NON-FINAL REJECTION
This application, filed Aug. 2, 2023, is a Continuation-in-Part of PCT/US23/12299, filed Feb. 3, 2023, which claims benefit of priority to provisional applications 63/306,271, filed Feb. 3, 2022; 63/327,625, filed Apr. 5, 2022; 63/352,180, filed Jun. 14, 2022; 63/432,243, filed Dec. 13, 2022; 63/434,327, filed Dec. 21, 2022, and 63/442,648, filed Feb. 1, 2023.
Claims 1-50, as amended, are pending.
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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Additionally, it is noted that the earliest support for the elected compound species, compound 78, is found in provisional application 63/352,180, filed Jun. 14, 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on May 24, 2024 (6) and Jun. 2, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to compounds; and the species of compound 78, having the structural formula,
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in the reply filed on Jan. 28, 2026 is acknowledged.
Compound 78 reads on formula (I) as recited by claims 1, 2, 4, 6, 8-11, 15, 16, 18, 20, and 25-27, wherein:
A is aryl (naphthyl), substituted by three R1 (fluoro, hydroxy, and ethyl);
B is pyrrolizidine, wherein R2 is halogen (fluoro) and n is 1; and R3 is H or n is 0;
L is a bond;
Z is C and R10 is halogen (fluoro);
R4 is halogen (fluoro) and each R6 is hydrogen;
Y1 and Y2 join to form diazepane, wherein X is -CH2N-; and two R7 on adjacent atoms of the diazepane join to form a fused heteroaryl (pyrazole) substituted with two R8: halogen (chloro) and -C(O)-N(CH3)2.
Claims 3, 5, 7, 12-14, 17, 19, 21-24, and 28-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on Jan. 28, 2026.
Claims 1, 2, 4, 6, 8-11, 15, 16, 18, 20, and 25-27 are currently pending and under consideration.
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.
Claims 1, 2, 4, 6, 8-11, 15, 16, 18, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (WO2022/068921, cited on the IDS dated 6/2/2025).
Zhang et al. exemplify compound 280a (pp. 717, 932), having the structural formula,
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which reads on formula (I) as recited by claims 1, 2, 4, 6, 8, 9, 11, 15, 16, and 18, wherein:
A is aryl (naphthyl), substituted by two R1 (fluoro and ethyl);
B is pyrrolizidine, wherein R2 is halogen (fluoro) and n is 1; and R3 is H or n is 0;
L is a bond;
Z is C and R10 is halogen (fluoro);
R4 is halogen (fluoro) and each R6 is hydrogen;
Y1 and Y2 join to form 3,8-diazabicyclo[3.2.1]oct-3-yl, wherein X is NH; and two R7 on non-adjacent atoms of the piperazine join to form a two-carbon (-CH2CH2-) bridge.
Zhang et al. further exemplify compound 285a (pp. 734, 934), having the structural formula,
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which reads on formula (I) as recited by claims 1, 2, 4, 6, 8, 10, 11, 15, 16, and 18, wherein:
A is aryl (naphthyl), substituted by two R1 (hydroxy and ethyl);
B is pyrrolizidine, wherein R2 is halogen (fluoro) and n is 1; and R3 is H or n is 0;
L is a bond;
Z is C and R10 is halogen (fluoro);
R4 is halogen (fluoro) and each R6 is hydrogen;
Y1 and Y2 join to form 3,8-diazabicyclo[3.2.1]oct-3-yl, wherein X is NH; and two R7 on non-adjacent atoms of the piperazine join to form a two-carbon (-CH2CH2-) bridge.
The compounds of Zhang et al. are disclosed in pharmaceutical compositions together with one or more pharmaceutical excipients (claim 19), as recited by claim 27.
Thus, Zhang et al. anticipates claims 1, 2, 4, 6, 8-11, 15, 16, 18, and 27.
Claims 1, 2, 4, 6, 9-11, 15, 16, 18, and 27 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Xiao et al. (WO2023/138583, cited on the IDS dated 6/2/2025).
Xiao et al. disclose compounds of formula (I-0) as KRAS G12D inhibitors, useful in the treatment of tumors, and pharmaceutical compositions comprising the compounds (para. [0006]).
In particular, Xiao et al. exemplify the compound of example 45 (p. 135; claim 12), having the structural formula,
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which reads on formula (I) as recited by claims 1, 2, 4, 6, 9-11, 15, 16, and 18, wherein:
A is aryl (naphthyl), substituted by three R1 (fluoro, hydroxy, and ethynyl);
B is pyrrolizidine, wherein R2 is halogen (fluoro) and n is 1; and R3 is H or n is 0;
L is a bond;
Z is C and R10 is halogen (chloro);
R4 is halogen (fluoro) and each R6 is hydrogen;
Y1 and Y2 join to form 3,8-diazabicyclo[3.2.1]oct-3-yl, wherein X is NH; and two R7 on non-adjacent atoms of the piperazine join to form a two-carbon (-CH2CH2-) bridge.
The compounds of Xiao et al. are disclosed in pharmaceutical compositions together with pharmaceutical excipients (claim 17), as recited by claim 27.
Thus, Xiao et al. anticipates claims 1, 2, 4, 6, 9-11, 15, 16, 18, and 27.
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 nonobviousness.
Claims 1, 2, 4, 6, 8-11, 15, 16, 18, 20, and 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over Xiao et al. (WO2023/138583) in view of Zhang et al. (WO2022/068921) (both cited on the IDS dated 6/2/2025).
Xiao et al. disclose compounds of formula (I-0) as KRAS G12D inhibitors, useful in the treatment of tumors, and pharmaceutical compositions comprising the compounds (para. [0006]).
In particular, Xiao et al. exemplify and claim compound 153 (p. 232, para. [1200]; claim 12, p. 287), having the structural formula,
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which reads on formula (I) as recited by claims 1, 2, 4, 6, 9, 10, 15, 16, 18, 20, and 25, to the extent that
A is aryl (naphthyl), substituted by three R1 (fluoro, hydroxy, and ethynyl);
B is pyrrolizidine, wherein R2 and R3 are each hydrogen and/or n is 0;
L is a bond;
Z is C;
R4 is halogen (fluoro) and each R6 is hydrogen;
Y1 and Y2 join to form diazepane, wherein X is -CH2N-; and two R7 on adjacent atoms of the diazepane join to form a fused heteroaryl (pyrazole) substituted with two R8: halogen (chloro) and -C(O)-N(CH3)2.
The compounds of Xiao et al. are disclosed in pharmaceutical compositions together with pharmaceutical excipients (claim 17), as recited by claim 27.
Compound 153 of Xiao et al. differs from the elected compound 78 as recited by claim 26, in that:
the substituent R10 is nitro instead of halogen (fluoro); as recited by claim 1;
one substituent R1 is ethynyl instead of ethyl, as recited by claim 8; and
the substituent R2 is hydrogen instead of fluorine, as recited by claim 11.
However, Xiao et al. exemplify compound 153 as a species of formula (I-0) (claim 1, p. 252), having the structural formula shown below (bottom left):
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Xiao et al. teach that compounds of Formula (I-0) encompass compounds wherein:
X1 is CRX1, and RX1 is selected from various electron-withdrawing substituents, many of which are exemplified, including nitro, cyano (e.g., compounds 22, 24, 26, 47), -CF3 (e.g., compound 50), or halogen, e.g., chloro (compounds 44-46);
R1-1 substituents on the naphthyl ring include C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
the pyrrolizidine may be substituted by, e.g., halogen, and exemplifies several compounds wherein pyrrolizidine is substituted by fluoro (e.g., compounds 10-18).
Thus, Xiao et al. explicitly disclose, teach, and suggest compounds of Formula (I-0) as KRAS G12D inhibitors, having a core structure identical to the elected compound species, bearing various substituents which may be modified to those of elected compound 78 with no loss of function.
In addition, Zhang et al. disclose and claim quinazoline compounds with activity as KRAS inhibitors, useful for the prevention and/or treatment of cancer mediated by KRAS mutation, e.g., a KRAS G12D mutant protein (abstract; claims 20-21).
In particular, Zhang et al. exemplify compounds 280a and 285a, demonstrating that modifying nitro to fluoro, ethynyl to ethyl, and hydrogen to fluorine results in compounds that retain biological activity as KRAS inhibitors:
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Therefore, it would have been predictable to one of ordinary skill in the art as of the effective filing date to modify compound 153 of Xiao et al. as taught by Zhang et al. to arrive at the elected species, compound 78, with a reasonable expectation of success, because both references exemplify compounds with the identical core structure and identical substituents as KRAS G12D inhibitors useful for treating cancer or tumors.
The rationale to modify the compounds of Xiao et al. is not derived from Applicant but from the references themselves, in that the prior art compounds are not only structurally similar to those claimed, but are also disclosed to have the same mechanism of action and biological activity, as inhibitors of KRAS, useful for the same purpose in the treatment of tumors or cancer.
As recognized by MPEP § 2144.09, a prima facie case of obviousness may be made when chemical compounds have (1) very close structural similarities and (2) 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).
The closer the chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., In re Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904 (and cases cited therein); and In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995).
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, 2, 4, 6, 8-11, 15, 16, 18, and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/563,357 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims encompass compounds falling within the scope of the examined claims.
Specifically, reference claim 1 is drawn to compounds of formula (I),
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which encompasses disclosed compound species including, e.g., the compound of Example 92,
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which reads on formula (I) as recited by examined claims 1, 2, 4, 6, 8-11, 15, 16, 18, and 27, wherein:
A is aryl (naphthyl), substituted by three R1 (fluoro, hydroxy, and ethyl);
B is pyrrolizidine, wherein R2 is halogen (fluoro), and R3 is H or n is 0;
L is a bond;
Z is C and R10 is hydrogen or absent;
R4 is halogen (fluoro) and each R6 is hydrogen; and
Y1 and Y2 join to form 3,8-diazabicyclo[3.2.1]oct-3-yl, wherein X is NH; and two R7 on non-adjacent atoms of the piperazine join to form a two-carbon (-CH2CH2-) bridge.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 4, 6, 10, 11, 15, 16, 18, and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-7, 9-12, and 14-35 of copending Application No. 18/034,852 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims encompass compounds falling within the scope of the examined claims.
Specifically, reference claim 26 recites the compound species,
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which reads on formula (I) as recited by examined claims 1, 2, 4, 6, 10, 11, 15, 16, 18, and 27, wherein:
A is aryl (naphthyl), substituted by one R1 (hydroxy);
B is pyrrolizidine, wherein R2 is halogen (fluoro), and R3 is H or n is 0;
L is a bond;
Z is C and R10 is hydrogen or absent;
R4 is halogen (fluoro) and each R6 is hydrogen; and
Y1 and Y2 join to form 3,8-diazabicyclo[3.2.1]oct-3-yl, wherein X is NH; and two R7 on non-adjacent atoms of the piperazine join to form a two-carbon (-CH2CH2-) bridge.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Citation of Additional Prior Art
Additional references made of record are considered pertinent to applicant's disclosure: Jia et al. (WO2023/213269, cited on PTO-892).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 9:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629