DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
This office action is in reply to Applicant’s Arguments/Remarks filed on 04/21/2026. This application 18/524,124 was filed on 11/30/2023, with PRO 63/589,283 filed on 10/10/2023 and PRO 63/429,755 filed on 12/02/2022. Claims 54-55, 64-65, and 67-69 are cancelled. Claims 52, 57-63, and 71 are amended. Claims 72-81 are new claims. Claims 52-53, 56-63, 66, and 70-81 are pending in the application. Claims 52- 53, 56-63, 66, and 70-81 are rejected.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/21/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
WITHDRAWN OBJECTIONS
The examiner withdraws the objections to claims 58, 60, 61, and 71 based on the Applicant’s amendments.
WITHDRAWN REJECTIONS
The examiner withdraws rejections to claims 54-55, 64-65, and 67-69 under 35 U.S.C. 112(a) and 35 U.S.C. 102 because the claims were cancelled by Applicant.
The examiner additionally withdraws rejections to claims 52-71 under 35 U.S.C. 112(a) based on the remarks and amendments to the claims made by Applicant.
The examiner further withdraws rejections to claim 60 under 35 U.S.C. 112(b) because the claim was amended by Applicant.
The rejection of Claims 52-53, 57-63, 66, and 70-81 under 35 U.S.C. 102(a)(1) as being anticipated by Ren et al. WO 2016/176177 (“Ren”; Published: November 3, 2016 and filed on April 26, 2016; IDS submitted on March 13, 2024) is withdrawn in light of Applicant’s claim amendments to require twice daily administration of a dosage equivalent range of about 9 mg/dose to about 24 mg/dose of Compound 1.
MAINTAINED AND/OR MODIFIED REJECTIONS
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:
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.
Claims 52-53, 56-63, 66, and 70-81 are rejected under 35 U.S.C. 103 as being unpatentable over Ren (Ren et al. WO 2016/176177 (5-HT2C Receptor Agonists and Compositions and Methods of Use Published: 11/03/2016) in view of Longboard Pharmaceuticals (Longboard Pharmaceuticals, Inc. Annual Report:2021 (December 31, 2021 SEC Filing).
Regarding claim 52, Ren teaches a method of treating preventing a 5-hydroxytryptamine (HT)2c receptor- associated disorder in a patient in need thereof (Pg. 38, lines: 23, 24). Ren further teaches wherein the method comprises administering to the patient (R)-N-(2,2-difluoroethyl)-7-methyl-1,2,3,4,6,7-hexahydro- [1,4] diazepino[6,7,1-hi] indole-8-carboxamide (Applicant’s Compound 1), or a pharmaceutically acceptable salt thereof (Pg. 97, Claim 1, Ren’s Compound No. 3; Claim 2 on page 99; Claim 24 on page 104), wherein Applicant’s Compound 1/Ren’s Compound 3, or a pharmaceutically acceptable salt thereof, is administered as two, three, four, or more sub-doses per day (Pg. 76, lines: 24,25). Ren further teaches representative doses include, but are not limited to, about 0.001 mg to about 5000 mg, narrowing it down to 0.001 mg to about 25 mg (Pg. 75, lines 34-37) that encompasses the recited dosage equivalent range of about 9 mg/dose to about 24 mg/dose of Applicant’s Compound 1
Although Ren may not explicitly indicate Compound 3 of Ren’s claim 1 is used as a treatment of a 5-hydroxytryptamine (HT)2c receptor- associated disorder such as seizure disorder, Ren’s claim 24 does indicate using one of the nine compounds recited in Ren’s claim 1 to treat seizure disorders. One of ordinary skill in the art would have at once envisaged selection of Compound 3 for the treatment of a seizure disorder because it is one of only nine specific compounds recited in Ren’s claim 1 (see In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962) and In re Schauman, 572 F.2d 312, 197 USPQ 5 (CCPA 1978)).
Furthermore, with regards to the dosage equivalent to from about 9 mg/dose to about 24 mg/dose of Compound 1, although Ren may not explicitly indicate this particular dosage amount, Ren teaches a range that encompasses Applicant’s range. The optimization of known percent amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences and a person of ordinary skill in the art would have been motivated with a reasonable expectation of success to identify the dosages with Ren’s range that provided the best clinical outcomes to patients suffering from various seizure disorders and would, thus, have arrived at Applicant’s range after partaking in routine optimization of a results effective parameter, such as the dosage of an active pharmaceutical ingredient. It has been held that the selection of optimal parameters, such as amounts of active agents, 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) and MPEP 2144.05. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II). The Examiner also notes that Applicant has not demonstrated that the particular dosage range is critical or leads to unexpected results.
Regarding claim 53, Ren teaches the method of claim 52, wherein the 5-hydroxytryptamine (HT)2c receptor- associated disorder is epilepsy (Pg. 38, lines: 37-38- the 5-HT2c receptor agonists such as compound 1 are useful for the treatment of epilepsy).
Regarding claim 57, Ren teaches or a method of treating a seizure disorder in a patient in need thereof (Pg. 38, lines: 23, 24). Ren further teaches wherein the method comprises administering to the patient (R)-N-(2,2-difluoroethyl)-7-methyl-1,2,3,4,6,7-hexahydro- [1,4] diazepino[6,7,1-hi] indole-8-carboxamide (Applicant’s Compound 1), or a pharmaceutically acceptable salt thereof (Pg. 97, Claim 1, Ren’s Compound No. 3; Claim 2 on page 99; Claim 24 on page 104), wherein Applicant’s Compound 1/Ren’s Compound 3, or a pharmaceutically acceptable salt thereof, is administered as two, three, four, or more sub-doses per day (Pg. 76, lines: 24,25). Ren further teaches representative doses include, but are not limited to, about 0.001 mg to about 5000 mg, narrowing it down to 0.001 mg to about 25 mg (Pg. 75, lines 34-37) that anticipates the claimed dosage range.
Although Ren may not explicitly indicate Compound 3 of Ren’s claim 1 is used as a treatment of a seizure disorder, Ren’s claim 24 does indicate using one of the nine compounds recited in Ren’s claim 1 to treat seizure disorders. One of ordinary skill in the art would have at once envisaged selection of Compound 3 for the treatment of a seizure disorder because it is one of only nine specific compounds recited in Ren’s claim 1 (see In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962) and In re Schauman, 572 F.2d 312, 197 USPQ 5 (CCPA 1978)).
Furthermore, with regards to the dosage equivalent to from 9 mg/dose to about 24 mg/dose of Compound 1, although Ren may not explicitly indicate this particular dosage amount. However, the optimization of known percent amounts for known active agents 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, such as amounts of active agents, 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) and MPEP 2144.05. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
Regarding claim 58, Ren teaches a method of claim 57, wherein seizure disorder is epilepsy or Dravet syndrome (claim 25, Claim 26, page 104). Ren further teaches wherein the method comprises administering to the patient (R)-N-(2,2-difluoroethyl)-7-methyl-1,2,3,4,6,7-hexahydro- [1,4] diazepino[6,7,1-hi] indole-8-carboxamide (Applicant’s Compound 1), or a pharmaceutically acceptable salt thereof (Pg. 97, Claim 1, Ren’s Compound No. 3; Claim 2 on page 99; Claim 24 on page 104), wherein Applicant’s Compound 1/Ren’s Compound 3, or a pharmaceutically acceptable salt thereof, is administered as two, three, four, or more sub-doses per day (Pg. 76, lines: 24,25).
Although Ren may not explicitly indicate Compound 3 of Ren’s claim 1 is used as a treatment of these specific seizure disorders, Ren’s claim 24 does indicate using one of the nine compounds recited in Ren’s claim 1 to treat seizure disorders. One of ordinary skill in the art would have at once envisaged selection of Compound 3 for the treatment of a seizure disorder because it is one of only nine specific compounds recited in Ren’s claim 1 (see In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962) and In re Schauman, 572 F.2d 312, 197 USPQ 5 (CCPA 1978)),
Regarding claim 59, Ren teaches a method of treating or preventing developmental and epileptic encephalopathy (DEE) in a patient in need thereof (Pg. 38 line 38 to Pg. 39, line 10, 5HT2C receptor agonists such as compounds provided herein, are useful for treatment of infantile spasms, childhood epilepsy, as well as others listed), wherein the method comprises administering to the patient (R)-N-(2,2-difluoroethyl)-7-methyl-1,2,3,4,6,7-hexahydro-[1,4]diazepino[6,7,1- hi]indole-8-carboxamide (Compound 1), or a pharmaceutically acceptable salt thereof, wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered twice daily (Pg. 76, lines: 24, 25). Ren further teaches representative doses include, but are not limited to, about 0.001 mg to about 5000 mg, narrowing it down to 0.001 mg to about 25 mg (Pg. 75, lines 34-37) that anticipates the claimed dosage range.
Although Ren may not explicitly indicate Compound 3 of Ren’s claim 1 is used as a treatment of a 5-hydroxytryptamine (HT)2c receptor- associated disorder such as DEE, Ren’s claim 24 does indicate using one of the nine compounds recited in Ren’s claim 1 to treat seizure disorders. One of ordinary skill in the art would have at once envisaged selection of Compound 3 for the treatment of a seizure disorder because it is one of only nine specific compounds recited in Ren’s claim 1 (see In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962) and In re Schauman, 572 F.2d 312, 197 USPQ 5 (CCPA 1978)).
Furthermore, with regards to the dosage equivalent to from 9 mg/dose to about 24 mg/dose of Compound 1, although Ren may not explicitly indicate this particular dosage amount. However, the optimization of known percent amounts for known active agents 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, such as amounts of active agents, 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) and MPEP 2144.05. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
Regarding claim 60, Ren teaches the method of claim 59, wherein the DEE is selected from Lennox-Gastaut syndrome (Pg. 39, line 20), Dravet syndrome (Pg. 39, line 10 and pg. 104, claim 26), Doose syndrome (EM AS), West syndrome (infantile spasms (Pg. 39, line 3), Landau-Kleffner syndrome, and genetic disorders such as CDKL5 encephalopathy (CDK5L deficiency disorder) or CHD2 encephalopathy (each sections cited states that 5HT2C receptor agonists such as the compounds taught by Ren are useful for the treatment).
Regarding claim 61, Ren teaches the method of claim 60, wherein the DEE is selected from Ohtahara syndrome (EIDEE), Lennox-Gastaut syndrome (Pg. 39, line 20) , Dravet syndrome (Pg. 39, line 10 and pg. 104, claim 26), Doose syndrome (EM AS), West syndrome (infantile spasms (Pg. 39, line 3), Landau-Kleffner syndrome, tuberous sclerosis complex,CDKL5 encephalopathy (CDKL5 deficiency disorder), dup15q syndrome, SCN2A related epilepsies, SCN8A related epilepsies, KCNQ2 related epilepsies, KCNQ3 related epilepsies, Angelman syndrome, KCNT1 related epilepsies, SynGAPI related epilepsies, Rett syndrome, PCDH19 epilepsy, ring 14 syndrome, ring 20 syndrome, CHD2 encephalopathy, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, and epileptic encephalopathy with continuous spike-wave (each sections cited states that 5HT2C receptor agonists such as the compounds taught by Ren are useful for the treatment).
Regarding claim 62 and 63 Ren teaches the method of claim 52, wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered in a dosage equivalent to about 9 mg/dose of Compound 1, about 12 mg/dose of Compound 1, about 15 mg/dose of Compound 1, about 18 mg/dose of Compound 1, about 24 mg/dose of Compound 1 (Pg. 75, lines: 29-31 and 35-37; range of dosages). Ren further teaches representative doses include, but are not limited to, about 0.001 mg to about 5000 mg, narrowing it down to 0.001 mg to about 25 mg (Pg. 75, lines 34-37) that anticipates the claimed dosage range.
Furthermore, with regards to the dosage equivalent to from 9 mg/dose to about 24 mg/dose of Compound 1, although Ren may not explicitly indicate this particular dosage amount. However, the optimization of known percent amounts for known active agents 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, such as amounts of active agents, 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) and MPEP 2144.05. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
Regarding claims 66, Ren teaches the method of claim 52, wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered via a titration scheme that comprises the up-titration of Compound 1, or a pharmaceutically acceptable salt thereof, until an optimized dosage is administered (Pg. 76, lines: 29; optimized dosage, deviate upward).
Regarding claims 70, Ren teaches the method of claim 52, wherein the Compound 1, or a pharmaceutically acceptable salt thereof, is an HCl salt of Compound 1 (Pg. 79, lines: 25-28; pharmaceutically acceptable acid addition salts prepared from pharmaceutically acceptable non-toxic acids including but not limited to hydrochloric acid).
Regarding claim 71, Ren teaches the method of claim 52 as discussed above. Additionally, given that claim 52 is directed towards treating or preventing a disorder and the qEEG results and their formats are not material to the administration of the treatment. Thus, the assessments to determine efficacy and its associated ranges would be an inherent part of the treating or preventing process. Thus, Ren’s treatment or prevention of seizure disorders would necessarily result in a ratio of a geometric mean steady-state Ctrough of Compound 1 in cerebrospinal fluid (CSF) to a geometric mean steady- state Ctrough of Compound 1 in plasma (CSF/P Ctrough) of at least about 1.4.
Regarding claims 72-81, Ren teaches the method of claim 52, 57 and 59 respectively, wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered in a dosage equivalent to about 9 mg/dose of Compound 1, about 12 mg/dose of Compound 1, about 15 mg/dose of Compound 1, about 18 mg/dose of Compound 1, about 24 mg/dose of Compound 1 (Pg. 75, lines: 29-31 and 35-37; range of dosages). Ren further teaches representative doses include, but are not limited to, about 0.001 mg to about 5000 mg, narrowing it down to 0.001 mg to about 25 mg (Pg. 75, lines 34-37) that anticipates the claimed dosage range.
Furthermore, with regards to the dosage equivalent to from 9 mg/dose, 12 mg/dose, 15 mg/dose, 18 mg/dose to about 24 mg/dose of Compound 1, although Ren may not explicitly indicate these particular dosage amounts. However, the optimization of known percent amounts for known active agents 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, such as amounts of active agents, 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) and MPEP 2144.05. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
As to claim 56, Ren teaches the method of claim 53 as discussed above.
However, Ren does not explicitly indicate wherein the epilepsy is a refractory epilepsy. Longboard Pharmaceuticals teaches wherein the epilepsy is a refractory epilepsy (Pg. 3, Part I, Item 1. LP352-LP359 is a 5HT2C super agonist used to treat seizures associated with different types of epilepsy including a group of severe early-childhood onset epilepsies characterized by refractory seizures and developmental delay and/or regression).
It would have been obvious to one of ordinary skill in the art before the effective filing date to incorporate the teachings of Longboard Pharmaceuticals into those of Ren in order to overcome known or perceived safety limitations of available drugs in the 5HT2C class.
Response to Arguments
The Remarks of April 21, 2026 have been fully considered but are not fully persuasive for the reasons below.
Applicant’s Argument:
Applicant argues in substance that Ren and Longboard do not teach or disclose “administration of (i) Compound 1, (ii) twice daily, in (iii) a dosage equivalent to about 9-24 mg/dose of Compound 1” (see remarks page 4).
Examiner’s Response:
The examiner appreciates Applicant’s arguments; however, respectively disagrees. At the onset, the proper scope of the claim should be realized. The claim recites the dosage is equivalent “to from about 9mg/dose to about 24mg/dose”. The term “about” is broad and suggests that the dosage need not be exactly 9mg/dose to 24mg/dose. Additionally, applicant hasn’t provided a threshold for how broad of a range the term “about” is meant to cover (i.e., Applicant has not defined “about”). Nevertheless, the claim recites a range within which a dosage should fall and that Compound 1 must be administered twice daily. Ren explicitly teaches on page 76 that Compound 1 can be administered twice daily. Furthermore, Ren teaches representative doses can include 0.001 mg to about 25 mg (Pg. 75, lines 34-37). It has also been held that optimization of known percent amounts for known active agents 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, such as amounts of active agents, 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) and MPEP 2144.05. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II). Ren explicitly discusses that dosage when using Compound 1 can vary within a wide limit but that is customary. A physician tailors the dosage to the individual based on the conditions of the individual case depending on nature and severity of the illness (Ren page 75, line 29-31). Thus, the examiner respectfully maintains that Ren teaches the scope of the limitations as currently claimed.
As per applicant’s arguments regarding Longboard, the examiner did not rely upon Longboard to teach the subject matter argued by applicant. Examiner maintains that Ren teaches administering Compound 1 twice daily in a dosage outlined in the claims.
Conclusion
No claims are allowed.
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office Action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/SAHAR INAM/
Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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