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 .
Applicants' arguments, filed November 25, 2025, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
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) 33 – 40 were rejected under 35 U.S.C. 103 as being unpatentable over Sessa et al. (WO 2022/150525; cited on June 28, 2024 IDS). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed August 20, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that the Sessa reference stating that milling may be necessary covers all possible scenarios and therefore teaches nothing. Stating that milling to less than about 200 mesh if an active agent is substantially insoluble means nothing since no solvent is specified, so it cannot be determined under which conditions this conditional statement applies. Even if water was assumed as the solvent, a person having ordinary skill would not be led to mill given that MDMA HCl is not insoluble in water and would not lead such a person to milling MDMA particles, let alone using a 200 mesh screen. Prophetic examples 1 and 2 use 125 or 62.5 mg MDMA free base as the dosage so even if motivated to pursue the formulations in these prophetic examples, this would not have led to claimed dosages and these examples provide no guidance to select different doses and use the HCl salt rather than the free base. Paragraph 240 lists every integer between 1 and 200 mg and the person of ordinary skill know that doses over 200 mg increases the risk of dangerous side effects citing to Exhibit A (Carvalho et al., cited on currently filed IDS and is 65 pages long but no specific citations are provided). Sessa basically teaches the entire universe of doses and therefore teaches nothing. These is no reasonable expectation of success given the broad disclosure and the claimed doses were arrived at through careful experimentation toward the goal of modular administration during therapy sessions and therapeutically effective response which is greater than routine experimentation.
These arguments are unpersuasive. A reference is not read in a vacuum and an evaluation of obviousness also takes into account the knowledge of the person of ordinary skill in the art. A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton (MPEP 2141(II)(C). Therefore one of ordinary skill would not take a statement such as that the material may be milled to meaning nothing or everything but rather that under some circumstance, the materials can be milled, which is known to alter particle size. The possibility of milling is clearly contemplated although is not a required step in every formulation, indicating to one of ordinary skill that particle size should be considered. The other highlighted statement indicates that in some cases, the appropriate threshold for milling is 200 mesh, which is well under the less than 400 µm particle size recited in the claims but provides a threshold value for at least some formulations. Prior art is relevant for all that is taught and is not limited to the examples and Sessa discloses the hydrochloride salt form of MDMA (3,4-methylenedioxymethamphetamine) even if not used in the examples. While numerous integers are given in Sessa for the dosage, the dosage of the therapeutic agent in a pharmaceutical dosage form is the epitome of a results effective variable that one of ordinary skill in the art would routinely optimize and Sessa also provides an explicit factors to be considered when carrying out such optimization of the dosage of the therapeutically active ingredient. The mere fact that numerous integer dosages are given does not mean that one of ordinary skill in the art would not have a reasonable expectation of success in arriving at the claimed dosage form. The disclosed dosages in Sessa do not exceed 200 mg, the threshold stated in the remarks to increase the risk of serious side effects. The instant claims are also drawn to a product and not a process of use and as with the other features claimed, there is no persuasive evidence of record as to the criticality of the claimed parameters such as dose or salt form. Applicants have presented no evidence that one of ordinary skill, in light of their knowledge and the explicitly disclosure of Sessa would have not been able to arrive at the claimed doses by routine optimization such as by establishing evidence as to the criticality of the claimed doses.
Applicants clarify that the reference to Table 3 in the declaration filed May 19, 2025 actually refers to Table 2. Additional sections of the declaration are repeated in the arguments including that one of ordinary skill in the art would readily understand that the unit for the various values in the declaration that are lacking in units would be µm particularly given the size of the screens that were used of 457 µm and 610 µm.*** Starch and mannitol were present in the compositions of Exhibit 1 and 2 respectively and it is unnecessary for the amounts of excipients to be disclosed or to be identical. The inertness and therapeutic inactivity of the excipient renders reporting of their amounts and particle sizes unnecessary. Exhibit 2 provides a controlled comparison of blend uniformity of samples with different processing histories and since this analysis focuses on processing variables rather than formulation differences, it is unnecessary to list the exact amount of excipients. Milling and sieving the MDMA HCl to have a smaller particle size imparts the critical feature necessary for the entire blend to have acceptable uniformity, rendering milling and sieving of the diluent and/or lubricant unnecessary so the characteristics and/or particle sizes of these ingredients is irrelevant. ### What is unexpected is that milling sieving of only one of the ingredients would result in blends having acceptable blend uniformity with Dv90 being of less than 420 µm being a critical process parameter in the previously filed declaration and data [without units for the size] support the claimed features relating to particle size. It is not necessary for the claimed ranges to precisely or narrowly encompass each percentile values in order to support non-obviousness since when a trend can be ascertained, the nonobviousness of a broad range can be proven by a smaller range and evidence for the entire range is not required.
These arguments are unpersuasive. Applicants do not provide any persuasive arguments that the only possible units for the particle sizes set forth in the declaration must be in µm. Screens let through particles of any size smaller and while the units could be µm, that is not an absolute possibility so to make such an inference would not be proper. A new declaration with units added could have been filed but was not. Regarding what can be disregarded, such statements were not made in the declaration and arguments without factual support are mere allegations and are not found persuasive. Amounts and type of ingredient need not be the same in samples being compared but introduce additional variables that influence what the expected results, which is why comparisons of completely specified formulation that only differ in one aspect can readily highlight the criticality of the aspect that does differ between the compositions being compared. Applicants discuss blend uniformity, which might be exactly the same appears content uniformity (CU) but appears to be a very similar factor considered in the pharmaceutical formulation art. Poor content uniformity can arise due to a combination of factors such as nonideal granule characteristics (particle size and assay distribution), low tablet dose, particle size differences with excipients, and segregation during manufacturing operations (p 4501, col 1, Rane et al., J Pharm Sci, 2012). While both population of particles in the studies carried out by Pinarbasli et al. (J Res Pharm, 2021) were drugs, the particle size of both the metformin and repaglinide was relevant as when mixed during tablet pres [sic] and segregation problems were observed (p 332, ¶ 6). Segregation is an action where a homogeneous mixture of granules with different properties (size, density, shape, etc.) tends to be heterogeneous and is one of the most important problems in the pharmaceutical industry that uses granular materials (p 332, ¶ 6). Studies were carried out to minimize susceptibility to segregation during the tablet press operation, thereby improving content uniformity, with the optimum particle size distribution and tapped density specifications for prepared granules before preparing final granule mixture were studied (p 332, ¶ 7). For this particular combination it was found that particle size distribution (D90, D50 and D10) of metformin HCl granule should be less than or equal to three times of particle size distribution (D90, D50 and D10) of repaglinide granule; and (ii) tapped density of metformin HCl granule should be less than or equal to two times of tapped density of repaglinide granule for optimal content uniformity (p 337, ¶ 1) as the particle size distribution and tapped density highly affecting the content uniformity of the drug product (p 337, ¶ 2). Rohrs et al. (J Pharm Sci, 2006) provides an in depth discussion of particle size limitation to meet USP (United States Pharmacopeia) content uniformity criteria. There are extensive theoretical and computational details provided but a practical product is Figure 3 that show the d50 particle size, distribution width δg and dose D need to have a 99% probability of passing USP Stage I content uniformity criteria (p 1050, col 2, ¶ 1). CU data on tablet lots manufactured from two-particle size distributions are used to test the limits and provide guidance on the selection of the width parameter from the actual distribution (p 1050, col 1, ¶ 4). When the width of the particle size distribution is reduced, one gains a significant increase in the maximum acceptable d50 (p 1054, col 1, last ¶). The state of the art indicates that properties of the other materials present during mixing and tableting such as the particle size distribution, tapped density and possibly others can influence content uniformity. Applicants are under no obligation to provide additional information on the materials tested but without additional information as to the particle size and particle size distribution of the ingredients present when mixed and what the expected results would be, the data provided in the previously filed declaration remains insufficient to establish that evidence of unexpected results that are reasonably commensurate in scope with the claims and outweigh the prima facie case of obviousness. ### By definition, unexpected results are not what is expected. It is not clear what data points are supposed to show a trend as the values given the table reproduced in the remarks, even if in µm, are closely clustered and Applicants have the burden of explaining evidence offered in support of alleged unexpected results (see MPEP 716.02 et seq. for a complete discussion of unexpected results) such as clearly identifying the data being used to establish as trend. Extrapolation to show a trend also requires any results that are unexpected to then behave in a predictable or expected manner across a broader range. This is where multiple data points, both inside and outside a claimed range, can be very useful to more clearly establish persuasive evidence of unexpected results without the need to provide data for every point within a claimed range. Such extrapolation of a trend over a broad range from a single data point or very closely spaced data points within the claimed range is more difficult to establish. Any evidence proffered in support of secondary considerations are carefully evaluated based on the rejection and evidence of record. All of the evidence currently of record has been evaluated and found not to outweigh the prima facie case of obviousness. The response of November 25, 2025 does not introduce any additional evidence and the arguments about what is of record do not establish evidence of unexpected results that is reasonably commensurate in scope with the claims that outweighs the prima facie case of obviousness. Therefore the rejection is maintained.
As to new claim 63, the DV50 range is the same as in previously rejected claim 36. It would have been obvious to optimize to one of ordinary skill in the art to optimize the particle size distribution reflected in the Dv90, Dv50 and Dv10 and there is no persuasive evidence of unexpected results that is reasonable commensurate in scope with the claims.
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.
Applicants traverse each provisional double patenting rejections set forth below on the grounds that that instant objection [sic] has been overcome by way of the amendments and remarks, so the provisional double patenting rejection are the only rejections remaining and should be withdrawn as the earlier filed application should be allowed to issue without requiring a terminal disclaimer (MPEP 804.I.B.1.(b)(i)).
These arguments are unpersuasive. The provisional double patenting rejections are not the only rejections remaining as the obviousness rejection above has been maintained. Even if these provisional double patenting rejections were the only rejections outstanding, the patent term filing date, which includes any benefit claims under 35 U.S.C. 120, 121, 365(c), or 386(c), is used when making a determination of which application is earliest filed. Only when the application under examination has an earlier patent term filing date, and not the same or later patent term filing date, is it proper to withdraw provisional double patenting rejections when they were the only rejections remaining in the application.
Claims 33 – 40 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33 - 54 of copending Application No. 19/005,354 (reference application). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed August 20, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 33 – 40 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33 - 54 of copending Application No. 19/005,376 (reference application). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed August 20, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 33 – 30 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33 - 57 of copending Application No. 19/005,409 (reference application). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed August 20, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 33 – 30 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33 - 57 of copending Application No. 19/005,427 (reference application). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed August 20, 2025 and those set forth herein.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618