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/US2022/024840, filed 14 April, 2022, which claims the benefit of U.S. Provisional Application 63/238,500, filed 30 August, 2021, 63/189,939, filed 18 May, 2021, 63/175,378, filed 15 April, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5 June, 2024 is acknowledged and has been considered.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 5 June, 2024, in the matter of Application N° 18/286,935. Said documents have been entered on the record.
Claims 5, 17-18, 20, 22, 24-25, 28, 32, and 35-37 are amended. Claims 6-16, 19, 21, 23, 26-27, 29-31, 33-34, and 38-41 are canceled. No new matter was introduced.
Therefore, Claims 1-5, 17-18, 20, 22, 24-25, 28, 32, and 35-37 represent all claims currently under consideration.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-5, 17-18, 20, 22, 24-25, 28, 32, and 35-37, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding Claim 3, the recited comparison to metabolite levels “in a patient who is administered the VMAT2 inhibitor alone” lacks an objective reference point. The claim does not specify whether the comparison is made to the same patient, a different patient, or a population baseline, nor does it define the conditions under which metabolite exposure is considered increased, rendering the scope of the claim unclear.
Although Claim 4, which depends upon Claim 3, specifies that metabolite exposure is measured as AUC or Cmax, this limitation does not resolve the ambiguity in Claim 3 regarding the comparator baseline or the condition under which exposure is considered increased.
Additionally, Claim 5, which depends upon Claim 3, recites that increased metabolite exposure increases the risk of one or more exposure-related adverse reactions without defining the baseline risk, the manner of assessing risk, or the degree of risk increase, further rendering the scope of the claim indefinite.
Claims 17-18, 20, 22, 24-25, 28 depend from Claim 3, and fail to cure the deficiencies as stated above.
Similarly Claim 32, which also depends from Claim 3, fails to cure the deficiencies as stated above. Additionally, the claim recites monitoring for “exposure-related adverse reactions” without defining the adverse reactions or providing an objective standard for identifying them, rendering the scope of the claim unclear.
Claims 36-37 depend from Claim 32, and fail to cure the deficiencies as stated above.
Similarly Claim 35, which also depends from Claim 3, fails to cure the deficiencies as stated above. Additionally, the claim requires informing the patient or a medical care worker of a potential QT-interval prolongation without specifying that the same entity performs both the treatment and informing steps, rendering the scope of the claim unclear as to who performs the claimed method.
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.
Claims 1-2, 17-18, 20, 22, 24-25, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stamler and Huang (WO 2016/144901 A1, cited in IDS.)
Regarding Claims 1-2, 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), wherein the daily amount of deutetrabenazine administered is less than or equal to about 36 mg for a subject concurrently receiving a strong CYP2D6 inhibitor (‘901, Pg. 8, Para 042.)
Regarding Claims 17-18, 20 and 22, 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 24, 25, and 28, Stamler and Huang teach daily amount of deutetrabenazine is chosen from about 12 mg, about 18 mg, and about 24 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.
Although Claims 17-18, 20, 22, 24-25, and 28, depend from one of Claims 1-3, the dependent claims encompass embodiments depending from Claims 1 or 2, which are anticipated by Stamler and Huang. Therefore, Claims 17-18, 20, 22, 24-25, and 28 are anticipated where the additional limitation is disclosed by the reference.
As such, Stamler and Huang anticipate Claims 1-2, 17-18, 20, 22, 24-25, and 28.
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.
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 3-5, 32, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Stamler and Huang (WO 2016/144901 A1, cited in IDS.)
The teachings of Stamler and Huang (2016) are set forth in the above 35 U.S.C. 102 Rejections and are incorporated herein. Stamler and Huang teach a method of treating abnormal involuntary movement in a subject, comprising administering to the subject a daily amount of deutetrabenazine of at least about 6 mg per day and less than about 36 mg, for a subject concurrently receiving a strong CYP2D6 inhibitor.
Regarding Claims 3-5, Stamler and Huang teach adjusting dosage based on tolerability and exposure-related effects (‘901, Pg. 5-6, Para 023 and Pg. 7, Para 033.)
Stamler and Huang fail to monitor specific metabolites by name, or compare metabolite exposure relative to monotherapy.
However, Stamler and Huang does teach that in humans d6-tetrabenazine is rapidly and extensively converted in the liver (similarly to non-isotopically enriched tetrabenazine) to major, active dihydrotetrabenazine (HTBZ) metabolites referred to as d6-a-HTBZ and d6-P-HTBZ (as a mixture of the + and - isomers) which are believed to drive clinical efficacy (‘901, Pg. 42, Para 0250.)
Therefore, it would have been prima facie obvious to one skilled in the art before the effective filing date of the invention to monitor concentrations of deutetrabenazine metabolites and reduce the administered dose when exposure is increased relative to monotherapy, as a routine and predictable way to implement the dose-adjustment teachings of Stamler and Huang with a reasonable expectation of success.
Regarding Claims 32 and 36-37, Stamler and Huang repeatedly emphasize that adverse reactions are clinically relevant considerations in determining appropriate dosing and that dose adjustment is used as a mechanism to manage safety and tolerability during treatment (‘901, Pg. Pg. 68, Para 0352, Pg. 10, Para 051-053, and Pg. 47, Table 12.)
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.
Regarding Claim 35, Stamler and Huang teach drug-drug interactions in the treatment of patients with Huntington’s Disease and other disorders involving abnormal involuntary movement may also be a serious concern (‘901, Pg. 121, Para 0519), to include the known risk for tetrabenazine to increase the QT interval (‘901, Pg. 121, Para 0520.) Stamler and Huang reported results support the fact that the differentiated pharmacokinetic profile and lower Cmax associated with deutetrabenazine compared with tetrabenazine improves the safety profile of deutetrabenazine by reducing the risk for life-threatening arrhythmias (‘901, Pg. 123, Para 0525.)
In view of these teachings, a person of ordinary skill in the art, before the effective filing date of the invention, would have found it obvious to inform a patient or a medical care worker of the potential QT-interval prolongation associated with administration of deutetrabenazine as communicating known safety risks is a routine and predictable aspect of clinical drug administration, with a reasonable expectation of success.
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 1-5, 17-18, 20, 22, 24-25, 28, 32, and 35-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claim 1-5, 19-20, 22, 24, 26, 30, 32, 34, and 38-39 of copending Application No. 18/286,944 (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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D.M.N./ Examiner, Art Unit 1627
/SARAH PIHONAK/ Primary Examiner, Art Unit 1627