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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/20/2025 has been entered.
Claim Status
Claims 1-19 are rejected.
No claims are allowable.
Maintained Claim Rejections - 35 USC § 103
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 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.
1. Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Tajiri et al., (US 2018/0243223 A1, Aug. 30, 2018) (cited by applicant on IDS 08/26/2022) (hereinafter Tajiri) in view of Kozaki et al., (US 2013/0035344 A1, Feb. 7, 2013) (hereinafter Kozaki) and Dax US 2020/0246317 A1, filed Oct. 16, 2019) (hereinafter Dax).
Tajiri discloses a pharmaceutical solid preparation comprising [(1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid monobenzenesulfonate (i.e. mirogabalin besylate) which is a compound represented by formula (I):
PNG
media_image1.png
166
414
media_image1.png
Greyscale
in combination with D-mannitol and carmellose calcium (Abstract). The pharmaceutical solid preparation may be a tablet coated with a coating agent ([0025]). An uncoated tablet comprises 0.5 to 25% by weight compound (I) (i.e., mirogabalin besylate), 50 to 90% by weight D-mannitol, 2 to 20% by weight carmellose calcium, and 0.5 to 5% magnesium stearate ([0049]-00052]). The D-mannitol has an average particle size of 100 μm or smaller ([0012]). Production example 5 discloses a 210 mg tablet comprising 8.78 mg compound (I) (mirogabalin besylate), 154.82 mg D-mannitol, 20 mg carmellose calcium, 4 mg magnesium stearate, 6.2 mg citric acid hydrate, 6.2 mg tocopherol, 10 mg OPADRY, 7.2 mg Hypromellose, 1.34 mg titanium oxide, 1.4 mg talc, 0.02 mg red iron sesquioxide, and 0.04 mg yellow iron sesquioxide ([0091]). OPADRY, Hypromellose, titanium oxide, talc, red iron sesquioxide, and yellow iron sesquioxide are part of the coating agent ([0082]-[0083]) and Table 2). The solid preparation is obtained by forming a tablet and optionally coating the surface of the resulting tablet ([0061]-[0064]).
Tajiri differs from the instant claims insofar as not disclosing wherein the citric acid hydrate has a particle size distribution x99 of less than 210 µm.
However, Kozaki discloses a solid pharmaceutical composition for oral administration comprising (A) compound a and (B) citric acid (Abstract). Citric acid has an action of remarkably improving the dissolubility of the compound a. As the citric acid, citric acid hydrate may be used and the average particle size of the citric acid is preferably 500 μm or less from the viewpoint of the effect of improving the dissolubility of the compound a ([0023]).
Accordingly, because Kozaki teaches that citric acid is a dissolving agent and its particle size affects dissolvability of a drug, it would have taken no more than the relative skills of one of ordinary skill in the art before the effective filing date of the instant application to have arrived at the claimed particle size distribution through routine experimentation in order to obtain the desired dissolvability of the drug of Tajiri. Where 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. See MPEP 2144.05.
The combined teachings of Tajiri and Kozaki do not disclose wherein the tocopherol is α-tocopherol and is 0.005 to 1% by weight based on the uncoated tablet.
However, Dax discloses a treating diabetic neuropathy and pain associated with diabetes by administering to an individual a therapeutically effective amount of a compound of Formula I (Compound 1) in an oral dosage form such as tablets (Abstract). The composition may include an antioxidant such as α-tocopherol in the range of about 0.01% to 0.3% ([0090]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. As discussed above, Tajiri discloses wherein the composition comprises tocopherol. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated α-tocopherol into the tablet of Tajiri since it is a known and effective tocopherol for tablets as taught by Dax.
It would have been prima facie obvious to one of ordinary skill in the art to have incorporated 0.01% to 0.3% α-tocopherol since this is a known and effective amount of α-tocopherol for when one wants to include the compound for use as an antioxidant as taught by Dax.
Regarding the amount of citric acid hydrate recited in instant claims 4, 5, 13 and 14, as discussed above, Tajiri discloses a tablet comprising 8.78 mg Compound I, 154.82 mg D-mannitol, 20 mg carmellose calcium, 4 mg magnesium stearate, 6.2 mg citric acid hydrate, and 6.2 mg tocopherol. Thus, Tajiri discloses 3.1% citric acid hydrate of an uncoated tablet. Regarding instant claims 5 and 14 reciting 2.9% citric acid hydrate, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). Accordingly, the claimed amount of 2.9% would have been obvious since it is close to 3.1% that one skilled in the art would have expected them to have the same properties.
Regarding the amount of mirogabalin besylate in terms of mirogabalin recited in instant claim 9, as discussed above, Tajiri discloses 0.5% to 25% Compound (I) (i.e., mirogabalin besylate). An amount of 0.5% to 25% mirogabalin besylate equates to 0.29% to 14.25% mirogabalin. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists. MPEP 2144.05 A.
Response to Applicant’s Arguments
Applicant argues that in the telephonic interview held October 15, 2025, both Examiners agreed that the instant application demonstrated unexpected results that were commensurate with the scope of the claims and that were not apparent in the cited references. Based on the Examiner's stated need for further review of the prior art, no formal agreement as to patentability was reached.
Applicant’s argument has been fully considered but found not to be persuasive. It is the understanding of the Examiner that it was agreed upon during the interview that the Applicant would consider submitting clarification of data regarding the unexpected results of a smooth tablet appearance due to the claimed citric acid particle size to overcome the rejection of all pending claims under 35 U.S.C. § 103 as being unpatentable over U.S. Patent Application Publication No. 2018/0243223 to Tajiri et al. (“Tajiri”) in view of U.S. Patent Application Publication No. 2013/0035344 to Kozaki et al. (“Kozaki”) and U.S. Patent Application Publication No. 2020/0246317 to Dax (“Dax”) and that an updated search would be performed to determine if the unexpected results were truly unexpected. This was stated in the 10/24/2025 interview summary. Specifically, as noted in Table 3 of the instant specification, Example 8 comprises citric acid hydrate that was sifted using a 100 Mesh having an opening of 150 µm and Example 9 comprises citric acid hydrate that was sifted using an 80 Mesh having an opening of 180 µm. Thus, one of ordinary skill in the art would expect all particles of Example 9 to be less than 180 µm in size since this is the size of the opening of the mesh. Further clarification was requested regarding this observation and is not noted in the response.
Applicant argues that the present application demonstrates that the claimed citric acid particle size distribution x99 of less than 210 µm, recited in independent claims 1, 2, and 12, provides for tablets having no dimples on the surface thereof, which is an unexpected result reported in Table 5 and not taught in the prior art. Applicant cites the x99 particle size distribution used in preparations "Example 4", "Example 7", and "Example 8" which were 112.6 µm, 125.6 µm, and 207.1 µm, respectively, as shown in Table 6, resulted in 0 tablets out of 100 showing any appearance change after one week of storage under humid conditions compared to Example 9 having an x99 particle size distribution of 271.4 µm and exhibiting fine dimples.
Applicant’s argument has been fully considered but found not to be persuasive. Applicant’s showing does not appear to be unexpected. As discussed above, as noted in Table 3 of the instant specification, Example 8 comprises citric acid hydrate that was sifted using a 100 Mesh having an opening of 150 µm and Example 9 comprises citric acid hydrate that was sifted using an 80 Mesh having an opening of 180 µm. Accordingly, one of ordinary skill in the art would expect all citric acid particles of Example 8 to be less than or equal to 150 µm and all citric acid particles of Example 9 to be less than or equal to 180 µm in size since this is the size of the opening of the mesh. Instant Table 5 discloses that 24 tablets of Example 9 show an appearance change during storage and 1 tablet of Example 8 shows an appearance change during storage. Thus, since tablets comprising citric acid particles of less than 150 µm and 180 µm in size, which falls within the claimed range of citric acid particles, demonstrated an appearance change (i.e., fine dimples) during storage, it is unclear how citric acid particles having the claimed particle size is related to preventing fine dimples.
Further, whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence it is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. See MPEP 716.02(d). As noted in Table 4 of the instant application citric acid hydrate was used in the formulation of instant Examples 4, 7, and 8. However, the claims as recited include citric acid anhydride having a particle size distribution x99 of less than 210 µm or citric acid hydrate having a particle size distribution x99 of less than 210 µm. The objective evidence presented in Tables 5 and 6 do not support wherein using citric acid anhydride having a particle size distribution x99 of less than 210 µm unexpectedly results in tablets having no dimples on the surface thereof. One of ordinary skill in the art would not reasonably expect the same results for a hydride and an anhydride since citric acid hydrate comprises a water molecule as opposed to citric acid anhydrous which does not possess a water molecule. Thus, one of ordinary skill in the art would not expect both types of citric acid to exhibit the same properties or behave the same in a moisture sensitive environment such as tableting. Therefore, the instant claims are not commensurate in scope with the supporting data.
Additionally, on page 23 of the instant application, Table 1 indicates that Comparative Examples 1 and 2 comprise citric acid hydrate. As shown on page 25 in Table 2 of the instant specification, Comparative Examples 1 and 2 are uncoated and contain citric acid that has not been treated, i.e., the particle size distribution x99 is not less than 210 µm. Comparative Examples 1 and 2 show no dimpling, as disclosed on Table 2. Table 2 also shows wherein Examples 1 and 2, which are substantially the same as Comparative Examples 1 and 2, respectively, except Examples 1 and 2 are coated, having tablets with dimples. Thus, it appears that Applicant’s results are specific for tablets that are coated. Examples 4, 7, and 8 are coated with Opadry ® ([Table 4]) and show little to no dimpling ([Table 5]). Opadry® used in the instant application refers to a mixture of hypromellose, talc, titanium oxide, iron sesquioxide, and yellow iron sesquioxide) in purified water (12.5 w/w%) to obtain a coating liquid), as noted in paragraph [0085] of the instant specification. Opadry® represents only one specific type of tablet coating option with specific ingredients that would result in a coating material comprising a specific consistency and thickness that may also affect tablet dimpling. However, the claims as written do not reflect this specific film coating but instead include any film coating. One of ordinary skill in the art would not expect any film coating to have the same consistency and thickness as the mixture of hypromellose, talc, titanium oxide, iron sesquioxide, and yellow iron sesquioxide (i.e., Opadry®) used in the instant invention since different coatings comprise different ingredients in different amounts and the type and amount of ingredients determines the consistency and thickness of a coating. Accordingly, the objective evidence of nonobviousness is not commensurate in scope with the claims which the evidence is offered to support.
For the foregoing reasons the rejection is maintained.
Maintained 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 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 9 of U.S. Patent No. US 12,083,226 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the compound of patent formula (I) is mirogabalin besylate, as evidenced the in the instant specification ([0032]). The patent claims are further directed to a tablet comprising: [(1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid monobenzenesulfonate of formula (I): D-mannitol; carmellose calcium; citric acid anhydride or citric acid hydrate, wherein the citric acid anhydride or citric acid hydrate is present at 1.125 to 2.9% by weight of the total weight of the uncoated tablet; and α-tocopherol, wherein the α-tocopherol is present at 0.005 to 0.5% by weight of the total weight of the uncoated tablet, wherein the tablet is a film-coated tablet.
Response to Applicant’s Arguments
Applicant requests the double patenting rejection be held in abeyance until the patentability of all claims is indicated.
Applicant’s argument has been fully considered but found not to be persuasive. Applicant’s arguments against the prior art rejections of the instant application were not found persuasive and Applicant has not filed an approved Terminal Disclaimer. Therefore, the rejection is maintained.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Samantha J Knight whose telephone number is (571)270-3760. The examiner can normally be reached Monday - Friday 8:30 am to 5:00 pm ET.
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, Ali Soroush can be reached at (571)272-9925. 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.
/S.J.K./Examiner, Art Unit 1614
/TRACY LIU/Primary Examiner, Art Unit 1614