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 .
Claims 1-7 are pending.
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.
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Claims 1-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of copending Application No. 18917157 (reference application) further in view of Zhang, An adaptive dose-finding design incorporating both toxicity and efficacy. Stat Med. 2006 Jul 30;25(14):2365-83 and Powell, Clin Pharmacol Ther 2020 Jul 12;109(1):65–72.
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claim contains overlapping subject matter:
Claim 6 of 18917157:
6. A method for treating or preventing a disease or disorder chosen from the group consisting of excessive daytime sleepiness (EDS), cataplexy, narcolepsy, sleep apnea (e.g., obstructive sleep apnea), sleep induced apnea, diurnal somnolence, severe fatigue, and idiopathic hypersomnia, comprising administering to a subject in need thereof a combination of claim 1
wherein claim 1 is a combination of a salt of pitolisant with an alkalinizing agent.
Note alkalinizing is anticipated to make the salt a free base corresponding to instant claim 1
The difference is that the instant method limits the dose to 50 mg-240 mg. Adjusting a medication dose is a standard and essential skill for a qualified physician. One of skill in the art (here Doctors) is expected to regularly tailor treatments by assessing the patient's individual body weight, age, metabolism, liver/kidney function, and their specific response to the therapy. According to Zhang, Novel therapies are challenging the standards of drug development. Agents with specific biologic targets and limited toxicity require novel designs to determine doses to be taken forward into larger studies. Also Powell titled ‘Drug Dosing Recommendations for All Patients: A Roadmap for Change’ teaches how and why of optimizing doses.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Likewise,
claims 1-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of copending Application No. 18917144 (reference application) further in view of Zhang, An adaptive dose-finding design incorporating both toxicity and efficacy. Stat Med. 2006 Jul 30;25(14):2365-83 and Powell, Clin Pharmacol Ther 2020 Jul 12;109(1):65–72.
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claim contains overlapping subject matter:
Claims 27. 33. 35, 43, of 18917144:
These claims are drawn to treatment of fatigue using the ‘a delayed release dosage form of the instant active ingredient’.
The difference is that the instant method limits the dose to 50 mg-240 mg. Adjusting a medication dose is a standard and essential skill for a qualified physician. One of skill in the art (here Doctors) is expected to regularly tailor treatments by assessing the patient's individual body weight, age, metabolism, liver/kidney function, and their specific response to the therapy. According to Zhang, Novel therapies are challenging the standards of drug development. Agents with specific biologic targets and limited toxicity require novel designs to determine doses to be taken forward into larger studies. Also Powell titled ‘Drug Dosing Recommendations for All Patients: A Roadmap for Change’ teaches how and why of optimizing doses.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims are drawn to pitolisant and its salts as active agents. As such reference to optical isomers, racemates, diastereoisomers or enantiomers implies chiral counter-ions of salt of the achiral pitolisant free base. These chiral compounds are not defined in the claims rendering the scope of the claims vague and indefinite. Further the dose range recited depends on the structural make-up of the active agent ((what salt, how much of water in sticking to make hydrate(s)). Except for the claim 7 (presumably drawn to hydrochloride salt), the chemical identity of the active ingredient is unclear in the claims. Also pitolisant is monoamine which means it will make salt with one molar equivalent of HCl. As such the term
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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.
Claim(s) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lehert, Clinical Drug Investigation, vol. 42, no. 1, 2 December 2021 (2021-12-02), pages 65-74; Causse, Journal of Sleep Research, 1 September 2020 (2020-09-01), pages 80-81; Pepin, A Randomized Trial", Chest United States 09 Feb 2018, Elsevier Inc, vol. 159, no. 4 31, March 2021 (2021-03-31), pages 1598-1609; Dauvillers, American Journal of Respiratory and Critical Care Medicine,, vol. 201, no. 9, 1 May 2020 (2020-05-01), pages 1135-1145; and Schwartz, British Journal of Pharmacology,, vol. 163, no. 4, 26 May 2011 (2011-05-26), pages 713-721).
Lehert titled “Efficacy of Pitolisant 20 mg in Reducing Excessive Daytime Sleepiness and Fatigue in Patients with Obstructive Sleep Apnoea Syndrome: An Individual Patient Data Meta-analysis" and Causse titled "Efficacy of Pitolisant 20 mg in reducing excessive daytime sleepiness for patients with obstructive sleep apnea syndrome: An individual patient data meta-analysis", independently are documents disclosing a meta-analysis of the two clinical trials mentioned in the present application, namely
HAROSA-1 and HAROSA-2.
HAROSA-1 is a clinical trial conducted in patients suffering from obstructive sleep apnea (OSA) adhering to CPAP treatment. CPAP stands for Continuous Positive Airway Pressure. It is a treatment that uses a bedside machine to pump a steady stream of pressurized air through a tube and mask. This gentle air pressure keeps your throat and airways open while you sleep, preventing pauses in breathing and loud snoring. In this trial pitolisant reduces the score on the Pichot Fatigue scale. Yet, the difference is not statistically significant. This study is disclosed in document Pepin. The Pichot Fatigue Scale is an 8-item self-report questionnaire used to assess subjective physical and mental fatigue. It tracks symptoms like lack of energy, concentration difficulties, and heaviness to determine the severity of fatigue. Scores above 22 (out of a maximum 32) indicate excessive fatigue. According to Pepin (section under Interpretation) pitolisant used as adjunct to CPAP therapy for OSA with residual sleepiness despite good CPAP adherence significantly reduced subjective and objective sleepiness and improved participant-reported outcomes and physician-reported disease severity.
HAROSA-2 is a clinical trial conducted in OSA patients not undergoing CPAP treatment. In this trial pitolisant statistically significant reduces the score on the Pichot Fatigue scale. This study is disclosed by Dauvillers. Dauvillers concludes that pitolisant significantly reduced self-reported daytime sleepiness and fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or nonadherent to continuous positive airway pressure.
The meta-analysis of these two studies presented in Lehert document and Causse document, comes to the conclusion that, overall, there is a statistically significant improvement of the relevant fatigue score as a result of treatment with pitolisant.
The presently claimed subject-matter differs from the prior at discussed above in the use of a higher dosage 50 mg and 240 mg once a day of pitolisant.
Optimizing dose for desired efficacy is within the purview of one of skill in the art. According to Schwartz titled ‘The histamine H3 receptor: from discovery to clinical trials with pitolsant’, According to Schwartz, at page 717, column A, full paragraph from bottom, “In healthy human volunteers, single oral doses up to 120 mg were well tolerated without any adverse, physiological, namely cardiovascular, or biological manifestation”.
Limitations of dependent claims are drawn to more specific patient selection with disease states such as narcolepsy (with and without cataplexy) which are within the purview of one of skill in the art and are also found throughout the cited references.
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art.
Accordingly, the claims do not recite an unobvious distinction over the prior art. Further, a reference is relevant not only for what it expressly teaches, but also for what it would have conveyed to one of ordinary skill in the art. See In re Opprecht, 12 USPQ2d 1235, 1236 (Fed. Cir. 1989); In re Bode, 193 USPQ 12 (CCPA 1976). In light of the foregoing discussion, the Examiner finds that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, in view of the cited references and the knowledge generally available in the art. Accordingly, the claims are rejected under 35 U.S.C. § 103.
The art made of record and not relied upon is considered pertinent to applicant's disclosure. Cheng, Pitolisant, a novel histamine H3-receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clin. trials, has propelled it into the spotlight of widespread societal attention on Apr. 3, 2023.Pharmacology Research & Perspectives (2024), 12(1), e1161.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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