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 filed 03/05/2026 has been received and considered entered. This is a response to amendments and arguments filed 03/05/2026 . Election/Restrictions Claim s 47-48 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species of host species (not bacterial) , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/22/2025 . Claims Status Claims 1-33 , 41, 43, 47-48 is/are cancelled and claims 60-65 is/are newly added. Claims 34-40, 42, 44-46, 49-65 is/are currently pending with claims 47-48 withdrawn. Claims 34-40, 42, 44-46, 49-65 is/are under examination. Information Disclosure Statement The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Claim Rejections - 35 USC § 112 112(a): 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. Claim s 34-40, 42, 44-46, 49-65 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. This rejection is maintained. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba , B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees ., Inc., 525 U.S. 55, 68, 119 S.Ct . 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”). Claim s 34 and 37 recite a plurality of amino acid residue alterations made to the amino acid sequence of SEQ ID NO:2 , claimed to all be “important for stability of the RNA-guided endonuclease or for stability of a complex formed between the RNA-guided endonuclease, one or more guide RNA (gRNA), and/or one or more DNA target sequence” , many of which amino acid residue alterations have not be sufficiently described (alterations of amino acid residues 34, 51, 54, 60, 61, 67, 82, 90, 112, 130, 131, 134, 150, 154, 159, 164, 166, 174, 185, 188, 194, 197, 244, 245, 287, 288, 294, 297, 344, 375, 448, 451, 455, 471, 507, 518, 521, 525, 554, 571, 574, 649, 669, 681, 682, 707, 709, 713, 715, 723, 747, 756, 833, 834, 836, 853, 860, 865, 876, 878, 927, 929, 930, 932, 1004, 1017, 1011, 1027, 1042, 1101, 1118, 1127, 1128, 1163, 1196, 1197, 1200, 1209, 1210, 1212 of SEQ ID NO:2). Furthermore, claim 34 recites a protein having at least 90 % and less than 100% sequence identity to SEQ ID NO:2, creating an enormous genus of proteins. Claims 62 and 63 further limit this genus to sequences at least 95% and 97% identical to SEQ ID NO:2, respectively, but the resulting genera of sequences are still enormous and insufficiently described. Based on the disclosure and the state of the art, it cannot be determined that the applicant was in possession of the full scope of the claimed genus of proteins, including specifically proteins comprising alterations of the above-listed amino acid residues. While claims 36 and 38-39 recite only the amino acid alterations which are sufficiently described, claims 36 and 38-39 still read on the breadth of proteins with at least 9 0% and less than 100% identity with SEQ ID NO:2, and thus also are not fully described. Claims 35, 40-46, and 49-59 do not further limit the amino acid sequences claimed by claim 34, and thus are also rejected for failing to comply with the written description requirement. Page 77 lines 18-35 of the specification and Tables 1-3 present amino acid residues of Mad7 of SEQ ID NO:2 which could be important for the thermostability of Mad7 or of a Mad7-gRNA-DNA complex. The specification discloses that these amino acid residues were identified using in silico modeling , using PyMOL ™ to identify residues important for the thermostability of Mad7 or a Mad7-gRNA-DNA complex . However, it is known in the art that in silico modeling is limited in its ability to predict amino acid residues relevant for thermostability of a protein , and the art further leaves unclear whether PyMOL ™ can be used to make such predictions, as the modeling programs used in the art for this purpose are not PyMOL ™ (see Peccati , 2023; Huang, 2020). Given this, alterations of amino acid residues 34, 51, 54, 60, 61, 67, 82, 90, 112, 130, 131, 134, 150, 154, 159, 164, 166, 174, 185, 188, 194, 197, 244, 245, 287, 288, 294, 297, 344, 375, 448, 451, 455, 471, 507, 518, 521, 525, 554, 571, 574, 586, 590, 649, 669, 681, 682, 707, 709, 713, 715, 723, 740, 747, 756, 833, 834, 836, 853, 860, 865, 876, 878, 927, 929, 930, 932, 1004, 1017, 1011, 1027, 1042, 1101, 1118, 1127, 1128, 1163, 1196, 1197, 1200, 1209, 1210, 1212 of SEQ ID NO:2 are not sufficiently described by the disclosure. Furthermore, the specification does not provide limitations to the genus of variant proteins with at least 9 0% and less than 100% identity with SEQ ID NO:2 beyond the specific amino acid residues and alterations recited in claims 34-39, and thus any additional amino acid residue alterations which result in a protein up to 1 0% divergent from the sequence of SEQ ID NO:2 are not described, and thus the full genus of variant sequences is not described. According to the MPEP § 2163, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")." The limitations of claim 34, as described above, create an enormous genus of proteins up to 1 0% divergent from the amino acid sequence of SEQ ID NO:2, which genus is not sufficiently described, and recite a plurality of amino acid residues and alterations of these residues which are claimed to be important for protein or ribonucleoprotein complex stability, but are not sufficiently described as such. As a result, the full scope of the genus of proteins with at least 9 0% and less than 100% identity to SEQ ID NO:2 is not sufficiently described, and amino acid residues 34, 51, 54, 60, 61, 67, 82, 90, 112, 130, 131, 134, 150, 154, 159, 164, 166, 174, 185, 188, 194, 197, 244, 245, 287, 288, 294, 297, 344, 375, 448, 451, 455, 471, 507, 518, 521, 525, 554, 571, 574, 649, 669, 681, 682, 707, 709, 713, 715, 723, 747, 756, 833, 834, 836, 853, 860, 865, 876, 878, 927, 929, 930, 932, 1004, 1017, 1011, 1027, 1042, 1101, 1118, 1127, 1128, 1163, 1196, 1197, 1200, 1209, 1210, 1212 of SEQ ID NO:2 are not sufficiently described in the disclosure as being important for protein or ribonucleoprotein complex stability as claimed. Claims 34-40, 42, 44-46, 49-65 thus fail to satisfy the written description requirement. Response to Arguments Applicant's arguments filed 03/05/2026 have been fully considered but they are not persuasive. Applicant has asserted that in amending the limitations of claim 34 to require at least 90% sequence identity to SEQ ID NO:2 (and claims 62 and 63 require at least 95% and 97% sequence identity, respectively) , the claims are sufficiently described. However, as described above, the claims are not sufficiently described because only a subset of potential amino acid alterations are recited and described, while the claims are not limited to only the described amino acid alterations and in fact encompass any amino acid alterations of SEQ ID NO:2, including alterations not described. Limitations not Found in Prior Art A search of the art for endonucleases at least 90% identical to SEQ ID NO:2 and comprising amino acid alterations at any of the residues recited in claim 34 did not yield any references claiming priority to or published on a date prior to the effective filing date encompassing the claimed invention. Conclusion 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 FILLIN "Enter examiner's name" \* MERGEFORMAT AFRICA M MCLEOD whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-1907 . The examiner can normally be reached FILLIN "Work schedule?" \* MERGEFORMAT Mon-Fri 9:00AM-6:00PM EST . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Ram Shukla can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-0735 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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The form may be filed via EFS-Web using the document description Internet Communications Authorized or Internet Communications Authorization Withdrawn to facilitate processing. See MPEP 502.03(II). Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AFRICA M MCLEOD/ Examiner, Art Unit 1635 /KIMBERLY CHONG/ Primary Examiner, Art Unit 1636