The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claims 1, 3-19 and 21-22 are presented for examination.
Acknowledgement is made of the present application as a continuation of U.S. Patent Application No. 16/634,055, filed January 24, 2020, now U.S. Patent No. 11,376,249 B2, which is a National Stage (371) entry of PCT Application No. PCT/US2018/043100, filed July 20, 2018, which claims benefit under 35 U.S.C. §119(e) to U.S. Provisional Patent Application Nos. 62/537,287, filed July 26, 2017, 62/639,244, filed March 6, 2018, and 62/682,546, filed June 8, 2018.
Requirement for Restriction/Election
Applicant’s election without traverse of (i) a drug dependency disorder as the single disclosed species of central nervous system disorder and (ii) the compound of formula (I) in which X is -NH-, L is -O- and Z is -O-, which has the chemical structure
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and is also identified as CAS Registry No. 2117619-00-6 and by the chemical name (6bR,10aS)-8-[3-(4-fluorophenoxy)propyl]-6b,7,8,9,10,10a-hexahydro-1H-pyrido[3’,4’:4,5]pyrrolo[1,2,3-de]quinoxalin-2(3H)-one, to which examination on the merits will be confined, as stated in the reply filed February 20, 2026, is acknowledged by the Examiner.
Upon further reconsideration of the subject matter as most recently amended, the elected species of “drug dependency disorder” will be rejoined with the additional non-elected species of claim 1 directed to “opiate dependency” and “opiate overdose” due to the overlap between such species.
Therefore, for the reasons above and those made of record at p.2-6 of the Office Action dated September 24, 2025, the requirement remains proper and is hereby made FINAL.
Claims 3-4 and 7 are withdrawn from consideration pursuant to 37 C.F.R. §1.142(b) as being directed to non-elected subject matter.
The claims that are drawn to the elected species are claims 1, 5-6, 8-19 and 21-22 and such claims are herein acted on the merits infra.
Information Disclosure Statement
Applicant’s Information Disclosure Statements filed June 3, 2022 (14 pages), July 6, 2023 (one page) and February 20, 2026 (five pages) have each been received and entered into the present application. As reflected by the attached, completed copies of form PTO-1449 or PTO/SB/08a (20 pages total), the Examiner has considered the cited references.
Objections to the Claims
Claim 1 is objected to for failing to recite the conjunction “and” between the definitions for L and Z at l.8-9 of the claim.
Appropriate correction is required.
Claim 8 is objected to for failing to recite the conjunction “and” between the final two listed chemical structures.
Appropriate correction is required.
Claim 9 is objected to for failing to recite the conjunction “and” between the final two listed chemical structures.
Appropriate correction is required.
Claims 16-17 are each objected to for failing to recite a comma between the limitations “wherein said patient is not responsive to” and “or cannot tolerate the side effects from”, which is grammatically awkward.
Appropriate correction is required.
Claim 17 is objected to for failing to recite proper Markush construction to define the “opioid drugs” (“selected from morphine … tapentadol, and anileridine”).
Proper Markush construction requires the language “selected from the group consisting of A, B, and C” (not “selected from A, B, and C” as recited). See MPEP §2173.05(h)(I) for clarification of Markush limitations.
Alternatively, Applicant may choose to clearly recite the list in the alternative to obviate the instant objection by using the conjunction “or” between the final two members of the list.
Appropriate correction is required.
Claim 19 is objected to for failing to recite proper Markush construction to define the “additional therapeutic agent” (“selected from buprenorphine, methadone, naloxone, and naltrexone”).
Proper Markush construction requires the language “selected from the group consisting of A, B, and C” (not “selected from A, B, and C” as recited). See MPEP §2173.05(h)(I) for clarification of Markush limitations.
Alternatively, Applicant may choose to clearly recite the list in the alternative to obviate the instant objection by using the conjunction “or” between the final two members of the list.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a) (Pre-AIA First Paragraph)
Scope of Enablement
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.
(1) Claims 1, 5-6, 8-19 and 21-22 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 method for treating a central nervous system (CNS) disorder that is drug dependency, opiate dependency, or opioid overdose via administering to a patient in need thereof a compound of formula (I) where X is –NH-, L is O and Z is –O- or –C(O)-, does not reasonably provide enablement for a method for treating a CNS disorder that is drug dependency, opiate dependency, or opioid overdose via administering to a patient in need thereof any other compound embraced by formula (I).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
In this regard, the application disclosure and claims have been compared per the factors indicated in the decision In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988) as to undue experimentation. The factors include:
1) the nature of the invention;
2) the breadth of the claims;
3) the predictability or unpredictability in the art;
4) the amount of direction or guidance presented;
5) the presence or absence of working examples;
6) the quantity of experimentation necessary;
7) the state of the prior art; and,
8) the relative skill of those skilled in the art.
The relevant factors are addressed below.
Note that the specification must be enabling as of the filing date. MPEP §2164.05(a)1.
Applicant’s invention is directed to a method for the treatment of a CNS disorder, wherein the CNS disorder is drug dependency, opiate dependency, or opioid overdose, comprising administering to a patient in need thereof a compound of formula (I), which has the chemical structure
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, wherein X is –NH- or –N(CH3)-; L is O; and Z is –CH(OH)-, -O- or –C(O)-; wherein the compound is in free or salt form (claim 1). Applicant further defines the drug dependency disorder as opioid use disorder (claim 18). Exemplary species of formula (I) include the compounds
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or
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(claims 8-9). Dependent claims further specify that the compound is administered in the form of a pharmaceutically acceptable composition comprising the compound in free or pharmaceutically acceptable salt form, in admixture with a pharmaceutically acceptable diluent or carrier, particularly wherein the diluent or carrier is a polymeric matrix, more particularly a biodegradable poly(d,l-lactide-co-glycolide) microsphere (claims 11-13). Applicant suggests the compounds are useful in “the treatment of diseases involving the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving D1 and D2 receptor signaling systems, and/or the -opioid receptor [MOP]” (p.1, para.[0001] of the as-filed specification).
Serotonin, dopamine and the MOP receptor were known in the prior and contemporaneous art to be involved in a variety of CNS conditions. Zhang et al. (“The Role of Serotonin 5-HT2A Receptors in Memory and Cognition”, Front. Pharmacol. 2015; 6:225, cited by Applicant on the 06/03/22 IDS) discusses the utility of targeting serotonin 5-HT2A receptors to treat various CNS disorders, noting that “[a]bnormal 5-HT2AR activity is associated with a number of psychiatric disorders and conditions, including depression, schizophrenia, and drug addiction” and that “[p]reclinical studies show that 5-HT2AR blockage has antipsychotic [citation omitted], antidepressant [citation omitted] and anxiolytic properties” (abstract; col.1, para.1, p.2). Pine et al. (“Dopamine, Time, and Impulsivity in Humans”, Journal of Neuroscience, 2010; 30(26):8888-8896, cited by Applicant on the 06/03/22 IDS) teaches the role of aberrant dopamine function in disorders such as addiction, ADHD and dopamine dysregulation syndrome, noting that excess dopamine (as a result of dopamine replacement therapy in Parkinson’s disease) has been observed to render patients prone to compulsive behaviors (e.g., excess gambling, shopping, or eating) by overweighting smaller-sooner or larger-later rewards (abstract; col.1, para.1, p.8888). Noble et al. (“The Opioid Receptors as Targets for Drug Abuse Medication”, British Journal of Pharmacology, 2015; 172:3964-3979, cited by Applicant on the 06/03/22 IDS) documents the functionality of -opioid receptor (MOP) antagonists (e.g., naloxone or naltrexone) in reducing cocaine self-administration in a rat model (thereby suggesting its usefulness as a target for therapeutic intervention in cocaine addiction), and further documents naloxone’s effects in attenuating cravings in amphetamine dependent and alcohol dependent subjects (col.2, para.3, p.3966; col.2, para.2, p.3967; col.1, para.2, p.3969).
Substituted heterocycle fused gamma-carboline compounds were known to exhibit activity at 5-HT2A, SERT and/or dopamine D2 receptors. See, e.g., Robichaud et al. (U.S. Patent No. 6,713,471 B1; 2004, cited by Applicant on the 06/03/22 IDS) (which teaches substituted heterocycle fused gamma-carboline compounds as agonists or antagonists of 5-HT2 serotonin receptors, particularly 5-HT2A and 5-HT2C receptors, for treating anxiety, depression, migraine and other conditions associated with cephalic pain, social phobias, etc., and further teaches that 5-HT2A antagonists were known to be effective for the treatment of schizophrenia, anxiety, depression, and migraines; col.2, l.33-36; col.3, l.30-41; col.3, l.65-col.7, l.45); Robichaud et al. (U.S. Patent No. 7,183,282 B2; 2007, cited by Applicant on the 06/03/22 IDS) (which also teaches substituted heterocycle fused gamma-carboline compounds for use in the treatment of addictive behaviors, noting further that 5HT2 receptors were known to be related to the symptoms associated with drug-dependent withdrawal; col.3, l.3-13; col.4, l.40-col.5, l.5); and Mates et al. (U.S. Patent No. 8,993,572 B2; 2015, cited by Applicant on the 06/03/22 IDS) (which teaches substituted heterocycle fused gamma-carboline compounds for use in the treatment of diseases involving 5-HT2A receptors, as well as SERT and/or pathways involving dopamine D2 receptor signaling systems; abstract; col.1, l.22-37; col.3, l.1-20), as well as Mates et al. (U.S. Patent Application Publication No. 2011/0071080 A1; 2011, cited by Applicant on the 06/03/22 IDS), which teaches substituted heterocycle fused gamma-carbolines for the treatment of disorders involving the 5-HT2A, SERT and/or dopamine D2 pathways (abstract; p.1, para.[0008]-p.2, para.[0009]; p.2, para.[0015]-[0017]), and Mates et al. (U.S. Patent Application Publication No. 2015/0080404 A1; 2015, cited by Applicant on the 06/03/22 IDS), which also teaches substituted heterocycle fused gamma-carbolines as 5-HT2A antagonists, noting further the usefulness of 5-HT2A antagonists in the treatment of aggressive and impulsive behaviors in animal models and the ability to reduce behavioral disturbances, such as agitation and irritability (p.2, para.[0008]-[0013]). Each of these structurally similar compounds, however, differ from instantly claimed Formula I in the following key aspects: (i) L substitution of the piperazine ring; (ii) the fully saturated pyrrolidine and piperidine rings of the fused tetracyclo ring system; and (iii) the particular alkylene linker with Z substitution attached to the terminal 4-fluorophenyl ring.
Yao et al. (WO 2017/132408 A1; Published August 3, 2017, Filed January 26, 2017, cited by Applicant on the 06/03/22 IDS) teaches substituted heterocycle fused gamma-carboline compounds of substantially similar structure to those of Applicant’s instant claim 1, further noting their function in “the treatment of diseases involving the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving D1 and D2 receptor signaling systems, and/or the -opioid receptor [MOP]” (p.1, para.[0001]). Yao exemplifies three specific substituted heterocycle fused gamma-carboline compounds – structurally identical to Applicant’s species recited in claim 9 – but experimentally identifies that the alteration of the substitution at position Z (in which Z is –CH(OH)) eliminates any binding affinity for any of the tested receptors (5-HT2A, D1, D2, SERT and MOP). The working examples of Yao et al. also demonstrate that those compounds in which X is –NH-, L is O, and Z is –O- or –C(O)- were effective to exhibit analgesic properties (Ex.7, p.52, para.[0120]-p.53, para.[0122]). Such teachings support the activity of the instantly claimed compounds of formula (I) in which X is –NH, L is O and Z is –O- or –C(O)- with binding affinity for the tested receptors (5-HT2A, D1, D2, SERT and/or MOP) – thus, supporting the reasonable expectation of efficacy in the treatment of drug use and drug dependency, as supported by the prior and contemporaneous art before the effective filing date of the claimed invention (as cited above).
Applicant’s claims, however, assert that the administration of any one of the compounds of instantly claimed formula (I) to a patient in need of treatment for drug dependency, opiate dependency or opiate overdose will treat the same. The concept that the skilled artisan would have been able to reasonably accomplish this objective without needing to resort to undue experimentation is not supported by the literature before the effective filing date of the claimed invention.
The working examples provided in the as-filed specification do not fully remedy this lack of adequate enabling guidance. Applicant’s Ex.1-3 present the synthesis of three species of compounds of formula (I) (the same three species recited in instant claim 9), which correspond to formula (I) in which (i) X is –NH-, L is O, and Z is –C(O) (Ex.1, also identified at p.10 as “Formula II-B”), (ii) X is –NH-, L is O, Z is –CH(OH) (Ex.2, also identified at p.11 as “Formula II-C”) and (iii) X is –NH-, L is O and Z is O (Ex.3) (p.57, para.[00124]-p.60, para.[0127]). Applicant’s Ex.4 tested the effects of “Formula II-B” (the compound of Ex.1) on the MOP receptor, noting its antagonistic properties (“[t]he compound of Formula II-B is found to have a (MOP) (h) (antagonist effect) with an IC50 of 1.3 x 10-6 M; and a KB of 1.4 x 10-7 M”; p.61, para.[0131]). Applicant’s Ex.5 tests the compounds of Ex.1 (Formula II-B), Ex.2 (Formula II-C) and Ex.3 to determine the receptor affinity of each compound as compared to the compound of Formula A (a compound of similar structure to Formula (I), wherein the L substitution is absent, X is –N(CH3)- and X is –C(O)), noting that the compounds of Ex.1 and 3 (in which X is –NH-, Z is –C(O) or –O-, and L is O) were effective inhibitors of 5-HT2A, D1 dopamine and the MOP receptor, but that the compound of Ex.2 (in which X is –NH-, Z is –CH(OH) and L is O) did not exhibit effective inhibition of any one or more of 5-HT2A, D1, D2, SERT or MOP (Table, p.63, para.[0137]). Applicant’s Ex.6 confirmed the 5-HT2 receptor antagonism of the compounds of Ex.1 and 3 in the DOI-induced head twitch model (p.63, para.[0138]-p.64, para.[0139]). Applicant’s Ex.7 observed that the compounds of Ex.1 and 3 were effective to induce analgesia as measured in the mouse tail flick test (p.64, para.[0140]-p.67, para.[0148]). Applicant’s Ex.10 surmises that – based on the fact that tested compounds of Ex.1 and 3 were found to be moderate antagonists of MOP with partial agonist activity – the compounds would be effective in the treatment of pain and/or opiate withdrawal “with lower risks of addiction” (p.69, para.[0157]-p.71, para.[0162]). Applicant’s Ex.11-12 demonstrates the functionality of the compound of Ex.3 to “dose-dependently reduce[s] the signs and symptoms of opiate withdrawal after the sudden cessation of opiate administration in opiate-dependent rats” (p.73, para.[0173]-p.75, para.[0177]), Ex.14 demonstrates the “non-addictive nature” of the compound of Ex.3 in “heroin-addicted rats” (p.77, para.[0183]-p.78, para.[0185]), and Ex.16-17 demonstrate the function of the compound of Ex.3 to “reverse[s] the inhibition of gastrointestinal motility caused by morphine” and also to have no significant depressive effect on respiratory function (p.79, para.[0190]-p.81, para.[0195]).
The working examples, however, fail to provide any disclosure relevant to establishing that any other compound of instantly claimed Formula I – aside from those compounds that are structurally consistent with the compounds of Ex.1 and 3 (i.e., in which X is –NH-, L is O and Z is –O- or –C(O)-) – would exhibit efficacy in the treatment of any drug dependency disorder (including opiate dependency) or opiate overdose as claimed. This conclusion is evidenced at least by the fact that Applicant’s working examples are strictly limited to the structurally similar compounds of Ex.1 and 3 and by the fact that a seemingly minor change in structure (in this case, the substitution at position Z to be -CH(OH)- in the compound of Ex.2) eliminates the binding affinity for any of the tested receptors (5-HT2A, D1, D2, SERT and MOP). As a result, the as-filed specification fails to clearly enable the use of any one or more compounds of formula (I) for the treatment of a drug dependency (including opiate dependency) and/or opiate overdose, aside from a compound of formula (I) in which X is –NH-, L is O and Z is –O- or –C(O)-. Applicant is reminded that the standard for enablement is providing sufficient guidance as to how to make and use the invention, not how to make and test the invention with essentially no promise of success.
While the lack of adequate working examples cannot be the sole factor in determining enablement, the unpredictable nature of the art and the absence of substantial evidence commensurate in scope with the breadth of the presently claimed subject matter provides additional weight to the present conclusion of insufficient enablement in consideration of the Wands factors as a whole.
The basis for the present rejection is not simply that experimentation would be required, since it is clear from the state of the pharmaceutical, medical and chemical arts that experimentation in this art is not uncommon, but that the level of experimentation required in order to practice these aspects of the invention in the absence of adequate enabling direction by Applicant would be undue. See In re Angstadt, 537 F.2d 498, 503, 190 USPQ 214, 219 (CCPA 1976), which states, “The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.”
In view of the discussion of each of the preceding seven factors, the level of skill in the art is high and is at least that of a pharmacologist or medical doctor with several years of experience in the art.
As the cited art and discussion of the above factors establish, the disclosure and supporting examples provided in the present specification, coupled with the state of the art at the time of the invention, fail to imbue the skilled artisan with a reasonable expectation or ability to make and/or use the full scope of the invention as instantly claimed. In order to actually make and/or use the full scope of the claimed invention, it is clear from the discussion above that the skilled artisan could not rely upon Applicant’s disclosure as required by 35 U.S.C. §112(a) (pre-AIA first paragraph) in order to practice the full scope of the invention presently claimed.
Claim Rejections - 35 USC § 112(b) (Pre-AIA Second Paragraph)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(2) Claims 1, 5-6, 8-19 and 21-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant’s claim 1 recites “[a] method for the treatment of a central nervous system disorder, comprising administering to a patient in need thereof a compound of a [f]ormula I”, in which “the disease or disorder is a drug dependency disorder, opiate dependency, opiate overdose, and combinations thereof”.
The “need” of the recited patient is not clearly set forth in the claim. For example, it is unclear if the “patient” is in need of treatment for a central nervous system disorder, or in need of the administration of a compound of formula (I) for any therapeutic purpose.
Clarification is required.
There is a lack of antecedent basis for the limitation “the disease or disorder” because the preceding text of claim 1 references only “a central nervous system disorder” – not “a central nervous system disease or disorder”.
Clarification is required.
As claims 5-6, 8-19 and 21-22 depend from claim 1 and do not remedy these points of ambiguity in claim 1, they must also be rejected on the same grounds applied thereto.
For these reasons, the claims fail to meet the tenor and express requirements of 35 U.S.C. §112(b) (pre-AIA second paragraph) and are, thus, properly rejected.
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 (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 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.
(3) Claims 1, 5-6, 8-15 and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yao et al. (WO 2017/132408 A1; 2017, cited by Applicant on the 06/03/22 IDS).
Yao et al. teaches compounds of Formula I, which has the chemical structure
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, wherein X is –NH-, L is O, and Z is –O- or –C(=O)-, and further wherein the compound may be in free or salt form (particularly isolated or purified free or salt form) for use in the treatment of CNS disorders (p.2-3, para.[0005]). Yao et al. further exemplifies the specific species of
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(l.27, p.5-6; Formula II-B, p.8). Yao et al. teaches that such compounds may be further formulated into a pharmaceutical composition in admixture with a pharmaceutically acceptable diluent or carrier, particularly wherein the diluent or carrier of the composition is a polymeric matrix, wherein biodegradable poly(d,l-lactide co-glycolide) is particularly preferred (p.13, para.[0014]-p.15, para.[0018]; p.38, para.[0070]). Yao et al. further teaches that the polymer matrix is employed in the form of a microparticle or nanoparticle (p.39-40, para.[0077]). Yao et al. teaches that the CNS disorder that may be treated using the disclosed compounds includes drug dependency (e.g., opiate dependency and/or alcohol dependency), or withdrawal from drug (e.g., opiate) or alcohol dependency, or mood disorders with substance use disorder (e.g., opiate abuse in patients with depression, anxiety, sleep disorders) (1.16, p.19-20; 1.28, p.21). Yao et al. teaches that the compounds are useful in the treatment of drug dependency, such as opiate dependency and/or alcohol dependency, by inhibiting the endogenous opiate response to illicit drug administration, as well as by inhibiting the direct effects of ingestion of illicit opiate drugs as a result of particularly good -opioid receptor antagonism using compounds in which X is –NH and L is O (p.34, para.[0058]).
Therefore, instant claims 1, 5-6, 8-15 and 18 are properly anticipated under AIA 35 U.S.C. §102(a)(1).
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.
Provisional Rejections
(4) Claims 1, 5-6, 8-10, 14-15, 18 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19-20 of U.S. Patent Application No. 18/567,743.
Claims 19-20 of the ‘743 application recite a method for the treatment of a human suffering from a disease or abnormal condition involving or mediated by the 5-HT2A receptor, serotonin transporter (SERT), dopamine D1/D2 receptor signaling pathways, and/or the mu-opioid receptor comprising administering to a patient in need thereof a therapeutically effective amount of a solid, crystalline salt of the compound (6bR,10aS)-8-(3-(4-fluorophenoxy)propyl)-6b,7,8,9,10,10a-hexahydro-1H-pyrido[3’,4’:4,5]pyrrolo[1,2,3-de]quinoxaolin-2(3H)-one2, wherein the disease or abnormal condition includes a drug dependency, such as opiate or opioid or alcohol dependency, opiate or opioid overdose, or opioid use disorder.
This is a provisional nonstatutory double patenting rejection.
(5) Claims 1, 5-6, 8-12, 14-15 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-23 of U.S. Patent Application No. 19/181,262.
Claims 15-17 of the ‘262 application recite a method for treating opiate addiction relapse, including detoxification and maintenance treatment of opioid addiction, comprising administering to a patient in need thereof the compound
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in free or pharmaceutically acceptable salt form. Claim 18 of the ‘262 application specifies that the compound is in the form of a pharmaceutically acceptable salt. Claim 19 of the ‘262 application further specifies that the compound is in the form of a pharmaceutical composition in admixture with a pharmaceutically acceptable diluent or carrier, and claim 20 of the ‘262 application further defines the composition as comprising the compound in a polymeric matrix. Claim 22 of the ‘262 application further specifies that the patient suffers from, inter alia, other drug dependencies, including stimulant dependency and/or alcohol dependency. Claim 23 of the ‘262 application defines the patient as having a history of substance use or substance abuse with an opiate or opioid drug.
The claims of the ‘262 application, thus, clearly embrace the treatment of a drug dependency, in particular, an opiate addiction or dependency, as instantly claimed.
This is a provisional nonstatutory double patenting rejection.
Non-Provisional Rejections
(6) Claims 1, 5-6 and 8-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-7 of U.S. Patent No. 10,245,260 B2.
Claim 1 of the ‘260 patent recites a method for the treatment of a CNS disorder comprising administering to a patient in need thereof a compound of formula (I), which is
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, in which X is -NH-, L is O, Z is -O- or -C(O)-, in free or salt form, and further wherein the CNS disorder is, inter alia, opiate dependency, cocaine dependency or alcohol dependency. Claim 3 of the ‘260 patent specifically identifies the compound of formula (I) as
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. Claim 4 of the ‘260 patent recites that the compound is in the form of a salt. Claim 5 of the ‘260 patent further limits the compound to the form of a pharmaceutical composition comprising the compound in free or pharmaceutically acceptable salt form in admixture with a pharmaceutically acceptable diluent or carrier. Claim 6 of the ‘260 patent defines the diluent or carrier as a polymeric matrix, and claim 7 of the ‘260 patent further defines the polymeric matrix as a biodegradable poly(d,l-lactide-co-glycolide) microsphere.
This is a nonprovisional nonstatutory double patenting rejection.
(7) Claims 1, 5-6 and 8-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-17 of U.S. Patent No. 10,799,500 B2.
Claim 1 of the ‘500 patent recites a compound of formula (I), which is
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, in which X is -NH-, L is O, Z is -O- or -C(O)-, in free or salt form, or pharmaceutically acceptable salt form. Claim 3 of the ‘500 patent defines Z as -O-. Claims 4-5 of the ‘500 patent further defines the compound of claim 3 as free form (claim 4) and a free, solid form (claim 5), and claims 6-7 of the ‘500 patent further defines the compound as a pharmaceutically acceptable salt. Claims 8, 11-12 and 15 of the ‘500 patent further define the compound as part of a pharmaceutical composition in admixture with a pharmaceutically acceptable diluent or carrier. Claims 9, 13 and 16 of the ‘500 patent further define the diluent or carrier as a polymeric matrix. Claims 10, 14 and 17 of the ‘500 patent further define the polymeric matrix as a biodegradable poly(d,l-lactide-co-glycolide) microsphere.
In the ‘500 patent, the patentee defines the use of the disclosed compounds in a method for treating diseases or disorders that include drug dependencies, such as opiate dependency, cocaine dependency, amphetamine dependency, and alcohol dependency (col.1, l.17-41), thereby demonstrating that this method of therapeutic use as instantly claimed was embraced by the claims of the ‘500 patent.
This is a nonprovisional nonstatutory double patenting rejection.
(8) Claims 1, 5-6, 8-14, 18-19 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-9 and 15-19 of U.S. Patent No. 11,376,249 B2.
Claims 1 and 15 of the ‘249 patent recite a method for the treatment of a CNS disorder comprising administering to a patient in need thereof a compound of formula (I), which is
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, in which X is -NH-, L is O, Z is -O- or -C(O)-, in free or salt form, optionally in an isolated or purified free or salt form, wherein the CNS disorder is traumatic pain disorder with opioid use disorder. Claim 3 of the ‘249 patent defines Z as -O-. Claim 4 of the ‘249 patent defines the compound in the form of a salt. Claim 5 of the ‘249 patent defines the compound in the form of a pharmaceutical composition in admixture with a pharmaceutically acceptable diluent or carrier. Claim 6 of the ‘249 patent further defines the diluent or carrier as a polymeric matrix and claim 7 of the ‘249 patent further defines the polymeric matrix as a biodegradable poly(d,l-lactide-co-glycolide) microsphere. Claim 8 of the ‘249 patent specifies that the patient is not responsive to, or cannot tolerate the side effects from, non-narcotic analgesics and/or opioid drugs, or wherein the use of opioid drugs are contraindicated in said patient, and claim 9 of the ‘249 patent further defines the opioid drugs as including, e.g., morphine, codeine, etc. Claims 16 and 18 of the ‘249 patent further specifies that an additional therapeutic agent is administered, in which the therapeutic agent is an agonist, partial agonist, inverse agonist or antagonist of the mu-opiate, kappa-opiate, delta-opiate and/or nociception/orphanin receptors, and claims 17 and 19 of the ‘249 patent further define such therapeutic agents as including naloxone, naltrexone, etc.
This is a nonprovisional nonstatutory double patenting rejection.
(9) Claims 1, 5-6, 8-11 and 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-9 and 12-13 of U.S. Patent No. 11,844,757 B2.
Claims 1, 4-6 and 12-13 of the ‘757 patent recite a method for the treatment of a CNS disorder comprising administering to a patient in need thereof a compound of formula (I), which is
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, in which X is -NH-, L is O, Z is -O- or -C(O)-, in free or pharmaceutically acceptable salt form, wherein the CNS disorder is, inter alia, a drug dependency selected from opiate dependency, cocaine dependency, amphetamine dependency, alcohol dependency, substance addiction, substance use disorder or substance induced disorder. Claim 3 of the ‘757 patent defines the compound of formula (I) as
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. Claim 7 of the ‘757 patent defines the compound in the form of a pharmaceutical composition in admixture with a pharmaceutically acceptable diluent or carrier. Claim 8 of the ‘757 patent specifies that the patient is not responsive to, or cannot tolerate the side effects from, non-narcotic analgesics and/or opioid drugs, or wherein the use of opioid drugs are contraindicated in said patient due to prior substance abuse or high potential for substance abuse, and claim 9 of the ‘757 patent further defines the drugs as including, e.g., morphine, codeine, etc.
This is a nonprovisional nonstatutory double patenting rejection.
(10) Claims 1, 5-6 and 8-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7-12, 14 and 16-17 of U.S. Patent No. 12,440,489 B2.
Claims 1, 7-12 and 14 of the ‘489 patent recites a method for the treatment of a CNS disorder comprising administering to a patient in need of such treatment the compound
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, in toluenesulfonic acid addition salt form, wherein the CNS disorder is, inter alia, opiate dependency, cocaine dependency, amphetamine dependency, alcohol dependency, substance addiction, substance use disorder or substance abuse disorder, wherein the patient is not response to, or cannot tolerate the side effects from, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) or antipsychotic agents. Claim 2 of the ‘489 patent defines the compound in the form of a pharmaceutical composition in admixture with a pharmaceutically acceptable diluent or carrier. Claim 3 of the ‘489 patent defines the diluent or carrier as a polymeric matrix, and claim 4 of the ‘489 patent defines the polymeric matrix as a biodegradable poly(d,l-lactide-co-glycolide) microsphere. Claim 16 of the ‘489 patent specifies that the patient is not responsive to, or cannot tolerate the side effects from, non-narcotic analgesics and/or opiate and opioid drugs, or wherein the use of opiate drugs are contraindicated in said patient due to prior substance abuse or high potential for substance abuse, and claim 17 of the ‘489 patent further defines the drugs as including, e.g., morphine, codeine, etc.
This is a nonprovisional nonstatutory double patenting rejection.
Conclusion
Rejection of claims 1, 5-6, 8-19 and 21-22 is proper.
Claims 3-4 and 7 are withdrawn from consideration pursuant to 37 C.F.R. 1.142(b).
No claims of the present application are allowed.
Applicant is requested to specifically point out the support for any amendments made to the disclosure in response to this Office action, including the claims (M.P.E.P. §§ 714.02 and 2163.06). In doing so, applicant is requested to refer to pages and line (or paragraph) numbers (if available) in the as-filed specification, not the published application. Due to the procedure outlined in M.P.E.P. § 2163.06 for interpreting claims, other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
Applicant is reminded that MPEP §2001.06(b) clearly states that “[t]he individuals covered by 37 C.F.R. 1.56 have a duty to bring to the attention of the examiner, or other Office official involved with the examination of a particular application, information within their knowledge as to other copending United States applications which are "material to patentability" of the application in question." See Armour & Co. v. Swift & Co., 466 F.2d 767, 779, 175 USPQ 70, 79 (7th Cir. 1972). MPEP §2001.06(b) clearly indicates that “if a particular inventor has different applications pending in which similar subject matter but patentably indistinct claims are present that fact must be disclosed to the examiner of each of the involved applications.” See Dayco Prod. Inc. v. Total Containment, Inc., 329 F.3d 1358, 1365-69, 66 USPQ2d 1801, 1806-08 (Fed. Cir. 2003).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Leslie A. Royds Draper whose telephone number is (571)272-6096. The examiner can normally be reached Tuesday to Thursday (08:30 AM to 05:00 PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S. Lundgren can be reached at (571)-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Leslie A. Royds Draper/Primary Examiner, Art Unit 1629
April 2, 2026
1 Applicant should note that the prior-filed provisional applications fail to provide adequate written support and/or enabling guidance as required under 35 U.S.C. §112(a) (pre-AIA first paragraph) to receive the benefit of an earlier filing date for the full scope of subject matter instantly claimed. As such, Applicant is not entitled to the benefit of the earlier filing dates of U.S. Provisional Patent Application Nos. 62/537,287, filed July 26, 2017, 62/639,244, filed March 6, 2018, or 62/682,546, filed June 8, 2018.
2 This is Applicant’s elected species of compound of formula (I) as identified in the response to restriction/election dated February 20, 2026.