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 .
Status of the Claims and Response to Restriction Requirement
Claims 1, 3, 7, 9, 13-17, 31-34, 36, 38-45 and 47-50 are pending as of the response filed on 01/08/2026. Claims 2, 4-6, 8, 10-12, 18-30, 35, 37 and 46 are cancelled. Applicant’s election of group I claims 1, 3, 7, 9, 13-17, 31-34, 36, 38-45 and 47-50 without traverse is acknowledged. It is noted that Applicants have cancelled the group II claims. Claims 1, 3, 7, 9, 13-17, 31-34, 36, 38-45 and 47-50 are examined herein.
Priority
This application claims priority to PRO 63/355,576 filed 06/25/2022.
Applicant’s claim for the benefit of a prior filed application under 35 U.S.C. 119(e) or under or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or earlier-filed nonprovisional application or provisional application for which benefit is claimed). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/355,576 fails to provide adequate support and enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The ‘576 application does not have support for the meso-tartrate (the ‘576 application indicates salt formation with meso-tartaric acid was unsuccessful, Para. [00031] of ‘576), as instantly claimed. The ‘576 application also does not disclose the specific crystalline salt forms as in instant claim 3. Accordingly, claims 1, 3, 7, 9, 13-17, 31-34, 36, 38-45 and 47-50 have an effective filing date of 05/30/2023, the filing date of the instant application.
Information Disclosure Statement
The information disclosure statement submitted on 01/08/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1, 3, 7, 9 and 44 are objected to because of the following informalities:
In claims 1, 3, 7, 9 the term “L-maleate” should read “L-malate” and in claim 44 the term “maleate” should read “malate” (as supported by example 15, Para. [00058] and Paras. [000112]-[000113] of the instant specification (maleic acid does not have a chiral center and therefore does not exist in D/L-forms).
Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 1, 3, 7, 9, 13-17, 31-34, 36, 38-45 and 47-50 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a composition or pharmaceutical composition of a salt of R-MDMA, wherein said salt is chosen from the group consisting of hydrobromide, phosphate, maleate, L-malate, D-tartrate, hemi-meso-tartrate, meso-tartrate, citrate, hemi-naphthalene-1,5-disulfonate, hemi-fumarate, fumarate, sulfate, mesylate, acetate, hemi-oxalate, and oxalate, does not reasonably provide enablement for a composition or pharmaceutical composition of the specific crystalline salt forms chosen from the group consisting of phosphate pattern A, phosphate pattern B, phosphate pattern C, HBr pattern A, HBr pattern B, HBr pattern C, hemi-L-tartrate pattern A, hemi-meso-tartrate pattern B, hemi-meso-tartrate pattern C, meso-tartrate pattern A, meso-tartrate pattern B, sulfate pattern A, sulfate pattern B, D-tartrate pattern A, D-tartrate pattern B, D-tartrate pattern C, D-tartrate pattern D, D-tartrate pattern E, L-malate pattern A, maleate pattern A, maleate pattern B, hemi naphthalene-1,5-disulfonate pattern A, hemi naphthalene-1,5-disulfonate pattern B, hemi-oxalate pattern A, hemi-oxalate pattern A', hemi-fumarate pattern A, hemi-fumarate pattern A', mesylate pattern A, acetate pattern A, citrate pattern A, fumarate pattern A, and oxalate pattern A. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation” would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In re Wands, 8 USPQe2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The breadth of the claims/The nature of the invention
The claims recite a composition or pharmaceutical composition of 32 specific crystalline salt forms of R-MDMA. The instant specification does not describe the exact procedures to synthesize these crystalline forms in sufficient detail. The nature of the invention is the provision of stable crystalline salt forms of R-MDMA suitable for scale up.
The state of the prior art/The level of predictability in the art
Variankaval et al. (From Form to Function: Crystallization of Active Pharmaceutical Ingredients, 03 June 2008, hereinafter Variankaval); Hilfiker et al. (Relevance of Solid-state Properties for Pharmaceutical Products, 2006, hereinafter Hilfiker).
Variankaval teaches that most small molecule drugs are delivered to patients in crystalline form and that a well-controlled crystallization of the active pharmaceutical ingredient (API) is often a vitally important operation in pharmaceutical manufacturing (Pg. 1682, first column, second paragraph). Variankaval teaches that there is immense complexity of anticipating packing arrangements of organic molecules in crystal lattices, thereby making predictions of the thermodynamically stable forms difficult (Pg. 1683, first column, last paragraph – second column, continued paragraph). Variankaval teaches solvent effects induce dramatic changes in crystal shape and seeded/unseeded crystallizations influence nucleation and growth of crystals (Pg. 1684, second column, last paragraph – Pg. 1685, first column, second full paragraph). Variankaval teaches the development of a robust, reproducible, scalable process is the most difficult to achieve (Pg. 1686, first column, second full paragraph – second column, second full paragraph). Variankaval highlights the complexity and challenges involved in screening for and developing successful crystallization processes.
Hilfiker teaches steps involved in screening for and selecting the optimal salt form (Pg. 8, second – third paragraph). Hilfiker teaches polymorph screening as an essential part of drug development for choosing the optimal form for further chemical and pharmaceutical development (Pg. 9, last paragraph). Hilfiker teaches solvent composition, concentration, cooling rate, seeding processes, as key parameters to optimize in designing reliable crystallization processes (Pg.12, last paragraph – Pg. 13, continued paragraph). Hilfiker teaches that developing the “right” solid form is critical for the success of a product (Pg. 15, second paragraph).
Therefore, the state of the prior art indicates challenges and unpredictability with respect to screening for and developing robust, reproducible, and scalable crystallization processes.
The level of one of ordinary skill in the art
The relative level of skill in the art is high, such as, a synthetic organic chemist, with advanced educational degrees (e.g., Ph.D.). Additionally, there is significant unpredictability in the art in the field of organic synthesis, especially with respect to developing thermodynamically stable crystalline forms of APIs.
The amount of direction provided by the inventor/The existence of working examples
Applicants have provided a general procedure for preparation of the R-MDMA salts in Paras. [00075]-[00082] of the instant specification. Table 1 indicates that the preparation of a L-tartaric acid salt was unsuccessful. Thus the hemi-L-tartrate salt is not enabled. While Applicants have disclosed the solvents used for the preparation of each of these salt forms in Table 1, it is not clear which solvents were used for preparing which specific salt forms of R-MDMA. For instance, while Applicant lists IPA, DCM and THF as solvents for preparation of phosphoric acid salts, it is unclear as to which solvent was used for preparing which specific phosphate salt form of R-MDMA, say, phosphate pattern A, phosphate pattern B and phosphate pattern C. It is unclear if these solvents were used individually or as a mixture. If a mixture of solvents were used, the proportion of each of the solvents used for the crystallization and precise steps followed have not been disclosed. A person of ordinary skill in the field of organic synthesis is well aware that optimization of the process for a specific salt form usually requires tailored experimental procedures for reproducibility. There is lack of direction or guidance regarding making and using the myriad of crystalline R-MDMA salt forms being claimed.
The quantity of experimentation needed
Considering the state of the art as discussed in the references above, the high degree of unpredictability in the field, and lack of sufficient guidance in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in scope with the claims.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 7 and 13-17 are rejected under 35 U.S.C. 102(a)(1)/35 U.S.C. 102(a)(2) as being anticipated by Duncton et al. (WO 2023/092044 A2, publication date 25 May 2023 and international filing date 17 November 2022, hereinafter Duncton, in the IDS).
Regarding instant claims 1 and 7, Duncton teaches solid forms of (R)-MDMA including crystalline forms of the salts, as well as polymorphs of the solid forms (Pg. 2, Lns. 9-12; Pg. 20, Lns. 24-33). Duncton teaches embodiments of a pharmaceutical composition, comprising a solid form of a disclosed compound or a salt thereof, and a pharmaceutically acceptable excipient (Pg. 4, Lns. 1-3). Duncton teaches the salt may be formed from an acid selected from fumaric acid, … naphthalene-1,5-disulfonic acid, citric acid, sulfuric acid, … methanesulfonic acid, … oxalic acid, … maleic acid, … phosphoric acid, … acetic acid, … (Pg. 3, Lns. 9-17). Therefore, Duncton anticipates a composition or pharmaceutical composition of a crystalline salt form or polymorph of R-MDMA, wherein the salt is chosen from fumarate, naphthalene-1,5-disulfonate, citrate, sulfate, mesylate, oxalate, maleate, phosphate or acetate.
Regarding instant claims 13-14, Duncton teaches the compositions can be formulated for slow release and teach that transdermal routes afford constant delivery for weeks or months (Pg. 120, Lns. 1-7; Pg. 117, Lns. 16-17). Therefore, Duncton anticipates a pharmaceutical composition formulated for continual slow release, via transdermal route.
Regarding instant claim 15, Duncton teaches the pharmaceutical composition can be formulated for intranasal administration (Pg. 117, Lns. 15-16). Duncton teaches formulating as aerosols (Pg. 121, Lns. 10-12). Therefore, Duncton anticipates a pharmaceutical composition formulated as a spray.
Regarding instant claim 16, Duncton teaches the pharmaceutical composition can be formulated in liquid form as solutions and suspensions (Pg. 118, Lns. 30-31). Duncton teaches other liquid dosage forms as emulsions (Pg. 119, Lns. 25-33), ointments, pastes (Pg. 121, Lns. 10-12). Therefore, Duncton anticipates a liquid dosage pharmaceutical composition.
Regarding instant claim 17, Duncton teaches the pharmaceutical composition can be formulated in solid dosage forms, such as powders, tablets, pills, capsules (Pg. 118, Lns. 6-7). Therefore, Duncton anticipates a solid dosage pharmaceutical composition.
Note from examiner : Although the fumarate salt of MDMA of Duncton has an XRPD pattern (Duncton, Pg. 22-23, Table 2) that partially overlaps the 2θ values of the fumarate salt of instant claim 34, the process of crystallization of Duncton uses acetone to obtain the hemi-fumarate form A (Pg. 578, Ln. 18 – Pg. 579, Ln. 5). However, the instant specification indicates IPA, DCM, THF as the solvent used in the preparation of the fumarate salt (TABLE 1 of instant specification).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3, 7, 9, 13-17, 31-34, 36, 38-45 and 47-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of co-pending Application No 18/611,400 in view of Duncton et al. (WO 2023/092044 A2, publication date 25 May 2023 and international filing date 17 November 2022, hereinafter Duncton, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a composition or pharmaceutical composition of specific crystalline salt forms of R-MDMA. The claims of the reference ‘400 application anticipate the specific crystalline salt forms of R-MDMA of claims 1, 3, 7, 9, 31-34, 36, 38-45 and 47-50.
The reference ‘400 application does not teach wherein said pharmaceutical composition is formulated in a continual slow-release formulation, as a transdermal patch; wherein said composition is formulated in an intranasal spray; wherein said composition is formulated in a liquid dosage form or a solid dosage form, as instantly claimed.
Duncton teaches solid forms of (R)-MDMA including crystalline forms of the salts, as well as polymorphs of the solid forms (Pg. 2, Lns. 9-12; Pg. 20, Lns. 24-33). Duncton teaches embodiments of a pharmaceutical composition, comprising a solid form of a disclosed compound or a salt thereof, and a pharmaceutically acceptable excipient (Pg. 4, Lns. 1-3). Duncton teaches the salt may be formed from an acid selected from fumaric acid, … naphthalene-1,5-disulfonic acid, citric acid, sulfuric acid, … methanesulfonic acid, … oxalic acid, … maleic acid, … phosphoric acid, … acetic acid, … (Pg. 3, Lns. 9-17). Therefore, Duncton anticipates a composition or pharmaceutical composition of a crystalline salt form or polymorph of R-MDMA, wherein the salt is chosen from fumarate, naphthalene-1,5-disulfonate, citrate, sulfate, mesylate, oxalate, maleate, phosphate or acetate. Duncton teaches the compositions can be formulated for slow release and teach that transdermal routes afford constant delivery for weeks or months (Pg. 120, Lns. 1-7; Pg. 117, Lns. 16-17). Duncton teaches the pharmaceutical composition can be formulated for intranasal administration (Pg. 117, Lns. 15-16). Duncton teaches formulating as aerosols (Pg. 121, Lns. 10-12). Duncton teaches the pharmaceutical composition can be formulated in liquid form as solutions and suspensions (Pg. 118, Lns. 30-31). Duncton teaches other liquid dosage forms as emulsions (Pg. 119, Lns. 25-33), ointments, pastes (Pg. 121, Lns. 10-12). Duncton teaches the pharmaceutical composition can be formulated in solid dosage forms, such as powders, tablets, pills, capsules (Pg. 118, Lns. 6-7). Therefore, the various formulations of the instant claims are rendered prima facie obvious in light of the teachings of Duncton.
The instant claims 1, 3, 7, 9, 13-17, 31-34, 36, 38-45 and 47-50 and claims 1-8 of co-pending Application No 18/611,400 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 3, 7, 9, 13-17, 31-34, 36, 38-45 and 47-50 are rejected.
Claims 1, 3, 7, 9 and 44 are objected to.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627