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. Status of Claims The amendments to the claims filed October 25, 2023 are acknowledged and entered. Claims 1-19 and 24-25 are pending. Priority This application is a 371 of PCT/GB2021/052573, filed October 5, 2021, which claims priority of GB 2107783.9, filed June 1, 2021; GB 2015985.1, filed October 8, 2020; and GB 2015832.5, filed October 6, 2020. Information Disclosure Statement Acknowledgement is made of the Information Disclosure Statements filed on March 24, 2023; June 13, 2025; and November 7, 2025 . All references have been considered except where marked with a strikethrough. Election/Restriction Applicant’s election with traverse of Group I (claims 1-19 and 25 , drawn to a compound of Formula I) and the species corresponding to Example 10 (pictured below for convenience) in the reply filed on November 7, 2025 is acknowledged. The traversal is on the ground(s) that the aforementioned groups are linked by a special technical feature and therefore have unity of invention under PCT Rule 13.1 and 13.2. For instance, all of the compounds of Formula (I) comprise a 9-membered heteroaromatic core and claim 24 recites the use of the compounds of Formula (I). This is not found persuasive because Tommasi et al, cited in the restriction requirement, teaches compounds comprising the 9-membered heteroaromatic core as required by the claims (see page 4 of restriction, compounds 19 and 24) . The requirement is still deemed proper and is therefore made FINAL. Claim 24 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on November 7, 2025. The elected species corresponds to Formula I wherein C 4 cycloalkyl; Y is wherein n is 1, and wherein the carbonyl group of Y binds directly to Z Applicant submits that claims 1, 6-7, 9-15, 18-19 and 24-25 encompass the elected species. Examiner notes that claim 24 corresponds to a non-elected invention and is therefore withdrawn. The guidelines in MPEP § 803.02 provide that upon examination if prior art is found for the elected species, the examination will be limited to the elected species. Relevant portion of MPEP § 803.02 is provided here for convenience: As an example, in the case of an application with a Markush-type claim drawn to the compound X-R, wherein R is a radical selected from the group consisting of A, B, C, D, and E, the examiner may require a provisional election of a single species, XA, XB, XC, XD, or XE. The Markush-type claim would then be examined fully with respect to the elected species and any species considered to be clearly unpatentable over the elected species. If on examination the elected species is found to be anticipated or rendered obvious by prior art, the Markush-type claim and claims to the elected species shall be rejected, and claims to the nonelected species would be held withdrawn from further consideration. A second action on the rejected claims can be made final unless the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). See MPEP § 706.07(a). If the elected species or group of patentably indistinct species is not anticipated by or obvious over the prior art, the examiner should extend the search and examination to a non-elected species or group of species that falls within the scope of a proper Markush grouping that includes the elected species. The search and examination should be continued until either (1) prior art is found that anticipates or renders obvious a species that falls within the scope of a proper Markush grouping that includes the elected species, or (2) it is determined that no prior art rejection of any species that falls within the scope of a proper Markush grouping that includes the elected species can be made. The examiner need not extend the search beyond a proper Markush grouping . In other words, the examiner need not extend the search to any additional species that do not share a single structural similarity and a common use with the elected species (i.e., do not belong to the same recognized physical or chemical class or to the same art-recognized class and/or do not have a common use and/or do not share a substantial structural feature of a chemical compound and a use that flows from the substantial structural feature). The examiner should continue examination of the Markush claim to determine whether it meets all other requirements of patentability (e.g., 35 U.S.C. 101 and 112 , nonstatutory double patenting, and proper Markush grouping). The elected species was not found in the prior art and the search was expanded to include the subgenus of Formula (I) wherein X is ; and Y is Claims 1-19 and 25 r ead on the expanded subgenus. Per MPEP § 803.02, the examiner need not expand the search beyond a proper Markush group. The search has thus been limited to the expanded subgenus above. Claims 1-19 and 25 (all in part, other than the above indicated subgenus) are additionally withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species. Specification The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification. Claim Objections Claim 18 is objected to for failing to comply with rule 1.141(a) (pasted below for convenience). Claim 18 has approximately 50 species. This number of compounds cannot be considered a reasonable number according to rule 1.141(a). In re Fressola , 22 USPQ 2nd 1828, indicates that the Examiner may reject for Applicants’ failure to follow a Rule. Claim 18 should be amended to depend from claim 1 . Failure to amend the claims consistent with the rules may result in a restriction requirement. § 1.141 Different inventions in one national application. (a) Two or more independent and distinct inventions may not be claimed in one national application, ex cept that more than one species of an invention, not to exceed a reasonable number, may be specifically claimed in different claims in one national application, provided the application also includes an allowable claim gen eric to all the claimed species and all the claims to species in excess of one are written in dependent form (§ 1.75) or otherwise include all the limitations of the generic claim. Claims 6-7, 12-13 and 16-17 are objected to because of the following informalities: The final lines of claims 6-7, 12-13 and 16-17 recite limitations which carry over from independent claim 1 (example from claim 6 provided below) . The extraneous phrases should be deleted because the limitations carry over from claim 1 and do not need to be repeated . For instance, claim 6, final line recites the extraneous text “ and R1a, R1b, R1a' and R2a are as defined in claim 1 ” Claim 1 has duplicate text. Claim 1 recites “Q2 is…amino…amino”. The amino groups appear to be duplicates. Examiner suggests deleting one. Appropriate correction is required. Improper Markush Grouping Rejection Claims 1-19 and 25 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch , 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi , 3 USPQ2d Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117. The Markush grouping of X, Y, and Z is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The compounds with the scope of Formula (I) recited in the instant claims are not all members of the same recognized physical or chemical class or the same art-recognized class. The possible structures of Formula (I) do not overlap and are comprised of different heterocyclic groups that have different classifications. B y varying the definitions of X, Y, and Z, the structure of Formula (I) changes such that the resultant compounds shar e no significant structural feature. Compounds of Formula (I) wherein X and Y are any group other than and simply share no significant common structure with justifies their inclusion in the same group. The claims are thus drawn to an improper Markush group, that is, the claims lack unity of invention. By changing the identify of X, Y, and Z several patentably distinct and independent compounds are claimed. In order to have unity of invention the compounds must have “a community of chemical or physical characteristics” which justify their inclusion in a common group, and that such inclusion is not repugnant to principles of scientific classification. In re JONES (CCPA) 74 USPQ 149 (see footnote 2). In this case, there is no substantial structural feature in common between the compounds of the instant claims. Note, the rejection may be overcome by amending claims consistent with the elected species . Claim Rejections - 35 USC § 112a 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 1-17, 19 and 25 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 formula (I) wherein X is , R 1a and R 1 are each H, and R 1b is C 1 alkyl or R 1b is –(CR 1c R 1d ) p -NR 1e R 1f wherein p is 1; R 1c and R 1d are each H; R 1e is H; and R 1f is –(CR 1g R 1h ) q -T 1 wherein q is 1; R 1g and R 1h are each H; and T 1 is C 3 -C 8 cycloalkyl; or R 1e R 1f form a mono- or bicyclic heterocyclic ring; Y is or ; and Z wherein each Z is optionally substituted with halo, oxo, C 1 alkyl, C1 alkoxy, CN, -C(O)NH 2 or morpholinyl does not reasonably provide enablement for all of the possible variations of optionally substituted X, Y, and Z groups presently claimed. The specification is not adequately enabling for the scope of the compounds claimed. The only useful compounds are those embodiments disclosed at Tables 4, 5 and 6 of specification and which are included in the subgenus of F ormula (I) indicated above. This narrow scope of compounds does not give a reasonable assurance that all, or substantially all of the thousands of structurally diverse compounds within the scope of the claim are useful. The claims are not drawn in terms of a recognized genus but are directed to a more or less artificial selection of compounds. There is no reason why a claim drawn in this way should not be limited to those compounds which are shown to be useful. An Applicant is not entitled to a claim for a large group of compounds merely on the basis of a showing that a selected few are useful and a general suggestion of a similar utility in the others. There is no statement of utility beyond that for inhibition of METTL3 activity (see [0044]) . Ex parte Lanham, 108 USPQ at 135 states “It was never intended that a patent be granted upon a product, or a process producing a product, unless such product be useful.” The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). These factors include the following: 1) Amount of guidance provided by applicant. The Applicant has demonstrated the embodiments at Tables 4-6 and which are described by the above indicated subgenus of Formula (I) , are inhibitors of METTL3 (Results on page 247) . However, there is no evidence to show the full scope of formula (I) which includes thousands of structurally diverse compounds have any use. 2) The nature of the invention and predictability in the art. It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved”. See In re Fisher , 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 3) Number of working examples. A compound of formula (I) comprising the subgenus indicated above, and which is supported by the embodiments at Table 4-6, represents a narrow subgenus for which applicant has provided sufficient guidance regarding how to use. However, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any compounds, compositions, or pharmaceutically acceptable salts of F ormula ( I ) beyond the narrow subgenus indicated above. Within the specification, “specific operative embodiments or examples of the invention must be set forth, Examples and description should be of sufficient scope as to justify the scope of the claims, Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p). 4) Scope of the claims. The scope of the claims involves the following formula: Wherein X is , ; Y is , or may be chosen from a group consisting of 18 distinct heterocyclic cores; and Z is chosen from a group consisting of 19 different heterocyclic cores. The scope of the claims is massive, inclu d es thousands of distinct compounds, and includes compounds which have no structural over l ap and for which no examples have been provided by Applicant. 5) Level of skill in the art . The artisan using applicant' s invention would be a scientist with a Ph.D. degree and having several years of research experience. 6) Undue experimentation. MPEP §2164.01 (a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." The conclusion is clearly justified here that applicant is not enabled for making these compounds Claim Rejections - 35 USC § 112b 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 applicant regards as his invention. Claims 1-19 and 25 are 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. [A] claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear (MPEP 2173.04). The following terms and/or phrases render the scope of the claims unclear because the specification does not provide sufficient direction for ascertaining the scope of the limitation indicated by the term or phrase. Accordingly, one skilled in the art could not ascertain the metes and bounds of the claimed invention. The claims are indefinite for the reasons that follow: C laim 1 provides two different R 1f groups which is confusing and renders the scope of the claims unclear. R 1f is defined as a substituent on X and also as a definition of R 1f : The claims recite X is ; and the claims also recite R 1b , R 1d and R 1f are selected from… . The intended scope of R 1f , and therefore metes and bound of the invention cannot be ascertained. Appropriate correction/clarification is required. Claims 2-17 and 25 depend from claim 1, fail to cure the abovementioned deficiency, and are also indefinite for this reason. The claims recite the limitation “including” (e.g. see claim 1: R 1e and R 1f are each selecte d from hydrogen (including deuterium). “Including” at each recitation renders the scope of the claim s unclear because the word including is open ended and does not exclude other groups. See MPEP 2111.03 “The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) ("[L] ike the term ‘comprising,’ the terms ‘containing’ and ‘mixture’ are open-ended."). The metes and bounds of the invention cannot be ascertained. Examiner recommends amending the claim to delete “including” and instead recite “consisting of”, or other similar definite language. The claims recite the limitation “ heterocyclyl ” (e.g. see claim 1, T1 is selected from … heterocyclyl ; Q2 is… heterocyclyl ). The term “ heterocyclyl ” is indefinite because the scope of “ heterocyclyl ” is unclear based on Applicant’s disclosure. A person skilled in the art understands what heterocyclyl generally means; however, the definition provided at [0092] is open ended . Accordingly, skilled artisans can have different interpretations of which groups meet the limitation and so the scope of the claims cannot be determined. Examiner suggests amending the claim to clarify ring sizes and number of type of heteroatoms for which Applicant has written support. The claims recite the limitation “heteroaryl” (e.g. see claim 1, T1 is selected from … heteroaryl; Q2 is… heteroaryl). The term “heteroaryl” is indefinite because the scope of “heteroaryl” is unclear based on Applicant’s disclosure. A person skilled in the art understands what heteroaryl generally means; however, the definition provided at [0094] is open ended. Accordingly, skilled artisans can have different interpretations of which groups meet the limitation and so the scope of the claims cannot be determined. Examiner suggests amending the claim to clarify ring sizes and number of type of heteroatoms for which Applicant has written support. The claims recite the limitation “spirocyclic carbocycle” (e.g. see claim 1, T1 is selected from … spirocyclic carbocycle). The phrase “spirocyclic carbocycle” is indefinite because the scope of “spirocyclic carbocycle ” is unclear based on Applicant’s disclosure. A person skilled in the art understands what spirocyclic carbocycle generally means; however, there appears to be no definit ion of this term and the specification provides no direction otherwise for understanding the scope of this limitation. Accordingly, skilled artisans can have different interpretations of which groups meet the limitation and so the scope of the claims cannot be determined. 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). In the present instance, the claims recite the broad recitation “heterocyclic ring system”, and the claim also recite “heteroaryl” and “ heterocyclyl ” which are the narrower statement s of the range/limitation (see claim 1, T1 is selected from heterocyclyl , heteroaryl…or heterocyclic ring system). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature 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 claims. The claims (e.g. claim 1) also recite the broad limitation Y is selected from , and the claim also recites which is the narrower limitation. The claims fail to indicate how “Y” is connect to either X or Z and therefore is included in the scope of . The claims are therefore indefinite for the reason indicated in entry 7 above. Claim 18 recites “A compound…in particular”. Examiner suggesting deleting the phrase “in particular” as such language leads to confusion over the scope of the invention. See MPEP 2173.05(d). For instance, what other compounds does Applicant intend other than those that are recited in the claim? In claim 19 , “an effective amount” of the compound of claim 1 would be required to be present for the pharmaceutical composition to be effective. Insertion of the phrase “an effective amount” following “comprising” is suggested to indicate that what is intended. 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 1-19 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over cla ims 1-18 of U.S. Patent No. US12,358,915 . Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the patent claims. The patent claims are drawn to a compound of Formula X-Y-Z wherein X is selected from and Y is selected from a group including ; and Z is selected from a group including The patented genus overlaps and therefore anticipates the instant claims. Conclusion No claim is allowed Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT KEVIN MARTIN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0917 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 8 am - 5 pm . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Jeffrey Murray can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-9023 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. December 18, 2025 /K.S.M./ Examiner, Art Unit 1624 /BRUCK KIFLE/ Primary Examiner, Art Unit 1624