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 .
Election/Restrictions
Applicant’s election without traverse of agitation associated with Alzheimer’s disease in the reply filed on August 18, 2025, is acknowledged. Claim 24 appears to be the only claim presently directed to a distinct subject population.
Status of the Claims
Claims 21-41 are pending. Claim 24 is withdrawn for being directed to depression, rather than agitation associated with AD.
The examiner notes that any allegation of unexpected results must be provided in each application that is prosecuted before the Office. The examiner cannot consider allegations and showings provided in related cases.
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 21-23 and 25-41 are rejected under 35 U.S.C. 103 as being unpatentable over Berg, (US20090111846) (cited in IDS), in view of Tod et al., “Quantitative Prediction of Cytochrome P450 (CYP) 2D6-Mediated Drug Interactions," Clin Pharmacokinetic 2011;50(8):519-530 (cited in IDS), and in view of Went et al., (US2006/0142398) (cited in IDS).
Berg teaches a method for treating depression, anxiety, cognitive disorders, and Alzheimer’s disease by administering a combination of dextromethorphan and quinidine, wherein 10 mg to 200 mg dextromethorphan is administered and 1 to less than about 50 mg quinidine is administered per day (prior art claim 1). Dextromethorphan acts as a non-competitive antagonist of N-methyl-D-aspartate-sensitive ionotropic glutamate receptor (par. 51). Additionally, Cytochrome P450 2D6 is the key enzyme that breaks down dextromethorphan to dextrorphan. Quinidine is a drug that inhibits the activity of the key enzyme that breaks down dextromethorphan, thereby increase the concentration of dextromethorphan in plasma (par. 52). Subjects were administered a combination of DEX/QUI twice daily for 28 consecutive days (par. 28). Additionally, “common dosage forms” can be administered by sustained release, delayed release, or controlled release (par. 155). They can be administered as oral formulations A dosage of 20 to 60 mg/day can be administered. See par. 19.
Berg does not teach bupropion for use with dextromethorphan.
Tod teaches in Table II, that 300 mg bupropion (daily) had an inhibition ratio on Cytochrome P450 2D6 that is similar to quinidine. Bupropion is confirmed as a strong inhibitor of CYP2D6 based on the metabolites erythrohydroxybupropion and threohydroxybupropion in vivo (p526, 1st par). Further, Figure 3 shows that the predicted AUC ratios in the presence of various inhibitors notes that the combinations of DEX/QUI and DEX/BUP yield the highest predicted AUC ratio.
Berg and Tod do not teach agitation associated with Alzheimer’s disease.
Went teaches composition for treating conditions including neuropsychiatric disorders, as well as depression and agitation. See par. 29. Further, the composition can treat agitation and Alzheimer’s disease and dementias. See par.’s 87 and 88. Also see prior art claim 32. The active agent for administration is a NMDA receptor antagonist including dextromethorphan. See par.’s 47 and 49. Metabolites such as dextrorphan are also taught for use. See par. 47.
The examiner believes that a person having ordinary skill in the art would be able to optimize the concentration of bupropion to use with the dosage of dextromethorphan taught by Berg based on the known mechanism of action and whether or not the DEX is immediate release or sustained release, e.g. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the instant application to combine the teachings of Berg, Tod, and Went to arrive at a method of treating agitation associated with AD by administering a combination of dextromethorphan and a CYP2D6 inhibitor, such as quinidine or bupropion. One would have been motivated to do so because Berg teaches such combination with prevent the enzymatic conversion of dextromethorphan to dextrorphan. Such prevention will prolong the efficacy of the DEX. Further, such combination is taught by Berg to treat AD and agitation and the overall dosage of DEX that is taught overlap the claimed dosage ranges. Thus, a person having ordinary skill would have a reasonable expectation of success in administering DEX/BUP and optimizing the concentration of each agent whether the formulation is an IR or a SR formulation based on the known mechanisms of action of each agent and the known efficacy in treating the claimed subject population having AD and agitation, as well as one associated with the other. Further, the claimed agents are each known result-effective variable and the PK of the combination is known is predictable with a road map to optimization provided by the cited prior art.
As such, no claim is allowed.
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 21-23 and 25-41 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 associated with AD);
US 12109178 B2 (claims 1-18, same combination expected to yield same PK);
US 11986444 B2 (claims 1-28, same combination expected to yield same PK);
US 12036191 B1 (claims 1-30, same combination expected to yield same PK);
US 12390428 B1 (claims 1-17, same combination expected to yield same PK);
US 11969421 B2 (claims 1-29 same combination expected to yield same PK);
US 11896563 B2 (claims 1-17 same combination expected to yield same PK);
US 11730706 B1 (claims 1-20, same combination expected to yield same PK);
US 11883373 B1 (claims 1-19, same combination expected to yield same PK);
US 12146889 B1 (claims 1-16, same combination expected to yield same PK);
US 12194005 B2 (claims 1-19, agitation associated with AD);
US 12364674 B2 (claims 1-25, agitation associated with AD);
US 11717518 B1 (claims 1-23, same combination expected to yield same PK);
US 11925636 B2 (claims 1-22, same combination expected to yield same PK);
US 12239642 B2 (claims 1-22, agitation associated with AD);
US 12263161 B2 (claims 1-22, agitation associated with AD);
US 12310961 B2 (claims 1-13, same combination expected to yield same PK);
US 11660274 B2 (claims 1-19, same combination expected to yield same PK);
US 11660273 B2 (claims 1-19, same combination expected to yield same PK);
US 11617747 B2 (claims 1-15, same combination expected to yield same PK);
US 11617728 B2 (claims 1-21, same combination expected to yield same PK);
US 11596627 B2 (claims 1-17, same combination expected to yield same PK);
US 11590124 B2 (claims 1-15, same combination expected to yield same PK);
US 11576909 B2 (claims 1-15, same combination expected to yield same PK);
US 11576877 B2 (claims 1-27, same combination expected to yield same PK);
US 11571417 B2 (claims 1-14, same combination expected to yield same PK);
US 11571399 B2 (claims 1-27, same combination expected to yield same PK);
US 11541021 B2 (claims 1-14, same combination expected to yield same PK);
US 11541048 B2 (claims 1-17, same combination expected to yield same PK);
US 11534414 B2 (claims 1-21, dose form expected to yield same PK);
US 11524007 B2 (claims 1-17, same combination expected to yield same PK);
US 11517543 B2 (claims 1-19, same combination expected to yield same PK);
US 11517542 B2 (claims 1-17, same combination expected to yield same PK);
US 11510918 B2 (claims 1-17, same combination expected to yield same PK);
US 11497721 B2 (claims 1-17, same combination expected to yield same PK);
US 11478468 B2 (claims 1-19, same combination expected to yield same PK);
US 11439636 B1 (claims 1-22, same combination expected to yield same PK);
US 11433067 B2 (claims 1-19, dose form expected to yield same PK);
US 11779579 B2 (claims 1-22, same combination expected to yield same PK);
US 11426370 B2 (claims 1-17, same combination expected to yield same PK);
US 11426401 B2 (claims 1-23, same combination expected to yield same PK);
US 11419867 B2 (claims 1-20, same combination expected to yield same PK);
US 11382874 B2 (claims 1-20, same combination expected to yield same PK);
US 11364233 B2 (claims 1-27, same combination expected to yield same PK);
US 11357744 B2 (claims 1-14, same combination expected to yield same PK);
US 11628149 B2 (claims 1-19, same combination expected to yield same PK);
US 11344544 B2 (claims 1-20, same combination expected to yield same PK);
US 11524008 B2 (claims 1-29 agitation associated with AD in dependent claim 13);
US 11311534 B2 (claims 1-12, same combination expected to yield same PK);
US 11298352 B2 (claims 1-20, agitation associated with AD in dependent claim 13);
US 11298351 B2 (claims 1-12, same combination expected to yield same PK);
US 11291638 B2 (claims 1-20, same combination expected to yield same PK);
US 11291665 B2 (claims 1-20, same combination expected to yield same PK);
US 11285146 B2 (claims 1-20, same combination expected to yield same PK);
US 11285118 B2 (claims 1-20, same combination expected to yield same PK);
US 11517544 B2 (claims 1-19, same combination expected to yield same PK);
US 11273134 B2 (claims 1-20, same combination expected to yield same PK);
US 11273133 B2 (claims 1-30, same combination expected to yield same PK);
US 11253491 B2 (claims 1-30, same combination expected to yield same PK);
US 11253492 B2 (claims 1-28, same combination expected to yield same PK);
US 11234946 B2 (claims 1-14, same combination expected to yield same PK);
US 11229640 B2 (claims 1-27, same combination expected to yield same PK);
US 11213521 B2 (claims 1-12, same combination expected to yield same PK);
US 11207281 B2 (claims 1-22, same combination expected to yield same PK);
US 11197839 B2 (claims 1-21, dose form expected to yield same PK);
US 11191739 B2 (claims 1-21, same combination expected to yield same PK);
US 11185515 B2 (claims 1-13, same combination expected to yield same PK);
US 11147808 B2 (claims 1-29, same combination expected to yield same PK);
US 11141388 B2 (claims 1-27, same combination expected to yield same PK);
US 11141416 B2 (claims 1-12, same combination expected to yield same PK);
US 11129826 B2 (claims 1-23, same combination expected to yield same PK);
US 11123344 B2 (claims 1-30, same combination expected to yield same PK);
US 11123343 B2 (claims 1-23, same combination expected to yield same PK);
US 11096937 B2 (claims 1-13, same combination expected to yield same PK);
US 11090300 B2 (claims 1-12, same combination expected to yield same PK);
US 11065248 B2 (claims 1-30, same combination expected to yield same PK);
US 11058648 B2 (claims 1-30 same combination expected to yield same PK);
US 11020389 B2 (claims 1-18 same combination expected to yield same PK);
US 11007189 B2 (claims 1-16, agitation associated with AD );
US 10980800 B2 (claims 1-23 same combination expected to yield same PK);
US 10966974 B2 (claims 1-12 same combination expected to yield same PK);
US 10966942 B2 (claims 1-20 same combination expected to yield same PK);
US 10966941 B2 (claims 1-22 same combination expected to yield same PK);
US 10945973 B2 (claims 1-29, same combination expected to yield same PK);
US 10940124 B2 (claims 1-20, same combination expected to yield same PK);
US 10933034 B2 (claims 1-12, same combination expected to yield same PK);
US 10925842 B2 (claims 1-20, same combination expected to yield same PK);
US 10898453 B2 (claims 1-10 same combination expected to yield same PK);
US 10894046 B2 (claims 1-27, same combination expected to yield same PK);
US 10894047 B2 (claims 1-13 same combination expected to yield same PK);
US 10881657 B2 (claims 1-9, same combination expected to yield same PK);
US 10874665 B2 (claims 1-15, same combination expected to yield same PK);
US 10874663 B2 (claims 1-14, same combination expected to yield same PK);
US 10874664 B2 (claims 1-10, same combination expected to yield same PK);
US 10864209 B2 (claims 1-12 same combination expected to yield same PK);
US 10813924 B2 (claims 1-23 same combination expected to yield same PK);
US 10799497 B2 (claims 1-14 same combination expected to yield same PK);
US 10786469 B2 (claims 1-24 same combination expected to yield same PK);
US 10780064 B2 (claims 1-23 same combination expected to yield same PK);
US 10772850 B2 (claims 1-28 same combination expected to yield same PK);
US 10688066 B2 (claims 1-24 same combination expected to yield same PK);
US 10512643 B2 (claims 1-11 same combination expected to yield same PK);
US 10105361 B2 (claims 1-30 same combination expected to yield same PK);
US 10786496 B2 (claims 1-20 same combination expected to yield same PK);
US 10105327 B2 (claims 1-28 same combination expected to yield same PK);
US 10548857 B2 (claims 1-22 same combination expected to yield same PK);
US 10092561 B2 (claims 1-29, same combination expected to yield same PK);
US 10596167 B2 (claims 1-26 same combination expected to yield same PK);
US 10080727 B2 (claims 1-22 same combination expected to yield same PK);
US 10780066 B2 (claims 1-19, same combination expected to yield same PK);
US 10058518 B2 (claims 1-27, same combination expected to yield same PK);
US 10806710 B2 (claims 1-19, same combination expected to yield same PK);
US 9968568 B2 (claims 1-30 same combination expected to yield same PK);
US 10463634 B2 (claims 1-20, same combination expected to yield same PK);
US 9867819 B2 (claims 1-29, same combination expected to yield same PK);
US 9861595 B2 (claims 1-29, same combination expected to yield same PK);
US 9763932 B2 (claims 1-29, same combination expected to yield same PK);
US 10092560 B2 (claims 1-24, same combination expected to yield same PK);
US 10881624 B2 (claims 1-19, same combination expected to yield same PK);
US 9707191 B2 (claims 1-30, same combination expected to yield same PK);
US 9700528 B2 (claims 1-29, same combination expected to yield same PK);
US 9474731 B1 (claims 1-29, same combination expected to yield same PK);
US 9457025 B2 (claims 1-30, same combination expected to yield same PK);
US 9457023 B1 (claims 1-25, same combination expected to yield same PK);
US 9700553 B2 (claims 1-30, same combination expected to yield same PK);
US 9408815 B2 (claims 1-30, same combination expected to yield same PK);
US 9198905 B2 (claims 1-18, same combination expected to yield same PK);
US 9205083 B2 (claims 1-14, same combination expected to yield same PK);
US 9238032 B2 (claims 1-20, same combination expected to yield same PK);
US 9314462 B2 (claims 1-17 same combination expected to yield same PK);
US 9370513 B2 (claims 1-28 same combination expected to yield same PK);
US 9375429 B2 (claims 1-27 same combination expected to yield same PK);
US 9421176 B1 (claims 1-19 same combination expected to yield same PK);
US 9168234 B2 (claims 1-12, same combination expected to yield same PK);
US 9278095 B2 (claims 1-17 same combination expected to yield same PK);
US 9486450 B2 (claims 1-30 same combination expected to yield same PK);
US 10064857 B2 (claims 1-30 same combination expected to yield same PK); and
US 10251879 B2 (claims 1-29 same combination expected to yield same PK).
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. The patents above include administration of the claimed combination to a subject population. Absent evidence to the contrary, the combination of BUP and DEX at optimized dosages would produce a claimed PK and there is no showing of record that such parameters or dosages are critical or unexpected.
This is a non-provisional NSDP rejection because the claims have been patented.
Claims 21-23 and 25-41 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 (1-22);
17/541,461 claims 1, 5, 7-12, 16, and 18-22);
18/156,825 (1-30) (pending request for express abandonment);
18/157,266 (1-4, 8-11, 15-16) (pending request for express abandonment);
18/157,393 (9-11, 16-18, 23-39);
18/158,268 (5-24);
18/170,120 (1-24) (pending request for express abandonment);
18/170,151 (1-22) (pending request for express abandonment);
18/172,555 (1-30) (pending request for express abandonment);
18/172,617 (1-25) (pending request for express abandonment);
18/173,291 (1-14);
18/173,372 (1-30) (pending request for express abandonment);
18/174,123 (1-24) (pending request for express abandonment);
18/175,865 (1-25) (pending request for express abandonment); and
18/175,862 (1-24) (pending request for express abandonment).
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. The patents above include administration of the claimed combination to the claimed subject population. Absent evidence to the contrary, the combination of BUP and DEX at optimized dosages would produce a claimed PK and there is no showing of record that such parameters or dosages are critical or unexpected.
This is a provisional NSDP rejection because the patentably indistinct claims have not been patented.
As such, no claim is allowed.
Conclusion
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 9-5 M-F.
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