DETAILED ACTION
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 .
This Final Rejection SUPERSEEDS the Final dated 12/11/2025
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 30th, 2025 was filed after the mailing date of the non-final rejection on July 30th, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
In light of the present amendments to the claims, the elected species disclosed in non-final office action mailed July 30th, 2025, was found to be free of the prior art, therefore, the election of species requirement is hereby withdrawn and the full scope of the claims is under examination herein. As a result, previously withdrawn claims 8-10 are rejoined and under examination.
Claim 26 stands withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 15th, 2025.
Status of the Claims
Claims 1-3, 5-10, 18-21, and 23-26 are pending in this application. Claims 4, 11-17, 22, and 27-58 have been cancelled by applicant. Claims 1-3, 5-10, 18-21, and 23-25 are under examination herein. Claim 26 is withdrawn from consideration.
Claim Rejections - 35 USC § 103
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.
Claims 1, 6-7, 10, 18-21, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Castanedo et al. (WO 2008/073785 A2 – cited in IDS) (“Castanado ‘08”).
Regarding claims 1 and 10, Castanedo ‘08 teaches compound Ib below (page 16, [0064]), which are disclosed as PI3 kinase modulators useful for treating neurological disorders [0019] – which is the same intended use as the instant invention. Castanado ‘08’s compounds render the instant compounds obvious when: X (corresponding to instant X) is O or S; R2 (corresponding to instant RA) is H, C1-6 alkyl, or C6-20 aryl; R1 (corresponding to instant R2) can be C6-20 aryl/ heteroaryl/ carbocycle/ or heterocycle; and R3 (corresponding to instant R1) can be a monocyclic heterocycle selected from pyrazolyl, pyrimidinyl, etc., specifically showing
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and
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[0103] and [0104], respectively.
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Castanado ‘08 specifically discloses the compounds 214 and 217 below (page 60), which read on the instant compounds, wherein the group corresponding to instant R2 is substituted aryl or heteroaryl. While Castanado ‘08’s compounds don’t show pyrimidin-6-yl substitution in the position corresponding to instant R1 (showing pyrimidin-5-yl substitution instead), Castanado ‘08’s disclosure that their R3 group can be
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( pyrimidin-6-yl) would have led one of ordinary skill to the present invention. Furthermore, while Castanado ‘08’s preferred embodiments only show S in the position corresponding to X, they also teach that their X group can also be O. Thus, Castanado ‘08 discloses a fairly narrow subgenus, which is encompassed by the instantly claimed genus of compounds.
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Therefore, regarding instant claims 1 and 10, one having ordinary skill would have found the claimed compounds prima facie obvious, since they are generically embraced by Castanado ‘08’s disclosed formula Ib and preferred embodiments 214 and 217 above; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Castanado ‘08. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Regarding claim 6, Castanado ‘08 discloses their compounds of Formula Ib wherein the group corresponding to instant RA can be C1-6 alkyl.
Regarding claim 7, Castanado ‘08 discloses their compounds of Formula Ib wherein the group corresponding to instant RA can be H, as in their compounds 214 and 217 shown above.
Regarding claim 18, Castanado ‘08 discloses their compounds of Formula Ib wherein the group corresponding to instant R1 can be
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, optionally substituted, as in their compounds 214 and 217 shown above.
Regarding claim 19-20, Castanado ‘08 discloses their compound 217 above, wherein the group corresponding to instant R2 is a substituted pyridine.
Regarding claim 21, Castanado ‘08 discloses their compound 292 below (page 76), wherein the group corresponding to instant R2 is a substituted piperidinyl. While this compound has the sulfur atom in the position corresponding to instant Y instead of X, Castanado ‘08 teaches their compounds Ib above, with the correct arrangement of atoms.
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Therefore, one having ordinary skill would have found the claimed compounds prima facie obvious, since they are generically embraced by Castanado ‘08’s disclosed formula Ib and preferred embodiments 292 above. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Castanado ‘08. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Regarding claim 25, Castanado ‘08 discloses a pharmaceutical composition comprising their compounds and an acceptable carrier (Castanado ‘08’s claim 23).
Claims 1, 8, 18-20, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Castanedo et al. (WO 2009/042607 A1) (“Castanado ‘09”).
Regarding claims 1 and 8, Castanedo ‘09 teaches compound Ia below (page 15, [0060]), which renders the instant compounds obvious when: instant X is S and Y is N; R1 (corresponding to instant R2) can be C6-20 aryl/ heteroaryl/ carbocycle/ or heterocycle; and R3 (corresponding to instant R1) can be a monocyclic heterocycle, specifically showing
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and
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[0094] and [0095], respectively.
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Castanedo ‘09 specifically discloses the compounds 114 and 120 below (pages 39, 40), which read on the instant compounds, wherein the group corresponding to instant R2 is substituted aryl or heteroaryl. While Castanedo ‘09’s compounds don’t show pyrimidin-6-yl substitution in the position corresponding to instant R1 (showing pyrimidin-5-yl substitution instead), Castanedo ‘09’s disclosure that their R3 group can be
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(pyrimidin-6-yl) would have led one of ordinary skill to the present invention. Thus, Castanedo ‘09 discloses a fairly narrow subgenus, which is encompassed by the instantly claimed genus of compounds.
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Therefore, regarding instant claims 1 and 8, one having ordinary skill would have found the claimed compounds prima facie obvious, since they are generically embraced by Castanedo ‘09’s disclosed formula Ib and preferred embodiments 114 and 120 above. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Castanedo ‘09. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Regarding claim 18, Castanedo ‘09 discloses their compounds of Formula Ib wherein the group corresponding to instant R1 can be
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, optionally substituted, as in their compounds 114 and 120 shown above.
Regarding claim 19-20, Castanedo ‘09 discloses their compound 120 above, wherein the group corresponding to instant R2 is a substituted pyridine.
Regarding claim 25, Castanedo ‘09 discloses a pharmaceutical composition comprising their compounds and an acceptable carrier ([0154] and Castanedo ‘09’s claim 36).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Castanedo et al. (WO 2009/042607 A1) (“Castanado ‘09”); as applied to claims 1, 8, 18-20, and 25; in view Castanedo et al. (WO 2008/073785 A2 – cited in IDS) (“Castanado ‘08”); further in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”).
The teachings of Castanedo ’09 are disclosed above and incorporated herein.
Castanedo ’09 teaches their compounds Ia (shown below) as PI3K inhibitors (abstract).
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While Castanedo ’09 does not teach their compounds Ia with an -O- instead of -S- in the position corresponding to instant X, as in instant formula Ic; the teachings of Castanedo ’08 and Meanwell are relied upon to leverage these differences.
Castanedo ’08 teaches their related PI3K inhibitors of Formula Ib below, which are disclosed as useful for treating neurological disorders [0019] – which is the same intended use as the instant invention; wherein X (corresponding to instant X) is -O- or -S-; R2 (corresponding to instant RA) is H, C1-6 alkyl, or C6-20 aryl; R1 (corresponding to instant R2) can be C6-20 aryl/ heteroaryl/ carbocycle/ or heterocycle; and R3 (corresponding to instant R1) can be a monocyclic heterocycle selected from pyrazolyl, pyrimidinyl, etc., specifically showing
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and
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[0103] and [0104], respectively.
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Meanwell teaches that the design of bioisosteres frequently introduces structural changes that can be beneficial depending on the context, with size, shape, electronic distribution, polarizability, dipole, polarity, lipophilicity, and pKa potentially playing key contributing roles in molecular recognition and mimicry. In the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (abstract). Meanwell teaches -O- and -S- as classical divalent bioisosteres (table 1, page 2529).
Therefore, one having ordinary skill in the art would have found the claimed compounds of Formula Ic prima facie obvious, since they are generically embraced by Castanedo ‘09’s disclosed compounds in view of Castanado ’08 and Meanwell. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of PI3K inhibitors disclosed by Castanedo ’09, with -S- in the position corresponding to instant X, in view of Castanedo ‘08’s PI3K inhibitors, with -O- in the position corresponding to instant X, which are useful for treating neurological conditions; further in view of Meanwell’s teaching that -O- and -S- are classical divalent bioisosteres. Accordingly, one having ordinary skill in the art would have been motivated to substitute the -S- of Castanedo ‘09’s compounds for -O- to arrive at the instant compounds of Formula Ic.
Claims 1-3, 5-7, 18, 21, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2015/137887 A1 – cited in IDS) (“Wang”).
Regarding claims 1 and 5, Wang teaches compound Ib below (page 30), as useful for the treatment of neurological disorders, which is the same as the instantly claimed intended use (page 5, lines 5-6). Wang’s compounds render the instant compounds obvious when: R1 is morpholino; R4 (corresponding to instant RA) is H or alkyl; R3 (corresponding to instant R2) can be pyrrolidine or piperidine; R2 (corresponding to instant R1) can be pyrimidinyl.
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Wang specifically discloses the compound below as a preferred embodiment, which read on the instant claims (pages 38 and 48).
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While this preferred embodiment shows pyrimidin-5-yl substitution in the position corresponding to instant R1, instead of pyrimidin-6-yl as claimed, Wang’s teaching that their R2 group can be pyrimidines would have led one of ordinary skill to explore the limited number of connectivities available for pyrimidine and the core of Wang’s compound. Furthermore, Wang discloses their compounds for the treatment of neurodegenerative or neurological conditions, which is the same use claimed in the instant invention (page 51, para. 1). Therefore, Wang discloses a fairly narrow subgenus, which overlaps with the instantly claimed genus of compounds.
Therefore, regarding instant claims 1 and 5, one having ordinary skill would have found the claimed compounds prima facie obvious, since they are generically embraced by Wang’s disclosed formula Ia and the preferred embodiment shown above. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Wang. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Regarding claims 2-3, Wang discloses their compounds of Formula Ib wherein the group corresponding to instant groups X and Y is N.
Regarding claim 6, Wang discloses their compounds of Formula Ib wherein the group corresponding to instant RA can be C1-6 alkyl.
Regarding claim 7, Wang discloses their compounds of Formula Ib wherein the group corresponding to instant RA can be H.
Regarding claim 18, Wang discloses their compounds of Formula Ib wherein the group corresponding to instant R1 can be pyrimidine.
Regarding claim 21, Wang discloses their compound above, wherein the group corresponding to instant R2 is a substituted piperidine.
Regarding claim 25, Wang discloses a pharmaceutical composition comprising their compounds and an acceptable excipient (Wang’s claim 45).
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, 5-7, 18-21, and 23-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 24, 29, 38, 40, and 89 of copending Application No. 18/717,172 (Copending ‘172).
Regarding instant claims 1-3, 5-7, 18-21, and 23-25, Copending ‘172 claims the compounds of Formula I below, which render the instant compounds obvious when X1 is N and X2 can be CRA, wherein RA can be H, alkyl, C6-10 aryl, etc.; R1 (corresponding to instant R3) can be pyrimidine, pyrazole, etc.; R3 (corresponding to instant R1) can be morpholino, etc.; and R2 (corresponding to instant RA) can be alkyl, aryl, heterocycle, etc.
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Copending ‘172’s compounds differ from the instant claims mainly in that their R1 and R3 groups are flipped from what they are in the instant claims.
Thus, Applicant is reminded that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results.
Regarding instant claim 25, Copending ‘172 claims a composition comprising their compounds and an acceptable excipient (Copending ‘172’s claim 89).
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 5-7, 18-21, and 23-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7, 10, 14, 21, 25-26, 28, 30-31, 259, and 335 of copending Application No. 18/717,174 (Copending ‘174). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1-3, 5-7, 18-21, and 23-25, Copending ‘174 claims the compounds of Formula I below, which anticipate the instant claims when Y can be N or CRA, and X can be NRA, wherein RA can be H, alkyl, C6-10 aryl, etc.; R1 (corresponding to instant R1) can be pyrimidine, pyrazole, etc.; R3 (corresponding to instant R3) can be morpholino, etc.; and R2 (corresponding to instant R2) can be aryl, heteroaryl, heterocycle, etc.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been added.
Specification
Applicant’s arguments, see page 16, filed October 30th, 2025, with respect to objections to the specification regarding trade name use have been fully considered and are persuasive. The objection of the specification has been withdrawn.
Amendments to the specification are acknowledged and have been entered.
Claim Objections
Applicant’s arguments, see page 16, filed October 30th, 2025, with respect to objections to the claims have been fully considered and are persuasive. The objection of the claims has been withdrawn.
Claim Rejections - 35 USC § 112(b)
Applicant’s arguments, see page 16, filed October 30th, 2025, with respect to 35 USC § 112(b) rejections of the claims have been fully considered and are persuasive. The 35 USC § 112(b) rejection of the claims has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s arguments, see pages 16-19, filed October 30th, 2025, with respect to 35 USC § 103 rejections of the claims over Castelhano et al. have been fully considered and are persuasive. In light of the claim amendments, the 35 USC § 103 rejections of the claims over Castelhano et al. have been withdrawn.
However, upon further consideration, a new ground of rejections is made in view of Castanedo ’08; Castanedo ’09; and Wang.
Non-Statutory Double Patenting Rejections
Applicant's arguments filed October 30th, 2025 have been fully considered but they are not persuasive.
Applicant requests that obviousness-type non-statutory double patenting rejections over US Application No. 18/007,797; 18/717,172; and 18/717,174 be held in abeyance until the application is in condition of allowance.
Claims stand rejected over obviousness-type non-statutory double patenting rejections over US Application No. 18/717,172; and 18/717,174.
Upon further consideration, the obviousness-type non-statutory double patenting rejections over US Application No. 18/007,797 has been withdrawn.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627