DETAILED ACTION The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. This application is a continuation of US 16/345,792, filed 04/29/2019 (now US Patent No. 11,857,513), which was the national stage of PCT/JP2017/037186, filed 10/13/2017, claiming foreign priority benefit to JP2016-213072, filed 10/31/2016. Information Disclosure Statement Regarding the information disclosure statement (IDS) filed 15 January 2025, the IDS fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because a complete citation for cite 6, Kagawa et al , was not provided; specifically, no date is present in either the citation or on the document itself. While the reference as filed is present in the application file, it has not been considered. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a). Claim Interpretation Regarding the limitation “malignant tumor patient expressing EGFR having exon 20 insertion mutation” (see independent claim 9 at lines 1-2), this language is interpreted as encompassing a patient expressing EGFR “having exon 20 insertion mutation in at least one part of the exon 20 region of EGFR”, where such expression is occurring in any type of patient tissue/cells/fluids, etc., as this is the broadest reasonable interpretation of the claim language consistent with the teachings of the specification (see, e.g., the discussion of such patients at page 11). Claim Rejections - 35 USC § 112(a) – Scope of Enablement 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 9 , 12, and 14-21 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 methods of treat ing a malignant lung tumor patient expressing EGFR having exon 20 insertion mutation, does not reasonably provide enablement for methods of treating any type of “malignant tumor patient expressing EGFR having exon 20 insertion mutation”, as recited in the claims. 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. There are many factors to be considered when determining compliance with the enablement requirement of 35 USC 112(a), including, but 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. In re Wands , 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). All evidence related to each of these factors has been considered, and the conclusion that enablement is lacking, as set forth below, is based on the evidence as a whole. ( MPEP 2164.01(a)). Instant independent claim 9 (which is the only independent claim) is drawn to a method “for treating a malignant tumor patient expressing EGFR having exon 20 insertion mutation, comprising administering to the malignant tumor patient an effective amount of (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide or a salt thereof” ; it is noted that (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide will be hereinafter referred to as “Compound A” (consistent with the terminology of the specification; see, e.g., page 12) . The claimed invention is thus directed to a method of “treatment” – i.e., a method that requires enablement of the use/practice of “treating” a patient - and the scope of the claim encompasses any “malignant tumor patient” expressing EGFR having a mutation as recited therein (such that any type of tumor/cancer is embraced by the claims) . It is noted that dependent claim 13, which requires that “the malignant tumor patient is a lung cancer patient”, has been excluded from the rejection, and that claim 12 is enabled to the extent that it is directed to a “patient with lung cancer”, but has been included in the rejection as it recites the alternatives of “breast cancer, head and neck cancer, brain tumor, uterine cancer, hematopoietic tumor, or skin cancer”. Dependent claims 14-21 recites more preferred types of EGFR exon 20 insertion mutations, but – like independent claim 9 – embrace any type of “malignant tumor patient”. It is unpredictable as to whether one of skill in the relevant art could actually use the invention in a manner commensurate in scope with the claims. The specification does not exemplify the successful treatment of any “malignant tumor patient”, but does provide examples of the effectiveness of Compound A in inhibiting growth of mutant EGFR-expression cell lines, which cell lines included cells expressing EGFR exon 20 insertion mutations (Examples 1-4), as well an “antitumor effect” of Compound A with respect to such cells (i.e., cells expressing EGFR exon 20 insertion mutations) – which include human pulmonary adenocarcinoma cells – when engrafted in nude mice and nude rats (Examples 5-7), as well as with respect to nude mice subcutaneously transplanted with a EGFR exon 20 insertion mutation-positive tumor derived from a human lung cancer patient (Example 8). The specification thus provides multiple types of data/evidence related to effectiveness of Compound A with respect to lung cancer and EGFR exon 20 insertion mutations, but fails to provide such data/evidence regarding other cancer/tumor types. When enabling guidance is lacking in the specification, one of skill in the art may look to the teachings of the prior art for further teachings and guidance regarding how to use a claimed invention. I n the instant case, the prior art as exemplified by Uno et al (CA 2922077 [26 February 2015]; cited herein) demonstrates effectiveness of a group of compounds including Compound A in inhibiting growth of human lung cancer cell lines expressing different types of EGFR mutations (i.e., mutations differing from those embraced by the present claims) (see entire reference, particularly the Examples at pages 125-128) . Taken together, the evidence provided in the specification in light of the teachings of the prior art are sufficient to support a conclusion that the instant claims are enabled with regard to the embodiment of lung cancer/a malignant lung tumor; however, the scope of the claims is much broader, encompassing any type of tumor/cancer. With regard to the amount of guidance/direction needed to enable a claimed invention, MPEP 2164.03 states: The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because in art areas having a high degree of uncertainty (i.e. the unpredictable arts) it is not reasonably predictable from the disclosure of one species, what other species will work. In the instant case, the claims are directed to treating cancer – an area involving biological and physiological activity and a high degree of unpredictability and uncertainty – and the limited data provided by the specification in light of the teachings of the art does not support a conclusion that the claims are enabled over their broad scope. Given the high level of skill of one skilled in the relevant art, it is certainly within the ability of such an artisan to conduct further experimentation aimed at establishing the extent to which Compound A is/is not effective to treat cancer s of various types ; however, the results of such testing are entirely unpredictable, and it possible (given the lack of data/evidence in the specification and prior art) that even an infinite amount of experimentation would be insufficient to enable the claims with regard to any type of tumor/cancer other than lung cancer. A s this type of experimentation is clearly undue, it would require undue experimentation to use the invention in a manner commensurate in scope with the present claims. With further regard to claim 12, it is reiterated that this claim is considered enabled with regard to the alternative of lung cancer; however the majority of cancer types recited in the claim cannot reasonably be considered as enabled. With regard to both this claim and claim 9 and its dependent claims more generally, it is noted that MPEP 2164.08(b) states that “ claims reading on significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative. Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA1971) ”. In the instant case, the language of the claims clearly embraces numerous embodiments for which enablement has not been established, and undue experimentation would be required to determine other operative embodiments (as discussed above). Regarding dependent claims 14-21, each of these claims also embraces any type of tumor/cancer, and therefore the claims lack enablement for the same reasons discussed above. 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 . Claims 9 and 12-21 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-9 of U.S. Patent No. 11,857, 513 (cited herein ). Although the claims at issue are not identical, they are not patentably distinct from each other because the ’513 claims anticipate the instant claims . Instant independent claim 9 (from which claims 12-21 depend) is drawn to a method “for treating a malignant tumor patient expressing EGFR having exon 20 insertion mutation, comprising: administering to the malignant tumor patient an effective amount of (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4- b]indolizin -8-yl)acrylamide or a salt thereof”. The claim thus encompass performing an “administering” as recited with respect to any “malignant tumor patient” meeting the criteria of “expressing EGFR having exon 20 insertion mutation”. The ‘513 claims are drawn to a method “of treating a subject with a malignant lung tumor” ( i.e., a method practiced with regard to a subject/patient having a more specific type of “malignant tumor” ), the method comprising “detecting whether the maligna nt lung tumor expresses EGFR having a mutation of exon 20 insertion” (i.e., the type of mutation recited in instant claim 9), and “if the malignant lung tumor expresses EGFR having mutation, administering to the subject an effect amount of an antitumor agent comprising (S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide or a salt thereof” (i.e., the same compound of instant claim 9). The ‘513 claims thus require performing the same type of treatment specified in the instant claims with respect to a type of patient established via performance of the “detecting” of the ‘513 claims as meeting the criteria of the instant claims. P erforming the method of the ‘513 claims thus results in performing a type of “treating” that is a species encompassed by the broader genus of instant claim 9 (as a subject with a “malignant lung tumor” expressing “EGFR having a mutation of exon 20 insertion” is encompassed by the more broadly recited subject type of the instant claims), and the ‘513 claims thus anticipate instant claim 9. With further regard to instant dependent claim 12-13, it is reiterated that lung cancer is recited in the ‘513 claims, such that at least the first alternative of claim 12 is suggested by the ‘513 claims, rendering the claim prima facie obvious over the ‘513 claims. Regarding claim 13, the claim requires that “the malignant tumor patient is a lung cancer patient”, such that this claim is also anticipated by the ‘513 claims. Regarding instant claims 14-21, these claims recite more preferred types of exon 20 insertion mutations that are also recited in ‘513 claims 2-5. To the extent that the instant claims recite the same preferred embodiment as is recited in a ‘513 claim, that claim is anticipated by the ‘513 claims; further, the recitation of the same types of insertion mutations in the ‘513 claims also suggest the types of preferred mutations recited in the instant claims, rendering each of the instant claims obvious over the ‘513 claims. Accordingly, instant claims 9 and 12-21 are not patentably distinct from ‘513 claims 1-9. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT DIANA B JOHANNSEN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-0744 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday-Friday, 7:30 am-3:30 pm 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 Wu-Cheng Winston Shen can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-3157 . 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. /DIANA B JOHANNSEN/ Primary Examiner, Art Unit 1682