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 1 March, 2022, is a national stage application of PCT/US20/49147, filed 3 September, 2020, which claims the benefit of U.S. Provisional Application 62/896,116, filed 5 September, 2019.
Information Disclosure Statement
Three information disclosure statements (IDS) submitted on 9 June, 2023; 7 August, 2023; and 7 March, 2024, are acknowledged and have been considered.
Election/Restrictions
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Applicant’s election without traverse of Group II (Formula I, wherein B1 is an optionally substituted heteroaryl), and Species – Compound 469, shown to the right, in the reply filed on 5 September, 2025 is acknowledged.
Claim 56 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Species, there being no allowable generic or linking claim; the AA selections available in this claim do not allow the 6-membered ring option necessary for the elected Species.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 5 September, 2025, in the matter of Application N° 17/639,401. Said documents have been entered on the record.
Claims 1 and 117 are amended. No new matter was introduced.
Thus, Claims 1-2, 5, 18, 24, 73, 91, 95, 116-118, 120-124, 126-127, and 131 represent all claims currently under consideration.
Claim Objections
Claims 1-2, 5, and 117 are objected to because of the following informalities: inconsistency in terminology between claims and specification. Specifically, the claims recite Markush selections that include both “aryl” and “heteroaryl” substituents. However, in the Specification (Pg. 6-7), the term “aryl” is defined in such a manner that it encompasses structures that contain heteroatoms, i.e., heteroaryl groups. While applicants are permitted to be their own lexicographer, the inconsistent use of “aryl” in the claims and specification renders the scope of the claims unclear. As currently presented, it is unclear whether “heteroaryl” is redundant or intended to be distinct from “aryl” as defined.
Appropriate correction is required.
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.
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 1-2, 5, 18, 24, 73, 91, 95, 116-118, 120-124, and 131 are rejected under 35 U.S.C. 103 as being unpatentable over Pitis et al. (WO 2018/231745 Al, cited in IDS), hereinafter Pitis, and Pitsch et al. (Molecular Neurobiology (2019) 56:1825–1840, Published 22 June 2018, Issue Date March 2019), hereinafter Pitsch.
Reference ‘745 shares the same Assignee with instant application.
Pitis teaches compounds, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for modulating the activity of S1P1 receptor and methods of using the same (‘745, Abstract.)
Regarding Claims 1 and 18, Pitis teaches methods of treating or preventing pain or cancer, the methods comprise administering one or more compounds of Formula I,
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, or a pharmaceutically acceptable salt thereof (‘745, Pg. 18, as in instant Claim 1), wherein AA is
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(as in instant Claim 18), W is O, X is O, n is 1, R2 is a C2 alkyl – an ethyl group, R3 is a C2 alkyl – an ethyl group, B2, B3, and B4 are each independently CR38, R38 is H, B1 is a non-substituted heteroaryl, and D1 is a non-substituted [hetero]aryl.
Regarding Claims 2 and 5, Pitis teaches D1 and B1 are
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(‘745, Pg. 19), wherein Z1 is N, Z2 is N, Z3 is O, and D1 is a non-substituted [hetero]aryl.
Regarding Claim 73, Pitis teaches
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(‘745, Pg. 24), wherein Z6 is NR40, R40 is H, Z7 is N, Z8 and Z9 are each independently CR41, R41 is H, R35 is H, and R36 is H.
Regarding Claim 91, Pitis teaches
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(‘745, Pg. 24.)
Regarding Claim 95 and 116, Pitis teaches Compound 469,
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(‘745, Pg. 25-26, 222, 270-271, and 349-350, Claim 116.)
Regarding Claim 117, Pitis teaches a pharmaceutical composition comprising one or more compounds as provided or described herein, and further, methods comprising administering pharmaceutical compositions thereof (‘745, Pg. 26-27.)
Regarding Claim 118, Pitis teaches pharmaceutical compositions comprising one or more compounds as described herein, which can also comprise a pharmaceutically acceptable carrier.
Regarding Claim 131, Pitis teaches amount of compound to be administered is that amount which is therapeutically effective (‘745, Pg. 139.)
Pitis fails to teach modulating the activity of S1P1 receptor is effective in methods for treating and/or preventing epilepsy and epilepsy-related syndromes.
However, Pitsch teaches therapeutic effects in temporal lobe epilepsy (TLE) with the immunomodulator fingolimod, which targets sphingosine-phosphate receptors (S1PRs), and found it exerted robust anti-convulsive activity in kainate-induced SE mice treated in the chronic TLE stage (as in instant Claims 120-124) and had neuroprotective and anti-gliotic effects and reduced cytotoxic T cell infiltrates (2019, Pg. 1825, Abstract.)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to employ the S1P1 modulating compounds taught by Pitis, for the treatment of epilepsy in view of Pitsch, which establishes that modulation of S1P1 is effective in reducing seizures associated with temporal lobe epilepsy. One would have been motivated to make this application because Pitis identifies the compound’s activity at S1P1, and Pitsch expressly links S1P1 modulation with anticonvulsant benefit, thereby suggesting that known S1P1 modulators, such as Pitis’s Compound 469, would be useful as anti-epileptic agents. A person of ordinary skill in the art would have had a reasonable expectation of success in doing so because Pitsch teaches that the mechanism of S1P1 modulation itself confers seizure control, making it obvious to apply the S1P1-modulating compound of Pitis to epilepsy broadly, including temporal lobe and other forms of epilepsy.
Claims 126-127 are rejected under 35 U.S.C. 103 as being unpatentable over Pitis (WO 2018/231745 Al), and Pitsch (Molecular Neurobiology (2019) 56:1825–1840), as applied to Claims 1-2, 5, 18, 24, 73, 91, 95, 116-118, 120-124, and 131 above, and further in view of Whalley et al. (WO 2012/093255 A1), hereinafter Whalley.
Regarding Claims 126-127, Whalley teaches a method for the treatment of epilepsy, which comprises administering to a subject in need thereof, cannabidiol (CBD) in combination with a standard antiepileptic drug (SAED) (‘255, Pg. 5-6, Para 0032), such as ethosuximide, valproate and Phenobarbital (‘255, Pg. 7, Para 0053.) The combinations are particularly well suited in the treatment of conditions generally considered refractory to existing medication, and have proven beneficial in one or more of the following: reducing the incidence of tonic-clonic seizures, increasing the amount of time a patient is seizure free, increasing the latency to onset of seizure, decreasing the overall duration of the seizure; and reducing the severity and mortality of the seizures (‘255, Pg. 6, Para 0037.)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to use the Compound 469 for the treatment of Epilepsy, in view of the teachings of Pitis and Pitsch, in combination with standard anti-epileptic drugs as taught by Whalley, because Whalley establishes that co-administration of novel agents with conventional AEDs is a recognized strategy in epilepsy treatment, and one would have reasonably expected that combining Compound 469 with standard AEDs would yield effective seizure control.
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, 5, 18, 24, 73, 91, 95, 116-118, 120-124, and 131 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-8 of U.S. Patent No. 11,912,693 in view of Pitsch (Molecular Neurobiology (2019) 56:1825–1840).
Patent ‘693 also teaches “Compound 469” (the instantly elected Species), for modulating the activity of S1P1 receptor, pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of using the same, but cite different conditions and diseases.
However, Pitsch teaches therapeutic effects in temporal lobe epilepsy (TLE) with the immunomodulator fingolimod, which targets sphingosine-phosphate receptors (S1PRs), and found it exerted robust anti-convulsive activity in kainate-induced SE mice treated in the chronic TLE stage and had neuroprotective and anti-gliotic effects and reduced cytotoxic T cell infiltrates (2019, Pg. 1825, Abstract.)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to employ the S1P1 modulating compounds taught by Patent ‘693, for the treatment of epilepsy in view of Pitsch, which establishes that modulation of S1P1 is effective in reducing seizures associated with temporal lobe epilepsy. One would have been motivated to use this compound because Patent ‘693 identifies the compound’s activity at S1P1, and Pitsch expressly links S1P1 modulation with anticonvulsant benefit, thereby suggesting that known S1P1 modulators, such as Compound 469, would be useful as anti-epileptic agents. A person of ordinary skill in the art would have had a reasonable expectation of success in doing so because Pitsch teaches that the mechanism of S1P1 modulation itself confers seizure control, making it obvious to apply the S1P1-modulating compound of Patent ‘693 to epilepsy broadly, including temporal lobe and other forms of epilepsy.
Claims 1-2, 5, 18, 24, 73, 91, 95, 116-118, 120-124, and 131 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 125-129 and 133-141 of copending Application No. 18/296,018 in view of Pitsch (Molecular Neurobiology (2019) 56:1825–1840).
‘018 teaches the genus of Formula 1 and the instantly elected species “Compound 469”, for modulating the activity of S1P1 receptor, pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of using the same, but cite different conditions and diseases.
However, Pitsch teaches therapeutic effects in temporal lobe epilepsy (TLE) with the immunomodulator fingolimod, which targets sphingosine-phosphate receptors (S1PRs), and found it exerted robust anti-convulsive activity in kainate-induced SE mice treated in the chronic TLE stage and had neuroprotective and anti-gliotic effects and reduced cytotoxic T cell infiltrates (2019, Pg. 1825, Abstract.)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to employ the S1P1 modulating compounds taught by ‘018, for the treatment of epilepsy in view of Pitsch, which establishes that modulation of S1P1 is effective in reducing seizures associated with temporal lobe epilepsy. One would have been motivated to use this compound because ‘018 identifies the compound’s activity at S1P1, and Pitsch expressly links S1P1 modulation with anticonvulsant benefit, thereby suggesting that known S1P1 modulators, such as Compound 469, would be useful as anti-epileptic agents. A person of ordinary skill in the art would have had a reasonable expectation of success in doing so because Pitsch teaches that the mechanism of S1P1 modulation itself confers seizure control, making it obvious to apply the S1P1-modulating compound of ‘018 to epilepsy broadly, including temporal lobe and other forms of epilepsy.
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