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 .
Priority
This application, filed 8 November, 2024, is a national stage application of PCT/US2023/022137, filed 12 May, 2023, which claims prior benefit of application PRO 63/341,358, filed 12 May, 2022.
Information Disclosure Statement
Two information disclosure statements (IDS) submitted on 12 September, 2025 and 8 May, 2026 are acknowledged and have been considered.
Status of the Application
Receipt is acknowledged of Applicant's claimed invention, filed 11 August, 2025, in the matter of Application N° 18/864,030. Said documents have been entered on the record.
Claims 4-5, 7, 14-17, 22-24, 26 and 28 are amended. Claims 8-13, 18-21, 27 and 29 are canceled. No new matter was introduced.
Thus, Claims 1-7, 14-17, 22-26 and 28 represent all claims currently under consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 25 and 28 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 25 is incomplete in itself because it incorporates subject matter from the specification (“…compound is selected from Table 1”). Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). See MPEP §2173.05(s).
Claim 28 recites contacting the compound with either “the ATXN3 pre-mRNA with a splice site sequence” or “cells comprising the ATXN3 pre-mRNA,” thereby appearing to provide alternative substrates or environments for the contacting step. However, the claim subsequently requires that the compound bind the ATXN3 pre-mRNA and modulate splicing of the ATXN3 pre-mRNA “in a cell of a subject.” It is unclear how the first alternative, wherein the compound is contacted with the ATXN3 pre-mRNA itself rather than with a cell comprising the pre-mRNA, relates to or satisfies the subsequently recited requirement that modulation occur “in a cell of a subject.” For example, the claim does not specify whether the ATXN3 pre-mRNA of the first alternative is present within the cell of a subject at the time of contacting, whether the contacted pre-mRNA is subsequently introduced into such a cell, or whether the first alternative encompasses an in vitro contacting step distinct from the subsequently recited cellular modulation. Conversely, if the first alternative necessarily refers to the ATXN3 pre-mRNA within a cell of a subject, the distinction between that alternative and the expressly recited “cells comprising the ATXN3 pre-mRNA” is unclear. Accordingly, one of ordinary skill in the art would not be reasonably apprised of the scope of the claimed method.
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.
Claims 1, 3-4, 15 and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chakraborti et al. (Bioorg. Med. Chem. Lett. 13 (2003) 1403–1408, cited in IDS), hereinafter Chakraborti.
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Chakraborti teaches Molecule 2a, which is CAS RN 568564-34-1, (2003, Pg. 1404, Table 1), shown top right, which is fully encompassed by instant Formula I (as in instant Claim 1), shown bottom right, wherein R21 is phenyl (as in instant Claim 3), X3 is CR23 wherein R23 is H (as in instant Claims 3-4), X4 is CR24 wherein R24 is H (as in instant Claim 15), and X8 is CR28 wherein R28 is butyl (as in instant Claim 24).
As such Chakraborti anticipates Claims 1, 3-4, 15 and 24.
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Claims 1, 24 and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kusakabe et al. (US20120059162 A1, cited in IDS), hereinafter Kusakabe.
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Kusakabe teaches isoxazolo[4,5-d]pyrimidin-7-amine, 3-(4-bromophenyl)-5-chloro-N-[(tetrahydro-2H-pyran-4-yl)methyl]-(ACl), which is CAS RN 1263425-96-2, (‘162, Pg. 133, Example 3-4, Col 2), shown top right, which is fully encompassed by instant Formula I (as in instant Claim 1), shown bottom right, wherein R21 is tetrahydropyranyl, X3 is N, X4 is CR24 wherein R24 is phenyl substituted with one R20d which is Br, and X8 is CR28 wherein R28 is Cl (as in instant Claim 24).
Kusakabe further teaches this compound as a pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier (‘162, Pg. 4, Para 0077, Pg. 36, Para 0732, and Pg. 37, Para 0736), as in instant Claim 26.
As such, Kusakabe anticipates Claims 1, 24 and 26.
Claims 1 and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nakajima et al. (WO 2018038265 A1, cited in IDS), hereinafter Nakajima.
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Nakajima teaches Compound 246, which is CAS RN 2199500-47-3 (‘265, Pg. 427, Para 0630), shown top right, which is fully encompassed by instant Formula I (as in instant Claim 1), shown bottom right, wherein R21 is phenyl substituted with two R1A which are both independently methoxy, X3 is N, X4 is CR24 wherein R24 is cyclohexyl, and X8 is CR28 wherein R28 is H (as in instant Claim 24).
As such, Nakajima anticipates Claims 1 and 24.
Claims 1 and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Crane (CA 2984073 A1, cited in IDS).
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Crane teaches Compound 1270, which is CAS RN 1358585-37-1 (‘073, Pg.279, DB Name N-0002468), shown top right, which is fully encompassed by instant Formula I (as in instant Claim 1), shown bottom right, wherein R21 is phenyl substituted with one R1A which is methoxy, X3 is N, X4 is CR24 wherein R24 is phenyl substituted with one R20d which is Cl, and X8 is CR28 wherein R28 is H (as in instant Claim 24).
As such, Crane anticipates Claims 1 and 24.
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 1-7, 14-17, 22-24, 26 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-6, 13-20, 22 and 24 of copending Application No. 18/707,166; Claims 1-6, 13-20, 22, 24 and 26 of copending Application No. 18/707,167; Claims 1-6, 13-20, 22 and 24 of copending Application No. 18/707,168; Claims 1-6, 13-20, 22, 24 and 26 of copending Application No. 18/707,170; Claims 1-7, 14-17, 22-24, 26 and 28 of copending Application No. 18/864,033; and Claims 1-7, 14-19, 21 and 23 of copending Application No. 18/864,033 in view of Ritchie and MacDonald (European Journal of Medicinal Chemistry 124 .2016. 1057e1068).
As illustrated therein, the respective claims are directed to closely related genera of compounds sharing substantially the same overall fused heterocyclic scaffold and substituent framework, with the principal distinctions residing in the identity and/or position of heteroatoms within the heterocyclic core. Such differences constitute closely related structural variations of the same underlying compound genus, as seen below.
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Instant Formula I
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18/707,166 Formula I
18/707,167 Formula I
18/707,168 Formula I
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18/707,170 Formula I
18/864,033 Formula I
18/864,035 Formula I
It was known in the art that modification of heteroaryl and heterocyclic scaffolds through substitution of one heteroatom for another and/or alteration of heteroatom position represents a conventional means of generating structurally related analogs while retaining the same general scaffold and associated utility. This conclusion is further supported by Ritchie and MacDonald which teaches the routine consideration of alternative heterocyclic ring systems, including variations in heteroatom identity and heteroatom position (regioisomers), in the design of structurally related compounds (2016, e.g., Tables 1-3 and Fig. 4). Ritchie and MacDonald specifically evaluate alternative N-, O-, and S- containing heterocycles as well as positional isomers differing in the location of ring nitrogen atoms, thereby evidencing that exploration of such heteroatom substitutions and positional variations was a recognized medicinal-chemistry approach for obtaining related analogs and optimizing compound properties.
Accordingly, absent evidence establishing a patentable distinction resulting from the particular heteroatom identity or placement recited in each application, the claimed compounds would have been obvious variants of the compounds claimed in the respective copending applications. The claims therefore are not patentably distinct from the claims of the identified copending applications.
Additionally, to the extent the copending applications contain claims directed to identically worded compositions and/or methods comprising or utilizing compounds of the overlapping or obvious compound genera discussed above, such claims likewise fail to define patentably distinct subject matter. This is particularly evident where the respective method claims recite identical methods differing only by reference to compounds encompassed by the overlapping or obvious genera.
This is a provisional nonstatutory double patenting rejection.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
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/D.M.N./Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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