DETAILED ACTION
Claims 1-7, 9, 12, 14, 16-17, 22, 24, 26, 28, 31, 35 and 48 are currently pending. Claims 1-7, 9, 12, 14, 16-17, 22, 24, 26, 28 and 31 are currently under examination.
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 .
Information Disclosure Statement
Applicant’s Informational Disclosure Statement, filed on 09/26/2025 has been considered. Please refer to Applicant's copy of the 1449 submitted herein.
Withdrawn Rejections
The prior rejection of claims 1-2, 5, 7-9 and 31 under 112(b) is withdrawn based on Applicant’s claim amendments to remove substantially continuously, such as language, parenthesis and commas.
The prior rejection of claims 1-2, 8-9, 12, 14 and 28 under 35 U.S.C. 103 as being unpatentable over WO 2006/053067 is withdrawn as a result of Applicant adding the claim limitation to R,R-tetrabenazine as the only active ingredient.
Examiner’s Note
Applicant's amendments and arguments filed 09/26/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 09/26/2025, it is noted that claims 1, 3-5, 12, 22, 24 and 31 have been amended and no new matter or claims have been added.
Modified Rejections:
The following rejections are modified based on Applicant’s claim amendments.
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.
Claim(s) 1-4, 7, 9, 12, 14, 16-17, 22, 26, 28 and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2006/0078604 (IDS dated 01/09/2024) in view of WO 2006/053067 (previously applied), US 7,897,768 (previously applied) and Yao et al. (previously applied).
Regarding claims 1-3 and 31, the limitation of administering to the subject a pharmaceutical comprising an active ingredient comprising R,R-tetrabenazine, wherein the administering bypasses first pass metabolism and continuously or substantially continuously deliver to the subject about 0.1 mg/day to about 20 mg/day of tetrabenazine wherein the administration continuous delivery of R,R-tetrabenazine to a subject for about 8 hours to about 192 hours is met by the ‘604 publication teaching topical application of one or more active agents in one or more polymer and/or adhesive carrier layers (abstract) for transdermal release [0002]. Therapeutically effective amounts are taught to be 0.1 mg to about 20,000 mg per 24 hours [0047] wherein substantially zero order release is taught [0050]. Tetrabenazine is taught as an active agent [0213]. The amount of drug taught to be incorporated in varies depending on the particular drug and the desired therapeutic effects and the time span for which the device is to provide therapy [0344]. The zero-order release delivery is for an extended period of time lasting up to 7 days or longer [0408]. The active agent is taught as incorporated into the carrier composition [0349]. the ‘604 publication teaching polyethylene glycol present in the carrier [0393] and antioxidants may be included [0394]. Non-functional or non-reactive acrylic based polymers are taught [0040].
Regarding claims 4 and 22, the limitation of wherein the adhesive composition comprises the active dispersed in a nonreactive acrylate pressure sensitive adhesive wherein the active is about 1 to 20% by weight and the non-reactive acrylate pressure sensitive adhesive is about 50 to 97% by weight is met by the ‘604 publication teaching the acrylic based polymers may be copolymers including methacrylate’s, 1-ethylhexyl acrylate ([0352]-[0356)]. The drug may be present from 0.1 to 50 wt%, preferably 0.5-15 wt% [0390] and the acrylic based polymer is 2 to 95% of the composition (claim 26) which is a pressure sensitive adhesive (claim 27).
Regarding claims 7 and 26, the limitation of wherein the adhesive composition further comprises a crystallization inhibitor selected form the group including polyethylene glycol is met by the ‘604 publication teaching polyethylene glycol present in the carrier [0393].
Regarding claim 12, the limitation of administering to the subject a pharmaceutical comprising an active ingredient comprising R,R-tetrabenazine is met by the ‘604 publication teaching topical application of one or more active agents in one or more polymer and/or adhesive carrier layers (abstract) for transdermal release [0002]. Therapeutically effective amounts are taught to be 0.1 mg to about 20,000 mg per 24 hours [0047] wherein substantially zero order release is taught [0050]. Tetrabenazine is taught as an active agent [0213]. The amount of drug taught to be incorporated in varies depending on the particular drug and the desired therapeutic effects and the time span for which the device is to provide therapy [0344]. The zero-order release delivery is for an extended period of time lasting up to 7 days or longer [0408].
Regarding claim 14, the limitation of wherein the administration is transdermal is met by the ‘604 publication teaching transdermal administration (abstract).
Regarding claim 16, the limitation of administration once a day or once in more than a day is met by the ‘604 publication teaching the release profile being up to 7 days or longer [0002], thus teaching once in more than a day.
Regarding claim 17, the limitation of composition is formulated to provide a dose of about 2mg/day of tetrabenazine for 4 days is met by the ‘604 publication teaching drug release profiles up to 7 days [0002] wherein drug loading is optimized [0021] wherein release is taught to be 0.1-500 mg per day [0047] administered at sustainably zero order release [0050].
The ‘604 publication does not specifically teach treating hyperkinetic movement disorders in a subject or R,R-tetrabenazine (claim 1), wherein the sole active ingredient is substantially pure R,R-isomer of tetrabenazine (claim 1, 12, 27) wherein the disease is Huntington’s (claim 9, 28).
The ‘604 publication does not specifically recite the effect of administration, e.g., plasma etc. in instant claim 12, 17 and 31.
The ‘067 publication teaching a method for treating hyperkinetic movement disorder in a human patient comprising administering an effective amount of tetrabenazine compound selected from a group which includes tetrabenazine (abstract). The RR form of tetrabenazine is taught (page 3, 20 to page 4 line 5, page 7, lines 10-20). The effective amount is taught to be the amount that reduces or relieves symptoms of hyperkinetic movement disorder being treated (page 7, lines 30-35) no greater than 100 mg per day (page 9, lines 1-5). Administration is taught to be transdermal (page 9, lines 5-10), which would bypass first pass metabolism. The ‘067 publication teaching RR isomer of tetrabenazine as a compound to be used (page 7, lines 10-15). The ‘067 publication teaching transdermal administration (page 9, lines 5-10) and treating Huntington’s disease (Example 1).
The ‘768 patent teaches method of preparing tetrabenazine compound (TBZ). A method is taught which can be used to prepare either enantiomeric form of tetrabenazine or may be used to form a racemic mixture (abstract) wherein a single enantiomer is taught (column 6, lines 65-68). Tetrabenazine has shown promise as an agent in the treatment of Huntington’s disease (column 1, lines 10-20).
Yao et al. teach that tetrabenazine is a known inhibitor of vesicular monoamine
transporter 2 (VMAT 2) (see page 1841 second column). They further detail a racemic mixture of the R,R isomer and S,S isomer forms that is marketed for use (see page 1841 first column). Yao et al. go on to teach that a pure R,R isomer form is 8000 more potent than the S,S isomer and was also more potent than the other stereoisomers (see figure 1, page 1842 first column first partial paragraph, and page 1844 second column last partial paragraph; instant claim 17). Yao teaches the TBZ to be used for the treatment of Huntingon’s disease and other hyperkinetic disorders (abstract) wherein it is administered as a single ingredient (page 1851, first column, first paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the transdermal drug delivery device as taught by the ‘604 publication to treat hyperkinetic movement disorders as the ‘604 publication teaches tetrabenazine in a transdermal patch and the ‘067 publication specifically teaches the use of tetrabenazine for treatment hyperkinetic movement disorders such as Huntington’s disease and may be used transdermally. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘604 publication teaches tetrabenazine as a possible active agent and the ‘067 publication specifically teaches tetrabenazine as an active agent to be applied transdermally for treatment of a specific disease. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed to use the RR form of tetrabenazine as the ‘067 publication teaches the R,R form of tetrabenazine to be used in the transdermal application. One of ordinary skill in the art would have a reasonable expectation of success as the ‘768 patent teaches that it is known to produce specific enantiomeric forms of tetrabenazine, wherein a single form is taught to be used. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add select a pure R,R isomer of tetrabenazine for the tetrabenazine for the transdermal patch of the ‘604 publication. This choice would have been obvious in light of Yao et al who teach its superiority over other stereoisomer forms administered as the sole active ingredient.
Claim(s) 3-4 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2006/0078604 in view of WO 2006/053067, US 7,897,768 and Yao et al. as applied to claims 1-4, 7, 9, 12, 14, 16-17, 22, 26, 28 and 31 above, and further in view of US 2002/0077437 (IDS dated 01/09/2024).
As mentioned in the above 103(a) rejection, all the limitations of claims 1-4, 7, 9, 12, 14, 16-17, 22, 26, 28 and 31 are taught by the combination of the ‘604 publication, the ‘067 publication and the ‘768 patent.
The combination of references does not exemplify an elected combination of monomers in the non-reactive adhesive polymer.
The ‘437 publication teaches non-reactive, pressure sensitive acrylic adhesive polymers for transdermal, drug-in-adhesive preparations (see abstract and paragraph 10). They detail a particular polymer variety that does not require post-polymerization crosslinking which can interfere with contained drugs (see paragraph 5). The polymer is a copolymer of methyl acrylate, ethylhexyl acrylate, and octyl acrylamide (see example 1; instant claims 4-7).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the non-reactive polymer of the ‘437 publication for the non-reactive polymer in the ‘604 publication. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement (e.g. no post-polymerization processing) and as the simple substitution of one known element for another in order to yield a predictable outcome.
Claim(s) 5 and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2006/0078604 in view of WO 2006/053067, US 7,897,768 and Yao et al.as applied to claims 1-4, 7, 9, 12, 14, 16-17, 22, 26, 28 and 31 above, and further in view of Muraoka et al. (JP-H1179980 – English translation referenced for citations, IDS dated 01/09/2024).
The ‘604 publication, the ‘067 publication and the ‘768 patent render obvious the limitations of instant claims 1-4, 7, 9, 12, 14, 16-17, 22, 26, 28 and 31. The presence of propyl gallate is not detailed.
Muraoka et al. teach a transdermal, drug-in-adhesive preparation where a non-reactive acrylic adhesive is employed in the drug-in-adhesive matrix (see paragraphs 1, 7, and 18). They additionally teach the inclusion of the antioxidant propyl gallate in order to reduce the decomposition of the drug that can occur in such preparations (see paragraphs 4, 7, 26, and 28; instant claims 12-13). They go on to detail the propyl gallate present at a preferable range of 0.03 to 2 wt% of the adhesive matrix (see paragraph 29; instant claim 13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add propyl gallate to the adhesive matrix of the ‘604 publication. at a concentration taught by Muraoka et al. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement (e.g. increased oxidation stability). The range of proportions overlaps with that instantly claimed, thereby rendering the claimed range obvious (see MPEP 2144.05; instant claim 13).
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2006/0078604 in view of WO 2006/053067, US 7,897,768 and Yao et al. as applied to claims 1-4, 7, 9, 12, 14, 16-17, 22, 26, 28 and 31 above, and further in view of US 2015/0148759 (IDS dated 01/09/2024).
The ‘604 publication, the ‘067 publication and the ‘768 patent render obvious the limitations of instant claims 1-4, 7, 9, 12, 14, 16-17, 22, 26, 28 and 31. The presence of a crystallization inhibitor is not detailed.
The ‘759 publication teaches a transdermal, drug-in-adhesive preparation (see abstract). They additionally teach the inclusion of a crystallization inhibitor to inhibit crystallization of the drug in the adhesive (see paragraph 76; instant claim 14). They go on to detail the crystallization inhibitor present at a range of 1 to 20 wt% of the adhesive matrix (see paragraph 76 instant claim 14). The ‘759 publication envisioned compounds to serve as crystallization inhibitors and name polyethylene glycol as one variety (see paragraph 76; instant claims 15-16).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add polyethylene glycol as a crystallization inhibitor to the adhesive matrix of the ‘604 publication at a concentration taught by the ‘759 publication. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement (e.g. reduced crystallization tendency). The range of proportions overlaps with that instantly claimed and detailed as yielding two weeks of stability, thereby rendering the claimed range obvious (see MPEP 2144.05; instant specification paragraph 67; instant claim 14). According to MPEP 2145II, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). In addition, the fact that an inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Thus the inhibition of crystal formation over two weeks would likely occur given that the claimed components are present at the claimed proportions.
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.
Claims 1-9, 12, 14, 17, 22, 24-28 and 31 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No.12,144,899 in view of WO 2006/053067. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and the ‘899 patent are directed to transdermal application of R,R-tetrabenazine as the sole active ingredient in a non-reactive acrylate pressure sensitive adhesive in overlapping concentrations, wherein the composition includes propyl gallate and a crystallization inhibitor and wherein the application is to treat hyperkinetic movement disorders. The ‘899 patent does not teach the specific release rate of tetrabenazine. The ‘067 publication teaches the desired dosage of tetrabenazine is 25 to 150 mg per day (page 6, lines 1-10). It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known delivery amounts of tetrabenazine for the transdermal patch containing tetrabenazine as taught by the ‘067 publication to obtain the desired effect to treat hyperkinetic movement disorders.
Response to Arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
103: the ‘304 publication in view of the ‘067 publication, the ‘768 patent and Yao
Applicant argues the ‘604 publication does not teach tetrabenazine transdermal patch, it is concerned with an occlusive backing. The ‘604 publication discloses clonidine transdermal patch. The ‘604 publication prefers molecular weight less than 300 Daltons.
In response, the ‘604 publication teaching topical application of one or more active agents in one or more polymer and/or adhesive carrier layers (abstract) for transdermal release [0002]. Therapeutically effective amounts are taught to be 0.1 mg to about 20,000 mg per 24 hours [0047] wherein substantially zero order release is taught [0050]. Tetrabenazine is taught as an active agent [0213].
Applicant argues the ‘067 publication does not particularly suggest a non-oral delivery of TBZ. The only example is TBZ is oral tablet. The ‘768 patent discloses R,R-TBZ however does not teach delivering continuously and bypassing first pass metabolism. Yao teaches different isomers of TBZ and dihydrotetrabenazine.
In response, the ‘067 publication teaches tetrabenazine to treat hyperkinetic disorders though transdermal administration (abstract, page 7, lines 30-35, page 9, lines 5-10). Yao teaches the TBZ to be used for the treatment of Huntingon’s disease and other hyperkinetic disorders (abstract) wherein it is administered as a single ingredient (page 1851, first column, first paragraph). It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the transdermal drug delivery device as taught by the ‘604 publication to treat hyperkinetic movement disorders as the ‘604 publication teaches tetrabenazine in a transdermal patch and the ‘067 publication specifically teaches the use of tetrabenazine for treatment hyperkinetic movement disorders such as Huntington’s disease and may be used transdermally.
Applicant argues the ‘437 publication does not remedy the deficiencies of the ‘604 publication, the ‘067 publication, the ‘768 patent and Yao.
In response, Applicant’s arguments regarding the ‘604 publication, the ‘067 publication, the ‘768 patent and Yao are addressed as first presented.
Applicant argues Muraoka does not remedy the deficiencies of the ‘604 publication, the ‘067 publication, the ‘768 patent and Yao.
In response, Applicant’s arguments regarding the ‘604 publication, the ‘067 publication, the ‘768 patent and Yao are addressed as first presented.
Applicant argues the ‘759 publication does not remedy the deficiencies of the ‘604 publication, the ‘067 publication, the ‘768 patent and Yao.
In response, Applicant’s arguments regarding the ‘604 publication, the ‘067 publication, the ‘768 patent and Yao are addressed as first presented.
Double Patenting:
Applicant argues the double patenting rejection be held in abeyance.
In response, Applicant has not presented any substantive arguments thus the rejections are maintained for reasons of record.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613