins or variants thereof to combine with a guide RNA under conditions sufficient to form ribonucleoprotein complexes in each sample; contacting each sample with a plurality of analysis substrates, under conditions sufficient for the genome engineering protein or variant thereof to act on one or more of the analysis substrates (see Figures 56 and 107A to 107E and [0162], [0560] to [0613], [0915] to [0925] and [1626] to [1701]). Discussion and Answer to Argument Applicant argues the when claim 1 is considered as a whole claim 1 is patent eligible subject matter (Reply, starting on page 7). As noted in the rejection above, the claim 1 limitations directed to the abstract idea of mental processes fail to add significantly more when combined with the claim 1 limitations directed to well understood, routine, conventional activity already engaged in by the scientific community Claim Rejections - 35 USC § 102- Necessitated by Amendment 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15 AIA Claim s 1-20 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Zhang et al. (06/07/2018) US Patent Application Publication 2018/0155716 A1 cited in the 4/24/2023 IDS (hereinafter known as "Zhang") . With regards to claims 1-20, Zhang teaches: a) as in claims 1-20, a method for providing a plurality of individual discrete samples comprising populations of cells, wherein each population of cells overexpresses both (i) a single genome engineering protein or a variant thereof and (ii) a reporter protein, wherein (i) and (ii) are expressed in a known ratio in the samples; the method comprising: lysing the cells to release the proteins; normalizing levels of the genome engineering proteins or variants thereof based on levels of the reporter protein; allowing the genome engineering proteins or variants thereof to combine with a guide RNA under conditions sufficient to form ribonucleoprotein complexes in each sample; contacting each sample with a plurality of analysis substrates, under conditions sufficient for the genome engineering protein or variant thereof to act on one or more of the analysis substrates; determining levels of each of the analysis substrate in each sample at a plurality of times; and calculating rate of depletion or enrichment of each of the analysis substrates from each sample; wherein the genome engineering protein is a nuclease; wherein the genome engineering protein can alter the genome of a living cell or genomic DNA in vitro; wherein (i) and (ii) are expressed in a known ratio from a single nucleic acid construct; wherein the reporter proteins are fluorescent; wherein expression levels of the reporter proteins is determined by spectrophotometry; wherein each different genome engineering protein or variant thereof is expressed in an identified discrete individual population of cells in a single well of a multi-well plate; wherein a normalized amount of each genome engineering protein is transferred to a second multi-well plate; wherein the genome engineering protein is or comprises a CRISPR nuclease, is mixed with a guide RNA to form ribonucleoprotein complexes, and is contacted with a population of analysis substrates, each comprising a spacer sequence and a PAM sequence, wherein the population comprises analysis substrates having a plurality of spacer sequences; wherein the genome engineering protein is or comprises a cytosine base editor, is mixed with a guide RNA to form ribonucleoprotein complexes, is contacted with a population of analysis substrates, each comprising a spacer sequence and a PAM sequence, wherein the population comprises analysis substrates having a plurality of spacer sequences, or plurality of PAM sequences, or both, and is contacted with an enzyme that converts C-to-U deamination events to double-strand breaks when they co-occur with SpCas9-HNH domain mediated DNA nicks; wherein the genome engineering protein is or comprises a adenine base editor, is mixed with a guide RNA to form ribonucleoprotein complexes, is contacted with a population of analysis substrates, each comprising a spacer sequence and a PAM sequence, wherein the population comprises analysis substrates having a plurality of spacer sequences, or plurality of PAM sequences, or both, and is contacted with an enzyme that converts a combination of a target strand nick and a non-target strand deamination event to a double strand break; wherein the guide RNA is expressed in the cells or is added to the samples; wherein the analysis substrates include identifying sequences; wherein determining levels of each of the analysis substrate in each sample at a plurality of times comprises using sequencing; wherein determining the rate of depletion of each analysis substrate from the population of analysis substrates over time is determined by modeling the depletion as exponential decay and determining the rate constant of depletion for each analysis substrate; further comprising identifying analysis substrates that are depleted at a faster rate as substrates for the genome engineering protein; wherein the known ratio is 1:1; wherein the single nucleic acid construct comprises a viral 2A sequence in between sequences encoding (i) and (ii), or a direct fusion between sequences encoding (i) and (ii) by a peptide linker; wherein the enzyme is Endonuclease V; wherein the identifying the sequence comprises a barcode that is 8-10 nucleotides in length (see Figures 56 and 107A to 107E and [0162], [0560] to [0613], [0915] to [0925] and [1626] to [1701]). Thus, Zhang anticipates the present claims. Discussion and Answer to Argument Applicant argues Zhang does not teach the claim 1 limitation of normalizing levels of the genome engineering proteins or variants thereof based on levels of the reporter protein (Reply, starting on page 9). As noted in the rejection above, Zhang teaches the claim 1 limitation of normalizing levels of the genome engineering proteins or variants thereof based on levels of the reporter protein (see [0157], [1654] and [1715]). Conclusion No claim is allowed. 07-40 AIA Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. 07-101 Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Christian Boesen whose telephone number is 571-270-1321. The Examiner can normally be reached on Monday-Friday 9:00 AM to 5:00 PM. 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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair- direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. 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 . /CHRISTIAN C BOESEN/Primary Examiner, Art Unit 1684 Application/Control Number: 17/794,520 Page 2 Art Unit: 1684 Application/Control Number: 17/794,520 Page 3 Art Unit: 1684 Application/Control Number: 17/794,520 Page 4 Art Unit: 1684 Application/Control Number: 17/794,520 Page 5 Art Unit: 1684 Application/Control Number: 17/794,520 Page 6 Art Unit: 1684 Application/Control Number: 17/794,520 Page 7 Art Unit: 1684 Application/Control Number: 17/794,520 Page 8 Art Unit: 1684 Application/Control Number: 17/794,520 Page 9 Art Unit: 1684
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