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
The information disclosure statement (IDS) submitted on 08/07/2025, have been received and entered into the instant application. As reflected by the attached, completed copies of form PTO-1449, the Examiner has considered the cited reference 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 19-43 are pending.
Applicants’ arguments, filed 08/07/2025, 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 Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn.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 08/07/2025, have each been entered into the record. Applicants have amended claim 41. Applicants have newly added claim 43. Therefore, claims 19-43 are subject of the Office action below.
Withdrawn Rejections:
The rejection of 19-42 on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. patent application Nos: 1) 16/864,955; 2) 18/418,133; and 3) 12/144,787 (U.S. Application No. 17/289,125), is withdrawn because:
i) the Applicants have submitted a Terminal Disclaimer under 35 C.F.R. § 1:321(c) in the reply filed on 08/07/2025. Please note that the Terminal Disclaimer is effective with respect to all claims in the instant application. See MPEP § 804.02.
ii) Applicants argue on the grounds that the ‘787 patent claims a method for treating Rhett syndrome, whereas, the instant application claims a method for treating LGS, and the ‘787 patent specification fails to disclose use of FFA for treating LGS (see page 18 of Remarks).
The provisional rejection of claims 19-42 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being unpatentable over claims of U.S. patent application Nos: 1) 17/430,033; 2) 17/579,135; and 3) 6) 17/992,254, is withdrawn because U.S. patent application Nos: 1) 17/430,033; 2) 17/579,135; and 3) 6) 17/992,254, have been abandoned.
Maintained Rejections:
Claim Rejections - 35 USC § 103-Maintained
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 19-21, 24-30, 33-36 and 38-42, is maintained and newly added claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Gastaut of record (J. Autism and Developmental Disorders, 1987) in view of Ceulemans of record (Epilepsia, 2012), for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
Independent claim 19 is drawn to a method of preventing or reducing seizures in a patient suffering from Lennox-Gastaut syndrome (LGS), with an oral dose of fenfluramine (FFA), in an amount ranging from 0.2 mg/kg/day to 0.8 mg/kg/day up to a maximum of 30 mg/day, wherein the selected from the group consisting of generalized tonic-clonic seizures (GTC), atonic seizures, tonic seizures and combinations thereof.
Regarding claim 19, Gastaut teaches a method of reducing tonic seizures (case 6) and intractable seizures (case 7), in LGS patients, using 1.5 mg/kg/day of oral FFA. Please see pages 392, 399-400,404 and Figure 5. Case 6 states:
“IG: This 13-year-old girl was referred at age 10 years for Lennox-Gastaut syndrome. A diagnosis of autism had been made at 2 years. Polygraphic recording showed tonic seizures with diffuse EEG spikes but the reported atypical absences, dating from age 4-5 years, were syncopes with cyanosis and trembling of the lips and fingers, following apneic periods lasting more than 1 minute (Figure 5).
Examination at 12½ years, prior to starting fenfluramine, suggested Rett syndrome with rnicrocephaly, spastic paraparesis, ataxic gait, stereotyped movements of the arms and hands, and loss of language which had begun to develop at 18-20 months. There was impaired contact with the environment and psychomotor instability. Tonic epileptic seizures occurred about 10 times daily. Prolonged apneas followed by hyperpnea occurred dozens of times daily, often followed by cyanotic episodes with syncope.
Fenfluramine 1.5 mg/kg per day was added to her medications. The CRS has been reduced considerably and epileptic seizures also became less frequent by about two-thirds. This effect was noticeable within 3 days and has persisted over 1 year of follow-up. Some improvement of autistic behavior was noted within 2 to 3 weeks with improved contact with the environment, some participation in her sister's play, reduction in hyperactivity, and the reappearance of a few words.”
Gastaut, page 399, Case 6 (emphasis added).
Although Gastaut teaches LGS using 1.5 mg/kg/day of FFA, Gastaut differs from claim 19 only insofar as that he is not explicit in teaching FFA in an amount ranging from 0.2 mg/kg/day to 0.8 mg/kg/day up to a maximum of 30 mg/day.
However, one or ordinary skill in the art would have a reasonable expectation of success reducing the dosage of Gastaut (1.5 mg/kg/day) to the claimed 0.2 to 0.8 mg/kg/day because FFA was well-known in the art to: 1) have serious adverse side-effects at higher drug concentrations1; and 2) shown to be safe and effective in treating seizures (including tonic clonic seizures and myotonic seizures) at a dosage range of 0.12 mg/kg/day to 0.9 mg/kg/day.
For example, see Ceulemans, who treats seizures including, but not limited to atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures (as in LGS, see discussions above), in patients suffering from Dravet syndrome (DS), a similar form of epilepsy to Lennox-Gastaut syndrome. 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, 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 claim 19, overlaps or lies inside ranges disclosed by the prior art (see discussions above), a prima facie case of obviousness exists.
Therefore, a person skilled in the art would have found it obvious to administer FFA within the dosage limitations disclosed in Ceulemans, to a patient suffering from LGS. The skilled artisan would have had a reasonable expectation that the administration of the FFA would treat seizures associated with LGS (e.g., atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures).
The obviousness here is based on the fact that, at the time of the instant invention, it was known in the art that:
i) FFA can be used to treat seizures in DS and LGS patients (see discussions above).
ii) many other seizure syndromes fulfill one or more criteria of seizure syndromes in LGS patients (see discussions above).
iii) the claimed range of FFA recited in claim 19, 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).
Therefore, claim 19 is obvious over Gastaut and Ceulemans.
Regarding claims 20-21 and 43, the cited references combine to teach GTC and tonic seizures (see discussions above).
Regarding claim 24, Gastaut teaches essentially FFA as the active ingredient (see discussions above).
Regarding claims 25-30 and 33, the recitation of the limitation of the method of claim 19 resulting reducing seizure frequency, is not given any patentable weight because each of the recited clause is 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). Since Gastaut and Ceulemans combine to disclose the method of claim 19 (see discussions above), the method of Gastaut and Ceulemans must necessarily produce the same outcomes of recited in claims 25-30 and 33, because each of the recited outcome is a natural process that flows from the subject and the orally administered FFA. Please see MPEP, 2111.04.
Regarding claims 34-36 and 42, Ceulemans teaches FFA can be combined with co-therapeutic agent selected from the list including, but not limited to topiramate, valproate and clobazam (see 1132).
Regarding claim 38, Ceulemans teaches FFA exposure duration ranging from 1-19 years (see abstract).
Regarding claim 39, Ceulemans teaches patients refractory to conventional antiepileptic medications (see pages 1132 and 1137).
Regarding claims 40-41, Ceulemans (see pages 1132), discloses that FFA patients underwent 4-h EEG. The specific findings for patients asleep during the EEG, must necessarily include showing of slow spike-wave complexes during sleep.
MPEP 2143(e) states: The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense.
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), alleging that instant claims 19-21, 24-30, 33-36 and 38-43 are non-obvious over Gastaut and Ceulemans on the grounds that:
1) Applicants merely cite a list of case law citations (see pages 6-7 of Remarks).
Response:
Applicants’ response fails to link the legal concepts to the facts of the application under examination.
2) A person skilled in the art would not have understood that cases 6 and 7 patients referred for LGS were diagnosed with LGS. Applicants cite ¶s 9, 11 of the Dr. Sullivan’s declaration (filed on 08/07/2025), in support of the Applicants’ allegations (see pages 7-8 and 10 of Remarks).
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because Gastaut on page 399 states:
Case 6
“IG: This 13-year-old girl was referred at age 10 years for Lennox-Gastaut syndrome. A diagnosis of autism had been made at 2 years. Polygraphic recording showed tonic seizures with diffuse EEG spikes but the reported atypical absences, dating from age 4-5 years, were syncopes with cyanosis and trembling of the lips and fingers, following apneic periods lasting more than 1 minute (Figure 5).
Examination at 12½ years, prior to starting fenfluramine, suggested Rett syndrome with rnicrocephaly, spastic paraparesis, ataxic gait, stereotyped movements of the arms and hands, and loss of language which had begun to develop at 18-20 months. There was impaired contact with the environment and psychomotor instability. Tonic epileptic seizures occurred about 10 times daily. Prolonged apneas followed by hyperpnea occurred dozens of times daily, often followed by cyanotic episodes with syncope.
Fenfluramine 1.5 mg/kg per day was added to her medications. The CRS has been reduced considerably and epileptic seizures also became less frequent by about two-thirds. This effect was noticeable within 3 days and has persisted over 1 year of follow-up. Some improvement of autistic behavior was noted within 2 to 3 weeks with improved contact with the environment, some participation in her sister's play, reduction in hyperactivity, and the reappearance of a few words.”
Gastaut, page 399, Case 6 (emphasis added).
Gastaut is a peer reviewed scientific publication, which suggests that this publication as whole would be viewed as trust worthy by a person of the ordinary skill in the art. The Examiner is required to presume that this publication is enabling of the teachings disclosed therein. Please see MPEP § 2128.
Applicants and the declarant arguments are confusing, because while Applicants and the declarant are alleging that cases 6 and 7 patients referred for LGS were not diagnosed with LGS (see pages 7-8 of Remarks and ¶ 9 of the Dr. Sullivan’s declaration), Applicants and the declarant are now arguing what appears to be the Applicants’ and the declarant’s position that the phrase “suggested Rhett syndrome” in the Gastaut disclosures (see discussions above), implies that the patients were diagnosed with Rhett syndrome (see page 9 of Remarks and ¶ 10 of the Dr. Sullivan’s declaration).
Applicants and the declarant appear not to rule out LGS in case 6 and 7 patients, wherein the Applicants and the declarant (see page 10 and ¶ 10 of the Dr. Sullivan’s declaration), state:
“Based on the symptoms described in Cases 6 and 7 of Gastaut, Dr. Sullivan's asserts that "[t]hese are symptoms which support a Rett diagnosis but are not typically found in LGS patients.”
3) Tonic and myoclonic seizures are not exclusive to LGS patients, citing: i) ¶s 10-11 of the Dr. Sullivan’s declaration; ii) Camfield (Epilepsia, 2011); and iii) Smeets et al (Mol, Syndromol, 2011), in support of the Applicants’ position. Please see pages 8-10 of Remarks.
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive, because the Office did not take a position that tonic and myoclonic seizures are exclusive to LGS patients.
4) Case 6 and 7 patients were incorrectly referred for LGS, citing: i) ¶ 12 of the Dr. Sullivan’s declaration; and ii) Camfield (Epilepsia, 2011), in support of the Applicants’ allegation. Please see pages 10-11 of Remarks.
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because Gastaut is a peer reviewed scientific publication, which suggests that this publication as whole would be viewed as trust worthy by a person of the ordinary skill in the art. The Examiner is required to presume that this publication is enabling of the teachings disclosed therein. Please see MPEP § 2128.
The Applicants and declarant appear to interject their personal opinions regarding what the referral in the Gastaut disclosure in, should be.
5) Gastaut fails to establish that case 6 and 7 patients suffer LGS because Gastaut did not disclose tonic seizures during sleep as a diagnosis criterion for LGS, citing: i) ¶ 13 of the Dr. Sullivan’s declaration; and ii) Camfield (Epilepsia, 2011), in support of the Applicants’ allegation. Please see pages 11-12 of Remarks.
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive, because the tonic seizures disclose in Gastaut necessarily encompass tonic seizures during sleep.
6) A person skilled in the art would not have had a reasonable expectation of success in treating LGS based on the teachings of Gastaut and Ceulemans, citing: i) ¶s 15-17 of the Dr. Sullivan’s declaration; and ii) pages 395-396 of Gastaut, in support of the Applicants’ allegation. Please see pages 12-14 of Remarks.
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive, because the reasons for the Office’s reliance on the teachings of Gastaut and Ceulemans, in order to reject the claimed invention are set forth in the discussions above. The Examiner, therefore, applies the same reasons hereto.
7) There are significant differences between DS and LGS, including underlying causes, pathologic features and symptoms. Applicants cite: i) ¶s 18-20 of the Dr. Sullivan’s declaration; ii) ¶s 23-24 of the declaration of Dr. Klitgaard (filed on 09/27/2024), in support of the Applicants’ allegations. Please see pages 10-12 of Remarks.
Response:
Applicants’ arguments have been fully considered but they are not found to be persuasive, because the Office did not take a position that DS and LGS have the same underlying causes, pathologic features and symptoms.
The rejection of the instant claims is based on the fact that, at the time of the instant invention, it was known in the art that:
i) FFA can be used to treat seizures in DS and LGS patients (see discussions above).
ii) many other seizure syndromes fulfill one or more criteria of seizure syndromes in LGS patients (see discussions above).
iii) the claimed range of FFA recited in claim 19, overlaps or lies inside ranges disclosed by the prior art. Please see discussions above.
It is therefore reasonable to conclude that the strength of correlation between the reduction of seizures including, but not limited to atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures (as in LGS, see discussions above), in a DS patient, gives rise to reasonable expectation of success in reducing atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures in an LGS patient.
Applicants have not provided any evidence on the record, which would support what appears to be the Applicants’ allegation on the grounds that one skilled in the art would not have had a reasonable expectation that the FFA in Ceulemans which reduces seizures including, but not limited to atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures (as in LGS, see discussions above), in a DS patient, would not reduce atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures in an LGS patient.
The rejection of claims 19, 22, 31-32 and 37 under 35 U.S.C. 103 as being unpatentable over Gastaut of record in view of Ceulemans of record, as applied to claim 19 above and further in view of: 1) Al-Baradie of record (Neuroscience, 2013); and 2) Conry of record (Epilepsia, 2009), 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 Gastaut and Ceulemans, are discussed above and hereby incorporated into the instant rejection.
The invention of claims 22, 31-32 and 37 are similar to claim 19, however, claims 22, 31-32 and 37 differ slightly from claim 19 in that the claims require seizures comprising drop seizures.
Although Gastaut and Ceulemans combine to disclose that FFA can be used to treat an epilepsy syndrome (e.g., LGS or DS, see discussions above), Gastaut and Ceulemans differ from claims 22, 31-32 and 37 only insofar as the cited references do not combine to explicitly teach an epilepsy syndrome comprising drop seizures.
However, the claimed inventions would have been obvious over Gastaut and Ceulemans, because at the time of the instant invention, it was known in the art that an epilepsy syndrome can comprise drop seizures. For example:
1) Al-Baradie discloses that myoclonic seizures, one of the defining features of DS, can comprise drop attacks. Please see page 13. It is noted that some of the Ceulemans patients treated with FFA, had myoclonic seizures (see Ceulemans at page 1132).
2) Conry discloses drop seizures in LGS patients (see abstract).
Therefore, one skilled in the art would have found it obvious to administer FFA to a patient suffering from an epilepsy syndrome comprising drop seizures (e.g., LGS or DS), with a reasonable expectation of treating the seizures in the patient.
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).
Regarding claims 31-32, the recitation of the limitation of the method of claim 22 resulting reducing seizure frequency, is not given any patentable weight because each of the recited clause is 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). Since Gastaut, Ceulemans, Al-Baradie and Conry combine to disclose the method of claim 22 (see discussions above), the method of Gastaut, Ceulemans, Al-Baradie and Conry must necessarily produce the same outcomes of recited in claims 31-32, because each of the recited outcome is a natural process that flows from the subject and the orally administered FFA. Please see MPEP, 2111.04.
Regarding claim 37, Ceulemans teaches FFA can be combined with a co-therapeutic agent (see 1132).
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 Gastaut and Ceulemans, Al-Baradie and Conry cannot be employed in order to address the deficiency in the teachings of Gastaut and Ceulemans. Please see pages 14-16 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 Gastaut 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 Al-Baradie and Conry in order to address the deficiency in the teachings of Gastaut and Ceulemans, is proper.
The rejection of claims 19 and 23 under 35 U.S.C. 103 as being unpatentable over Gastaut of record in view of 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 Office action mailed on 06/27/2024, of which said reasons are herein reiterated.
The limitation of claim 19 as well as the corresponding teachings of Gastaut and Ceulemans, are discussed above and hereby incorporated into the instant rejection.
The invention of claim 23 is similar to claim 19, however, claim 23 differs slightly from claim 19 in that claim 23 requires FFA in the form of a liquid formulation.
Gastaut and Ceulemans do not combine to explicitly teach the limitation of claim 23.
However, the claimed inventions would have been obvious over Gastaut and Ceulemans because at the time the instant invention was filed, it was known in the art that FFA can be formulated in the form of a liquid formulation.
For example, Ceulemens2014 teaches that FFA can be administered as a monotherapy and alternatively, FFA can be co-administered with a co-therapeutic agent such as stiripentol (see ¶ 0058). The dose of FFA administered can be formulated in any pharmaceutically acceptable 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).
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 a liquid form of FFA to a patient in need of treatment for a seizure disorder (e.g., LGS or DS, would treat the seizure in the patient.
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 Gastaut and Ceulemans, Ceulemens2014 cannot be employed in order to address the deficiency in the teachings of Gastaut and Ceulemans. Please see pages 16-17 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 Gastaut 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 Gastaut and Ceulemans, is proper.
Response to the Declarations.
Declaration of Dr. Klitgaard
The declaration of Dr. Klitgaard (see pages 1-20 of the declaration of Dr. Klitgaard filed on 09/27/2024), was addressed in the previous Office action mailed on 11/08/2024. The Examiner, therefore, applies the same response hereto.
Declaration of Dr. Sullivan
The declarations of Dr. Sullivan (filed on 08/07/2025), have been fully considered but they are not found to be persuasive for the following reasons.
The declarant states that in his opinion:
¶ 1:
i) the instant claims are non-obvious over cited references fail (see page 1);
ii) a person skilled in the art would not have understood that a referred patient was diagnosed (see page 1)
iii) a patient exhibiting tonic or myoclonic seizures does not necessarily have LGS; and
iv) incorrect referrals for suspected LGS were relatively common (see page 1).
Response
The declarant’s arguments have been fully considered but they are not found to be persuasive, because:
i) the reasons for the Office’s reliance on the teachings of cited references, in order to reject the claimed invention are set forth in the discussions above. The Examiner, therefore, applies the same reasons hereto.
ii) the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
iii) the Office did not take a position that only LGS patients exhibit tonic or myoclonic seizures.
iv) the declarant fails to provide any evidence that would support what appears to be the declarant’s allegation that patients referred for LGS in Gastaut, were incorrectly referred.
Gastaut is a peer reviewed scientific publication, which suggests that this publication as whole would be viewed as trust worthy by a person of the ordinary skill in the art. The Examiner is required to presume that this publication is enabling of the teachings disclosed therein. Please see MPEP § 2128.
The declarant appears to interject his personal opinions regarding what the referral in the Gastaut disclosure in, should be.
¶ 2: there are significant differences between DS and other epilepsies such as LGS, including underlying causes, pathologic features and symptoms ad one skilled in the art would not have had a reasonable expectation of success in treating LGS with FFA (see page 2).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 9: case 6 and 7 of Gastaut do not support a diagnosis of LGS (see page 4).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 10: tonic and myoclonic seizures are not exclusive to patients with LGS (see pages 4-5).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 11: the declarant reiterates same arguments in ¶ 9 above (see pages 5-6).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 12: incorrect LGS referrals were not uncommon (see pages 6-7).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 13: Gastaut fails to establish that case 6 and 7 patients suffer from LGS (see page 7).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 14: One skilled in the art would have had a reasonable expectation of success in treating LGS with FFA, based on the teachings of Gastaut (see pages 7-8).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 15: there is nothing in Gastaut to support an expectation that FFA would treat LGS (see page 8).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 16: the declarant reiterates same arguments in ¶ 9 above (see pages 8-9).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 17: the declarant disagrees with the Office’s position that one skilled in the art would have had a reasonable expectation that the FFA in Ceulemans which reduces seizures including, but not limited to atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures (as in LGS, see discussions above), in a DS patient, would not reduce atypical absence seizures, generalized tonic-clonic seizures and myoclonic seizures in an LGS patient (see page 9).
Response:
The declarant’s disagreement is acknowledged. However, the Office’s position is maintained.
¶s 18-19: the declarant reiterates same arguments in ¶ 2 above (see pages 9-10).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 20: the declarant reiterates same arguments in ¶ 15 above (see page 10).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
¶ 21: the declarant reiterates same arguments in ¶s 2, 13 and 15 above (see page 10).
Response:
The declarant’s arguments have been fully considered but they are not found to be persuasive, because the declarant’s arguments are similar to the arguments above, which have been addressed. The Examiner, therefore, applies the same responses hereto.
For the reasons made of record in the previous Office action, the rejections are maintained.
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.
1) The rejection of claims 19-42 is maintained and newly added claim 43 is rejected 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, for the reasons of record set forth in the previous Office action.
Response to Applicants’ Arguments/Remarks
Applicants have not properly addressed the specific grounds of rejections as discussed in the previous Office action setting. Applicants request that the obvious-type double patenting rejections be held in abeyance. Please see pages 17-18 of Remarks.
Response
Applicants’ comments are acknowledged. However, the rejections 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.
Non-Statutory Obviousness-Type Double Patenting
New Grounds of Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. patent No. 12,144,787 (‘787 patent), in view of: 1) Gastaut of Record and Ceulemans of Record.
The corresponding teachings of Gastaut and Ceulemans, are discussed above and hereby incorporated into the instant rejection.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application and the reference patents are similarly drawn to a method of using FFA. For example, the claims of the instant application (e.g., claim 1), are drawn to a method of preventing or reducing seizures in a patient suffering from LGS with FFA, in an amount ranging from 0.2 mg/kg/day to 0.8 mg/kg/day up to a maximum of 30 mg/day, whereas, the claims of the ‘787 patent (e.g., claims 1,4), are drawn to a method of treating, preventing and/or ameliorating seizures in a patient suffering Rett syndrome, with FFA, in an amount between 0.2 mg/kg/day to 0.8 mg/kg/day up to a maximum of 30 mg/day.
Although the ‘787 patent is not explicit in claiming a method for treating LGS, a method of treating LGS from the ‘’787 patent embodiment, would have been obvious in view of Gastaut and Ceulemans.
Therefore, there is sufficient overlap between the claim scopes to render them obvious over each other. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the reference application subject matter.
Conclusion
No claim is allowable.
If Applicants should amend the claims, a complete and responsive reply will clearly identify where support can be found in the disclosure for each amendment. Applicants should point to the page and line numbers of the application corresponding to each amendment, and provide any statements that might help to identify support for the claimed invention (e.g., if the amendment is not supported in ipsis verbis, clarification on the record may be helpful). Should the Applicants present new claims, Applicants should clearly identify where support can be found in the disclosure.
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
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).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “Because of the possible cardiac adverse effects (valve thickening, pulmonary hypertension) associated with use of fenfluramine, it was withdrawn from the market in 2001.” Ceulemans, Abstract.