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 .
Information Disclosure Statement
Applicant’s Information Disclosure Statement filed 04/02/2026, has been received and entered into the present application. As reflected by the attached, completed copies of form PTO-1449, the Examiner has considered the cited references to the extent that they comply with the provisions of 37 C.F.R. §1.97, §1.98 and MPEP §609.
Status of the Claims
Claims 19-51 are pending.
Applicants’ arguments, filed on 04/02/2026 and 05/26/2026, have been fully considered. Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Applicants’ amendments filed on 04/02/2026 and 05/26/2026, have been entered into the record. Applicants have amended claims 19 and 37. Applicants have newly added claims 41-51. Therefore, claims 19-51 are subject of the Office Action below.
Withdrawn Rejections
The provisional rejection of 19-40 on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent Application Nos: 1) 16/864,955; and 2) 18/418,121, is withdrawn because the Applicants have submitted a Terminal Disclaimer under 37 C.F.R. § 1:321(c) in the response filed on 04/02/2026.
The provisional rejection of 19-40 on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent Application Nos: 1) 17/430,033; 2) 17/579,135 and 3) 17/992,254, is withdrawn because the U.S. Patent Application Nos: 1) 17/430,033; 2) 17/579,135 and 3) 17/992,254, have been abandoned.
The rejection of 19-40 on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent Nos: 1) 11,406,606; 2) 10,950,331; 3) 11,571,397; 4) 11,759,440; 5) 11,786,487; and 6) 11,634,377, is withdrawn because the Applicants have submitted a Terminal Disclaimer under 37 C.F.R. § 1:321(c) in the response filed on 04/02/2026.
Maintained Rejections
Non-Statutory Double Patenting Rejection-Maintained
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The rejection of claims 19-40 is maintained and newly added claims41-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Application Nos: i) 17/289,125; and ii) 17/737,626, for the reasons of record set forth in the previous Office action.
Response to the Applicants’ Arguments
Applicants argue on the grounds that:
1) each of the U.S. Application Nos: i) 17/289,125; and ii) 17/737,626, has an earliest filing date than the instant application. Please see pages 15-16 of Remarks.
Response:
Applicants’ arguments have been fully considered but they are not found to be persuasive, because the provisional nonstatutory obviousness-type double patenting rejection is not the only rejection remaining in the instant application.
2) Applicants request that the obvious-type double patenting rejections be held in abeyance (see page 16 of Remarks).
Response:
Applicant’s comments are acknowledged, however the rejection will be maintained until a terminal disclaimer is filed or the claims are amended to obviate the rejections.
For the reasons made of record in the previous Office action, the rejections are maintained.
Claim Rejections - 35 USC § 103
Maintained/New Grounds of Rejections Necessitated by Applicants’ Claim Amendments
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.
The rejection of claims 19-35 and 37-40, is maintained and newly added claims 41-51 are rejected under 35 U.S.C. 103 as being unpatentable over Nieto-Barrera of record (Revista de neurologia, 2002, 35(1), S88-95, SciFinder Scholar Abstract Translation) in view of Ceulemans of record (Epilepsia, 2012, 53(7), 1131-1139), for the reasons of record set forth in the previous office action, of which said reasons are herein reiterated.
By way of a background, Applicants’ invention (e.g., see ¶s 0001, 0088, 0091 and 0095 of the specification), is directed to a method for treating seizures in a patient with Lennox-Gastaut syndrome (LGS), comprising administering a well-known therapeutic approach such as an anti-epileptic drug (AED, e.g., topiramate), and fenfluramine (FFA).
Under the broadest reasonable interpretation (BRI), consistent with the specification, independent claim 19 is being interpreted as a method for treating seizures in an LGS patient with an AED and from 0.2 mg/kg/day to 0.8 mg/kg/day up to a maximum of 30 mg/day, of FFA.
Similar to the Applicants’ invention (see discussions above), Nieto-Barrera (see abstract), teaches a method of using topiramate (TPM), in order to treat seizures including but not limited to generalized tonic clonic seizures, absence seizures, tonic seizures and myoclonic seizures, in patients with epileptic syndromes selected from the group that include LGS and Dravet syndrome (DS).
Although Nieto-Barrera teaches a method of using an AED (e.g., TPM), for treating seizures in patients with epileptic syndromes selected from the group that include LGS and DS (see discussions above), Nieto-Barrera differs from claim 19 only insofar as Nieto-Barrera is not explicit in teaching using TPM in combination with FFA.
However, a person skilled in the art would have had a reasonable expectation of success administrating an AED (e.g., TPM) and FFA, because it was well-known in the art to administer an AED (e.g., TPM) and FFA to an epileptic syndrome patient in order to treat seizures in the patient.
For example, similar to Nieto-Barrera (see discussions above), see Ceulemans, who treats seizures including, but not limited to atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures, in DS patients. Ceulemans also teaches a method for treating another severe form of epileptic seizures and the accompanying seizures in DS patients, using FFA in an amount ranging from 0.12 mg/kg/day to 0.9 mg/kg/day (see abstract), up to a maximum of 20 mg/day (see page 1138, 2nd ¶ on left column). Ceulemans states:
“…In the year before the start of fenfluramine treatment, all patients had generalized tonic–clonic seizures, and seven patients also had myoclonic seizures. Four patients had partial seizures, and four patients had atypical absence seizures. Five patients still had frequent status epilepticus episodes in the year before inclusion. Daily seizures were observed in two patients, weekly seizures in five patients, and monthly seizures in three patients. Two patients had only a few seizures per year.
……Fenfluramine was prescribed in rather small dosages, with a mean of 0.34 (0.12–0.90) mg/kg/day. In all patients, fenfluramine was combined with valproate. Nine patients received at least triple combination therapy. Six patients were treated with topiramate and benzodiazepines (clobazam, lorazepam, or ethyl loflazepate), two patients were treated with lamotrigine, and one patient was treated with levetiracetam and ethosuximide. Once the patients became seizure-free, the medication was no longer changed.” Ceulemans, page 1132, right column (emphasis added).
It is also noted that the specification (see ¶ 0079), also discloses different seizures in LGS including but not limited to atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures.
Regarding the claimed FFA dosage limitations (claims 19 and 43-49), it is noted that the specification (see ¶ 0010), discloses that FFA in an amount of from 0.5 mg/kg/day to 1 mg/kg/day, has been reported to reduce seizures in patients with refractory epilepsy. Applicants’ admissions also constitute as a prior art (see MPEP § 2129).
A prima facie case of obviousness exists in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" (see MPEP § 2144.05). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close (see MPEP § 2144.05). As recognized by MPEP § 2144.05.
In the instant case, because the claimed range of FFA recited in claims 19 and 43-49, overlaps or lies inside ranges disclosed by the prior art (see discussions above), a prima facie case of obviousness exists.
It is noted that no criticality has been demonstrated in the specification with regard the claimed range of FFA recited in claims 19 and 43-49.
Therefore, a person skilled in the art would have found it obvious to administer an AED (e.g., TPM) and FFA within the dosage limitations disclosed in Ceulemans, to an epileptic syndrome patient (e.g., an LGS patient). The skilled artisan would have had a reasonable expectation that the administration of the AED and FFA would treat seizures (e.g., atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures), in the patient.
The obviousness here is based on the fact that, at the time of the instant invention, it was known in the art that:
i) an AED (e.g., TPM) is a well-known therapeutic option for treating seizures in an epileptic syndrome patient, and an AED (e.g., TPM) and FFA can be used to treat seizures in DS and LGS patients (see discussions above).
ii) the claimed range of FFA recited in claims 19 and 43-49, overlaps or lies inside ranges disclosed by the prior art. Please see discussions above.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
A person skilled in the art would have considered administering an AED (e.g., TPM) and FFA, with a reasonable expectation that the combination therapy of the AED (e.g., TPM) would broaden the spectrum of activity and exhibit a greater therapeutic efficacy, when compared to a monotherapy of, for example, AED alone.
Therefore, claims 19 and 43-49 are obvious over Nieto-Barrera and Ceulemans.
Regarding claim 20, Ceulemans discloses, wherein patients were unresponsive to AED treatment and present multiple seizures prior to start of FFA treatment (see page 1132 and Table 1).
Regarding claims 21, 25-27, 35, 37 and 50-51, each of the recited AED and FFA administration schedule of, is a result-effective variable that would have been routinely determined and optimized by a person skilled in the art through test series.
MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality has been demonstrated in the specification with regard to the claimed AED and FFA administration schedules recited in claims 21, 25-27, 35, 37 and 50-51.
Regarding claims 21, 25, 30, 39-40 and 42, the cited references combine to disclose seizures including, but not limited to atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures (see discussions above).
Regarding claims 22-23 and 41, Ceulemans discloses valproate (see discussions above).
Regarding claims 24-25, Ceulemans discloses, wherein at least two different AEDs are administered (see discussions above).
Regarding claims 28-34, the recited intended outcomes of the method of claim 19 resulting in reducing seizure frequency (e.g., claim 28) or duration (e.g., claim 32) or severity (e.g., claim 34), is not given any patentable weight because the clauses are simply expressing the intended result of a process positively recited. Please see Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003). In the instant case, Nieto-Barrera and Ceulemans combine to teach a method of claim 19 (see discussions above).
Therefore, the method of Nieto-Barrera and Ceulemans must necessarily produce the same outcomes of recited in claims 28-34. This is because each of the outcomes recited in claims 28-34, is a natural process that flows from the patient and the administered AED and FFA of claim 19.
Regarding claim 38, Ceulemans (see page 1135 and Table 1), teaches use of EEG to evaluate epileptic activity and treatment effectiveness. Therefore, it would have been obvious to a person skilled in the art that diagnosing a patient in need of treatment for seizure, would have including use of EEG.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Response to Applicants’ Arguments/Remarks
Applicants raised several arguments (see pages 6-14 of Remarks filed on 04/02/2026), alleging that the claimed invention is non-obvious over the cited references because:
1) Applicants cite a list of case law citations therein (see pages 6-7 of Remarks).
Response:
Applicants’ response fails to link the legal concepts to the facts of the application under examination.
2) Applicants cite an expert declaration under 37 C.F.R. § 1.132, from Henrik Valdermar Klitgaard, Ph.D. (“Dr, Klitgaard’s Declaration”), submitted herewith (see pages 7-14 of remarks).
Response
A review of the Applicants’ submissions filed on 04/02/2026 and 05/26/2026, failed to reveal an expert declaration under 37 C.F.R. § 1.132, from Henrik Valdermar Klitgaard, Ph.D., on the record.
3) Nieto-Barrera does not disclose use of FFA for any epilepsy (see page 8 of Remarks).
Response:
The Office did not take a position that Nieto-Barrera discloses use of FFA for any epilepsy. The limitation of use of FFA for any epilepsy, was disclosed by Ceulemans (see discussions above).
4) Ceulemans does not teach or suggest use of FFA as an add-on treatment for LGS (see page 8 of Remarks).
Response:
Nieto-Barrera teaches a method of using an AED (e.g., TPM), for treating seizures in patients with epileptic syndromes selected from the group that include LGS and DS (see discussions above). Similar to Nieto-Barrera (see discussions above), see Ceulemans, who treats seizures including, but not limited to atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures, in DS patients. Ceulemans also teaches a method for treating another severe form of epileptic seizures and the accompanying seizures in DS patients, using FFA in an amount ranging from 0.12 mg/kg/day to 0.9 mg/kg/day (see abstract), up to a maximum of 20 mg/day (see page 1138, 2nd ¶ on left column). Ceulemans states:
“…In the year before the start of fenfluramine treatment, all patients had generalized tonic–clonic seizures, and seven patients also had myoclonic seizures. Four patients had partial seizures, and four patients had atypical absence seizures. Five patients still had frequent status epilepticus episodes in the year before inclusion. Daily seizures were observed in two patients, weekly seizures in five patients, and monthly seizures in three patients. Two patients had only a few seizures per year.
……Fenfluramine was prescribed in rather small dosages, with a mean of 0.34 (0.12–0.90) mg/kg/day. In all patients, fenfluramine was combined with valproate. Nine patients received at least triple combination therapy. Six patients were treated with topiramate and benzodiazepines (clobazam, lorazepam, or ethyl loflazepate), two patients were treated with lamotrigine, and one patient was treated with levetiracetam and ethosuximide. Once the patients became seizure-free, the medication was no longer changed.” Ceulemans, page 1132, right column (emphasis added).
Therefore, a person skilled in the art would have found it obvious to administer an AED (e.g., TPM) and FFA within the dosage limitations disclosed in Ceulemans, to an epileptic syndrome patient (e.g., an LGS patient). The skilled artisan would have had a reasonable expectation that the administration of the AED and FFA would treat seizures (e.g., atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures), in the patient.
The obviousness here is based on the fact that, at the time of the instant invention, it was known in the art that:
i) an AED (e.g., TPM) is a well-known therapeutic option for treating seizures in an epileptic syndrome patient, and an AED (e.g., TPM) and FFA can be used to treat seizures in DS and LGS patients (see discussions above).
ii) the claimed range of FFA recited in claims 19 and 43-49, overlaps or lies inside ranges disclosed by the prior art. Please see discussions above.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
A person skilled in the art would have considered administering an AED (e.g., TPM) and FFA, with a reasonable expectation that the combination therapy of the AED (e.g., TPM) would broaden the spectrum of activity and exhibit a greater therapeutic efficacy, when compared to a monotherapy of, for example, AED alone.
The rejection of claims 19 and 36 under 35 U.S.C. 103 as being unpatentable over Nieto-Barrera of record and Ceulemans of record, as applied to claim 19 above and further in view of Ceulemens2014 of record (U.S. Pub. No. 20140343162), is maintained for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
The limitation of claim 19 as well as the corresponding teachings of Nieto-Barrera and Ceulemans, are discussed above and hereby incorporated into the instant rejection.
The invention of claims 36 is similar to claim 19, however, claims 36 differs slightly from claim 19 in that claim 36 requires FFA in the form of a liquid formulation.
Although the cited references do not combine to explicitly teach the limitation of claim 36, it would have been obvious for a skilled artisan to formulate FFA in the form of a liquid formulation. This is because at the time of the instant invention, it was known in the art that FFA can be formulated in the form of a liquid formulation.
For example, Ceulemens2014 teaches that the dose of FFA administered can be formulated in any pharmaceutically acceptable oral dosage form including, but not limited to a liquid (see ¶ 0056). Ceulemens2014 also relates to a method of using FFA for treating seizure in a patient diagnosed with DS (see abstract and ¶ 0043). FFA can be administered as a monotherapy and alternatively, FFA can be administered with a co-therapeutic agent such as topiramate (see ¶ 0058).
At the time of the filing, one skilled in the art would have found it obvious to formulate FFA in any pharmaceutically acceptable dosage form including, but not limited to a liquid. The person skilled in the art would have had a reasonable expectation that the administration of an AED (e.g., TPM) and a liquid form of FFA to a patient in need of treatment for a seizure disorder, would treat the seizure in the patient.
A person skilled in the art would have considered administering an AED (e.g., TPM) and FFA, with a reasonable expectation that the combination therapy of the AED (e.g., TPM) would broaden the spectrum of activity and exhibit a greater therapeutic efficacy, when compared to a monotherapy of, for example, AED alone.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Response to Applicants’ Arguments/Remarks
Applicants argue on the grounds of what appears to be the Applicants’ position that because claim 19 is allegedly non-obvious over Nieto-Barrera and Ceulemans, Ceulemens2014 cannot be employed in order to address the deficiency in the teachings of Nieto-Barrera and Ceulemans (see pages 14-15 of Remarks).
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive.
This is because the Applicants’ allegations that instant 19 is allegedly non-obvious over Nieto-Barrera and Ceulemans, are similar to the arguments above, which have been addressed in the discussions above. The Examiner, therefore, applies the same reasons hereto. Therefore, the use of Ceulemens2014 in order to address the deficiency in the teachings of Nieto-Barrera and Ceulemans, is proper.
For the reasons above, and those made of record in the previous Office action, the rejections are maintained.
Conclusion
No claim is allowable.
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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Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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