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. Election/Restrictions Applicant’s election without traverse of claims 1-4, 6, 8, and 11-12 (Group I) in the reply filed on 10/27/2025 is acknowledged. Claims 14, 16, 18-19, 21, 23-24, 26, 28-29, 32, and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/27/2025. Accordingly, claims 1-4, 6, 8, and 11-12 are pending and under consideration. Priority Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S .C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc. , 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed applications, Application Nos. 62/913,647 and 63/0114,425, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Neither application provides support for the claimed invention for the reasons given below in the rejections under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph. Claims 1-4, 6, 8, and 11-12 have an effective filing date of 04/11/2022, which is the filing date of the instant application. Information Disclosure Statement Receipt of information disclosure statements on 04/11/2022 and 06/28/2022 is acknowledged. The signed and initialed PTO-1449‘s have been mailed with this action. Specification The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at least at page 29, line 12 (links to InvivoGen ) ; page 21, line 8 (links to NCBI); page 35, lines 14-16 (links to GenScript and IDT) ; page 40, line 16 (links to rgenome ) . 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 disclosure is further objected to because of the following informalities: The instant specification discloses that “quantification of allelic frequencies is shown above the plots and in Table S4” (page 10, line 15). There is no Table S4 in the instant specification. It would be remedial to update the language of the instant specification to clarify what Table is being referenced. The instant specification discloses that “PCR primers for off-target analysis are indicated in Table S7” (page 40, lines 18-19). There is no Table S7 in the instant specification. It would be remedial to update the language of the instant specification to clarify what Table is being referenced. Example 7 (page 48, line 19-page 50, line 29) discloses that paternal, maternal, and heterozygous alleles are identified as green, red, and blue dots, respectively (page 48, lines 31-33). However, neither the specification nor the drawings include color. Should Applicant wish to file color drawings, a petition under 37 CFR 1.84(a)(2) must be filed (see MPEP § 608.01(f)). It would be remedial to either update the descriptors in Example 7 to remove references to color or to file a petition under 37 CFR 1.84(a)(2) to include color drawings showing the indicated colors. Appropriate correction is required. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification. Drawings The drawings are objected to because: Figures 1D and 1E are bar graphs depicting the type and frequency of indels in human pluripotent stem cells (per the instant specification; page 7, lines 6-9). However, neither the drawing itself nor the instant specification discloses a legend indicating what the different shades of gray signify in the bar graphs therein . It would be remedial to include a legend indicating what the different shades of gray indicate in the bar graphs of Figures 1D and 1E. Figure 3B includes a legend indicating what the different shades of gray signify in the bar graphs therein . However, the shades of gray corresponding to “ EYS wt /indel ” and “ EYS wt ” are indistinguishable. The associated description of Figure 3B in the instant specification (page 8, lines 22-23) does not offer any further clarification. It would be remedial to update the legend of Figure 3B to ensure that the shades of gray are distinguishable, thereby rendering the figure interpretable by one of ordinary skill in the art. Figures 4C and 4D include legends indicating what the different shades of gray signify in the bar graphs therein. However, the shades of gray corresponding to “ wt (maternal)” and “MMEJ/NHEJ” (Figure 4C), as well as “ EYS wt ” and “indel” (Figure 4D) are indistinguishable. The associated descriptions of Figures 4C and 4D in the instant specification (page 10, lines 2-6) do not offer any further clarification. It would be remedial to update the legends of Figures 4C and 4D to ensure that the shades of gray are distinguishable, thereby rendering the figures interpretable by one of ordinary skill in the art. Figure 4E depicts a schematic of the cell division products observed after a single cell cycle following Cas9-RNP injection (instant specification; page 10, lines 6-9). The legends within Figure 4E purportedly facilitate distinguishing between paternal and maternal chromosomes, as well as aneuploidies. However, these legends are of limited help in interpreting Figure 4E. For example, no maternal aneuploidy corresponding to the legend is readily identifiable in Figure 4E. It would be remedial to ensure the legends of Figure 4E clearly facilitate figure interpretation by one of ordinary skill in the art. Figure 4H also depicts a schematic of the cell division products observed after a single cell cycle following Cas9-RNP injection (instant specification; page 10, lines 10-22). However, as with Figure 4E, the legend of Figure 4H is of limited help in interpreting Figure 4H, as the color schemes to distinguish paternal and maternal chromosomes are not readily and easily visible/interpretable in Figure 4H. It would be remedial to ensure that the legend of Figure 4H clearly facilitates figure interpretation by one of ordinary skill in the art. Figure 5A includes a legend indicating what the different shades of gray signify in the bar graphs therein. However, the shades of gray corresponding to “on target” and “spontaneous” are indistinguishable. The associated description of Figure 5A in the instant specification (page 11, lines 4-6) does not offer any further clarification. It would be remedial to update the legend of Figure 5A to ensure that the shades of gray are distinguishable, thereby rendering the figure interpretable by one of ordinary skill in the art. Figures 6A-6D all include an unidentified white box at the top left-hand corner of each Figure. The associated description of Figure 6 in the instant specification (page 11, lines 22-32) does not offer any further clarification. It would be remedial to either indicate what the unidentified white box signifies or to delete these boxes to facilitate clear interpretation of the Figures. Corrected drawing sheets in compliance with 37 CFR 1.121(d) 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. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. 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. Nucleotide and/or Amino Acid Sequence Disclosures REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES Items 1) and 2) provide general guidance related to requirements for sequence disclosures. 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted: In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying: the name of the ASCII text file; ii) the date of creation; and iii) the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying: the name of the ASCII text file; the date of creation; and the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended). When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical. Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Figure 1F depicts two chromatograms, each accompanied by a sequence of nucleotides. While one of the sequences is identified as SEQ ID NO: 26 (on the top) , the other sequence (on the bottom) is not identified at all. While the unidentified sequence appears to be part of SEQ ID NO: 26, it must nonetheless be identified properly as it is presented separately, either in the drawing itself or in the instant specification. Required response – Applicant must provide: Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers; AND/OR A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Claim Objections Claim 3 is objected to because of the following informalities: Claim 3 recites (in part) “two to eight guide RNAs or DNA encoding the guide RNAs are introduced into the embryos ” (bolded emphasis added). The Examiner notes that the methods recited at claims 1 and 2 both recite a single embryo, rather than the plural embryos of claim 3. It appears that this is a simple typographical error meant to invoke the single embryo of claims 1 and 2. It would be remedial to amend the instant claim language such that claim 3 recites a single embryo, as is recited at instant claims 1 and 2 , for purposes of internal consistency . Appropriate correction is required. Claim Rejections - 35 USC § 112 The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 1-4, 6, 8, 11, and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 1-4, 6, 8, 11, and 12 are drawn to a method of correcting an aneuploidy in an embryo, said method comprising introducing into the embryo at least one guide RNA (or DNA encoding the same). Dependent claim 3 limits the at least one guide RNA (or DNA encoding the same) to two to eight guide RNAs (or DNA encoding the same). The rejected claims thus comprise editing compositions comprising at least one guide RNA (or DNA encoding the same), with explicit recitation of two to eight guide RNAs (or DNA encoding the same) at instant claim 3. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes simultaneous administration of up to three guide RNAs (Example 10: see specifically page 97, lines 11-17) . However, n o description is provided of simultaneous administration of more than three guide RNAs, as encompassed by the ranges of the limitations of “at least one guide RNA” (recited at or inherited by claims 1, 2, 4, 6, 8, 11, and 12) and “two to eight guide RNAs” (recited at claim 3). Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of simultaneous administration of three guide RNAs . The results are not necessarily predictive of simultaneous administration of an unlimited number of guide RNAs, as encompassed by the limitation of “at least one . ” Furthermore, t he prior art does not appear to offset the deficiencies of the instant specification in that it does not describe simultaneous administration of an unlimited number of guide RNAs, as encompassed by the limitation of “at least one . ” While methods of correcting aneuploidies with multiple guide RNAs are known in the art (i.e. 14 guide RNAs; disclosed in Zuo et al., 2017: see Figure 5), the limitation of “at least one” necessarily encompasses up to an unlimited number of guide RNAs, which is not supported by either the instant specification or by the prior art. Furthermore, neither of the earlier-filed provisional applications (Application Nos. 62/913,647 and 63/0114,425) disclose simultaneous administration of an unlimited number of guide RNAs, as encompassed by the limitation of “at least one . ” Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1-4, 6, 8, 11, and 12 . 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. 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 1-4, 6, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Adikusuma et al., 2017 (hereinafter Adikusuma ; as cited in the IDS filed 04/11/2022) in view of Zuo et al., 2017 (hereinafter Zuo ) and US 2018/0291454 A1 (hereinafter Bluegnome ; as cited in the IDS filed 04/11/2022 ) . With regard to claim 1, which recites “a method of correcting an aneuploidy in an embryo comprising introducing into the embryo at least one guide RNA or DNA encoding at least one guide RNA, wherein the at least one guide RNA targets a single nucleotide polymorphism flanking the centromere of an extra chromosome; and an RNA-guided endonuclease, or DNA encoding an RNA-guided endonuclease, wherein the endonuclease introduces a single double-stranded break in a targeted site resulting in the loss o r elimination of the extra chromosome,” Adikusuma discloses methods of correcting an aneuploidy , for example by introducing a guide RNA (gRNA) pair compatible with CRISPR/Cas9 machinery and targeting two unique sequences immediately flanking the centromere of the Y chromosome (page 1736, column 1, paragraph 1-column 2, paragraph 1 ; page 1738, column 1, paragraph 3 ; Figure 1 ) . Adikusuma discloses that the methods taught therein are envisioned to be applied to modeling of aneuploidy syndromes and therapeutic intervention by targeting polymorphisms (page 1738, column 1, paragraph 3). Thus, while Adikusuma discloses a method of correcting an aneuploidy, said method comprising introducing at least one guide RNA targeting unique sequences immediately flanking the centromere of the targeted chromosome in order to introduce a single double-stranded break at each targeted site, thereby resulting in the loss or elimination of the extra chromosome, they are silent as to the utility of this method in embryos specifically, as well as to specifically targeting single nucleotide polymorphisms. These deficiencies are cured by Zuo and Bluegnome . Zuo discloses methods for therapeutic intervention for aneuploidies (abstract). While Zuo is primarily drawn to single-guide RNAs (sgRNAs) that target multiple chromosome-specific sites or a cocktail of multiple sgRNAs, each targeting one specific site, for targeted chromosome elimination (abstract; Figure 1), they also disclose selective chromosome elimination in zygotes by administering multiple sgRNAs, each targeting a chromosome-specific single-copy sequence (i.e. a SNP), thereby each generating a single double-strand break to selectively eliminate the targeted chromosome (Figure 5). Per Zuo , this approach of targeting SNPs facilitates targeting of only one of the homologous chromosomes without introducing indels and large deletions (page 7, column 1, paragraph 1; page 13, column 2, paragraph 2-page 14, column 1, paragraph 1). Thus, Zuo establishes that not only are SNP loci useful for assessing risk of aneuploidy (as disclosed in Bluegnome ) but also that they are attractive targets for selective chromosome elimination, as targeting these SNPs facilitates selective elimination of only one of the homologous chromosomes without introducing indels and large deletions. Furhermore , Bluegnome discloses methods and materials for detecting abnormalities of the number of whole chromosomes or chromosome regions, such as the use of centromeric heterozygosity (CH) in assessing risk of aneuploidy by genotyping for single nucleotide polymorphisms (SNPs) close to and flanking the centromeres (abstract; paragraph s [0018], [0019], and [0033] ). Per Bluegnome , assessing SNP loci present across a plurality of chromosomes can detect or determine risk of aneuploidy in a fertilized egg or embryo (paragraphs [0122]-[0126]) . Specifically, Bluegnome discloses that SNPs flanking the centromere within 5 Mb are particularly informative, with low heterozygous SNP proportions indicating low probability of aneuploidy and high heterozygous SNP proportions indicating high probability of aneuploidy (Figure 5) . Therefore , Adikusuma , Zuo , and Bluegnome collectively disclose a method of correcting an aneuploidy in an embryo by introducing at least one guide RNA targeting a SNP flanking the centromere for elimination following introduction of a single double-stranded break by an RNA-guided endonuclease such as Cas9, as instantly claimed. With regard to claim 2, which recites “the method of claim 1, wherein more than one guide RNA or DNA encoding the guide RNA is introduced into the embryo, wherein a first at least one guide RNA or DNA encoding the guide RNA targets a single nucleotide polymorphism flanking one side of the centromere of the extra chromosome and a second at least one guide RNA or DNA encoding the guide RNA targets a single nucleotide polymorphism flanking an opposite side of the centromere of the extra chromosome,” as set forth above, Adikusuma and Zuo disclose methods for therapeutic intervention for aneuploidies by targeting polymorphisms such as SNPs ( Adikusuma : page 1738, column 1, paragraph 3 ; Zuo : page 7, column 1, paragraph 1; page 13, column 2, paragraph 2-page 14, column 1, paragraph 1 ), while Bluegnome discloses that embryonic SNPs flanking the centromere within 5 Mb are particularly useful markers of aneuploidy (Figure 5) . Additionally, Adikusuma discloses targeting sequences flanking opposite sides of the centromere to selectively eliminate a targeted (Figure 1A -centro 2X ). As set forth above, Zuo discloses that SNPs are ideal sequences to target for selective chromosome elimination, especially for avoiding introduction of indels and large deletions (Figure 5; page 7, column 1, paragraph 1; page 13, column 2, paragraph 2-page 14, column 1, paragraph 1). Per Bluegnome , SNPs flanking both sides of centromeres have been identified (Figure 6; paragraphs [0153] and [0154]). Therefore, Adikusuma , Zuo , and Bluegnome collectively disclose a method of correcting an aneuploidy in an embryo by introducing more than one guide RNA, wherein at leas t one guide RNA targets a SNP flanking one side of the centromere of the extra chromosome and at least one guide RNA targets a SNP flanking the opposite side of the centromere of the extra chromosome, thereby targeting the extra chromosome for elimination following introduction of a single double-stranded break by an RNA-guided endonuclease such as Cas9, as instantly claimed. With regard to claim 3, which recites “the method of claim 2, wherein two to eight guide RNAs or DNA encoding the guide RNAs are introduced into the [embryo], wherein at least one guide RNA or DNA targets a single nucleotide polymorphism flanking one side of the centromere of the extra chromosome and at least one guide RNA or DNA encoding the guide RNA targets a single nucleotide polymorphism flanking an opposite side of the centromere of the extra chromosome,” as set forth above, Adikusuma and Zuo disclose methods for therapeutic intervention for aneuploidies by targeting sequences flanking opposite sides of the centromere (i.e. polymorphisms such as SNPs) ( Adikusuma : Figure 1A -centro 2X ; page 1738, column 1, paragraph 3; Zuo : page 7, column 1, paragraph 1; page 13, column 2, paragraph 2-page 14, column 1, paragraph 1), while Bluegnome discloses that embryonic SNPs flanking the centromere within 5 Mb are particularly useful markers of aneuploidy and are known to flank both sides of the centromere (Figure 5; Figure 6; paragraphs [0153] and [0154]). While Adikusuma explicitly discloses introduction of two guide RNAs targeting sequences flanking opposite sides of the centromere of the targeted chromosome (Figure 1A -centro 2X), they do not disclose that these targeted sequences are SNPS, as instantly claimed. However, as set forth above, both Zuo and Bluegnome disclose that SNPs are useful markers of aneuploidy and are ideal targets for selective chromosome elimination, as they target only one of the homologous chromosomes without introducing indels and large deletions ( Zuo : page 7, column 1, paragraph 1; page 13, column 2, paragraph 2-page 14, column 1, paragraph 1; Bluegnome : Figure 5). Therefore, Adikusuma , Zuo , and Bluegnome collectively disclose a method of correcting an aneuploidy in an embryo by introducing two guide RNAs, wherein at least one guide RNA targets a SNP flanking one side of the centromere of the extra chromosome and at least one guide RNA targets a SNP flanking the opposite side of the centromere of the extra chromosome, thereby targeting the extra chromosome for elimination following introduction of a single double-stranded break by an RNA-guided endonuclease such as Cas9, as instantly claimed. With regard to claim 4, which recites “the single nucleotide polymorphism flanking the centromere [of the method of claim 1] is within about 1 to about 5 Mb from the centromere,” the Examiner notes that the instant specification defines the term “about” to encompass variations of 20%, 10%, 5%, 1%, 0.5%, or even 0.1% of the specified amount (page 12, lines 14-16). Therefore, the instant claim language has been interpreted to recite that the SNP flanking the centromere is within 0.8 to 6 Mb from the centromere (i.e. + 20% of the claimed range). As set forth above, Bluegnome discloses that embryonic SNPs flanking the centromere within 5 Mb are particularly useful markers of aneuploidy (Figure 5). Therefore, given that SNPs within 5 Mb of the centromere fall within the claimed range, it is considered that Adikusuma , Zuo , and Bluegnome collectively disclose a method of correcting an aneuploidy in an embryo by targeting CRISPR/Cas9 machinery to SNPs within 5 Mb of the centromere of the targeted extra chromosome, as instantly claimed. With regard to claim 6, which recites “the RNA-guided endonuclease [of the method of claim 1] is a Cas nuclease,” as set forth above, Adikusuma and Zuo disclose methods for therapeutic intervention for aneuploidies by targeting polymorphisms such as SNPs ( Adikusuma : page 1738, column 1, paragraph 3; Zuo : page 7, column 1, paragraph 1; page 13, column 2, paragraph 2-page 14, column 1, paragraph 1). Both Adikusuma and Zuo disclose targeting these polymorphisms with gRNAs compatible with Cas9 ( Adikusuma : page 1, column 1, paragraph 1; Figure 1; Zuo : abstract; page 2, column 1, paragraph 2; page 5, column 2, paragraph 2), which is a Cas nuclease, as instantly claimed. Therefore, both Adikusuma and Zuo disclose that Cas nucleases such as Cas9 are compatible with the methods of correcting an aneuploidy by targeting the extra chromosome for introduction of a single double-stranded break by an RNA-guided endonuclease taught therein, wherein said RNA-guided endonuclease (i.e. Cas9) is directed to the targeted locus by at least one guide RNA. With regard to claim 11, which recites “the aneuploidy [corrected by the method of claim 1] is chosen from the group consisting of trisomy 8 ( Warnany Syndrome), trisomy 9, trisomy 13 (Patau syndrome), trisomy 16, trisomy 18 (Edwards syndrome), trisomy 21 (Down syndrome), trisomy 22, trisomy X (Klinefelter syndrome) and trisomy Y (Jacob syndrome),” as set forth above, Adikusuma and Zuo disclose methods for therapeutic intervention for aneuploidies by targeting polymorphisms such as SNPs ( Adikusuma : page 1738, column 1, paragraph 3; Zuo : page 7, column 1, paragraph 1; page 13, column 2, paragraph 2-page 14, column 1, paragraph 1). Adikusuma explicitly discloses that the methods taught therein are envisioned to have therapeutic potential for aneuploidies such as Down syndrome (page 1, column 1, paragraph 1) , while Zuo explicitly discloses that the methods taught therein are envisioned to have therapeutic potential for aneuploidies such as Down syndrome (trisomy 21 or DS; page 2, column 1, paragraph 2; page 14, column 1, paragraph 4) and Klinefelter syndrome (page 14, column 1, paragraph 4). Therefore, both Adikusuma and Zuo disclose that aneuploidies such as Down syndrome and Klinefelter syndrome may be corrected/treated by the methods taught therein and set forth above. Given that Adikusuma discloses methods for therapeutic intervention for aneuploidies by targeting sequences (such as polymorphisms) flanking opposite sides of the centromere of the targeted chromosome with gRNAs compatible with Cas9, that Zuo discloses selective chromosome elimination in zygotes by administering multiple sgRNAs, each targeting a chromosome-specific single-copy sequence (i.e. a SNP), thereby each generating a single double-strand break to selectively eliminate the targeted chromosome while avoiding the introduction of indels or large deletions, and that Bluegnome discloses that embryonic SNPs within 5 Mb of the centromere are useful for assessing risk of aneuploidy, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify the methods of Adikusuma and Zuo to specifically target SNP loci within 5 Mb of the centromere of the targeted chromosome with Cas9-compatible gRNAs to predictably eliminate the targeted chromosome without introducing indels or large deletions, thereby treating aneuploidies such as Down syndrome and Klinefelter syndrome. One would have been motivated to make such a modification in order to receive the expected benefit of effectively targeting and eliminating extra chromosomes early in embryonic development without introducing indels or large deletions, thereby preventing the development of aneuploidy-related disorders while maintaining chromosomal integrity. Claims 8 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Adikusuma et al., 2017 (hereinafter Adikusuma ; as cited in the IDS filed 04/11/2022) in view of Zuo et al., 2017 (hereinafter Zuo ) and US 2018/0291454 A1 (hereinafter Bluegnome ; as cited in the IDS filed 04/11/2022) , as applied to claim 1 above, and further in view of WO 2018/195418 A1 (hereinafter Oregon HSU; as cited in the IDS filed 04/11/2022). The combined disclosures of Adikusuma , Zuo , and Bluegnome are described above and applied as before. However, these disclosures do not teach the ribonucleoprotein complex of instant claim 8 or the preimplantation genetic screening of instant claim 12. With regard to claim 8, which recites “the at least one guide RNA and the RNA-guided endonuclease [of the method of claim 1] are introduced to the embryo in a ribonucleoprotein complex,” as set forth above, Adikusuma , Zuo , and Bluegnome collectively disclose the method of claim 1. However, they do not disclose that the at least one guide RNA and the RNA-guided endonuclease of said method are introduced to the embryo in a ribonucleoprotein complex, as instantly claimed. T his deficiency is cured by Oregon HSU, which discloses methods of correcting mutant alleles in embryos (abstract), said methods including editing of a gene of interest with the CRISPR-Cas9 system in an embryo (page 2, lines 16-29), wherein utilization of the CRISPR-Cas9 system comprises the introduction of at least one guide RNA and an associated RNA-guided endonuclease in a ribonucleoprotein system (page 22, lines 11-16 ; page 61, lines 26- 30 ) . Therefore, Oregon HSU discloses each and every additional limitation of instant claim 8, wherein the guide RNA and its associated RNA-guided endonuclease are introduced to the embryo in a ribonucleoprotein complex. With regard to claim 12, which recites “the method of claim 1 further compris [es] performing preimplantation genetic screening of the embryo prior to the introduction of the at least one guide RNA…and the RNA-guided endonuclease,” as set forth above, Adikusuma , Zuo , and Bluegnome collectively disclose the method of claim 1. However, they do not disclose that this method further comprises preimplantation genetic screening prior to the practice of said method. This deficiency is cured by Oregon HSU, which discloses methods of correcting mutant alleles in embryos (abstract). Oregon HSU further teaches that preimplantation genetic testing is a standard approach for preventing implantation and development of mutant embryos by facilitating selection of non-mutant embryos for transfer (i.e. in the context of an in vitro fertilization cycle) (page 2, lines 4-7). Finally, Oregon HSU discloses correction of mutant alleles in embryos via CRISPR-Cas9 prior to implantation (page 7, lines 15-21), as determined by assaying for successful correction (i.e. by Sanger sequencing or whole-genome sequencing) (claims 1, 2, 12, 13, and 15). Therefore, Oregon HSU discloses each and every additional limitation of instant claim 12, wherein preimplantation genetic screening is performed to detect mutant and non-mutant embryos, thereby preventing implantation and development of mutant embryos. Given that Adikusuma , Zuo , and Bluegnome collectively disclose the method of correcting an aneuploidy in an embryo set forth at claim 1 , and that Oregon HSU discloses methods of correcting mutant alleles in embryos with CRISPR-Cas9 (delivered as a ribonucleoprotein complex with its associated gRNA(s)) prior to implantation (as determined by Sanger sequencing or whole-genome sequencing) , it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to deliver the Cas endonuclease and gRNA(s) of the method of Adikusuma , Zuo , and Bluegnome as a ribonucleoprotein complex (a standard practice, as disclosed in Oregon HSU) to the embryo prior to implantation, followed by screening to ensure successful editing with CRISPR-Cas9 to predictably select embryos with corrected aneuploidies for implantation, thereby preventing the development of aneuploidy-related disorders while maintaining chromosomal integrity . One would have been motivated to make such a modification in order to receive the expected benefit of preventing the development of aneuploidy-related disorders while maintaining chromosomal integrity . Conclusion No claims are allowed. Claim 3 is objected to. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Sarah E Allen whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-0408 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-Th 8-5, F 8-12 . 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /SARAH E ALLEN/ Examiner, Art Unit 1637 /J. E. ANGELL, Ph.D./ Primary Examiner, Art Unit 1637