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 .
Withdrawn Objections/Rejections
The objection to claim 7 is withdrawn in view of the claim amendments.
The rejections of claims 1-13 under 35 U.S.C. 112(b) are withdrawn in view of the claim amendments.
Claim Status
Applicant’s amendments and arguments filed 02/19/2026 have been fully considered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the
complete set presently being applied to the instant application.
Claims 14-26 are withdrawn.
Claims 1-13 are under current examination.
Information Disclosure Statement
The information disclosure statement (IDS) filed 10/08/2025 has been considered by the Examiner.
Claim Interpretation
The instant specification does not set forth a definition of “configured to” nor define how the limitation “the anhydrous suspension is configured to self-emulsify when administered to an aqueous environment of the oral cavity of the subject to form a mixed micelle and liposome delivery system for transmucosal delivery of the naltrexone within the oral cavity” limits the structural components of the claimed topical composition. The specification suggests that a composition comprising an anhydrous base vehicle consistent with the anhydrous suspension of instant claim 1 is capable of such self-emulsification upon addition of water (see paragraphs [0071]-[0072] and [00108]).
Giving the claims their broadest reasonable interpretation in light of the specification, it is interpreted that a topical composition that meets the structural components of claim 1 (a topical composition comprising an anhydrous suspension comprising naltrexone, medium chain triglycerides, between 0.5% w/w and 10% w/w phosphatidylcholine, between 0.1 % w/w and 1 % w/w lysophosphatidylcholine, glyceryl distearate, and glyceryl monostearate) is capable of carrying out the function of self-emulsifying and forming mixed micelles and liposomes within an aqueous environment of an oral cavity, and thus meets the limitation of being “configured to” this function. Per MPEP 2111.04 (emphasis added) “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure.”
Rejections Maintained, Slightly Modified to Address Claim Amendments
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.
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.
Claims 1-4 and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Staniforth (US 2010/0159007 A1, published June 24, 2010; included on IDS submitted 07/15/2025) in view of Pergolizzi et al. (US 2025/0114370 A1, filed October 8, 2024; of record), hereafter “Pergolizzi”, and Amano (US 11,571,385 B2, patented February 7, 2023; included on IDS submitted 07/15/2025).
Staniforth teaches compositions for transmucosal administration intended for buccal and/or sublingual delivery (abstract) that comprise submicron particles comprising an active agent (claim 1); the compositions are particularly suitable for administering therapeutically active agents which have an effect on the central nervous system (abstract). Example drugs include those that are intended to provide rapid or acute treatment of symptoms with a site of action within the central nervous system, and include naltrexone (paragraphs [0064], and [0069]-[0071]). In an embodiment, the composition comprises one or more drugs including naltrexone and is preferably for treating drug dependency (paragraph [0093]). The compositions of Staniforth have the submicron particles dispersed within one or more inert materials which form a matrix (claim 23). The inert material is selected to dissolve or disperse rapidly and is selected from those including non-aqueous media, surfactants, self-emulsifying glyceryl monostearate, glyceryl distearate, and phospholipids, especially those that can aid adhesion to and/or spreading across mucosal surfaces such as phosphatidyl choline and lyso-phosphatidylcholine (paragraph [0040]). As the compositions of Staniforth are taught to have particles dispersed in non-aqueous media, they are interpreted as an anhydrous suspension.
Staniforth does not teach the inclusion of medium chain triglycerides (instant claim 1), or that the medium chain triglycerides comprise caprylic/capric triglycerides (instant claim 2) present in an amount between 60% and 95% w/w (instant claim 3), between 50% and 81% w/w (instant claim 4), or between 60% and 90% w/w (instant claim 9). Staniforth further does not teach the inclusion of peppermint flavor, spearmint flavor, or both (instant claim 7). Staniforth further does not teach that the glyceryl distearate and glyceryl monostearate are each present in an amount between 0.5% and 5% w/w (instant claims 8 and 9).
Pergolizzi teaches administration of a pharmaceutical composition comprising a respiratory stimulant and an opioid antagonist of naltrexone for the treatment of drug overdose (claims 1, 12, 16, and 18). Administration can be by the buccal route (claim 27) or sublingual route (paragraph [0202]) and suitable dosage forms include suspensions of the active ingredient in an oily vehicle such as an oily ester (paragraphs [0203] and [0210]). In certain embodiments, suitable pharmaceutically acceptable excipients include natural or synthetic triglycerides such as caprylic/capric triglyceride (paragraph [0248]). Pharmaceutically acceptable excipients further include glyceryl monostearate (paragraphs [0222] and [0224]) and glyceryl distearate (paragraph [0238]). Pharmaceutically acceptable excipients may be included individually or cumulatively in a concentration ranging from about 5 wt % to about 99 wt %, or any subrange therein (paragraph [0265]). Pergolizzi further teaches liquid suspensions can include flavorings (paragraph [0210]), and that in certain embodiments, pharmaceutically acceptable excipients include a flavor extract, and exemplary flavoring agents include spearmint (paragraph [0230]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the composition of Staniforth to include the medium-chain triglycerides of caprylic/capric triglycerides in an amount overlapping the claimed ranges and adjust the amount of glyceryl monostearate and glyceryl distearate to each be in a concentration of about 5 wt %, as suggested by Pergolizzi.
One of ordinary skill would have been motivated to do so with a reasonable expectation of success in order to incorporate an oily vehicle and suitable excipients in amounts known to form suspensions for the effective buccal or sublingual delivery of naltrexone, as suggested by Pergolizzi. There is a reasonable expectation of success as the compositions of Staniforth are for the buccal and/or sublingual administration of the therapeutically active agent naltrexone, and comprise an oil solvent (see Staniforth, claim 28). Further, per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
It would further have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the composition of Staniforth to include the spearmint flavoring agent taught by Pergolizzi. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to incorporate a flavoring agent that improves the taste of a buccal or sublingual formulation for the delivery of naltrexone, as suggested by Pergolizzi. There is a reasonable expectation of success as such the compositions of Staniforth are used for buccal and/or sublingual delivery and comprise naltrexone.
Staniforth does not teach that the phosphatidylcholine is present between 0.5% w/w and 10% w/w or that the lysophosphatidylcholine is present between 0.1 and 1% w/w.
Amano teaches a self-emulsifiable composition including a monoacyl phospholipid, a diacyl phospholipid, oils and fats, and a polyhydric alcohol, wherein the content ratio between the monoacyl phospholipid and the diacyl phospholipid is in the range of 1:9 to 9:1 as a mass ratio (abstract). The monoacyl phospholipid is preferably lysophosphatidylcholine (column 5, lines 1-7), and examples of the diacyl phospholipid include phosphatidylcholine (column 5, lines 32-36). The composition can be used as a pharmaceutical product when the water content is less than 5% by mass and a substantially non-water-based composition is obtained (column 8, lines 51-55). A nanoemulsion forms when the self-emulsifiable composition is mixed with an aqueous solution (column 10, line 65-column 11, line 3). Amano further teaches that the total content of the monoacyl phospholipid and the diacyl phospholipid is not particularly limited; however, for example, the total content may be from 0.1 % by mass to 70% by mass based on the total amount of the composition; in this range, a self-emulsifiable composition that can produce a nanoemulsion by a simple operation such as addition of an aqueous solution can be suitably obtained (column 6, lines 1-16). Thus, Amano suggests amounts of lysophosphatidylcholine and phosphatidylcholine overlapping those of the instant claims; as just one example, the ranges of Amano are inclusive of lysophosphatidylcholine present at 0.1% w/w and a weight ratio of 1:9 with phosphatidylcholine, or 0.9% w/w of phosphatidylcholine. Amano further suggests that these amounts can be adjusted to provide the desired self-emulsification properties of a non-water based pharmaceutical composition upon addition of an aqueous solution.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the compositions comprising phosphatidylcholine and lysophosphatidylcholine of Staniforth with the amounts overlapping the claimed ranges suggested by Amano. One of ordinary skill in the art would have been motivated to do so in order to use amounts of lysophosphatidylcholine and phosphatidylcholine which allow a pharmaceutical non-water based self-emulsifiable composition to form a nanoemulsion upon addition of water. There is a reasonable expectation of success as the compositions of Staniforth are taught to be non-aqueous and comprise self-emulsifying components; further, the compositions of Staniforth are intended for buccal and/or sublingual delivery (abstract), the mouth being an aqueous environment (paragraph [0024]). Further, per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)” and per 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).”
The limitation of instant claim 1 that the topical composition is “for administration to an oral cavity of a subject and oral absorption therein to treat opioid use disorder (OUD) or alcohol use disorder (AUD)” recites the intended use of the claimed topical composition and does not structurally limit the composition. The combination of Staniforth in view of Pergolizzi and Amano renders obvious the claimed composition, and arrives at a composition for transmucosal administration (via buccal and/or sublingual delivery) comprising naltrexone and self-emulsifying components that can be used to treat drug dependency. Thus, the compositions of the modified Staniforth are capable of performing the intended use as claimed.
As set forth above, it is interpreted that a topical composition that meets the structural components of claim 1 (a topical composition comprising an anhydrous suspension comprising naltrexone, medium chain triglycerides, between 0.5% w/w and 10% w/w phosphatidylcholine, between 0.1 % w/w and 1 % w/w lysophosphatidylcholine, glyceryl distearate, and glyceryl monostearate) is capable of carrying out the function of self-emulsifying and forming mixed micelles and liposome delivery system within an aqueous environment of an oral cavity, and thus meets the limitation of being “configured to” this function. The combination of Staniforth in view of Pergolizzi and Amano renders obvious the structural components of claimed composition, and arrives at a composition for transmucosal administration (via buccal and/or sublingual delivery) comprising self-emulsifying components. Thus, the compositions of the modified Staniforth are interpreted to meet the limitation of being “configured to self-emulsify when administered to an aqueous environment of the oral cavity of the subject to form a mixed micelle and liposome delivery system for transmucosal delivery of the naltrexone within the oral cavity”.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Staniforth in view of Pergolizzi and Amano as applied to claims 1-4 and 7-9 above, and further in view of Pauletti et al. (US 2003/0219472 A1, published November 27th, 2003; included on IDS submitted 07/15/2025), hereafter “Pauletti”.
The teachings of the modified Staniforth are described above.
The combination of Staniforth, Pergolizzi, and Amano does not teach the limitation of instant claim 5 that the anhydrous suspension further comprises polycarbophil in an amount between 0.2% and 2% w/w or of instant claim 6 that the anhydrous suspension further comprises polycarbophil in an amount between 0.17% and 2% w/w.
Pauletti teaches compositions for buccal transmucosal delivery of drugs (abstract) which assert a therapeutic effect when delivered to the systemic circulation through the vaginal, nasal, or buccal mucosa (paragraphs [0081]). The compositions can be formulated as a suspension for buccal delivery (paragraph [0096]). The compositions may comprise a mucoadhesive agent to bring the drug into prolonged, close contact with the mucosal surface, and examples of mucoadhesive agents include polycarbophil (paragraph [0066]). The mucoadhesive agent is present between about 0.05-25% by weight, and more preferably about 0.02-7.5% for buccal delivery (paragraph [0071]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to include a polycarbophil mucoadhesive agent in an amount overlapping the claimed range, as suggested by Pauletti, in the composition of the modified Staniforth.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to bring the drug into prolonged, close contact with the buccal mucosa, as suggested by Pauletti. There is a reasonable expectation of success as and the compositions of the modified Staniforth are used for transmucosal administration (via buccal and/or sublingual delivery) of active agents. Staniforth further teaches that promotion or enhancement of mucosal adhesion can improve transmucosal delivery of an active agent (paragraph [0014]), and the inclusion of macromolecules to aid adhesion to mucosal surfaces (paragraph [0040]). Further, per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
Claims 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Staniforth in view of Pergolizzi and Amano as applied to claims 1-4 and 7-9 above, and further in view of Lewis (US 4,935,428, patented June 19th, 1990, of record).
The teachings of the modified Staniforth are described above. Regarding instant claim 11, as set forth above, the combined teachings of Staniforth, Pergolizzi, and Amano arrive at concentrations of phosphatidylcholine and lysophosphatidylcholine overlapping the claimed ranges. Particularly, Amano suggests amounts of lysophosphatidylcholine and phosphatidylcholine overlapping those of the instant claims; as just one example, the ranges of Amano are inclusive of lysophosphatidylcholine present at 0.3% w/w and a weight ratio of 1:9 with phosphatidylcholine, or 2.7% w/w of phosphatidylcholine. Amano further suggests that these amounts can be adjusted to provide the desired self-emulsification properties of a composition. Per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
Regarding instant claim 12, Staniforth further teaches the inclusion of magnesium stearate in the inert material of the compositions for transmucosal administration of naltrexone (paragraph [0040]). Pergolizzi further teaches the inclusion of fillers such as microcrystalline cellulose (paragraph [0240]). The formulations of Staniforth are taught to include inert materials which form a matrix, and it would have been prima facie obvious to one of ordinary skill before the effective filing date to incorporate the filler of microcrystalline known to be used in buccal or sublingual suspension drug delivery systems for the delivery of naltrexone, as taught by Pergolizzi.
Regarding instant claim 13, Staniforth further teaches the inclusion of agents to provide rapid disintegration and release of the submicron particles, including cross-linked sodium carboxymethylcellulose (croscarmellose) (paragraph [0051]). Pergolizzi further teaches the inclusion of lubricants/release agents such as colloidal silica (paragraph [0233]). As the formulations of Staniforth are taught to include release agents, it would have been prima facie obvious to one of ordinary skill before the effective filing date to incorporate the lubricant/release agent of colloidal silica known to be used in buccal or sublingual suspension drug delivery systems for the delivery of naltrexone, as taught by Pergolizzi.
The combination of Staniforth, Pergolizzi, and Amano does not teach the limitation of instant claim 10 that the naltrexone is present in an amount between about 3 mg/mL and about 15 mg/mL.
Lewis teaches a sublingual pharmaceutical composition for maintenance treatment of opiate addicts comprising buprenorphine and an amount of naltrexone sufficient to substantially attenuate the euphorigenic effect of buprenorphine (abstract, claim 3). Lewis exemplifies a sublingual solution containing 10 mg/mL of naltrexone (column 4, Example 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to adjust the amount of naltrexone in the composition of the modified Staniforth to 10 mg/mL, as suggested by Lewis. This could be achieved by routine optimization in order to achieve an amount of naltrexone for sublingual delivery that attenuates the effects of euphorigenic drugs in the treatment of opiate addictions, as suggested by Lewis.
There is a reasonable expectation of success as the composition of the modified Staniforth is preferably for treating drug dependency and can include buprenorphine (Staniforth, paragraph [0093]). Per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)” and per 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).”
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 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 19/067,176 in view of Staniforth (US 2010/0159007 A1, published June 24, 2010; included on IDS submitted 07/15/2025) and Pergolizzi et al. (US 2025/0114370 A1, filed October 8, 2024; of record), hereafter “Pergolizzi”.
Both the instant claims and those of copending Application No. 19/067,176 recite a topical composition for administration to an oral cavity of a subject and oral absorption therein comprising an anhydrous suspension comprising an active ingredient, medium chain triglycerides comprising caprylic/capric triglycerides, phosphatidylcholine, lysophosphatidylcholine, glyceryl distearate, glyceryl monostearate, polycarbophil, peppermint flavor, spearmint flavor, or both, magnesium stearate, microcrystalline cellulose, and croscarmellose sodium. Both sets of claims recite that the anhydrous suspension is configured to self-emulsify in an aqueous environment of the oral cavity of the subject to form a mixed micelle and liposome delivery system for transmucosal delivery. Both sets of claims recite overlapping amounts of active ingredient, caprylic/capric triglycerides, phosphatidylcholine, lysophosphatidylcholine, glyceryl distearate, glyceryl monostearate and polycarbophil.
The claims of copending Application No. 19/067,176 differ from those of the instant claims in that the anhydrous suspension requires the active ingredient of sumatriptan, while the anhydrous suspension of the instant claims requires naltrexone. The claims of copending Application No. 19/067,176 further do not require that the anhydrous suspension comprises colloidal silicon dioxide, as required by instant claim 13.
Staniforth teaches compositions for transmucosal administration intended for buccal and/or sublingual delivery (abstract) that comprise submicron particles comprising an active agent (claim 1). The composition can comprise one or more anti-migraine agents such as sumatriptan (paragraph [0087]; claim 42) and can comprise one or more drugs for treating drug dependency including naltrexone (paragraph [0093]). The compositions of Staniforth have the submicron particles dispersed within one or more inert materials which form a matrix (claim 23). The inert material is selected to dissolve or disperse rapidly and is selected from those including non-aqueous media, surfactants, self-emulsifying glyceryl monostearate, glyceryl distearate, and phospholipids, especially those that can aid adhesion to and/or spreading across mucosal surfaces such as phosphatidyl choline, lyso-phosphatidylcholine (paragraph [0040]). As the compositions of Staniforth are taught to have particles dispersed in non-aqueous media, they are interpreted as an anhydrous suspension.
Pergolizzi teaches administration of a pharmaceutical composition comprising a respiratory stimulant and an opioid antagonist of naltrexone for the treatment of drug overdose (claims 1, 12, 16, and 18). Administration can be by the buccal route (claim 27) or sublingual route (paragraph [0202]) and suitable dosage forms include suspensions of the active ingredient in an oily vehicle such as an oily ester (paragraphs [0203] and [0210]). Pergolizzi further teaches the inclusion of lubricants/release agents such as colloidal silica (paragraph [0233]).
It would have been prima facie obvious to one of ordinary skill in the art to substitute the sumatriptan recited in the claims of copending Application No. 19/067,176 with the naltrexone taught by Staniforth. Simple substitution of one active agent known for delivery via transmucosal administration in an inert material comprising non-aqueous media, surfactants, self-emulsifying glyceryl monostearate, glyceryl distearate, phosphatidylcholine and lysophosphatidylcholine for another such agent is within the purview of the skilled artisan and would yield predictable results (see MPEP 2143 B).
It would further have been prima facie obvious to one of ordinary skill before the effective filing date to incorporate the colloidal silicon dioxide, suggested by Pergolizzi, into the composition of copending Application No. 19/067,176. One of ordinary skill in the art would have been motivated to do so in order to incorporate an excipient that achieves a lubricant/releasing effect to suspensions for buccal or sublingual delivery of a suspension of active pharmaceutical ingredients.
This is a provisional nonstatutory double patenting rejection.
Claims 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 19/067,198 in view of Staniforth (US 2010/0159007 A1, published June 24, 2010; included on IDS submitted 07/15/2025).
Both the instant claims and those of copending Application No. 19/067,198 recite a topical composition for administration to an oral cavity of a subject and oral absorption therein comprising an anhydrous suspension comprising an active ingredient, medium chain triglycerides comprising caprylic/capric triglycerides, phosphatidylcholine, lysophosphatidylcholine, glyceryl distearate, glyceryl monostearate, polycarbophil, peppermint flavor, spearmint flavor, or both, magnesium stearate, microcrystalline cellulose, and colloidal silicon dioxide. Both sets of claims recite that the anhydrous suspension is configured to self-emulsify in an aqueous environment of the oral cavity of the subject to form a mixed micelle and liposome delivery system for transmucosal delivery. Both sets of claims recite overlapping amounts of active ingredient, caprylic/capric triglycerides, phosphatidylcholine, lysophosphatidylcholine, glyceryl distearate, glyceryl monostearate and polycarbophil.
The claims of copending Application No. 19/067,198 differ from those of the instant claims in that the anhydrous suspension requires the active ingredient of tadalafil or vardenafil, while the while the anhydrous suspension of the instant claims requires naltrexone. The claims of copending Application No. 19/067,198 further do not require that the anhydrous suspension comprises croscarmellose sodium, as required by instant claim 13.
Staniforth teaches compositions for transmucosal administration intended for buccal and/or sublingual delivery (abstract) that comprise submicron particles comprising an active agent (claim 1). The composition can comprise one or more drugs for treating sexual dysfunction including tadalafil and vardenafil (paragraph [0094]) and can comprise one or more drugs for treating drug dependency including naltrexone (paragraph [0093]). The compositions of Staniforth have the submicron particles dispersed within one or more inert materials which form a matrix (claim 23). The inert material is selected to dissolve or disperse rapidly and is selected from those including non-aqueous media, surfactants, self-emulsifying glyceryl monostearate, glyceryl distearate, and phospholipids, especially those that can aid adhesion to and/or spreading across mucosal surfaces such as phosphatidyl choline, lyso-phosphatidylcholine (paragraph [0040]). As the compositions of Staniforth are taught to have particles dispersed in non-aqueous media, they are interpreted as an anhydrous suspension. Staniforth further teaches the inclusion of agents to provide rapid disintegration and release of the submicron particles, including cross-linked sodium carboxymethylcellulose (croscarmellose) (paragraph [0051]).
It would have been prima facie obvious to one of ordinary skill in the art to substitute the tadalafil and vardenafil recited in the claims of copending Application No. 19/067,198 with the naltrexone taught by Staniforth. Simple substitution of one active agent known for delivery via transmucosal administration in an inert material comprising non-aqueous media, surfactants, self-emulsifying glyceryl monostearate, glyceryl distearate, phosphatidylcholine and lysophosphatidylcholine for another such agent is within the purview of the skilled artisan and would yield predictable results (see MPEP 2143 B).
It would further have been prima facie obvious to one of ordinary skill before the effective filing date to incorporate the sodium croscarmellose, suggested by Staniforth, into the composition of copending Application No. 19/067,198. One of ordinary skill in the art would have been motivated to do so in order to incorporate an excipient that provides rapid release of the active agent to compositions for buccal or sublingual delivery of a suspension of active pharmaceutical ingredients.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments filed 02/19/2026 have been fully considered.
Regarding the rejections under 35 U.S.C. § 103, Applicant argues that the combination of Staniforth, Pergolizzi, and Amano fails to teach the composition of claim 1 at least because the references teach fundamentally incompatible approaches to transmucosal drug delivery that one skill in the art would not combine as alleged. Particularly, Applicant argues that Staniforth relies on submicron particles that are “sticky” and that remain in an undissolved state until positioned in the micro-environment adjacent to the mucosal membrane. Applicant argues that Amano is in direct contrast to Staniforth in teaching a liquid self-emulsifying composition that spontaneously disperses into the aqueous solution that are mobile in the aqueous phase and do not exhibit the adhesive “stickiness” central to Staniforth’s delivery mechanism; one of ordinary skill would recognize that combining Amano’s self-emulsifying system with Staniforth would defeat Staniforth’s purpose of adhering to oral mucosa. Applicant further argues that Amano does not contemplate self-emulsification in saliva, but rather greater volumes of aqueous solution; Amano’s only discussion of oral administration relates to either pre-formed nanoemulsion or adding aqueous solution at the time of use.
These arguments are unpersuasive. The Examiner first respectfully maintains that Staniforth reasonably suggests the inclusion of phosphatidylcholine, lysophosphatidylcholine, and self-emulsifying components in compositions for the transmucosal (buccal and/or sublingual) administration of naltrexone, as set forth above. While Staniforth does not teach the amounts of phosphatidylcholine and lysophosphatidylcholine of instant independent claim 1, per MPEP 2144.05 II. A., differences in concentration will generally not support patentability unless there is evidence that such concentration is critical. The Examiner finds no evidence of record that the claimed amounts of lysophosphatidylcholine and phosphatidylcholine are critical.
However, the Examiner notes that, per MPEP 2144.05 III. A., “Applicants can rebut a prima facie case of obviousness by showing the criticality of the range. "The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. . . . In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range." In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).” Applicant is encouraged to provide or point to evidence on the record demonstrating the criticality of the claimed range.
Further, the Examiner respectfully disagrees that the self-emulsification approach of Amano is incompatible with that of Staniforth. By teaching the inclusion of self-emulsifying components, Staniforth reasonably suggests to one of ordinary skill in the art that self-emulsification is compatible with their transmucosal delivery approach. Further, while Amano does not exemplify emulsification in saliva, the Examiner notes that the test for obviousness is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Here, Amano reasonably suggests the use of the self-emulsifying composition as a substantially non-water-based pharmaceutical product (column 8, lines 51-55) and formation of a nanoemulsion when a self-emulsifiable composition is mixed with an aqueous solution (column 10, line 65-column 11, line 3). Staniforth explicitly recognizes the mouth as an aqueous environment (paragraph [0024]), and teaches inclusion of the same phospholipids used in the self-emulsifying compositions of Amano, suggesting that the approaches can be combined with a reasonable expectation of success.
Applicant further argues that Pergolizzi does not clearly link caprylic/capric triglyceride to the “oily vehicle” formulations it describes and mentions it only once in a generic excipient list. Applicant argues that Pergolizzi does not teach or suggest that oily formulations are suitable for buccal or sublingual administration as it separately describes oily suspensions as one of many possible dosage forms and lists buccal and sublingual among many routes of administration. Applicant further argues that Staniforth states that in oral liquids for transmucosal administration there is a likelihood of swallowing much of the active agent, and disparages oral liquids such as syrup, solutions, or suspension (paragraphs [0011]) Applicant argues that suspending the drug of Staniforth in Pergolizzi’s oily vehicle would reduce particle “stickiness” and destroy Staniforth’s adhesion-based delivery mechanism of Staniforth, and there would be no reasonable expectation of success in combining these references for transmucosal drug delivery.
These arguments are unpersuasive. While Staniforth exemplifies solid dosage forms, Staniforth explicitly contemplates compositions comprising an oil solvent (claim 28). Per MPEP 2123 I., “A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).” The compositions of Staniforth are taught to comprise naltrexone (paragraphs [0064], and [0069]-[0071]), and are intended for buccal and/or sublingual delivery (abstract). Pergolizzi reasonably suggests to one of ordinary skill in the art that pharmaceutical compositions comprising naltrexone are delivered by the buccal route (claims 1, 12, 16, 18, and 27), and that conventional methods can be used to suspend the active ingredient in an oily vehicle, including oily esters (paragraph [0210]), with caprylic/capric triglycerides taught as a known excipient (paragraph [0248]) (caprylic/capric triglycerides being known in the art as an ester of glycerin and coconut oil fatty acids, i.e., an oily ester). As Staniforth claims the inclusion of an oil solvent, one of ordinary skill in the art would be motivated to include the oily ester of caprylic/capric triglycerides suggested by Pergolizzi in order to incorporate an oily vehicle known in the art to be capable of forming suspensions for the effective buccal delivery of naltrexone.
Further, the Examiner notes that in paragraph [0011], cited in Applicant’s arguments, Staniforth is providing background information on limitations of previously known formulations for transmucosal delivery via the sublingual or buccal mucosa. Staniforth highlights limitations in many types of known delivery systems, including solid formulations (see paragraphs [0011]-[0013]). Staniforth suggests that their invention improves on these known issues by providing compositions which provide effects such as improved transmucosal absorption upon administration by promoting or enhancing mucosal adhesion, persistence at the mucosa, enhancement of transmucosal flux, etc. (paragraph [0014]).
In view of the foregoing, and as further detailed in the above rejections, the Examiner maintains that the instant claims are prima facie obvious over the teachings of the modified Staniforth.
Regarding the nonstatutory double patenting rejections over the claims of co-pending Applications 19/067,198 and 19/067,176, Applicant requests that the provisional rejections be held in abeyance until the subject matter that will mature into a patent is known.
In response, the Examiner notes that a request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see MPEP 37 CFR 1.111(b) and 714.02). Thus, the double patenting rejections set forth above have been maintained as no action regarding these rejections has been taken by Applicant at this time.
Conclusion
Applicant’s arguments are considered unpersuasive. Accordingly, 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 JUDITH M KAMM whose telephone number is (703)756-4575. The examiner can normally be reached M-F 8:00 am-4:30 pm EST.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611
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