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 Application
This Office Action is in response to applicant’s arguments filed on 7/31/26. Claims 2-3, 5-8, 10, 15-16, 21-34 have been cancelled. Claims 1, 4, 9, 11-14, 17-20, 35-37 are pending. Claims 1 and 17 have been amended. Claims 1, 4, 9, 11-14, 17-20, 35-37 are examined herein.
Applicant’s arguments have been fully considered but found not persuasive. The rejections of the last Office Action are maintained for reasons of record and modified below due to the claim amendments.
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 1, 4, 9, 11-14, 17-20, 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42-60 of copending Application No. 18/988,194. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite a method of treating fibromyalgia by sublingual administration of a total dose of 5.6 mg of 75% ± 2% cyclobenzaprine HCl and 25% ± 2% β-mannitol by weight eutectic with a basifying agent. It is noted that the limitation regarding “wherein the associated symptom of pain is reduced by 30% or greater” is considered obvious since it is drawn to a resulting property of the claimed method steps, which has been taught by the referenced claims.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1, 4, 9, 11-14, 17-20, 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-50 of copending Application No. 19/421,039. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite a method of treating fibromyalgia and its associated symptoms of pain, sleep disturbance, and fatigue by sublingual administration of a total dose of 5.6 mg of 75% ± 2% cyclobenzaprine HCl and 25% ± 2% β-mannitol by weight eutectic with a basifying agent. It is noted that the limitation regarding “wherein the associated symptom of pain is reduced by 30% or greater” is considered obvious since it is drawn to a resulting property of the claimed method steps, which has been taught by the referenced claims.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Response to Arguments
Examiner acknowledges Applicant’s request that the double patenting rejection(s) be held in abeyance until allowable subject matter is identified.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham vs John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1, 4, 9, 11-14, 17-20, 35-37 are rejected under 35 U.S.C. 103(a) as being obvious over Lederman et al. (WO 2016/044796, of record) in view of Lederman et al. ("Bedtime, Rapidly Absorbed Sublingual Cyclobenzaprine (TNX-102 SL) for the Treatment of Fibromyalgia: Results of a Phase 2b Randomized, Double-Blind, Placebo- Controlled Study, 2015, Abstract 2309, of record) and ("History of Changes for Study: NCT04172831; A Study To Evaluate The Efficacy And Safety Of TNX -102 SL In Patients With Fibromyalgia (RELIEF)", ClinicalTrails.gov, 2020, 10 pages, of record).
The instant claims are directed to a method of treating fibromyalgia by administering a total dose of 5.6 mg of 75% ± 2% cyclobenzaprine HCl and 25% ± 2% β-mannitol by weight eutectic.
Lederman et al. 2016 teach that cyclobenzaprine is known to be useful for the treatment of fibromyalgia and sleep disturbances caused by chronic fatigue and chronic pain disorder (paragraph 0003). Fibromyalgia is traditionally characterized by pain, sleep disturbances, and fatigue (paragraph 0063). A preferred embodiment of cyclobenzaprine is the eutectic 75% ± 2% cyclobenzaprine HCl and 25% ± 2% β-mannitol with the basifying agent, K2HPO4 (paragraph 0005). Transmucosal administration is taught, for example sublingual tablets, films, liquids, powders, and sprays (paragraph 0061). Doses and dosing regimens can be determined by one of skill in the art according to the needs of a subject to be treated. The skilled worker may take into consideration factors such as the age or weight of the subject, the severity of the disease or condition being treated, and the response of the subject to treatment. A composition of the invention can be administered, for example, as needed or on a daily basis. In some embodiments, a composition can be administered immediately prior to sleep or several hours before sleep. Administration prior to sleep may be beneficial by providing the therapeutic effect before the onset of the symptoms of the disease or condition being treated. Dosing may take place over varying time periods. For example, a dosing regimen may last for 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, or longer (paragraph 0062). The table on page 12 shows a dosage of 10 mg of cyclobenzaprine HCl. It is noted that fatigue on average will be reduced compared to placebo since Lederman et al. teach that cyclobenzaprine is useful in treating fatigue associated with fibromyalgia. However, Lederman et al. 2016 fail to disclose a total dose of 5.6 mg of cyclobenzaprine HCl divided into two 2.8 mg dosage units.
Lederman et al. 2015 teach the safety and efficacy of a rapidly absorbed sublingual cyclobenzaprine (TNX-102 SL) for the treatment of fibromyalgia, characterized by pain and sleep disturbance. TNX-102 SL is a eutectic sublingual tablet formulation of low-dose cyclobenzaprine HCl (2.8 mg) designed for rapid absorption and long-term bedtime use. Patients were randomized to receive TNX-102 SL or a placebo and outcome measures included daily pain and sleep diaries using the numerical rating scale (NRS). Data was analyzed by mean change from baseline. Responder analysis of week 12 daily diary pain showed greater than 30% improvement from baseline. All measure of sleep quality improved compared to placebo.
ClinicalTrails.gov teaches a study evaluating the efficacy and safety of TNX-102 SL in patients with fibromyalgia (title) where a total of 5.6 mg (2 x 2.8 mg) of TNX-102 SL was administered daily at bedtime (page 3).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, at the time the claimed invention was made, to optimize the 10 mg dosage of cyclobenzaprine HCl in the method of treating fibromyalgia, as taught by Lederman et al. 2016, to a total of 5.6 mg (2 x 2.8 mg), as taught by Lederman et al. 2015 and ClinicalTrails.gov.
A person of ordinary skill in the art would have been motivated to optimize cyclobenzaprine HCl to a total dose of 5.6 mg (2 x 2.8 mg) because Lederman et al. 2015 teach that 2.8 mg of cyclobenzaprine HCl and ClinicalTrails.gov teach that 2 doses of 2.8 mg for a total of 5.6 mg of cyclobenzaprine HCl are both known, useful, and effective for treating fibromyalgia. Therefore, the skilled artisan would have had a reasonable expectation of success in treating fibromyalgia by administering a total dose of 5.6 mg of 75% ± 2% cyclobenzaprine HCl and 25% ± 2% β-mannitol by weight eutectic.
Generally, mere optimization of ranges will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d at 1382; lt has been held that it is within the skills in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. In re Boesch, 205 USPQ 215 (CCPA 1980) MPEP 2114.04
Response to Arguments
Applicant argues that Lederman 2016’s actual examples do not refer to transmucosal administration of the eutectic and that administration is only being mentioned as one of several possible administration routes, with no suggestion that any route would have any different therapeutic effects than another. Rather Lederman 2016 suggests oral administration.
This is not persuasive because Applicant is reminded that the reference clearly teaches transmucosal administration in paragraph 0061.
Applicant argues that although Lederman 2015 teaches a dose of 2.8 mg, the reference fails to teach a total dose of 5.6 mg. There would have been no motivation to double the dose. Furthermore, Applicant argues that the results of the ClinicalTrials.gov study were not available until after the Applicant’s priority date of 12/7/2020.
This is not persuasive because Applicant is reminded that Lederman 2016 already teaches cyclobenzaprine is known to be useful for the treatment of fibromyalgia and sleep disturbances caused by chronic fatigue and chronic pain disorder (paragraph 0003). Therefore, the secondary references were merely used to show that cyclobenzaprine can be safely administered in lower doses, for example 2 x 2.8 mg.
Conclusion
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 extension fee 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 Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623
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