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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 10, 2025 has been entered.
DETAILED ACTION
3. Claims 1 – 2, 4 – 5, 8, 11, 16, 19, 22 – 24, 27 – 30, 33 – 35 and 37 – 38 are pending in this application. Applicant’s Amendment and Remarks, filed October 10, 2025, is entered, wherein claims 1 – 2, 11, 22 – 23, and 35 are amended, claims 8, 33 – 35, and 37 are withdrawn, and claims 3, 6 – 7, 9 – 10, 12 – 15, 17 – 18, 20 – 21, 25 – 26, 31 – 32, and 36 are canceled.
Claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38 are examined on the merits herein.
Priority
4. This application is a national stage application of PCT/US2020/015898, filed January 30, 2020, which claims benefit of domestic application 62/800,369, filed February 1, 2019.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) 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 original nonprovisional application or provisional application). 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. 62/800,369, fails to provide adequate support or 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 domestic application 62/800,369 does not provide support for the limitations of “alkyl-OH, alkyl-O-alkyl, cycloalkyl, alkyl-cycloalkyl, alkyl-aryl or alkyl-heteroaryl” recited in claims 1, 22, and 38 and “-NH(CO)-alkyl, -NH(CO)NH-alkyl, -NH(CO)-aryl, or -NH(CO)NH-aryl” recited in claims 1, 22, and 38. Thus, the priority date of claims 1, 22, and 38 and their dependent claims 4 – 5, 11, 16, 19, 23 – 24, and 27 – 30 is January 30, 2020.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed October 10, 2025, have been fully considered and are found to be persuasive.
As claim 2 is amended to no longer recite “alkyl-OH, alkyl-O-alkyl, cycloalkyl, alkyl-cycloalkyl, alkyl-aryl or alkyl-heteroaryl” and “-NH(CO)-alkyl, -NH(CO)NH-alkyl, -NH(CO)-aryl, or -NH(CO)NH-aryl”, the priority date of claim 2 is February 1, 2019.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Gassaway et al. (WO2017165738A1).
a. Regarding claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38, Gassaway et al. teaches a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
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wherein X is N; R1 is OH; R2 is -alkyl; R3 is -alkyl; R4 is -alkyl; α is present; β is absent; and χ is present, or a pharmaceutically acceptable salt of ester thereof, wherein the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 3, lines 20 – 25; page 4, lines 1 – 16). A compound with a level of deuterium at any site of hydrogen atom in the compound that has been enriched to be greater than its natural abundance of 0.0156% over its non-enriched counterpart (page 45, line 37; page 46, lines 1 – 2). In some embodiments, the compound wherein R2, R3, and R4 are each methyl (page 9, lines 20 – 21). In some embodiments, the compound having the structure:
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wherein R1 is -OH (page 14, lines 19 – 22). In some embodiments, the composition wherein the isotopic purity at each position of the R2 methyl group is 95% or greater in deuterium; the isotopic purity at each position of the R3 methyl group is 95% or greater in deuterium; and the isotopic purity at each position of the R4 methyl group is 95% or greater in deuterium (page 17, lines 10 – 14). Gassaway et al. also discloses that any notation of a hydrogen in structure throughout, when used without further notation, are intended to represent all isotopes of hydrogen, such as 1H, 2H (D), or 3H (T) (page 45, lines 22 – 25). Moreover, Gassaway et al. teaches a pharmaceutical composition in unit dosage form, which comprises (i) an amount of any compound recited and (ii) an amount of an NMDA receptor antagonist (page 43; lines 4 – 9), wherein the NMDA receptor antagonist is ibogaine or noribogaine (page 37, lines 26 – 27).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute a deuterium isotope at the R6 position of the claimed compound because Gassaway et al. explicitly teaches that all hydrogen atoms are representative of isotopes, including deuterium. Especially, Gassaway et al. discloses (page 3, line 23):
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and also discloses that the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 4, lines 15 – 16). As the structure specifically shows that the H atom at the R6 position of the claimed compound, it is expected that one would have been motivated to replace the H atom at that particular position for a deuterium. The position of the deuterium would be optimized by routine experimentation to discover the best location(s) for the deuterium to obtain the optimal treatment characteristics. One of skill in the art would have been motivated to apply the level of deuterium at position R2, R3, and R4 as taught by Gassaway et al. to other location of the deuterium because of the predictable results. The reasonable expectation of success in substituting hydrogen with deuterium would also have motivated one of ordinary skill to make this substitution at the R6 position. Gassaway et al. broadly teaches compositions wherein isotopic substitutions are within the scope of the invention, as well as compounds where isotopic purity at specific positions (e.g. R2, R3, and R4) is explicitly enriched to 95% or greater in deuterium. This demonstrates that isotopic enrichment, including substitution of deuterium, is a desirable and obvious modification for achieving compositions with altered properties.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed October 10, 2025, have been fully considered and are found to be not persuasive.
Regarding Gassaway et al., Applicant argues that Gassaway et al. do not teach deuterium at the R6 position, whereas deuterium at the R6 position is a common feature shared by the exemplified compounds, which is not specifically taught by Gassaway et al. As the structure specifically shows that the H atom at the R6 position of the claimed compound, it is expected that one would have been motivated to replace the H atom at that particular position for a deuterium because Gassaway et al. teach the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 3, lines 20 – 25; page 4, lines 1 – 16). The position of the deuterium would be optimized by routine experimentation to discover the best location(s) for the deuterium to obtain the optimal treatment characteristics.
Applicant argues unexpected results based on mitragynine and 3-deuteromitragynine (3-DM), whereas 3-DM exhibits enhanced metabolic stability compared to mitragynine. Applicant argues that compounds having deuterium enrichment at the R6 position possess unexpected superior properties of attenuating the formation of toxic metabolites. However, Gassaway et al. disclose deuterated mitragynine and the unexpected results must be a comparison to the closest prior art. Since the prior art already teaches deuterated mitragynine, the closest art is other deuterated analogs, not the parent compound mitragynine. Failing to compare 3-DM to other deuterate forms fails to show that the position-specific deuteration at the 3-position yields unexpected results relative to what was already known. Moreover, the results only refer to the deuterium at the R6 location, whereas claim 1 recites “R6 is a deuterium-enriched-H site”, “at least one of R7, R8, or R9 is a deuterium-enriched-H site”, and “one or more or all of H1-H11 are deuterium-enriched”. These limitations are not demonstrated in the results. Therefore, the unexpected results do not 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.
Claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 58 of copending Application No. 17/938,003 in view of Gassaway et al. (WO2017165738A1).
a. Regarding claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38, ‘003 teaches a pharmaceutical composition comprising (A) a compound of the formula:
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; and
(B) an excipient (claim 58).
However, ‘003 does not teach the compound with deuterium at the R6 position of the claimed compound. ‘003 does not teach the pharmaceutical composition comprising a pharmaceutically acceptable carrier and further comprising NMDA receptor antagonist, such as ibogaine or noribogaine. ‘003 also does not teach the level of deuterium at the deuterium-enriched -H site.
Gassaway et al. teaches a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
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wherein X is N; R1 is OH; R2 is -alkyl; R3 is -alkyl; R4 is -alkyl; α is present; β is absent; and χ is present, or a pharmaceutically acceptable salt of ester thereof, wherein the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 3, lines 20 – 25; page 4, lines 1 – 16). A compound with a level of deuterium at any site of hydrogen atom in the compound that has been enriched to be greater than its natural abundance of 0.0156% over its non-enriched counterpart (page 45, line 37; page 46, lines 1 – 2). In some embodiments, the compound wherein R2, R3, and R4 are each methyl (page 9, lines 20 – 21). In some embodiments, the compound having the structure:
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wherein R1 is -OH (page 14, lines 19 – 22). In some embodiments, the composition wherein the isotopic purity at each position of the R2 methyl group is 95% or greater in deuterium; the isotopic purity at each position of the R3 methyl group is 95% or greater in deuterium; and the isotopic purity at each position of the R4 methyl group is 95% or greater in deuterium (page 17, lines 10 – 14). Gassaway et al. also discloses that any notation of a hydrogen in structure throughout, when used without further notation, are intended to represent all isotopes of hydrogen, such as 1H, 2H (D), or 3H (T) (page 45, lines 22 – 25). Moreover, Gassaway et al. teaches a pharmaceutical composition in unit dosage form, which comprises (i) an amount of any compound recited and (ii) an amount of an NMDA receptor antagonist (page 43; lines 4 – 9), wherein the NMDA receptor antagonist is ibogaine or noribogaine (page 37, lines 26 – 27).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the hydrogen as taught in ‘003 with a deuterium isotope at the R6 position of the claimed compound in view of Gassaway et al. because Gassaway et al. explicitly teaches that all hydrogen atoms are representative of isotopes, including deuterium. Gassaway et al. discloses (page 3, line 23):
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and also discloses that the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 4, lines 15 – 16). As the structure specifically shows that the H atom at the R6 position of the claimed compound, it is expected that one would have been motivated to replace the H atom at that particular position for a deuterium. The position of the deuterium would be optimized by routine experimentation to discover the best location(s) for the deuterium to obtain the optimal treatment characteristics. One of the skills in the art would have been motivated to apply the level of deuterium at position R2, R3, and R4 as taught by Gassaway et al. to other location of the deuterium because of the predictable results. The reasonable expectation of success in substituting hydrogen with deuterium would also have motivated one of ordinary skill to make this substitution at the R6 position. Gassaway et al. broadly teaches compositions wherein isotopic substitutions are within the scope of the invention, as well as compounds where isotopic purity at specific positions (e.g. R2, R3, and R4) is explicitly enriched to 95% or greater in deuterium. This demonstrates that isotopic enrichment, including substitution of deuterium, is a desirable and obvious modification for achieving compositions with altered properties.
This is a provisional nonstatutory double patenting rejection.
Claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2, 4, 33, 127, and 139 of copending Application No. 17/304,713 in view of Gassaway et al. (WO2017165738A1).
b. Regarding claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38, ‘713 teaches a compound of Formula (I’):
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and further teaches a compound as shown below:
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(claims 1 – 2, 4, 33, and 127).
‘713 also teaches a pharmaceutical composition comprising the compound and optionally a pharmaceutically acceptable carrier (claim 139).
However, ‘713 does not teach the compound with deuterium at the R6 position of the claimed compound. ‘713 does not teach the pharmaceutical composition comprising NMDA receptor antagonist, such as ibogaine or noribogaine. ‘713 also does not teach the level of deuterium at the deuterium-enriched -H site.
Gassaway et al. teaches a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
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wherein X is N; R1 is OH; R2 is -alkyl; R3 is -alkyl; R4 is -alkyl; α is present; β is absent; and χ is present, or a pharmaceutically acceptable salt of ester thereof, wherein the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 3, lines 20 – 25; page 4, lines 1 – 16). A compound with a level of deuterium at any site of hydrogen atom in the compound that has been enriched to be greater than its natural abundance of 0.0156% over its non-enriched counterpart (page 45, line 37; page 46, lines 1 – 2). In some embodiments, the compound wherein R2, R3, and R4 are each methyl (page 9, lines 20 – 21). In some embodiments, the compound having the structure:
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wherein R1 is -OH (page 14, lines 19 – 22). In some embodiments, the composition wherein the isotopic purity at each position of the R2 methyl group is 95% or greater in deuterium; the isotopic purity at each position of the R3 methyl group is 95% or greater in deuterium; and the isotopic purity at each position of the R4 methyl group is 95% or greater in deuterium (page 17, lines 10 – 14). Gassaway et al. also discloses that any notation of a hydrogen in structure throughout, when used without further notation, are intended to represent all isotopes of hydrogen, such as 1H, 2H (D), or 3H (T) (page 45, lines 22 – 25). Moreover, Gassaway et al. teaches a pharmaceutical composition in unit dosage form, which comprises (i) an amount of any compound recited and (ii) an amount of an NMDA receptor antagonist (page 43; lines 4 – 9), wherein the NMDA receptor antagonist is ibogaine or noribogaine (page 37, lines 26 – 27).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the hydrogen as taught in ‘713 with a deuterium isotope at the R6 position of the claimed compound in view of Gassaway et al. because Gassaway et al. explicitly teaches that all hydrogen atoms are representative of isotopes, including deuterium. Gassaway et al. discloses (page 3, line 23):
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and also discloses that the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 4, lines 15 – 16). As the structure specifically shows that the H atom at the R6 position of the claimed compound, it is expected that one would have been motivated to replace the H atom at that particular position for a deuterium. The position of the deuterium would be optimized by routine experimentation to discover the best location(s) for the deuterium to obtain the optimal treatment characteristics. One of the skills in the art would have been motivated to apply the level of deuterium at position R2, R3, and R4 as taught by Gassaway et al. to other location of the deuterium because of the predictable results. The reasonable expectation of success in substituting hydrogen with deuterium would also have motivated one of ordinary skill to make this substitution at the R6 position. Gassaway et al. broadly teaches compositions wherein isotopic substitutions are within the scope of the invention, as well as compounds where isotopic purity at specific positions (e.g. R2, R3, and R4) is explicitly enriched to 95% or greater in deuterium. This demonstrates that isotopic enrichment, including substitution of deuterium, is a desirable and obvious modification for achieving compositions with altered properties.
This is a provisional nonstatutory double patenting rejection.
Claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 5, 7, and 9 of U.S. Patent No. 11912707B2 in view of Gassaway et al. (WO2017165738A1).
c. Regarding claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38, ‘707B2 teaches a compound having the structure (claim 1):
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‘707B2 further teaches a compound having the structure (claims 2 – 4):
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The compound is deuterium enriched (claim 5). ‘707B2 also discloses a pharmaceutically composition comprising the compound and a pharmaceutically acceptable carrier (claim 7). The composition, wherein R2, R3, and R4 are each methyl and isotopic purity at each position of the R2 methyl group is 95% or greater in deuterium; the isotopic purity at each position of the R3 methyl group is 95% or greater in deuterium; and the isotopic purity at each position of the R4 methyl group is 95% or greater in deuterium (claim 9).
However, ‘707B2 does not teach the compound with deuterium at the R6 position of the claimed compound. ‘707B2 does not teach the pharmaceutical composition comprising NMDA receptor antagonist, such as ibogaine or noribogaine.
Gassaway et al. teaches a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
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wherein X is N; R1 is OH; R2 is -alkyl; R3 is -alkyl; R4 is -alkyl; α is present; β is absent; and χ is present, or a pharmaceutically acceptable salt of ester thereof, wherein the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 3, lines 20 – 25; page 4, lines 1 – 16). A compound with a level of deuterium at any site of hydrogen atom in the compound that has been enriched to be greater than its natural abundance of 0.0156% over its non-enriched counterpart (page 45, line 37; page 46, lines 1 – 2). Gassaway et al. also discloses that any notation of a hydrogen in structure throughout, when used without further notation, are intended to represent all isotopes of hydrogen, such as 1H, 2H (D), or 3H (T) (page 45, lines 22 – 25). Moreover, Gassaway et al. teaches a pharmaceutical composition in unit dosage form, which comprises (i) an amount of any compound recited and (ii) an amount of an NMDA receptor antagonist (page 43; lines 4 – 9), wherein the NMDA receptor antagonist is ibogaine or noribogaine (page 37, lines 26 – 27).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the hydrogen as taught in ‘707B2 with a deuterium isotope at the R6 position of the claimed compound in view of Gassaway et al. because Gassaway et al. explicitly teaches that all hydrogen atoms are representative of isotopes, including deuterium. Gassaway et al. discloses (page 3, line 23):
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and also discloses that the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 4, lines 15 – 16). As the structure specifically shows that the H atom at the R6 position of the claimed compound, it is expected that one would have been motivated to replace the H atom at that particular position for a deuterium. The position of the deuterium would be optimized by routine experimentation to discover the best location(s) for the deuterium to obtain the optimal treatment characteristics. One of the skills in the art would have been motivated to apply the level of deuterium at position R2, R3, and R4 as taught by Gassaway et al. to other location of the deuterium because of the predictable results. The reasonable expectation of success in substituting hydrogen with deuterium would also have motivated one of ordinary skill to make this substitution at the R6 position. Gassaway et al. broadly teaches compositions wherein isotopic substitutions are within the scope of the invention, as well as compounds where isotopic purity at specific positions (e.g. R2, R3, and R4) is explicitly enriched to 95% or greater in deuterium. This demonstrates that isotopic enrichment, including substitution of deuterium, is a desirable and obvious modification for achieving compositions with altered properties.
Claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 4, 6 – 11, and 16 – 22 of copending Application No. 18/437,646 in view of Gassaway et al. (WO2017165738A1).
d. Regarding claims 1 – 2, 4 – 5, 11, 16, 19, 22 – 24, 27 – 30, and 38, ‘646 teaches a compound having the structure (claims 1 and 16):
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‘646 further teaches the compound having the structure (claims 2 – 4 and 16 – 18):
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The compound taught is deuterium enriched at the positions of R2, R3, and R4 (claims 6 – 7 and 19 - 20). ‘646 further teaches a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier (claim 8). The pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (claims 9 and 16), wherein the isotopic purity at each position of the R2, R3, and R4 methyl group is 95% or greater in deuterium (claim 10 – 11 and 21 – 22).
However, ‘646 does not teach the compound with deuterium at the R6 position of the claimed compound. ‘646 does not teach the pharmaceutical composition comprising NMDA receptor antagonist, such as ibogaine or noribogaine.
Gassaway et al. teaches a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
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wherein X is N; R1 is OH; R2 is -alkyl; R3 is -alkyl; R4 is -alkyl; α is present; β is absent; and χ is present, or a pharmaceutically acceptable salt of ester thereof, wherein the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 3, lines 20 – 25; page 4, lines 1 – 16). A compound with a level of deuterium at any site of hydrogen atom in the compound that has been enriched to be greater than its natural abundance of 0.0156% over its non-enriched counterpart (page 45, line 37; page 46, lines 1 – 2). Gassaway et al. also discloses that any notation of a hydrogen in structure throughout, when used without further notation, are intended to represent all isotopes of hydrogen, such as 1H, 2H (D), or 3H (T) (page 45, lines 22 – 25). Moreover, Gassaway et al. teaches a pharmaceutical composition in unit dosage form, which comprises (i) an amount of any compound recited and (ii) an amount of an NMDA receptor antagonist (page 43; lines 4 – 9), wherein the NMDA receptor antagonist is ibogaine or noribogaine (page 37, lines 26 – 27).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the hydrogen as taught in ‘646 with a deuterium isotope at the R6 position of the claimed compound in view of Gassaway et al. because Gassaway et al. explicitly teaches that all hydrogen atoms are representative of isotopes, including deuterium. Gassaway et al. discloses (page 3, line 23):
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and also discloses that the pharmaceutical composition is enriched in the compound that contains deuterium in place of -H (page 4, lines 15 – 16). As the structure specifically shows that the H atom at the R6 position of the claimed compound, it is expected that one would have been motivated to replace the H atom at that particular position for a deuterium. The position of the deuterium would be optimized by routine experimentation to discover the best location(s) for the deuterium to obtain the optimal treatment characteristics. One of the skills in the art would have been motivated to apply the level of deuterium at position R2, R3, and R4 as taught by Gassaway et al. to other location of the deuterium because of the predictable results. The reasonable expectation of success in substituting hydrogen with deuterium would also have motivated one of ordinary skill to make this substitution at the R6 position. Gassaway et al. broadly teaches compositions wherein isotopic substitutions are within the scope of the invention, as well as compounds where isotopic purity at specific positions (e.g. R2, R3, and R4) is explicitly enriched to 95% or greater in deuterium. This demonstrates that isotopic enrichment, including substitution of deuterium, is a desirable and obvious modification for achieving compositions with altered properties.
This is a provisional nonstatutory double patenting rejection.
Responses to Applicant’s Remarks:
Regarding the claims, Applicant requests that the rejections be held in abeyance until otherwise allowable subject matter has been identified. As Applicant does not file any terminal disclaimer and does not provide other remarks, the double patenting rejections are maintained.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693