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 .
Claim Status
Pending claims 1, 27-29, 33, 37-41, 51, 55, 69-70, 72-77 have been examined on the merits.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office
action.
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, 33, 37-41, 55, 69-70, and 72-77 are rejected under 35 U.S.C. 103 as being unpatentable over Hill et al. WO2022072621 in view of Saporito et al. US20180296487, in further view of Sim et al., Int J Neuropsychopharmacol. 2015 Jul 7;19(2):-1-13.
Regarding claims 1, 69, and 74-75, Hill (abstract; page 7) teaches a method of treating a central nervous system related disorder in a human subject, wherein the pharmaceutical composition is an oral formulation that comprises a compound of Formula (I), ATN-10155, a neuroactive steroid or neurosteroid, comparable to the instant claim:
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Hill (page 4, line 21-22) teaches the central nervous system related disorder, comprising postpartum depression, seizure disorders, and mood disorders. In fact, Hill (page 1, line 18- 25) teaches neuroactive steroids have been used or developed for depressive disorders, including but not limited to major depressive disorder (MDD). Given MDD is a common mood disorder, and treatable with neuroactive steroid, thus, a person of ordinary skill in the art (POSITA) would understand that Hill’s teachings are applicable to MDD.
While Hill’s compound differs from the claimed compound, bearing a methyl substituent instead of a hydrogen at the decalin scaffold of the neuroactive steroid compound; however,
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Saporito (page 10 and 12) discloses a compound of formula I that is structurally similar to the claimed invention and is effective against depression, including major depressive disorder (MDD) and severe depression, as example. Therefore, it would have been obvious to a POSITA to either combine Hill and Saporito’s teachings or modify Hill’s teachings in view of Saporito to arrive at the claimed invention, because both Hill and Saporito teach the same class of compound, which is effective against mood disorder, including but limited to MDD.
While Hill (page 17, line 4-20; page 24, line 12-13) teaches compound of formula I can be formulated as oral or injectable, but Saporito only teaches only injectable forms. Given both Hill and Saporito teach the same class of compound, thus, it would have been obvious to a POSITA to formulate the injectable composition of Saporito’s teachings for oral administration, making the combined teachings of Hill and Saporito predictable to arrive at the claimed invention. This is supported by the specification (page 54, [00212] and [00213]), indicating the compound can be formulated as oral and injectable:
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The combine teachings of Hill and Saporito do not explicitly teach “performing an initial treatment course” and “0, 1, or 2 subsequent treatment courses.”
However, Hill (page 18, line 3-22) teaches dosing may be provided at any suitable interval including but not limited to once per day, once every 48 hours, once every five days, at least 2 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months or more, as an example. Therefore, it would have been obvious to a POSITA at the time of filing of the instant application to recognize that long-term management of mood and depressive disorders with ATN-10155 inherently involves repeated courses or continued dosing over many weeks or months. It is important to note that breaks between courses and re-initiation upon recurrence of symptoms are standard clinical practice in MDD or depressive disorder management.
This is supported by Sim’s teachings (page 2) establish that MDD is a chronic, recurrent disorder and that it is standard practice to continue or re-initiate effective antidepressant treatment for at least 6-12 months following remission due to high relapse rates. Given the combine teachings of Hill and Saporito disclose compounds of formula (I) against depressive disorders, including MDD, and Sim also teaches MDD treatment normally involves continuation/maintenance therapy over 6-12 months due to expected recurrences; therefore, it would have been obvious to a POSITA to combine the teachings of Hill, Saporito and Sim to treat MDD with compound of formula I by administering an initial treatment course followed by one or more subsequent treatment courses to symptoms recurrence over a 12 month period. It is then evident that claim limitation to “0, 1, or 2” subsequent courses within a 12-month period represent an obvious implementation of the clinical guidelines described by Sim for managing relapse and recurrence in MDD. Thus, a POSITA would have understood that administering one or more additional treatment course within a year is a routine and predictable aspect of MDD management.
Regarding claims 33, 37-40, 55, and as applied to claims 1, 74-75 above, Hill (page 18, line 3-22) in view of Saporito teaches an oral neuroactive-steroid compound of formula I at doses of about 5 to about 90 mg (including 5 mg, 15 mg, 30 mg, 60 mg), administered once per day, for periods including at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 months, at least 12 months or more. Therefore, it would have been obvious to a POSITA to recognize Hill’s teachings can be extended or repeated over multi-week to multi-month periods, thereby indicating treatment and follow-up intervals spanning several weeks, such as a 14-day once daily courses and repeat course upon recurrence. Given that relapse and recurrence in depressive disorder are commonly assessed within weeks of initial treatment, as an example; thus, a POSITA would definitely find it as a routine to schedule repeat courses, such as 14 days, with inter-course intervals of at least 4, 6 and 8 weeks in order to monitor durability of response and manage cumulative exposure. Thus, the claimed limitation represents nothing more than routine optimization of a known neuroactive-steroid regimen for MDD as disclosed by the combined teachings of Hill, Saporito and Sim.
Regarding claim 70, the combined teachings of Hill, Saporito and Sim do not explicitly teach depression rating scales such as HAM-D.
However, HAM-D, MADRS, and PHQ-9 are standardized and widely used methods for quantifying depression severity, monitoring response and detecting relapse in depressive-disorder treatment. For these reasons, clinical guidelines explicitly recommend these depression rating scales to determine whether a patient should be further evaluated for a depressive disorder or change in treatment regimen. As evidence by Bryan Bruno teaches:
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Therefore, a POSITA would expect to use one or more of the depression rating scales when managing any depressive-disorder treatment, including to identify recurrence, even if the combined teachings of Hill, Saporito and Sim do not explicitly mention them. This then indicate that the claimed invention simply adopts routine monitoring methods that a POSITA would expect to include in a method of treating a patient with depressive disorder, such as MDD.
(Bryan Bruno, https://www.midcitytms.com/how-psychiatrists-use-depression-rating-scales/, retrieved 01/07/2026).
Regarding 41 and 72-73, and as applied to claims 1, 33, 37-40, 55, and 74-75 above, Hill (page 3) teaches administering a compound of formula I at doses from about 5 mg up to about 90 mg, which overlap with the disclosed therapeutic range. Hill (page 9-10 and 15) teaches that the compound may be administered as a pharmaceutically acceptable salt and defines such salts as possessing the same pharmacological activity as the parent compound. While Hill does not explicitly disclose doses of the salt forms, however, a POSITA would reasonably understand the disclosed doses from about 5 mg up to about 90 mg to refer to the active compound itself, i.e., the free base. In addition, a POSITA would also recognize that equivalent doses of a free base and its pharmacologically acceptable salt are inherently understood and expected to be equivalent in the art; particularly, given the established relationship that salts provide the same pharmacological activity as the parent compound. Therefore, as disclosed by Hill, administering a salt in an amount equivalent to the free base to achieve the desired therapeutic effect would have been routine and predictable, even if not explicitly stated by Hill.
Regarding claim 76-77, as applied to claim 1 above, Hill (page 3, line 9-12) teaches:
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Claims 27 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Hill, Saporito, Sim, as applied to claims 1 above, in further view of Li et al., Hum Brain Mapp. 2021 Jun 1;42(8):2593-2605.
Regarding claim 27 and 29, the combined teaching of Hill, Saporito and Sim teach a method of treating MDD with compound of formula I, by administering an initial treatment course followed by one or more subsequent treatment courses to symptoms recurrence over a 12-month period. Hill, Saporito and Sim do not explicitly teach “treatment naïve.”
However, Li (page 1-5) discloses first episode, drug-naive MDD patients treated with standard antidepressants, evaluating treatment effectiveness in subjects with no prior antidepressant exposure. Given that first-line antidepressants are standard for MDD, a POSITA would expect that evaluating a treatment in treatment-naive patients to be a routine practice to assess efficacy relative to the established therapy, such as antidepressants. Therefore, a POSITA would have been motivated to combine the teachings of Hill, Saporito and Sim in view of Li to administer compound of formula I to treatment-naïve MDD patients who had not previously received any pharmacologic treatment for depression and evaluate the treatment efficacy and arrive at the claimed invention. Furthermore, a POSITA would have had a reasonable expectation of success in treating treatment-naïve MDD patient, because the combine teachings of Hill, Saporito, and Sim in view of Li teach the same class of compound, which is effective against mood disorder, including but limited to MDD.
Claims 28 is rejected under 35 U.S.C. 103 as being unpatentable over Hill, Saporito, Sim, as applied to claims 1 above, in further view of view Kanes et al. US 2020/0113917.
Regarding claim 28, the combined teaching of Hill, Saporito and Sim teach a method of treating MDD with compound of formula I, by administering an initial treatment course followed by one or more subsequent treatment courses to symptoms recurrence over a 12-month period. Hill, Saporito and Sim do not explicitly teach “wherein the subject has been on a stable dose of an additional antidepressant for at least 60 days.”
However, as applied to claim 1 above, Kanes (abstract) teaches a method for treating depression, such as postpartum depression or major depressive disorder, in a subject in need thereof, using compound (I) comparable to the claimed invention. Kanes (page 16, [0153]) teaches the following:
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Subject Matter Free of the Art of Record
The subject matter of claims 51 is free of the art of record. The closest prior art is the Hill et al. WO2022072621. While Hill teaches a method of treating a central nervous system related disorder in a human subject, wherein the pharmaceutical composition comprising a compound of Formula (I), a neuroactive steroid or neurosteroid; however, there is no motivation for a POSITA to modify the teaching of Hill to arrive at the crystalline form. However, the claim is not allowed because of its dependency on a rejected claim. As a result, until this issue is remedied or resolved; the claim cannot be subject of allowance.
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, 29, 51, 55, and 74-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-10, 13-15, 18-19 of U.S. Patent No. US11884696.
Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ‘696 are comparable to those of the instant claims. For example, claims 1-4, 9-10, 13-15, 18-19 of the US patent ‘696 recites a method for treating a CNS-related disorder, including MDD, in a subject in need thereof, by administering orally a crystalline solid Form C of Compound I, reading on the instant claims 1, 29, 55, and 74-75:
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US patent ‘696 also discloses crystalline solid Form C XRPD patterns, which are identical to those recited in the instant claim 51:
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The instant claims mainly differ from the US patent ‘696 in that they recite administering the compound in an “initial treatment course” followed by o, 1, or 2 subsequent treatment courses over a defined period. These differences merely define a treatment schedule and frequency of administration and do not amount to patentably distinct invention, as repeated or continued administration of a therapeutic compound to threat the same disorder would have been obvious modification of the claimed method of the US patent ‘696.
Given that the method of treatment of the instant claim is comparable to that of the US patent ‘696, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term.
Claims 1, 29, 55, and 74-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-7, and 10-16 of U.S. Patent No. US10342810.
Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ‘810 are comparable to those of the instant claims. For example, claims 1, 4-7, and 10-16 of the US patent ‘810 recites a method of treating a sleep disorder or a mood disorder in a human subject in need thereof, by administering orally an effective amount of a compound of the formula, reading on the instant claims 1, 29, 55, and 74-75:
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While US patent ‘810 does not explicitly disclose MDD, it is well known in the art that MDD is a mood disorder; thus, a POSITA would understand that US patent ‘810’s teachings encompass treatment of MDD.
The instant claims mainly differ from the US patent ‘810 in that they recite administering the compound in an “initial treatment course” followed by 0, 1, or 2 subsequent treatment courses over a defined period. These differences merely define a treatment schedule and frequency of administration and do not amount to patentably distinct invention, as repeated or continued administration of a therapeutic compound to threat the same disorder would have been obvious modification of the claimed method of the US patent ‘810.
Given that the method of treatment of the instant claim is comparable to that of the US patent ‘810, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term.
Claims 1, 29, 55, and 74-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. US10172871.
Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ‘871 are comparable to those of the instant claims. For example, claims 1-12 of the US patent ‘871 recites a method for positively modulating a GABAA receptor in a subject with CNS-related disorder, including mood disorders, by administering an effective amount of compound I, including oral and parenteral administration, reading on the instant claims 1, 29, 55, and 74-75:
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While US patent ‘871 does not explicitly disclose MDD, it is well known in the art that MDD is a mood disorder; thus, a POSITA would understand that US patent ‘871’s teachings encompass treatment of MDD.
The instant claims mainly differ from the US patent ‘810 in that they recite administering the compound in an “initial treatment course” followed by 0, 1, or 2 subsequent treatment courses over a defined period. These differences merely define a treatment schedule and frequency of administration and do not amount to patentably distinct invention, as repeated or continued administration of a therapeutic compound to threat the same disorder would have been obvious modification of the claimed method of the US patent ‘810.
Given that the method of treatment of the instant claim is comparable to that of the US patent ‘810, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES H ALSTRUM-ACEVEDO can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622