DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of claims
Claims 1-2, 9, and 11 are original. Claims 3-8, 10, and 12-15 are currently amended. Claims 1-15 are pending and under examination.
Priority
This application is a 371 of PCT/EP2022/067655, filed on 06/28/2022. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. EP 21382581.3, filed on 06/30/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/14/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112 (b)
Claims 1-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “a solvent of the glycol, or glycol ether or glycol ether ester family”. It is unclear whether the phrase “family” applies to all three listed types (i.e., glycol, glycol ether, glycol ether ester) or only to glycol ether ester. Furthermore, the term “family” does not provide clear boundaries as to which specific compounds are encompassed within the claimed solvent class. The claim also fails to clarify whether the recited group is intended to be a closed Markush group or an open group of solvent classes. Accordingly, a person of ordinary skill in the art would be unable to determine with reasonable certainty which solvents fall within the scope of the claim, rendering it indefinite. Applicant could consider going to Markush format with “a solvent selected from the group consisting of a glycol, a glycol ether, and a glycol ether ester” or if desired “a solvent selected from the group consisting of a glycol, a glycol ether, a glycol ether ester, and a combination thereof”.
Claims 2-15 are also indefinite for being dependents of indefinite claim 1.
Claim 12 recites “component e) has a caprylic acid percentage of about 55% to about 60% and a capric acid percentage of about 40% to about 45%”. However, the claim fails to specify the units of the recited percentages (e.g., w/w, v/v, w/v, molar percentage). Because the claim does not specify the measurement basis for the percentages, a person of ordinary skill in the art would be unable to determine the scope of the claim with reasonable certainty, rendering it indefinite.
Claim 14 recites the limitation "direct application onto the skin”. There is insufficient antecedent basis for this limitation in the claim. Its independent claim 1 recites that the nano-emulsion is for “topical drug delivery”. The term “topical” does not necessarily limit administration to the skin, as topical administration may also include delivery to mucosal surfaces, and there is no reference to a subject that would inherently have skin, since this is a composition claim. Therefore, there is not proper antecedent basis for skin. Applicant may amend the recitation to “direct application onto skin”.
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 (i.e., changing from AIA to pre-AIA ) 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 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.
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 inventions 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.
Claims 1-4, 7-9, 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Kandavalli et al. (US20160184431A1) in view of Tamarkin et al. (US20080299220A1).
Kandavalli et al. discloses topical compositions comprising a corticosteroid and at least one penetration enhancing agent, wherein the composition may be substantially free of propylene glycol (abstract). Kandavalli et al. teaches that the topical compositions of the present invention may be in the form of nanoemulsions (¶ 88). Kandavalli et al. teaches that the composition may be used for treating skin diseases (¶ 62). Kandavalli et al. teaches that the composition may include one or more additional active agents that are useful in the management of psoriasis and associated pathological conditions (¶ 66). Kandavalli et al. teaches that the composition may include one or more pharmaceutically acceptable excipient, which may act as carriers, emulsifiers, co-emulsifiers, solvents, co-solvents, emollients, antioxidants, preservatives, gelling or thickening agents, polymers, surfactants, soothing agents, pH modifiers, solubilizers, humectants, moisturizers, oily bases, and the like (¶ 96). Kandavalli et al. teaches that the term “solvent” refers to components that aid in the dissolution of the drug in the formulation (¶ 105), which would thus include emulsifiers. Kandavalli et al. teaches that such solvents include diethylene glycol monomethyl ether (¶ 105), which satisfies element C of present claim 1. Kandavalli et al. teaches that the composition may include polyoxyl 40 hydrogenated castor oil as an emulsifier (¶ 98), which satisfies element D of present claim 1. Kandavalli et al. teaches that the composition may include caprylic/capric triglycerides as a water immiscible solvent (¶ 105), which satisfies element E of present claim 1. Kandavalli et al. teaches that the composition may include water (¶ 91), which satisfies element F of present claim 1. Kandavalli et al. teaches that the composition may include cetrammonium chloride (¶ 110), which satisfies all required elements of present claims 8 and 9. Kandavalli et al. teaches that the composition may include solvents––previously stated to include polyoxyl 40 hydrogenated castor (has an HLB of 15) in addition to caprylic and capric triglycerides––at concentrations of 1% w/w to 30% w/w based on the total weight of the composition (¶ 106), which overlaps with the claimed concentration ranges and ratios of present claim 13, thus wholly satisfying it. Kendall allows for one or more additional active agents that are useful in management of psoriasis and associated pathological conditions (paragraph 66). In a single embodiment (¶ 137, example 2), an emulsion was made with an anti-inflammatory agent and various excipients including surfactants, providing a point of reference for modifying such compositions.
However, Kandavalli et al. fails to teach the limitations of elements A and B in present claim 1, in addition to the limitations of present claims 2-4, 7, 15.
Tamarkin et al. discloses a substantially waterless composition suitable for delivery of an active agent to a body surface or cavity (abstract). Tamarkin et al. teaches that the composition may however comprise up to 10% of water (¶ 34). Tamarkin et al. teaches that the target site of the composition may be the skin (¶ 55), and further states that the composition may be applied to the skin (¶ 125). Tamarkin et al. teaches that the composition may include surfactants to form emulsions such as oil-in-water (o/w) emulsions (¶ 236). Tamarkin et al. teaches that the composition may include therapeutic agents such as diclofenac (which is intrinsically a free acid), its salts, and mixtures thereof (¶ 667), and specifically includes Diclofenac sodium as an example (¶ 84) ––covering the active agents stated in elements A and B of present claim 1 in addition to the active agents stated in present claims 2 and 3. Tamarkin et al. teaches that the composition may include about 0.01% to about 5% by weight of at least one therapeutic agent (¶ 51), which satisfies the active agent percentages stated in elements A and B of present claim 1 in addition to the active agent ratios and percentages stated in present claims 2 and 3. Tamarkin et al. states that the term “Surface-active agents” is synonymous to “surfactants” (¶ 236). Tamarkin et al. teaches that the composition may contain about 0% to about 10% of at least one surface-active agent (¶ 57) such as a cationic surface-active agent (¶ 245) to stabilize the two phases (¶ 131), which satisfies all required elements of present claim 4. Tamarkin et al. teaches that the composition may be substantially alcohol-free to reduce skin-irritating effects (¶ 210), which covers all required elements of present claim 7. Tamarkin et al. teaches that the therapeutic agent in the composition may include a non-steroidal anti-inflammatory agent (¶ 624) that treats or prevents a disease involving inflammation (¶ 626), thus covering all required elements of present claim 15.
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate the drugs, excipients, concentrations, and treatment teachings disclosed in Tamarkin et al. into the topical nanoemulsion composition of Kandavalli et al. This is because both references are directed towards topical delivery systems for administration of active agents to the skin and both references teach formulations that may be in emulsion form. Kandavalli et al. expressly teaches that its compositions may include excipients that overlap with those claimed such as nonionic surfactants, caprylic/capric triglyceride, and C8-C16-alkyl trimethylammonium salts, with caprylic/capric triglyceride and nonionic surfactants being at concentrations and ratios that overlap with those in the present claims. Additionally, Kandavalli et al. teaches that its composition may include active agents useful to treat pathological conditions, thereby suggesting addition or substitution of other well-known anti-inflammatory agents. Concurrently, Tamarkin et al. teaches diclofenac, its salt forms, and mixtures thereof, are suitable therapeutic agents for such compositions to treat inflammation topically, in addition to teaching that the cationic surfactants taught in Kandavalli et al. may be at concentrations overlapping with those in the present claims and that such composition may be alcohol-free. A person of ordinary skill in the art would therefore have been motivated to substitute or incorporate the diclofenac, cationic surfactant concentrations, and alcohol-free teachings of Tamarkin et al. into the emulsion vehicles of Kandavalli et al. to obtain a predictable topical anti-inflammatory composition, with a reasonable expectation of success because the references employ compatible formulation technologies (emulsions comprising surfactants and oils) routinely used to delivery active ingredients to the skin. Furthermore, a person of ordinary skill in the art would have understood that drugs such as diclofenac may exist in free acid and salt forms, and that inclusion of both forms can be used to balance solubility and permeability characteristics in topical formulations, rendering the presence of both forms of diclofenac (free acid and alkali metal salt) an obvious design choice. Overall, selecting concentrations and ratios of the above drugs and excipients constitutes routine optimization of result-effective variables through ordinary experimentation, which does not confer patentability. Accordingly, the claimed composition would have been obvious over the combined teachings of Kandavalli et al. and Tamarkin et al. with a reasonable expectation of success, given that both references employ conventional emulsifiable components routinely used for topical delivery of therapeutics.
Claims 5-6, 10-11, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Kandavalli et al. (US20160184431A1) in view of Tamarkin et al. (US20080299220A1) in further view of Nicolosi et al. (US20110206739A1) as evidenced by Murgia et al. (Murgia S, Fadda P, Colafemmina G, et al. Characterization of the Solutol® HS15/water phase diagram and the impact of the Δ9-tetrahydrocannabinol solubilization. J Colloid Interface Sci. 2013;390(1):129-136. doi:10.1016/j.jcis.2012.08.068).
Kandavalli et al. and Tamarkin et al. collectively teach all the limitations of present claims 1 and 4.
However, Kandavalli et al. and Tamarkin et al. fail to collectively teach the limitations of present claims 5-6, 10-11, and 14.
Nicolosi et al. discloses compositions and methods of forming nanoemulsions, e.g., containing an active component, in combination with lipophilic components such as oils, hydrophilic components such as water, and one or more surfactants (abstract). Nicolosi et al. teaches that nanoemulsions may contain anti-inflammatory agents (¶ 3). Nicolosi et al. teaches that the nanoemulsion compositions of the disclosure can be effective for delivery of therapeutic products to the skin (¶ 64), and may be done so topically (¶ 138). Nicolosi et al. teaches that such nano-emulsions of the invention can be developed via temperature-dependent phase inversion of a surfactant, also termed self-assembled nanoemulsions (self emulsifying) (¶ 8), which satisfies all required elements of present claim 5. Nicolosi et al. teaches such nano-emulsions to be transparent (¶ 3), which satisfies all required elements of present claim 6. Nicolosi et al. teaches that the compositions in this invention may contain a polyethylene glycol 660 hydroxystearate surfactant (e.g., Solutol® HS15) (¶ 11), also known to be polyoxyethylene esters of hydroxystearic acids (e.g., a polyoxyethylene ester of 12-hydroxystearic acid such as the surfactant sold under the tradename SOLUTOL® HS15) (¶ 81), thus satisfying all required elements of present claims 10 and 11. This is further evidenced by Murgia et al., which teaches that Solutol® HS15 consists of poly-ethylene glycol mono and di-esters of 12-hydroxystearic acid (HS) and of about 30 wt.% of free poly-ethylene glycol (PEG) (page 130, Section 2.1 - Materials). Nicolosi et al. teaches that such compositions can be delivered in kits for therapeutic use (¶ 140), with such kits containing administration (or application) instruments such as pipettes and patches (¶ 141), which thus satisfies all required elements of present claim 14.
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate the nanoemulsion formation techniques, surfactant selections, and delivery formats taught by Nicolosi et al. into the nanoemulsion composition collectively taught by Kandavalli et al. and Tamarkin et al. This is because all three references are directed towards topical delivery systems employing emulsified formulations for administering therapeutic agents to the skin. Nicolosi et al. expressly teaches self-assembled nano-emulsions formed via phase-inversion processes, which are conventional methods to produce stable nano-emulsions, and further teaches that such nanoemulsions may be transparent, thereby suggesting predictable formulation characteristics obtainable using known emulsification techniques. Additionally, Nicolosi et al. teaches Solutol® HS15 to function as a known surfactant suitable for nanoemulsion systems similar to those described in Kandavalli et al. and Tamarkin et al. Furthermore, Nicolosi et al. teaches delivery of nanoemulsion composition kits comprising application devices such as pipettes, thereby predicting delivery of such compositions with an applicator as recited in the present claims. A person of ordinary skill in the art would have therefore been motivated to apply the nanoemulsion preparations methods, surfactant selections, and delivery formats of Nicolosi et al. into the composition of Kandavalli et al. as modified by Tamarkin et al. to obtain a predictable topical nanoemulsion formulation with known stability, transparency, and administration characteristics. This would have been done with a reasonable expectation of success because the references employ compatible formulations technologies routinely used for topical delivery of therapeutic agents. Overall, selecting particular nanoemulsion preparation methods, surfactant species, and delivery configurations constitutes routine optimization of result-effective variables through ordinary experimentation, which does not confer patentability. Accordingly, the claimed invention would have been obvious over the combined teachings of Kandavalli et al., Tamarkin et al., and Nicolosi et al. with a reasonable expectation of success.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kandavalli et al. (US20160184431A1) in view of Tamarkin et al. (US20080299220A1) in further view of Dhingra et al. (US20180021349A1) as evidenced by Hasan (Hasan NM. Role of medium-chain fatty acids in the emulsification mechanistics of self-micro-emulsifying lipid formulations. Saudi Pharm J. 2014;22(6):580-590. doi:10.1016/j.jsps.2014.02.005).
Kandavalli et al. and Tamarkin et al. jointly teach all limitations of claim 1.
However, Kandavalli et al. and Tamarkin et al. fail to collectively teach the limitations of claim 12.
Dhingra et al. teaches formulations for drug delivery of a lipophilic therapeutic agent, providing enhanced modulation of solubility, stability, absorption, metabolism, and/or pharmacokinetic profile of the therapeutic agent (abstract). Dhingra et al. teaches that the composition may be in the form of a self-dispersing nano-emulsion (¶ 36). Dhingra et al. teaches that the administration method of the composition may be topical and transdermal (¶ 169). Dhingra et al. teaches that the composition may include diclofenac (¶ 75). Dhingra et al. teaches that the composition may include solubilizers (¶ 189) including Miglyol 812 (¶ 195), which possesses characteristics that overlap with all material and concentration elements of claim 12, thus wholly satisfying it. This is further evidenced by Hasan, which teaches that the fatty acid distribution in Miglyol 812 according to the manufacturer is: caprylic (C8): 50–65%, capric (C10): 30–45% (page 582, Section 2.1 – Materials).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate the Miglyol 812 teachings of Dhingra et al. into the nanoemulsion composition collectively taught by Kandavalli et al. and Tamarkin et al. This is because all three references are directed towards topical delivery systems employing emulsified formulations for administering therapeutic agents to the skin. Kandavalli et al. and Tamarkin et al. jointly teach that the nanoemulsions in its compositions may include substances such as caprylic/capric triglycerides to aid in the dissolution of active agents, While Dhingra et al. teaches Miglyol 812 to be an example of such triglycerides used in these nanoemulsions as a solubilizer. Therefore, a person of ordinary skill in the art would have been motivated to incorporate the teachings of Dhingra et al. into the joint teachings of Kandavalli et al. and Tamarkin et al. to further enhance the dissolution characteristics of the composition. Additionally, because all three of these references, especially Dhingra et al., teach such excipients to be compatible for these formulations and delivery methods, one of ordinary skill in the art would have incorporated the Miglyol 812 teachings of Dhingra et al. into the compositions taught by Kandavalli et al. and Tamarkin et al. with a reasonable expectation of success to reach the claimed invention.
Conclusions
No claim is found allowable.
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Arya A. Bazargani, Ph.D.
Patent Examiner
Art Unit 1613
/MARK V STEVENS/ Primary Examiner, Art Unit 1613