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 . 1
Status of the Claims
Claims 11, 23, 35-38, and 83-101 are pending in this application.
Information Disclosure Statement and Relevant References
The information disclosure statement (IDS) submitted on Feb 20 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Copies of Cleveland Clinic and Care Counseling Postpartum websites as background knowledge of postpartum depression (PPD) patients, and a copy of a Federal Circuit opinion, In re Lalu are cited on the PTO-892 form.
Response to Arguments
Applicant’s arguments, filed Feb 20 2026 with respect to the rejection of Claims 11, 23, 35-38, and 83-101 rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/061537 A1, in view of Hantsoo et al. Psychopharmacology (2014) 231:939–948 have been fully considered but are not persuasive and rejection maintained.
Maintained Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicants are advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 11, 23, 35, 36, 37, 38, 88, 95, 96, 97, 98, 99 and 101 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/061537 A1, published April 21, 2016.
Claim 11 is directed to a method of treating post-partum depression in a subject in need thereof, the method comprising administering Compound 12, a known GABA-A modulator, identified as Zuranolone/ SAGE-217
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to the subject, once daily for about two weeks, wherein the subject is an adult.
Regarding claim 11, WO 537 discloses a method of treating postnatal depression (PND, the equivalent to postpartum depression, PPD) in a human subject in need with a therapeutic agent (with the claimed compound) in therapeutically effective amounts, see page 3 and page 55, with compounds of the present invention (i.e., WO 537).
Claim 42 of WO 537 discloses a method of treating a CNS related disorder (post-partum depression, see claim 48) with a compound of generic formula I,
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where A is heteroaryl; R1 is C1-6 alkyl (i.e. methyl); R3 is hydrogen; and R2a/R2b are hydrogen or alkyl/alkyl.
WO 537 discloses examples of formula I to be used with its method of treatment such as
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. See claim 28
While teaching compounds of formula I, as represented by the above two claim 28 compounds, WO 537 does NOT teach the claimed compound, the difference being the claimed compound has two hydrogens at equivalent positions R2a and R2b, where the WO 537 compounds have hydrogen and methyl at positions for R2a/R2b.
However a person having ordinary skill in the art (PHOSITA) would routinely optimize the claimed method using a compound as claimed (where R2a/R2b is hydrogen/hydrogen), as such compounds are known in the art. See WO 537, page 55, Example 2, synthesis of compounds 3 and 4 (i.e., the two compounds of claim 28) from compound A2, i.e. the claimed compound in Applicant’s claim 11.
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The two compounds of claim 28, where R2a/R2b is hydrogen/methyl are mere obvious homologs of the claimed compound (identified in WO 537 as A2), as they differ by the presence of a methyl group, or absence of a hydrogen atom at the same position between the differing compounds.
With regard to the limitations of two weeks, while in the context of long term sedation, WO 537 teaches periods of treatment for two weeks. See paragraph 47, 3rd paragraph. Further, periods of postpartum depression are known to a skilled artisan to last for periods of two weeks.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of WO 537 to treat postpartum depression with the two compounds of claim 28, determined to be chemical homologs of the claimed compound, modified by the teachings of WO 537 teaching compound A2 at example 2, which is the claimed compound.
The PHOSITA would have had a reasonable expectation of success because one would routinely optimize methods of treatment as claimed due to compounds being chemical homologs of one another (successive addition of same chemical group, in this case the one carbon alkyl, methyl). See MPEP 2144.093
Regarding claim 23, WO 537 teaches treatment of severe postpartum depression in a subject and can only be a human female adult. See claim 48 of WO 537. See top of page 3 of WO 537, where PPD is taught as being post-natal depression associated with severe anxiety.
Regarding claims 35 and 95, WO 537 teaches a PHOSITA to administer therapeutically effective amounts “sufficient to provide a therapeutic benefit in the treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition.” See page 39 last paragraph. Accordingly, a PHOSITA would routinely optimize the reduction of a dose of a dose of compound 1, following the occurrence of a severe adverse event, to reduce the amount administered.
Regarding claims 36-37 and 96-97, WO 537 notes that those “skilled in the art will recognize or be able to ascertain no more than routine experimentation . . . . [to] equivalents to the specific embodiments described therein.” See page 64, first paragraph. WO 537 notes its compounds can be used for methods to induce sedation, starting at page 45. It is noted that treatment periods of post-partum depression occur post-delivery and it would be routine for a skilled artisan to optimize treatment for two weeks known to inclusive of periods of post-partum depression, that overlap periods of time taught by WO ‘537 with regard to sedation and administration of its compounds. Accordingly, a PHOSITA knowing the sedative effects of WO 537 compounds, would routinely optimize dosing these compounds in the evening or with an evening meal, such as dinner, in consideration of possible sedative effects.
Regarding claims 38 and 98, WO 537 teaches typical unit dosage forms such as capsules. See page 48, last paragraph.
Regarding claim 88, as detailed above, WO 537 teaches the treatment of such an adult subject with compound 1, as detailed in the rejection of claim 11 detailed above. With regard to the limitation of once daily dosing for about two weeks, WO 537 teaches one to five oral doses, per day. See page 49 first paragraph. With regard to the limitations of two weeks, while in the context of long term sedation, WO 537 teaches periods of treatment for two weeks. See paragraph 47, 3rd paragraph. Further, periods of postpartum depression are known to a skilled artisan to last for periods of two weeks.
With regard the limitation there being no substantial change in cognitive function, such property would be naturally present, whether taught or not.
Regarding claims 99 and 101 and the dose limitation of about 10 to about 50 mg of Compound 1, WO 537 teaches oral doses from about 0.1 to about 10 mg/kg, and especially about 1 to about 5 mg/kg. See page 49, first paragraph. WO 537 teaches human patients can weigh from 40 kg to 80 kg. See page 49, third paragraph. Based on these values, a PHOSITA could routinely optimize doses as claimed based on kg weight of patients and the mg/kg dose range taught.
Claims 11, 23, 35-38, and 83-101 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/061537 A1, in view of Hantsoo et al. Psychopharmacology (2014) 231:939–948.
While WO 537 teaches the limitations of claims 11, 23, 35, 36, 37, 38, 88, 95, 96, 97, 98, 99, and 101 so as to render them obvious, see above, it is noted that it is deficient on teaching the limitations of claims 83, 84, 85, 86, 87, 89, 90, 91, 92, 93, 94 and 100 in particular, regarding the claimed post-partum subject in need being treated for depression and having the recited HAM-D scores. However, one of ordinary skill in the art would treat these patients, as detailed below, where reduction of HAM-D scores as claimed would obvious to the PHOSITA.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of WO 537 to treat postpartum depression with the two compounds of claim 28, which are obvious chemical homologs of the claimed compound, to treat a post-partum depressed subject with the HAM-D scores claimed and to reduce said scores by 50% or more from baseline..
The PHOSITA would have had a reasonable expectation of success because one would routinely optimize methods of treatment as claimed due to compounds being chemical homologs of one another (See MPEP 2144.09), where measurement of HAM-D and reduction of said scores via treatment is well known in the art.
Regarding claim 83, Hantsoo teaches treating a subject with a Hamilton Racing Scale for Depression (HAM-D) total greater than or equal to 26 at baseline, as per treating a post-partum depression subject (clinical study), Figure 3 measures the treatment effect to reduce HAMD-D scores by week approaching a score of 26, just under 25 at base line. See page 945. Hantsoo teaches included study have a score of at least 18 and less than 32 on the 19 item HAM-D score. See page 941, first column, section Methods: Subjects. As required, Hantsoo teaches subjects were considered “much improved” or “very much improved” with HAM-D scores of less than or equal to 10, or a 50% reduction in HAM-D score from baseline. See page 941, column 2.
Regarding claim 84, as detailed above, WO 537 teaches the treatment of such an adult subject with compound 1, as detailed in the rejection of claim 11 detailed above. With regard to the limitation of once daily dosing for about two weeks, WO 537 teaches one to five oral doses, per day. See page 49 first paragraph. With regard to the limitations of two weeks, while in the context of long term sedation, WO 537 teaches periods of treatment for two weeks. See paragraph 47, 3rd paragraph. Further, periods of postpartum depression are known to a skilled artisan to last for periods of two weeks. With regard the limitation there being no substantial change in cognitive function, such property would be naturally present, whether taught or not.
While WO 537 teaches the limitations of treating the claimed post-partum depressed patient as claimed, it does not teach the limitations of baseline Hamilton Racing Scale for Depression (HAM-D) score of 26 or greater, or 50% reduction of said score.
To address this treatment of a subject with claimed HAM-D score, Hantsoo teaches Figure 3 that measuring the effect of treatment (clinical study of PPD) to reduce HAMD-D scores by week approaching a score of 26, just under 25 at base line. See page 945. Hantsoo teaches patients to be included in the study having a score of at least 18 and less than 32 on the 19 item HAM-D score. See page 941, first column, section Methods: Subjects. Hantsoo teaches subjects were “much improved” or “very much improved” with HAM-D scores of less than or equal to 10, or a 50% reduction in HAM-D score from baseline. See page 941, column 2.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of WO 537 to treat postpartum depression with the two compounds of claim 28, which are obvious chemical homologs of the claimed compound, to treat a post-partum depressed subject with the HAM-D scores claimed and to reduce said scores by 50% or more from baseline.
The PHOSITA would have had a reasonable expectation of success because one would routinely optimize methods of treatment as claimed due to compounds being chemical homologs of one another (See MPEP 2144.09), where measurement of HAM-D and reduction of said scores via treatment is well known in the art.
Regarding claims 86-87, WO 537 teaches the claimed method of claim 11 as detailed above of there being no substantial change in the cognitive function in the subject (including after two weeks of admin. of cmpd. 1) would naturally be present in subjects treated as claimed and taught by the art, including after two weeks of administration of Compound 1.
Claims 89-90 claim wherein the subject exhibits the claimed HAM-D score >= total score to 26 also indicated by a >= to about 50% reduction of HAM-D total score from baseline. Hantsoo teaches Figure 3 that measuring the effect of treatment (clinical study of PPD) to reduce HAMD-D scores by week approaching a score of 26, just under 25 at base line. See page 945. Hantsoo teaches patients to be included in the study having a score of at least 18 and less than 32 on the 19 item HAM-D score. See p. 941, col 1., section Methods: Subjects. Hantsoo teaches subjects were “much improved” or “very much improved” with HAM-D scores of less than or equal to 10, or a 50% reduction in HAM-D score from baseline. See p. 941, col. 2.
Regarding claim 91, WO 537 teaches a PHOSITA to administer therapeutically effective amounts “sufficient to provide a therapeutic benefit in the treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition.” See page 39 last paragraph. Accordingly, a PHOSITA would routinely optimize the reduction of a dose of a dose of compound 1, following the occurrence of a severe adverse event, to reduce the amount administered.
Regarding claims 92-93, WO 537 notes that those “skilled in the art will recognize or be able to ascertain no more than routine experimentation . . . . [to] equivalents to the specific embodiments described therein.” See page 64, first paragraph. WO 537 notes its compounds can be used for methods to induce sedation, starting at page 45. Accordingly, a PHOSITA knowing the sedative effects of WO 537 compounds, would routinely optimize dosing these compounds in the evening or with an evening meal, such as dinner, in consideration of possible sedative effects.
Regarding claim 94, WO 537 teaches typical unit dosage forms such as claimed capsules. See page 48, last paragraph.
Regarding claim 100 and the dose limitation of about 10 to about 50 mg of Compound 1, WO 537 teaches oral doses from about 0.1 to about 10 mg/kg, and especially about 1 to about 5 mg/kg. See page 49, first paragraph. WO 537 teaches human patients can weigh from 40 kg to 80 kg. See page 49, third paragraph. Based on these values, a PHOSITA could routinely optimize doses as claimed based on kg weight of patients and the mg/kg dose range taught.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response starts the rebuttal of the obviousness rejection noting compounds 12 and 13 of WO '537 only differ from presently claimed Compound 1 at the R2a/R2b position, but also at the R3 position (in Compounds 12 and 13 of WO '537, the hydrogen in the alpha position have a TBPS activity of "C" vs. Compounds 3 and 4 of WO '537, which are beta position hydrogens, have respectively, TBPS activity of "A" and "B". The Attorney response notes Compound 1 is also a beta position hydrogen, and because of these differences in TBPS, a PHOSITA would not modify the R2a/R2b and R3 positions to arrive at claimed Compound 1.
With regard to the alternative activity levels of prior art compounds, “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). While the Attorney response argues alternative alpha and beta at position R3 of compounds 12 and 13 vs. 3 and 4, teach away from modifying the hydrogen at that position, it is noted that at position R3 of formula I, alpha and beta positions are the only two alternatives for said hydrogen, with differences in activity and NOT necessarily a lack of activity. Applicant’s arguments regarding different alpha and beta positions and different activity do not overcome the rejection, as these alternative positions are limited, are envisaged by the cited prior art as alternatives and note only differences of degree of activity, rather than total inactivity.
The Attorney response states because compound A2 (i.e., claimed compound 1) of WO ‘537 is an intermediate, rather than a drug compound (final product) administered to a patient, referencing MPEP 2144.09 (VI), citing to In re Lalu,4 a PHOSITA would not stop with an intermediate to investigate different uses of it.
In response, the dicta quoted by Applicant based upon a very fact specific situation from In re Lalu,5 where the Federal Circuit held that
Ultimately our analysis of the obviousness or nonobviousness of appellants' claimed compounds [**13] requires inquiry as to whether there is anything in the Oesterling [U.S. Pat. 3,130,221] reference which would suggest the expected properties of the claimed compounds or whether Oesterling discloses any utility for the intermediate sulfonyl chlorides which would support an expectation that the claimed compounds would have similar properties. In re Lalu, 747 F.2d at 707.
In overturning the PTAB decision finding of obviousness over Oesterling, the Court held:
There is no disclosure that the Oesterling compounds would have any properties in common with those of appellants' compounds, as those properties of the former relate to the use of the compounds for base neutralization, catalysis, metal cleaning, and fuel. . . . In re Lalu, 747 F.2d at 707.6
While not explicitly cited to In re Lalu, the same basic premise and holding regarding intermediates from the Federal Circuit is summarized as follows:
MPEP 2144.09(VI) states “If the prior art does not teach any specific or significant utility for the disclosed compounds, then the prior art is unlikely to render structurally similar claims prima facie obvious in the absence of any reason for one of ordinary skill in the art to make the reference compounds or any structurally related compounds.”
In contrast to the Federal Circuit’s finding in In re Lalu and its fact pattern, the facts of the here demonstrate a specific and significant utility from WO 537, treatment of PPD as claimed, with structurally similar compounds 12 and 13 to claimed compound 1 (among others). See page 3 and page 55 of WO ‘537 teaching treatment of post-natal depression (aka PND or postpartum depression, PPD) in a human subject in need with therapeutically effective amounts.
Dosing Regimen
The Attorney response argues the disclosure of two weeks in WO ‘537 is not a treatment period. The Attorney response argues duration of sedation may be distinct from the dosing
regimen used to achieve that sedation or induce/maintain sedation for 2 weeks. Sedation is argued to be different from PPD treatment (reduction of patient response to external stimulation versus durable improvement in a patient mood disorder), therapeutic goals, clinical endpoints and patient considerations.
In response, it is noted that treatment periods of post-partum depression occur post-delivery and it would be routine for a skilled artisan to optimize treatment for two weeks known to be inclusive of periods of post-partum depression, that overlap periods of time taught by WO ‘537 with regard to sedation and administration of its compounds. See Cleveland Clinic (page 2) and Care Counseling (page 2) websites about Postpartum Depression, cited on the PTO-892 form, demonstrating the two week period of PPD post-delivery is known.7
Unexpected results
The Attorney response quotes the reference Meltzer-Brody et al.8 for the premise that SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) are not approved by the FDA to treat PPD but are used off-label, with or without psychotherapy (p. 583). Post-filing of the claimed application, the Attorney response states brexanolone (March 2019) and Zuranolone, claimed compound 1 (August 2023) were FDA approved for PPD.
The Attorney response states, noted by the Examiner to be in the space of treating mood disorders (not necessarily PPD), SSRIs require 6-12 weeks before some patients begin to experience their full effects, along with dosing adjustments/up-titration; unlike the claimed 2-week dosing. (Meltzer-Brody publication, p. 589). The Attorney response states a dosing regimen of once daily, 2-week administration for treatment of PPD would not have been "routine optimization" as alleged by the Office.
In response, it is noted that PPD’s two week period post-delivery is known. See Cleveland Clinic (page 2) and Care Counseling (page 2) websites about Postpartum Depression, cited on the PTO-892 form, demonstrating the two week period of PPD post-delivery is known.9
The Attorney response, points to Example 1 demonstrating compound 1 effectiveness to treat PPD versus placebo, calling this efficacy to be unexpected.
Initially, in response, a demonstration of active drug compound efficacy versus a placebo would not be unexpected results to overcome a prima face case of obviousness.
Further in response to the allegation of unexpected results, while MPEP 716.02(a) discusses unexpected results in light of a Rule 132 declaration, it has relevance here where it notes “Evidence Must Show Unexpected Results.). In this case, a demonstration of superior effectiveness of a drug (compound 1) in treating a disease state (PPD) over a placebo would not be unexpected.
The Attorney response not only references Example 1 but points to the reference Meltzer-Brody as evidence of unexpected results, where patients experienced a significantly larger improvement in PPD treatment by Day 15 compared to SSRIs; deemed to be critical in early stages of PPD; demonstrated indirectly by a larger improvement in EPDS; where the Attorney response notes the EPDS score improvements were overestimated for SSRIs and underestimated for Compound 1 due to linear interpolation of Indirect treatment comparison (ITC) analysis. (page 589).
In response, per MPEP 716.02(b), and its relevance to unexpected results, the burden is upon Applicant to demonstrate how a comparison of not only claimed compound 1 superior (unexpected) effectiveness versus placebo and SSRIs in treating PPD, are comparative tests against the cited prior art, as being probative of nonobviousness as argued by Applicant. On its face, a comparison of compound 1 being more effective than known SSRIs to treat PPD as per Meltzer-Body, is not necessarily comparative as the combination of cited prior art teaching treatment of PPD with compound 1 analogs and teaching compound 1 per se, overcomes the prima face case.
Maintained 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.
RESPONSE TO ATTORNEY ARGUMENTS:
Applicant has requested the obviousness type double patenting rejections be held in abeyance until all other claim rejections are withdrawn or overcome. In response, the ODP rejections are maintained.
Claims 11, 23, 35-38, and 83-101 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-32, 35-37, 39-40, 42 and 48-51 of copending Application No.18/006141 in view of WO 2016/061537 A1 and Hantsoo et al. Psychopharmacology (2014) 231:939–948.
Regarding claim 11, although the claims at issue are not identical to the reference application claims, they are not patentably distinct from each other because the examined application and reference applications claims are all directed to compositions comprising the claimed compound 1, as reproduced below from reference application claim 29.
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While teaching the claimed compound 1 of examined claim 11 in a pharmaceutical composition, it does not teach the treatment of post-partum in a female adult human subject in need as claimed.
However, it would be obvious to treat a post-partum depressed subject in need as claimed as, WO 537 discloses a method of treating postnatal depression (PND, the equivalent to postpartum depression, PPD) in a human subject in need with a therapeutic agent (with the claimed compound) in therapeutically effective amounts, see page 3 and page 55, with compounds of the present invention (i.e., WO 537), with obvious chemical homologs generically taught by claim 1 of WO 537
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, where the individual obvious homologs are
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. See claim 28
Claim 42 of WO 537 discloses a method of treating a CNS related disorder with a compound of generic formula I. 10
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the reference application in view of WO 537 to treat postpartum depression.
The PHOSITA would have had a reasonable expectation of success because one would routinely optimize methods of treatment as claimed due to compounds being chemical homologs of one another (successive addition of same chemical group, in this case the one carbon alkyl, methyl) See MPEP 2144.09.
Similarly with regard to claims 84 and 88, it would be obvious to treat postpartum depression as per the composition of claim 29 of the reference application, in view of WO 537 teaches treatment of post-partum depression with obvious chemical homologs of the compound of reference application’s claim 29.
Regarding claim 23, WO 537 teaches treatment of severe postpartum depression in an adult, human, female subject. See claim 42 and top of page 3 of WO 537, where postpartum depression is taught to be associated with severe anxiety.
Regarding claims 35, 91 and 91, WO 537 teaches a PHOSITA to administer therapeutically effective amounts “sufficient to provide a therapeutic benefit in the treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition.” See page 39 last paragraph. Accordingly, a PHOSITA would routinely optimize the reduction of a dose of a dose of compound 1, following the occurrence of a sever adverse event.
Regarding claims 36-37 and 92-23 and 96-97 and the administration of compound 1 in the evening or with food, WO 537 notes that those “skilled in the art” will routinely optimize via experimentation doses as needed. See page 64, first paragraph. WO 537 notes its compounds can be used for methods to induce sedation, starting at page 45. Accordingly, a PHOSITA knowing the sedative effects of WO 537 compounds, would routinely optimize dosing these compounds in the evening or with an evening meal, such as dinner.
Regarding claims 38, 94 and 98 and the limitation of a capsule, WO 537 teaches typical unit dosage forms such as capsules. See page 48, last paragraph.
Regarding claims 83-84 and the treatment of a subject with a Hamilton Racing Scale for Depression (HAM-D) total of greater than or equal to 26 at baseline, Hantsoo teaches in a clinical study to treat postpartum depression in subject, Figure 3 measures the effect of treatment to reduce HAMD-D scores by week approaching a score of 26, just under 25 at base line. See page 945. Also note Hantsoo teaches patients to be included in the study having a score of at least 18 and less than 32 on the 19 item HAM-D score. See page 941, first column, section Methods: Subjects. As required by the claim, Hantsoo teaches subjects were to be considered “much improved” or “very much improved” with HAM-D scores of less than or equal to 10, or a 50% reduction in HAM-D score from baseline. See page 941, column 2.
Regarding claim 84 and treatment of PPD with a therapeutically effective amount of Compound 1 once daily for about two weeks, wherein the subject is an adult, as detailed above, WO 537 teaches the treatment of such subject with compound 1, as detailed in the rejection of claim 11 detailed above. With regard to the limitation of once daily dosing for about two weeks, WO 537 teaches one to five oral doses, per day. See page 49 first paragraph. With regard to the limitations of two weeks, while in the context of long term sedation, WO 537 teaches periods of treatment for two weeks. See paragraph 47, 3rd paragraph. The limitations of claim 84 and HAM-D are taught by Hantsoo as discussed above.
Regarding claims 85-87, WO 537 teaches the claimed method of claim 11 as detailed above, the property of there being no substantial change in the cognitive function in the subject would naturally be present in subjects treated as claimed and taught by the art.
Regarding claim 88 and treatment of PPD with a therapeutically effective amount of Compound 1 once daily for about two weeks, wherein the subject is an adult, as detailed above, this subject limitation is taught by WO 537 as detailed in the rejection of claim 11 detailed above. Further, WO 537 teaches one to five oral doses, per day. See page 49 first paragraph. WO 537 teaches periods of treatment for two weeks. See paragraph 47, 3rd paragraph. With regard the limitation there being no substantial change in cognitive function, such property would be naturally present, whether taught or not.
Claims 89-90 claim wherein the subject exhibits the claimed HAM-D score >= total score to 26 also indicated by a >= to about 50% reduction of HAM-D total score from baseline. Hantsoo teaches Figure 3 that measuring the effect of treatment (clinical study of PPD) to reduce HAMD-D scores by week approaching a score of 26, just under 25 at base line. See page 945. Hantsoo teaches patients to be included in the study having a score of at least 18 and less than 32 on the 19 item HAM-D score. See p. 941, col 1., section Methods: Subjects. Hantsoo teaches subjects were “much improved” or “very much improved” with HAM-D scores of less than or equal to 10, or a 50% reduction in HAM-D score from baseline. See p. 941, col. 2.
Regarding claims 99-101 and the dose limitation of about 10 to about 50 mg of Compound 1, WO 537 teaches oral doses from about 0.1 to about 10 mg/kg, and especially about 1 to about 5 mg/kg. See page 49, first paragraph. WO 537 teaches human patients can weigh from 40 kg to 80 kg. See page 49, third paragraph. Based on these values, a PHOSITA could routinely optimize doses as claimed based on kg weight of patients and the mg/kg dose range taught. This is a provisional nonstatutory double patenting rejection.
Claims 11, 23, 35-38, and 83-101 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application Nos. 17993020, 18557691 and 18557705 in view of Hantsoo et al. A randomized, placebo-controlled, double-blind trial of sertraline for postpartum depression Psychopharmacology (2014) 231:939–948 and WO 2016/061537 A1.
The subject matter of claims 11, 23, 35-38, and 83-101 are disclosed and incorporated herein.
As required by the examined claims, claims 121, 30 and 1 of the reference applications are all directed to methods of treating PPD in a human female subject comprising administering a composition comprising compound 1, and various salt and crystal forms. Further, as required by the examined claims, the reference application claims teach treatment periods of about 2 weeks; overlapping doses, for example about 20 mg to about 55 mg; oral dosing; obvious dosage forms such as tablets and capsules; served with or without food.
While teachings methods of treating post-partum depression with compound 1 as claimed, it does not teach treatment of subjects with the claimed HAM-D scores and reduction of such scores by 50% as claimed.
Hantsoo teaches in a clinical study to treat postpartum depression in subject, Figure 3 measures the effect of treatment to reduce HAMD-D scores by week approaching a score of 26, just under 25 at base line. See page 945. Also note Hantsoo teaches patients to be included in the study having a score of at least 18 and less than 32 on the 19 item HAM-D score. See page 941, first column, section Methods: Subjects. As required by the claim, Hantsoo teaches subjects were to be considered “much improved” or “very much improved” with HAM-D scores of less than or equal to 10, or a 50% reduction in HAM-D score from baseline. See page 941, column 2.
Also, the reference claims do not necessarily teach various limitations claimed such as reduction of dose in light of adverse reactions, administration in the evening etc. However, WO 537 teaches a PHOSITA to administer therapeutically effective amounts “sufficient to provide a therapeutic benefit in the treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition.” See page 39 last paragraph. Accordingly, a PHOSITA would routinely optimize the reduction of a dose of a dose of compound 1, following the occurrence of a severe adverse event. Also, WO 537 notes that those “skilled in the art” will routinely optimize via experimentation doses as needed. See page 64, first paragraph. WO 537 notes its compounds can be used for methods to induce sedation, starting at page 45. Accordingly, a PHOSITA knowing the sedative effects of WO 537 compounds, would routinely optimize dosing these compounds in the evening or with an evening meal, such as dinner. This is a provisional nonstatutory double patenting rejection.
Claims 11, 23, 35-38, and 83-101 remain rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of US Patents 10342810 and 11884696, in view of Hantsoo et al. A randomized, placebo-controlled, double-blind trial of sertraline for postpartum depression Psychopharmacology (2014) 231:939–948 and WO 2016/061537 A1
The subject matter of claims 11, 23, 35-38, and 83-101 are disclosed and incorporated herein.
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent, regarding examined claim 11, discloses the claimed compound, for the treatment of a mood disorder such as (post-natal) postpartum depression. See claim 13.
The reference ’810 patent claims 13-16 are directed to methods of treating postnatal depression in a human subject in need thereof with the claimed compound.
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The reference ‘696 patent claims 13-16 are directed to methods of treating CNS related disorder (mood disorder inclusive of depression and/or anxiety) in a human subject in need thereof with the claimed compound.
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As required by the examined claims, the reference patent claims are all directed to methods of treating CNS mood disorders and PPD in a human female subject comprising administering a composition comprising compound 1, and various salt and crystal forms. Further, as required by the examined claims, the reference patent claims pharmaceutical compositions.
While teachings methods of treating post-partum depression with compound 1 as claimed, it does not teach treatment of subjects with the claimed HAM-D scores and reduction of such scores by 50% as claimed.
Hantsoo teaches in a clinical study to treat postpartum depression in subject, Figure 3 measures the effect of treatment to reduce HAMD-D scores by week approaching a score of 26, just under 25 at base line. See page 945. Also note Hantsoo teaches patients to be included in the study having a score of at least 18 and less than 32 on the 19 item HAM-D score. See page 941, first column, section Methods: Subjects. As required by the claim, Hantsoo teaches subjects were to be considered “much improved” or “very much improved” with HAM-D scores of less than or equal to 10, or a 50% reduction in HAM-D score from baseline. See page 941, column 2.
Also, the reference claims do not necessarily teach various limitations claimed such as reduction of dose in light of adverse reactions, administration in the evening, and other limitations as claimed.
However, WO 537 teaches and suggests treatment periods of about 2 weeks; overlapping doses; oral dosing; obvious dosage forms such as tablets and capsules; served with or without food, as discussed above.
WO 537 teaches a PHOSITA to administer therapeutically effective amounts “sufficient to provide a therapeutic benefit in the treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition.” See page 39 last paragraph. Accordingly, a PHOSITA would routinely optimize the reduction of a dose of a dose of compound 1, following the occurrence of a severe adverse event. Also, WO 537 notes that those “skilled in the art” will routinely optimize via experimentation doses as needed. See page 64, first paragraph. WO 537 notes its compounds can be used for methods to induce sedation, starting at page 45. Accordingly, a PHOSITA knowing the sedative effects of WO 537 compounds, would routinely optimize dosing these compounds in the evening or with an evening meal, such as dinner.
Conclusion and Correspondence
In summary, no claims are allowed.
THIS ACTION IS MADE FINAL. 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 WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a 371 National Stage Application of PCT/US2019/036848 06/12/2019. International Application PCT/US2019/036848 claims priority to 62/841,645 filed on 05/01/2019; 62/789,329 filed on 01/07/2019; 62/684,155 filed on 06/12/2018.
2 CAS Reg. No. 1632051-40-1; 1-[(3α,5β)-3-Hydroxy-3-methyl-20-oxo-19-norpregnan-21-yl]-1H-pyrazole-4-carbonitrile (ACI);
SAGE-217; S-812217; SGE 797; Zuranolone/ Zurzuvae
3 2144.09 Close Structural Similarity Between Chemical Compounds (Homologs, Analogues, Isomers) [R-01.2024] I. REJECTION BASED ON CLOSE STRUCTURAL SIMILARITY IS FOUNDED ON THE EXPECTATION THAT COMPOUNDS SIMILAR IN STRUCTURE WILL HAVE SIMILAR PROPERTIES
A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and 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). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08, subsection II.A.4.(c).
II. HOMOLOGY AND ISOMERISM ARE FACTS WHICH MUST BE CONSIDERED WITH ALL OTHER RELEVANT FACTS IN DETERMINING OBVIOUSNESS
Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
4 MPEP 2144.09(VI): "if the prior art merely discloses compounds as intermediates in the production of a final product, one of ordinary skill in the art would not ordinarily stop the reference synthesis and investigate the intermediate compounds with an expectation of arriving at claimed compounds which have different uses. In re Lalu, 747 F.2d 703, 223 USPQ 1257 (Fed. Cir. 1984)."
5 In re Lalu 747 F.2d 703, 223 USPQ 1257 (Fed. Cir. 1984). The claimed invention in dispute of In re Lalu was perfluoroalkyl sulfonyl chlorides and bromides having the formula: C[n]F[2n+1](CH[2])[b]SO[2]Z
wherein the perfluoroalkyl group C[n]F[2n+1] is defined by n being a number between 1 and 20, Z is a chlorine or bromine atom, and the bridging group (CH[2])[b] is defined by b being a number [**2] between 2 and 20. In re Lalu, 747 F.2d at 703-705. See claim 13 of Oesterling, U.S. Pat. 3,130,221
“Claims 14-22 depend from claim 13 and further limit the parameters n, b, and Z which define the length of the perfluoroalkyl group, the length of the bridging group, and the nature of the Z halide group, i.e., a chlorine or bromine atom.” Id. at 704. In In re Lalu, the Federal Circuit held, “Oesterling does not teach the isolation and investigation of the intermediate sulfonyl chlorides [as claimed], but rather discloses, as an optional step, the isolation and purification [**14] of the intermediate to obtain a purer sulfonic acid end product. The isolation and subsequent use of the intermediate sulfonyl chlorides in the production of the corresponding useful sulfonic acids is not motivation sufficient to support the structural obviousness rejection. The board has therefore failed to properly establish that the claimed compounds would have been prima facie obvious in view of Oesterling.” Id. at 704.
6 The mere fact that Oesterling's sulfonyl chlorides can be used as intermediates in the production of the corresponding sulfonic acids does not provide adequate motivation for one of ordinary skill in the art to stop the Oesterling synthesis and investigate the intermediate sulfonyl chlorides with an expectation of arriving at appellants' claimed sulfonyl halides for use as corrosion inhibiting agents, surface active agents, or leveling agents. In re Lalu, 747 F.2d at 707.
7 Cleveland Clinic website Postpartum Depression (PPD)_Accessed May 9 2026 https://my.clevelandclinic.org/health/diseases/9312-postpartum-depression (Year: 2026)
Care Counseling Website Different Postpartum Depression Stages, Signs, and Symptoms, Accessed 5_9_2026 https://care-clinics.com/different-post-partum-depression-stages-signs-and-symptoms/ (Year: 2026)
8 Journal of Medical Economics -Meltzer-Brody et al. "Indirect comparisons of relative efficacy estimates of zuranolone and selective serotonin reuptake inhibitors for postpartum depression," which presents results from an Applicant-funded study estimating the relative efficacy of zuranolone (Compound 1) vs. selective serotonin reuptake inhibitors (SSRis) and combination therapies used to treat PPD in the United States (hereinafter the "Meltzer-Brody publication").
9 Cleveland Clinic website Postpartum Depression (PPD)_Accessed May 9 2026 https://my.clevelandclinic.org/health/diseases/9312-postpartum-depression (Year: 2026)
Care Counseling Website Different Postpartum Depression Stages, Signs, and Symptoms, Accessed 5_9_2026 https://care-clinics.com/different-post-partum-depression-stages-signs-and-symptoms/ (Year: 2026)
10 where A is heteroaryl; R1 is C1-6 alkyl (i.e. methyl); R3 is hydrogen; and R2a/R2b are hydrogen or alkyl/alkyl, WO 537 specifically teaches the CNS disorder as post-partum depression, see specifically claim 48.
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