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 .
DETAILED ACTION
Final Rejection
Claim Status
Claims 1-24 are pending examination.
Priority Status
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Examiner Responses to Arguments/Amendments
The issues raised in the Office Action mailed 11/05/2025, are addressed below:
I. Claim Objections –
Upon amendment entry, the objection to Claim 12 as being a substantial duplicate of Claim 9, is acknowledged as corrected; objection is withdrawn.
II. Claim Amendments –
Upon amendment entry, Claim 1 was modified with the added limitation:
“A method of reducing suicidal ideation and suicidal behavior in a person, the method comprising orally administering twice-a-day (BID) a single unit dose comprising nefazodone hydrochloride and risperidone, wherein the person is suffering from a psychiatric disorder having a Global Impression of Severity of Suicidality-revised (CGI-SS-r) score of >2,wherein,the method comprises a period of acute therapy, followed by a period of ongoing maintenance, the strength of the unit doses administered during the acute therapy differs from the strength of the unit doses administered during the maintenance therapy, the strength of the unit doses administered during the maintenance therapy can vary, the acute therapy comprises a loading dose, and the period of ongoing maintenance is long-term and continuous.”
III. Claim Rejections under 35 USC § 103 –
Claims 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over P. Migaly in
US 7,973,043 B2 (“Patent’043”) in view of H. Rozjabek, et al., as evidenced by PubChem (nefazodone hydrochloride).
Applicant' s arguments, filed 11/05/2025, with respect to claims have been fully considered but they are not persuasive.
With respect to Applicant’s argument that the Examiner has not met the burden for establishing a prima facie finding of obvious this argument has been considered but is not found to be persuasive for the following reasons:
As stated in the prior Office Action, the art discloses the matter of the claims. The Examiner made the case for a single dosage unit as indicated in col. 6, lns. 16-58 (see below) of Patent’043. The Examiner has shown the art is good for the claims when reciting “orally administering twice-a-day (BID) a single unit dose.”
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In regards to the claims reciting “a single dosage unit, administered twice-a-day, comprising nefazodone hydrochloride and risperidone,” under KSR-Prong A – both medications are known in the art, as well as their mechanism of action, for being used by a person suffering from a psychiatric disorder. Nefazodone is a SARI (serotonin antagonist and reuptake inhibitor), while risperidone is an atypical antipsychotic that acts as a potent 5-HT2A and dopamine receptor antagonist. Nefazodone (as seen in Patent’043; col. 8, lns. 7-22) and risperidone (as seen in Patent’043; col. 8, lns. 56-63) combination is known in the prior art, as the elements are combined using techniques that are standard or known to a person of ordinary skill in the art.
The nefazodone-risperidone combination product does not produce a new or unexpected function in treating a patient in need. Its combination restate the key benefits of the combination already known. Nefazodone is used for treatment-resistant depression (col. 8, lns. 7-22), and adding an antipsychotic like risperidone can boost the overall antidepressant effect. Risperidone (col. 8, lns. 56-60) is effective for schizophrenia, bipolar mania, and, when combined with antidepressants, can help manage irritability, aggression, or psychotic symptoms.
Therefore, Applicant’s argument is not persuasive.
With respect to Applicant’s argument stating: “References, alone or in combination, do not teach every limitation of the invention, as presently claimed. The cited references fail to satisfy the "all claim limitations taught or suggested" prong because multiple elements of amended claim 1 are neither disclosed nor suggested when Rozjabek (2022) and Migaly (US 7,973,043) are read alone or in combination.”
Examiner disagrees. In response to the argument above, under KSR-Prong A – both medications are known in the art, as well as their mechanism of action, for being used by a person suffering from a psychiatric disorder. Nefazodone is a SARI (serotonin antagonist and reuptake inhibitor), while risperidone is an atypical antipsychotic that acts as a potent 5-HT2A and dopamine receptor antagonist. Nefazodone (as seen in Patent’043; col. 8, lns. 7-22) and risperidone (as seen in Patent’043; col. 8, lns. 56-63) combination is known in the prior art, as the elements are combined using techniques that are standard or known to a person of ordinary skill in the art.
Therefore, Applicant’s argument is not persuasive.
With respect to Applicant’s argument stating: “the claim's patient-selection criterion requiring a baseline Global Impression of Severity of Suicidality-revised (CGI-SS-r) score of >2 is absent from Migaly and, while Rozjabek defines and analyzes CGI-SS-r in esketamine MDD trials, it does not disclose treatment using nefazodone/risperidone or any dosing schema tied to CGI-SS-r thresholds”
Examiner disagrees. In response to Applicants argument over the drug combination & the Global Impression of Severity of Suicidality-revised (CGI-SS-r), Patent’043 recites col. 12, lns. 23-40 and col. 12, lns. 48-55:
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This, in summary, indicates that though there is not a CGI-SS-r score associated with the nefazodone-risperidone combination, there are still key motivations:
To treat patients who were not just experiencing suicidal thoughts, but were actively and significantly suicidal (mildly suicidal to extremely suicidal). The >2 cut-off is designed to select patients with adequate "therapeutic windows" to show a response.
This threshold is also strategy to enhance sensitivity of studies to detect accurate treatment effects by enrollment of a population with at least, "mild" level of active risk.
A lower threshold may also have too many patients with "Normal, not at all suicidal" (score of 1) ratings, which results in a plateau effect where further improvement isn’t possible. This yields a reduced ability to show differences between treatments and placebos.
In the intended population, with suicidality studies, methods are often targeting patients with major depressive disorder who have acute suicidal ideation. A CGI-SS-r captures patients who are experiencing at least questionable or minimal suicidal thoughts, allowing for the analysis of rapid reduction in suicide risk within hours or days.
With the above included, an obvious motivation is that there is a guarantee there is focus on a symptomatic population rather than a healthy one,. This allows for an honest assessment of the medication's capacity to reduce suicidal severity.
Additionally, in col. 13, lns. Patent’043 states the following:
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Thus, this would motivate one in the art to use KSR-Prong A since the combination of an SSRI-atypical neuroleptic (a.k.a. antipsychotics) combinations is known. Since neuroleptics inhibit dopamine receptors in the nervous system, reducing the positive symptoms of psychosis (hallucinations/delusions) the nefazodone-risperidone combination is one that is already known.
Also, in the example provided in Patent’043, (Ex. 1; col. 10, ln. 45 to col. 11, ln. 5) the antidepressant used is fluoxetine. The prior art recites in col. 8, lns. 7-22 that nefazodone is also an option. Therefore, according to KSR-Prong B, it would be obvious to substitute fluoxetine (Prozac) with nefazodone. Nefazodone and fluoxetine equivalently are antidepressants with established efficacy, As the antipsychotic is still risperidone, the substitution of nefazodone with fluoxetine is one that has been suggested within the art and gives motivation as worthwhile combination for success.
Therefore, Applicant’s argument is not persuasive.
With respect to Applicant’s argument stating “The Office Action's combination is not a "finite number of identified, predictable solutions" amenable to routine optimization.
Rather, the cited art presents broad menus across multiple independent axes-selection of antidepressant (e.g., nefazodone among many), selection of atypical antipsychotic (e.g., risperidone among many), co-formulation versus separate administration, BID versus other frequencies, CGI-SS-r-based patient selection and improvement targets, presence of a loading dose, and phase-dependent and variable maintenance strengths-without directing the skilled artisan to the specific alignment recited in the claims or to predictable results from that alignment.
In this context, the claimed regimen is not a routine adjustment of known variables within a finite, predictable set, but a specific, multi-parameter design that the references do not identify or motivate.
Examiner disagrees. In response to Applicant’s rebuttal of “The Office Action's combination is not a "finite number of identified, predictable solutions" amenable to routine optimization.” The Examiner has stated above rationale used for establishing the 35 U.S.C. 103 rejection. In addition, the 35 USC § 103 rejection prior art recites the acute loading phase (col. 11, lns. 55-67) transitioning to long-term continuous maintenance (col. 15, lns. 20-56), both which reads upon the Applicant’s Claims.
Hence, Applicant’s argument is not persuasive.
The 35 USC § 103 rejection is maintained.
IV. Maintained Rejections –
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.
Joint Inventors
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.
Claim(s) 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over P. Migaly in US 7,973,043 B2 (for Claims 1-16; 20-24; hereinafter “’043”) in view of H. Rozjabek, et. al in “Assessing the meaningful change threshold of Quality of Life in Depression Scale…” (for Claims 17-19 & 21; hereinafter “Rozjabek”) as evidenced by PubChem (Nefazodone hydrochloride).
With respect to Claim 1-5, Patent ’043 teaches “the method comprises administering an effective amount of an antipsychotic medication or dopamine system stabilizer in combination with a newer antidepressant, to patients who have not been diagnosed as treatment-resistant, or bipolar disorder, and who do not have psychotic symptoms. Preferably the antipsychotic medication is an atypical antipsychotic. In one embodiment, the antidepressant is a selective serotonin reuptake inhibitor. Furthermore, this combination may specifically target the prevention of suicide” (col. 4, lns. 20-26). Patent ’043 further teaches embodiments of specific antidepressants including selective serotonin reuptake inhibitors such as nefazodone (nefazodone-Serzone; col. 8, lns. 5-18) This reads on the claims since nefazodone hydrochloride is also known as Serzone (as evidenced by PubChem, Nefazodone hydrochloride). Patent ’043 further teaches atypical antipsychotics which include risperidone (col. 8, lns. 56-63).
Patent ’043 continues teaching with respect to Claim 1 , “determination of the appropriate dosage is well within the ability of one skilled in the art; antidepressants and antipsychotics have been prescribed for years. When used in the combination of the present invention, dosage of the anti-depressant will be similar to the dosage amount needed when prescribed alone, while the amount of antipsychotic drug needed will be somewhat less than the amount used when that class of drug is prescribed alone for a patient experiencing psychotic symptoms (which reads on orally administering twice-a-day (BID) a unit dose since it is based on physician recommendation; col. 6, lns. 16-58).
Patent ’043 continues teaching with respect to Claim 1, two examples in which the subjects are suffering from a psychiatric disorder and illustrates the invention as a method of acute therapy following by maintenance period, change in dosage strength and period of ongoing maintenance (col. 10, lns. 45-67 to col. 11, lns. 1-54).
Patent ’043 fails to teach the use of the Global Impression of Severity of Suicidality-revised (CGI-SS-r) however it must be noted that Patent ’043 does teach that the patient population suffering from this disorder would be under the care of a physician(s) or health care provider(s) indicating that the physician prescribing the treatment is trained to use this test or others similarly used in the field of art.
Rozjabek (in Claims 1-5) teaches “The CGI-SS-r is included in Module 7 of the Suicide Ideation and Behavior Assessment Tool (SIBAT)… The CGI-SS-r in Module 7 summarizes the clinician’s overall impression of severity of suicidality on a 7-point scale (0-normal, 1-questionably, 2-mildly, 3-moderately, 4-markedly, 5-severely, and 6-most extremely suicidal) based on the totality of information available to the clinician, including information from the completed modules of the SIBAT. The category ratings in the CGI-SS-r are directly interpretable as different levels of suicidality and a 1-point change in a CGI scale is consistent with a clinically observable change (pg. 3, col. 2, para. 1).”
It would therefore be obvious to combine Patent ’043 and Rozjabek as both teach the scope of the claims in dealing with treating psychiatric disorders to reduce suicidal ideation. Patent ’043 and Rozjabek include relevant data on psychiatric disorders (as cited above) treating persons suffering from various types of depression, including major depressive disorder, who are at risk for suicide (col. 3, lns. 45-51). As seen in KSR – Prong A there is motivation to combine these prior arts because use of these methods helps to aid in the reduction of suicide ideation in patients suffering from this psychiatric disorder. Since combining prior art elements according to known methods yields predictable results, one skilled in the art could have combined the elements by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
This additionally indicates that though there is not a CGI-SS-r score associated with the nefazodone-risperidone combination, there are still key motivations:
To treat patients who were not just experiencing suicidal thoughts, but were actively and significantly suicidal (mildly suicidal to extremely suicidal). The >2 cut-off is designed to select patients with adequate "therapeutic windows" to show a response.
This threshold is also strategy to enhance sensitivity of studies to detect accurate treatment effects by enrollment of a population with at least, "mild" level of active risk.
A lower threshold may also have too many patients with "Normal, not at all suicidal" (score of 1) ratings, which results in a plateau effect where further improvement isn’t possible. This yields a reduced ability to show differences between treatments and placebos.
In the intended population, with suicidality studies, methods are often targeting patients with major depressive disorder who have acute suicidal ideation. A CGI-SS-r captures patients who are experiencing at least questionable or minimal suicidal thoughts, allowing for the analysis of rapid reduction in suicide risk within hours or days.
With the above included, an obvious motivation is that there is a guarantee there is focus on a symptomatic population rather than a healthy one,. This allows for an honest assessment of the medication's capacity to reduce suicidal severity.
With respect to claims 6-16 , Patent ’043 teaches:
Claim 6: wherein the person is suffering from a psychiatric disorder for at least 6 weeks (col. 3, lns. 59-64).
Claim 7: which effectively reduces the incidence of suicidal ideation and suicidal behavior in a person suffering from a major depressive episode (col. 7, lns. 34-54).
Claim 8: which effectively reduces the severity of depressive symptoms in the person (Examples 1 & 2; col. 10, lns. 45-67 to col. 11, lns. 1-54).
Claim 9: wherein the person is afflicted with treatment-refractory depression (also known as treatment-resistant depression; col. 3, lns. 59-64; which reads ).
Claim 10: wherein the person was previously prescribed an antipsychotic drug (risperidone; col. 8, lns. 56-63).
Claim 11: wherein the person was previously prescribed an antidepressant drug (SSRI – nefazodone - Serzone; col. 8, lns. 5-18).
Claim 12: wherein the person is afflicted with treatment-refractory depression (also known as treatment-resistant depression; col. 3, lns. 59-64).
Claim 13: wherein treatment comprises acute therapy, such that the unit dose is administered in a hospital emergency department, psychiatric hospital, urgent care center, or other short-term stay facility (col. 6, lns. 5-10).
Claim 14: wherein the treatment comprises maintenance therapy, such that the unit dose is a maintenance drug, orally administered on a regular, recurring, and long-term basis to the person in outpatient care as an ongoing maintenance in reducing suicidal ideation and suicidal behavior (Examples 1 & 2; col. 10, lns. 45-67 to col. 11, lns. 1-67).
Claim 15: wherein the unit dose is an oral tablet, an oral capsule, an oral soluble film, an oral solution, an oral suspension, an oral powder, or oral granules (col. 6, lns. 45-65).
Claim 16: wherein the unit dose is an oral solid (col. 6, lns. 45-65).
Patent ’043 teaches several embodiments of antidepressant/antipsychotic combinations, it also continues teaching Claims 20 -24 in the following:
Claim 20: wherein the unit dose comprises 50-300 mg nefazodone hydrochloride (Examples 1 & 2; col. 10, lns. 45-67 to col. 11, lns. 1-67, which details a patient receiving an SSRI of 50 mg that reads on the claim range) and 0.20-1.0 mg risperidone (col. 6, lns. 30-31; for risperidone 0.5-1 mg -which reads within the claim range).
Claim 21: wherein the unit dose is a scored tablet comprising 50-300 mg nefazodone hydrochloride (Examples 1 & 2; col. 10, lns. 45-67 to col. 11, lns. 1-67, which details a patient receiving an SSRI of 50 mg that reads on the claim range) and 0.20-1.0 mg risperidone (col. 6, lns. 30-31; for risperidone 0.5-1 mg -which reads within the claim range).
Claim 22: wherein the period of acute therapy is up to 2 weeks (Examples 1 & 2; col. 10, lns. 45-67 to col. 11, lns. 1-67; acute therapy for Example 2 patient started under care of physician for 2 weeks, col. 11, lns. 5-55).
Claim 23: wherein the period of acute therapy is up to 1 month (Examples 1 & 2; col. 10, lns. 45-67 to col. 11, lns. 1-67; acute therapy for Example 2 patient continued for two months, col. 11, lns. 5-55).
Claim 24: wherein the long-term and continuous period of ongoing maintenance is at least 6 months (Examples 1 & 2; col. 10, lns. 45-67 to col. 11, lns. 1-67; acute therapy for Example 1 & 2 patient continued for at least 12 months, col. 11, lns. 35-43).
Though Patent ’043 fails to teach all of the limitation of Claim 21, wherein the unit dose is a scored tablet - the patent does teach that suitable dosage forms can range from “two tablets each containing one drug to be administered in a single dose form, it further teaches the medication components can various methods to form a delivery system whether within the same delivery system or concomitate use…. (single) capsule, tablet (including "sprinkle", fast dissolving, "melt away"(col. 6, lns. 45-65).” Under BRI this indicates that the tablet can be in any manner desired by the physician to maximize taking necessary medication for the patient, including scoring the tablets.
For Claims 17-19: wherein, wherein during the period of treatment, or at the conclusion thereof, the person experiences an improvement of ( >2 units) – (>4 units) in the Global Impression of Severity of Suicidality-revised (CGI-SS-r) evaluation score, Rozjabek teaches the following:
Rozjabek teaches “The CGI-SS-r is included in Module 7 of the Suicide Ideation and Behavior Assessment Tool (SIBAT)… The CGI-SS-r in Module 7 summarizes the clinician’s overall impression of severity of suicidality on a 7-point scale (0-normal, 1-questionably, 2-mildly, 3-moderately, 4-markedly, 5-severely, and 6-most extremely suicidal) based on the totality of information available to the clinician, including information from the completed modules of the SIBAT. The category ratings in the CGI-SS-r are directly interpretable as different levels of suicidality and a 1-point change in a CGI scale is consistent with a clinically observable change (pg. 3, col. 2, para. 1).” A physician maintaining care over their patient would check this scale to consistently see improvement to the medication treatment being given as well as to whether there is need to adjust or optimize the treatment for the patient based on their assessment of the antidepressant/antipsychotic therapeutic use in their lives.
It would therefore be obvious to combine Patent ’043 and Rozjabek as both teach the scope of the claims in dealing with treating psychiatric disorders to reduce suicidal ideation. Patent ’043 and Rozjabek include relevant data on psychiatric disorders (as cited above) treating persons suffering from various types of depression, including major depressive disorder, who are at risk for suicide (col. 3, lns. 45-51). As seen in KSR – Prong A there is motivation to combine these prior arts because use of these methods helps to aid in the reduction of suicide ideation in patients suffering from this psychiatric disorder. Since combining prior art elements according to known methods yields predictable results, one skilled in the art could have combined the elements by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
Conclusion
Claim(s) 1-24 are rejected.
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 Josmalen M. Ramos-Lewis whose telephone number is (571)272-0084. The examiner can normally be reached M-F 9:30-5:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. 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.
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Josmalen M. Ramos-Lewis, Ph.D.
Patent Examiner
Art Unit 1621
/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621