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 .
Election/Restrictions
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/17/2025 has been entered.
Status
Claims 1, 32-34, 36-37, 39-46, and 49 are pending presented for examination.
Election/Restrictions
Applicant elected Group I (a prodrug compound) comprising a psychoactive base substance attached to an amino acid, in the reply filed on 4/12/2023.
Priority
This application claims priority to provisional application number 63/115,245, filed 11/18/2020. The claim to priority is acknowledged.
Information Disclosure Statement
The Information Disclosure Statement filed 9/17/2025 has been considered by the Examiner. The submission(s) is/are in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
Withdrawn Rejection
Claim 1, 31, 35, 38, 47, and 48 were rejected under 35 U.S.C. 102(a)(2) as being anticipated by COMPASS PATHFINDER LTD. (WO 2022/053696 A1). Applicant’s amendment and corresponding reply pertaining to the newly added limitation have overcome the rejection made of record in the previous Office Action, specifically, the removal of lysine, aspartic acid, glutamic acid, tryptophan, and tyrosine from the claims.
Claims 1 was rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,896,670. Applicant’s amendment and corresponding reply pertaining to the newly added limitation have overcome the rejection made of record in the previous Office Action, specifically, the removal of lysine, aspartic acid, glutamic acid, tryptophan, and tyrosine from the claims.
Therefore, the rejections are hereby withdrawn.
Claim Rejections - 35 USC § 103
Rejection maintained
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 1, 32-34, 36-37, 39-46, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Mickle et al. (USPN 7,105,486) in view of Vig et al. (Advanced Drug Delivery Reviews; Volume 65, Issue 10, 15 October 2013, Pages 1370-1385.)
Claimed invention
A compound comprising MDMA bound to an amino acid which is alanine, arginine, asparagine, cysteine, glutamine, histidine, isoleucine, leucine, methionine, proline, phenylalanine, serine, threonine, or valine.
Prior art
Mickle discloses prodrugs of amphetamine (and its derivatives) covalently attached to moieties such as amino acids and peptides to reduce abuse and overdose potential and modify pharmacokinetics. See abstract; col. 3:~58-65; col. 14:54-58; col. 30:21-27; col. 56:25-30. “The amino acid or peptide may comprise one or more of the naturally occurring (L-) [and (D-)] amino acids: alanine, arginine, asparagine, aspartic acid, cysteine, glycine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, and valine.” See col 11:37-48. That is, Mickle teaches all 20 canonical amino acids. Preferably, the amino acid is lysine, serine, phenylalanine or glycine. Most preferably, said amino acid is lysine. See 19:43-45. Mickle defined “amphetamine [to] mean any of the sympathomimetic phenethylamine derivatives which have central nervous system stimulant activity, such as [inter alia] 3,4-methylenedioxymethamphetamine [MDMA].” See col. 10:13-19. The amino acid includes a natural acid. See col. 4:12,48-50. Mickle specifically teaches lysine-amphetamine, i.e., a prodrug comprising amphetamine and the lysine amino acid. See col. 10:~33-34; see also Claim 1.
While Mickle teaches that 1) “amphetamines” covalently attached to moieties such as amino acids (e.g., alanine, arginine, asparagine, aspartic acid, cysteine, glycine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, and valine) to reduce abuse and overdose potential and modify pharmacokinetics and 2) may be specifically exemplified by the drug amphetamine attached to the lysine amino acid in order to modify the pharmacokinetics of amphetamine and reduce its abuse potential, Mickle does not expressly exemplify MDMA bound to the claimed canonical amino acids.
However, as mentioned above, Mickle teaches amphetamine can be attached to a single amino acid and teaches amino acid examples include the 20 canonical amino acids: alanine, arginine, asparagine, aspartic acid, cysteine, glycine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, and valine. Furthermore, Mickle states that the amphetamine may include MDMA. The Vig reference teaches the use of amino acid prodrugs to improve poor solubility, poor permeability, sustained release, intravenous delivery, drug targeting, and metabolic stability of the parent drug. See abstract. Vig teaches canonical amino acid prodrugs have a proven track of improving oral delivery of the drugs that have poor solubility and permeability. More recently, amino acid prodrugs have been successfully used to achieve sustained release, intravenous delivery, and improve metabolic stability. Importantly, amino acid prodrugs have proven commercial and regulatory track, which is beneficial in bringing such drugs to the patients. See ‘Conclusion’ at p. 1383.
A person of ordinary skill in the art (POSA) would have found it obvious to replace MDMA as the “amphetamine” and bound it to one of the canonical amino acids because Mickle teaches that the “amphetamine” has the potential to be abused and an amino acid (alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, or valine) can be covalently attached to it in order to reduce its abuse potential while Vig further teaches that attaching a canonical amino acid to a drug can be used to achieve sustained release, intravenous delivery, improve metabolic stability, modify permeability, modify release, and modify the targeting of the parent drug. Vig further teaches that amino acid prodrugs have a proven commercial and regulatory track, which is beneficial in bringing such drugs to the patients. Therefore, the POSA would have sought to combine the different canonical amino acids to MDMA to modify release, delivery, metabolic stability, permeability, pharmacokinetics and/or abuse potential of MDMA.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Claims 32-34, 36-37, 39-46, and 49 are each individually directed to one specific canonical amino acid – particularly, alanine, arginine, asparagine, cysteine, glutamine, histidine, isoleucine, leucine, methionine, proline, phenylalanine, serine, threonine, and valine. As mentioned above each one of the Mickle and Vig references teach alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, and valine as the amino acid that may be attached to the drug.
Response to arguments
Applicant argues the Mickle reference teaches stimulants, not empathogens, and because MDMA is an empathogen, it is distinct from the stimulants taught in the reference. Applicant's arguments have been fully considered but have not been found to be persuasive. Mickle explicitly defines “amphetamines” to include substituted derivatives having CNS stimulant activity, and lists MDMA among them (col. col. 10:13-19). While the behavioral pharmacology of MDMA may differ, patentability of the claimed compound is based on structural and functional similarity, not therapeutic intent. Mickle’s disclosure of amino acid-linked amphetamines therefore, reasonably suggests MDMA-amino acid conjugates. Therefore, Applicant’s remarks about Mickle preventing euphoria while MDMA producing euphoria are also not persuasive for the same reason, particularly, the therapeutic intent is noncontrolling of the obviousness of the structural modification here.
Applicant alleges there is no motivation to combine Mickle with Vig. However, Vig provides a well-recognized rationale – amino acid-conjugation to improve solubility, permeability, and metabolic stability – directly applicable to any amine-containing drug. Mickle identifies MDMA as an amphetamine derivative to be conjugated for the invention:
The invention provides covalent attachment of amphetamine and derivatives or analogs thereof to a variety of chemical moieties. The chemical moieties may include any Substance which results in a prodrug form, i.e., a molecule which is converted into its active form in the body by normal metabolic processes. The chemical moieties may be for instance, amino acids…
See col. 3. Emphasis added.
Amphetamine’ shall mean any of the sympathomimetic phenethylamine derivatives which have central nervous system stimulant activity, such as but not limited to, amphetamine, methamphetamine…and 3,4-methylenedioxymethamphetamine [MDMA].
See col. 10. Emphasis added.
Given that MDMA is disclosed as one of the conjugated amphetamines of the invention of Mickle, the POSA would have reasonably expected the amino acid conjugation strategy of Mickle to work for MDMA and would have sought to do so for any one of several benefits described by both references (e.g., mitigate abuse potential of MDMA).
Applicant argues that Vig is silent on MDMA and cannot cure the deficiency of Mickle’s disclosure. While Vig may be silent on MDMA, the art provides a teaching that can be applied to the amphetamine drugs of Mickle. Vig discloses most amino acid prodrugs are either esters or amides in which the α-amine or α-carboxylic group of the amino acid is attached to the parent functional group (e.g., amine - Vig, sentence bridging columns at p. 1372) and further recognizes amino acid-prodrug linkage is well-established (Vig, sentence bridging columns at p. 1382) that improves physiochemical and pharmacokinetic properties of the drug (Vig, p. 1383). Mickle teaches MDMA as an amphetamine derivative with an amine group may be conjugated with moieties including amino acids. A POSA would reason that benefits described for amine-containing prodrugs (amphetamines) conjugated with an amino acid can be extrapolated to an MDMA-amino acid conjugate, given that MDMA (3,4-methylenedioxymethamphetamine) is an amine-containing drug.
Therefore, the rejection is deemed to still be proper and is, therefore, maintained.
Double Patenting – Non-Statutory
Rejections maintained
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.
A. Claims 1, 32-34, 36-37, 39-46, and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 of copending Application No. 18/191,632 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims are drawn to a compound and methods of using same containing a psychoactive base substance and an amino acid, wherein the amino acid is selected from lysine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine whereas the psychoactive is selected from MDMA and MDMA-like compounds (e.g., MDA, MDEA, MBDB and others).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
Applicant states that a terminal disclaimer may be provided upon indication of the allowance of the pending claims. Because the application is not in condition for allowance, the rejection is maintained.
B. Claims 1, 32-34, 36-37, 39-46 and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5 of copending Application No. 18/198,058 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims are drawn to a compound containing a psychoactive base substance and an amino acid, wherein the amino acid is selected from lysine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine whereas the psychoactive is selected from MDMA and MDMA-like compounds such as MDA, MDEA, MBDB and others.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
Applicant states that a terminal disclaimer may be provided upon indication of the allowance of the pending claims. Because the application is not in condition for allowance, the rejection is maintained.
C. Claims 1, 32-34, 36-37, 39-46 and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-11 and 13-15 of copending Application No. 17/734,100 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims are drawn to a method of using a prodrug comprising R(-)MDMA bound to an amino acid, wherein the amino acid is selected from lysine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
Applicant states that a terminal disclaimer may be provided upon indication of the allowance of the pending claims. Because the application is not in condition for allowance, the rejection is maintained.
Conclusion
No claims are allowed.
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 CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622