DETAILED ACTION
Claims 1-8, 15, 17, 19, 25, 27, 30, 39-41, 43, 48, 51 and 54-55 are currently pending in the instant application.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to claims 1-8, 15, 39-41, 43, 48, 51 and 54-55 and election of species
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in the reply filed on 09/15/2025 is acknowledged.
Claims 17, 19, 25, 27, 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/15/2025.
In accordance with the MPEP, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species and the claims drawn to the elected species are allowable, the search of the Markush-type claim will be extended (see MPEP 803.02). If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Id.
Applicants' elected species of
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does not appear allowable, therefore the search and examination of the claims has not been extended beyond the elected species (see the following 35 USC 103(a) rejection). However during the search of the species, the Examiner has identified additional art relevant to the claims as discussed below.
Priority
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Information Disclosure Statement
Applicant's Information Disclosure Statements filed on 05/03/2022, 08/22/2023, 08/24/2023, 11/03/2023, 02/05/2024, 02/19/2024, 04/17/2024, 06/11/2024, 07/08/2024, 12/03/2024, 01/21/2025, 06/30/2025, 09/16/2025 and 10/02/2025 have been considered. Please refer to Applicant's copies of the 1449 submitted herewith.
Improper Markush Rejection
Claims 1-8 and 15 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of a compound of formula (1a), (1b) and (1c) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
It cannot be said that all members of the Markush group have a single structural similarity. Specifically, the species of the Markush group do not share a “single structural similarity” because there are no required structural features in common such that each member of formula I would have at least one structural feature, which feature is essential to the activity/function of the claimed compounds. The variables X1, X2, X3, X4, X5, Y1, Y2, R1, R2, L in compound of formula (1a), and A1, A2, A3, Z1, Z3, Z4, Z5, R5, R6 in a compound of formula (1b) and R13 in a compound of formula (1c) prevent the core structure from being an art-recognized physical or chemical class.
For example, X1, X2, X3, X4 and X5 are independently -C, -N, -S or -O wherein at least two of X1, X2, X3, X4 and X5 are -N while Y1 and Y2 are independently -C or -N. Within the compound of formula (Ia), R1 can be selected from a variety of variables, including unsubstituted phenyl, a phenyl substituted with C1-C4 alkyl, F, Cl, Br, I, -CN, a substituted or unsubstituted biphenyl or -(C═O)-R3, wherein R3 is a substituted or unsubstituted aryl or 5- to 6-membered heteroaryl, R2 is independently a substituted or unsubstituted C3-C8 cycloalkyl, a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C1-C6 alcohol, a substituted or unsubstituted 6-membered heteroaryl, a halogen, or -O-CH2-R4, wherein R4 is a substituted or unsubstituted 5- or 6-membered heteroaryl. Further, Z1, Z3, Z4, and Z5 are independently -C, -N, -S or -O, A1, and A2 and A3, are independently -C, -N, or -C(C═O)-O-R7, or
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where B1, B2, B3 or B4 also have multiple definitions. Additionally, R13 is independently a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted C1-C3 alkyl, oxygen or hydrogen. As a result, each of these 3 formulas encompass numerous structures and there is no substantial core structure that is shared by all species within Formula (Ia), (Ib) and (Ic). In fact, Formula (Ia), (Ib) and (Ic) is drawn to multiple core structures and claims a variety of species that are structurally distinct due to their unique core structures.
In addition, each alternatively usable member of the Markush group does not share a common use. Rather, the specification discloses that the compounds treat epilepsy. However, there is no common core in the compounds of formula (1a), (1b) and (1c) that is known to impart the activity of treating epilepsy. It is suggested that applicant amend the claims to contain only proper Markush groupings to compounds sharing a single structural similarity and a common use, wherein the common use shared by the compounds is a result of the structural similarity essential to the function of the compounds.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims1-8, 15, 39-41, 43, 48, 51 and 54-55 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by TOCZKO (see WIPO Pub No. 2021081147, pub. 04/29/2021 which claims priority to US Prov. Appl. No. 62/924,276, filed 10/22/2019).
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
TOCZKO teaches salts and polymorphs of 2’,6-difluoro-5’-[3-(1-hydroxy-1-methylethyl)-imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile, including crystalline form of the sulfate sate of said compound:
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(see paragraph [0004]). Further crystalline forms of the free base, bromide, tosylate, phosphate are taught (see Fig. 49-58) with phosphate form A having XRPD patterns corresponding to those of claim 43 (see paragraph [0088]). This compound is taught to be used in composition for treating epilepsy, including Focal epilepsy, Generalized epilepsy, Dravet Syndrome, Childhood absence epilepsy (CEA), Juvenile absence epilepsy, Juvenile myoclonic epilepsy (JME), West Syndrome, Lennox-Gastaut syndrome (LGS), Sunflower Syndrome, Status epilepticus, Nerve agent induced seizures, Tremors from alcohol withdrawal, Traumatic Brain Injury, Tuberous Sclerosis Complex, Doose Syndrome, Rasmussen’s Syndrome, Early myoclonic encephalopathy (see paragraph [0012]). TOCZKO teaches dosing of the phosphate polymorphic form A in 1 mg/kg (see Examples 17-18).
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.
Claim(s) 1-8 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over BETTATI (see WO 2002/038568, filed 11/08/2001 and pub. 05/16/2002, cited in IDS filed 12/03/2024) as applied to claims 1-8, 15 above, and further in view of Greenfield (see Seizure, Vol. 22, 2013, p. 589-600) and CATTERALL (see US Pub. No. 2015/0313913, pub. 11/05/2015, cited in IDS filed 05/03/2022).
BETTATI teaches compounds of formula
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with compound
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(see p. 19, 1st compound) which corresponds to the elected species taught. BETTATI teaches the compounds as GABAA receptor subtype binding for the α2, α3, or α5 subunit (see p. 4-5) and in a method for treatment and/or prevention in a patient suffering from epilepsy or a related disorder by administering a compound, pharmaceutically acceptable salt or prodrug thereof (see p. 24, lines 20-25). BETTATI teaches the limitations of claim 1 except BETTATI does not name the specific epileptic conditions such as generalized epilepsy, etc of claim 1.
Greenfield teaches that most agents that enhance GABAA receptor function have antiseizure properties due to their ability to increase inhibitory neurotransmitter tone. Several animal models of epilepsy have altered GABAA receptor number or function (see p. 589). Further, GABAAR subunit expression is altered in patients with temporal lobe epilepsy. GABAAR modulation by GABAergic ASDs is likely critical to their antiseizure activity (see p. 589, 2nd column). CATTERALL teaches compounds as selective modulators of α2, α3, and/or α5 subtypes of GABA-A receptor (See paragraph [0151], p. 11) and said compounds can be used as anticonvulsants for treatment of epilepsy and epilepsy associated disorders, including Lennox-Gastaut syndrome, Dravet’s disease and generalized epilepsy with febrile seizures (see paragraph [0158], p. 12).
Thus, it would be obvious to one of ordinary skill in the art that the compounds of BETTATI taught to treat epilepsy and have good affinity as ligands for the α2 and/or α3 subunit of the human GABAA receptor. Although BETTATI does not name specific epileptic conditions, Greenfield and CATTERALL teach compounds acting on GABAA receptors, specifically those which act as selective modulators of α2, α3 subtypes of GABA-A receptor, the same activity as the compounds of BETTATI, are useful in treatment of temporal lobe epilepsy, Dravet’s disease and generalized epilepsy.
Further, in regards to claim 2, artisans of ordinary skill may not recognize inherent characteristics or functioning of the prior art. However, the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer. See Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347-49 (Fed. Cir. 1999); accord Toro Co. v. Deere & Co., 355 F.3d 1313, 1320-21 (Fed. Cir. 2004). However, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. Although the prior art is silent regarding if the epileptic condition is epilepsy associated with a mutation in a sodium channel by practicing the method made obvious by the prior art: "A method of treating an epileptic condition in a subject comprising administering a therapeutically effective amount of a compound ", one will also be meeting the limitations of "the epilepsy associated with a mutation in a sodium channel”, even though the prior art was silent as to these parameters. MPEP 2145 II states: "The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art, cannot be the basis for patentability when the differences would otherwise be obvious". Ex parte Obiaya, 227 USPQ 58, 60. (FP 7.37.07, MPEP 707.07(f)).
Claims 39-41, 51 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over BETTATI (see WO 2002/038568, filed 11/08/2001 and pub. 05/16/2002, cited in IDS filed 12/03/2024). Regarding treating an epileptic condition using the compound of claims 39-40, these limitations are taught by BETTATI as discussed above. Regarding the limitations of the dosage of the compound administered found in claims 39-40, BETTATI teaches that a suitable dosage level is about 0.01 to 250 mg/kg per day (see p. 10). According to MPEP 2144.05, Section II, “[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.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Thus, given that BETTATI teaches suitable dosing for the compound, one of ordinary skill in the art would have a starting point upon which to vary the dosage of the compound in order to attain treatment of the epileptic condition.
Regarding pharmaceutically acceptable salts, BETTATI teaches such salt may be formed by mixing a solution of the compound with solution of pharmaceutically acceptable acid such as sulphuric acid, phosphoric acid (see p. 6, lines 1-5). When a person of ordinary skill is faced with “a finite number of identified, predictable solutions” to a problem and pursues “the known options within his or her technical grasp,” the resulting discovery “is likely the product not of innovation but of ordinary skill and common sense.” KSR, 127 S. Ct. at 1742. So too, “[g]ranting patent protection to advances that would occur in the ordinary course without real innovation retards progress.” Id. at 1741. Thus since BETTATI teaches compounds in treatment of epilepsy and pharmaceutically acceptable addition salts, including phosphate and sulfate and how to form said salt, the art of BETTATI renders claim 41 obvious.
Claim(s) 40, 48 and 54 is/are rejected under 35 U.S.C. 103 as being unpatentable over BETTATI (see WO 2002/038568, filed 11/08/2001 and pub. 05/16/2002, cited in IDS filed 12/03/2024) further in view of Greenfield (see Seizure, Vol. 22, 2013, p. 589-600) and CATTERALL (see US Pub. No. 2015/0313913, pub. 11/05/2015, cited in IDS filed 05/03/2022).
The limitations of claim 40 are discussed above. Regarding the limitations of claim 48 and 54, directed towards specific epileptic conditions being treated by the elected species, this is discussed in the rejection of claim 1 above.
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 1-8, 15, 39-41, 43, 48, 51 and 54-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-7, 12-14-16, 18, 20, 22, 24, 26-27, 29-33 of copending Application No. 17/770, 928 (hereafter referred to as ‘928) in view of Greenfield (see Seizure, Vol. 22, 2013, p. 589-600) and CATTERALL (see US Pub. No. 2015/0313913, pub. 11/05/2015, cited in IDS filed 05/03/2022). ‘928 teaches crystalline form of compound
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and salts thereof and method of treating condition or disorder associated with GABA receptors, specifically a2/a3 GABAA receptor wherein the condition is selected from epilepsies. Although ‘928 does not disclose the specific epilepsy, Greenfield teaches that most agents that enhance GABAA receptor function have antiseizure properties due to their ability to increase inhibitory neurotransmitter tone. Several animal models of epilepsy have altered GABAA receptor number or function (see p. 589). Further, GABAAR subunit expression is altered in patients with temporal lobe epilepsy. GABAAR modulation by GABAergic ASDs is likely critical to their antiseizure activity (see p. 589, 2nd column). CATTERALL teaches compounds as selective modulators of α2, α3, and/or α5 subtypes of GABA-A receptor (See paragraph [0151], p. 11) and said compounds can be used as anticonvulsants for treatment of epilepsy and epilepsy associated disorders, including Lennox-Gastaut syndrome, Dravet’s disease and generalized epilepsy with febrile seizures (see paragraph [0158], p. 12).
Thus, it would be obvious to one of ordinary skill in the art that the compounds of ‘928 taught to treat epilepsy and have good affinity as ligands for the α2 and/or α3 subunit of the human GABAA receptor to treat specific types of epilepsy such as temporal lobe epilepsy, Dravet’s disease and generalized epilepsy as taught by Greenfield and CATTERALL.
Regarding dosing, it would be obvious to one of ordinary skill in the art to optimize the dosing using starting parameters such as found in TOCZKO (see WIPO Pub No. 2021081147, pub. 04/29/2021 which claims priority to US Prov. Appl. No. 62/924,276, filed 10/22/2019) regarding the dosing. Also see MPEP 2144.05, Section II, “[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.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
This is a provisional nonstatutory double patenting rejection.
Claims 1-8, 15, 39-41, 48, 51 and 54-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4-12, 18-19 of copending Application No. 18/089,661 (hereafter referred to as ‘661). ‘661 teaches a method for modulating a2/a3 GABAA receptor activity by administering a compound of
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to treat epilepsy, including generalized epilepsy, juvenile myoclonic epilepsy, etc (see claim 19). Regarding dosing, it would be obvious to one of ordinary skill in the art to optimize the dosing using starting parameters such as found in TOCZKO (see WIPO Pub No. 2021081147, pub. 04/29/2021 which claims priority to US Prov. Appl. No. 62/924,276, filed 10/22/2019). Also see MPEP 2144.05, Section II, “[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.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN CHENG whose telephone number is (703)756-4699. The examiner can normally be reached M-F, 9AM-6PM PST.
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/KAREN CHENG/Primary Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623