The 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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/22/2026 has been entered.
Status of Claims
Claims 2 and 4- 6 are pending and under examination in this office action.
Priority
The instant application 17/757,672 filed on 06/17/2022, is a 371 of PCT/US2020/065891 filed 12/18/2020, which claims the benefit of priority to U.S. Provisional Application No. 62/951,638 filed 12/20/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/22/2026 is in compliance with the provisions of 37 CFR1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Response to Declaration
The Declaration under 37 CFR 1.132 by Dr. Larisa Reyderman, filed 05/22/2026 is fully considered, but NOT persuasive to overcome rejections of claims 2, 4-6 over NCT03440424, Murphy and Moline under 35 USC 103 on the record.
Reyderman Declaration argues: “A person of ordinary skill in the art would not have a reasonable expectation of success in treating a patient population with moderate hepatic impairment (HI) classified in Child-Pugh class B under Child-Pugh Classification with a maximum dose of 5 mg of lemborexant because the dosages that are studied in Murphy and Moline are for treating non-hepatically compromised patients. A clinician or a pharmacologist would not be able to extrapolate from any of the cited references that a maximum of dosage of 5 mg would be either effective or safe to treat hepatically impaired patients. The maximum of dosage of 5 mg for a patient with moderate hepatic impairment (HI) classified in Child-Pugh class B under Child-Pugh Classification would require extensive and rigorous research” (Declaration, ¶ 6)
RESPONSE: Please note reasonable expectation of success does not require absolute predictability or certainty of outcome. It requires only reasonable basis, in light of prior art, that a skilled artisan expect the claimed invention work for its intended purpose.
As MPEP 2143.02.I. stated : “Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute"))”.
In instant case, Murphy and Moline already teach 5-10mg of lemborexant is effective in treating insomnia in regular patient. NCT03440424 establishes the study of evaluating 10mg of lemborexant in hepatically impaired patients. It’s understood that hepatic impairment commonly necessities downward adjustment relative to the dose used in patients with normal hepatic function. Given this titration down practice in hepatic impaired patients, a POSA would have been motivated to evaluate dose below 10mg e.g. 5mg when adapting/adjusting dose regimen of lemborexant for patients with hepatic impairment. A POSA would reasonably expect 5mg of lemborexant which is already established effective dose by Murphy and Moline at the lower end of dose regimen, would likewise be effective while presenting a reduced risk of exposure compared with 10mg of lemborexant in hepatic impaired patients.
Reyderman Declaration argues dose reduction in patients with HI is not a routine or universally
applicable optimization strategy for dual orexin receptor antagonists (DORAs) (See ¶ 7-10)
RESPONSE: As elaborated in previous office action, the examiner agrees that each dual orexin receptor antagonists (DORAs) has unique pharmacokinetic properties/ metabolic pathways, enzyme involvement, and hepatic clearance rates. Dose reduction in patients with hepatic impairment might not be necessary for Suvorexant or other dual orexin receptor antagonists (DORAs). In instant case, NCT03440424 was specifically designed to assess the effect/ pharmacokinetics (PK) of 10mg lemborexant in mild and moderate hepatic impaired population. A skilled artisan would have known lemborexant is metabolized through liver enzymes and patients with liver problems may experience higher levels of lemborexant in their blood, increasing potential side effects, so dose adjustments/reduction of lemborexant might be needed for patients with mild or moderate liver impairment which is consistent with NCT03440424. Thus, dose adjustment/reduction of lemborexant for patients having hepatic impairment is NOT unexpected.
Reyderman Declaration argues the cited reference NCT03440424 is a clinical trial design for evaluating the pharmacokinetics of a single 10 mg dose of lemborexant in subjects with mild and moderate hepatic impairment compared to healthy subjects. The study design document does not show any testing results. Based on this document and other cited references that did not concern hepatic patients, a person of ordinary skill would not know whether lemborexant can be safely administered to patients with hepatic impairment in a single dose or more than a single dose, and if it can be safely administered, in what amount. Without research, a person of ordinary skill in the art would not have predicted an appropriate dose for treating a patient having moderate hepatic impairment is 5 mg, or 2.5 mg, or none at all (Declaration, ¶ 12-13).
RESPONSE: Although no results are provided for NCT03440424, the absence of clinical results does not negate the fact that a POSA recognize the need of assessing/ evaluating lemborexant in patients with mild and moderate hepatic impairment. Rather, the selection of 10mg, a dose taught by Murphy and Moline, as the starting point for study of lemborexant in the hepatic impaired population itself is evidence that a POSA would have looked to the dose range disclosed by Murphy and Moline in regular patients when adjusting lemborexant dose regimen in hepatic impaired population.
The mere fact that other numerical value exist between 0 and 10mg only establish they were mathematically possible which is not relevant inquiry. Please note the 5mg dose is not an arbitrary dose point only rely on optimization of unbounded set of possible doses. The rejection is based on the application of an already art-recognized effective dose of Lemborexant (5mg) to a population for which reduced dose would reasonably expect to be effective. Murphy teaches lemborexant dose greater than or equal to 5 mg decreased the amount of time spent awake after sleep onset and doses above 10 mg did not show consistently greater efficacy than the 10 mg dose and were associated with higher rates of somnolence. Moline explicitly claims the therapeutically effective amount is single 5 mg daily dose that achieves desired mean AUC(0-t). A skilled artisan would reasonably expect 5 mg of lemborexant provide sufficient efficacy for treating insomnia without higher rate of somnolence in patients with hepatic impairment.
The need of research to confirm a dose’s efficacy and safety does not, by itself, establish the dose was not obvious based on the combined teaching of prior art and general knowledge of dose adjustment for patients with hepatic impaired functions. Reyderman Declaration does not provide any unexpected or surprising result that efficacy of 5 mg of lemborexant in hepatic impaired patients deviates from what a POSA would have been expected from Murphy and Moline’s teaching. Thus, claims 2 and 4-6 remain rejected under 35 USC 103.
Response to Arguments
Applicant’s remarks filed 05/22/2026 have been fully considered. Applicant’s argument about reasonable expectation of success is similar as Reyderman Declaration. Please see Response to Declaration which also apply to double patenting rejections.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2 and 4- 6 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03440424 (version 2, 09/05/2018 ) in view of Murphy et al. (Journal of Clinical Sleep Medicine, Vol. 13, No. 11, 2017, Applicant’s IDS dated 06/05/2024, Cite No. 1, Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results from a Bayesian, Adaptive, Randomized, Double-Bind, Placebo-Controlled Study).
NCT03440424 is an open-label, parallel-group study to evaluate the pharmacokinetics of lemborexant (E2006) and its metabolites in subjects with mild and moderate hepatic impairment compared to healthy subjects. The study design of NCT03440424 was first available online on 02/14/2018.
NCT03440424 disclosed Experimental: Cohort A: Mild Hepatic Impairment (Child Pugh Class A), wherein participants with mild hepatic impairment receive a single 10 mg) dose (1 × 10 mg) lemborexant (E2006) tablet in the morning with 240 milliliters (mL) of water following an overnight fast of at least 10 hours (See Arms and Interventions). Cohort B: Moderate Hepatic Impairment (Child Pugh Class B) Participants with moderate hepatic impairment receive a single 10mg dose (1 × 10 mg) lemborexant [E2006] tablet in the morning with 240 mL of water following an overnight fast of at least 10 hours. Cohort C: Healthy participants (Control) Healthy participants matched to participants in Cohorts A and B receive a single 10 mg dose (1 × 10mg lemborexant [E2006] tablet) in the morning with 240 mL of water following an overnight fast of at least 10 hours.
Regarding the limitation of claim 6, NCT03440424 disclosed the inclusion criteria for Cohorts A, B and C wherein the hepatic impairment level of patient is determined and documented by medical history and a physical examination (See Inclusion Criteria, page 9/14).
Regarding the limitation of bedtime administration recited in claims 2 and 6, the difference between NCT03440424 and instant claims are the administration time of lemborexant: in the morning vs immediately before going to bed. It’s common practice to administer sleep medicine before going to bed and dosage adjustment (administration timing, frequency, etc.) is routine practice in treating insomnia. It would have been prima facie obvious to one of ordinary skilled in the art to explore administrating lemborexant to patient having mild to moderate hepatic impairment classified under Child Pugh classification before going to bed and adjust the dose accordingly based on patient’s condition.
NCT03440424 is silent about 5mg of lemborexant as single daily dose. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. MPEP 2144.05. NCT03440424 teaches single daily dose of lemborexant for treating insomnia (10mg) and limitation of hepatic impairment classified under Child Pugh classification. A skilled artisan would have known to titration down the dose of lemborexant based on hepatic function of patient accordingly.
Murphy teaches clinical development of lemborexant and identified lemborexant doses (2.5mg -10mg) that maximize insomnia treatment efficacy and minimize residual morning sleepiness, based on randomized, double-blind, placebo-controlled, parallel-group clinical trial NCT01995838 (See Brief Summary, Conclusion, entire article). Murphy teaches lemborexant (e.g. 5mg, 10mg per day) was taken 30 minutes before subject’s median habitual bedtime and assessment with 8h polysomnography PSG (See Study Design and Procedure, Table 2, Figure 1, page 1291) (which reads on bedtime limitation of instant claim 2 and 6). Murphy teaches “Statistically significant improvements in mean sSE compared with placebo were observed at lemborexant doses of ≥ 5 mg on days 1 to 7 (P < .01), with differences ranging from 6.0% (5 mg) to 9.4% (10 mg) higher than placebo” (See page 1293, right column, 2nd last para). Murphy teaches lemborexant dose greater than or equal to 5 mg decreased the amount of time spent awake after sleep onset, and doses above 10 mg did not show consistently greater efficacy than the 10 mg dose and were associated with higher rates of somnolence (See Conclusion).
Dosage adjustment (administration timing, frequency, etc.) based on patient’s condition (e.g. hepatic function ) is routine practice in treating insomnia as shown in Murphy. It’s understood that hepatic impairment commonly necessities downward adjustment relative to the dose used in patients with normal hepatic function. It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of instant claimed invention to further explore dosage regimen of lemborexant (e.g. administration timing, etc.) in patients with hepatic impairment based on the combined teachings of NCT03440424 and Murphy, together with optimization based on general knowledge of lemborexant and insomnia treatment and arrive at instant claimed invention with reasonable expectation of success. NCT03440424 teaches single daily dose of lemborexant for treating insomnia (10mg) in patients having hepatic impairment classified under Child Pugh classification. An ordinary skilled in the art would have known oral tablet of lemborexant can be administered at single daily dose 5-10mg for treating insomnia as taught by Murphy. Murphy teaches lemborexant (e.g. 5mg, 10mg per day) was taken 30 minutes before bedtime and 8h polysomnography PSG. An ordinary skilled would be motivated to combine the teachings of NCT03440424 and Murphy because both teachings are directed to method of treating insomnia with lemborexant. A skilled artisan would reasonably expect the lower dose of lemborexant (5mg) exhibit lower drug exposure than 10mg of lemborexant, thus safer for patient population with hepatic impairment. The combined teachings of NCT03440424 and Murphy, together with general knowledge of lemborexant and insomnia treatment would provide an alternative safe administration regimen for patients with impaired hepatic function.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the teachings of prior art and general knowledge of lemborexant and insomnia treatment. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 2 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Moline et al. ( US 20170252342 A1, hereafter “Moline ‘342”, corresponding to U.S. Patent No. 10188652 B2), in view of NCT03440424 (version 2, 09/05/2018 ), as evidenced by FDA Guidance for Industry Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling, May 2003
Claim interpretation: As evidenced by lemborexant at PubChem ( https://pubchem.ncbi.nlm.nih.gov/compound/Lemborexant ) and disclosed by instant specification([0020], lemborexant has chemical name (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl) cyclopropanecarboxamide.
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Moline ‘342 disclosed compound A (i.e. lemborexant) is a potent orexin receptor antagonists useful in the treatment of sleep disorder(e.g. insomnia) (See abstract, [0006], [0168], Examples 1-4, claim 1). Moline ‘342 teaches compound A may be in the form of free base or a pharmaceutically acceptable salt, etc. ( See [0166]). Moline ‘342 teaches methods of treating insomnia comprising administrating orally various dosage amount (e.g. 5 mg, 10mg, etc.) of compound A (i.e. Lemborexant), wherein said single daily dose achieve desired mean maximum plasma concentration Cmax (See [0157], [0158], [0168], [0188], Examples 1-4, Tables 1-4, Figure 2). Moline ‘342 disclosed randomized, double blind, placebo- controlled, sequential, single- dose study to evaluate the safety, tolerability and pharmacokinetics of compound A after single doses administered orally (See Example 1, [0181]- [0200]).
Regarding the administration time recited in instant claims 2 and 6, Moline ‘342 teaches single oral dosing of compound A is administered in the evening approximately 30 minutes prior to subject’s bedtime (See [0182],[0190]), and blood samples are collected at various period for assessment of pharmacokinetics (See [0191]- [0196], Table 1). Moline ‘342 teaches 8-hour PSG was performed starting at the subject’s bedtime (See [0199]).
Regarding the dose limitation, Moline ‘342 explicitly teaches the therapeutically effective amount is single 5 mg daily dose, wherein said single daily dose achieves desired mean AUC(0-t) (See [0038], claim 27, 32, 37, 42).
Moline ‘342 collectively teaches a method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof to a patient in need thereof at a single daily dose ranging from 5 mg to 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, before going to bed.
Moline ‘342 is silent about subjects having hepatic impairment classified under Child-Pugh classification. However, Moline ‘342 disclosed multiple clinical trials, wherein subjects with impaired hepatic functions were not explicitly excluded. In other words, Moline ‘342 method of treating insomnia was administered to subjects in need thereof including subjects having impaired hepatic functions.
As elaborated in preceding 103 rejection and applied as before, NCT03440424 teaches a single daily dose of lemborexant (10 mg ) for treating insomnia in subjects with hepatic impairment classified under Child Pugh classification.
It’s common practice to administer sleep medicine before going to bed and dosage adjustment (administration timing, frequency, etc.) based on patient’s condition (e.g. hepatic function) is routine practice in treating insomnia. FDA guidance 2003 teaches hepatic function of subject might have effects on PK and PD of a drug. FDA guidance 2003 teaches Child-Pugh classification in patients with impaired hepatic function and provides guidance for study design, data analysis of pharmacokinetics and impact on dosing and labeling. FDA guidance 2003 is considered as common knowledge for a skilled artisan in drug discover/development in pharmaceutical industry.
It would have been prima facie obvious to one of ordinary skilled in the art to explore the method of treating insomnia with 5 mg to 10 mg of orally administered lemborexant taught by Moline ‘342 in different patient population with hepatic impairment as taught by NCT03440424, together with exploration/optimization based on general knowledge of lemborexant and insomnia treatment and arrive at instant claims with reasonable expectation of success. An ordinary skilled would be motivated to combine the teachings of Moline ‘342 and NCT03440424 because all teachings are directed to method of treating insomnia with lemborexant. A skilled artisan would reasonably expect the lower end of lemborexant dose regimen (5mg) exhibit lower drug exposure than 10mg of lemborexant, thus safer for patient population with hepatic impairment. The combined teachings of Moline ‘342 and NCT03440424, together with general knowledge of lemborexant and insomnia treatment would provide an alternative safe administration regimen for patients with impaired hepatic function.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the teachings of prior art and general knowledge of lemborexant and insomnia treatment. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2 and 4-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10188652 B2 in view of NCT03440424 (version 2, 09/05/2018 ) and Murphy et al. (Journal of Clinical Sleep Medicine, Vol. 13, No. 11, 2017, Applicant’s IDS dated 06/05/2024, Cite No. 1, Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results from a Bayesian, Adaptive, Randomized, Double-Bind, Placebo-Controlled Study).
Reference claims 1-13 are directed to a method of treating insomnia, comprising administrating orally a dosage form comprising a therapeutically effective amount of compound A (i.e. lemborexant), wherein said therapeutically effective amount is a single daily dose ranging from about 2.5 mg to about 10 mg to achieve desired pharmacokinetic profile (e.g. mean Cmax) in human subjects. Reference claims 2, 5, 8 and 13 further recite therapeutically effective amount of Compound A (i.e. lemborexant) is single 5 mg daily dose.
Reference claims are silent about subjects having hepatic impairment classified under Child-Pugh classification and administration before bedtime.
As elaborated in preceding 103 rejection and applied herein as before, NCT03440424 teaches single daily dose of lemborexant for treating insomnia and limitation of hepatic impairment classified under Child Pugh classification. Murphy teaches lemborexant (e.g. 5mg, 10mg per day) was taken 30 minutes before bedtime and 8h polysomnography PSG.
It’s common practice to administer sleep medicine before going to bed and dosage adjustment (administration timing, frequency, etc.) based on patient’s condition (e.g. hepatic function) is routine practice in treating insomnia. It would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of reference claims, NCT03440424 and Murphy, together with exploration/optimization based on general knowledge of lemborexant and insomnia treatment and arrive at instant claims with reasonable expectation of success. An ordinary skilled would be motivated to combine the teachings of reference claims, NCT03440424 and Murphy because all teachings are directed to method of treating insomnia with lemborexant. A skilled artisan would reasonably expect the lower end of lemborexant dose regimen (5mg) exhibit lower drug exposure than 10mg of lemborexant, thus safer for patient population with hepatic impairment. The combined teachings of reference claims, NCT03440424 and Murphy, together with general knowledge of lemborexant and insomnia treatment would provide an alternative safe administration regimen for patients with impaired hepatic function.
The instant application shares at least one common inventor with reference patent. The instant application is not related to reference patent on the record and thus no 35 USC 121 shield exists.
Claims 2 and 4-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 22-24 of U.S. Patent No. 8268848 B2 in view of NCT03440424 (version 2, 09/05/2018 ) and Murphy et al. (Journal of Clinical Sleep Medicine, Vol. 13, No. 11, 2017, Applicant’s IDS dated 06/05/2024, Cite No. 1, Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results from a Bayesian, Adaptive, Randomized, Double-Bind, Placebo-Controlled Study).
Reference claims are directed to compound (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (i.e. lemborexant) and method for treating sleep disorder (e.g. insomnia) with lemborexant.
Reference claims are silent about subjects having hepatic impairment classified under Child-Pugh classification and administration before bedtime.
As elaborated in preceding 103 rejection and applied herein as before, NCT03440424 teaches the single daily dose of lemborexant for treating insomnia and limitation of hepatic impairment classified under Child Pugh classification. Murphy teaches lemborexant (e.g. 5mg, 10mg per day) was taken 30 minutes before bedtime and 8h polysomnography PSG.
It’s common practice to administer sleep medicine before going to bed and dosage adjustment (administration timing, frequency, etc.) based on patient’s condition (e.g. hepatic function) is routine practice in treating insomnia. It would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of reference claims, NCT03440424 and Murphy, together with exploration/optimization based on general knowledge of lemborexant and insomnia and arrive at instant claims with reasonable expectation of success. An ordinary skilled would be motivated to combine the teachings of reference claims, NCT03440424 and Murphy because all teachings are directed to method of treating insomnia with lemborexant. A skilled artisan would reasonably expect the lower end of lemborexant dose regimen (5mg) exhibit lower drug exposure than 10mg of lemborexant, thus safer for patient population with hepatic impairment. The combined teachings of reference claims, NCT03440424 and Murphy, together with general knowledge of lemborexant and insomnia treatment would provide an alternative safe administration regimen for patients with impaired hepatic function.
The instant application shares at least one common inventor with reference patent. The instant application is not related to reference patent on the record and thus no 35 USC 121 shield exists.
Claims 2 and 4-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 9-10, 12, 26, 28, 41 and 43 of copending Application No. 17/443,650 in view of NCT03440424 (version 2, 09/05/2018 ) and Murphy et al. (Journal of Clinical Sleep Medicine, Vol. 13, No. 11, 2017, Applicant’s IDS dated 06/05/2024, Cite No. 1, Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results from a Bayesian, Adaptive, Randomized, Double-Bind, Placebo-Controlled Study). This is a provisional nonstatutory double patenting rejection.
Reference claims are directed to a method of improving sleeping quality/efficiency (e.g. continuity of nocturnal sleep) and/or treating various sleep disorder (e.g. excessive daytime sleepiness) in a subject with irregular sleep-wake rhythm disorder, comprising administering to a subject in need thereof an effective amount of lemborexant or pharmaceutically acceptable salts thereof.
Reference claims are silent about subjects having hepatic impairment classified under Child-Pugh classification and administration before bedtime.
The rationale of combining reference claims with NCT03440424 and Murphy is similar as elaborated in preceding non-statutory double patenting rejections. The combined teachings of reference claims, NCT03440424 and Murphy, together with general knowledge of lemborexant and sleep disorder treatment would provide an alternative administration regimen for treating sleep disorder (e.g. insomnia ) in patients with impaired hepatic function.
The instant application shares at least one common inventor with reference patent. The instant application is not related to reference patent on the record and thus no 35 USC 121 shield exists.
Claims 2 and 4-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33, 47 and 50 of copending Application No. 17/597,074 in view of NCT03440424 (version 2, 09/05/2018 ). This is a provisional nonstatutory double patenting rejection. Notice of Allowance for 17/597,074 is mailed on 04/01/2026 and 06/05/2026.
Reference claims are directed to a method for treating insomnia comprising administering orally a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof.
Reference claims 47 and 50 recite a method for treating insomnia, comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the method comprising orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein if the 5 mg dose is well tolerated but not effective, then the dose can be increased to 10 mg once daily.
Reference claims are silent about subjects having hepatic impairment classified under Child-Pugh classification.
The rationale of combining reference claims with NCT03440424 is similar as elaborated in preceding non-statutory double patenting rejections. The combined teachings of reference claims and NCT03440424, together with general knowledge of lemborexant and sleep disorder treatment would provide an alternative safe administration regimen for treating sleep disorder (e.g. insomnia ) in patients with impaired hepatic function.
The instant application shares at least one common inventor with reference patent. The instant application is not related to reference patent on the record and thus no 35 USC 121 shield exists.
Conclusion
No claim is allowed.
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/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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