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 .
DETAILED ACTION
This office action is response to communication filed on 12/19/2025.
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on 12/19/2025, wherein R8 in compound of Formula V of claim 1 is amended to remove hydrogen, halogen, etc..
Election/Restriction
Applicant elected un-deuterated compound species (Example 146, page 205) with following structure, in the reply filed on 08/25/2025.
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The elected species, Example 146, N-{6-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]-5- methoxy-1,2-benzoxazol-3-yl}-4-[(2S)-1,4-dioxan-2-yl]-2,6-dimethoxybenzene-1- sulfonamide (CAS # 3081460-45-6 , entered STN on May 2025 ) is free of anticipatory prior art and rejected on the ground of non-statutory double patenting. Claim 1 in the claim set of 12/19/2025 is amended to remove hydrogen from R8 which was previously searched and rejected in last office action mailed on 09/26/2025. The examiner has expanded the search/ examination to non-elected species of compound Formula V, wherein R3, R4, R5, R6, R7 is H or methoxy, R10 is H, R8 is 5-8 membered heteroaryl which are rejected under following 103 rejection and on the ground of non-statutory double patenting over copending Application No. 18/903,849, and made Final. Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. It should be noted that prior art search will not be extended unnecessarily to cover all non-elected species.
Status of Claims
Claims 1-20 are pending in the instant application.
Claims 2, 12, 14-15 and 19-20 are withdrawn, being drawn to nonelected species.
Claims 1, 3-11, 13, and 16-18 are currently under examination.
Action Summary/ Response to Arguments
Applicant's Remarks filed 12/19/2025 have been fully considered. Any objection and rejection found in the previous Office Action and not repeated herein has been withdrawn in view of amendment and Applicant’s remarks .The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Copending US Application No. 19/241,666 is amended to recite one single compound species on 11/25/2025. As such, the provisional rejection on the ground of double patenting over copending Application No. 19/241,666 is withdrawn in light of amendment.
Applicant's arguments filed 12/19/2025 have been fully considered but they are NOT persuasive to overcome: 1) rejection of claims 1, 3-10, and 16 under 35 USC § 103 over Bozikis in view of Cheng, and 2) rejection of 1, 3-11, 13, and 16-18 on the ground of double patenting over copending Application No. 18/903,849.
Applicant argues “The Office Action has not established a prima facie case that the claimed compounds would have been obvious over the asserted combination of Bozikis, Cheng, and Patani.
As an initial matter, the rejection relies on impermissible hindsight to select Bozikis compounds 39 and 119 to be modified... The first step is to determine whether POSA would have selected the prior art compound as a lead compound for further development efforts.” (Remarks, page 19-20).
In RESPONSE to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Regarding the lead compound, Bozikis compounds 39 and 119 are only exemplary modification based on combined teaching of Bozikis and Cheng that could have arrived at instant claimed compound of Formula V. Other Bozikis compounds might also be modified based on Cheng’s teaching and general knowledge of structure similarity/ bioisosteric modification of SAR. Both Bozikis’ 946 and Cheng are directed to Lysine Acetyl Transferase KAT6 inhibitors comprising similar benzisoxazole sulfonamide scaffold. Please note Cheng embodiments wherein X is NR7 (R7 is H) read on instantly claimed compounds comprising NH between benzisoxazole sulfonamide and pyrazole moiety. X is selected from C, O and NR7 and CR or N in Y, Z moiety of Cheng further demonstrate C and N as commonly used bioisosteres for SAR study. Bioisosteric modification from CH2 to NH based on Grimm’s Hydride Displacement Law are commonly known practice as taught by Patani and Cheng.
Applicant argues “even a POSA had been motivated to replace the CH2 linker of any Bozikis compound with a new linker, armed with the teachings of Cheng, she would have been motivated to select an "O" or "S" linker rather than an NH linker. Cheng does not disclose any compounds with NH linkers” (Remarks, page 21-22)
RESPONSE: Although Cheng does not disclose any compounds with NH linker between benzisoxazole and pyrazole moiety, a skilled artisan would have known compounds with NH linker are encompassed by Cheng embodiments wherein X is NR7 (R7 is H). “O” or “S” linker in Cheng’s disclosed compound species might exhibit improved properties, it does not discourage a skilled artisan to explore “N” linker As stated in MPEP 2123(I): “A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Applicant argues Bozikis does not teach or suggest -(CHR11)n -4-8 membered heterocycloalkyl, 5-8 membered heteroaryl, or 9-10 membered heteroaryl as options for substitutions on the phenyl ring.
RESPONSE: Regarding the amended R8 of instant Formula V, R8c of Cheng’s Formula III comprising
C2-9 heterocycloalkyl, C2-9 heteroaryl are considered as read on the amended R8 of Formula V comprising 5-8 membered heteroaryl, or 9-10 membered heteroaryl. A skilled artisan would have reasonable expectation of success to arrive at modified compound comprising 5-8 membered heteroaryl in general as R8 that exhibit inhibition activity against Lysine Acetyl Transferase KAT6. As such, rejection of claims 1, 3-10, and 16 under 35 USC§ 103 is maintained/revisited in light of amendment for the reasons set forth herein. Please note claims 11,13 and 17-18 reciting compound species comprising specific heteroaryl moiety are not rejected under 35 USC§ 103.
Priority
This instant application 19/210,024, filed 05/16/2025, is a continuation of U.S. application No 18/903,849 filed 10/01/2024, and claims benefit of U.S. provisional application No. 63/542,051 filed October 2, 2023, U.S. provisional application No. 63/546,442 filed October 30, 2023, U.S. provisional application No. 63/566,213 filed March 15, 2024, U.S. provisional application No. 63/633,660 filed April 12, 2024, U.S. provisional application No. 63/665,990 filed June 28, 2024, and U.S. provisional application No. 63/697,154 filed September 20, 2024.
It’s noted U.S. provisional patent application No. 63/542,051 only disclosed Examples 1-138;
U.S. provisional application No. 63/546,442 filed October 30, 2023 disclosed Examples 1-143;
U.S. provisional application No. 63/566,213 filed March 15, 2024 disclosed Examples 1-145;
U.S. provisional application No. 63/633,660 filed April 12, 2024 disclosed Examples 1-153;
U.S. provisional application No. 63/665,990 filed June 28, 2024 disclosed Examples 1-179;
U.S. provisional application No. 63/697,154 filed September 20, 2024 disclosed Examples 1-276.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-10, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Bozikis et al. ( WO2020/254946 A1, hereafter “Bozikis’ 946, family member of US 11492346 B2, Applicant’s IDS dated 08/27/2025), in view of Cheng (WO2023/088233A1, Applicant’s IDS dated 08/27/2025) and Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: p 3147-3176)(maintained/reiterated necessitated by amendment).
Bozikis’ 946 teaches benzisoxazole sulfonamide, compound of Formula I, Ia, II, III, IV, V, VI or salt thereof, as Lysine Acetyl Transferase (KAT) inhibitors of the MYST family, pharmaceutical compositions thereof, and methods of treating abnormal cell growth (e.g. cancer ) with aforementioned benzisoxazole sulfonamide (See abstract; page 1, lines 1-10; page 6, lines 1-20; page 13, line 15; page 16, lines 7-23; Examples, 1-133; Tables 1- 18, claims 1-34).
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Bozikis’ 946 Formula II-VI comprising substituted phenyl as ring A and R2 comprising pyrazole ring are very similar to instant claimed core structure except CH2 vs NH between the substituted pyrazole and benzisoxazole.
Bozikis’ 946 teaches compound species that are very similar to instantly claimed benzisoxazole sulfonamide (See Table 1, Examples 11, 14-15, 17, 19, 26-28, 39-40, 96-98, 130, 119, 124, etc.) that read on instantly claimed R groups, e.g. R3 is hydrogen ( instant claim 3), R4, R5 is hydrogen (instant claim 5 and 6), R6 and R7 is methoxy (instant claim 8 ), R8 is hydrogen or methoxy (instant claim 9). Bozikis’ 946 also teaches embodiments comprising cyclopropyl as different R group (See page 13, lines 19, 21; page 16, lines 12, 14, 16; compound 96-97, 88, 130,etc. ).
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Bozikis’ 946 collectively teaches benzisoxazole sulfonamide comprising pyrazole moieties and variety of groups (H, methoxy, cyclopropyl, etc.) as Lysine Acetyl Transferase KAT6 inhibitor that are similar to instant claimed compounds.
The difference of Bozikis’ 946 and instantly claimed compounds is CH2 vs NH between benzisoxazole and pyrazole moiety. A skilled artisan would have known CH2, NH, O are classical bioequivalent isosteres due to interchangeable N and CH taught by Grimm’s Hydride Displacement Law: “Atoms anywhere up to four places in the periodic system before an inert gas change their properties by uniting with one to four hydrogen atoms, in such a manner that the resulting combinations behave like pseudoatoms, which are similar to elements in the groups one to four places respectively, to their right” as taught by Patani ( See p 3148-3149).
Further, Cheng teaches benzisoxazole sulfonamide, compound of Formula I, I’, II, III or salt thereof, as Lysine Acetyl Transferase KAT6 inhibitor, pharmaceutical compositions thereof, and methods of treating disease/disorder associated with KAT 6A with aforementioned benzisoxazole sulfonamide (See abstract; [0003], [0011, Examples ; Table 1, claims 1-98).
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Please note Cheng embodiments wherein X is NR7 (R7 is H) read on instantly claimed compounds comprising NH between benzisoxazole sulfonamide and pyrazole moiety. X is selected from C, O and NR7 and CR or N in Y, Z moiety of Cheng further demonstrate C and N as commonly used bioisosteres for SAR study.
R8c of Cheng’s Formula III comprising C2-9 heterocycloalkyl, C1-9 heteroaryl are considered as read on instant amended R8 of Formula V.
Cheng collectively teaches variety of R groups at different positions of benzisoxazole sulfonamide, e.g. R1 is C1-9 heteroaryl (e.g. pyrazole ) further substituted with R15 (e.g. C3-10 cycloalkyl), R8 is hydrogen, C3-6 cycloalkyl, C2-9 heterocycloalkyl, etc.) that are very similar to instant claimed R groups(e.g. H, methoxy, cyclopropyl, etc.). Cheng teaches embodiments wherein R1 is selected from pyrazole, imidazolyl, oxazolyl, etc. further substituted with R15, and compound species that are very similar to instantly claimed benzisoxazole sulfonamide (See [0018], [00227]-[00229], [00231], Table 1, claim ) that read on instantly claimed R groups, e.g. R3 is hydrogen, R4, R5 is hydrogen, R6, R7 and R8 are hydrogen or methoxy.
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According to MPEP 2144.09 (I), A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). Please note prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979), See MPEP 2144.09 III.
It would have been obvious for one of ordinary skilled in the art to further explore more benzisoxazole sulfonamide as Lysine Acetyl Transferase KAT6 inhibitor based on combined teachings of Bozikis’ 946 and Cheng, together with experimentation/optimization based on general knowledge of structure similarity/ bioisosteric modification of SAR study, and arrive at instantly claimed invention with reasonable expected success. For example, compound 39 and 119 taught by Bozikis’ 946 could have been modified by replacing CH2 with NH based on Grimm’s Hydride Displacement Law as taught by Patani and Cheng, which could be further modified based on the combined teaching of R groups as taught by Bozikis’ 946 and Cheng. Cheng also teaches R8c could be C2-9 heterocycloalkyl, C1-9 heteroaryl which are considered as read on instant amended R8 of Formula V.
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A skilled artisan would be motivated to combine the teachings of Bozikis’ 946 and Cheng because both teachings are directed to Lysine Acetyl Transferase KAT6 inhibitors comprising similar benzisoxazole sulfonamide scaffold. Bioisosteric modification from CH2 to NH based on Grimm’s Hydride Displacement Law are commonly known practice as taught by Patani and Cheng. Cheng collectively teaches variety of R groups at different positions of benzisoxazole sulfonamide, e.g. R1 is pyrazole further substituted with R15 (e.g. C3-10 cycloalkyl), R8 is hydrogen, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C1-9 heteroaryl, etc. that are similar to instant claimed compounds. Further exploration/optimization based on the combined teachings of prior art, together with general knowledge of structure similarity/ bioisosteric modification of SAR would provide alternative benzisoxazole sulfonamide compounds that are expected to have inhibitory activity on Lysine Acetyl Transferase KAT6 for treating disease/disorder associated with KAT6 (e.g. cancer).
Regarding the amended R8 of instant Formula V, a skilled artisan would have reasonable expectation of success to arrive at compound comprising 5-8 membered heteroaryl in general as R8 as Lysine Acetyl Transferase KAT6 inhibitors. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1, 3-11, 13, and 16-18 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21- 32 of copending Application No. 18/903,849. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented(maintained).
Reference claim 21 are directed to compound of V comprising the same core structure as instant compound of Formula V with the same scope of substituents.
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Reference claim 22- 24 recite compound species that read on instant elected species and instant claims 11 and 13.
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Reference claim 32 reciters pharmaceutical composition that read on instant claims 16-18. Reference claims anticipate instant claims. As such, reference claims anticipate instant claims.
Instant application is continuation of reference application. There is no Restriction Requirement in 18/903,849 on the record, thus no 35 USC 121 shield exists. See MPEP 804.01.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on (571)272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LIYUAN MOU/ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628