NON-FINAL REJECTION
Receipt is acknowledged of Applicants' Amendments and Remarks, filed Jan. 15, 2026.
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The rejections and/or objections set forth below are either maintained or newly applied, and constitute the complete set presently applied to the instant claims.
STATUS OF THE CLAIMS
Claim 8 has been canceled.
Claim 1 has been amended and incorporates no new matter.
No new claims have been added.
Claims 6, 7, 9-14, and 18-21 stand withdrawn as drawn to nonelected inventions and/or species.
Thus, claims 1-5 and 15-17 are currently pending and under consideration.
INFORMATION DISCLOSURE STATEMENT
The information disclosure statement (IDS) submitted on Jan. 15, 2026 was filed after the mailing date of the non-final action on Oct. 20, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the examiner.
MAINTAINED REJECTIONS
The following rejection is maintained from the previous Office Action dated Oct. 20, 2025, on the ground that the references cited therein continue to read on the limitations of the amended claims.
Double Patenting Rejections
Claims 1-5 and 15-17 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 6-14 of U.S. Patent No. 12/227,501.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed compounds of generic formula (I) largely overlap, with only minor variations on the common structural core, as shown side-by-side below for comparison:
Examined Claim 1 (instant application)
Reference Claim 1 ('501 patent)
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L is C-C or C=C,
unsubstituted or substituted by C1-3 alkyl, etc.
R13a and R13b are H, C1-4 alkyl, etc.
R1, R2a, R2b, R2c is
H, -OH, cyano, halo, etc.
R1, R2a, R2b, R2c can be
H, -OH, cyano, halo, etc.
A is selected from
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A is selected from
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X is methylene or ethylene
X is methylene or ethylene
Y is phenyl or heteroaryl
Y is phenyl or heteroaryl
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In particular, reference claim 4 recites the compound of Example 61, (col. 333, lines 17-19; col. 211, lines 1-40), having the structural formula,
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which is identical to the compound of Example 28 as recited by examined claim 5 (fifth compound listed on p. 14); and reads on examined claims 1-4 and 15-17.
Reference claim 12 recites a pharmaceutical composition comprising a compound of general formula (I) together with at least one pharmaceutically acceptable auxiliary (excipient), as recited by examined claim 15.
Reference claims 6-11 and 13 recite methods of administering a compound of general formula (I) to treat lymphoma, lung cancer, colon cancer, and metastases thereof in a subject, as recited by examined claim 16.
Reference claim 14 recites a combination comprising one or more first active ingredients selected from a compound of general formula (I), and one or more second active ingredients selected from chemotherapeutic anti-cancer agents and target-specific anti-cancer agents, as recited by examined claim 17.
For the foregoing reasons, examined claims 1-5 and 15-17 would be anticipated by and/or prima facie obvious over USPN 12,227,501.
RESPONSE TO ARGUMENTS
Applicant’s arguments filed Jan. 15, 2026, with respect to (1) the rejection of claims 1-4, 15, and 16 under 35 U.S.C. § 103, and (2) the rejection of claims 1-5 and 15-17 on the ground of nonstatutory double patenting over Application No. 18/018,207 (see Remarks, p. 25) have been fully considered and are persuasive. Therefore, the rejections have been withdrawn.
However, upon further consideration, new grounds of rejection are made in view of Graham et al. (WO 2016/120196), as detailed below.
Applicant's arguments do not address the rejection of claims 1-5 and 15-17 on the ground of nonstatutory double patenting over USPN 12,227,501. Therefore, the rejection is maintained.
NEW REJECTIONS
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 1-4 and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Graham et al. (WO 2016/120196, cited on the IDS dated 4/21/2023) in view of Vernier et al. (US2004/0209897, of record).
Graham et al. disclose compounds of formula (I) for use in the treatment or prophylaxis of hyperproliferative diseases, e.g., hematological or solid tumors, such as cervical, breast, non-small cell lung, prostate, colon, and melanoma, and/or metastases thereof (claims 7-10).
The compounds of Graham et al. are claimed in pharmaceutical compositions together with at least one pharmaceutically acceptable excipient; and in combinations comprising one or more second active ingredients selected from chemotherapeutic anti-cancer agents and target specific anti-cancer agents (claims 11-13), as recited by claims 15-17.
Graham et al. disclose compounds of formula (I) (claim 1), having the structural formula,
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which includes, e.g., the compound of Example 14 (pp. 105-106), having the structural formula,
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which reads on claims 1-4 to the extent that A is phenyl; L is -C-C-; R1, R2a, R2b, R2c, R8a, R8b, R18, and R19 are each hydrogen; and X is methylene.
Compound 14 of Graham et al. differs from the instant claims in that the claims require R17 to be substituted by C1-3-alkyl, C1-3-alkoxy, C1-3-haloalkyl, or C3-6-cycloalkyl-C1-4-alkyl.
However, formula (I) of Graham et al. encompasses compounds wherein RA is hydrogen or C1-4-alkyl. Thus, Graham et al. explicitly teach and suggest that compounds of formula (I) may be unsubstituted or substituted by, e.g., methyl, at R17.
Furthermore, where a compound is disclosed to have a particular utility, one of ordinary skill in the art would have a reasonable expectation that modifying the compound by the interchange of hydrogen and alkyl would yield compounds having similar properties, and thus have been held to be obvious variants. See, e.g., In re Wood, 582 F.2d 638, 199 USPQ 137 (CCPA, 1978).
Formula (I) of Graham et al. encompasses compounds wherein the pyridine ring is substituted by R8,
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wherein R8 is selected from, e.g., -NH-C(O)-R11, where R11 is C1-4-alkyl, C3-6-cycloalkyl, C1-4-haloalkyl or C3-6-halocycloalkyl (claim 1, p. 143, lines 20-21).
Thus, while formula (I) of Graham et al. encompasses compounds having an amide-alkyl linker between the pyridine ring and a C3-6-cycloalkyl ring (saturated), Graham et al. differs from the claimed compounds in that the reference does not teach or suggest compounds wherein R11 (Y) is phenyl or heteroaryl (unsaturated).
Vernier et al. disclose compounds of formula (V) (paras. [0359]-[0387]),
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useful for preventing and treating diseases and disorders that are mediated by TNFα, including hyperproliferative and neoplasia disorders, tumors, and cancers (abstract; para. [0430]).
Specifically, Vernier et al. exemplify compound 686, having the structural formula,
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which was found to be a highly potent inhibitor of MK-2 with an average IC50 of 1.06 μM (Table I, p. 231; Example 837). Compound 686 reads on claim 1 to the extent that R1, R2a, R2b, and R2c are hydrogen; L is CH2-CH2; X is ethylene; and Y is unsubstituted phenyl.
In addition, Formula (V) encompasses compounds wherein Y'' is CR5 (para. [0393]); R5 is, e.g., NHR7 (para. [0361]); and R7 is, e.g., aryl, heteroaryl, or aralkyl (para. [0362]). While this feature is not exemplified by Vernier et al., it is shown in compound 14 of Graham et al., shown side-by-side for comparison with Vernier et al. compound 686:
Graham et al.
Compound 14
Vernier et al.
Compound 686
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One of ordinary skill in the art would have been motivated to modify the compounds of Graham et al. in view of Vernier et al. to arrive at the claimed compounds with a reasonable expectation of success, because Formula (V) of Vernier et al. encompasses Formula (I) of Graham et al., and the compounds of both references are disclosed for the treatment of the same diseases (hyperproliferative and neoplastic disorders, tumors, and cancers).
In particular, compound 14 of Graham et al. falls within the scope of the claimed compounds except for the terminal aryl or heteroaryl substituent (Y), and is disclosed to be a highly potent inhibitor of Bub-1 kinase with a median IC50 of 1.83 E-8 mol/L (Table, p. 140).
The compounds of Graham et al. are disclosed to inhibit, block, reduce, or decrease cell proliferation and/or cell division, and/or produce cell death/apoptosis, and thus have utility for treating many different types of hyper-proliferative disorders, including solid tumors, such as cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid, and their distant metastases; as well as lymphomas, sarcomas, and leukemias (p. 72, line 7 to p. 73, line 28).
Compound 686 of Vernier et al. is disclosed to be a highly potent inhibitor of MK-2 with an average IC50 of 1.06 μM (Table 1, p. 231). The compounds of Vernier et al. are also taught to be useful for treating cancers, neoplasms, tumors, sarcomas, and carcinomas in many different tissues and organs (para. [0430]).
Graham et al. Compound 14 modified in view of Vernier et al. Compound 686
Claimed Formula (I)
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While the compounds of Graham et al. and the compounds of Vernier et al. are disclosed to have different mechanisms of action, they share the identical 2-pyridin-4-yl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one structural core with the claimed compounds, and are disclosed to be useful in treating the same diseases in the same patient populations, regardless of the mechanism of action.
Therefore, it would have been predictable to one of ordinary skill in the art as of the effective filing date to modify the compounds of Graham et al. by adding a terminal aryl, aralkyl, or heteroaryl group as taught by Vernier et al. to arrive at the claimed compounds with a reasonable expectation of success, because Formula (V) of Vernier et al. encompasses Formula (I) of Graham et al.; both references exemplify compounds which share the identical core structure with the claimed compounds; and both are disclosed to have the same utility as the claimed compounds in treating a wide variety of cancers.
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 688 at 693, 16 USPQ2d 1897 (Fed. Cir. 1991) and In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995).
While the compounds of Graham et al. and Vernier et al. are not explicitly disclosed to have the same mechanism of action asserted by Applicants – as inhibitors of casein kinase 1A (CSNK1A) – this is an inherent property of the claimed compounds when administered to treat the same diseases in the same patient population, and is not in itself sufficient to distinguish the claimed genus from the prior art.
Obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).
Double Patenting Rejections
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 1-5 and 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-15, and 17 of copending Application No. 18/018,207 (reference application) in view of Graham et al. (WO 2016/120196, cited on the IDS dated 4/21/2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because reference formula (I) and examined formula (I) are identical with the exception of the -NH- linker to the A-ring, as shown side-by-side below for comparison:
Examined Claim 1 (instant application)
Reference Claim 1 ('207)
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A is phenyl, pyridine, other monocyclic heteroaryl
A is phenyl, pyridine, other monocyclic heteroaryl with no NH linker
R1 is H, C1-4 alkyl, C3-6 cycloalkyl, etc.
R1 is H, C1-4 alkyl, C3-6 cycloalkyl, etc.
L is C-C or C=C
L is C-C or C=C
R2a, R2b, R2c are H, -OH, cyano, halo, etc.
R2a, R2b, R2c are H, -OH, cyano, halo, etc.
X is methylene or ethylene
X is methylene or ethylene
Y is phenyl or heteroaryl
Y is phenyl or heteroaryl
Compounds of formula (I) of reference claims 1-5 differ from the examined claims only in that the reference compounds lack the -NH- linker between the A ring and the pyrrole ring.
However, Graham et al. disclose compounds of formula (I) (claim 1), having the structural formula,
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wherein E is, e.g., pyridine; and A is phenyl or pyridine.
Thus, Graham et al. explicitly disclose, teach, and suggest that compounds of formula (I) may be substituted on the pyrrole ring by NH-aryl or NH-heteroaryl for use in treating various types of hyperproliferative disorders, including solid tumors, such as cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid, and their distant metastases; as well as lymphomas, sarcomas, and leukemias (p. 72, line 7 to p. 73, line 28).
Modifying the reference compounds by including an NH linker to ring A (aryl or heteroaryl), as taught by Graham et al., yields compounds which fall within the scope of formula (I) as recited by the examined claims.
It would have been predictable to one of ordinary skill in the art as of the filing date to modify the reference compounds by adding an -NH- linker between the A ring substituent (aryl or heteroaryl) and the pyrrole ring to arrive at the compounds of the examined claims with a reasonable expectation of success, because both the reference compounds and the compounds of Graham et al. are disclosed to be useful for treating the same diseases, such as cancer, tumors, and neoplasms, in the same patient populations.
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).
Reference claim 15 recites a pharmaceutical composition comprising a compound of general formula (I) together with at least one pharmaceutically acceptable auxiliary (excipient), as recited by examined claim 15.
Reference claims 8-14 recite methods of treating or preventing hematological tumors, solid tumors and/or metastases thereof by administering a compound of general formula (I), as recited by examined claim 16.
Reference claim 17 recites a combination comprising one or more first active ingredients selected from a compound of general formula (I), and one or more second active ingredients selected from chemotherapeutic anti-cancer agents and target-specific anti-cancer agents, as recited by examined claim 17.
For the foregoing reasons, examined claims 1-5 and 15-17 would have been prima facie obvious over US Application No. 18/018,207 in view of Graham et al.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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