DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Claims
Pursuant to the amendment dated 11/07/2025, claims 1-5, 9-13, and 30 have bee cancelled. Claims 6-8, 19, 20, and 22-24 have been cancelled in a prior communication.
Claims 14-18, 21, and 25-29 are pending and under current examination.
All rejections not reiterated have been withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 21 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
This is a new matter rejection. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
With regard to claims 21, the full scope of the limitation “cellulose ether” having the property of being a pore former is not supported by the as filed application. The recitation of several species of cellulose ether polymers that are pore formers does not provide sufficient support for the entire subgenus of cellulose ethers having the property of being a pore former.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the new matter concerns outlined above.
Response to Arguments
Applicant's arguments filed 11/07/2025 have been fully considered but they are not persuasive. Applicant’s comment on page 4 of the remarks that the claims have been amended to obviate the new matter rejections is noted; however, claim 21 has not been amended and therefore remains rejected under 35 USC 112(a) as set forth above.
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 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 pre-AIA 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, 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 v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 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 pre-AIA 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 pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 14-18, 21, 25, and 27-29 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sesha (WO 2011/008298; publication date: 01/20/2011, cited in Applicant’s IDS) and Breder I (WIPO Publication No. WO 2010/127120; publication date: 11/04/2010, cited in Applicant’s IDS), and Venkatesh (US PGPub No. 2006/0246134; publication date: 11/02/2006; cited in Applicant’s IDS), and further in view of Bayliss et al. (Br J. Clin Pharmacol pages 209-214; publication year: 1975, cited in Applicant’s IDS) and Breder II (US 2010/0069390; publication date: 03/18/2010) as evidenced by Guittard et al. (US 2001/0005728; publication date: 2001/0005728).
The examiner notes that the PTAB issued a new grounds of rejection under 35 USC 103 in the decision mailed 03/26/2025 in Appeal No. 2024-002750. In this action, the examiner adopts the boards reasoning in whole and for this reason the ‘2750 decision is incorporated by reference in its entirety.
The examiner also notes that the PTAB stated on page 19 of the decision “that how the references are put together (A in view of B, or B in view of A, or the designation of a primary and secondary reference) is immaterial, as it is the combination together that is important”. On page 19 of the decision, the PTAB cited In re Bush as further support for this statement. In this case, the examiner considers each cited reference to provide important instruction and/or motivation to formulate viloxazine as a controlled release multiparticulate formulation having the claimed release profile.
Sesha discloses an extended release formulation for drug delivery (abstract).
More specifically, Sesha makes the following statements:
“candidate([s] for sustained release” encompass] all the characteristics of a drug which make it a candidate for formulating it into an extended release fashion like a short elimination half life and consequent dosing of more than once a day, a single dose product given in an extended fashion to achieve better clinical results and avoid side effects associated with an immediate release etc. (0050)
The term “delayed-release dosage forms” or dosage forms which exhibit a delayed-release of the drug. The dosage forms administered once daily that do not substantially release drug immediately following administration but at a later time. Delayed-release dosage forms provide a time delay prior to the commencement of drug-absorption. Such dosage forms will desirably be coated with a delayed release coat. (0051)
The term “extended-release dosage forms” or dosage forms which exhibit an “extended release” of drug . . . is defined to mean dosage forms administered once daily that release drug slowly, so that plasma concentrations of the drug are maintained at a therapeutic level for an extended period of time such that the sustained-release dosage form provides therapeutic benefit over a 12-24-hour period. (0056)
Sesha establishes that dosage forms, such as slow release dosage forms, with pH-dependent release coatings such that drug is released “in desired areas of the gastro-intestinal (GI) tract, e.g., the stomach or small intestine,” were known in the art (Abstr; 0114: Sesha discloses the use of “pH-dependent coatings to obtain formulations,” wherein “unprotected drug is coated over the enteric coat and is released in the stomach, while the remainder, being protected by the enteric coating, is released further down the gastrointestinal tract.”).
Breder I discloses a method of treating depression by administering 20-800 mg viloxazine per day (Breder I: claims 5 and 9). The disclosure of Breder I is directed towards diminishing the side effects of viloxazine when it is used as an anti-depressant (Breder I: claim 1).
Venkatesh discloses timed pulsatile release formulations for optimizing controlled release and discloses mores specifically that “active pharmaceutical ingredients [(APIs)] suitable for incorporation into . . . [its] time-controlled pulsatile release systems include basic bioactive molecules or their salts” (emphasis added) 0046). Venkatesh:
[R]elates to the development of timed, pulsatile release bead populations comprising one or more alkaline pharmaceutical actives exhibiting release of the drug after a predetermined delay (lag time) of more than about 5 hours and to the production of oral drug delivery systems to target PK (pharmacokinetics, i.e., plasma concentration-time) profiles suitable for a twice- or once daily dosing regimen, thereby minimizing potential risks of adverse side effects, enhancing patient compliance and therapeutic efficacy, and reducing cost of treatment (0001; emphasis added).
Venkatesh discloses: “The unique pharmacokinetic profile needed can be calculated from a simulated modeling developed using the pharmacokinetic parameters, knowledge of drug solubility, absorption along the gastrointestinal tract and elimination half-life” (Venkatesh 0002; see id. 0008 (Venkatesh discloses “[s]pecific factors that can affect the lag-time include, but are not limited to, the therapeutic agent’s alkalinity/acidity, solubility, elimination half-life, and dosing (twice-daily or once-daily) regimen”)). Venkatesh discloses that “psychotherapeutic agents” are among the types of drugs that can be incorporated into its system (0046).
Venkatesh’s “pulsatile delivery system comprises one or more bead populations, such as immediate release (IR) [b]eads and timed, pulsatile release (TPR) bead populations,” wherein “[e]ach TPR bead population releases the drug as a rapid burst or as a sustained-release profile after a predetermined lag-time (for example, 10 hours or longer is achievable) upon oral administration” (Venkatesh 0008; see id. (Venkatesh discloses that its “finished dosage form . . . contain[s] the active substance alone or a combination of two or more coated bead populations to provide target plasma concentrations suitable for a once or twice-daily dosing regimen.”)).
Venkatesh discloses:
For example, a once-daily dosage form of an active with an elimination half-life of about 7 hours may contain a mixture of an IR bead population which allows immediate release, a second, TPR bead population with a shorter lag-time (about 3-4 hours), which allows a delayed “burst” release and a third, TPR bead population with a longer lag-time (about 6-9 hours), which allows a delayed, typically sustained-release profile of an active
with an elimination half-life of about 7 hours, thus enhancing safety, therapeutic efficacy and patient compliance while reducing cost of treatment.
Venkatesh discloses formulations with drug-release periods over about 5-20 hours(0022); Venkatesh discloses formulations with “a lag-time of about 3 hours or less” or “about 6 hours or longer” (0025); Venkatesh discloses formulations “exhibiting a lag-time of up to about 10 hours or longer” (0031); Venkatesh discloses formulations wherein drug release is “delayed for up to about 10-15 hours after oral administration”(0036); Venkatesh discloses a formulations having “[a] single targeted sustained-release profile over several hours after oral administration, with or without an immediate release pulse, . . . in accordance with certain of the timed pulsatile release drug delivery systems” disclosed by Venkatesh (0037).
Venkatesh discloses that “the active core of the dosage form may comprise an inert particle, which is coated with a drug-containing film forming formulation,” wherein “[t]he amount of drug in the core will depend on the drug and the dose that is desired,” and “[t]hose skilled in the art will be able to select an appropriate amount of drug for coating or incorporation into the core to achieve the desired dosage form (0018). Venkatesh discloses “Alternatively in accordance with other embodiments, drug-containing microgranules or pellets may be prepared by rotogranulation, high-shear granulation and extrusion-spheronization or compression (as mini-/micro-tablets) of the drug, a polymeric binder and optionally fillers/diluents” (0019). ([T]he active core may be prepared by rotogranulation, or by granulation followed by extrusion-spheronization or tableting into micro/mini-tablets. The drug substance, a binder, an optional dissolution rate controlling polymer, and optionally other pharmaceutically acceptable excipients (e.g., diluents/fillers) may be blended together in a high-shear granulator” (0021).
Venkatesh discloses that because “the polymer blend system typically utilized to delay the onset of drug-release by several hours upon oral administration is a mixture of water-insoluble and enteric polymers, the extent of delayed onset depends on the acidity/alkalinity of the API” (0017).
Venkatesh discloses:
The composition and thickness of the barrier coating, composition and thickness of the lag-time coating, ratio of IR beads to one or more TPR bead populations and total dose may be varied depending on the alkalinity, pH-dependent solubility and elimination half-life of the active ingredients to achieve target PK profiles (suitable for a once or twice daily dosing regimen) in patients in need of such medications (Abstract).
Bayliss discloses viloxazine has an in vivo half-life of 2-5 hours (Bayliss: abstract) and therefore requires multiple doses of an immediate release formulation to be consumed daily in order to maintain therapeutic plasma concentrations (Bayliss, figure 3, page 212). Bayliss discloses further that viloxazine exhibits maximum blood levels occurring in 1-4 [hours] of the oral dose,” “viloxazine is rapidly and almost totally absorbed after an oral dose,” and, thus, viloxazine therapy “should be easily controllable” (Abstract). Bayliss discloses four separate studies that investigated the “pharmacokinetic characteristics of [the] . . . antidepressant, viloxazine hydrochloride” (Abstract). Bayliss discloses the “[m]ean blood level curve . . . from four male volunteers over a 9 [hour] period during which three single doses of viloxazine hydrochloride . . . were taken at 4 hourly intervals” (Bayliss 212: Figure 3, legend; see also id. at Table 1 (Bayliss discloses “[m]aximum mean blood level . . . of viloxazine, and the time . . . of achieving maximum mean blood level in twelve males and four females who took single doses of viloxazine hydrochloride between 10 and 100 mg.”).
Breder II discloses a method of selecting a pharmaceutical agent suitable for treating ADHD in humans, which “comprises the steps of: (1) selecting one or a combination of active agents with known activity inhibiting either serotonin or noradrenergic reuptake transporters,” (2)-(3) performing receptor screening assays, “(4) selecting among the screened active agents at least one that targets the most of the different types of ADHD-associated receptors; and (5) optimizing the total dosage of the selected active agent(s)” (0019 (emphasis added); Breder II discloses that viloxazine is its preferred pharmaceutical agent (0020); Breder II discloses that the “term ‘viloxazine’ includes viloxazine and all pharmaceutically acceptable salts thereof (0031). Breder II discloses that “ADHD or ADHD-related disorders can be treated in human subjects by administering viloxazine in a total daily dose that is . . . approximately 20 to 800 mg for pediatric (agent 6 to 17) and adult population[s]” (0030); Breder II discloses the
administration of viloxazine “in an amount of from 10 to 600 mg/day.” (0031).
It would have been prima facie obvious for a person of ordinary skill in the art at the time of the instant invention to combine the respective teachings of Sesha, Venkatesh, Breder I, Bayliss, and Breder II as follows: Together, Venkatesh and Sesha provide detailed instructions on the parameters to optimize in an multiparticulate dosage for to achieve a desired drug release profile for any particular basic drug (see detailed description of teachings above). Venkatesh and Sesha explain that the amount, identity, and arrangement of the excipients as well as combinations of particles having different release profiles were known variables to adjust in order to achieve any target release profile. The skilled Artisan would have been motivated to take advantage of the versatility of the similar sustained release delivery systems disclosed by Sesha and Venkatesh in order to fine tune the release profile of viloxazine because this drug has an in vivo half-life of 2-5 hours (Bayliss: abstract) and therefore requires multiple doses of an immediate release formulation to be consumed daily in order to maintain therapeutic plasma concentrations (Bayliss, figure 3, page 212). Viloxazine has a number of undesirable side effects (Breder I, para 0017) and careful control over plasma levels is important for minimizing unwanted effects of a drug (Sesha: para 0050). One of ordinary skill in the art would have been further motivated to formulate viloxazine as a controlled release formulation in the manner disclosed by Sesha and Venkatesh in order to reduce side effects and increase patient compliance. With regard to the limitations of instant claims 1 and 14 that viloxazine or a salt thereof be the sole pharmaceutical ingredient in the composition, this is considered prima facie obvious because one having ordinary skill in the art would predict that the drug viloxazine could be formulated to have a sustained release profile by following the teachings contained teachings Sesha and Venkatesh regarding these standard, well-known, and routine dosage forms and would be motivated to do so in view of Breder I and Bayliss, as detailed above.
With regard to claims 1 and 14, the formulations disclosed by Sesha, contain a sustained release carrier (i.e. an extended release component) that causes sustained release of the active agent upon exposure to the g.i. tract. The composition may be further coated with an enteric polymer (para 0052). With regard to instant claim 1, Sesha discloses coating a matrix sustained release component comprising drug (Sesha: para 0085) and the formulation may be in the form of minitablets or coated microparticles (para 0052). With regard to instant claim 14, in another embodiment, the drug may be formulated as beads having an inert core that are subsequently coated with drug and then with the sustained release coating comprising the sustained release carrier (i.e. the extended release component is in the form of a layer; para 0085). Thus, Sesha discloses delayed release formulations (para 0051) having the structure required by instant claims 1 and 14. Venkatesh makes similar disclosures of these arrangements of drug within the particle, as summarized above.
With regard to claims 1 and 14, as noted above, Sesha discloses coating with an enteric polymer. Sesha discloses further that the enteric (i.e. pH-dependent) polymer protects the drug from release in the stomach and is released further down in the gastrointestinal tract (00114). The examiner considers the limitation “wherein the viloxazine or salt thereof in the DR component of the formulation is released when the formulation is exposed to a pH of 4.5 or above” to be a routine use of enteric polymers (i.e. polymers that do not dissolve in the low pH of the stomach and do dissolve at higher pH of the lower gastrointestinal tract). Venkatesh makes similar disclosures, as summarized above.
While Sesha does not expressly disclose coating inert beads with an immediate release drug layer, combining immediate release coated beads with extended release coated beads was a known method for optimizing pharmacokinetic profiles at the time of the instant invention. Venkatesh discloses that ratio of IR beads to TPR (timed pulsatile release; i.e. extended and delayed release) beads can be varied to accomplish a desired drug plasma concentration (abstract). Thus, combining, for example, extended release coated inert particles with immediate release coated inert beads was prima facie obvious at the time of the instant invention in view of Sesha and Venkatesh.
With regard to the limitation of instant claims 1 and 14 that the viloxazine be present in an amount effective to treat ADHD, the examiner notes that the amount of viloxazine disclosed by 20-800 mg viloxazine per day (Breder I: claims 5 and 9) falls entirely within the scope of the instant claims, therefore the prior art is considered to inherently teach an amount of viloxazine sufficient to treat ADHD. However, it also would have been prima facie obvious to include viloxazine in a quantity effective for treating ADHD. Breder II discloses that viloxazine can be used to treat ADHD (0004). It would have been prima facie obvious for one of ordinary skill in the art to optimize the quantity of viloxazine for ADHD treatment because the drug was known to have been effective for this purpose at the time of the instant invention. This would merely have required routine testing of several concentrations of viloxazine followed by measurement of ADHD symptoms, a standard practice in the pharmaceutical arts as of the instant effective filing date. See MPEP 2144.05.
With regard to expectation of success, The composition disclosed by Sesha is used to deliver basic drugs (See: Sesha, where pages 30-45 detail formulations of axomadol, CAS Registry No. 187219-99-4, pKa = 14.2 and pages 46-47 disclose a formulation of memantine, CAS Registry No. 19982-08-2, pKa 10.8), therefore one would have had a reasonable expectation of success formulating viloxazine because it is a basic drug (CAS No. 46187-91-8, pKa = 8.47). Also, as summarized above, both Sesha and Venkatesh establish that controlled release multiparticulate formulations having populations of beads that release drugs in order to achieve a target plasma concentration over time based upon the known pharmacokinetics of the drug were known at the time of the instant invention, and Bayliss provides this type of information for viloxazine. Moreover, Venkatesh discloses formulations that minimize potential risks of adverse side effects and relates specifically to formulation of alkaline agents. Sesha and Venkatesh provide a list of known compounds that are recognized by those of ordinary skill in the art to meet known extended release requirements. See KSR int’l Co. v. Teleflex Inc. (550 US 398, 416 (2007)): “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results”; “a person of ordinary skill is a person of ordinary creativity, not an automaton”. Breder II explains that those of ordinary skill in the art would have found it prima facie obvious to determine the total dosage of an active ingredient such as viloxazine for treatment of ADHD using routine optimization; and Bayliss discloses that viloxazine is rapidly and almost totally absorbed after an oral dose thus viloxazine therapy should be easily controllable. Finally, Sesha contemplates delivery of viloxazine in this formulation (para 0068), providing additional evidence that one having ordinary skill would have expected a sustained release multiparticulate formulation for viloxazine to be achievable..
Claims 1 and 14 have been amended on 05/23/2025 to require the presence of a pore former either in the matrix core (claim 1) or in the coating (claim 14).
With regard to claim 1, as noted above Venkatesh discloses “Alternatively in accordance with other embodiments, drug-containing microgranules or pellets may be prepared by rotogranulation, high-shear granulation and extrusion-spheronization or compression (as mini-/micro-tablets) of the drug, a polymeric binder and optionally fillers/diluents” (0019). ([T]he active core may be prepared by rotogranulation, or by granulation followed by extrusion-spheronization or tableting into micro/mini-tablets. The drug substance, a binder, an optional dissolution rate controlling polymer, and optionally other pharmaceutically acceptable excipients (e.g., diluents/fillers) may be blended together in a high-shear granulator” (0021). Thus, Venkatesh also describes matrix core multiparticulates coated with release rate controlling polymers. In para 0038 Venkatesh discloses that the binder for granulated (i.e. matrix core) embodiments of Venkatesh’s invention is hydroxypropyl cellulose (i.e. a cellulose ether; see Guittard: para 0038) and may be present in an amount of from 0.5 to 10% (0040). This it would have been prima facie obvious to employ the binder hydroxypropyl cellulose in the core of the controlled release particles because Venkatesh teaches its inclusion in this formulation type. The examiner notes that the instant specification identifies hydroxypropyl cellulose as a pore former (see e.g. page 16), thus, the binder described by Venkatesh is also a pore former (see MPEP 2112.01(II): "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). With regard to the ratio of release rate controlling polymer to pore former required by instant claim 1, Venkatesh discloses a range of 0.5 to 10% for the binder in their granulate (i.e. matrix core; 0040). This would provide a starting point for optimization of the binder content and the examiner considers it to be prima facie obvious to adjust the amount of dissolution rate controlling polymer per Venkatesh’s nomenclature (i.e. release rate controlling polymer) to achieve control over the dissolution rate. Absent evidence of the criticality of the claimed ratio, the examiner does not consider this limitation to patentably define over the cited prior art. See MPEP 2144.05(II)(A): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With regard to instant claims 14 and 21, Sesha discloses that “flux-enhancing agents” can be included in the membrane and include substances such as hydroxypropyl cellulose (para 0096; hydroxypropyl cellulose is a cellulose ether, see Guittard: para 0024). The examiner considers arriving at a ratio of release rate controlling compound to pore former to be a matter of testing several amounts of pore former according to routine methods of evaluating drug release and therefore does not consider the limitations of instant claim 20 to patentably define over the cited prior art. Moreover, Venkatesh also provides guidance as to the ratio of release rate controlling polymers (e.g. a water insoluble polymer) and the water soluble polymer (which would dissolve on contact with an aqueous environment leaving a pore where the dissolvable polymer had been): In claim 9, Venkatesh indicates that a particle core is provided with a barrier coating comprising a water-insoluble polymer alone or in combination with a water soluble polymer at a ratio of from about 9:1 to 5:5. This would provide further guidance to the artisan of ordinary skill for optimization of release kinetics. See MPEP 2144.05.
With respect to instant claims 2 and 15, regarding the amount of viloxazine that may be present in the instant invention, Sesha disclose example compositions containing from 50 to 250 mg of axomadol (see examples on pages 30-47). The skilled Artisan looking to create a sustained release preparation of viloxazine would optimize the amount of drug based upon the dosage required for the intended patient population as well as the efficacy of the formulation in drug release. Sesha teaches that it was known at the time of the instant invention to modulate release profile by adjusting the amount of drug loaded in the formulation. Given the broad range in drug loading that can be accomplished by following the formulation strategies disclosed by Sesha, the examiner considers arriving at a viloxazine loading falling within the broad ranges recited in instant claims 2 and 15 to be a matter of routine optimization, absent unexpected results. Please refer to MPEP 2144.05, which addresses the obviousness of optimization of ranges.
With respect to instant claims 3 and 16, as noted above Sesha discloses formulations may be minitablets, microparticles etc. (para 0052).
With regard to instant claims 4 and 17, the slow release matrix disclosed by Sesha, whether in the form of a matrix core as required by instant claim 1 or a coat over an inert core may comprise hydrophilic or hydrophobic polymers at a concentration ranging from 1-80 % by weight (para 80, limitations of instant claim 6). The range for polymer concentration overlaps with that recited in instant claim 6. See MPEP 2144.05 regarding overlapping ranges: “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.”
With regard to instant claims 5 and 18, ethyl cellulose is a preferred hydrophobic polymer (para 00115).
With regard to instant claims 6 and 22, enteric (i.e. pH-dependent) polymers disclosed by Sesha include cellulose acetate phthalate (para 00114).
With respect to instant claims 9 and 25, Breder I discloses administering 20-800 mg viloxazine per day (Breder I: claims 5 and 9).
Claims 1, 11, 12, 14, 27, and 28 require the following limitations that are not expressly described by Sesha or Breder I: wherein at least 80% of the viloxazine or salt thereof in the formulation is released from the formulation over a period of time of at least 2 hours and up to 14 hours; the formulation provides for a maximum steady state plasma concentration (Cmax) of viloxazine that is higher than the minimal therapeutically effective concentration and is in the range of 50% to 125% relative to the maximum plasma concentration produced by administration of viloxazine as an IR formulation TID or BID; and that the formulation provides for relative steady state area under the viloxazine plasma concentration time profiles for a 24 hour dosing interval (AUCtau) in the range of 80% to 125% as compared to viloxazine administered as an immediate release formulation TID or BID. The combined teachings of the cited prior art render obvious a formulation comprising viloxazine or a pharmaceutically acceptable salt thereof, wherein said formulation comprises at least one of an extended release component and a delayed release component, and wherein said delayed release component comprises an enteric compound, wherein the release rate of active agent can be finely tuned, but do not explicitly disclose the limitations as recited in instant claims 1, 11, 12, 14, 27, and 28. The examiner considers the release of viloxazine to be optimizable based upon the teachings of Sesha and Venkatesh. See MPEP 2144.05(II)(A): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With regard to instant claims 13 and 29, as noted above, Sesha discloses multiple standard dosage forms for the formulation including coated minibeads (i.e. sprinkles) or minitablets (i.e. beads).
Claim 26 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sesha (WO 2011/008298; publication date: 01/20/2011, cited in Applicant’s IDS) and Breder I (WIPO Publication No. WO 2010/127120; publication date: 11/04/2010, cited in Applicant’s IDS), in view of Venkatesh (US PGPub No. 2006/0246134; publication date: 11/02/2006; cited in Applicant’s IDS), and further in view of Bayliss et al. (Br J. Clin Pharmacol pages 209-214; publication year: 1975, cited in Applicant’s IDS), and Breder II (US 2010/0069390; publication date: 03/18/2010) as evidenced by Guittard et al. (US 2001/0005728; publication date: 2001/0005728) as applied to claims 14-18, 21, 25, and 27-29 above, and further in view of Pasternak et al. (US PGPub No. 2010/0256106; publication date: 11/07/2010, cited in Applicant’s IDS).
The relevant disclosures of Sesha, Venkatesh, Breder I, Bayliss et al., and Breder II are set forth above. None of these references specifically discloses a formulation with the properties listed above comprising viloxazine HCl, however forming an addition salt between a poorly soluble drug and a pharmaceutically acceptable acid such as hydrochloride is well known in the prior art: For example, the publication by Pasternak et al. reports forming a pharmaceutically acceptable salts of viloxazine (para 0224, lines 1-3), to include the hydrochloride salt (para 0160, line 1 and para 0160, line 32). The Artisan of skill would have been motivated to use the hydrochloride salt of viloxazine as part of routine optimization of solubility properties during formulation of sustained release preparations (Pasternak: para 0160, lines 35-38). The skilled Artisan would have had a reasonable expectation of success because using hydrochloride salts was routine practice in pharmacology at the time of the instant invention.
Response to Arguments
Applicant's arguments filed 11/07/2025 have been fully considered but they are not persuasive.
On page 4, Applicant argues the cited references do not teach or suggest "the weight ratio of the at least one release rate controlling compound to the at least one pore former [in the second layer of the DR component surrounding the first layer of the DR component] [being] 19:1 to 8.5:1.5" as claim 14 recites. On page 5, Applicant argues further that one of ordinary skill in the art would not have any reason or motivation to use Venkatesh's teaching in its paragraph [0040] for its matrix core for optimizing "the weight ratio of the at least one release rate controlling compound to the at least one pore former" in the second layer of the DR component surrounding the first layer of the DR component. Any prima facie case of obviousness is more than overcome by the evidence of criticality for "the weight ratio of the at least one release rate controlling compound to the at least one pore former [in the second layer of the DR component surrounding the first layer of the DR component] [being] 19:1 to 8.5:1.5" provided in Figures 7-9 of the present application.
With regard to the statement that one of ordinary skill would have no motivation to optimize the weight ratio of pore former in a shell based upon the prior art’s teaching of amount of pore former in a matrix core, the examiner respectfully disagrees for the reasons set forth in the rejection. The record establishes that the structure recited in the instant claims is a well-known structure to achieve any desired drug release profile for a basic drug having a short half-life. The Federal Circuit in Perfect Web also discussed the role of common sense in the determination of obviousness. The district court had cited KSR for the proposition that "[a] person of ordinary skill is also a person of ordinary creativity, not an automaton," and found that "the final step [of the claimed invention] is merely the logical result of common sense application of the maxim ‘try, try again.’" In affirming the district court, the Federal Circuit undertook an extended discussion of common sense as it has been applied to the obviousness inquiry, both before and since the KSR decision. With regard to Applicant’s arguments that the prima facie case of obviousness is overcome by evidence of criticality of the claimed range, insomuch as this may be an assertion of unexpected results, please refer to MPEP 716.02(b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims. In the instant case, the claims are much broader in structure than the specific compositions evaluated in the cited experiments.
On page 5, Applicant argues that the weight ratio recitations in the parent applications, which are similar to the weight ratio recitation in claim 14, led to allowance of the parent applications now issued as U.S. Patents No. 9,358,204; 9,603,853; 9,662,338 and 10,265,319.
The examiner points out that each of the patents cited above recite additional limitations besides the ratio of pore former. Importantly, the issuance of other patents in the same field of technology is not a ground for challenging the rejection of a subsequent application. Each application is examined on its own merits for compliance with pertinent statutory requirements. See In re McDaniel, 293 F.3d 1379, 1387 (Fed. Cir. 2002) (“It is well settled that the prosecution of one patent application does not affect the prosecution of an unrelated application.”); In re Gyurik, 596 F.2d 1012, 1018–19 n.15 (CCPA 1979) (“Each case is determined on its own merits. In reviewing specific rejections of specific claims, this court does not consider allowed claims in other applications or patents.”); In re Wertheim, 541 F.2d 257, 264 (CCPA 1976) (“[I]t is immaterial in ex parte prosecution whether the same or similar claims have been allowed to others.”). See In Re Mohapatra , No. 20-1935 (Fed. Cir. 2021).
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 14-18, 21, and 25-29 are provisionally are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-26 of copending Application No. 19093755 (reference application); and
claims 1-14 of copending Application No. 19171852 (reference application)
as evidenced by Guittard et al. (US 2001/0005728; publication date: 2001/0005728) in view of Venkatesh (US PGPub No. 2006/0246134; publication date: 11/02/2006; cited in Applicant’s IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims.
Inter alia the claims of the ‘716, ‘755, and ‘852 applications embrace formulations of viloxazine or viloxazine HCl for once or twice daily administration in the form of a plurality of particles containing an extended release component (XR) matrix core comprising viloxazine and a release rate controlling compound.
The claims of the ‘716, ‘755, and ‘852 applications require a pore former in the particulates, specifically inter alia hypromellose, hydroxyethyl cellulose, hydroxypropyl cellulose hydroxypropyl cellulose is a cellulose ether, see Guittard: para 0024).
The amount of viloxazine in the formulations of the ‘716 and ‘755 applications as well as the identity of the release rate component are the same. The examiner considers it a matter of routine for one of ordinary skill to optimize release profile (i.e. Cmax and AUC of the formulation). See MPEP 2144.05. The compositions may be in the form of tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, and sprinkles.
Both applications expressly embrace a formulation comprising a population of coated XR drug/polymer matrix core particles; whereas, claim 14 requires a population of coated XR particles having an inert core and drug/polymer coatings rather than drug/polymer matrix core particles.
Venkatesh discloses that multiparticulate formulations containing an inert particle coated with an active ingredient and a polymeric binder or multiparticulate formulations comprising a pellet or mini- or micro-tablet containing the active ingredient, a polymeric binder and a diluent/filler, prepared by rotogranulation, granulation-extrusion-spheronization or granulation-tableting can be used to achieve a target drug release profile for any basic drug by optimizing inter alia, the identity of known release-rate controlling polymers. (See Venkatesh claims 1 and 5 and abstract).
It would have been prima facie obvious to one of ordinary skill in the art to include coated inert core multiparticulates to achieve the drug release profile recited in the instant claims because one having ordinary skill in the art would have recognized these as a suitable alternative design choice (see MPEP 2144.04(VI)(C)).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 14-18, 21, and 25-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over
Claims 1-13 of U.S. Patent No. 9,358,204 (of record);
Claims 1-14 of U.S. Patent No. 9,662,338 (of record); and
Claims 1-20 of U.S. Patent No. 10,265,319 (of record);
in view of Sesha (WO 2011/008298; publication date: 01/20/2011, cited in Applicant’s IDS), ) as evidenced by Guittard et al. (US 2001/0005728; publication date: 2001/0005728).
Inter alia the claims of the ‘204, ‘338, and ‘319 patents embrace formulations of viloxazine or viloxazine HCl for once or twice daily administration in the form of a plurality of particles containing an immediate release component comprising viloxazine and an excipient and an extended release component comprising viloxazine and a release rate controlling compound.
The amount of viloxazine in the formulations of the ‘204, ‘338, and ‘319 patents as well as the identity of the release rate component are the same. The examiner considers it a matter of routine for one of ordinary skill to optimize release profile (i.e. Cmax and AUC of the formulation). See MPEP 2144.05. The compositions may be in the form of tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, and sprinkles.
The claims of the ‘204, ‘338, and 319 patents are silent with respect to coating the extended release beads with an enteric compound.
Sesha discloses compositions that may be designed to deliver viloxazine (0068) and that these composition may be further coated with an enteric polymer (para 0052).
It would have been prima facie obvious to coat the plurality of particles of the ‘204, ‘338, and ‘319 patents with an enteric coating in order to deliver viloxazine to the lower G.I. tract. One of ordinary skill in the art would have been motivated to do so in order to improve absorption through the G.I. mucosa.
The enteric polymers disclosed by Sesha include cellulose acetate phthalate (para 00114).
With regard to the structural requirements placed on the delayed release component of the instant invention recited in claims 1 and 14, the claims of the ‘204 and ‘338 patents embrace a delayed release component comprising an inert core, a first layer comprising viloxazine surrounding the core and a second layer comprising a release rate controlling compound surrounding the first layer. The claims of the ‘319 patent embrace a delayed release component comprising viloxazine and an extended release matrix having at least one release rate controlling compound. While the structure of the delayed release component of the ‘204 and ‘338 or the ‘319 patents differ from either the limitations of claim 14 or claim 1, respectively, Sesha indicates that these are known alternative designs for accomplishing sustained release of pharmaceutical actives (para 0085). For this reason the examiner does not find the claims of the ‘204, ‘338, and ‘319 patents to be patentably distinct from the instant claims.
With regard to instant claims 19-21, Sesha discloses that “flux-enhancing agents” can be included in the membrane and include substances such as hydroxypropyl cellulose (para 0096; hydroxypropyl cellulose is a cellulose ether, see Guittard: para 0024). The examiner considers arriving at a ratio of release rate controlling compound to pore former to be a matter of testing several amounts of pore former according to routine methods of evaluating drug release and therefore does not consider the limitations of instant claim 20 to patentably define over the cited prior art. See MPEP 2144.05.
Response to Arguments
Applicant’s comment on page 9 of the remarks filed 11/07/2025 that Applicant will address the nonstatutory double patenting rejections when these are the only remaining issue in the application are noted.
Conclusion
No claims are allowed.
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 KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617