Prosecution Insights
Last updated: April 19, 2026
Application No. 17/865,375

Programmable Modification of DNA

Non-Final OA §101§102§103§112
Filed
Jul 14, 2022
Examiner
LEONARD, ARTHUR S
Art Unit
1631
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Massachusetts Institute Of Technology
OA Round
1 (Non-Final)
51%
Grant Probability
Moderate
1-2
OA Rounds
3y 6m
To Grant
99%
With Interview

Examiner Intelligence

Grants 51% of resolved cases
51%
Career Allow Rate
255 granted / 503 resolved
-9.3% vs TC avg
Strong +51% interview lift
Without
With
+51.2%
Interview Lift
resolved cases with interview
Typical timeline
3y 6m
Avg Prosecution
62 currently pending
Career history
565
Total Applications
across all art units

Statute-Specific Performance

§101
3.5%
-36.5% vs TC avg
§103
39.8%
-0.2% vs TC avg
§102
17.5%
-22.5% vs TC avg
§112
21.2%
-18.8% vs TC avg
Black line = Tech Center average estimate • Based on career data from 503 resolved cases

Office Action

§101 §102 §103 §112
Notice of Pre-AIA or AIA Status The present application is being examined under the pre-AIA first to invent provisions. 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 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. DETAILED ACTION Claim status Claims 1-16 are pending Claims 1-6 and 13-16 are withdrawn Claims 7-12 are under examination Election/Restrictions Applicant’s election of the following invention without traverse in the reply filed on 8/19/2025 is acknowledged. The requirement is still deemed proper and is therefore made FINAL. Group II, claims 7-12, drawn to a self-reconfiguring genome comprising a cassette coding for a guide RNA, a reverse transcriptase, a donor RNA. Claims 1-6 and 13-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim. Priority The instant application was filed Thursday 7/14/2022, and is a CON of 15/905,817 filed 2/26/2018, and abandoned 12/29/2020, and then revived on Friday 7/15/2022. This application is claiming the benefit of prior-filed application No. 15/905,817 under 35 U.S.C. 120, 121, 365(c), or 386(c). Copendency between the current application and the prior application is required at the time of filing of instant application (see MPEP 201.07: ‘The continuation application must be filed before the patenting or abandonment of or termination of proceedings on the prior application.’). Since the applications were not copending at the time of filing, the benefit claim to the prior-filed application is improper. Applicant is required to delete the claim to the benefit of the prior-filed application, unless applicant can establish copendency at the time of filing between the applications. Thus the instant claims are being given the filing date of 7/14/2022. Information Disclosure Statement No information disclosure statement (IDS) has been submitted. Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Claim Objections Claim 12 is objected to because of the following informalities: Applicant is advised that should claim 11 be found allowable, claim 12 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 706.03(k). Claim Rejections - 35 USC § 112(b) 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 7-12 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 pre-AIA the applicant regards as the invention. Claim 7 recites the limitation that the targets are selected according to a “desired” genomic self-reconfiguration. A claim may be rendered indefinite by reference to subjective term (see MPEP 2173.05(b), IV). Specifically, the term “desired” is a subjective term which renders the claim indefinite. The term “desired" is not defined by the claim, the specification does not provide a standard for some standard for measuring the scope of the term, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent claims 8-12 are included in the basis of this rejection because they do not clarify the “desired” genomic self-reconfiguration. Furthermore, Claims 11 and 12 recite the limitation "reconfigure" in regard to Claim 7. There is insufficient antecedent basis for this limitation in the claims because Claim 7 is directed to “self-reconfiguration”, thereby rendering Claims 11 and 12 indefinite. Appropriate correction is required. Claim Rejections - 35 USC § 101 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 7-12 are rejected under 35 U.S.C. 101 because the claimed invention isdirected to non-statutory subject matter. Section 33(a) of the America Invents Act reads as follows:Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism. Claims 7-12 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). In the instant case the scope of invention as claimed (see claims 7-12) is drawn to a CRISPR modified self-reconfiguring genome, which encompasses humans and the genomes therein. It is PTO policy not to allow claims to humans (supra). Changing the scope of instant claims to a self-reconfiguring bacterial genome, would overcome this rejection. Claim Rejections - 35 USC § 102 assuming no priority and a AIA filing date 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 7-12 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Jakimo et al., (US2014/0349400, filed 3/17/2014, published 11/27/2014). With respect to claims 7-12, a self-reconfiguring genome comprising a cassette coding for a guide RNA, a reverse transcriptase, a donor RNA, and a CRISPR cleavage enzyme, further comprising a counter, data logger configured to log the presence of a small molecule, peptide, protein, DNA, RNA, heat or light, and configured to reconfigure one or more of an organisms metabolic pathways (Abstract, [0013], see Claims 1-5) Accordingly, Jakimo anticipates instant claims. Claim Rejections - 35 USC § 103 assuming perfected priority and a pre-AIA filing date The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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. Claims 7, and 11-12 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Esvelt et al. (Mol Syst Bio, 2013, 9:641, published Jan 22, 2013), in view of Wang et al. (Meth Enzy, 2011, 498:409-426) and Liu et al. (US2014/0113375, published 4/24/2014, filed 10/19/2013, with priority to 61/716,592 filed 10/21/2012) In regard to claim 7, Esvelt reviews genome-scale engineering for cell systems and synthetic biology. Esvelt teaches the scientific concept of self-reconfiguring genomes comprising sequence modifications to at least two distinct regions of genome in order “to rationally build useful organisms that cannot be easily generated by harnessing evolution alone” (p. 2. 3rd & 4th para.). Specifically, Esvelt teaches in order to make and use a self-reconfiguring genome a CRISPR Cas9 nuclease is employed with a donor construct (see Figs 2 & 3), and that genomic modification via DSB-stimulated HR is accomplished by simply providing an expression cassette comprising the Cas9 and guide RNA spacer sequence matching the target sequence (p. 6-7, RNA-guided CRISPR nucleases). Esvelt goes on to explain that targeting a wild-type locus with nucleases would catalyze DSB repair using a transgenic cassette as a template, conceptually similar to ‘gene-drives’ used to allow self-configuring genomes in transgenic organisms (p. 13, 1st para.). Thus, Esvelt teaches the scientific concept of self-reconfiguring genomes and reasonable suggests expression cassettes comprising DNA encoding a CRISPR Cas9 and a guide RNA for generating a DSB at a target site, and a donor template for integration into the DSB of the target site in the genome. However, Esvelt is silent to the guide RNA and donor template designed to have the ability to target the promoter region or ribosomal binding sites (RBS) of a target gene. Nevertheless, Esvelt cites the prior art of Wang (2011), who is a co-author of Esvelt et al., for the making and using of self-configuring genomes that undergo multiplex automated genome engineering (p. 7, 2nd para.). In regard to claim 7, Wang teaches that the multiplex automated genome engineering targets the nuclease/recombinase to the promoter region and/or RBS of the target gene (p. 413, last para.). Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have prepared the self-reconfiguring genome as suggested by Esvelt and choose the target sequence for nuclease cleave in the promoter region or RBSs of a gene of interest as taught by Wang with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Wang because targeting the promoter region and/or RBS results in the generation of optimal regulatory modules that allow the tuning target gene expression (p. 410, Introduction, 1st para., p. 415, 2nd para., p. 418, last para.). However, although Esvelt teaches the self-reconfiguring genome can utilize a donor RNA precursor, with respect to the CRISPR Cas9 nucleases Esvelt et al. teach a DNA sequences that code for donor DNA (see Fig. 3, “Directed nucleases”), and are silent to DNA sequence that code for donor RNA and a reverse transcriptase. In regard to claim 7, Liu teaches systems for modifying the genome of a cells comprising a cassete comprising DNA sequences that code for a donor RNA and a reverse transcriptase (p. 2-3 of priority document) [AltContent: textbox ([img-media_image1.png])] Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to prepared the self-reconfiguring genome as suggested by Esvelt and substitute the donor DNA for donor RNA and a reverse transcriptase as taught by Liu with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because Liu teaches this allows the production of a donor DNA that is amplified tens of thousands of times, thereby allowing large quantities of the donor DNA to enter the host cells’ nuclease for homologous recombination with the target genomic DNA (p. 2 of priority document, and see modified Fig. 3 of Esvelt adjacent). In regard to claims 11 and 12, Esvelt teaches the target genes to be modified are involved with an organism’s metabolic pathways (p. 1, last para., pgs. 8-9 “Genome-scale metabolic engineering”, see also Fig. 2) Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary. Claims 8-10 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Esvelt et al. (Mol Syst Bio, 2013, 9:641, published Jan 22, 2013), in view of Wang et al. (Meth Enzy, 2011, 498:409-426) and Liu et al. (US2014/0113375, published 4/24/2014, filed 10/19/2013, with priority to 61/716,592 filed 10/21/2012), as applied to claim 7, in further view of Collins et al. (US 2012/0003630, filed 12/22/2009, published 1/05/2012) As discussed previously, Esvelt et al. suggest a self-reconfiguring genome comprising a cassette comprising DNA sequences that code for a CRISPR Cas9 nuclease, guide RNA, and donor RNA. However, although Esvelt et al. cite the prior art of Collins et al. throughout the review, they are silent with respect to a counter or data logger that are configured to log the presence of a stimulus. Nevertheless, Collins et al. (2012) teach a counter or data logger (i.e., single invertase memory module, i.e., SIMM), which can be integrated by targeted insertion into a host cell’s genome, and logs the presence of a small molecule (Abstract, [0009-0011, 0178], see Figs. 1-3). Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have prepared the self-reconfiguring genome as suggested by Esvelt and combine a SIMM based counter or data logger as taught by Collins with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Collins because it allows for the maintenance of memory of prior stimulus and provides the ability to count between discrete states (Abstract, [0009]). Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary. Conclusion No claims are allowed. Examiner Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0765. 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. /ARTHUR S LEONARD/Examiner, Art Unit 1631
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Prosecution Timeline

Jul 14, 2022
Application Filed
Nov 01, 2025
Non-Final Rejection — §101, §102, §103 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
51%
Grant Probability
99%
With Interview (+51.2%)
3y 6m
Median Time to Grant
Low
PTA Risk
Based on 503 resolved cases by this examiner. Grant probability derived from career allow rate.

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