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 1-2, 5, 17, 19, and 26-30 with species election of 12:40364850_T_C, rs3761863, and SEQ ID NO:93150 in the reply filed on March 9, 2026 is acknowledged. Status of Claims Claims 1-2, 5, 10-11, 16-17, 19, 26, and 28 are currently pending in the instant application. Claims 10-11 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim. Accordingly, claims 1-2, 5, 17, 19, 26, and 28 are under examination on the merits in the instant application. Information Disclosure Statement The listing of references in the specification , see pages 128-131, is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Specification The disclosure is objected to because of the following informalities: Pages 3, 7, and 8 of the specification contains a large blank area. For instance, page 3 contains only two lines of disclosure. It is unclear whether a disclosure is missing. Clarification and/or appropriate correction is required. Claim Rejections - Improper Markush Grouping Claims 2, 5, 17, 19, 26, and 28 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch , 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi , 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination of process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. Note that the instant rejection is judicially approved as set forth in “Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. 112 and for Treatment of Related Issues in Patent Applications” in Federal Register, Volume 76, Number 27, published on February 9, 2011, which expressly states the following: “A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use…When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate.” See page 7166, middle column. Note that “the phrase "Markush claim” means any claim that recites a list of alternatively useable species regardless of format.” See MPEP §2173.05(h). The Markush grouping of the first RNA molecules targeting the different mutations of claim 2 and different SNPs of claim 3 is improper because the different first RNA molecule alternatives do not share a single nucleotide sequence similarity as evidenced by the different SEQ ID NOs of the first RNA molecules recited in claims 2, 5, 17, 19, 26, and 28. For instance, a first RNA molecule targeting 12:40364850_T_C in claim 2 or rs3761863 SNP in claim 3 comprises applicant’s elected SEQ ID NO:93150 (5’-UCUAGGGAGGUAACGGUAAAAG), whereas a first RNA molecule targeting 12: 40222364_G_A in claim 2 or rs1388598 in claim 3 comprises SEQ ID NO: 30107 (5’-GGAAAUUCAUUUUGAAUGAC), wherein the two alternatively recited first RNA molecules share no significant nucleotide sequence similarity with each other. To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternatives within a single claim in fact share a single structural similarity as well as a common use. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b ) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the appl icant regards as his invention. Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 5 recites the broad recitation regarding the “SNP position” such that it is “in an exon or intron of the LRRk2 mutant allele, or within 3,000 basepairs upstream of the transcription start site or within 3,000 basepairs downstream of the 3’ UTR of the LRRK2 mutant allele” and the claim also recites specific SNP positions (e.g., rs4374003, and rs7962370”), which are the narrower limitation of the broadly recited range/limitation pertaining to “exon or intron” or “upstream” or “downstream” within certain sequences of the LRRK2 mutant allele. The claim(s) are considered indefinite because there is a question or doubt as to whether the specifically recited SNP positions introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). 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 1-2, 5, 17, 19, 26, and 28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for a method of editing rs3761863 T>C in cells in vitro comprising contacting the cells having the “C” base mutation with SEQ ID NO:93150 with OMNI-I59, does not reasonably provide enablement for the entire scope. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The factors to be considered in determining whether undue experimentation is required are summarized In re Wands , 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’.” (Wands , 8 USPQ2d 1404). There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include , but are not limited to : (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP §2164. Each factor is analyzed below. (A) The breadth of the claims The instant claims are drawn to a method performed in vitro, ex vivo, and in vivo in a cell comprising a mutant LRRK2 allele associated with monogenic Parkinson’s disease comprising introducing to the cell a composition comprising a guide sequence RNA of 17-50 nucleotides in length, wherein the RNA is not limited to but includes 103,606 different sequences of SEQ ID NOs:1-103,606 , and wherein the RNA is claimed to have up to “5 nucleotide mismatches” against the target sequence. (B) The nature of the invention The claimed subject matter encompasses a CRISPR-Cas system-based Parkinson’s disease treatment method comprising using an RNA that is not limited to SEQ ID NOs:1-103,606. (C) The state of the prior art The state of the prior art pertaining to the claimed method in its entire scope encompassing use of 103,606 different gRNA sequences of SEQ ID NOs:1-103,606 as well as a myriad of sequence variants thereof comprising 1-5 mismatches with “higher targeting specificity” than a gRNA comprising no mismatch or a higher level of sequence complementarity with the target LRRK2 mutant allele is deemed nascent as there is no single prior art reference that teaches all of the limitations recited in claims 17 and 19, for instance. In addition, a Parkinson’s disease treatment method by LRRK2 mutant allele editing by targeting the recited SNP positions as encompassed by the instant claims was not practiced in the prior art thus is deemed nascent. (D) The level of one of ordinary skill As of the filing date sought in the instant case, one of ordinary skill in the art was equipped with the knowledge and skills to make and test gRNAs against a given target sequence in a cell in vitro . However, (E) The level of predictability in the art The level of predictability pertaining to the claimed method in its entire scope, in particular relating to the gRNA sequences and variants thereof encompassing “SEQ ID NOs: 1-103,606”, “17-50” lengths, and “SEQ ID NOs: 1-103,606 modified to contain 1, 2, 3, 4, or 5 nucleotide mismatches” is considered low for the following reasons: The instant specification, s ee paragraph 0197 , discloses the following: “A decrease in the level of LRRK2 mRNA was detected only for guide molecules “g8” and “g9_alt,” out of a total of nine gRNAs tested in A549 cells. That is, although seven other gRNAs showed a high % editing of LRRK2 as shown in Figure 1, they failed to reduce the expression level of LRRK2 mRNA when compared to the negative control (NT) as shown in Figure 2. Even better, Figures 3-4 of the instant application expressly demonstrate a high level of gRNA- and CRISPR nuclease-dependent unpredictability in the mutant LRRK2 allele editing activity such that “g 5 _alt” (SEQ ID NO: 61854 ) targeting “rs1 427263 ( C>A )” in the presence of “OMNI- I 59” CRISPR nuclease provided about 37% editing of the mutant LRRK2 allele, whereas “g4_alt” (SEQ ID NO:61889) targeting the same SNP in the presence of “OMNI-79 V5570” provided only about 8% editing, wherein the nucleotide sequences share a 14-mer sequence, thereby sharing about 63.6% sequence homology. That is, there is about a 5-fold difference in vitro in HeLa cells between the two gRNA sequences having about 63.6% sequence identity and targeting the same LRRK2 mutant SNP in the presence of two different CRISPR nucleases as demonstrated in the instant application. Hence, Further, it was known in the art that even a single mismatch introduced into a gRNA was known to decrease target editing efficiency as taught by Zhang (US 2014/0170753 A1). See Figures 3A-B showing that the gRNAs having a mismatched base (see “m1 7”, “m15”, and “m13”) provided indel % of 5.6, 7.5, and 8.8, respectively, compared to the gRNA containing no mismatch (see “wt”) that provided indel % of 9.7. (F) The amount of direction provided by the inventor The instant specification does not provide any useful direction pertaining to making and using all of the first RNA molecule variants encompassed by the instantly claimed scope encompassing, for instance, the RNA molecules having up to 5 mismatches are required to provide “higher targeting specificity” compared to an RNA having a perfect sequence complementarity against the LRRK2 mutant allele sequence. That is, the instant specification does not provide any enabling disclosure commensurate in scope of all of the sequence variants of “SEQ ID NOs: 1-103,606 modified to contain 1, 2, 3, 4, or 5 nucleotide mismatches”, wherein the sequence variants are “17-50” nucleotides in length, wherein such sequence variants provide “higher targeting specificity”. The instant specification also does not provide any useful direction in sufficient detail for the first RNA molecule structure that is as short as 17 nucleotides in length (which would have only 12 nucleotides that are complementary to the target if there are 5 mismatches) and as long as 50 nucleotides in length, wherein such RNA molecule structure must have the function of modifying the mutant LRRK2 allele in a cell in vitro, ex vivo, and in vivo. (G) The existence of working examples The instant specification at best provides an enabling working example disclosure pertaining to a cell line-based in vitro method (see Figure 3) , wherein the HeLa cell comprises two mutant LRRK2 alleles rs3761863 (CC) and is treated with “g11_alt”, which is identified as SEQ ID NO:93150 (see Table 3), which provided about 70% editing. The aforementioned working example pertaining to Figure 3 disclosed in the instant application is not commensurate in scope with the claims as currently written, which encompass a myriad of SEQ ID NOs and variants thereof, which are required to provide the mutant LRRK2 allele editing function in cells in a Parkinson’s disease patient in vivo as broadly and generically written. (H) The quantity of experimentation In view of the factors (A)-(G) analyzed above, the quantity of additional experimentation one of ordinary skill in the art to perform in order to practice the entire scope of the claims would be extremely undue. In view of the totality of factors (A)-(H) analyzed above, it is concluded that the instant specification fails to provide an enabling disclosure commensurate in scope with claims 1-2, 5, 17, 19, 26, and 28. Claim Rejections - 35 USC § 102 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim 1 is rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhang et al. (US 2023/0165909 A1). Zhang discloses a method of editing/correcting the rs34637584 SNP within human LRRK2 resulting in a G2019S mutation associated with Parkinson’s disease in cells comprising contacting the cells with a CRISPR/Cas9 system comprising sgRNAs, wherein the CRISPR/Cas9 system provides “a double strand break (DSB) at a cleavage site”. See FIG. 1; paragraphs 0142, 0150, 0154 , and 0171-0172. Accordingly, claim 1 is described by Zhang et al. Claim 1 is rejected under 35 U.S.C. 102 (a)(1) and 102(a)(2) as being anticipated by Offen et al. (WO 2019/111258 A1) . Offen discloses a method comprising contacting a cell with a CRISPR-Cas system comprising Cas9 and a gRNA of 20 nucleotides in length that specifically binds to a mutant allele (e.g., rs34805604 SNP) of the LRRK2 gene associated with Parkinson’s disease, wherein the CRISPR-Cas system “generates a double-stranded break (DSB) in the DNA”. See pages 4-5; Table 1; claim 1. Accordingly, claim 1 is described by Offen et al. Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vermilyea et al. ( Scientific Reports , published online on February 26, 2020, 10:3447). Vermilyea discloses a method of editing a mutant allele of LRRK2 in a cell comprising contacting the cell with CRISPR/Cas9 and a gRNA of 20 nucleotides in length targeting a mutated LRRK2 sequence (G6055A) encoding G2019S mutation causing Parkinson’s disease, wherein the CIRSPR/Cas9 and the gRNA provide targeted “double-stranded DNA breaks”. See pages 1-2; Figure 1. Accordingly, claim 1 is described by Vermilyea et al. 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. 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. Claim s 1-2, 5, 17, 19, 26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Offen et al. (WO 2019/111258 A1) in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 20 06 , 14:322-331 ) , GenBank Accession Number AY792511.1 (November, 2004) , and Zhang et al. (US 2019/0010471 A1). Offen discloses a method comprising contacting a cell with a CRISPR-Cas system comprising Cas9 and a gRNA of 20 nucleotides in length that specifically binds to a mutant allele (e.g., rs34805604 SNP) having the “G2019S mutation (G6055A transition)” of the LRRK2 gene associated with Parkinson’s disease, wherein the CRISPR-Cas system “generates a double-stranded break (DSB) in the DNA”. See pages 1 and 4-5; Table 1; claim 1. Offen does not teach targeting rs3761863 of the mutant LRRK2 having the T to C base change, causing a pathological mutation associated with Parkinson’s disease. Offen also does not teach that the gRNA having a mismatch has a higher specificity than a gRNA having no mismatch. Di Fonzo teaches that “rs3761863” in LRRK2 has a T to C base change in exon 49 of LRRK2 at position 7190 (“c.7190T>C”) of GenBank “accession number AY792511”, resulting in the protein change/mutation of “M2397T” that is associated with Parkinson’s disease. See the entire reference including Figure 1 and Table 1. The nucleotide sequence of AY792511.1 representing the wild-type LRRK2 sequence discloses that position 7190 has the “T” base as shown below, wherein a box is added to indicate the base at position 7190, which is mutated to “C”, resulting in the LRRK2 protein mutation associated with Parkinson’s disease. Zhang teaches that it is possible to design and use a gRNA comprising “mismatches to the distal end of the gRNA” , wherein such gRNA “can demonstrate enhanced specificity” because “the mismatches thermodynamically optimize specificity.” See paragraphs 0500-0501. Zhang teaches that the guide RNA sequence for S. pyogenes Cas9 is selected for a 20-mer preceding “XGG” sequence. See paragraphs 0568. It is noted that the “XGG” is at positions 7205-7207 in AY7892511.1 shown above , wherein the 20-mer preceding the “XGG” is 5’-GGTAA T GGTAAAAGAAAACA, wherein the underlined “T” base would be a “C” base in the mutated LRRK2 allele. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Offen’s method by replacing the gRNA targeting the rs34805604 SNP of the LRRK2 gene with a gRNA targeting the rs3761863 SNP (“c.7190T>C”) of the LRRK2 gene. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to investigate and develop potential CRISPR/Cas9 system-based therapeutic method for potentially treating Parkinson’s disease (PD) by targeting other PD-associated SNPs than the rs34805604 SNP already targeted by Offen because there were only a finite number of SNPs known to result in LRRK2 protein mutation s associated with PD as shown in Table 1 of Di Fonzo, wherein the mutations include M2397T associated with the rs3761863 SNP (“c.7190T>C”). When making a gRNA useful with S. pyogenes Cas9 for targeting the mutated LRRK2 sequence having the “T” base at position 7190 mutated to a “C” base, one of ordinary skill in the art would have followed the gRNA design guideline taught by Zhang and would have had a reasonable expectation of success in identifying a 20-mer sequence containing position 7190 that is followed by the “XGG” sequence. That is, it was within the technical grasp of one of ordinary skill in the art to obtain the nucleotide sequence of “accession number AY792511” and identify the 20-mer at positions 7185-7204 of AY792511 containing the nucleotide position 7190 having a “T” base, which is mutated to “C” in the mutant LRRK2 allele resulting in the mutated protein having M2397T, wherein the 20-mer sequence is 5’-GGTAA T GGTAAAAGAAAACA , which would correspond to a 20-mer RNA sequence of 5’-GGUAA C GGUAAAAGAAAACA when the underlined “T” is changed to “C”, wherein the above-identified 20-mer RNA sequence is found 100% identical to SEQ ID NO:93060 claimed in the instant case. Hence, one of ordinary skill in the art would have had a reasonable expectation of success in modifying or inactivating the LRRK2 mutant allele comprising the rs3761863 SNP (“c.7190T>C”) in cells in vitro . It would also have been obvious to one of ordinary skill in the art before the effective filing date to introduce at least one mismatch in the 20-mer RNA sequence rendered obvious hereinabove and use the modified sequence in order to modify the rs3761863 SNP (“c.7190T>C”) of the LRRK2 gene in cells. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in an attempt to potentially increase specificity of the gRNA, thereby resulting in an improved editing result because it was expressly suggested in the art that “mismatches to the distal end of the gRNA” can provide “enhanced specificity” because “the mismatches thermodynamically optimize specificity” as disclosed by Zhang. Accordingly, claims 1-2, 5, 17, 19, 26, and 28 taken as a whole would have been prima facie obvious before the effective filing date. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claim s 1 -2, 5, 17, 19, 26, and 28 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 29-39 of U.S. Patent No. 11,666,641 B2 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 is anticipated by the ‘641 patent claims, which are drawn to a method of modifying “a target site in the genome of a mammalian cell” comprising introducing a CRISPR nuclease and an sgRNA comprising “a guide sequence portion of 17-24 nucleotides and that is complementary to a sequence in a target DNA site”, wherein the target DNA site is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘641 patent specification. See Tables A-B. Regarding claims 2, 5, 17, 19, 26, and 28, it would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘641 patent claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 15-21 of U.S. Patent No. 11,946,077 B2 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 is anticipated by the ‘077 patent claims, which are drawn to a method of modifying “a nucleotide sequence at a target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and an sgRNA, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘077 patent specification. See Tables A-B. Regarding claims 2, 5, 17, 19, 26, and 28, it would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘077 patent claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claim s 19-23 of U.S. Patent No. 12, 091,688 B2 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 is anticipated by the ‘ 688 patent claim, which is drawn to a method of modifying “a nucleotide sequence at a target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and a sgRNA , wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘ 688 patent specification. See Tables A-B. Regarding claims 2, 5, 17, 19, 26, and 28, it would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘688 patent claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claim 7 of U.S. Patent No. 12,529,043 B2 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 is anticipated by the ‘043 patent claim, which is drawn to a method of modifying “a nucleotide sequence at a target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and “one or more RNA molecules”, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘043 patent specification. See Tables A-B. Regarding claims 2, 5, 17, 19, 26, and 28, it would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘043 patent claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 59-60, 75, and 84-86 of copending Application No. 18/249,950 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘950 claims, which are drawn to a method of modifying “a nucleotide sequence at a DNA target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and “one or more RNA molecules”, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘950 specification. See Tables A-B. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘950 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 62-63 of copending Application No. 18/251,667 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘667 claims, which are drawn to a method of modifying “a nucleotide sequence at a DNA target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and “a guide sequence portion”, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘667 specification. See Tables A-B. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘667 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 161-167 of copending Application No. 18/264,552 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘552 claims, which are drawn to a method of modifying “a nucleotide sequence at a DNA target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and “a single-guide (sgRNA) molecule”, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘552 specification. See Tables A-B. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘552 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 25-34 and 39-41 of copending Application No. 18/419,697 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322- 331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘697 claims, which are drawn to a method of modifying “a nucleotide sequence at a target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and an sgRNA, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘697 specification. See Tables A-B. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘697 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 291-297 of copending Application No. 18/556,591 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘591 claims, which are drawn to a method of modifying “a nucleotide sequence at a DNA target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and “one or more RNA molecules”, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘591 specification. See Tables A-B. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘591 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 41-49 of copending Application No. 18/682,982 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘982 claims, which are drawn to a method of gene editing in “a DNA target site” in a “mammalian cell” comprising introducing “an active CRISPR system”, wherein the “the DNA target site” is within “a pathogenic allele” of a gene that is “LRRK2” as recited in claim 47. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘982 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 51-57 of copending Application No. 18/683,113 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘113 claims, which are drawn to a method of modifying “a nucleotide sequence at a DNA target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and “one or more RNA molecules”, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘113 specification. See Tables A-B. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘113 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 15-20 of copending Application No. 18/711,632 . Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the ‘632 claims, which are drawn to a method of modifying “a nucleotide sequence at a DNA target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and “one or more RNA molecules”, wherein the “target site” as broadly recited is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘632 specification. See Tables A-B. In addition, the RNA molecule targeting LRRK2 is defined to read on the RNA sequence of SEQ ID NO:2596 (see Table 5 and paragraph 00735), which is 100% identical to applicant’s elected species of SEQ ID NO:93150. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 28 and 30 of copending Application No. 18/715,759 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘759 claims, which are drawn to a method of gene editing in “a DNA target site” in a “mammalian cell” comprising introducing a “CRISPR system” comprising “a guide RNA molecule that targets a DNA target site”, wherein the “the DNA target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘759 specification. See Tables A-B. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘759 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Claims 1-2, 5, 17, 19, 26, and 28 are provisionally rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 62-64 of copending Application No. 18/717,266 in view of Di Fonzo et al. ( European Jou rnal of Human Genetics , 2006, 14:322-331), GenBank Accession Number AY792511.1 (November, 2004), and Zhang et al. (US 2019/0010471 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘266 claims, which are drawn to a method of modifying “a nucleotide sequence at a DNA target site” in “the genome of a cell” comprising introducing a CRISPR nuclease and an RNA molecule, wherein the “target site” is defined to read on “LRRK2” that is associated with Parkinson’s disease as defined in the ‘266 specification. See Tables A-B. It would have been obvious to make, modify, and use a 20-mer gRNA of 5’-GGUAA C GGUAAAAGAAAACA, which is found 100% identical to SEQ ID NO:93060 claimed in the instant case, when targeting a mutated LRRK2 nucleotide sequence associated with PD as encompassed by the ‘266 claims in view of the combined teachings of Di Fonzo, GenBank Accession Number AY792511.1, and Zhang for the same reasons provided in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT DANA H SHIN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-8008 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday-Thursday: 8am - 6:30pm . 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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. /DANA H SHIN/ Primary Examiner, Art Unit 1635