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 .
Foreign Priority
The present application claims priority to the application: 63/359,712, with the effective filing date of 8 July 2022.
Claim Status
This Office Action is in response to Applicant’s Amendment filed, 26 January 2026, wherein Applicant amended claims 1, 8, 15, 17, 20-21, 27, 29, 32-33, and 39-40 and canceled claims 16 and 28.
Claims 1, 4, 8, 11, 15, 17-27, and 29-40 are pending.
Information Disclosure Statement
The Information Disclosure Statement filed on 26 January 2026 and the references cited therein have been considered, unless indicated otherwise.
Rejections Withdrawn
Claim Objections
1. Claim 8 was objected to for the limitation of “protecting the amine (11) with di-tert butyl decarbonate as ethyl (S)-(1-benzo[d][1,3]dioxol-5-yl)propan-2-yl)carbamate (12).” Applicant’s amendment, see page 8, with respect to claim 8 has been fully considered. The objection of claim 8 has been withdrawn.
2. Claim 21 was objected to for the typographic error of “di-tert-butyl decarbonate.” Applicant’s amendment, see page 8, with respect to claim 21 has been fully considered. The objection of claim 21 has been withdrawn.
Claim Rejections - 35 USC § 112
3. Claims 16-26 were rejected for failing to further limit the subject matter upon which it depends. Claim 15 was amended to recite a method of manufacturing “(R)-1- (benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine ((R)- MDMA) or a salt thereof.” Applicant’s amendment, see page 9, with respect to claims 16-26 has been fully considered. Claim 16 was canceled. The rejection of claims 1 has been withdrawn.
4. Claims 28-38 were rejected for failing to further limit the subject matter upon which it depends. Claim 27 was amended to recite a method of manufacturing “(S)-1- (benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine ((S)- MDMA) or a salt thereof.” Applicant’s amendment, see page 9, with respect to claims 28-38 has been fully considered. Claim 28 was canceled. The rejection of claims 29-38 has been withdrawn.
5. Claim 21 was rejected for specifying the protecting step is performed with di-tertbutyl decarbonate or ethyl chloroformate, but claim 20 specifies the amine (5) was protected as ethyl carbamate. Claim 21 was amended to recite that di-tert-butyl dicarbonate is the reagent for the protecting step, and claim 20 is amended to recite that amine (5) is protected as the tert-butyl carbamate. Applicant’s amendment, see page 10, with respect to claim 21 has been fully considered. The rejection of claim 21 has been withdrawn.
6. Claim 33 was rejected for specifying the protecting step is performed with di-tertbutyl decarbonate or ethyl chloroformate, but claim 32 specifies the amine (11) was protected as ethyl carbamate. Claim 33 was amended to recite that di-tert-butyl dicarbonate is the reagent for the protecting step, and claim 32 is amended to recite that amine (11) is protected as the tert-butyl carbamate. Applicant’s amendment, see page 10, with respect to 33 has been fully considered. The rejection of 33 has been withdrawn.
Claim Rejections - 35 USC § 102
7. Claim 15 was rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Harkness (U.S. Patent No. 6,288,057, issued 11 Sept 2001, of record, see PTO-892 filed 27 Oct 2025).
Applicant amended claim 15 to incorporate the subject matter of claim 16. Applicant’s argument, see page 10, with respect to claim 15 has been fully considered. The 102(a)(1) and 102(a)(2) rejection of claim 15 has been withdrawn.
Rejections: New/Modified or Maintained
Claim Rejections - 35 USC § 102
8. (New/Modified) Claim 39 was rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Harkness (U.S. Patent No. 6,288,057, issued 11 Sept 2001, of record, see PTO-892 filed 27 Oct 2025).
Applicant’s arguments, see page 10, with respect to the rejection(s) of claim(s) 39 under 102(a)(1) and 102(a)(2) have been fully considered and is persuasive. However, upon further consideration, a new ground(s) of rejection is made in view of Dunlap (ACS Chem. Neurosci., 2018, 9, 2408-2427, of record, see IDS filed 17 Oct 2025).
Dunlap teaches Compound 14 in Figure 3A, which is Compound 4 of claim 39 (Figure 3A, page 2410). Additionally, Dunlap teaches Compound 5 of the claimed invention, which is the product of subjecting Compound 14 to di-tert-butyl dicarbonate in step 1 of the synthesis of Compound 1 (Figure 2, page 2410).
Therefore, claim 39 is rejected under 102(a)(1) as being anticipated by Dunlap.
Claim Rejections - 35 USC § 103
9. (Maintained) Claims 1, 4, and 15-26 were rejected as being unpatentable over Dunlap (ACS Chem Neurosci., 2018, 9, 2408-2427, of record, see IDS filed 17 Oct 2025) in view of Harkness (U.S. Patent No. 6,288,057, issued 11 Sept 2001, of record, see PTO-892 filed 27 Oct 2025) and Shi (J. Chemical Research, October 2004, 681-683, of record, see PTO-892 filed 27 Oct 2025). Claim 16 was canceled.
Applicant's arguments filed 26 January 2026 have been fully considered but they are not persuasive.
Applicant argues that the Office does not articulate a reason apart from knowledge of the present claims why a skilled artisan would have selected various elements from Dunlap, Harkness, and Shi and combined them in a way to arrive at the claimed invention. Applicant states that Dunlap teaches multiple directions with diverse intermediate compounds and methods of obtaining enantiopure MDMA, such as in Figure 3. Applicant further states that there is nothing in Dunlap that teaches the specific reaction in the scheme of Figure 3B is advantageous over the other methods disclosed in Dunlap. Applicant then states that Harkness does not teach compounds that are similar to MDMA and is vastly different to Dunlap. Applicant then states that Shi is directed to amphetamine compounds and that the Examiner is using Applicant’s disclosure to select the specific reaction within Shi for the obviousness rejection.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to Applicant's argument that a person or ordinary skill in the art facing the synthesis of MDMA in enantiomeric excess would have had no reason to combine the selected reactions from Harkness, Dunlap, and Shi, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, one of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Dunlap teaches multiple methods of synthesizing R-MDMA, protecting the amine, and reducing the protected amine in high enantiomeric purity,
-Dunlap teaches motivations to investigate new syntheses due to renewed interest in using psychedelic compounds like psilocybin and MDMA to treat neuropsychiatric disorders and that there are distinct differences pharmacologically between the R- and S-enantiomers of MDMA,
-Harkness teaches setting the stereocenter as soon as possible to form enantiomerically enriched alcohols in high purity,
-Shi teaches functionalizing a side chain of a related psychoactive small molecule (amphetamine-precursor), in particular alcohols to amines through the similar transformations in a chiral method, and treating amphetamine with acid to form a salt, and
-Shi teaches that amphetamine and its analogues are of pharmacological interest because of their effects on the central nervous system in humans as well as their anti-inflammatory activity.
As such, a person or ordinary skill would have been motivated to combine the selected reactions from Harkness, Dunlap, and Shi to develop a synthesis of MDMA in enantiomeric excess.
Additionally, Applicant makes the assertion that it is only with Applicant’s disclosure for guidance that Dunlap, Harkness, and Shi are combined to support an obviousness rejection. However, all citations in the previous obviousness rejection are not to Applicant’s specification but are to the prior art. Thus, there is no evidence to point to that the Examiner used Applicant’s specification to support an obviousness rejection.
Thus, the rejection of claims 1, 4, 15, and 17-26 as being unpatentable over Dunlap in view of Harkness and Shi is maintained.
10. (Maintained) Claims 8, 11, and 27-38 were rejected as being unpatentable over Dunlap (ACS Chem Neurosci, 2018, 9, 2408-2427, of record, see IDS filed 17 Oct 2025) in view of Harkness (U.S. Patent No. 6,288,057, issued 11 Sept 2001, of record, see PTO-892 filed 27 Oct 2025) and Shi (J Chemical Research, October 2004, 681-683, of record, see PTO-892 filed 27 Oct 2025) and further in view of Taguri (European Journal of Organic Chemistry, 2013, 30, 6924-6933, of record, see PTO-892 filed 27 Oct 2025). Claim 28 was canceled.
Applicant's arguments filed 26 January 2026 have been fully considered but they are not persuasive.
Applicant argues that Taguri is directed to linear alkyl compounds, which are different from MDMA compounds and further argues that the Examiner would only know the specific reaction within Taguri to be selected from among others disclosed in Taguri due to construction of the obviousness rejection.
In response to Applicant’s argument that Taguri is directed to linear alkyl compounds, Taguri teaches (R)-propylene oxide performs similarly to (S)-propylene oxide in Grignard additions, which Harkness teaches. Additionally, Taguri teaches that (R)-propylene oxide is commercially available and inexpensive. Further, as previously stated, the substitution of the (S)-propylene oxide reagent to the (R)-propylene oxide reagent is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters to achieve a beneficial effect is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980), Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007), and MPEP § 2143(B).
Additionally, Applicant makes the assertion that it is only with Applicant’s disclosure for guidance that Dunlap, Harkness, Shi, and Taguri are combined to support an obviousness rejection. However, all citations in the previous obviousness rejection are not to Applicant’s specification but are to the prior art. Thus, there is no evidence to point to that the Examiner used Applicant’s specification to support an obviousness rejection.
Thus, the rejection of claims 8, 11, 27, and 29-38 as being unpatentable over Dunlap in view of Harkness and Shi and further in view of Taguri is maintained.
11. (New/Modified) Claim 40 was rejected as being unpatentable over Harkness (U.S. Patent No. 6,288,057, issued 11 Sept 2001, of record, see PTO-892 filed 27 Oct 2025) in view of Taguri (European Journal of Organic Chemistry, 2013, 30, 6924-6933, of record, see PTO-892 filed 27 Oct 2025).
Applicant’s arguments, see page 15, with respect to the rejection(s) of claim(s) 40 under 103 have been fully considered and is persuasive. However, upon further consideration, a new ground(s) of rejection is made in view of Dunlap (ACS Chem Neurosci., 2018, 9, 2408-2427, of record, see IDS filed 17 Oct 2025), Harkness (U.S. Patent No. 6,288,057, issued 11 Sept 2001, of record, see PTO-892 filed 27 Oct 2025), Shi (J. Chemical Research, October 2004, 681-683, of record, see PTO-892 filed 27 Oct 2025), and Taguri (European Journal of Organic Chemistry, 2013, 30, 6924-6933, of record, see PTO-892 filed 27 Oct 2025).
As stated above, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to exemplify the methods of Dunlap, Harkness, Shi, and Taguri to access a method of preparing (S)-MDMA and intermediates thereof with the opposite enantiomer, (R)-propylene oxide. Dunlap teaches Compound 14 in Figure 3A, which is Compound 4 of claim 39 (Figure 3A, page 2410). Additionally, Dunlap teaches Compound 5 of claim 39, which is the product of subjecting Compound 14 to di-tert-butyl dicarbonate in step 1 of the synthesis of Compound 1 in Figure 2 (page 2410). Accordingly, the methods of Dunlap, Harkness, Shi, and Taguri teach Compounds 11 and 12 of the claimed invention.
Therefore, claim 40 is rejected under 103 as obvious in view of Dunlap, Harkness, Shi, and Taguri.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
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/MADELINE M. DEKARSKE/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622