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 1-4, 6, 8-12, 15, 18, 28-33, 38 and 61 are pending.
Claims 33, 32 and 61 remain withdrawn.
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 1-4, 6, 8-12, 15, 18, 28-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Montemurro Am J Respir Crit Care Med. 2019;199(10):1267–1276, Cheng, J Sleep Res. 2020;29:e13021. Liguori, Sleep Medicine Volume 56, April 2019, Pages 171-176, Gallina, B-ENT, 2009, 5, 245-250.
Base claim 1: A method of treating a subject having a condition associated with pharyngeal airway collapse, the method comprising administering to a subject in need thereof an effective amount of (i) a norepinephrine reuptake inhibitor (NRI) and (ii) Lemborexant or a pharmaceutically acceptable salt thereof.
Montemurro teaches that the main cause of sleep-related hypotonia of the pharyngeal muscles (pharyngeal airway collapse) to be the central reduction of norepinephrine from wakefulness to sleep. Montemurro teaches the combination of atomoxetine and oxybutynin greatly reduces obstructive sleep apnea severity. Specifically at page 1288 column B, Montemurro many combination of drugs, specifically at page 1288, column C, norepinephrine reuptake inhibitor (atomoxetine) administered in combination with an antimuscarinic drug combination with an antimuscarinic drug (oxybutynin), synergistic effects (at page 1274, column A). Montemurro concludes that pharmacological resolution of OSA is possible using a combination of noradrenergic and antimuscarinic drugs with specific neurotransmitter receptor binding profiles that activate the upper airway dilator muscles during sleep and that his discovery opens new possibilities for the future treatment of obstructive sleep apnea.
Thus while Montemurro teaches combination of NRI with antimuscarinic drug to treat condition associated with pharyngeal airway collapse,
Montemurro does not teach combination of NRI with Lemborexant drug to treat condition associated with pharyngeal airway collapse.
The teachings of Cheng, Liguori and Gallina are invoked to cure the deficiency of Montemurro.
Cheng teaches at page 1 of 7 Abstract that that Lemborexant is a dual orexin receptor antagonist indicated for the treatment of adult and elderly individuals with insomnia. More specifically, Cheng teaches Lemborexant demonstrated respiratory safety after single and multiple doses in adult and elderly participants with mild OSA. The incidence of treatment-emergent adverse events was low and similar for lemborexant and placebo. Lemborexant demonstrated respiratory safety in this study population and was well tolerated.
Cheng teaching is consistent with the teachings of Liguori and Gallina with regards to the inherent biochemical property of Lemborexant, as Liguori obstructive sleep apnea may induce orexinergic system. Likewise, Gallina teaches that obstructive sleep apnea syndrome (OSAS) is a sleep disorder caused by an excessive narrowing of the pharyngeal wall that collapses during inspiration, resulting in increased negative intrathoracic pressure, which further exacerbates the condition.
Taken together, the combination of Lemborexant with NRI is therefore suggested by the cited references, for synergistic and or additive effect, to treat condition associated with pharyngeal airway collapse, for claim 1 (and dependent claims 11, 12 daily, oral; claims 15, 18 additional additive, claims 28, 29, 30, by definition, claims 30-32 wakefulness) are found in the teachings of Montemurro.
For NRI claims 2-4, 6, see Montemurro page 1268 column B and C) dose claims 8-11 see Montemurro page 1268 column C under Methods
Note that the NRI atomoxetine and Lemborexant are established drugs known independently for insomnia, as Strattera and Dayvigo respectively.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Obstructive Sleep Apnea Treatment Market Size, Companies:
Motivation: $359 million in 2023; Growth rate 17%
Anaclet,. "Orexin/Hypocretin and Histamine: Distinct Roles in the Control of Wakefulness Demonstrated Using Knock-Out Mouse Models". Journal of Neuroscience. 29 (46): 14423–14438 (2009).
Response to Remarks filed 07/09/2026:
Applicants’ remarks are considered but are not persuasive as explained below.
Applicant’s argument focuses on the biochemical properties (specific receptor activity) of the active agents and OSA severity.
Response:
Montemurro is invoked for the idea of ‘combination’.
Secondary references such as Cheng teach the established drug lemborexant was safe to treat insomnia in patients with mild OSA.
Montemurro does not teach the combination with Lemborexant was discussed in the previous action.
Cheng does not teach the OSA severity is irrelevant here, as the severity is not a limitation of the claim. The term OSA appears in dependent claim 29.
According to specification [0060] the invention determines the effect of the combination of atomoxetine and lemborexant on OSA severity and sleep. This is consistent disclosed data and also consistent with the focus of Applicants Remarks as to ‘surprising’ results. Again, the claims are not limited to this specific combination. Reiterating the ‘unpredictability’ in the art for ‘combination of drugs’, overlooks the breadth of claims with respect to NRI.
The rejection is not under 35 USC § 102.
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.
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 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.
Claim(s) 1-4, 6, 8-12, 15, 18, 28-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11123313. Montemurro Am J Respir Crit Care Med. 2019;199(10):1267–1276, Cheng, J Sleep Res. 2020;29:e13021. Liguori, Sleep Medicine Volume 56, April 2019, Pages 171-176, Gallina, B-ENT, 2009, 5, 245-250. Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims contain overlapping subject matter.
The difference between the base claim(s) is:
11123313: active ingredient combination is NRI Plus muscarinic receptor antagonist
Instant: active ingredient combination is NRI Plus Lemborexant
The position taken is that the replacement of muscarinic receptor antagonist by Lemborexant is suggested by the combined teachings of Montemurro, Cheng, Liguori, and Gallina which are elaborated below:
The following is awkward reiteration of prior art teachings (mandated by Examination guidelines).
Montemurro teaches that the main cause of sleep-related hypotonia of the pharyngeal muscles (pharyngeal airway collapse) to be the central reduction of norepinephrine from wakefulness to sleep. Montemurro teaches the combination of atomoxetine and oxybutynin greatly reduces obstructive sleep apnea severity. Specifically at page 1288 column B, Montemurro many combination of drugs, specifically at page 1288, column C, norepinephrine reuptake inhibitor (atomoxetine) administered in combination with an antimuscarinic drug combination with an antimuscarinic drug (oxybutynin), synergistic effects (at page 1274, column A). Montemurro concludes that pharmacological resolution of OSA is possible using a combination of noradrenergic and antimuscarinic drugs with specific neurotransmitter receptor binding profiles that activate the upper airway dilator muscles during sleep. This discovery opens new possibilities for the future treatment of obstructive sleep apnea.
Thus, while Montemurro teaches combination of NRI with antimuscarinic drug to treat condition associated with pharyngeal airway collapse, does not teach combination of NRI with Lemborexant drug to treat condition associated with pharyngeal airway collapse.
Cheng teaches at page 1 of 7 Abstract that that Lemborexant is a dual orexin receptor antagonist indicated for the treatment of adult and elderly individuals with insomnia. More specifically, Cheng teaches Lemborexant demonstrated respiratory safety after single and multiple doses in adult and elderly participants with mild OSA. The incidence of treatment-emergent adverse events was low and similar for lemborexant and placebo. Lemborexant demonstrated respiratory safety in this study population and was well tolerated.
Cheng teaching is consistent with the teachings of Liguori and Gallina with regards to the inherent biochemical property of Lemborexant, as Liguori obstructive sleep apnea may induce orexinergic system. Likewise, Gallina teaches that obstructive sleep apnea syndrome (OSAS) is a sleep disorder caused by an excessive narrowing of the pharyngeal wall that collapses during inspiration, resulting in increased negative intrathoracic pressure, which further exacerbates the condition.
Also note that comparison of working examples and Figures indicate that there is no significant technical effect in the replacement of oxybutynin with Lemborexant.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Anaclet,. "Orexin/Hypocretin and Histamine: Distinct Roles in the Control of Wakefulness Demonstrated Using Knock-Out Mouse Models". Journal of Neuroscience. 29 (46): 14423–14438 (2009).
Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804
Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32
(2010) 324–330.
Claim(s) 1-4, 6, 8-12, 15, 18, 28-33, 38, 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11911351. 11123313 Montemurro Am J Respir Crit Care Med. 2019;199(10):1267–1276, Cheng, J Sleep Res. 2020;29:e13021. Liguori, Sleep Medicine Volume 56, April 2019, Pages 171-176, Gallina, B-ENT, 2009, 5, 245-250. Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims contain overlapping subject matter.
The difference between the base claim(s) is:
11911351: active ingredient combination is NRI Plus oxybutynin
Instant: active ingredient combination is NRI Plus Lemborexant
The position taken is that the replacement of oxybutynin, a muscarinic receptor antagonist by Lemborexant is suggested by the combined teachings of Montemurro, Cheng, Liguori, and Gallina which are elaborated below:
The following is awkward reiteration of prior art teachings (mandated by Examination guidelines).
Montemurro teaches that the main cause of sleep-related hypotonia of the pharyngeal muscles (pharyngeal airway collapse) to be the central reduction of norepinephrine from wakefulness to sleep. Montemurro teaches the combination of atomoxetine and oxybutynin greatly reduces obstructive sleep apnea severity. Specifically at page 1288 column B, Montemurro many combination of drugs, specifically at page 1288, column C, norepinephrine reuptake inhibitor (atomoxetine) administered in combination with an antimuscarinic drug combination with an antimuscarinic drug (oxybutynin), synergistic effects (at page 1274, column A). Montemurro concludes that pharmacological resolution of OSA is possible using a combination of noradrenergic and antimuscarinic drugs with specific neurotransmitter receptor binding profiles that activate the upper airway dilator muscles during sleep. This discovery opens new possibilities for the future treatment of obstructive sleep apnea.
Thus, while Montemurro teaches combination of NRI with antimuscarinic drug to treat condition associated with pharyngeal airway collapse, does not teach combination of NRI with Lemborexant drug to treat condition associated with pharyngeal airway collapse.
Cheng teaches at page 1 of 7 Abstract that that Lemborexant is a dual orexin receptor antagonist indicated for the treatment of adult and elderly individuals with insomnia. More specifically, Cheng teaches Lemborexant demonstrated respiratory safety after single and multiple doses in adult and elderly participants with mild OSA. The incidence of treatment-emergent adverse events was low and similar for lemborexant and placebo. Lemborexant demonstrated respiratory safety in this study population and was well tolerated.
Cheng teaching is consistent with the teachings of Liguori and Gallina with regards to the inherent biochemical property of Lemborexant, as Liguori obstructive sleep apnea may induce orexinergic system. Likewise, Gallina teaches that obstructive sleep apnea syndrome (OSAS) is a sleep disorder caused by an excessive narrowing of the pharyngeal wall that collapses during inspiration, resulting in increased negative intrathoracic pressure, which further exacerbates the condition.
Also note that comparison of working examples and Figures indicate that there is no significant technical effect in the replacement of oxybutynin with Lemborexant.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Anaclet,. "Orexin/Hypocretin and Histamine: Distinct Roles in the Control of Wakefulness Demonstrated Using Knock-Out Mouse Models". Journal of Neuroscience. 29 (46): 14423–14438 (2009).
Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804
Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32
(2010) 324–330.
Response to Remarks filed 07/09/2026.
Applicants’ arguments rely on the Applicants Remarks to overcome rejection under 35 USC § 103.
Applicants’ arguments are not persuasive. The rejection here is not Statutory 101 type double patenting rejection.
The response to Applicant Remarks is invoked here.
Telephone conversation.
In the week of Aug 17, Examiner discussed with Attorney of record Andrew S Chipouras how to go forward for a favorable office action.
Examiner suggested the following to place the case in condition for allowance.
To overcome 103 and double patenting rejections:
Roll in limitation of claim 8 and claims 9/10 into claim 1 with a wherein clause.
Amend dependent claims accordingly.
DELETE withdrawn claims.
Even though Applicant understood Examiner’s position and agreed to get back soon, a timely response was not received.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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