DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-50 are pending in the present application.
Election/Restrictions
Claims 30-35 and 41-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12 March 2025.
Therefore, claims 1-29, 36-40 and 47-50 are examined herein.
Priority
The present application is a CIP of 16/143,821, which is a CIP of 15/791,249, which is a CIP of 15/717,859, which is a CIP of 15/587,364, which claims the benefit of provisional application 62/331,996. Instant claims 1, 29, 36 and 47 recite, “the prodrug having a half-life of less than one minute”. Claims 47-50 recite a Tmax and Cmax for the pharmaceutical film. The priority documents do not provide support for these limitations. Therefore, the effective filing date for claims 1-29, 36-40 and 47-50 is the filing date of the instant application, 13 December 2021.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant asserts that the property, “the prodrug having a half-life of less than one minute”, is an inherent property that has support in the priority documents.
The examiner respectfully argues that Applicant did not point to any specific portions of the priority documents where support can be found. Some of the priority documents teach an ester of epinephrine or dipivefrin, but they do not provide support for selecting an epinephrine prodrug with a half-life of less than one minute. While the half-life of a compound is an inherent property, the priority documents do not provide support for selecting an epinephrine prodrug having the property instantly claimed. The inherent properties of dipivefrin or other specifically recited compounds are supported by the priority documents where they are disclosed, but the inherent properties of compounds that have not been disclosed in the priority documents does not get support in the priority documents. The priority documents do not provide support for any and all prodrugs of epinephrine having a certain property when those prodrugs have not been disclosed in the priority documents.
Claim Objections
Claim 1 is objected to because of the following informalities: the status identifier states “Currently amended”, but the claim does not contain any amendments. The status identifier should state “Original”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-29 and 47-50 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schobel et al. (US 2017/0348251 A1; which was published prior to the effective filing date of the instant claims).
Regarding instant claim 1, Schobel et al. disclose a pharmaceutical composition, comprising: a polymeric matrix; a pharmaceutically active component including epinephrine in the polymeric matrix; and an adrenergic receptor interacter (Claim 1).
Regarding instant claim 2, Schobel et al. disclose the pharmaceutical composition according to claim 1, further comprising a permeation enhancer (Claim 2).
Regarding instant claim 3, Schobel et al. disclose the pharmaceutical composition according to claim 1, wherein the composition is a film further comprising a polymeric matrix, the pharmaceutically active component being contained in the polymeric matrix (Claim 3).
Regarding instant claim 4, Schobel et al. disclose the pharmaceutical composition according to claim 2, wherein the permeation enhancer includes a phenylpropanoid (Claim 4).
Regarding instant claim 5, Schobel et al. disclose the pharmaceutical composition according to claim 2, wherein the permeation enhancer includes farnesol or Labrasol (Claim 5).
Regarding instant claim 6, Schobel et al. disclose the pharmaceutical composition according to claim 2, wherein the permeation enhancer includes linoleic acid (Claim 6).
Regarding instant claim 7, Schobel et al. disclose the pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a film further comprising a polymeric matrix, the pharmaceutically active component being contained in the polymeric matrix (Claim 7).
Regarding instant claim 8, Schobel et al. disclose the pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a chewable or gelatin based dosage form, spray, gum, gel, cream, tablet, liquid or film (Claim 8).
Regarding instant claim 9, Schobel et al. disclose the pharmaceutical composition according to claim 4, wherein the phenylpropanoid is eugenol or eugenol acetate (Claim 9).
Regarding instant claim 10, Schobel et al. disclose the pharmaceutical composition according to claim 4, wherein the phenylpropanoid is a cinnamic acid, cinnamic acid ester, cinnamic aldehyde or hydrocinnamic acid (Claim 10).
Regarding instant claim 11, Schobel et al. disclose the pharmaceutical composition according to claim 4, wherein the phenylpropanoid is chavicol (Claim 11).
Regarding instant claim 12, Schobel et al. disclose the pharmaceutical composition according to claim 4, wherein the phenylpropanoid is safrole (Claim 12).
Regarding instant claim 13, Schobel et al. disclose the pharmaceutical composition according to claim 1, wherein the adrenergic receptor interacter is a phytoextract (Claim 13).
Regarding instant claim 14, Schobel et al. disclose the pharmaceutical composition according to claim 13, wherein the phytoextract further includes an essential oil extract of a clove plant (Claim 14).
Regarding instant claim 15, Schobel et al. disclose the pharmaceutical composition according to claim 13, wherein the phytoextract further includes an essential oil extract of a leaf of a clove plant (Claim 15).
Regarding instant claim 16, Schobel et al. disclose the pharmaceutical composition according to claim 13, wherein the phytoextract further includes an essential oil extract of a flower bud of a clove plant (Claim 16).
Regarding instant claim 17, Schobel et al. disclose the pharmaceutical composition according to claim 13, wherein the phytoextract further includes an essential oil extract of a stem of a clove plant (Claim 17).
Regarding instant claim 18, Schobel et al. disclose the pharmaceutical composition according to claim 13, wherein the phytoextract is synthetic or biosynthetic (Claim 18).
Regarding instant claim 19, Schobel et al. disclose the pharmaceutical composition according to claim 13, wherein the phytoextract further includes 40-95% eugenol (Claim 19).
Regarding instant claim 20, Schobel et al. disclose the pharmaceutical composition according to claim 1, wherein the adrenergic receptor interacter includes a terpenoid, terpene or a sesquiterpene (Claim 20).
Regarding instant claim 21, Schobel et al. disclose the pharmaceutical composition according to claim 1, wherein the polymer matrix includes a polymer (Claim 21).
Regarding instant claim 22, Schobel et al. disclose the pharmaceutical composition according to claim 21, wherein the polymer is a water soluble polymer (Claim 22).
Regarding instant claim 23, Schobel et al. disclose the pharmaceutical composition according to claim 21, wherein the polymer includes a polyethylene oxide (Claim 23).
Regarding instant claim 24, Schobel et al. disclose the pharmaceutical composition according to claim 21, wherein the polymer includes a cellulosic polymer is selected from the group of: hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, methylcellulose and carboxymethyl cellulose (Claim 24).
Regarding instant claim 25, Schobel et al. disclose the pharmaceutical composition according to claim 21, wherein the polymer includes a cellulosic polymer is selected from the group of: hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, methylcellulose and carboxymethyl cellulose (Claim 25).
Regarding instant claim 26, Schobel et al. disclose the pharmaceutical composition according to claim 21, wherein the polymeric matrix comprises at least one polymer selected from the group of: pullulan, polyvinyl pyrrolidone, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, ethylene oxide-propylene oxide co-polymers, collagen, albumin, poly-amino acids, polyphosphazenes, polysaccharides, chitin, chitosan, and derivatives thereof (Claim 26).
Regarding instant claim 27, Schobel et al. disclose the pharmaceutical composition according to claim 1, further comprising a stabilizer (Claim 27).
Regarding instant claim 28, Schobel et al. disclose the pharmaceutical composition according to claim 1, wherein the polymeric matrix comprises a dendritic polymer or a hyperbranched polymer (Claim 28).
Regarding instant claim 29, Schobel et al. disclose a method of making a pharmaceutical composition comprising: combining an adrenergic receptor interacter with a pharmaceutically active component including epinephrine and forming a pharmaceutical composition including the adrenergic receptor interacter and the pharmaceutically active component (Claim 29).
Regarding instant claims 47-50, Schobel et al. disclose compositions comprising the same components as instantly claimed. In the absence of evidence to the contrary, the compositions according to Schobel et al. would inherently possess a Tmax and Cmax that is within the scope of the instant claims.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant asserts that the claims have been amended, thereby mooting this rejection.
The examiner respectfully argues that the instant claims do not contain amendments.
Applicant further argues that this cited reference is not prior art.
The examiner respectfully argues that the priority documents do not provide support for the instant claims. Therefore, Schobel et al. was published prior to the effective filing date of the instant claims.
Claim Rejections - 35 USC § 103
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 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 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 1-11, 13-27, 29, 36, 38 and 47-50 are rejected under 35 U.S.C. 103 as being unpatentable over Hill (US 2007/0293581 A1) in view of Nicolazzo et al. (Journal of Pharmaceutical Sciences, 2004), Booles (US 2012/0058158 A1), Schobel et al. (US 2012/0009260 A1), Fuisz et al. (US 8,617,589), Myers et al. (US 8,936,825), Hassan et al. (Expert Opinion Drug Delivery, 2010), Razafimamonjison et al. (International Journal of Basic and Applied Sciences, 2014), Gopalakrishnan et al. (Journal of the Science of Food and Agriculture, 1990), Juglal et al. (Journal of Food Protection, 2002) and Quay (US 2007/0275893 A1).
Regarding instant claims 1-6 and 9-20, Hill teaches buccal, lingual or sublingual dosage forms comprising epinephrine ([0083]-[0092]). Hill teaches that the buccal, lingual or sublingual dosage forms can be in the form of tablets or films, including muco-adhesive films ([0016], [0026], [0037], [0048], [0059], [0075]-[0079], [0084] and [0104]-[0106]). Hill further teaches that the buccal, lingual or sublingual dosage forms may include absorption enhancers to maximize the release rate of the epinephrine into the systemic circulation, wherein the absorption enhancer may be a transmucosal absorption enhancer, including chelators, non-ionic surfactants, cationic surfactants, anionic surfactants, bile salts and other steroidal detergents, fatty acids, non-surfactants, phospholipids, cyclodextrins and various glycosides ([0086]).
Hill teaches that the buccal, lingual and sublingual epinephrine dosage forms can be formulated comprising absorption enhancers to maximize the release rate of the epinephrine into the systemic circulation, wherein the absorption enhancer is a transmucosal absorption enhancer, including chelators, non-ionic surfactants, cationic surfactants, anionic surfactants, bile salts and other steroidal detergents, fatty acids, non-surfactants, phospholipids, cyclodextrins and various glycosides ([0016], [0086] and [0136]).
Hill does not explicitly disclose that the buccal, lingual or sublingual dosage forms comprise an adrenergic receptor interacter, as instantly claimed. However, Booles teaches sublingual delivery of medicaments comprising a mucosal penetration enhancer and a flavoring agent, wherein the flavoring or mucosal penetration enhancer preferably comprises an essential oil such as clove oil. The addition of such an essential oil surprisingly has three benefits: (1) the essential oils act as penetration enhancers, improving the rate and extent of uptake of such medicaments by the sublingual mucosa; (2) the essential oils, in many cases, act as co-solvents thereby increasing the solubility of medicaments; and (3) the essential oils provide a flavor component, giving organoleptic feedback to a user of the medicament, to confirm that is has been successfully delivered ([0024]).
Schobel et al. teach films suitable for delivery to buccal, sublingual, and other mucosal tissue ([0006]), wherein the films may include penetration and permeation enhancers, including the following terpenoids: a-terpineol, terpinen-4-ol, carvol, carvone, pulegone, piperitone, menthone, a-pinene oxide, and 1,8-cineole ([0172]); fatty acids such as linoleic acid ([0172]); glycerol and polyethylene glycol esters (e.g., Labrasol) ([0170]), monoterpenes ([0173]); etc.
Fuisz et al. teach biocompatible films for delivery to the oral mucosa (col. 2, ln. 24-30), wherein the films include pharmaceutical bioactive agents, such as epinephrine (col. 7, ln. 23 and 45; col. 11, ln. 61-62), and a mucosal absorbing enhancer, such as menthol, thymol, oleic acid, fatty acids, terpenes, etc. (col. 14, ln. 1-34).
Therefore, it would have been prima facie obvious for a person having ordinary skill in the art prior to the effective filing date of the instant invention to prepare the buccal, lingual or sublingual dosage forms according to Hill comprising epinephrine in the form of a film and further comprising a penetration and permeation enhancer. A person having ordinary skill in the art would have been motivated to include an absorption enhancer because Hill teaches that absorption enhancers maximize the release rate of the epinephrine into the systemic circulation. Further, a person having ordinary skill in the art would have been motivated to select adrenergic receptor interacters as the absorption enhancers because Schobel et al. and Fuisz et al. each teach that absorption enhancers that can be included in films for delivery of an active agent to the mucosa includes adrenergic receptor interacters, such as clove oil, and Booles teaches that clove oil is a flavoring or mucosal penetration enhancer that has three benefits: (1) the essential oils act as penetration enhancers, improving the rate and extent of uptake of such medicaments by the sublingual mucosa; (2) the essential oils, in many cases, act as co-solvents thereby increasing the solubility of medicaments; and (3) the essential oils provide a flavor component, giving organoleptic feedback to a user of the medicament, to confirm that is has been successfully delivered.
It is noted that Booles does not explicitly disclose that the clove oil is derived from the leaf, flower bud or stem of the plant. However, Razafimamonjison et al. teach that the clove oil derived from the leaf, flower bud and stem all have eugenol (~72-97%), β-caryophyllene (a sesquiterpene) and eugenyl acetate as main components to varying degrees, as well as methyl salicylate, chavicol, α-copaene (a sesquiterpene), methyl eugenol, iso-eugenol, α-humulene, and caryophyllene oxide (Table 2).
Also, Gopalakrishnan et al. teach that clove oil comprises farnesol (Tables 1-5); and Juglal et al. teach that cinnamic acid is an essential component of clove (Figure 1). Furthermore, Quay teaches that cinnamic acid, cinnamic acid esters, cinnamic aldehyde and hydrocinnamic acid are suitable penetration enhancers ([0346]).
Schobel et al. teach films suitable for delivery to buccal, sublingual, and other mucosal tissue ([0006]), wherein the films may include penetration and permeation enhancers, including the following terpenoids: a-terpineol, terpinen-4-ol, carvol, carvone, pulegone, piperitone, menthone, a-pinene oxide, and 1,8-cineole ([0172]); fatty acids such as linoleic acid ([0172]); glycerol and polyethylene glycol esters (e.g., Labrasol) ([0170]), monoterpenes ([0173]); etc.
Fuisz et al. teach biocompatible films for delivery to the oral mucosa (col. 2, ln. 24-30), wherein the films include pharmaceutical bioactive agents, such as epinephrine (col. 7, ln. 23 and 45; col. 11, ln. 61-62), and a mucosal absorbing enhancer, such as menthol, thymol, oleic acid, fatty acids, terpenes, etc. (col. 14, ln. 1-34).
Myers et al. teach dissolvable film dosage forms for delivery to the mucosal region of the body (col. 3, ln. 16-18), wherein the films comprise actives and may comprise penetration and permeation enhancers, including the following terpenoids: a-terpineol, terpinen-4-ol, carvol, carvone, pulegone, piperitone, menthone, a-pinene oxide, 1,8-cineole and menthol (col. 25, ln. 4-25); fatty acids such as linoleic acid; glycerol and polyethylene glycol esters (e.g., Labrasol), monoterpenes; etc. (col. 23, ln. 51 to col. 24, ln. 10). Myers et al. further teach that combinations of penetration and permeation enhancers from different classes are also useful (col. 23, ln. 64-65; col. 25, ln. 14-33).
Hassan et al. teach that the buccal drug delivery system has been accepted as a potential non-invasive route of drug administration, with the advantages of avoidance of the first-pass metabolism, sustained therapeutic action and better patient compliance (pg. 97, Abstract). Hassan et al. teach that terpenes are a very safe and effective class of penetration enhancers obtained from natural sources (pg. 105, col. 2, Section 5.3). Hassan et al. teach that terpenes, including sesquiterpenes, have excellent permeation-enhancing effects to facilitate transdermal drug delivery, wherein terpenes can enhance the permeation of both lipophilic and hydrophilic drugs (pg. 106, col. 1). Hassan et al. teach that terpene permeation enhancers include menthol, cineole, α-terpineol and linalool, which are terpenoids (pg. 106, col. 1). Hassan et al. teach that the mechanism of enhancement is due to the partition coefficient enhancing effects of the terpene; and the interaction with the membrane components for L-menthol, increasing the diffusibility of the active (pg. 106, col. 1).
Hill also teaches that the buccal, lingual and sublingual epinephrine dosage forms can be formulated comprising absorption enhancers to maximize the release rate of the epinephrine into the systemic circulation, wherein the absorption enhancer is a transmucosal absorption enhancer, including chelators, non-ionic surfactants, cationic surfactants, anionic surfactants, bile salts and other steroidal detergents, fatty acids, non-surfactants, phospholipids, cyclodextrins and various glycosides ([0016], [0086] and [0136]). Also, Myers et al. further teach that combinations of penetration and permeation enhancers from different classes are also useful (col. 23, ln. 64-65; col. 25, ln. 14-33).
Regarding instant claims 7-8 and 21-27, Hill teaches that the buccal, lingual and sublingual epinephrine dosage forms may also comprise diluents, such as starch and HPMC ([0088]); and binders, such as cellulose derivatives, polyvinylpyrrolidone/vinyl acetate copolymers, crospovidone, povidone, starch, acacia gum, traganth gum, polyvinylpyrrolidone, and polyethylene glycol ([0089]). Hill also teaches that the buccal, lingual, or sublingual rapidly dissolving oral films can comprise a film-forming agent and optionally a stabilizing agent, wherein the film-forming agent is selected from pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, soy protein isolate, whey protein isolate, casein and mixtures thereof ([0104]).
Also, a person having ordinary skill in the art would have been motivated to include phenylpropanoids as well as linoleic acid, terpenes and sesquiterpene and/or clove oil, which comprises farnesol and cinnamic acid, as the absorption enhancers because Schobel et al., Fuisz et al., Myers et al. and Hassan et al. each teach that absorption enhancers that can be included in films for delivery of an active agent to the mucosa includes terpenoids, fatty acids, and terpenes, and Booles teaches that clove oil is a flavoring or mucosal penetration enhancer that has three benefits: (1) the essential oils act as penetration enhancers, improving the rate and extent of uptake of such medicaments by the sublingual mucosa; (2) the essential oils, in many cases, act as co-solvents thereby increasing the solubility of medicaments; and (3) the essential oils provide a flavor component, giving organoleptic feedback to a user of the medicament, to confirm that is has been successfully delivered. Also, Hassan et al. clearly teach that terpenes, which include terpenoids, have excellent permeation-enhancing effects to facilitate transdermal drug delivery.
Regarding instant claim 29, Hill teaches combining epinephrine with a penetration enhancer ([0085]-[0086], [0093]-[0105]).
Regarding instant claim 36, Hill teaches treating an allergic emergency, such as anaphylaxis, in a patient ([0009]; Claim 1).
Regarding instant claim 38, Hill teaches that compositions comprising epinephrine are suitable for treatment of anaphylaxis ([0108])., mydriasis and asthma ().
Regarding instant claims 47-50, it would have been obvious to prepare pharmaceutical compositions comprising epinephrine, a polymer matrix and an adrenergic receptor interacter, as discussed above. The compositions would necessarily possess the instantly claimed Tmax and Cmax.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant asserts that they submitted a July 2021 Declaration of Stephen Wargacki for clarification.
The examiner respectfully argues that the declaration has not been filed in this application. Applicant refers to an affidavit or declaration filed in the prior application. Affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132, filed during the prosecution of the prior application do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make the remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application.
Applicant further argues that Hill does not teach any adrenergic receptor interacter at all. None of the secondary references supply this omission, alone or in combination. Booles is directed generally to medicaments including a mucosal penetration enhancer and flavoring agents. Nicolazzo teaches that permeability is enhanced with sodium dodecyl sulfate at concentrations resulting in intercellular lipid solubilization. Schobel 2012 teaches a corona comprising a plurality of ligands covalently linked to the core, wherein at least one of said ligands comprises a carbohydrate moiety. Razafimamonjison discloses clove oil sources, but does not describe, teach or suggest an adrenergic receptor interacter. Fuisz teaches a biocompatible film comprising a single layer having a plurality of components. Myers is directed to a film dosage in general. Hassan teaches a buccal delivery system as a non-invasive route for medication, and notes that this is "still very challenging." Page 97. Razafilmamonjison teaches clove oil in dental care and as an antiseptic. Gopalakrishman is cited for teaching clove oil comprising farnesol. Schobel is cited for teaching film delivery devices. Juglal teaches that cinnamic acid is a component of clove. Quay teaches cinnamic acids and similar derivatives as penetration enhancers.
None of these references, alone or in combination teach or suggest an adrenergic receptor interacter.
The examiner respectfully argues that a person having ordinary skill in the art would have been motivated to select adrenergic receptor interacters as the absorption enhancers because Schobel et al. and Fuisz et al. each teach that absorption enhancers that can be included in films for delivery of an active agent to the mucosa includes adrenergic receptor interacters, such as clove oil, and Booles teaches that clove oil is a flavoring or mucosal penetration enhancer that has three benefits: (1) the essential oils act as penetration enhancers, improving the rate and extent of uptake of such medicaments by the sublingual mucosa; (2) the essential oils, in many cases, act as co-solvents thereby increasing the solubility of medicaments; and (3) the essential oils provide a flavor component, giving organoleptic feedback to a user of the medicament, to confirm that is has been successfully delivered.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Hill (US 2007/0293581 A1) in view of Booles (US 2012/0058158 A1), Schobel et al. (US 2012/0009260 A1), Fuisz et al. (US 8,617,589), Myers et al. (US 8,936,825), Hassan et al. (Expert Opinion Drug Delivery, 2010), Razafimamonjison et al. (International Journal of Basic and Applied Sciences, 2014), Gopalakrishnan et al. (Journal of the Science of Food and Agriculture, 1990), Juglal et al. (Journal of Food Protection, 2002) and Quay (US 2007/0275893 A1) as applied to claims 1-11, 13-27, 29, 36, 38 and 47-50, and further in view of Unger (US 6,028,066).
Regarding instant claim 12, Hill does not explicitly disclose buccal, lingual and sublingual epinephrine dosage forms comprising safrole, as instantly claimed. However, Hill teaches that the films may further comprise excipients, including the flavorants eugenol and safrole ([0091]). Also, Unger teaches that safrole is a penetrating and/or solubilizing agent suitable for application to mucosal membranes (col. 83, ln. 12-41).
Therefore, it would have been prima facie obvious for a person having ordinary skill in the art to include safrole in the compositions according to Hill. Such would have been obvious because Hill teaches that safrole may be included as a flavorant, and Unger teaches that safrole is a suitable penetrating and/or solubilizing agent for application to the mucosal membrane. A person having ordinary skill in the art would have been motivated to include safrole in the compositions according to Hill in order to enhance the penetration and/or solubility of the epinephrine as well as to provide a flavorant.
Response to Arguments
Applicant's arguments are the same as above. The examiner’s response above is repeated here as well.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Hill (US 2007/0293581 A1) in view of Booles (US 2012/0058158 A1), Schobel et al. (US 2012/0009260 A1), Fuisz et al. (US 8,617,589), Myers et al. (US 8,936,825), Hassan et al. (Expert Opinion Drug Delivery, 2010), Razafimamonjison et al. (International Journal of Basic and Applied Sciences, 2014), Gopalakrishnan et al. (Journal of the Science of Food and Agriculture, 1990), Juglal et al. (Journal of Food Protection, 2002) and Quay (US 2007/0275893 A1) as applied to claims 1-11, 13-27, 29, 36, 38 and 47-50, and further in view of Cheng et al. (Journal of Pharmaceutical Sciences, 2008) and Tülü et al. (A Search for Antibacterial Agents, Chapter 6, 2012).
Regarding instant claim 28, Hill does not explicitly disclose buccal, lingual and sublingual epinephrine dosage forms comprise dendritic polymer or hyperbranched polymer, as instantly claimed. However, Cheng et al. teach that dendrimers are hyperbranched and monodisperse polymers, wherein the dendrimers are suitable for drug delivery through the mucosa (pg. 123, col. 1, paragraph 1; and pg. 138, col.1, paragraph 2). Also, Tülü et al. teach that cationic dendrimers may have intrinsic mucoadhesive properties for use in the oral cavity, as mucin is negatively charged, thus creating an electrostatic attraction between mucus and dendrimer wherein an encapsulated active may be slowly released into the oral cavity (pg. 97, paragraph 1).
Therefore, it would have been prima facie obvious for a person having ordinary skill in the art to prepare the buccal, lingual or sublingual dosage forms according to Hill wherein the compositions comprise a dendritic polymer or hyperbranched polymer. Such would have been obvious because Cheng et al. teach that dendrimers are suitable for drug delivery through the mucosa, and Tülü et al. teach that dendrimers may have an intrinsic mucoadhesive property in the oral cavity and can slowly release an encapsulated active agent.
Response to Arguments
Applicant's arguments are the same as above. The examiner’s response above is repeated here as well.
Claims 37 and 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Hill (US 2007/0293581 A1) in view of Booles (US 2012/0058158 A1), Schobel et al. (US 2012/0009260 A1), Fuisz et al. (US 8,617,589), Myers et al. (US 8,936,825), Hassan et al. (Expert Opinion Drug Delivery, 2010), Razafimamonjison et al. (International Journal of Basic and Applied Sciences, 2014), Gopalakrishnan et al. (Journal of the Science of Food and Agriculture, 1990), Juglal et al. (Journal of Food Protection, 2002) and Quay (US 2007/0275893 A1) as applied to claims 1-11, 13-27, 29, 36, 38 and 47-50, and further in view of Stanczak et al. (Pharmacological Reports, 2006).
Regarding instant claims 37 and 39-40, Hill does not explicitly disclose buccal, lingual and sublingual epinephrine dosage forms further comprising dipivefrin, as instantly claimed. However, Stanczak et al. teach that dipivefrin is a prodrug of epinephrine formed by the diesterification of epinephrine and pivalic acid, wherein dipivefrin is converted to epinephrine by enzymatic hydrolysis. Stanczak et al. teach that the dipivefrin prodrug delivery system is a more efficient way of delivering the therapeutic effects of epinephrine, with fewer side effects than are usually associated with conventional epinephrine therapy (pg. 601, col. 1, paragraph 1).
Therefore, it would have been prima facie obvious for a person having ordinary skill in the art to prepare the buccal, lingual or sublingual dosage forms according to Hill wherein the compositions comprise dipivefrin as a prodrug of epinephrine. Such would have been obvious because Stanczak et al. teach that dipivefrin is a prodrug of epinephrine, and the dipivefrin prodrug delivery system is a more efficient way of delivering the therapeutic effects of epinephrine, with fewer side effects than are usually associated with conventional epinephrine therapy.
Response to Arguments
Applicant's arguments are the same as above. The examiner’s response above is repeated here as well.
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 1-29 and 47-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,191,737. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a pharmaceutical composition comprising a polymeric matrix, epinephrine and an adrenergic receptor interacter. US ‘737 claims an adrenergic receptor interacter and a permeation enhancer, wherein the adrenergic receptor interacter and the permeation enhancers are the same as the instant claims. Also, the phenylpropanoids of the instant claims and US ‘737 include the same compounds, such as eugenol, eugenol acetate, cinnamic acid, cinnamic acid ester, cinnamic aldehyde, hydrocinnamic acid, chavicol and safrole. US ‘737 also claims a mucoadhesive polymer matrix, whereas the instant claims merely claim a polymer matrix. However, the polymers of the instant claims and US ‘737 overlap. Therefore, the instant claims and the claims of US ‘737 significantly overlap.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant states that they will address these rejections when the claims are deemed allowable.
Therefore, the examiner’s rejection is maintained.
Claims 1-29, 36-40 and 47-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-58 of U.S. Patent No. 11,273,131. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a pharmaceutical composition comprising a polymeric matrix, a pharmaceutically active component and an interacter. US ‘131 claims a benzodiazepine active including epinephrine. Also, US ‘131 claims an adrenergic receptor interacter which includes phenylpropanoids.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant states that they will address these rejections when the claims are deemed allowable.
Therefore, the examiner’s rejection is maintained.
Claims 1-29, 36-40 and 47-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 12,023,309. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a composition comprising a polymeric matrix, a pharmaceutically active component including epinephrine or a salt or ester thereof in the polymeric matrix and an adrenergic receptor interacter. The polymeric matrix comprises the same polymeric components as instantly claimed, and the interacters include the same compounds as instantly claimed.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant states that they will address these rejections when the claims are deemed allowable.
Therefore, the examiner’s rejection is maintained.
Claims 1-29, 36-40 and 47-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-36 of copending Application No. 16/143,678 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a method of treating a medical condition comprising administering a composition comprising a polymeric matrix, epinephrine in the polymeric matrix and an interacter. The pharmaceutically active component of the reference application includes the same components as instantly claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant states that they will address these rejections when the claims are deemed allowable.
Therefore, the examiner’s rejection is maintained.
Claims 1-29, 36-40 and 47-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29, 33, 36-40, 42-46 and 51-56 of copending Application No. 16/143,821 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a composition comprising a polymeric matrix, a pharmaceutically active component including epinephrine or its prodrug in the polymeric matrix and an adrenergic receptor interacter. The polymeric matrix comprises the same polymeric components as instantly claimed, and the interacters include the same compounds as instantly claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-29, 36-40 and 47-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 and 22-30 of copending Application No. 18/413,556 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a composition comprising a polymeric matrix, a pharmaceutically active component including an ester of epinephrine in the polymeric matrix and an adrenergic receptor interacter. The polymeric matrix comprises the same polymeric components as instantly claimed, and the interacters include the same compounds as instantly claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant states that they will address these rejections when the claims are deemed allowable.
Therefore, the examiner’s rejection is maintained.
Claims 1-29, 36-40 and 47-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 31 of copending Application No. 19/051,762 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a composition comprising a polymeric matrix, a pharmaceutically active component including epinephrine or a salt or ester thereof in the polymeric matrix and an adrenergic receptor interacter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 29 October 2025 have been fully considered but they are not persuasive. Applicant states that they will address these rejections when the claims are deemed allowable.
Therefore, the examiner’s rejection is maintained.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nathan W Schlientz whose telephone number is (571)272-9924. The examiner can normally be reached on 10:00 AM to 6:00 PM, Monday through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached on (571) 272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/N.W.S/Examiner, Art Unit 1616
/Mina Haghighatian/Primary Examiner, Art Unit 1616