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 September 3, 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.
Priority
In view of Applicant’s arguments and citations provided, the effective filing dates for claims that do receive the benefit of at least one earlier filed application are as follows:
Claims 33, 50, 51, 52 and 54 – December 5, 2022
Claims 34, 40 – 50 and 53 – May 1, 2023
Claim 38 has been canceled and claim 39 remains pending but depends from claim 35 which as detailed below contains new matter and is also not supported by any of the earlier filed applications. As such, claims 35 – 37 and 39 as currently presented do not receive the benefit of an effective filing date based on any of the applications to which benefit is claimed.
Drawings
The drawings were received on September 3, 2025. These drawings are not acceptable and have not been entered.
The replacement drawings have not been entered because new matter has been introduced in Figure 14. Most but not all cells in the cells above and to the right of diagonal of the Figure previously contained various oval shades in varying shades of gray along with a shaded scale bar for values ranging from 1 to -1 on the right hand side. The version of Figure 14 filed September 3, 2025 contains an oval of some shape with no coloring or shading in every cell above and to the right of diagonal of the Figure and with no scale bar. The addition of a symbol that means something to previously empty cells is new matter. The deletion of the scale bar that provided information as to what the various degrees of shading and the lack of information being provided as to the meaning of the new shapes set forth in the upper right portion of the table is also new matter. These changes also problematic because now the figure conveys information with the shapes in each cell but there is no indication as to the meaning of those shapes. The shadings previously present were aligned with the scale bar that is no longer present and something conveying similar information aligning the shape with that information has not been added.
Note that the deletion of blank panels in the other figures that were blank in the disclosure as originally filed does not constitute new matter. It is also not necessary to submit all figures when only some figures are amended.
Response to Amendment
The declaration under 37 CFR 1.132 filed September 30, 2025 is insufficient to overcome the rejection of claims 33 – 37 and 39 – 54 based upon Sessa et al. as set forth in the last Office action because: the declaration fails to establish a nexus of the materials tested with the claimed subject matter, establish what the expected results would in part because the composition and parameters of the comparative material are not specified and the composition and parameters of all ingredients in the inventive formulations, or present results of unexpected results that are reasonably commensurate in scope with the instant claims. It is noted the Exhibit 3 was not found in the file wrapper but no reference is made to any data that would fully remedy all of these issues.
The declaration focuses on capsule formulations comprising MDMA and based on the flow charts such as that on p 7 of Exhibit 2, the formulations also comprised mannitol manno gem onyx powder passed through an 850 µm hand screen and magnesium stearate passed through a 600 µm hand screen although the Examiner was unable to locate any information as to the amounts of these excipients used in the formulations prepared or the particle size parameters such as average or median particle size, Dv10, Dv90 or particle size range. The declaration reports that in Phase II clinical trials, there was variability in the results seen from different trials and as reported in greater detail in Exhibit 1, there was variability in the % label claim and dissolution profiles amongst the different capsules used in the different trials. Improvements to preparation process including controllable and scalable milling using a conical mill and sieve were added proper to blending. The most relevant sections of the declaration are sections 13 and 14, which report the particle size distribution of various batches including 3 commercial scale MDMA-HCl lots. The data from these two sections including the lack of length units for any of the reported samples is shown below.
Dv10
Dv50
Dv90
Particle Size Range
Average particle size
200601-004
27
157
349
-
-
200601-005
20
157
314
-
-
05112020-201101 unmilled
331
605
857
-
-
05112020-201101 milled
26.5
149
339
-
-
09112020-201102 unmilled
376
512
844
-
-
09112020-201102 milled
23.4
151
341
-
-
11112020-201103 unmilled
361
617
951
-
-
11112020-201103
22.9
147
356
-
-
Claimed parameter
-
About 100 µm – about 200 µm
Less than 420 µm (claim 47)
Less than 400 µm (claim 47)
50 – 400 µm (claim 47)
Average or mean particle size is not necessarily the same as Dv50 that appears to represent the median, not mean, particle size and Dv50 is the only size parameter required by all the claims of this application. Section 14 states that after milling, the commercial materials “met the acceptance criteria for blend uniformity and had particle size characteristics that fell within the scope of the pending claims.” However, this blanket statement does not permit adequate analysis such as showing how the criticality of the claimed ranges was established. While the Dv90 value is below the upper limit of particle size range, such Dv90 values can be obtained for samples having particles larger than 400 µm and the particle size range information is not reported. Section 15 of the declaration states that based on the evidence, a Dv90 of less than 420 µm was identified as critical. While an opinion as to a legal conclusion is not entitled to any weight, the underlying basis for the opinion may be persuasive. In re Chilowsky, 306 F.2d 908, 134 USPQ 515 (CCPA 1962) (MPEP 716.01(c)). As the underlying basis of this conclusion of criticality is not sufficiently set forth, this conclusion is not given any weight. The materials reported as having Dv90 values in the 800 – 900 µm range, well above the claim limit of 420 µm, were allegedly not good while those ranging from 314 – 356 µm were allegedly good, below the claim limit of less than 420 µm. The particle size and/or identity of the other excipients in and blend uniformity are not recited in the instant claims.
Applicants bear the burden of explaining the evidence offered in support of allegation of unexpected results, which includes but is not limited to what the expected results would be and clearly indicating all ingredients and there amounts in the comparative and inventive compositions for a complete evaluation of the comparison carried out. (Please see MPEP 716.02 et seq. for a complete discussion of unexpected results). Here Applicants have also not stated why the comparison given represents the closest prior art which is not necessarily a commerically available material. That the tested inventive formulations meet all the limitations of the claimed formulations has not been clearly established with actual values to see how the actual values compared to the limitations in the claims.
The alleged unexpected results appear to be for capsules formulated using the milled materials contained amounts of MDMA more closely aligned with the label claim amounts and that such milled formulations showed less batch to batch variation. Neither of these parameters are claimed. Data and/or reasoning supporting the conclusion that the absolute particle size and distribution parameters led to the variations was not located by the Examiner. As can be seen in the table above, even if all the values reported are in microns, the unmilled and milled materials lie well above and squarely within the claimed range for Dv50 respectively end points of the claimed range.
Even if there was a nexus established with the claimed subject matter tested in a comparison with the closest prior that was used as the basis for comparison, the data is for a particular composition with mannitol and magnesium stearate as the only other excipients and those materials were also screened, although the particle size and other parameters relating to the excipients was not given. One of skill in the art would reasonably expect that size mismatch between excipient and drug particles, regardless of the absolute size of the particles of various ingredients, could lead to variation but samples with drug and excipient particle sizes close to one another could blend more uniformly. Other than the amount of drug and the various particle parameters of the drug particles that are claimed, the claims are open to any form of pharmaceutical compositions with any excipients of any size. Therefore the evidence of record would not be considered to be reasonably commensurate in scope with the instant claims. The evidence in support of the alleged unexpected results does not outweigh the prima facie case of obviousness and therefore the rejection is maintained.
Claim Rejections - 35 USC § 112 – New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 35 – 37 and 39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 35, from which all the other rejected claims depend, has been amended to recite that “about 80% to about 100% of the mass of the MDMA particles dissolves in water at 15 minutes.” This amount of dissolution and time frame is not supported by the disclosure of the instant application or any of the applications to which benefit is claimed.
¶ [0167] of the PGPub of the instant application states that “[i]n some embodiments, the dissolution rate in water is greater than or equal to 50% (e.g., 60%, 70%, 80%, 85%, 90%, 95%, 98%, or 99%) of the mass of the MDMA” and the following sentence contains the phrasing was previously present in claim 35. For the shorter time frame of 15 minutes now required by amended claim 35, dissolution amounts of greater than or equal to 90% and greater than or equal to 95% of the mass of the MDMA are disclosed in ¶ [0167]. However, the phrasing in the disclosure relating to the lower end points of “greater than or equal to” does not permit any values below the stated value. Previously presented claim 38 recites “at least 80% of the mass of the MDMA particles dissolve in water at 15 minutes”. For example, 79.9% could be considered about 80% but is not greater than or equal to 80% or at least 80%. The maximum amount of MDMA that can dissolve is 100% but that is not the same about 100% which permits some amount less than complete dissolution in the stated time frame. Therefore the claimed range of about 80% to about 100% dissolution of the mass of MDMA within 15 minutes is not sufficiently supported and therefore constitutes new matter.
The dependent claims fall therewith as no dependent claim is limited to subject matter that was fully supported by the instant disclosure or any of the applications to which benefit is claimed.
If Applicant is in disagreement with the Examiner regarding support for the amended claim, Applicant is respectfully requested to point to page and line number wherein support may be found for the instant invention.
Claim Rejections - 35 USC § 112 – Written Description
Claims 35 – 37 and 39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This written description rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed March 6, 2025 and those set forth herein.
Applicants traverse on the grounds that example 4 and the dissolution profile data in Figure 13 are sufficient as the compositions have corresponding dissolution values are representative across the scope of the feature “characterized in that about 80% to about 100% of the mass of the MDMA particles dissolves in water at 15 minutes.”
These arguments are unpersuasive. The slight change in the amount of dissolution and time frame made to the claims does not result in the species set forth in examples and disclosure as filed being a representative number of species within the genus of formulations that provide such a function. The claimed function does not relate to the composition or unit dosage form as shown in Figure 13 but to the MDMA particles themselves and is calculated based on the total mass of the MDMA. While likely to be correlated, that data for the dissolution profile of the capsule composition as a whole is not the same as the dissolution of the MDMA particles themselves which is the parameter claimed has not been established. The cited formulations use capsules with the only excipients present being mannitol and magnesium stearate. This represents just one formulation amongst a very large number of possible formulations both in the terms of ingredients and forms (e.g., tablet, capsule or suspension) that could possibly have this function. Therefore possession of the full scope of pharmaceutical compositions with MDMA that are provide the claimed function of dissolution of about 80 to about 100% of the mass of the MDMA particles by 15 minutes has not been established and therefore the written description rejection is maintained.
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 33 – 37 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Sessa et al. (WO 2022/150525; cited on January 15, 2025 IDS). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed March 6, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that Wang describes studies demonstrating the effectiveness of MDMA in conjunction with therapy in treating PTSD but is entirely silent with respect to MDMA features such as those relating to particle size. The disclosure of Sessa provides no guidance to one skilled in the art as to selection of specific MDMA particle size. The two prophetic examples are silent as to the hydrochloride salt of MDMA, average particle size, Dv90, particle size range and dissolution time frame as claimed. These examples provide no meaningful guidance to the skilled artisan regarding specific particle size selection for either the free base or HCl forms of MDMA, the latter form being recited in the instant claims and no motivation towards the presently claimed formulation. There is no reasonable expectation that a complete departure from the parameters recited in the prophetic examples would provide a safe and effective formulation of MDMA. ¶ [201] of Sessa cited by the example conveys that it may be necessary to mill the active agent but no mesh size is provided with substantially insoluble active agents being ordinarily milled to a particle size less than 200 mess. The necessity to milling is a tautology that by definition is always true as it covers all possible scenarios and means nothing. The statements regarding substantially insoluble drugs but since the solvent is not specified, it cannot be determined under which circumstances this conditional statement applies so it also teaches nothing. If solvent is assumed to be the water and if the person of ordinary skill were led to use MDMA-HCl, this compound is not insoluble in water so one of ordinary skill in the art would not be led to mill such particles, let alone mill them using a 200 mesh screen.
These arguments are unpersuasive. These claims are not rejected solely based on the teachings of Wang et al. but the combination of the teachings of the applied prior art and the knowledge of one of ordinary skill in the art. Prior art is relevant for all that is taught and the teachings are not limited to the examples. While the cited examples do not use the HCl salt as claimed, MDMA as used in Sessa et al. refers to the salt such as hydrochloride or free base form (¶ [0143] and p 9 of March 6, 2025 Office Action). In addition to the explicit teachings of the applied prior art, the implicit and inherent teachings of the prior art and knowledge of one of ordinary skill in the art must also be considered when evaluating obviousness. Any 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). 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. 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 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.
Applicants also reference the declaration filed under 37 CFR § 1.132 which was discussed in detail above and will not be discussed in detail here as the deficiencies in the declaration such as the lack of units for all the measurements and therefore the evidence does not form a nexus with the claimed subject matter were addressed above.
Applicants also argue that the application as filed indicates that larger particles (average particle size > 600 µm) are inadequate for batch consistency and a coarse MDMA with a typical Dv90 from about 800 – about 1600 µm and typical particle size range of about 500 to about 1,100 µm leads to uneven distribution of the API (active pharmaceutical ingredient) and excipient, leading to an unacceptably high rate of batch failure and variability in dissolution profile. Additional data from the declaration regarding dissolution profiles and variability are cited.
These arguments are unpersuasive. For all but instant claim 47, the only claimed particle parameter is the Dv50, which is not necessarily the same as the average particle size. Conclusory statements regarding parameters which are not claimed are set forth in the specification without data to support those conclusions. While dissolution of the MDMA particles themselves is claimed, overall dissolution of the dosage form is not claimed and that is the data presented in the disclosure as filed. There are no claim limitations as to batch consistency, batch failure and/or dissolution profile variability. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The prior art need not explicitly disclose all claimed parameters and Applicants have not successfully rebutted the presumption that one of ordinary skill would optimize the particle size of the drug and established the criticality of the claimed particle size parameters. As discussed above, the declaration does not provide units from the size values given. The dissolution rate for the particles is determined by their composition and size, and there is no evidence of record that such a dissolution does not occur for a formulation with an optimized particle size.
Claim(s) 40 – 49 are rejected under 35 U.S.C. 103 as being unpatentable over Sessa et al. further in view of Bosse et al. (US2009/0175939). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed March 6, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that Bosse et al. does not cure the deficiencies of Wang and Sessa. There is no motivation for a person having ordinary skill in the art to select MDMA from among the 26 stimulants in ¶ [0174]; mannitol from among the list of 12 specific diluents and four classes of diluents in ¶ [0335] and magnesium stearate from among the list of 9 specific lubricants in ¶ [0246]. There is nothing to further select specific amounts of each component falling with the claimed ranges.
These arguments are unpersuasive. That the pharmaceutically active ingredient is MDMA is taught by Sessa et al. The disclosure of this amongst the agents that can be present in the formulations of Bosse et al. indicates that such excipients were contemplated for use in formulations comprising MDMA. That other excipients can be selected and used in the formulations does not render the selection of mannitol and magnesium stearate nonobvious. The selection of a known material based on its suitability for its intended use as disclosed in the prior art supports a prima facie obviousness determination (see MPEP 2144.07) and there is no persuasive evidence of record as to the criticality of the particular excipients and/or their amounts. Broad ranges for the amounts of excipients are claimed and the diluents, also known as fillers, are used to increase the bulk of the formulation while the exemplary amounts of magnesium stearate used in the example of Bosse et al. lie squarely within the claimed range.
Claim(s) 50 is rejected under 35 U.S.C. 103 as being unpatentable over Sessa et al. and Bosse et al. further in view of Al-Tabakha (J Pharm Pharmaceut Sci, 2010). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed March 6, 2025 and those set forth herein.
Applicants reiterate the alleged deficiencies of Wang et al., Sessa et al. and Bosse et al. that are discussed in greater detail above. Al-Tabakha et al. is a review article covering the use of HPMC capsules and lacks any disclosure or meaningful guidance to the claimed compositions and therefore does not remedy the deficiencies of Wang, Sessa and/Bosse.
These arguments are unpersuasive. Wang et al., Sessa et al. and Bosse et al. are not deficient as alleged by Applicants so Al-Tabakha et al. need not remedy the alleged deficiencies.
Terminal Disclaimer
The terminal disclaimers filed on September 3, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of any patent granted on Application Numbers 18/611,564; 19/005,354; 19/005,376 or 19/005,409 have been reviewed and are accepted. The terminal disclaimers have been recorded.
Accordingly, the provisional nonstatutory double patenting rejections based on each application has been withdrawn.
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