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 .
Note: The examiner of this application has changed. Applicant is requested to address all documents pertaining this application to examiner VALERIE RODRIGUEZ-GARCIA, AU 1621. Receipt of claim amendments and arguments filed on 11/05/2025 and 01/23/2026 is acknowledged. Claims 59-65 have been added. Therefore, claims 31, 43, 46, 50-53 and 59-65 are now pending and under examination.
Rejection and objections not reiterated herein have been withdrawn.
Priority
The examiner finds that the new limitation: “for immediate release”, does not find support in some of the priority documents. The examiner finds that the earliest priority document that provides support for this limitation is the provisional application 61/975,702, of filing date 04/04/2014. Therefore, the effective filing date of the amended claims is found to be April 4, 2014.
Terminal Disclaimer
The terminal disclaimer filed on 01/23/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent 9,956,227, US Patent 10,960,009 and US Patent 11,026,591 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action.
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.
Claim(s) 31, 43, 46, 50-53 and 59-65 are rejected under 35 U.S.C. 103 as being unpatentable over Mates et al. (US 2011/0071080, previously cited), in view of Ennis (US Patent 6,849,640) and Nyol et al. (Journal of Drug Delivery & Therapeutics; 2013, 3(2), 155-161), and further as evidenced by US 2007/0203231, US 2009/0246276 and Van Noord (European Psychiatry 2011; 26 (S2):1289-1289).
Applicant claims:
PNG
media_image1.png
570
610
media_image1.png
Greyscale
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Teachings by Mates
Mates et al. discloses a method of treating depression comprising administering to a patient in need thereof an effective amount of a compound of Formula
PNG
media_image2.png
140
312
media_image2.png
Greyscale
(Compound A-lumateperone) or a pharmaceutically acceptable salt thereof, such as the tosylate salt, alone, and in combination with other therapeutic agents for the treatment of depression (see whole document, particularly abstract, para [0092-0093], [0095-0100]). Mate teaches that the combination with a therapeutic agent is a combination with an anti-depressant selected from
PNG
media_image3.png
160
388
media_image3.png
Greyscale
. See at least para [0119-0120], [0142], [0158] and claim 16.
Mates discloses that an example of the pharmaceutically acceptable salt is the “toluenesulfonic salt in amorphous or crystal form”. See para [0161]:
PNG
media_image4.png
78
420
media_image4.png
Greyscale
and claim 35. The pharmaceutical compositions comprising the compound use conventional diluents or excipients and are prepared in oral dosage forms that include capsules (para [0162], claim 31). The dosages employed will vary depending, e.g. on the particular compound used, the mode of administration and the therapy desired. Satisfactory results for the treatment of a combination of diseases such as a combination of at least depression, psychosis, e.g., psychosis, in a patient suffering from depression; are obtained on oral administration at dosages of 1 mg to 100 mg once daily, preferably 10 mg, 20 mg, 30 mg, 40 mg or 50 mg in free or pharmaceutically acceptable salt form, once daily (taken as “effective amounts”), preferably via oral administration (p [0159]).
See Example 2 for the “Effectiveness of the Compounds of Formula I as Antidepressant in Chronic Animal Model of Depression” and the following disclosure:
PNG
media_image5.png
100
420
media_image5.png
Greyscale
In para [0182], Mates discloses that “Normal mice treated with Compound A once daily for 30d are healthy and normal-appearing and gained weight normally”. And socially-defeated mice treated with Compound A, exhibited a significant increase in social behavior. The administration of the compound significantly reverses the behavioral preference of spending significantly more time in the distant Control Zones.
Teachings by Ennis
Ennis taught compounds that have activity as 5-HT receptor ligands for the treatment of depression, major depressive disorder and other disorders, which are of formula (II)
PNG
media_image6.png
114
192
media_image6.png
Greyscale
(col. 2-3, 5). Ennis also disclose that for oral therapeutic administration, the compounds may be combined in capsules with suitable excipients, such as corn starch, potato starch, magnesium stearate and others (col. 17-18).
Immediate drug release
Immediate drug release dosage forms of anti-depressants are valuable because they provide rapid disintegration after administration, enhanced dissolution rates, faster onset of action when compared to conventional formulations and convenience of oral administration. See Nyol et al. (Journal of Drug Delivery & Therapeutics; 2013, 3(2), 155-161). Nyol also taught suitable excipients for immediate drug release dosage forms.
Immediate release formulations of antidepressants have been used for the treatment of major depressive disorder. See at least US 2007/0203231, US 2009/0246276 and Van Noord (European Psychiatry 2011; 26 (S2):1289-1289).
Ascertainment of the Difference Between the Prior Art and the Claims
(MPEP §2141.012)
Regarding instant claims 31, 46-53 and 59-65, the difference is that Mates does not particularly teach 60 mg per day of the Compound of Formula I measured as the weight of the salt, and formulated for immediate release.
Claim 43 additionally differs in that Mates does not specify the pharmaceutically acceptable excipient in the formulation.
Finding of prima facie obviousness--rational and motivation (MPEP §2142-2413)
One of ordinary skill in the art is a chemist practitioner with the knowledge and skills of the authors of the references cited to support the examiner's position. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer an effective amount of Compound A toluenesulfonic salt in crystal form combined with the particular anti-depressants, as taught by Mates et al., to treat a patient suffering from symptoms of depression and major depressive disorder because 1) Mates teaches that Compound A is to be used for the treatment of depression, and the data therein demonstrates that daily administration of Compound A induces a behavioral response in socially-stressed mice consistent with antidepressant efficacy and comparable to that elicited by anti-depressant medications such as fluoxetine, 2) compounds of similar core and similar mechanism of action (5-HT activity) were known to treat depression symptoms and major depressive disorder (per Ennis), and 3) the artisan knew that the particular anti-depressants used as second agent in reference Mates were also used for the treatment of major depressive disorder (see at least the secondary references). The references would have provided a reasonable expectation of success in treating symptoms of depression and major depressive disorder in a patient.
One of ordinary skill in the art would have been motivated to administer the combination of Mates in which Compound A toluenesulfonic salt in crystal form is in a capsule for oral administration and is administered at an effective amount of 60 mg per day, because Mates et al. taught oral administration in capsule form of the anti-depressant Compound A or its salts at dosages of 1 mg to 100 mg once daily, preferably 10 mg, 20 mg, 30 mg, 40 mg or 50 mg, once daily. The artisan would have been motivated to determine the optimal amounts of Compound A in toluenesulfonic salt in crystal form within the range of the prior art, since the optimization of effective amounts of known agents to be administered, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. The dosage amount is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization.
“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
The artisan would have been further motivated to make the combination formulation of Mates an immediate release formulation because of all the advantages that immediate release formulations have. See above Nyol et al., US 2007/0203231, US 2009/0246276 and Van Noord et al.
With respect to claim 43, it would have been prima facie obvious to use the well-known and suitable excipients for drug formulations, as Mate teaches. Particularly, those excipients that have been known to be suitable with antidepressants and in immediate release dose formulations. See the secondary references for the use of potato starch, polyvinyl pyrrolidone, and others.
In regards to the recitation “wherein the method does not result in hyperprolactinemia, EPS/akathisia, weight gain or cardiovascular side effects”, it is pointed these recitations are a necessary result or property of administering the Compound A or toluene sulfonic acid addition salt to a patient suffering from major depressive disorder. The properties of such a claimed composition will be present, and are also clearly rendered obvious by the prior art teachings since Mates showed that upon administration of the Compound A (of formula I), mice were healthy and normal-appearing and gained weight normally Thus, administration does not result in hyperprolactinemia, EPS/akathisia, weight gain or cardiovascular side effects.
Applicant's arguments filed 11/05/2025 have been fully considered but they are not persuasive.
Applicant submitted references (A) through (E) and discussed that references (C) and (D) support that SSRIs and SNRIs require several weeks to achieve clinical efficacy and that there is still a need for faster-acting antidepressant agents. Applicant discussed that reference (E) Machado-Vieira, supports the contention that currently available antidepressant medications all exhibit a delayed onset of antidepressant response. In response, current antidepressant medication is available as extended-release and immediate-release formulation for major depressive disorder. See the secondary references above. The ordinary skilled artisan knew that immediate-release formulations have the benefits of rapid disintegration after administration, enhanced dissolution rates, faster onset of action when compared to conventional formulations and convenience of oral administration, as discussed above, and thus, the ordinary artisan would have been motivated to make immediate release formulations to overcome the problems that applicant’s references (C), (D) and (E) discuss.
Applicant additionally discussed the Durgam references as allegedly supporting unexpected results of the claimed invention.
PNG
media_image7.png
244
574
media_image7.png
Greyscale
.
Applicant argues that the Durgam references show a rapid onset of therapeutic efficacy in patients treated with 42mg of lumateperone + antidepressant therapy (ADT). First, it is noted that the claims require treatment with lumateperone in an amount of about 60 mg per day, in the form of crystalline lumateperone tosylate. What is claimed is not the same as in the Durgam references. In addition, Applicant repeats part of Table 1 of Durgam 1 and of Table 2 of Durgam 2. Applicant discussed that Table 1 showed that the patients selected for the study were patients for which the current antidepressant therapy was failing, and that Durgam 2 summarizes the patients concurrent antidepressant treatment. In response, this is not particularly relevant to the alleged unexpected results over the art. The patient’s previous and different antidepressant therapy does not reveal that the new antidepressant therapy of lumateperone combination of prior art Mates posseses unexpected properties.
Applicant then discussed that the results demonstrated that lumateperone 42 mg plus ADT provided “significant improved MADRS Total Score at Day 43 compared with placebo + ADT in patients with MDD” per Durgam 1. Applicant provided Figures 1 and 2 of Durgam 1 to also support that “significantly greater MADRS Total score reductions occurred at Day 8 and persisted throughout the study.” Applicant further discussed that patients continued to improve in their depression symptom, and that the results are substantially better than the antidepressant norms described in Tian, Pereira and Machado.
However, one cannot say that these results are unexpected over the prior art. Lumateperone was disclosed as an antidepressant in a chronic animal model of depression in prior art Mates (Example 2). In addition, lumateperone was disclosed as having improved selectivity profile with respect to off-target interactions associated with many side effects compared to other antipsychotic drugs and are therefore also useful as antipsychotic agents in patients who are unable to tolerate the side effects of convention antipsychotic drugs. While applicant here provides data for the treatment of depression symptoms with the combination of lumateperone + unidentified ADT, Applicant has not compared the data with the treatment with lumateperone alone of the prior art. There is no evidence that applicant’s result is a substantial and unexpected improvement over the treatment with lumateperone alone. Thus, one cannot say that applicant’s results are unexpected. In addition, applicant’s attention is drawn to the results in Durgam (Lumateperone for the Treatment of Major Depressive Disorder With Mixed Features or Bipolar Depression With Mixed Features 2025), provided by applicant in the IDS of 11/05/2025. Compared to this reference, there are no unexpected results.
In addition, Mates instructs to treat depression/depressive symptoms with a combination of lumateperone and an anti-depressant selected from
PNG
media_image3.png
160
388
media_image3.png
Greyscale
, as discussed above.
The administration of the combination of Mates would inherently result in the argued significant improvements in the treatment of depression/depressive symptoms because a chemical composition and its properties are inseparable. MPEP § 2112.01. The identical composition must inherently have the same claimed activity.
MPEP 2145 II. Prima Facie Obviousness is not Rebutted by Merely Recognizing Additional Advantages or Latent Properties Present But Not Recognized in the Prior Art
"The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").
Double Patenting
Applicant’s arguments regarding the ODP rejections over applications or patents that are later-expiring are found persuasive, and those rejections have been withdrawn.
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 31, 43, 46, 50-53 and 59-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the following pending claims of copending application (reference application) 18/975,550 (claims 40-47 and 49-53), in view of Mates (US 2011/0071080), and further in view of Ennis (US Patent 6,849,640) and Nyol et al. (Journal of Drug Delivery & Therapeutics; 2013, 3(2), 155-161), and as evidenced by US 2007/0203231, US 2009/0246276 and Van Noord (European Psychiatry 2011; 26 (S2):1289-1289).
Although the claims at issue are not identical, they are not patentably distinct from each other. Instant claims are drawn to a method for the treatment of major depressive disorder comprising
administering to a patient in need thereof an effective amount of a Compound of Formula I as in instant claim 31 in crystalline toluenesulfonic acid addition salt form; wherein the effective amount of the Compound of Formula I is about 60 mg per day, measured as the weight of the salt;
wherein the Compound of Formula I is formulated in a capsule for oral administration and for immediate release,
wherein the method does not result in hyperprolactinemia, EPS/akathisia, weight gain or cardiovascular side effects;
and wherein the Compound of Formula I is used in combination with, or for co- administration with, another active therapeutic agent, wherein the other active therapeutic agent is an anti-depressive agent.
The claims of the below copending application teach treating depression or depressive disorders comprising administering the same compound of Formula I in toluenesulfonic acid salt form in crystal form (copending claims 44 and 52). Copending claim 46 further recites combining the compound with an antidepressant, and copending claim 47 recites the various antidepressants that are recited in the instant claims.
The claims of the below copending application do not explicitly teach treating major depressive disorder wherein the compound is formulated in capsule for oral administration and for immediate release, wherein the effective amount of the Compound of Formula I is about 60 mg per day. However, the instant claims are obvious further in view of Mates and the other secondary references as discussed above in the 35 U.S.C. 103 rejection.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer an effective amount of Compound A toluenesulfonic salt in crystal form combined with the particular anti-depressants, as taught by the copending claims, to treat a patient suffering from symptoms of depression and major depressive disorder because 1) Mates teaches that Compound A is to be used for the treatment of depression, and the data therein demonstrates that daily administration of Compound A induces a behavioral response in socially-stressed mice consistent with antidepressant efficacy and comparable to that elicited by anti-depressant medications such as fluoxetine, 2) compounds of similar core and similar mechanism of action (5-HT activity) were known to treat depression symptoms and major depressive disorder (per Ennis), and 3) the artisan knew that the particular anti-depressants used as second agent in reference Mates were also used for the treatment of major depressive disorder (see at least the secondary references). The references would have provided a reasonable expectation of success in treating symptoms of depression and major depressive disorder in a patient.
One of ordinary skill in the art would have been motivated to administer the combination of the copending claims and Mates in which Compound I (A) toluenesulfonic salt in crystal form is in a capsule for oral administration and is administered at an effective amount of 60 mg per day, because Mates et al. taught oral administration in capsule form of the anti-depressant Compound A or its salts at dosages of 1 mg to 100 mg once daily, preferably 10 mg, 20 mg, 30 mg, 40 mg or 50 mg, once daily. The artisan would have been motivated to determine the optimal amounts of Compound A in toluenesulfonic salt in crystal form within the range of the prior art, since the optimization of effective amounts of known agents to be administered, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. The dosage amount is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization.
“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
The artisan would have been further motivated to make the combination formulation of the copending claims an immediate release formulation because of all the advantages that immediate release formulations have. See above Nyol et al., US 2007/0203231, US 2009/0246276 and Van Noord et al.
With respect to claim 43, it would have been prima facie obvious to use the well-known and suitable excipients for drug formulations, as Mate teaches. Particularly, those excipients that have been known to be suitable with antidepressants and in immediate release dose formulations. See the secondary references for the use of potato starch, polyvinyl pyrrolidone, and others.
In regards to the recitation “wherein the method does not result in hyperprolactinemia, EPS/akathisia, weight gain or cardiovascular side effects”, it is pointed these recitations are a necessary result or property of administering the Compound A or toluene sulfonic acid addition salt to a patient suffering from major depressive disorder. The properties of such a claimed composition will be present, and are also clearly rendered obvious by the prior art teachings since Mates showed that upon administration of the Compound A (of formula I), mice were healthy and normal-appearing and gained weight normally Thus, administration does not result in hyperprolactinemia, EPS/akathisia, weight gain or cardiovascular side effects.
This is a provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented.
Claims 31, 43, 46, 50-53 and 59-65 are rejected on the ground of nonstatutory double patenting as being unpatentable over the allowed claims of the following U.S. Patents, in view of Mates (US 2011/0071080), and further in view of Ennis (US Patent 6,849,640) and Nyol et al. (Journal of Drug Delivery & Therapeutics; 2013, 3(2), 155-161), and as evidenced by US 2007/0203231, US 2009/0246276 and Van Noord (European Psychiatry 2011; 26 (S2):1289-1289).
Although the claims at issue are not identical, they are not patentably distinct from each other. Instant claims are drawn to a method for the treatment of major depressive disorder comprising
administering to a patient in need thereof an effective amount of a Compound of Formula I as in instant claim 31 in crystalline toluenesulfonic acid addition salt form; wherein the effective amount of the Compound of Formula I is about 60 mg per day, measured as the weight of the salt;
wherein the Compound of Formula I is formulated in a capsule for oral administration and for immediate release,
wherein the method does not result in hyperprolactinemia, EPS/akathisia, weight gain or cardiovascular side effects;
and wherein the Compound of Formula I is used in combination with, or for co- administration with, another active therapeutic agent, wherein the other active therapeutic agent is an anti-depressive agent.
The claims of the below patents teach treating depression or depressive disorders comprising administering compound of Formula I or a pharmaceutically acceptable salt thereof. However, the claims of the below patents do not explicitly teach treating major depressive disorder wherein the compound of Formula I is crystalline toluene sulfonic acid salt formulated in capsule for oral administration and for immediate release, wherein the effective amount of the Compound of Formula I is about 60 mg per day.
However, the instant claims are obvious over the patented claims in view of Mates and the other secondary references as discussed above in the 35 U.S.C. 103 rejection.
US 9,708,322
US 10,117,867
US 10,472,359
US RE 48,839
US 11,680,065
11,958,852
12,264,160 (claims 14-17, 19-22, 24-27)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer an effective amount of instant compound of Formula I or a salt thereof such as toluene sulfonic acid addition salt in crystalline form combined with the particular anti-depressants claimed, as taught by Mates et al., to treat a patient suffering from symptoms of depression and major depressive disorder because 1) Mates teaches that Compound I (A) is to be used for the treatment of depression, and the data therein demonstrates that daily administration of Compound A induces a behavioral response in socially-stressed mice consistent with antidepressant efficacy and comparable to that elicited by anti-depressant medications such as fluoxetine, 2) compounds of similar core and similar mechanism of action (5-HT activity) were known to treat depression symptoms and major depressive disorder (per Ennis), and 3) the artisan knew that the particular anti-depressants used as second agent in reference Mates were also used for the treatment of major depressive disorder (see at least the secondary references). The references would have provided a reasonable expectation of success in treating symptoms of depression and major depressive disorder in a patient.
From the patented claims, it would have been obvious to a person of ordinary skill in the art to administer the same Compound (instant compound of Formula I) in crystalline toluene sulfonic acid salt form, in a capsule for oral administration and administered at an effective amount of 60 mg per day, because Mates et al. taught that the Compound is also useful as the crystalline toluene sulfonic acid salt form, and also taught the oral administration in capsule form of the anti-depressant Compound or its salts at dosages of 1 mg to 100 mg once daily, preferably 10 mg, 20 mg, 30 mg, 40 mg or 50 mg, once daily. The artisan would have been motivated to determine the optimal amounts of Compound in toluenesulfonic salt in crystal form, since the optimization of effective amounts of known agents to be administered, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. The dosage amount is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05.
“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
The artisan would have been further motivated to make the combination formulation of the copending claims an immediate release formulation because of all the advantages that immediate release formulations have. See above Nyol et al., US 2007/0203231, US 2009/0246276 and Van Noord et al.
With respect to claim 43, it would have been prima facie obvious to use the well-known and suitable excipients for drug formulations, as Mate teaches. Particularly, those excipients that have been known to be suitable with antidepressants and in immediate release dose formulations. See the secondary references for the use of potato starch, polyvinyl pyrrolidone, and others.
In regards to the recitation “wherein the method does not result in hyperprolactinemia, EPS/akathisia, weight gain or cardiovascular side effects”, it is pointed these recitations are a necessary result or property of administering the Compound A or toluene sulfonic acid addition salt to a patient suffering from major depressive disorder. The properties of such a claimed composition will be present, and are also clearly rendered obvious by the prior art teachings since Mates showed that upon administration of the Compound A (of formula I), mice were healthy and normal-appearing and gained weight normally Thus, administration does not result in hyperprolactinemia, EPS/akathisia, weight gain or cardiovascular side effects.
Response to Arguments
Applicant's arguments filed on 11/05/2025 and 01/23/2026 have been fully considered. They were found partially persuasive, making the examiner to withdraw several ODP rejections. However, they are not found persuasive for the ODP rejections above. The examiner was not persuaded for the same reasons discussed in the 103 rejection above.
Conclusion
Claims 31, 43, 46, 50-53 and 59-65 are rejected. No claim is allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-5:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
Prosecution Insights