DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response of 05/07/2026, including amendments to the instant specification and replacement drawings, has been received and entered into the application file.
Claim 3 was amended in the claim set filed 05/07/2026.
Claims 1-4, 6, 8, 11, 12, 14, 16, 18, 19, 21, 23, 24, 26, 28, 29, 32, and 40 are pending, of which claims 14, 16, 18, 19, 21, 23, 24, 26, 28, 29, 32, and 40 were previously withdrawn.
Accordingly, claims 1-4, 6, 8, 11, and 12 are pending and under consideration.
Status of Prior Objections/Rejections
RE: Priority
►It was previously set forth that Applicant had not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e), as claims 1-4, 6, 8, and 11-12 were rejected under 35 U.S.C. § 112(a).
Applicant has traversed this assertion, stating that the provisional applications provide sufficient support under 35 U.S.C. § 112(a).
In response, this is found persuasive. The earliest effective filing date to which the instant application is entitled is 10/10/2019.
RE: Specification
►The disclosure was previously objected to for various informalities.
The amendments to the instant specification have obviated most, but not all, of the objections of record. Those objections not repeated below are hereby withdrawn.
Furthermore, further review of the instant specification has revealed additional references to color, which are set forth below.
RE: Drawings
►The drawings were previously objected to for various informalities.
The replacement drawings have obviated some, but not all, of the objections of record. Those objections not repeated below are hereby withdrawn.
RE: Nucleotide and/or Amino Acid Sequence Disclosures
►The drawings were previously indicated to include a sequence lacking a sequence identifier.
The replacement drawings have obviated the basis of the sequence disclosure issue set forth previously. The drawings now comply with sequence disclosure requirements.
RE: Claim Objections
►Claim 3 was previously objected to for minor informalities.
The amendments to claim 3 have obviated the basis of the objection of record. The objection of record is hereby withdrawn.
RE: Claim Rejections - 35 USC § 112
►Claims 1-4, 6, 8, 11, and 12 were previously 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.
Applicant has traversed the rejection of record, asserting that the application as filed clearly describes the claimed subject matter, including specifically the recitation of claim 3 or two to eight guide RNAs.
In response, this is found persuasive. Accordingly, the rejection of record is hereby withdrawn.
RE: Claim Rejections - 35 USC § 103
►Claims 1-4, 6, and 11 were previously 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).
►Claims 8 and 12 were previously 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).
Applicant has traversed the rejection of record, asserting that the cited art does not teach the use of a single sgRNA that targets a single nucleotide polymorphism, which is required by all of the instant claims.
In response, this is not found persuasive.
As set forth previously, Adikusuma discloses a method of correcting an aneuploidy by 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. While Adikusuma is silent as to targeting single nucleotide polymorphisms in embryos, as noted by Applicant, these deficiencies are cured by Zuo and Blugnome.
As set forth previously, Zuo discloses that targeting single nucleotide polymorphisms with sgRNAs offers a method of removing a specific chromosome without affecting the homologous chromosome. Furthermore, as set forth previously, Bluegnome discloses that genotyping for single nucleotide polymorphisms is useful for assessing risk of aneuploidy in a fertilized egg or embryo.
Therefore, the prior art teaches and/or motivates each and every limitation of the instantly claimed method, including targeting of a single nucleotide polymorphism with a single sgRNA. Applicant asserts that Zuo teaches use of a single-guide RNA that targets multiple chromosome-specific sites or a cocktail of multiple sgRNAs, each targeting one specific site. Therefore, by Applicant’s own admission, Zuo thus discloses at least one sgRNA, wherein each sgRNA targets one single nucleotide polymorphism, which reads on the instantly claimed “at least one guide RNA target[ing] a single nucleotide polymorphism flanking the centromere of an extra chromosome.” Furthermore, as set forth previously, Bluegnome specifically motivates targeting single nucleotide polymorphisms flanking the centromere within 5 Mb (as instantly claimed), as these are particularly informative for determining risk of aneuploidy.
Therefore, the rejection of record is hereby maintained, as set forth in greater detail below.
New/Maintained Grounds of Objection/Rejection
Specification
The disclosure is objected to because of the following informalities:
The amendments to the instant specification filed 05/07/2026 disclose colors, including red and green at the brief description of Figure 4. As previously set forth, neither the specification nor the instant 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 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.
Furthermore, 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. While Applicant amended the instant specification (filed 05/07/2026), these amendments to not overcome the basis of the objection of record. All of the amendments to the instant specification are either identical to the originally disclosed hyperlinks or only delete the “https://” prefix, while leaving the “www.” prefix that still links to a hyperlinked web-browser code.
Appropriate correction is required.
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 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 thereof. 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.
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.
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; of record) in view of Zuo et al., 2017 (hereinafter Zuo; of record) and US 2018/0291454 A1 (hereinafter Bluegnome; as cited in the IDS filed 04/11/2022; of record).
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 or 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.
Furthermore, 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; paragraphs [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 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 amended 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; of record) in view of Zuo et al., 2017 (hereinafter Zuo; of record) and US 2018/0291454 A1 (hereinafter Bluegnome; as cited in the IDS filed 04/11/2022; of record), 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; of record).
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. This 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.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAH E ALLEN/Examiner, Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637
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