Prosecution Insights
Last updated: April 19, 2026
Application No. 17/288,849

COMPOSITIONS AND METHODS FOR SELECTING BIALLELIC GENE EDITING

Non-Final OA §103
Filed
Apr 26, 2021
Examiner
DUNN, MCKENZIE A
Art Unit
1678
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The United States Department of Veterans Affairs
OA Round
3 (Non-Final)
58%
Grant Probability
Moderate
3-4
OA Rounds
4y 1m
To Grant
99%
With Interview

Examiner Intelligence

Grants 58% of resolved cases
58%
Career Allow Rate
39 granted / 67 resolved
-1.8% vs TC avg
Strong +50% interview lift
Without
With
+49.5%
Interview Lift
resolved cases with interview
Typical timeline
4y 1m
Avg Prosecution
45 currently pending
Career history
112
Total Applications
across all art units

Statute-Specific Performance

§101
12.9%
-27.1% vs TC avg
§103
38.9%
-1.1% vs TC avg
§102
18.7%
-21.3% vs TC avg
§112
21.7%
-18.3% vs TC avg
Black line = Tech Center average estimate • Based on career data from 67 resolved cases

Office Action

§103
DETAILED ACTION Claims 1-10, 19-21, and 40 are pending. Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/13/2025 has been entered. Status of Claims Claims 1-10, 19-21, and 40 are pending. Claim 1 has been amended. Claim 40 is newly added. Claims 1-10, 19-21, and 40 are under examination. Claim Rejections - 35 USC § 103 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 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. 1.Claim 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Fuenzalida et al., (WO 2017129811 A1) (IDS filed on 10/31/2022), in view of Pedersen (WO 2015052231 A2) (IDS filed on 10/31/2022). Fuenzalida teaches a method comprising a. administering Cas-9 to a population of cells, wherein Cas-9 is administered using CRISPR technology, where gRNA against a marker gene, gRNA against a target sequence are administered using CRISPR technology to the same population of cells prior to a negative selection step (see [0063] “In a further preferred embodiment the invention provides an in vitro method for enriching eukaryotic cells which are modified by homologous recombination, comprising (a) subjecting a population of cells transformed with a nucleic acid molecule or a composition of the invention to means for selecting for said marker indicating heterologous recombination and separate transformed cells expressing said selection marker indicating heterologous recombination in said eukaryotic cell; and (b) subjecting the non- separated cells to means for selecting for said marker indicating homologous recombination in order to enrich transformed cells comprising said homologous recombination." See [0036] “The nucleotide sequence encoding a selection marker indicating homologous recombination may be removed by excision or recombination or cleavage after depositing a modification into the genome. The removal of the nucleotide sequence encoding a selection marker indicating homologous recombination may be performed by the use of a recombinase, transposase, RNA guided nuclease or nuclease.”, see [0048] “The term "CRISPR Cas" as used herein relates to the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Type II system which is a bacterial immune system that has been modified for genome engineering. CRISPR consists of two components: a "guide" RNA (gRNA) and a non- specific CRISPR-associated endonuclease (Cas9). The gRNA is a short synthetic RNA composed of a "scaffold" sequence necessary for Cas9-binding and a user-defined ~20 nucleotide "spacer" or "targeting" sequence which defines the genomic target to be modified. Thus, one can change the genomic target of Cas9 by simply changing the targeting sequence present in the gRNA. CRISPR/Cas can be used for gene engineering by co-expressing a gRNA specific to the sequence to be targeted and the endonuclease Cas9.”, see [0048] teaching the use of CRISPR Cas-9 and gRNA being administered together, thus teaching them being applied to the sample population), b. performing FACS-based negative selection on the population of cells to establish an enriched cell population of negatively selected cells (see [0036] “Cells that have undergone removal of the nucleotide sequence encoding a selection marker indicating homologous recombination may further be enriched by the selection of cells that lost the fluorescence signal by FACS or fluorescence microscopy.”); wherein the negatively selected cells do not comprise a marker encoded by the marker gene and do comprise a mutation in the target sequence (see [0064] “In the second selection step (b) non-separated cells (cells which are not positive for the selection marker indicating heterologous recombination) are selected for said marker indicating homologous recombination indicating a site-specific integration of the nucleic acid molecule or the composition of the invention. Said second selection step separates cells which do not comprise the selection marker, indicating that said cells were not successfully transformed.”). Fuenzalida teaches encoding a selection marker (see abstract “The present invention relates to a nucleic acid molecule at least one nucleotide sequence encoding a selection marker indicating homologous recombination in a eukaryotic cell and at least one nucleotide sequence encoding a selection marker indicating heterologous recombination in said eukaryotic cell.”) (instant claim 1). Fuenzalida teaches wherein the CRISPR technology knocks out the marker gene (see [0036] “Cells that have undergone removal of the nucleotide sequence encoding a selection marker indicating homologous recombination may further be enriched by the selection of cells that lost the fluorescence signal by FACS or fluorescence microscopy.”, see [0062] “one nucleic acid molecule comprises a selection marker gene”) and mutates the target sequence ([0064] “non-separated cells (cells which are not positive for the selection marker indicating heterologous recombination) are selected for said marker indicating homologous recombination indicating a site-specific integration of the nucleic acid molecule or the composition of the invention.”, [0039] “Such a mismatch in the homology arms may be employed in order to introduce mutations in the nucleic acid sequence of interest.”) (instant claim 2). Fuenzalida is does not teach towards the use of sgRNA and the maker gene encoding a cell surface protein B2M and the cell surface protein not being essential for cell survival. Pedersen teaches multiplex editing systems (see abstract) and teaches the use of sgRNA against a marker gene (see pg. 98 lines 1-5 “The targeted integration system is based on three DNA parts: (a) a vector expressing Cas9 which is 2A-linked to a fluorescent marker (for example GFP); (b) donor DNA with homology arms towards the integration site containing an expression cassette inside the donor arms and a fluorescent marker gene (for example mcherry) outside the homology arms; and (c) a sgRNA targeting the selected integration site (Figure 18).”). Pedersen teaches the use of CRISPR Cas-9 (pg. 21 lines 9-11 “In preferred embodiments, the endonuclease or variant thereof is Cas9 or a variant thereof, and the targeting means are gRNAs that enable precise targeting of Cas9 to the TES.”, abstract “Also provided herein are a method for editing nucleic acids and a cell comprising a stably integrated endonuclease.”, pg. 21 lines 9-12 “In preferred embodiments, the endonuclease or variant thereof is Cas9 or a variant thereof, and the targeting means are gRNAs that enable precise targeting of Cas9 to the TES. Cas9 is a CRISPR-associated nuclease originally discovered in Streptococcus pyogenes.”) (instant claim 1). Pedersen teaches wherein the marker gene encodes b-2 microglobulin (B2M) (see pg. 41 lines 32-35 “For experiment part 4 we are constructing several CRESC's each with an FP as SM and a "housekeeping gene" (e.g. GADPH, B2M, etc.) because they are easy/cheap to detect/quantify with RT-qPCR and not likely to cause disturbances in the cells.”) (instant claim 5). Regarding claims 3 and 4, Pedersen teaches a marker gene that encodes b-2 microglobulin (B2M) (see pg. 41 lines 32-35). B2M is a major histocompatibility complex (MHC) class I molecule. MHC class I molecules are found on the cells surface. B2M is inherently a cell surface protein Thus, Pedersen teaches wherein the marker gene encodes a cell surface protein (see pg. 41 lines 32-35). It would have been obvious that the B2M is not essential for cell survival because there are known cells, such as red blood cells, that exist without B2M. It would have been obvious to one of ordinary skill in the art at the time the application was filed to modify Fuenzalida’s methods with the teachings of Pedersen for the purpose of multiplex editing of nucleic acids, in particular of genomes, by allowing repeated use of advantageous target locations (see pg. 1 lines 24-25 “multiplex editing of nucleic acids, in particular of genomes, by allowing repeated use of advantageous target locations.”). Given the high level of skill as evidenced by Fuenzalida and Pedersen, one of ordinary skill in the art would have combine Fuenzalida’s methods of selecting transformed cells with Pedersen’s teachings of using sgRNA for multiplex editing. Fuenzalida provides motivation by teachings that when CRISPR-Cas9 is used a point mutation in the protospacer adjacent motif (PAM) sequence is introduced (see [0082], and that the PAM sequence is absolutely necessary for target binding and the exact sequence is dependent upon the species of Cas9 (see [0048]). Pedersen provides motivation by teaching that their methods would be used to allow multiple insertions of genes of interest, i.e., multiplex editing of nucleic acids, in particular of genomes, by allowing repeated use of advantageous target locations”). It would have been obvious to one of ordinary skill in the art at the time of the application to use constructs that express Cas-9, sgRNA against a marker gene and target sequence. The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed. 2.Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Fuenzalida and Pedersen as applied to claims 1-5 above, and in further view of Oji, Asami et al. “CRISPR/Cas9 mediated genome editing in ES cells and its application for chimeric analysis in mice.” Scientific reports vol. 6 31666. 17 Aug. 2016, doi:10.1038/srep31666 (2016). The teachings of Fuenzalida and Pedersen as they pertain to claims 1-5 are discussed in the 35 USC 103 rejection above. Fuenzalida and Pedersen do not teach the mutation being a biallelic indel mutation. Regarding claim 9, Oji teaches wherein the mutation is a biallelic indel mutation (see pg. 1 “Here we show that large deletions with two sgRNAs as well as dsDNA-mediated point mutations are efficient in mouse embryonic stem cells (ESCs). The dsDNA-mediated gene knockins are also feasible in ESCs. Finally, we generated chimeric mice with biallelic mutant ESCs for a lethal gene, Dnajb13, and analyzed their phenotypes.”, see fig. 1). It would have been obvious to one of ordinary skill in the art at the time the application was filed to combine the methods of Fuenzalida with the teachings of Pedersen and the teachings of Oji as they all teach genome editing. Given the high level of skill as evidenced by Fuenzalida, Pedersen, and Oji one of ordinary skill in the art would have combined Fuenzalida’s methods of selecting transformed cells with Pedersen’s teachings of using sgRNA for multiplex editing with Oji’s methods of biallelic genome editing. Oji provides motivation by teaching that most embryonic stem cell clones are biallelic mutant after sgRNA/CAS9-mediated genome editing, allowing for the ability to analyze the effects of genome editing by differentiating the mutant embryonic stem cells in vitro (pg. 5). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed. 3.Claims 10, 19-20, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Fuenzalida and Pedersen as applied to claims 1-5 above, and in further view of Doench, John G et al. “Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation.” Nature biotechnology vol. 32,12 (2014): 1262-7. doi:10.1038/nbt.3026. The teachings of Fuenzalida and Pedersen as they pertain to claims 1-5 are discussed in the 35 USC 103 rejection above. Fuenzalida and Pedersen do not teach wherein the Cas-9, sgRNA against a marker gene, and sgRNA against a target sequence are expressed from different constructs. Doench teaches using CRISPR-Cas9 and sgRNA sequences for gene editing and genetic screening (see abstract). Regarding claim 10, Doench teaches wherein the Cas-9, sgRNA against a marker gene (see pg. 1262 “These sgRNAs were cloned as a pool into a lentiviral vector that simultaneously delivers CRISPR-associated protein (Cas)9, confers puromycin resistance, and expresses a sgRNA, as previously described. A second pool targeting the coding sequence of three human cell surface markers and also including negative controls was separately cloned into a lentiviral vector that expresses only the sgRNA (Fig. 1a and Supplementary Table 2).”), and sgRNA against a target sequence are expressed from different constructs (see pg. 1262 "We designed sgRNAs that targeted a panel of mouse genes in all exons and all flanking intronic sequences at all 20 nucleotide (nt) target sites that preceded the NGG PAM required by S. pyogenes Cas9 and added a large number of negative control sgRNAs (Fig. 1a and Supplementary Table 1)”. The marker gene is human, whereas the target gene is mouse). Regarding claim 19, Doench teaches wherein FACS-based negative selection comprises administering an antibody capable of binding to the marker (see fig. 1, see pg. 1262 “Our strategy was to target cell surface markers in a large cell population, delivering one sgRNA per cell, and then isolating complete (biallelic) knockout cells by fluorescence-activated cell sorting (FACS), thereby separating the most active sgRNAs. We designed sgRNAs that targeted a panel of mouse genes in all exons and all flanking intronic sequences at all 20 nucleotide (nt) target sites that preceded the NGG PAM required by S. pyogenes Cas9 and added a large number of negative control sgRNAs (Fig. 1a and Supplementary Table 1) …We transduced EL4 cells, a mouse thymic cell line, with the mouse sgRNA pool. Nine days after transduction, we stained cells for each of nine cell surface markers and analyzed them by FACS. Endogenous Thy1, H2-K, Cd45, Cd43, Cd28 and Cd5 exhibited good resolution of marker-negative cell populations (Fig. 1b), whereas Cd2, Cd3e and Cd53 were poorly expressed and excluded from subsequent analyses (Supplementary Fig. 1).”, Online Methods “FACS. Human and mouse cell surface markers were selected the basis of homogeneity of expression as assessed by antibody staining profiles. Only cell lines which showed expression of a particular cell surface marker in >98% cells were chosen for analysis. EL4 cells were independently stained and sorted on a FACS Aria flow cytometer 8 d after transduction. Antibodies used in this study included: eBioscience 17-5958-80 Anti-Mouse MHC Class I (H-2Kb) APC”). MOLM13, NB4 and TF1 cells were stained and sorted on a BD-FACS Aria II 8 d after transduction with the human sgRNA library. Antibodies used in this study included: BD Pharmingen 555450 CD33-PE; BD Pharmingen 555394 CD13-PE; BD Pharmingen 562371 CD15-PE.”). Regarding claim 20, Doench teaches wherein the antibody is an anti-MHC I antibody (see Online Methods “Antibodies used in this study included: eBioscience 17-5958-80 Anti-Mouse MHC Class I (H-2Kb) APC”).”). Regarding claim 40, Doench teaches wherein sgRNA against a marker gene targets an endogenous marker gene (see abstract “We created a pool of sgRNAs, tiling across all possible target sites of a panel of six endogenous mouse and three endogenous human genes and quantitatively assessed their ability to produce null alleles of their target gene by antibody staining and flow cytometry.”). It would have been obvious to one of ordinary skill in the art at the time the application was filed to combine the methods of Fuenzalida with the teachings of Pedersen and the teachings of Doench as they all teach gene editing. Given the high level of skill as evidenced by Fuenzalida, Pedersen, and Doench one of ordinary skill in the art would have considered combining Fuenzalida’s methods of selecting transformed cells with Pedersen’s teachings of using sgRNA for multiplex editing with Doench’s teachings of using CRISPR-Cas9 and sgRNA sequences for gene editing and genetic screening. Doench provides motivation by teaching that CRISPR-Cas9 programmed with a single guide RNA (sgRNA) to generate site-specific DNA breaks (abstract). Doench provides further motivation by teaching that using a sequence that correlates to on-target activity of the Cas9: sgRNA complex enables more effective applications of CRISPR technology when editing the genome and probe gene function (pg. 1266). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed. 4.Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Fuenzalida and Pedersen as applied to claims 1-5 above, and in further view of Liu, Yongzhen et al. “CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice.” Scientific reports vol. 7,1 2796. 5 Jun. 2017, doi:10.1038/s41598-017-03070-8. The teachings of Fuenzalida and Pedersen as they pertain to claims 1-5 are discussed in the 35 USC 103 rejection above. Fuenzalida and Pedersen do not teach the target sequence being a nucleic acid sequence encoding PTEN, MYC, or ZMIZ1. Regarding claim 7, Liu teaches towards the target sequence being a nucleic acid sequence encoding PTEN (see pg. 2 “To induce p53 and Pten gene mutation simultaneously, we constructed a dual sgRNA cassette plasmid by inserting sgRNAs of p53 and Pten into the pSpCas(BB)-2A-GFP (PX458) vector. The sgRNAs specific for p53 or Pten were designed to target the first exon of mouse p53 or Pten gene, respectively.”). It would have been obvious to one of ordinary skill in the art at the time the application was filed to combine the methods of Fuenzalida with the teachings of Pedersen and the teachings of Liu as they all teach genome editing. Given the high level of skill as evidenced by Fuenzalida, Pedersen, and Doench one of ordinary skill in the art would have combined Fuenzalida’s methods of selecting transformed cells with Pedersen’s teachings of using sgRNA for multiplex editing with Liu’s teachings of using Pten as a target sequence. Liu provides motivation by teaching that p53 and altered Pten expression are the two most common genetic events in Hepatitis B virus infection related to hepatocellular carcinoma (HCC). Liu goes on to teach that in addition to p53 mutation, the inactivation of the phosphatase and tensin homolog (Pten) through genetic or post-translation modifications is found in about half of HCC patients (see pg. 1). Liu goes on to teach that liver-specific knockout of Pten in mice results in fatty liver disease and late-onset liver cancer (see pg.1). Lastly, Liu suggests that the loss of Pten function plays a pivotal role in promoting carcinogenesis of HCC (see pg. 1). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed. 5.Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Fuenzalida, Pedersen, and Doench as applied to claims 10, 19-20. And 40 above, and in further view of Meissner, Torsten B et al. “Genome editing for human gene therapy.” Methods in enzymology vol. 546 (2014): 273-95. doi:10.1016/B978-0-12-801185-0.00013-1. The teachings of Fuenzalida, Pedersen, and Doench as they pertain to claims 10, 19-20, and 40 are discussed in the 35 USC 103 rejection above. Fuenzalida, Pedersen, and Doench do not teach the antibody being an anti-B2M antibody. Regarding claim 21, Meissner teaches wherein the antibody is an anti-B2M antibody (see pg. 276 “In the case of B2M, which is expressed at the cell surface, successful targeting can be confirmed by monitoring loss of B2M expression by means of a simple surface staining with an anti-B2M antibody, followed by fluorescence-activated cell sorting (FACS) analysis.”). It would have been obvious to one of ordinary skill in the art at the time the application was filed to combine the methods and teachings of Fuenzalida, Pedersen, and Doench, and the teachings of Meissner as they all teach genome editing. Given the high level of skill as evidenced by Fuenzalida, Pedersen, Doench and Meissner one of ordinary skill in the art would have combined Fuenzalida’s methods of selecting transformed cells with Pedersen’s teachings of using sgRNA for multiplex editing with Doench’s teachings of using CRISPR-Cas9 and sgRNA sequences for gene editing and genetic screening, with Meissner’s teachings of using an anti-B2M antibody for genome editing. Meissner provides motivation by teaching that the use of a surface antigen (B2M) allows the detection of successful targeting with a simple FACs staining using a fluorescently labeled antibody against the targeted protein (see pg. 282). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed. Response to Arguments Applicant's arguments filed 08/13/2025 have been fully considered but they are not persuasive. On pp. 7 applicant argues that Fuenzalida and Petersen fail to teach Cas-9, sgRNA against a marker gene and against a target sequence to the same population of cells. However, Fuenzalida teaches that CRISPR consists of two components: a “guide” RNA (gRNA) and a non-specific CRISPR-associated endonuclease (Cas9) (see [0048]). Fuenzalida teaches applying CRISPR Cas-9 to a group (population) of cells (see claims 1 and 12). Further, Fuenzalida teaches that the population of cells consist of eukaryotic cells (see [0007], [0017], and claims 19 and 22). Fuenzalida does not explicitly teach the use of sgRNA against a marker, however, Petersen teaches using sgRNA against a marker gene (see pg. 98 lines 1-5). It would have been obvious to one of ordinary skill in the art at the time of the instant application to use the sgRNA taught by Petersen with the methods taught by Fuenzalida because Petersen teaches that Cas9 and sgRNA used successfully together. On pp.7 applicant argues that Fuenzalida fails to tech the use of sgRNA. Fuenzalida teaches the use of gRNA with Cas-9 ([0048]). Fuenzalida does not teach sgRNA, however, Petersen teaches the use of sgRNA (see pg. 98 lines 1-5). One of ordinary skill in the art would have a reasonable expectation of success when using sgRNA and Cas-9 together, as Pedersen teaches that sgRNA is beneficial as it allows for multiplex editing (see abstract). On p. 7-8 applicant argues that Fuenzalida and Petersen fail to teach administering Cas-9, sgRNA against a marker gene, and sgRNA against a target sequence to a population of cells, wherein Cas-9, sgRNA against a marker gene, and sgRNA against a target sequence were administered using CRISPR technology to the same population of cells prior to a negative selection step. Applicant argues that Fuenzalida teaches first inserting the marker gene, then mutating the genome, then using the marker gene to identify the cells with the mutation, and then perform the selection step. However, Fuenzalida does teach the steps of administering Cas-9, gRNA against a marker gene, and gRNA against a target sequence, by using CRISPR technology to the same population of cells prior to a negative selection step (see [0048], [0063], and [0064]). On p. 8-9 applicant argues that Fuenzalida and Petersen fail to teach performing FACS-based negative selection on a population of cells. However, Fuenzalida teaches using FACS for cell selection on a population of cells (see [0007], [0009], [0020], and [0057]). Further, Petersen also teaches using FACs-based negative selection on a population of cells (see claim 13). On pp. 9-10 applicant argues that Oji fails to remedy the deficiencies of Fuenzalida and Petersen. The arguments pertaining to Fuenzalida and Petersen are discussed above. Oji teaches biallelic indel mutations (see page 1). On p. 10 applicant argues that Doench fails to remedy the deficiencies of Fuenzalida and Petersen. The arguments pertaining to Fuenzalida and Petersen are discussed above. Doench teaches wherein the Cas-9, sgRNA against a marker gene and sgRNA against a target sequence are expressed from different constructs (see page 1262). Doench further teaches wherein FACS-based negative selection comprises administering an antibody capable of binding to the marker, the antibody being an anti-MHC I antibody, and the sgRNA marker targeting an endogenous marker gene. On p. 11 applicant argues that Liu fails to remedy the deficiencies of Fuenzalida and Petersen. The arguments pertaining to Fuenzalida and Petersen are discussed above. Liu teaches the target sequence being a nucleic acid sequence encoding PTEN (see page 2). On pp. 11-12 applicant argues that Meissner fails to remedy the deficiencies of Fuenzalida and Petersen. The arguments pertaining to Fuenzalida and Petersen are discussed above. Meissner teaches wherein the antibody is an anti-B2M antibody (see page 276). Allowable Subject Matter Claims 6 and 8 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The prior art does not teach or suggest administering CAS-9, a sgRNA against a marker gene, where the sgRNA against a marker gene comprises SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 (instant claim 6), and an sgRNA against a target sequence to a population of cells, where the sgRNA against a target sequence comprises SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 (instant claim 8). Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MCKENZIE A DUNN whose telephone number is (571)270-0490. The examiner can normally be reached Monday-Tuesday 730 am -530pm, Wednesday-Friday 730 am-430 pm. 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, Gregory Emch can be reached at (571)272-8149. 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. /MCKENZIE A DUNN/Examiner, Art Unit 1678 /GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Read full office action

Prosecution Timeline

Apr 26, 2021
Application Filed
Aug 21, 2024
Non-Final Rejection — §103
Feb 27, 2025
Response Filed
May 05, 2025
Final Rejection — §103
Aug 13, 2025
Request for Continued Examination
Aug 14, 2025
Response after Non-Final Action
Nov 24, 2025
Non-Final Rejection — §103 (current)

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Expected OA Rounds
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Grant Probability
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4y 1m
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