DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 19-40 are pending.
Priority
This application filed on 01/19/2024, is a CON of U.S. application No. 16/864,955, filed on 05/01/2020 (ABN), which is a CON of U.S. application No. 15/246,346, filed on 08/24/2016 (ABN), which claims benefit of U.S. provisional application No. 62/209,090, filed on 08/24/2015.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/05/2024 and 11/05/2024, were in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents were considered. A signed copy of Form PTO-1449 is enclosed herewith.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 19-35 and 37-40 are rejected under 35 U.S.C. 103 as being unpatentable over Nieto-Barrera (Revista de neurologia, 2002, 35(1), S88-95, SciFinder Scholar Abstract Translation used in the instant rejection) in view of Ceulemans et al (hereinafter, “Ceulemans”, Epilepsia, 2012, 53(7), 1131-1139).
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 TPM and 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, 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.
It is noted that no criticality has been demonstrated in the specification with regard to the claimed 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.
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 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).
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, claim 19 is 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 and 37, 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 and 37.
Regarding claims 21, 25, 30 and 39-40, 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, 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.
Claims 19 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Nieto-Barrera and Ceulemans, as applied to claim 19 above and further in view of Ceulemens et al (hereinafter “Ceulemens2014”, U.S. Pub. No. 20140343162, published 11/20/2014).
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.
Non-Statutory Obviousness-Type 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 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 19-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. patent Nos:
11,406,606 (claims 1-22);
10,950,331 (claims 1-10);
11,571,397 (claims 1-21);
11,759,440 (claims 1-10);
11,786,487 (claims 1-9); and
11,634,377 (claims 1-16).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the above cited patents are similarly drawn to a method of treating seizure.
For example, the claims of the instant application are drawn to a method of treating seizures in a patient suffering from LGS comprising administering an AED in combination with FFA (see instant claim 19), whereas, the claims of the reference patents (e.g., U.S. patent No. 11,406,606), are directed to a method of treating seizures in a patient population that includes LGS (see reference patent claims 1 and 4), comprising administering stiripentol (an AED, see instant claim 22) in combination with FFA.
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.
Claims 19-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. patent application Nos:
16/864,955 (claims 27-46);
18/418,121 (claims 19-43);
17/289,125 (claims 15-16, 18-29 and 31);
17/430,033 (claims 1-2, 7, 12-14, 16-17, 22-23);
17/579,135 (claims 1-22);
17/992,254 (claims 1 and 8-15); and
17/737,626 (claims 22 and 35-53).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the above cited patent applications are similarly drawn to a method of treating seizure by administering FFA.
For example, the claims of the instant application are drawn to a method of treating seizures in a patient suffering from LGS comprising administering an AED in combination with FFA (see instant claim 19), whereas, the claims of the reference patent applications (e.g., reference patent application No. 16/864,955), are directed to a method of treating in a patient suffering from LGS (see reference application claims 27, 30 and 38), comprising administering an agent selected from the group that includes stiripentol (an AED, see instant claim 22) in combination with FFA.
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.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusions
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.
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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).
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.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629