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 .
Priority
This application, filed 13 October, 2023, is a national stage application of PCT/US2022/024848, filed 14 April, 2022, which claims the benefit of U.S. Provisional Application 63/238,502, filed 30 August, 2021, 63/189,946, filed 18 May, 2021, 63/175,379, filed 15 April, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 23 July, 2026 is acknowledged and has been considered.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 23 July, 2026, in the matter of Application N° 18/286,944. Said documents have been entered on the record.
Claims 1, 19-20, 22, 24, 26, 30 and 32 are amended. Claims 2-5, 34 and 38-39 are canceled. Claim 44 is new. No new matter was introduced.
Therefore, Claims 1, 19-20, 22, 24, 26, 30, 32 and 44 represent all claims currently under consideration.
Response to Amendment/Arguments
The amendment to the Specification has overcome the previous objection.
Claims 2-5, 34 and 38-39 have been canceled. Therefore, the rejections of these claims under 35 U.S.C. 112(b), 103 and nonstatutory double patenting are moot.
Applicant’s amendments are sufficient to overcome the remaining rejections under 35 U.S.C. 112(b).
Applicant's arguments filed 23 July, 2026 regarding rejections under 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant first argues that Stamler and Huang do not teach or suggest the claimed “maximum total daily dose” because the reference identifies a maximum total daily dose of 36 mg/day for certain subjects, whereas instant Claim 1 requires a maximum total daily dose between about 6 mg/day and about 30 mg/day. Applicant further distinguishes a “maximum total daily dose” from an individual dose that happens to fall within the claimed range (Remarks, Pg 7-8).
The Examiner agrees that administration of an individual daily dose of 30 mg does not, by itself, necessarily establish that 30 mg is the maximum permissible dose of the treatment regimen. However, the rejection is maintained under 35 U.S.C. 103 rather than anticipation. Stamler and Huang expressly teach titrating deutetrabenazine according to therapeutic response and tolerability, including increasing or decreasing the daily dose depending upon efficacy and whether the administered amount is tolerated (‘901, Para 0023 and 0033). Stamler and Huang further define tolerability in terms of adverse events and expressly contemplate increasing the amount until adequate control is achieved or a “maximal allowable dose is reached,” thereby recognizing that the dosing regimen includes an upper permissible dose selected in view of efficacy and safety considerations (‘901, Para 309).
Stamler and Huang further recognize the clinical significance of impaired CYP2D6 metabolism. As discussed in the rejection, the reference teaches that poor metabolizers, whether due to genetics or concomitant CYP2D6-inhibiting medication, exhibit altered metabolism and increased exposure, and that such subjects are dosed lower. Accordingly, one of ordinary skill in the art would have been motivated to optimize the maximum allowable daily dose for a CYP2D6 poor metabolizer by selecting a lower upper limit, including about 30 mg/day, in order to manage increased drug exposure while maintaining efficacy and tolerability. As set forth in MPEP §2144.05(II.A), "[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). Here, Stamler and Huang expressly recognize dose as affecting therapeutic response and tolerability and teach adjustment of that dose in response to those results.
Applicant’s reliance on Stamler and Huang’s disclosure of a 36 mg/day maximum for subjects receiving strong CYP2D6 inhibitors does not establish nonobviousness (Remarks, Pg 7-8). The fact that the reference discloses one workable upper limit does not preclude the obviousness of selecting a lower upper limit where the same reference teaches individualized dose adjustment, lower dosing for subjects having impaired CYP2D6 function, and expressly identifies 30 mg/day as an available deutetrabenazine dose. The distinction between a 36 mg/day maximum and the presently claimed maximum of about 30 mg/day therefore represents the very optimization relied upon in the rejection rather than a teaching inconsistent with the proposed modification.
Applicant also argues that Stamler and Huang teach away from the claimed maximum because subjects having impaired CYP2D6 function were administered mean doses of 34.8 mg/day, with some subjects receiving doses as high as 42 mg/day, without additional adverse events (Remarks, Pg 8-9). This argument is not persuasive. As set forth in MPEP §2145(X.D.1) "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). A disclosure that higher doses may be tolerated by some patients does not criticize, discredit, or otherwise discourage use of a lower maximum dose. To the contrary, Applicant’s cited discussion acknowledges that poor metabolizers were dosed lower and that deutetrabenazine dosing may be clinically managed. The cited data therefore demonstrate that dose is adjusted according to patient characteristics and tolerability; they do not teach that a 30 mg/day maximum should be avoided or would be unsuitable. Accordingly, Stamler and Huang do not teach away from the claimed dosing regimen.
Applicant further argues that Stamler and Huang are limited to a clinical trial setting (Remarks, Pg 9). This argument is likewise unpersuasive. Although the reference reports results obtained in clinical studies, its disclosure is directed broadly to therapeutic methods of administering deutetrabenazine to subjects, including individualized dose selection, dose reduction, chronic administration, and physician management of treatment. Stamler and Huang expressly state that the amount administered to a patient depends upon the particular patient and clinical circumstances and is within the responsibility of the attending physician (‘901, Para 0344-0346). The disclosed therapeutic methods are therefore not limited to performance within a clinical trial or experimental environment. Recitation that administration occurs “outside of a clinical trial setting” does not impart a structural or operational distinction sufficient to overcome the cited teachings.
Accordingly, Applicant’s arguments do not overcome the rejection and as such the rejection under 35 U.S.C. 103 over Stamler and Huang is maintained.
Additionally, Applicant requests that the nonstatutory double patenting rejections be held in abeyance until the scope of allowable subject matter is determined. The request is acknowledged; however, the nonstatutory double patenting rejections are maintained.
Claim Rejections - 35 USC § 103
(claims updated based on amendment and MAINTAINED)
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.
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.
Claims 1, 19-20, 22, 24, 26, 30, 32 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Stamler and Huang (WO 2016/144901 A1, of previous record.)
Regarding Claims 1, Stamler and Huang teach a method of treating abnormal involuntary movement in a subject, comprising administering to the subject an initial daily amount of deutetrabenazine of at least about 6 mg per day; (‘901, Pg. 5-6, Para 023), and is less than about 36 mg (‘901, Pg. 8, Para 042.)
Although Stamler and Huang do not expressly require selecting patients based on CYP2D6 poor metabolizer status, the reference acknowledges that reduced CYP2D6 metabolic capacity results in increased exposure to deutetrabenazine and its metabolites (‘901, Pg. 86, Para 0413.) At the time of the invention, it is well known that CYP2D6 poor metabolizers exhibit reduced metabolic activity and increased exposure to CYP2D6-substrate drugs. A person of ordinary skill in the art would therefore have been motivated to apply the dose-limiting teachings of Stamler and Huang to patients who are CYP2D6 poor metabolizers as a predictable and routine optimization to manage exposure-related safety concerns, with a reasonable expectation of success.
The recitation that the method is performed “outside of a clinical trial setting” does not distinguish the claimed methods form the prior art. Stamler and Huang is directed to therapeutic methods of administering deutetrabenazine to patients and is not limited to performance within a clinical trial or experimental setting. The exclusion of a clinical trial environment merely reflects the intended context of use and does not impose a structural or operational limitation on the claimed method.
Regarding Claims 19-20, 22, 24, Stamler and Huang teach wherein the abnormal involuntary movement is caused by a movement disorder (‘901, Pg. 6, Para 024), wherein the movement disorder is chosen from chorea, Huntington's Disease, and tardive dyskinesia (‘901, Pg. 6, Para 025.)
Regarding Claims 26, 30, 32 and 44, Stamler and Huang teach a daily amount of deutetrabenazine is chosen from about 12 mg, about 18 mg, about 24 mg, and about 30 mg (‘901, Pg. 7, Para 036.) The recitation of “maximum” daily dose does not distinguish over the prior art as Stamler and Huang expressly disclose administration of deutetrabenazine at daily doses at or below the claimed maximum, which necessarily satisfies the claimed limitation.
In view of these teachings, a person of ordinary skill in the art would have been motivated to include an explicit step of monitoring patients for exposure-related adverse reactions when practicing the disclosed treatment methods, as monitoring for adverse effects is a routine and predictable means of implementing the safety-driven dosing strategies described in Stamler and Huang. Further, specifying particular known adverse reactions, such as somnolence – the most common AE observed in the deutetrabenazine group (‘901, Pg. 47, Para 0414) – and sedation, or other adverse reactions disclosed in the reference, would have been an obvious refinement of such monitoring, as these adverse reaction are recognized, expected, and directly related to the deutetrabenazine exposure. A person of ordinary skill in the art would have had a reasonable expectation of success in monitoring for such adverse reactions and using that information to guide safe administration of the drug.
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, 19-20, 22, 24, 26, 30, 32 and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claim 1-5, 17-18, 20, 22, 24-25, 28, 32, and 36-37 of copending Application No. 18/286,935 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because they differ only in the manner in which CYP2D6 impairment is characterized, and would have been obvious variants of one another to a person skilled in the art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 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.
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/D.M.N./ Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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