DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-21 are pending.
Priority
This application is filed on 10/22/2024 and claims the benefit of domestic priority as below:
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Information Disclosure Statements
Two IDS(s) received on 11/12/2024 have been considered unless marked with a strikethrough.
Claim Interpretation
Claims are interpreted in accordance with the broadest reasonable interpretation (BRI) standard consistent with the specification (See MPEP 2111).
In claim 1, the term “major depressive disorder (MDD)” is interpreted consistent with the specification as encompassing MDD patients experiencing anxiety or anhedonia. The specification states that anhedonia is a core feature of MDD (page 15, lines 7-11), and reports anxiety symptoms in patients with MDD (conclusions section in page 54).
The claimed “combination” is interpreted consistent with the specification as the recited dextromethorphan/bupropion combination, including recited salt or molar equivalent forms. The claims use the opened transitional term “comprising”, thus, additional unrecited components or steps are not excluded.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-3, 14, 15, 18 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS).
With respect to claims 1 and 18, Tabuteau teaches 1) the Hamilton Anxiety Scale (HAM-A) as a measure of the severity of anxiety, wherein a score of 56 which represents the most severe form of anxiety; the lowest possible score is 0, which represents an absence of anxiety (paragraph [203]); 2) the human being that is treated with a combination of dextromethorphan and bupropion, e.g. for a type of depression, has, or is selected for having, a HAM-A score that is at least about 20 (paragraph [204]); and administering the combination of dextromethorphan and bupropion results in the human being having a reduction in the human being’s HAM-A score as compared with baseline (paragraph [205]). Accordingly, Tabuteau discloses selecting a patient having depression and clinically measured anxiety and administering the combination of dextromethorphan and bupropion to reduce the severity of that anxiety.
Tabuteau further teaches about 105 mg of bupropion hydrochloride and about 44 mg to about 46 mg of dextromethorphan hydrobromide administered orally once or twice daily (claims 8 and 9), and that the depression is major depressive disorder (claim 11). The disclosed range of about 44 mg to about 46 mg includes 45 mg. (see MPEP 2131.03) Accordingly, Tabuteau discloses selecting a human patient experiencing anxiety and major depressive disorder and treating the patient’s anxiety by administering 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride, as required by claims 1 and 18.
With respect to claims 2 and 3, Tabuteau teaches the human being that is treated with a combination of dextromethorphan and bupropion, e.g. for a type of depression, has, or is selected for having, a HAM-A score that is at least about 20 (paragraph [204]), which satisfies a HAM-A score of at least 10 and at least 15, as required in claims 2 and 3. (see MPEP 2131.03)
With respect to claims 14 and 20, Tabuteau teaches about 105 mg of bupropion hydrochloride and about 44 mg to about 46 mg of dextromethorphan hydrobromide administered orally once or twice daily (claims 8 and 9), as required in claims 14 and 20. (see MPEP 2131.03)
With respect to claim 15, Tabuteau teaches the human being that is treated with a combination of dextromethorphan and bupropion, e.g. for a type of depression, has, or is selected for having, a MADRS score that is at least about 25 (paragraph [160]).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 4-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS) in view of Axsome Therapeutics Announces Topline Results of the Stride-1 Phase 3 Trial in Treatment Resistant Depression and Expert Call to Discuss Clinical Implications, March 2020 (pub’d 03/03/2020, retrieved from internet on 09/14/2026, made of record in the IDS, hereinafter "Stride-1"), and further in view of Trivedi et al. (J. Clin. Psychiatry., 62(10), 776-81, pub'd 10/01/2001).
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tabuteau, as discussed above.
With respect to claims 4-6, the claims recite a specific HAM-A reduction as about 3 to about 4 after 1 week of treatment, about 5 to about 6 after 2 weeks of treatment, or about 8 to about 9 after 6 weeks of treatment.
Tabuteau fails to teach the specific HAM-A reduction in weeks 1, 2, and 6.
Stride-1 teaches administering AXS-05 (45 mg dextromethorphan/105 mg bupropion) twice daily for six weeks to patients with treatment resistant depression (about the STRIDE-1 Trial section). Stride-1 further teaches that AXS-05 rapidly and significantly reduced anxiety symptoms as compared to bupropion, assessed using the Hamilton Anxiety Scale (HAM-A) (Anxiety Symptoms section).
The combination of Tabuteau and Stride-1 fails to teach that the specific HAM-A reduction recited in claims 4-6.
Trivedi teaches use of the 14-item HAM-A in patients with recurrent MDD and calculates reduction in baseline HAM-A at each treatment week to evaluate the magnitude and time course of anxiolytic activity (abstract, and result section).
It would have been obvious to a PHOSITA at the time of the invention to combine the rapid and significant HAM-A improvement with AXS-05 taught by Stride-1, while the longitudinal, week-by-week HAM-A assessment during antidepressant treatment of MDD taught by Trivedi. A PHOSITA would have been motivated to use Trivedi’s longitudinal HAM-A assessment to quantify the anxiety reducing clinical advantage taught by Stride-1. A PHOSITA would have had a reasonable expectation of successfully making the combination because Stride-1 already teaches HAM-A improvement and Trivedi establishes HAM-A reduction can be measured longitudinally during MDD treatment.
The combination of Tabuteau, Stride-1 and Trivedi fails to teach the exact reduction of about 3-4 points at week 1, 5-6 points at week 2, and 8-9 points at week 6. However, the teachings recognize the magnitude of HAM-A reduction over the course of antidepressant treatment as a treatment response parameter that varies with treatment duration. Tabuteau teaches that administering the combination of dextromethorphan and bupropion results in the human being having a reduction in the HAM-A score that is at least about 10%, at least about 20%, at least about 30%, at least about 40%, or at least about 50% as compared to baseline or placebo (paragraph [205]), Trivedi teaches week base evaluation for the magnitude and time course of anxiolytic activity, and Stride -1 teaches that the primary endpoint was the change from baseline in the MADRS after 6 weeks of treatment. The key secondary endpoints were the change from baseline in the MADRS after 1 week of treatment, after 2 weeks of treatment, the average change over entire 6-week double-blind treatment period, and the Sheehan Disability Scale (SDS). Other pre-specified secondary efficacy variables included the Cognitive subscale of the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), and the Hamilton Anxiety Scale (HAM-A) (about the STRIDE-1 Trial section).
Thus, the combination of Tabuteau, Stride-1 and Trivedi recognize the relationship between the duration of antidepressant treatment and the magnitude of HAM-A reduction at the treatment time points specified in the claims, based on standard longitudinal assessments.
In the absence of evidence that the specific HAM-A reduction values recited in claims 4–6 yield critical or unexpected results, determining such values would have been within the ordinary skill of a person skilled in the art. (see In re Antonie, 559 F.2d 618 (CCPA 1977), In re Aller, 220 F.2d 454 (CCPA 1955), and MPEP 2144.05).
With respect to claim 7, the claims recite the human patient achieves remission of anxiety based upon the human patient's HAM-A score after one or more weeks of treatment.
Stride-1 teaches that the primary endpoint was the change from baseline in the MADRS after 6 weeks of treatment. The key secondary endpoints were the change from baseline in the MADRS after 1 week of treatment, after 2 weeks of treatment, the average change over entire 6-week double-blind treatment period, and other pre-specified secondary efficacy variables included HAM-A (about the STRIDE-1 Trial section). Accordingly, claim 7 would have been obvious for the same reasons discussed with respect to claims 4-6.
Claim(s) 8, 9, 16, 17, 19, and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS) in view of Tomarken et al., (J. Affect. Disord., 78(3), 235-41, pub'd 03/15/2004).
With respect to independent claim 8, the claim recites that a method of treating anhedonia in a human patient experiencing major depressive disorder, comprising: selecting a human patient experiencing anhedonia and major depressive disorder, and administering, to the human patient, a combination of 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of another salt of dextromethorphan or the free base form of dextromethorphan, and 105 mg of bupropion hydrochloride, or a molar equivalent amount of another salt of bupropion or the free base form of bupropion.
Tabuteau teaches the claimed dextromethorphan hydrobromide and bupropion hydrochloride regimen for MDD, as discussed in the 35 USC 102 rejection.
Tabuteau fails to teach selecting an MDD patient experiencing anhedonia for the purpose of treating anhedonia.
Tomarken teaches that bupropion SR is evaluated in depressed patients for its effects on symptoms of anhedonia/positive effect, and that bupropion produces greater declines than placebo on the assessed mood dimensions, with the weakest placebo effects observed on anhedonia (abstract). Tomarken concludes that the catecholaminergic effects of bupropion SR tended to produce more robust effects on anhedonia/positive effect than placebo (abstract).
It would have been obvious to a PHOSITA at the time of the invention to apply the dextromethorphan/ bupropion MDD treatment taught by Tabuteau to a MDD patient experiencing anhedonia to obtain both enhanced antidepressant activity and effects on anhedonia/positive effect in depressed patients taught by Tomarken. A PHOSITA would have been motivated to use Tabuteau’s combination therapy for MDD patients suffering from anhedonia to simultaneously obtain the antidepressant effect proposed by Tabuteau and the bupropion-related improvement in anhedonia described by Tomarken. Given that bupropion is a component of Tabuteau’s combination therapy and that Tomarken demonstrates that symptoms of anhedonia and positive affect in depressed patients respond to bupropion treatment, a PHOSITA would have had a reasonable expectation of successfully implementing the combination therapy. Furthermore, anhedonia is a recognized symptomatic dimension of depression.
With respect to claims 9, 16, 17, 19 and 21, the claims recite that the human patient is selected for having a CGI-S score of at least 4 prior to treatment in claim 9, the combination is administered twice a day in claim 16, the human patient is selected for having a MADRS score of at least 25 prior to treatment in claim 17, the combination comprises 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride in claim 19, and the combination is orally administered to the human patient in claim 21.
Tabuteau’s example 6 teaches a total of 327 patients with a confirmed diagnosis of moderate to severe MDD were randomized in a 1:1 ratio to receive 45 mg dextromethorphan/105 mg bupropion (DM/BU) (n=163), or placebo (n=164) once daily for the first 3 days (day 1, day 2, and day 3) and twice daily thereafter (starting day 4) for a total of 6 weeks. Baseline inclusion criteria included: Male or female 18-65 years of age, meeting DSM-5 criteria for current MDD without psychotic features, a Montgomery-Asberg Depression Rating Scale (MADRS) total score of at least 25, and CGI-S score of at least 4 (paragraph [486]-[487]). Tabuteau further teaches that the method or the use wherein about 44 mg to about 46 mg of dextromethorphan hydrobromide, or a molar equivalent amount of: 1) another salt form of dextromethorphan or a 2) free base form of dextromethorphan, is orally administered once daily or twice daily (claims 8 and 9).
Therefore, Tabuteau’s example 6 teaches 1) the human patient is selected for having a CGI-S score of at least 4 prior to treatment, as required in claim 9; 2) the combination is administered twice a day, as required in claim 16; 3) the human patient is selected for having a MADRS score of at least 25 prior to treatment, as required in claim 17; 4) the combination comprises 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride in claim 19, as required (see MPEP 2144.05); and 5) the combination is orally administered to the human patient, as required in claim 21. Accordingly, claims 9, 16, 17, 19 and 21 would have been obvious for the same reasons discussed with respect to claim 8.
Claim(s) 10 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS) and Tomarken et al., (J. Affect. Disord., 78(3), 235-41, pub'd 03/15/2004) as applied to claim 8 above, and further in view of Watanabe et al. (Neuropsychiatr. Dis. Treat., 18, 363-373, pub'd 02/19/2022).
With respect to claims 10 and 11, the claims recite that the human patient is selected for having a Montgomery-Asberg Depression Rating Scale (MADRS) Anhedonia score of at least 15 or at least 19 prior to treatment.
The combination of Tabuteau and Tomarken fails to teach selecting patients using the claimed MADRS Anhedonia factor thresholds.
Watanabe teaches a MADRS Anhedonia factor comprising MADRS items 1, 2, 6, 7, and 8 and stratifies MDD patients into baseline groups of 0-17 and ≥18 (abstract). Watanabe’s ≥18 group falls within the border claimed population having MADRS anhedonia scores ≥15, as required in claim 10.
Watanabe fails to teach the precise ≥19 cutoff, however, Watanabe uses ≥18 to identify the higher baseline anhedonia subgroup and reports mean baseline MADRS anhedonia factor scores of approximately 19.4-19.7 within that higher anhedonia subgroup (table 1). In the absence of evidence that the proposed cutoff of ≥19 leads to decisive or unexpected clinical outcomes, selecting adjacent ≥19 threshold to identify a subgroup of patients with MDD exhibiting similarly high levels of anhedonia could be considered a natural variation of Watanabe’s severity-based patient classification approach. (MPEP 2144.05)
It would have been obvious to a PHOSITA at the time of the invention to use a MADRS anhedonia factor to MDD patients according to the severity of anhedonia taught by Watanabe in the method of treating anhedonia in a human patient experiencing major depressive disorder, comprising: selecting a human patient experiencing anhedonia and major depressive disorder, and administering, to the human patient, a combination of dextromethorphan hydrobromide and bupropion hydrochloride taught by Tabuteau and Tomarken. A PHOSITA would have been motivated to use Watanabe’s objective MADRS anhedonia measurement method to identify patients exhibiting significant symptoms of anhedonia for the purpose of applying the treatment disclosed by Tabuteau and Tomarken. Since applying an established method for MDD related anhedonia to other antidepressant therapies for MDD constitutes a predictable clinical application of said assessment method, a person having ordinary skill in the art would have had a reasonable expectation of successfully implementing such combination therapy.
Claim(s) 12 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS) and Tomarken et al., (J. Affect. Disord., 78(3), 235-41, pub'd 03/15/2004) as applied to claim 8 above, and further in view of Cao et al. (Front Psychiatry., 10:17, pub'd 01/31/2019).
With respect to claims 12 and 13, the claims recite a specific MADRS Anhedonia score reduction as about 4 to about 5 after 1 week of treatment, or about 9 to about 10 after 6 weeks of treatment.
The combination of Tabuteau and Tomarken fails to teach the specific MADRS Anhedonia score reduction as about 4 to about 5 after 1 week of treatment, or about 9 to about 10 after 6 weeks of treatment.
Cao teaches using the MADRS anhedonia factor to quantitatively evaluate anhedonia during antidepressant treatment of MDD and reports statistically significant improvement over time (abstract). Cao defines the MADRS anhedonia factor as MADRS items 1, 2, 6, 7, and 8 (outcome measures section), and reports a mean reduction in the MADRS anhedonia factor of 3.8 points at Week 2 and 7.1 points at Week 8 relative baseline (table 2).
It would have been obvious to a PHOSITA at the time of the invention to apply quantitative monitoring of anhedonia improvement using the MADRS anhedonia factor taught by Cao to the antidepressant treatment and anhedonia related benefit taught by Tabuteau and Tomarken. A PHOSITA would have been motivated to apply Cao’s MADRS anhedonia assessment to the treatment of Tabuteau and Tomarken to quantify the expected anti-anhedonia benefit. Furthermore, Cao suggests the clinical value of alleviating anhedonia by linking such improvement to enhanced functioning and quality of life (the correlation between anhedonia and functional impairment, and discussion section). Given that Tomarken shows anhedonia improvement with bupropion administration, and Cao shows that MADRS anhedonia scores are measurable and change progressively during antidepressant treatment for MDD, a PHOSITA would have had a reasonable expectation of achieving a measurable degree of anhedonia improvement through Tabuteau’s treatment regimen involving bupropion.
The combination of Tabuteau, Tomarken, and Cao does not specify the exact magnitude of reduction about 4–5 points at week 1 and about 9–10 points at week 6. However, for the same reasons previously discussed regarding claims 10 and 11, determining the extent of the reduction in the MADRS anhedonia factor at the specified treatment time points would have constituted a routine part of evaluating known treatment response relationships. Absent evidence demonstrating that the specific reduction magnitudes of about 4–5 points at week 1 and about 9–10 points at week 6 are critical or yield unexpected results of a different nature, the claimed numerical results would not have rendered the otherwise obvious treatment method nonobvious. (see MPEP 2144.05)
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 10,894,046 B2 in view of Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS), Axsome Therapeutics Announces Topline Results of the Stride-1 Phase 3 Trial in Treatment Resistant Depression and Expert Call to Discuss Clinical Implications, March 2020 (pub’d 03/03/2020, retrieved from internet on 09/14/2026, made of record in the IDS, hereinafter "Stride-1"), Trivedi et al. (J. Clin. Psychiatry., 62(10), 776-81, pub'd 10/01/2001), Tomarken et al., (J. Affect. Disord., 78(3), 235-41, pub'd 03/15/2004), Watanabe et al. (Neuropsychiatr. Dis. Treat., 18, 363-373, pub'd 02/19/2022), and Cao et al. (Front Psychiatry., 10:17, pub'd 01/31/2019).
The claims 1 and 3 of the ‘046 patent are directed to a method of treating major depressive disorder by orally administering twice daily a combination comprising about 45 mg of dextromethorphan hydrobromide and about 105 mg of bupropion hydrochloride.
The instant claims are directed to the same dextromethorphan/bupropion treatment of MDD, with additional limitations relating to selection and treatment of MDD patients experiencing anxiety or anhedonia, baseline HAM-A, MADRS, and specified HAM-A or MADRS anhedonia treatment response outcome.
The teachings of Tabuteau, Stride-1, Trivedi, Tomarken, Watanabe, and Cao are as discussed supra in the 35 U.S.C. 102 and 35 U.S.C. 103 rejection and are herein incorporated by reference in their entirety.
The anxiety and anhedonia related patient selection criteria, clinical rating scale limitations, and treatment response limitations recited in the instant claims 1-21 would have been prima facie obvious to one of ordinary skill in the art to variations of the MDD treatment of ‘046 patent in view of the combined teachings of Tabuteau, Stride-1, Trivedi, Tomarken, Watanabe, and Cao for the same reasons discussed supra in the 35 U.S.C. 102 and 35 U.S.C. 103 rejection, which reasons are herein incorporated by reference in their entirety.
Claim 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, and 10 of U.S. Patent No. 10,780,064 B2 in view of Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS), Axsome Therapeutics Announces Topline Results of the Stride-1 Phase 3 Trial in Treatment Resistant Depression and Expert Call to Discuss Clinical Implications, March 2020 (pub’d 03/03/2020, retrieved from internet on 09/14/2026, made of record in the IDS, hereinafter "Stride-1"), Trivedi et al. (J. Clin. Psychiatry., 62(10), 776-81, pub'd 10/01/2001), Tomarken et al., (J. Affect. Disord., 78(3), 235-41, pub'd 03/15/2004), Watanabe et al. (Neuropsychiatr. Dis. Treat., 18, 363-373, pub'd 02/19/2022), and Cao et al. (Front Psychiatry., 10:17, pub'd 01/31/2019).
The claims 1, 6, and 10 of the ‘064 patent are directed to a method of treating major depressive disorder by orally administering twice daily a combination comprising about 45 mg of dextromethorphan hydrobromide and about 105 mg of bupropion hydrochloride, wherein the treated patient is selected for being of Asian descent.
The instant claims are directed to the same dextromethorphan/bupropion treatment of MDD, with additional limitations relating to selection and treatment of MDD patients experiencing anxiety or anhedonia, baseline HAM-A, MADRS, and specified HAM-A or MADRS anhedonia treatment response outcome.
The teachings of Tabuteau, Stride-1, Trivedi, Tomarken, Watanabe, and Cao are as discussed supra in the 35 U.S.C. 102 and 35 U.S.C. 103 rejection and are herein incorporated by reference in their entirety.
The anxiety and anhedonia related patient selection criteria, clinical rating scale limitations, and treatment response limitations recited in the instant claims 1-21 would have been prima facie obvious to one of ordinary skill in the art to variations of the MDD treatment of ‘064 patent in view of the combined teachings of Tabuteau, Stride-1, Trivedi, Tomarken, Watanabe, and Cao for the same reasons discussed supra in the 35 U.S.C. 102 and 35 U.S.C. 103 rejection, which reasons are herein incorporated by reference in their entirety.
Claim 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 7 of U.S. Patent No. 10,925,842 B2 in view of Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS), Axsome Therapeutics Announces Topline Results of the Stride-1 Phase 3 Trial in Treatment Resistant Depression and Expert Call to Discuss Clinical Implications, March 2020 (pub’d 03/03/2020, retrieved from internet on 09/14/2026, made of record in the IDS, hereinafter "Stride-1"), Trivedi et al. (J. Clin. Psychiatry., 62(10), 776-81, pub'd 10/01/2001), Tomarken et al., (J. Affect. Disord., 78(3), 235-41, pub'd 03/15/2004), Watanabe et al. (Neuropsychiatr. Dis. Treat., 18, 363-373, pub'd 02/19/2022), and Cao et al. (Front Psychiatry., 10:17, pub'd 01/31/2019).
The claims 1, 3, and 7 of the ‘842 patent are directed to a method of treating major depressive disorder by orally administering twice daily a combination comprising about 45 mg of dextromethorphan hydrobromide and about 105 mg of bupropion hydrochloride, wherein the patient is selected for having received prior first line treatment in the patient’s current major depressive episode.
The instant claims are directed to the same dextromethorphan/bupropion treatment of MDD, with additional limitations relating to selection and treatment of MDD patients experiencing anxiety or anhedonia, baseline HAM-A, MADRS, and specified HAM-A or MADRS anhedonia treatment response outcome.
The teachings of Tabuteau, Stride-1, Trivedi, Tomarken, Watanabe, and Cao are as discussed supra in the 35 U.S.C. 102 and 35 U.S.C. 103 rejection and are herein incorporated by reference in their entirety.
The anxiety and anhedonia related patient selection criteria, clinical rating scale limitations, and treatment response limitations recited in the instant claims 1-21 would have been prima facie obvious to one of ordinary skill in the art to variations of the MDD treatment of ‘842 patent in view of the combined teachings of Tabuteau, Stride-1, Trivedi, Tomarken, Watanabe, and Cao for the same reasons discussed supra in the 35 U.S.C. 102 and 35 U.S.C. 103 rejection, which reasons are herein incorporated by reference in their entirety.
Claims 1-21 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 2, 4, 5, 6, 7, 10, 11, and 19 of copending Application No. 18/967,488 in view of Tabuteau (WO 2020/146412 A1, pub'd 07/16/2020, made of record in the IDS), Axsome Therapeutics Announces Topline Results of the Stride-1 Phase 3 Trial in Treatment Resistant Depression and Expert Call to Discuss Clinical Implications, March 2020 (pub’d 03/03/2020, retrieved from internet on 09/14/2026, made of record in the IDS, hereinafter "Stride-1"), Trivedi et al. (J. Clin. Psychiatry., 62(10), 776-81, pub'd 10/01/2001), Tomarken et al., (J. Affect. Disord., 78(3), 235-41, pub'd 03/15/2004), Watanabe et al. (Neuropsychiatr. Dis. Treat., 18, 363-373, pub'd 02/19/2022), and Cao et al. (Front Psychiatry., 10:17, pub'd 01/31/2019).
This is a provisional nonstatutory double patenting rejection.
The claims 1, 2, 4, 5, 6, 7, 10, 11, and 19 of the ‘488 application are directed to a method of treating major depressive disorder by orally administering twice daily a combination comprising about 40-55 mg of dextromethorphan hydrobromide and about 90-140 mg of bupropion hydrochloride, wherein the combination therapy is carried out for at least 8 consecutive days; wherein orally administering the dosage form results in the human being experiencing a reduction in the human being's Montgomery-Asberg Depression Rating Scale (MADRS) score; and wherein the dosage form comprises about 105 mg of bupropion hydrochloride, or a molar equivalent amount of the free base or another salt form of bupropion, and about 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of the free base or another salt form of dextromethorphan dosage form comprises about 105 mg of bupropion hydrochloride.
The instant claims are directed to the same dextromethorphan/bupropion treatment of MDD, with additional limitations relating to selection and treatment of MDD patients experiencing anxiety or anhedonia, baseline HAM-A, MADRS, and specified HAM-A or MADRS anhedonia treatment response outcome.
The teachings of Tabuteau, Stride-1, Trivedi, Tomarken, Watanabe, and Cao are as discussed supra in the 35 U.S.C. 102 and 35 U.S.C. 103 rejection and are herein incorporated by reference in their entirety.
The anxiety and anhedonia related patient selection criteria, clinical rating scale limitations, and treatment response limitations recited in the instant claims 1-21 would have been prima facie obvious to one of ordinary skill in the art to variations of the MDD treatment of ‘488 application in view of the combined teachings of Tabuteau, Stride-1, Trivedi, Tomarken, Watanabe, and Cao for the same reasons discussed supra in the 35 U.S.C. 102 and 35 U.S.C. 103 rejection, which reasons are herein incorporated by reference in their entirety.
Conclusion
Claims 1-21 are rejected.
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/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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