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 .
Response to Amendments
Applicant’s amendments to the claims of October 27, 2025, in response to the Office Action of July 30, 2025, are acknowledged.
Response to Arguments
The rejection of claim 20 is withdrawn in view of the cancelation of claim 20. The statutory DP rejection is withdrawn in view of the amendments to the claims.
The examiner notes, as evidenced by Hildebrand et al., “Determination of dextromethorphan metabolizer phenotype in healthy volunteers,” Eur J Clin Pharmacol. 1989;36(3):315-8: a substantial majority of individuals are extensive metabolizers (i.e., about 90%).
The examiner withdraws the application of Galer because the claims are limited to BUP and DEX as sole active agents and Galer also requires a GABA analog.
Caruso teaches a therapeutic composition with bupropion HCl (prior art claim 2) and at least one NMDA receptor antagonist dextromethorphan (prior art claim 13). Further, Caruso provides 46 Examples of specific combinations. As noted in the previous Office Action, Example 21 is a tablet comprising 100 mg bupropion hydrochloride and 30 mg dextromethorphan hydrobromide. See par 19, Example 21. The claims have been amended to require no additional active steps or structural limitations required of the claimed products. As such, the claims are directed to a result of the administration of the claimed combination of agents as the sole active agents. There is no specific subject population required in independent claim 1 of the claims that depend therefrom. The APIs claims and taught are recognized result effective variables that can be optimized through nothing more than routine experimentation. In this case, claim 1 includes 30 mg DEX, which is the amount taught by Caruso in an example. Treatment would be expected to continue if efficacious.
As evidenced by Atee et al., “Pain in Dementia: Prevalence and Association With Neuropsychiatric Behaviors,” Journal of Pain and Symptom Management, Vol 61, No. 6 June 2021: “pain is very common in all dementia subtypes and strongly linked to agitation, aggression, and depression in this population. See p1215, 1st par. Aggression/agitation was the most frequently represented behavior (94%) for those in pain and was 3.8 times as frequent compared to those in the no pain group. See p1219. 1st par. Of those with AD, 64.3% were in pain. See Table 3. Figure 1 shows the prevalence of aggression and agitation as well as depression.
Caruso teaches treating neuropathic pain with the claimed combination. As evidenced above, pain is very common in AD and has a strong nexus to agitation, neuropathic pain, and depression.
The examiner also applies Went et al., (US2006/0142398) as necessitated by the Amendments to the claims. Went teaches controlled, sustained, and immediate release formulations. See par. 9, 17, and others. The compositions treat pain, depression, agitation, AD, and neuropathic pain. See prior art claim 32, The NMDA receptor antagonist includes dextromethorphan. See par. 47.
The examiner notes that any plasma concentration is a product of the dosage and/or APIs administered. There are no additional structural limitations provided. Further, the newly cited prior art shows an ability to alter the release profile of NMDA receptor antagonist from faster than immediate release to slower than immediate release and includes formulations that comprise both. Such release profile provides a tunability and can be optimized through nothing more than routine experimentation of a known result-effective variable. Unexpected results have not been shown or alleged. In totality, a substantial majority of subjects are extensive metabolizers of DEX. Further, a subject with AD is also most typically and symptomatically a subject with neuropathic pain, agitation, and depression. There is a strong symptomatic nexus among established by the cited art and the knowledge of those in the field. Thus, when prior art teaches treating neuropathic pain and/or AD, e.g., with a claimed combination, it would not be interpreted to exclude a most typical subject therewith.
The examiner also notes that if Applicant contends that a specific formulation is not optimizable to arrive at the functionality (i.e., plasma concentrations) claimed, the examiner will require structural limitations required to achieve the same be incorporated into the claims.
As such, the claims are rejected below.
Unexpected Results:
The examiner notes that any allegation of unexpected results must be provided in each application in which they are alleged. Further, such results must be compared to the closest prior art and the claims must be commensurate in scope with any showing.
The examiner has added the unpublished filed applications to the provisional Double Patenting Rejections below.
Status of the Claims
Claims 1, 5, 7, 8, 10-12, 16, 18, 19, 21, and 22 are examined. Claims 2-4, 6, 13-15, and 17 are withdrawn.
Claim Rejections - 35 USC § 103
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.
Claims 1, 5, 7, 8, 10-12, 16, 18, 19, 21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Caruso (US2002/0035105 A1), in view of Went et al., (US2006/0142398).
Caruso teaches combining an antidepressant with an NMDA receptor antagonist for treatment of neuropathic pain. In one embodiment, the NDMA antagonist is dextromethorphan. See par. 6. The antidepressant compound can be bupropion. See par. 11. Each of BUP and DEX are preferred. See par.’s 11 and 12. The DEX can be used in a concentration of 50-360 mg/day. See par. 13. Further, Example 21 is a tablet comprising 100 mg bupropion hydrochloride and 30 mg dextromethorphan hydrobromide. See par 19, Example 21. In each combination the NMDA antagonist significantly potentiates the neuropathic pain alleviating activity of the antidepressant. See par. 20.
Went teaches controlled, sustained, and immediate release formulations. See par. 9, 17, and others. The compositions treat pain, depression, agitation, AD, and neuropathic pain. See prior art claim 32, The NMDA receptor antagonist includes dextromethorphan. See par. 47. The release profile can be faster and even slower than the immediate release form of drug and can release 0.1%-20% within one hour or up to 86% within one hour. See par. 17. Almost any desired release is achievable and described.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Caruso and Went. One would be motivated to do so because DEX and BUP are taught to treat neuropathic pain when used in combination. When this combination is administered together to a subject the results that naturally follow such administration will occur, absent evidence to the contrary. Additionally, the combination has been shown to be synergistic when used together to treat neuropathic pain by potentiating the effect of the antidepressive agent. Similar concentrations are used and the claimed agent can be administered as a single formulation or separately. Further, the APIs can be formulated for controlled and immediate release. The claimed dosages can be optimized through nothing more than routine experimentation. See M.P.E.P. § 2144.05. As such, using DEX and BUP to treat an anxiety disorder has a reasonable and predictable expectation of success in view of the cited prior art. Even further, neuropathic pain, AD, depression, and agitation are common comorbidities and Went teaches NMDAr antagonist will treat each of these conditions. Thus, the totality of the prior art establishes a prima facie showing of obviousness.
Double Patenting (Non-Statutory)
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5, 7, 8, 10-12, 16, 18, 19, 21, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over the following claims of the following U.S. Patent Nos.:
US 12194036 B2 (claims 1-18, agitation and AD);
US 12156914 B2 (claims 7-17);
US 12357697 B2 (claims 1-17);
US 12109178 B2 (claims 1-18);
US 11986444 B2 (claims 1-28);
US 12036191 B1 (claims 1-30);
US 11969421 B2 (claims 1-29);
US 11896563 B2 (claims 1-17);
US 11844797 B1 (claims 1-14);
US 11730706 B1 (claims 1-20);
US 11752144 B1 (claims 1-14);
US 11839612 B1 (claims 1-18);
US 11883373 B1 (claims 1-19);
US 12042473 B2 (claims 1-9, DEX and BUP w/ L-cysteine);
US 12146889 B1 (claims 1-16);
US 12194005 B2 (claims 1-19);
US 12364674 B2 (claims 1-25, agitation and AD);
US 11717518 B1 (claims 1-23);
US 11925636 B2 (claims 1-22);
US 12239642 B2 (claims 1-22, agitation and AD);
US 12263161 B2 (claims 1-22, AD);
US 12310961 B2 (claims 1-13);
US 11660274 B2 (claims 1-19);
US 11660273 B2 (claims 1-19);
US 11617747 B2 (claims 1-15);
US 11617728 B2 (claims 1-21);
US 11596627 B2 (claims 1-17);
US 11590124 B2 (claims 1-15);
US 11576909 B2 (claims 1-15);
US 11576877 B2 (claims 1-27);
US 11571417 B2 (claims 1-14);
US 11571399 B2 (claims 1-27);
US 11541021 B2 (claims 1-14);
US 11541048 B2 (claims 1-17);
US 11534414 B2 (claims 1-21);
US 11524007 B2 (claims 1-17);
US 11517543 B2 (claims 1-19);
US 11517542 B2 (claims 1-17);
US 11510918 B2 (claims 1-17);
US 11497721 B2 (claims 1-17);
US 11478468 B2 (claims 1-19);
US 11439636 B1 (claims 1-22);
US 11433067 B2 (claims 1-19);
US 11779579 B2 (claims 1-22);
US 11426370 B2 (claims 1-17);
US 11426401 B2 (claims 1-23);
US 11419867 B2 (claims 1-20);
US 11382874 B2 (claims 1-20);
US 11364233 B2 (claims 1-27);
US 11357744 B2 (claims 1-14);
US 11628149 B2 (claims 1-19);
US 11344544 B2 (claims 1-20);
US 11524008 B2 (claims 1-29);
US 11311534 B2 (claims 1-12);
US 11298352 B2 (claims 1-20);
US 11298351 B2 (claims 1-12);
US 11291638 B2 (claims 1-20);
US 11291665 B2 (claims 1-20);
US 11291639 B2 (claims 1-19, Huntington’s disease);
US 12102606 B2 (claims 1-19, ADHD);
US 11285146 B2 (claims 1-20);
US 11285118 B2 (claims 1-20);
US 11517544 B2 (claims 1-19);
US 11273134 B2 (claims 1-20);
US 11273133 B2 (claims 1-30);
US 11253491 B2 (claims 1-30);
US 11253492 B2 (claims 1-28);
US 11234946 B2 (claims 1-14);
US 11229640 B2 (claims 1-27);
US 11213521 B2 (claims 1-12);
US 11197839 B2 (claims 1-21);
US 11191739 B2 (claims 1-21);
US 11185515 B2 (claims 1-13);
US 11147808 B2 (claims 1-29);
US 11141388 B2 (claims 1-27);
US 11141416 B2 (claims 1-12);
US 11129826 B2 (claims 1-23);
US 11123344 B2 (claims 1-30);
US 11123343 B2 (claims 1-23);
US 11096937 B2 (claims 1-13);
US 11090300 B2 (claims 1-12);
US 11065248 B2 (claims 1-30);
US 11058648 B2 (claims 1-30);
US 11020389 B2 (claims 1-18);
US 11007189 B2 (claims 1-16, agitation and AD );
US 10980800 B2 (claims 1-23);
US 10966974 B2 (claims 1-12);
US 10966942 B2 (claims 1-20);
US 10966941 B2 (claims 1-22);
US 10945973 B2 (claims 1-29);
US 10940124 B2 (claims 1-20);
US 10933034 B2 (claims 1-12);
US 10925842 B2 (claims 1-20);
US 10898453 B2 (claims 1-10);
US 10894046 B2 (claims 1-27);
US 10894047 B2 (claims 1-13);
US 10881657 B2 (claims 1-9);
US 10874665 B2 (claims 1-15);
US 10874663 B2 (claims 1-14);
US 10874664 B2 (claims 1-10);
US 10864209 B2 (claims 1-12);
US 10813924 B2 (claims 1-23);
US 10799497 B2 (claims 1-14);
US 10786469 B2 (claims 1-24);
US 10780064 B2 (claims 1-23);
US 10772850 B2 (claims 1-28);
US 10688066 B2 (claims 1-24);
US 10512643 B2 (claims 1-11);
US 10105361 B2 (claims 1-30);
US 10786496 B2 (claims 1-20);
US 10105327 B2 (claims 1-28);
US 10548857 B2 (claims 1-22);
US 10092561 B2 (claims 1-29);
US 10596167 B2 (claims 1-26);
US 10080727 B2 (claims 1-22);
US 10780066 B2 (claims 1-19);
US 10058518 B2 (claims 1-27);
US 10806710 B2 (claims 1-19);
US 9968568 B2 (claims 1-30);
US 10463634 B2 (claims 1-20);
US 9867819 B2 (claims 1-29);
US 9861595 B2 (claims 1-29);
US 9763932 B2 (claims 1-29);
US 10092560 B2 (claims 1-24);
US 10881624 B2 (claims 1-19);
US 9707191 B2 (claims 1-30);
US 9700528 B2 (claims 1-29);
US 9474731 B1 (claims 1-29);
US 9457025 B2 (claims 1-30);
US 9457023 B1 (claims 1-25);
US 9700553 B2 (claims 1-30);
US 9408815 B2 (claims 1-30);
US 9198905 B2 (claims 1-18);
US 9205083 B2 (claims 1-14);
US 9238032 B2 (claims 1-20);
US 9314462 B2 (claims 1-17);
US 9370513 B2 (claims 1-28);
US 9375429 B2 (claims 1-27);
US 9421176 B1 (claims 1-19);
US 9168234 B2 (claims 1-12);
US 9278095 B2 (claims 1-17);
US 9486450 B2 (claims 1-30);
US 10064857 B2 (claims 1-30);
US 10251879 B2 (claims 1-29); and
US 11207281B2 (claims 1-22).
Each of the above are in view of Caruso (US2002/0035105 A1), in view of Went et al., (US2006/0142398), and as evidenced by Atee et al., “Pain in Dementia: Prevalence and Association With Neuropsychiatric Behaviors,” Journal of Pain and Symptom Management, Vol 61, No. 6 June 2021.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and the claims of the patents cited above are drawn to a method of administering a combination of dextromethorphan and bupropion to a human being in need of treatment. The dosages and pharmacokinetic parameters that are a direct product of administration are optimizable through nothing more than routine experimentation. The resulting pharmacokinetic parameters, including AUC, are a result of the administration of the combination of DEX and BUP are optimizable dosages. The advantages of administration are considered a result of the combination not a specific claimed dosage or excipient absent evidence to the contrary. Anxiety is a symptom and common comorbidity of depression. The patents above include administration of the claimed combination to the claimed subject population.
This is a non-provisional NSDP rejection because the claims have been patented.
Claims 1, 5, 7, 8, 10-12, 16, 18, 19, 21, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the following pending claims of copending Application Nos.
18/333,944 (1-8, 12-20, 22);
18/601,603 (1-15);
18/397,220 (1-17);
17/187,454 claims 1-20;
17/183,645 claims 1-20;
17/541,461 claims 1-22;
17/571,110 claims 21-40; and
17/730,814 claims 21-40.
18/156,825 (1-30);
18/157,266 (1-4, 8-11, 15-16);
18/157,393 (9-11, 16-18, 23-39);
18/158,268 (5-24);
18/169,571 (1-35);
18/170,120 (1-24);
18/170,151 (1-22);
18/172,555 (1-30);
18/172,617 (1-25);
18/173,291 (1-14);
18/173,372 (1-30);
18/174,123 (1-24);
18/174,278 (1-19);
18/175,865 (1-25);
18/175,862 (1-24);
18/405,416;
18/968,681;
18/815,581;
19/056,484;
19/181,167;
19/182,010;
19/219,972;
19/219,986;
19/249,959;
19/255,952;
19/258,712;
19/264,750;
19/278,703;
19/278,734;
19/300,204; and
19/308,044.
Each of the above are in view of Caruso (US2002/0035105 A1), in view of Went et al., (US2006/0142398), and as evidenced by Atee et al., “Pain in Dementia: Prevalence and Association With Neuropsychiatric Behaviors,” Journal of Pain and Symptom Management, Vol 61, No. 6 June 2021.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and the claims of the patents cited above are drawn to a method of administering a combination of dextromethorphan and bupropion to a human being in need of treatment. The dosages and pharmacokinetic parameters that are a direct product of administration are optimizable through nothing more than routine experimentation. The resulting pharmacokinetic parameters, including AUC, are a result of the administration of the combination of DEX and BUP are optimizable dosages. The advantages of administration are considered a result of the combination not a specific claimed dosage or excipient absent evidence to the contrary. Anxiety is a symptom and common comorbidity of depression. The patents above include administration of the claimed combination to the claimed subject population.
This is a provisional NSDP rejection because the patentably indistinct claims have not been patented.
As such, no claim is allowed.
Conclusion
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 extension fee 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 JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628