DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Drawings, Amendments to the Specification and the Claims, and Arguments/Remarks filed 16 March 2026, in response to the Office Correspondence dated 16 December 2025, are acknowledged.
The listing of Claims filed 16 March 2026, have been examined. Claims 1, 5, 8, 9, 11, 12, 14, 16, 18, 20, 23, 24, 26, 28-30, 41, 56, 59, and 60 are pending. Claims 1, 5, 8, 11, 12, 14, 23, 29, 56, are amended, claims 9, 16, 18, 20, 24, 26, 28, 30, and 41 are previously presented, new claims 59 and 60 have been added, and claims 2-4, 6, 7, 10, 13, 15, 17, 19, 21, 22, 25, 27, 31-40, 42-55, 57 and 58 are canceled.
Information Disclosure Statement
The Information Disclosure Statement, filed 16 March 2026, is acknowledged and has been considered.
Response to Amendment
The applicant has submitted replacement drawing sheets with higher resolution and clearer text. Accordingly, the Drawings objection is withdrawn.
The applicant has amended claims 11, 14, and 56 to address the prior objections. Regarding claims 11 and 14, the applicant has amended these claims to include "% w/v" after the first value in the recited range (i.e., "about 1% w/v to about 10% w/v"), thereby resolving the inconsistency in unit placement. Accordingly, the objection to claims 11 and 14 is withdrawn.
Regarding claim 56, the applicant has amended claim 56 to recite "comprising the compositions" (plural), resolving the antecedent basis issue. Thus, the objection to claim 56 regarding the singular/plural inconsistency is withdrawn. However, the applicant has not addressed the fundamental inconsistency between % w/w units in claim 56 and % w/v units in claim 1 and its dependents. Claim 1 recites all percentages as % w/v. Claim 56, which is an independent claim directed to a different statutory category (device vs. composition), recites all percentages as % w/w. While not an objection per se, this inconsistency across the claim set creates potential confusion regarding the scope of the invention. The applicant remains advised to consider conforming the unit basis across all claims or providing a clear statement in the specification regarding the density assumptions for conversion. No formal objection is maintained at this time.
The applicant has traversed the indefiniteness rejections under 35 U.S.C. § 112(b) and has made amendments to claims 1, 8, 12, 23, 29, and 56. The § 112(b) rejection of claim 1 and dependent claims 5, 8, 9, 11, 12, 14, 16, 18, 20, 23, 24, 26, 28, 29, 30, and 41 regarding the percentage basis is withdrawn. The applicant argues that one of skill in the art would appreciate that "% w/v" amounts are relative to the total composition, and that the amendment adding "in the composition" resolves the indefiniteness. The Examiner agrees that the amendment clarifies the reference basis. Accordingly, the rejection of claims 1, 8, and 23 for failing to specify the percentage basis is withdrawn.
The applicant has amended claim 12 to replace "Transcutol® P" with "diethylene glycol monoethyl ether." The Examiner acknowledges this amendment. The rejection under 35 U.S.C. § 112(b) for incorporation of a trademark is withdrawn as to claim 12. However, claim 12 still recites "azone". The applicant is advised to replace "azone" with the chemical name 1-dodecylazacycloheptan-2-one or define the term in the specification. The applicant has amended claim 23 to remove the extraneous underscore character in "0.1%_w/v." The Examiner acknowledges this correction. The 35 U.S.C. § 112(b) rejection based on this typographical error is withdrawn.
The applicant has amended claim 29 to add the application rate (12.5 µl/cm²), porosity (<15s/100cc/in²), moisture vapor transmission rate (about 6200 g/m²/day), and thickness (about 0.17mm) of the porous acrylate substrate. The applicant has also amended the specification to include these parameters and argues the claim amendments resolve the indefiniteness. The Examiner disagrees because adding the physical characteristics of the substrate does not cure the failure to define the non-occluded control or the drying conditions. The claim remains indefinite because the claim recites "as a fraction compared to a non-occluded control" but still fails to define the "non-occluded control". The specification at ¶[00135] describes a "non-film forming control applied to only the porous tape," but does not specify what that control composition is (e.g., pure solvent, no treatment, vehicle without active agent, or something else). One of ordinary skill cannot determine the denominator of the claimed fraction with reasonable certainty because the control is not defined (see Interval Licensing LLC v. AOL, Inc., 766 F.3d 1364, 1371 (Fed. Cir. 2014)).
Second, the claim recites "dried" but fails to specify drying conditions (temperature, humidity, time). The specification at ¶[0135] describes drying at "ambient conditions," but "ambient" is not an objective boundary. Drying at 20°C vs. 30°C, or at 30% relative humidity versus 70% relative humidity, will materially affect the water vapor transmission rate. Because the claimed property depends on unclaimed, uncontrolled variables, the claim fails to inform the public of its scope with reasonable certainty (see Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 910 (2014)). Accordingly, claim 29 remains rejected under 35 U.S.C. § 112(b) as indefinite.
The applicant has amended claim 56 to use % w/w throughout and to clarify that percentages are relative to "a total amount of the first composition and the second composition." The applicant argues that amending claim 56 to use % w/w throughout and to specify the basis as "relative to the total amount of the first composition and the second composition" resolves the indefiniteness. The Examiner disagrees because expressing percentages relative to the combined total weight of two compositions whose relative amounts are not specified renders the claim scope ambiguous.
The claim remains indefinite because the film-forming excipient appears only in the second chamber (claim 56(b): "about 5% w/w to about 7% w/w film forming excipient"). Because the percentage is expressed relative to the total weight of both compositions, and the weight ratio of the first composition to the second composition is not specified, one of ordinary skill cannot determine the absolute amount of film-forming excipient in the second chamber or the concentration of film-forming excipient within the second chamber itself.
The claim purports to define a device with two chambers, but the percentage basis renders the scope ambiguous because the total weight of the two chambers is not fixed and the relative amounts of the two compositions are not disclosed (see Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 910 (2014)). Accordingly, claim 56 remains rejected under 35 U.S.C. § 112(b) as indefinite. The previous rejection of claim 56 under 35 U.S.C. § 112(b) has been withdrawn and new rejection has been made for claims 56, 59 and 60. Dependent claims 59 and 60 are likewise indefinite, as they do not cure the defect in claim 56 noted above.
For the reasons set forth below in the Response to Arguments, the applicant’s amendments and arguments have been fully considered but are not persuasive, and the amendments fail to overcome the prior art rejections under 35 U.S.C. § 103. The rejection of claims 1, 5, 9, 11, 12, 14, 16, 20, 23, 24, 26, 28-30, and 41 under 35 U.S.C. § 103 as being unpatentable over Dandiker in view of Zhang is maintained. The rejection of claims 1, 8, and 18 under 35 U.S.C. § 103 as being unpatentable over Dandiker in view of Zhang and Kim is maintained and the rejection of claim 56 under 35 U.S.C. § 103 as being unpatentable over Dandiker in view of Zhang, Kim and Ruiz de Gopegui is maintained. New claims 59 and 60 recite specific polymers already disclosed in Dandiker (i.e., methacrylic acid/methyl methacrylate copolymers and Eudragit-type polymers), therefore, new added claims 59 and 60 are rejected under 35 U.S.C. § 103, as set for below.
The rejection of claims 1, 5, 8-9,11-12,14,16,18, 20, 23-24, 26, 28-31, 33, 41, and 56 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-8, 10-16 of US Patent No. 11,523,994 B2 and US Patent No. 12,208,169 B2; on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, and 5 of US Patent No. 12,186,326 B2; provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 11, 15-18, 20, 25, 29-31, 33, 38, 42, 49-51, and 53 of co-pending US Application No. 17/761,507; and provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 36, 44, 52, 53 and 69 of co-pending US Application No. 18/502,863 are maintained. The applicant argues that one of ordinary skill would not find it obvious to substitute spironolactone for testosterone in the reference formulations due to alleged differences in physicochemical properties and crystallization tendencies. The applicant's arguments are unpersuasive as set forth below in the Response to Arguments. In addition, the applicant's request to hold the provisional rejections in abeyance is denied. Newly added claims 59 and 60 are rejected under on the ground of nonstatutory double patenting and provisionally rejected on the ground of nonstatutory double patenting, as set for below as well.
New objections to amended claims 8 and 12 have been made to address newly introduced typographical errors, as outlined below.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 16 December 2025, since the art which was previously cited continues to read on the amended/newly cited limitations.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. § 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which Applicant regards as his invention.
Claim 29 is 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, regards as the invention.
Claim 29 is indefinite for failing to define essential parameters of the testing method. Claim 29 recites "as a fraction compared to a non-occluded control" but fails to define what constitutes the "non-occluded control." The specification at ¶[00135] describes a "non-film forming control applied to only the porous tape," but does not specify what that control composition is (e.g., pure solvent, no treatment, vehicle without active agent, or something else). One of ordinary skill would not know with reasonable certainty whether the control is an untreated substrate, a substrate treated with solvent alone, a substrate treated with a composition lacking the film-forming excipient, or some other control. One of ordinary skill cannot determine the denominator of the claimed fraction with reasonable certainty because the control is not defined (see Interval Licensing LLC v. AOL, Inc., 766 F.3d 1364, 1371 (Fed. Cir. 2014)).
The claim also recites "dried" but fails to specify drying conditions (i.e., temperature, humidity, time), which materially affect water vapor transmission rate. The specification at ¶[0137]-[0138] describes drying at "ambient conditions," but "ambient" varies widely (e.g., 20°C vs. 30°C, 30% RH vs. 70% RH) and does not provide objective boundaries. Drying at 20°C versus 30°C, or at 30% relative humidity versus 70% relative humidity, will materially affect the water vapor transmission rate. Because the claimed property depends on unclaimed, uncontrolled variables, the claim fails to inform the public of its scope with reasonable certainty (see Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 910 (2014)).
Issues remain that the test protocol is incomplete (e.g., humidity conditions, temperature, apparatus). The recited substrate parameters do not fully define reproducibility. Further, incorporation of characteristics of a commercial product (3M Transpore™) remains problematic because the claim does not require the actual product, only approximated parameters and variability across batches is not addressed. Accordingly, claim 29 remains rejected under 35 U.S.C. § 112(b) as indefinite.
To overcome this rejection, the applicant is advised to amend claim 29 to specify the non-occluded control (e.g., "compared to a control consisting of the porous acrylate substrate without any composition applied"), to specify drying conditions (e.g., "dried at 25°C ± 2°C and 50% ± 5% relative humidity for 30 minutes") and fully define reproducibility without reliance on the current 3M Transpore™ product, which may vary overtime rendering the scope of the claim unclear.
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 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.
Claims 1, 5, 9, 11, 12, 14, 16, 20, 23, 24, 26, 28-30, and 41 are rejected under 35 U.S.C. § 103 as being unpatentable over Dandiker (US20210236514A1; published 05 August 2021) in view of Zhang et al. (US20070189980A1; published 16 August 2007, hereinafter referred to as “Zhang”).
Dandiker teaches a "sprayable liquid solution" that forms a "washable film" when sprayed on the skin that can prevent crystallization of the active steriods, comprising: (1) an active steroid mixture (estradiol and testosterone), (2) one or more solvents, (3) one or more film-forming excipients soluble in water at a pH between 1 and 10 dissolved in water, and (4) one or more penetration enhancers (claim 74), wherein the solvents may be aliphatic solvents (e.g., ethanol, isopropyl alcohol, acetone; ¶[0048]).
The concentration of the active steroid mixture is from about 0.01-10% w/w of estradiol and about 0.1-25% w/w of testosterone (claim 75), providing a range of about 0.11-35% w/w active steroid concentration in the composition. Assuming a density for a hydroalcoholic film-forming spray containing ethanol, polymers and water of about 0.9 g/mL, the approximate active steroid mixture concentration in the composition would range from about 0.099-31.5% w/v, encompassing the instant claim 1 active steroid range of about 1-20% w/v spironolactone or canrenone. Dandiker teaches wherein the pH can also be below pH 5.0 and above pH 4 (¶[0048]), which is a standard, physiologically compatible pH for topical products and represents an obvious optimization, thus a pH of about 4-5 of instant claim 24 is taught by Dandiker.
Dandiker teaches the use of about 30-95% w/w ethanol and about 10-40% w/w isopropyl alcohol (¶[0059]), which would convert to approximately 27-85.5% w/v ethanol and 9-36% w/v isopropyl alcohol, using a composition density of about 0.9 g/mL, resulting in a combined concentration ranging from about 36-100% w/v aliphatic solvent. Given the use of the term “about” having a meaning of ± 10% w/v solvent (¶[0090]), rendering a concentration ranging from about 26-100% w/v aliphatic solvent by Dandiker, which encompasses the instant claim 1 range of 30-97% w/v aliphatic solvent.
The one or more film-forming excipients of the invention by Dandiker is used in the composition is from about 1-10% w/w (¶[0053]), or about 0.9-9% w/v given a 0.9 g/mL composition density, wherein 30 parts or less of water can be used to dissolve one part of said film-forming excipient (claim 74), which would give a maximum of about 96.77% allowance of water of the 1-10% w/w, or about 0.97-9.7% w/w water or less. When using an approximate composition density of about 0.9 g/mL, the water content is calculated to be about 0.87-8.7% w/v or less in the composition. Given the use of the term “about” having a meaning of ± 10% w/v (¶[0090]), rendering a concentration ranging from 0.81-9.9% w/v film-forming excipients and 0.78-9.57% w/v water or less taught by Dandiker, which almost entirely overlaps with the instant claim 1 range of about 1-10% w/v water and the instant claim 11 range of 1-10% w/v film-forming excipients. Nevertheless, including 1-10% w/v water as part of the solvent system or for other formulation purposes would be an obvious variation and choice of the specific range is a routine adjustment as a matter of experimental optimization of formulations.
Similarly, Dandiker teaches the use of a concentration of the one or more penetration enhancers in the composition from about 1-10% w/w (¶[0057]), which is about 0.9-9% w/v given a 0.9 g/mL composition density. Given the use of the term “about” having a meaning of ± 10% w/v (¶[0090]), rendering a concentration ranging from 0.81-9.9% w/v penetration enhancers taught by Dandiker, which almost entirely overlaps with the instant claim 14 range of 1-10% w/v penetration enhancers.
Dandiker teaches the composition wherein the film-forming excipient comprises polyacrylates, such as Eudragit® L100 or S100 (methacrylic acid and methyl methacrylate copolymer 1:1 or 1:2, respectivaly), Eudragit® E100 (poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1) and celluloses, such as hypromellose, hydroxypropyl cellulose, and ethyl cellulose (¶[0052]), thus teaching the limitation of instant claim 9.
Dandiker teaches the composition containing one or more penetration enhancers such as azone, isopropyl myristate, octisalate, oleic acid, and/or Transcutol® P (¶[0056]), thus teaching the limitation of instant claim 12. Dandiker also teaches the composition containing a washability enhancer including polyethylene glycol 400. (¶[0054]), thus teaching the limitation of instant claim 16.
Dandiker teaches the composition wherein, “A very thin layer of solution is formed on the skin [film] when this spray is applied. In only a few minutes, preferably less than 3 minutes or less than 2 minutes, the solvent/s in the spray evaporate leaving behind a film containing estradiol, testosterone, or both, if both are present in the formulation.” (¶[0042]), thus teaching the limitation of instant claim 26. Dandiker also teaches the composition wherein the viscosity is less than about 50 cPs at room temperature, preferably about 1-20 cPs (¶[0077]), thus a target of less than 30 cPs is an obvious equivalent range for a sprayable liquid, teaching the limitation of instant claim 28.
Dandiker teaches the composition having a water vapor transmission rate, as a fraction compared to a non-occluded control, not less than 0.50 over a 48-hour period when applied and dried on a porous substrate (i.e., porous surgical tape; ¶[0085]-[0086]), thus teaching the limitation of instant claim 29.
Dandiker teaches the composition packaged as a bulk solution containing multiple doses in a pump action spray system comprising a sealed container fitted with a spray pump, preferably a metering spray pump, wherein the pump action sprays require the application of external pressure for actuation, for example, external manual, mechanical or electrically initiated pressure and may also include a dose indicator or dose counter. The composition may also contain one or more additional ingredients (¶[0044]- [0047]). Dandiker also teaches the composition contained in a spray container comprising a metering valve (claim 91), thus teaching the limitation of instant claims 30 and 31. However, Dandiker does not explicitly teach the composition in a spray container, wherein the container further comprises a propellent.
Dandiker also does not teach the use of the specific steroid-based active ingredients spironolactone or canrenone, nor the use of the composition as a method to of treating acne, male and female pattern hair loss, hirsutism, hidradenitis suppurativa, polycystic ovary syndrome (PCOS), or combinations thereof in a subject.
Zhang teaches a topical film-forming dermal delivery formulation peelable and washable with water (claims 44-46) for the delivery of drugs for treating alopecia [male and female pattern hair loss] (¶[0002]), stored in a pressurized container and applied to the skin [surface of a subject] by spraying (¶[0044]) including a propellant for pressurized spray-on application (claim 50), wherein the drug substance(s) include member(s) selected from the group consisting of minoxidil, spironolactone, finasteride, and combinations thereof (claim 7) in a volatile solvent system comprising water and at least one solvent selected from the group consisting of ethanol, isopropyl alcohol, ethyl acetate, and combinations thereof (claims 14-16) from about 10-85% w/w (¶[0049]) with solidifying agents that are film-forming polymers, many with water solubility including polyvinyl alcohol, polyvinylpyrrolidone, butyl methacrylate and methyl methacrylate copolymer, hypromellose, ethyl cellulose, and other listed polymers (claims 26-28), wherein the amount of solidifying agent is adjusted to achieve desired viscosity and film properties (¶[0059]), thus a range of 1-10% w/v would have been an obvious optimization.
Numerous non-volatile solvents that also function as penetration enhancers (e.g., isopropyl myristate, oleic acid; claims 19 and 20) are also included in the composition taught by Zhang, and taught to be adjustable (¶[0059]), thus a range of 1-10% w/v for a penetration enhancer component would have been an obvious optimization. In addition, polyethylene glycols are included as non-volatile solvents ¶[0052], thus selecting the specific species of polyethylene glycol 400 to modify washability would have been an obvious given it is compatible as it is specifically mentioned in ¶[0051].
The formulations of the invention may further comprise a pH modifying agent for adjusting the pH of the formulation to a point or a range most suitable for the delivery of the drug (¶[0064]), wherein citrate buffers are standard pharmaceutical buffers and adjusting pH to 4-5 is a standard range for topical formulations to match skin pH and minimize irritation. This would have been an obvious optimization. The formulations of Zhang are designed for sustained delivery from a solidified matrix, implying the drug remains solubilized or molecularly dispersed to enable delivery and does not crystallize (¶[0043]).
Zhang does not disclose the use of specific concentration ranges for minoxidil (1-10%) and finasteride (0.1-1.0%), however Zhang teaches the use of “effective amount,” “therapeutically effective amount,” or “therapeutically effective rate(s)” of a drug refers to sufficient amounts or delivery rates of a drug which achieves appreciable level of hair growth, with the understanding that this may be dependent in some instances on biological factors, and achievement of therapeutic effects may be measured by a physician or other qualified medical personnel using evaluations known in the art, recognizing that individual variation and response to treatments may make the achievement of therapeutic effects a subjective decision (¶[0022]). Applying conventional doses in formulation using the film-forming system of Zhang would have been obvious to try.
Evidentiary reference, Bharadwaj et al. (Comparative Efficacy of Topical Finasteride (0.25%) in Combination with Minoxidil (5%) Against 5% Minoxidil or 0.25% Finasteride Alone in Male Androgenetic Alopecia: A Pilot, Randomized Open-Label Study. Int J Trichology. 2023 Mar-Apr;15(2):56-62. Epub 28 Jul 2023), provides evidence that topical minoxidil 5% and finasteride 0.25% is clinically efficacious for hair loss (androgenetic alopecia) without significant side effects (Abstract Conclusion), which is encompassed within the instant claim 23 range. Further 5% minoxidil was seen to be superior to 2% and 10% formulations, when considering efficacy and side effects, and 0.1% finasteride has been extensively evaluated as a combination solution with minoxidil, wherein 0.25% finasteride solution was considered the most efficacious concentration without reports of serious side effects via systematic review (page 2, paragraph 3 and 5). Thus, it would be considered a matter of routine experimental optimization when using a different delivery system to adjust the range ± the optimal concentration taught by the evidentiary reference Bharadwaj et al., to arrive at that of the instant claim 23 range.
Drying time is taught by Zhang to be adjustable including embodiments from 0.5 minutes to about 5 minutes (¶[0062). A barrier film forming in less than 3 minutes is an obvious optimization of the volatile solvent system (e.g., using more volatile solvents like acetone/ethyl acetate). Zhang teaches initial viscosities from 100 to 3,000,000 cP (claim 38), however Zhang also teaches the formulation can have a viscosity suitable for application and adhesion to a skin surface prior to evaporation of the volatile solvent system, and, after being applied to a skin surface as a layer, can form a solidified, coherent, flexible, and continuous layer after at least partial evaporation of the volatile solvent system (¶[0046]). Thus, achieving a viscosity below 30 cP by adjusting solvent ratios for sprayability would have been an obvious variation, especially for spray embodiments. Zhang does not include measures of water vapor transmission rate; however, this is a standard technique for characterizing film occlusivity. Selecting film-forming excipients and solvent ratios to achieve a specific instant claimed water vapor transmission rate would have been a routine experimentation for one of ordinary skill to formulate a film with desired breathability.
As noted, the Zhang explicitly teaches spray application using a propellant in a pressurized container (claim 50), wherein including a metering valve and dose indicator are standard features for such pharmaceutical spray containers. Separating components in a dual-chamber device to improve stability is a known formulation technique.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to substitute the specific steroid-based active ingredients spironolactone or canrenone for the steroid-based actives estradiol/testosterone in the invention of Dandiker. Dandiker provides a comprehensive teaching of a sprayable, film-forming topical composition for steroids, teaching the selection of solvents, polymers, and enhancers to achieve a washable, non-crystallizing film. The primary point of distinction from the instant invention, other than obvious routine formulation and packaging optimizations, being the substitution of spironolactone for estradiol/testosterone. Spironolactone taught by Zhang is a well-known topical steroid used for treating related androgen-associated dermatological conditions (e.g., acne, hirsutism). Given the similar physicochemical properties (e.g., lipophilicity, molecular weight) and androgen pathway therapeutic target of spironolactone compared to testosterone, it would have been obvious to substitute spironolactone as the active ingredient in the disclosed film-forming spray platform. The claimed range of 1-20% w/v is commensurate with the active ranges taught by Dandiker and represents routine optimization for a different drug.
Both Dandiker and Zhang teach packaging the composition in a spray container, although Dandiker does not explicitly teach wherein the container further comprises a propellent, Zhang teaches spray application using a propellant in a pressurized container, making obvious and motivating the substitution to the invention of Dandiker. Although not explicitly taught by Dandiker or Zhang, separating formulation components in a dual-chamber packaging container to improve stability is a known formulation technique.
In addition to the use of spironolactone, Zhang teaches combination active ingredient formulations including minoxidil and finasteride at effective amounts, however does not explicitly require specific concentration ranges of 1-10% minoxidil and 0.1-1.0% finasteride. The instant claimed concentration ranges would have been obvious to try, as effective amounts taught by Zhang, based on applying conventional doses in topical formulations (as evidence by Bharadwaj et al.).
A person of ordinary skill in the art would have been motivated to apply the successful platform of Dandiker to another problematic steroid with solubility challenges, such as spironolactone, with a reasonable expectation of achieving the same beneficial film formation, washability, anti-crystallization properties. A person of ordinary skill in the art would have also recognized the advantages of convenience, dose uniformity, cosmetic desirability in converting a topical spironolactone formulation, as described by Zhang, to a sprayable film using the teachings of Dandiker for a similar steroid and possessed the routine skill to make reformulation adjustments (e.g., standard predictable substitutions, adjusting the water content, volatile solvent and a film-forming polymer) to optimize the formulation. The instant claimed modifications involve routine optimization, predictable selection from known ingredients, and the application of standard formulation and device design techniques that are well within the ordinary skill of a formulator in this art. Therefore, the claimed subject matter would have been obvious.
Claims 1, 8 and 18 are rejected under 35 U.S.C. § 103 as being unpatentable over Dandiker (US20210236514A1; published 05 August 2021) in view of Zhang et al. (US20070189980A1; published 16 August 2007, hereinafter referred to as “Zhang”), in further view of Kim et al. (EP0410348A1; published 30 January 1991, hereinafter referred to as “Kim”).
Dandiker in view of Zhang teaches the limitations of instant claim 1, as described above, from which the instant claims 8 and 18 depend, however does not explicitly teach the specific limitations of instant claims 8 and 18. Dandiker nor Zhang explicitly teach wherein the aliphatic solvent is about 15-60% w/v ethyl acetate, about 10-65% w/v di-isopropyl adipate and about 5-60% w/v ethanol or wherein the pH buffer specifically comprises sodium citrate, citric acid buffer, or combinations thereof.
Dandiker teaches the composition of the present invention may also include other formulation excipients, added, e.g., to achieve a desired consistency or appearance, or to protect the formulation components from degradation and oxidation. Such excipients include, for example, viscosity increasing agents, pH adjusting agents, stabilizing agents, antioxidants, humectants, preservatives, colorant and fragrance agents known in the art of formulation (¶[0062]), however does not teach the specific use of sodium citrate buffer, citric acid buffer, or combinations thereof in the composition.
Dandiker teaches acetone, ethanol, and isopropyl alcohol as solvents (¶[0059]). Zhang teaches the teach the use of at least one non-volatile solvent in combination with one or more volatile solvents (claim 1), with use of volatile solvents ethanol and ethyl acetate combinations (claims 14-16) from concentrations of about 10-85% w/w (¶[0049]), or about 9.0-76.5% w/v at a density of 0.90 g/mL, which encompasses the instant claim 8 range of about 15-60% w/v ethyl acetate and about 5-60% w/v ethanol. Zhang further teaches a second volatile solvent (e.g., ethanol) can be formulated into the solidified layer to reduce the water content but maintain a sufficient amount of water to keep the film-forming polymer in solution to optimize drying time, reducing it for the solidifying formulation (¶[0050]).
Zhang also teaches the use of non-volatile solvents oleic acid (claim 19), isopropyl myristate (claim 20), and dibutyl sebecate (claim 20; a sebacic acid diester rather than a adipic acid diester) as adjustable concentration components relative to the solidifying agent from about 0.1:1 to about 10:1 to optimize film flexibility, rigidity, tensile strength, elasticity, and adhesiveness (¶[0059]). However, Zhang does not explicitly teach the use of di-isopropyl adipate as a non-volatile solvent at about 10-65% w/v, but does teach that certain volatile and/or nonvolatile solvent(s) that are irritating to the skin and it is desirable to add compounds that are both capable of preventing or reducing skin irritation and are compatible with the formulation (¶[0055]), providing the motivation to optimize the combination of solvents used and adjust the percentages thereof to achieve the desired solubility and/or permeability of the drug while reducing or preventing skin irritation. Ethanol and isopropyl alcohol are known to be dehydrating to the skin, which can lead to dryness, irritation, and contact dermatitis, particularly with repeated use or in individuals with sensitive or already compromised skin. Ethyl acetate and di-isopropyl adipate are generally considered to be gentler on the skin, reducing the risk of such adverse effects, thus their use represents an obvious optimization of the solvent system. Diisopropyl adipate is generally considered in the art to be minimally irritating and maybe a preferred substitution for oleic acid or isopropyl myristate to avoid the potential irritation or comedogenicity issues sometimes associated with high concentrations of oleic acid or isopropyl myristate in certain individuals, in addition to providing a lighter, less greasy, and improved spray flow and spreading formulation for a sprayable product.
Kim teaches that diisopropyl adipate is used as a suitable solvent for topical spironolactone compositions (¶[0008], Claim 1) comprising "from about 1.0 to about 12.0 weight percent of spironolactone" (Claim 3). This range overlaps with that of instant claim 1. Optimizing the concentration up to 20% w/v for different indications (e.g., alopecia) is routine. Further, Kim details that The use of a solvent such as diisopropyl adipate which is a good solvent for spironolactone but does not readily degrade it and the maintenance of the pH at from about 4 to about 6 using an appropriate buffering system as well as the use of emulsifiers which will work in an acid pH all contribute to the stability of the spironolactone composition (¶[0016]).
Kim explicitly teaches using a citrate buffers (i.e., sodium citrate and citric acid; claim 2b) and teaches maintaining a pH from about 4.0-6.0 via buffering agents (¶[0009]; claim 3), the specific use of the weak acid salts, sodium citrate dihydrate and citric acid monohydrate, are further disclosed in claim 10. Selecting pH 4-5 is an obvious and preferred sub-range within this taught range for skin compatibility and spironolactone stability.
Kim explicitly teaches the use of its topical spironolactone composition for treating acne, hirsutism, and other disorders caused by excess androgenic activity such as alopecia (Claims 20-24). Applying the obvious, improved sprayable composition of claim 1 to treat these same conditions is an obvious method.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to replace the one or more solvents such as acetone, ethanol, and/or isopropyl alcohol taught by Dandiker (¶[0058]) or incorporate additional or alternative enhancers like diisopropyl adipate, taught by Kim, for the oleic acid or isopropyl myristate taught by Zhang with the specific combination and ratio of solvents of instant claim 8 as a matter of routine experimentation to optimize delivery. One of ordinary skill would have been motivated to adjust the relative amounts of ethyl acetate and ethanol as volatile solvents and substitute the non-volatile solvent di-isopropyl adipate taught by Kim to be a suitable solvent for topical spironolactone compositions to achieve desired drying time, viscosity, and film properties. It also would have been obvious to one of skill in the art to specifically use citrate buffers as pH modifying agent for adjusting the pH of the formulation in Dandiker and Zhang where it is not explicitly specified, as Kim teaches the use of citrate buffers in formulating topical spironolactone compositions to be appropriate for use in adjusting the pH of formulations for skin compatibility and maintaining spironolactone stability. These variations would have been obvious optimizations.
Claim 56 is rejected under 35 U.S.C. § 103 as being unpatentable over Dandiker (US20210236514A1; published 05 August 2021) in view of Zhang et al. (US20070189980A1; published 16 August 2007, hereinafter referred to as “Zhang”), in further view of Kim et al. (EP0410348A1; published 30 January 1991, hereinafter referred to as “Kim”) and Ruiz de Gopegui and Wang (US7789278B2; published 07 September 2010, hereinafter referred to as “Ruiz de Gopegui”).
Dandiker, Zhang and Kim render a spray composition comprising subranges of 1-10% w/w spironolactone, about 15- 20% w/w ethyl acetate, about 10% di-isopropyl adipate, about 50-60% w/w ethanol, about 4-7% octisalate, about 5-7% w/v butyl methacrylate and methyl copolymer (3:1) and about 1.5% w/w polyethylene glycol 400 obvious, based on the facts presented above for the proceeding instant claims.
Dandiker, Zhang and Kim do not teach a dual chamber device suitable for providing a spray composition comprising, separating the spironolactone, ethyl acetate and di-isopropyl adipate in a first chamber and ethanol, octisalate, butyl methacrylate and methyl copolymer (3:1) and polyethylene glycol 400 in a second chamber.
Ruiz de Gopegui teaches an aerosol spray delivery device with an outer housing for an active composition and an inner housing containing a propellant mixed with other materials that are not compatible with the active composition. When activated, the propellant draws the active composition through a tube, effectively mixes the components of both housings at the nozzle via the venturi effect, and dispenses it as a spray. The device includes an actuator, which inherently includes a means for dispensing a metered amount (i.e., a metering valve function is inherent in the valve mechanism described) (Abstract). Adding a dose indicator is a well-known, conventional feature in pharmaceutical and consumer spray containers to track usage. Therefore, it would have been obvious to modify the composition packaging container of Ruiz de Gopegui to include this conventional feature. The specific compositions in each chamber are obvious combinations of ingredients taught by Dandiker, Zhang and Kim, given ethyl acetate is hydrolytically unstable in alcoholic solutions (i.e., ethanol), particular with the polymer acid and base sites and octisalate present, which could destabilize spironolactone and modify solubility leading to crystallization, degrade esters and precipitate the polymer. Separating the hydrophobic phase (i.e., spironolactone, ethyl acetate, and di-isopropyl adipate) from the hydrophilic polymer phase (i.e., ethanol, octisalate, butyl methacrylate and methyl copolymer (3:1), and polyethylene glycol 400) would be an obvious composition component separation choice to optimize formulation stability.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to one of ordinary skill in the art, seeking to deliver the topical film-forming composition of Dandiker and Zhang in a convenient, metered spray application suggested by the references, to combine the composition with the use of an aerosol spray dispenser packaging container known in the art to have a successful spray mechanism by the teachings of Ruiz de Gopegui with the expectation of achieving a predictable result of improved composition stability and convenient application. One would be motivated to integrate the teachings, as the packaging device taught by Ruiz de Gopegui is directed to solving the problem of spraying compositions where components, like an active and a propellant or other incompatible ingredients, are kept separate until dispensing, a scenario that is directly applicable to a two-part film-forming spray, wherein ethyl acetate is hydrolytically unstable in ethanol. A formulator would be motivated to avoid storing ethyl acetate and ethanol in the same packaging chamber to avoid changes in the solvent composition, a pH shift of the formulation which could result in skin irritation, and potential precipitation from components in the composition that could result in a concentration of spironolactone beyond solubility leading to crystallization.
Claim Rejections – Nonstatutory 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).
Claims 1, 5, 8, 9,11, 12, 14, 16, 18, 20, 23, 24, 26, 28-30, 41, and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-8, 10-16 of US Patent No. 11,523,994 B2 (US Application No. 16/960,428; granted 13 December 2022, hereinafter referred to as reference “’428”) and US Patent No. 12,208,169 B2 (US Application No. 18/054,816; granted 28 January 2025, hereinafter referred to as reference “’816”). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant claims are directed to an obvious variant of the same inventive concept disclosed in the commonly owned patents ’428 and ‘816, and merely substitutes one known steroidal active pharmaceutical ingredient with another while maintaining the same inventive vehicle platform and critical functional properties.
References ’428 and ‘816 claims disclose a sprayable liquid film-forming composition for topical application of a steroidal drug (i.e., testosterone; claims 1, 5, 11, and 13) comprising a solvent system of one or more solvents (claim 1), specifically acetone, ethanol, or isopropyl alcohol (claims 5, 14 and 15); one or more water soluble film-forming excipients to prevent crystallization of the active ingredient during solvent evaporation (claim 1), selected from the group consisting of for example, methacrylic acid and methyl methacrylate copolymers (1:1 and 1:2) and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1 (claim 5, 7, and 12); one or more penetration enhancers (claims 1, 11 and 12), selected from the group consisting of azone, glycerol monooleate, isopropyl myristate, octisalate, oleic acid, and diethylene glycol monoethyl ether [including Transcutol® P] (claims 5 and 7); and one or more washability enhancers (claims 1, 5 and 11), comprising polyethylene glycol (claims 2, 6, and 16), including polyethylene glycol 400 (claim 8); wherein the composition is contained in a container comprising a spray pump with metering valve (claims 4 and 10). Claiming a more specific combination of aliphatic solvent of about 15-60% w/v ethyl acetate, 10-65% w/v di-isopropyl adipate, and 5-60% w/v ethanol as in instant claim 8, is a matter of routine formulation experimentation to optimize the formulation.
A person of ordinary skill in the art would have found it obvious to modify the testosterone film-forming spray to treat related dermatological conditions disclosed by ’428 and ‘816 by substituting testosterone with another steroidal active pharmaceutical ingredient known for topical use, such as spironolactone or canrenone, while using the same vehicle platform designed to solve identical formulation challenges. The shared inventive concept is a topical, sprayable, film-forming liquid vehicle for a steroidal active pharmaceutical ingredient, utilizing specific polymers to maintain the active pharmaceutical ingredient in an amorphous state upon application to prevent crystallization and enhance delivery. Both sets of claims solve the identical problems: delivering a high concentration of a crystallizable steroidal drug, forming a functional film on the skin, and ensuring the drug remains in a therapeutically effective amorphous state during evaporation. The reference explicitly identifies crystallization prevention as a critical feature of its invention (claim 1), and the pending claims claim the same feature for spironolactone.
The substitution of the testosterone (an androgen) in ’428 or ‘816 for the instant claimed active pharmaceutical ingredient spironolactone/canrenone (anti-androgens), which are structurally related steroidal compounds used in topical dermatology to modulate androgen pathways is an obvious variation. One of ordinary skill, seeking to formulate a spray for spironolactone, a drug with known crystallization tendencies, would have been directly motivated to employ the successful vehicle platform disclosed by ’428 or ‘816 that is specifically designed to prevent crystallization of steroidal drugs. The overlap is not just in general categories but in specific, film-forming excipients (e.g., methacrylic acid and methyl methacrylate copolymer 1:1, 1:2, and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1 Eudragit® polymers), penetration enhancers (e.g., azone, isopropyl myristate, octisalate, oleic acid, and Transcutol® P), washability enhancer (i.e., polyethylene glycol 400), and solvents (e.g., ethanol and isopropyl alcohol) that perform the same functions. This demonstrates the claims are directed to the same invention with a trivial change in the active ingredient.
Instant claim 41 is an obvious method claim variant of the method of administering the composition to provide testosterone replacement therapy in males for conditions such as hypogonadism (specification ‘428, page 5, column 10, lines 28-33 and specification ‘816, page 5, column 10, lines 19-24) composition taught by ’428 and ‘816. It would have been obvious to use an obvious variant of that composition containing the anti-androgen spironolactone to treat dermatological conditions mediated by androgens, such as acne, hirsutism, or pattern hair loss, which are well-established therapeutic uses for topical spironolactone. The spray container claimed in instant claims 30, 31, 33 and 56 are obvious variants of the ’428 and ‘816 composition spray container (claims 4 and 10) or a method of use. Claiming a container with the use of a propellant or dual-chamber device containing the obvious composition variant does not render the claims patentably distinct. Adding additional synergistic active ingredients such as minoxidil, finasteride, dutasteride, niacinamide or combinations thereof to the composition within known effective topical concentration dose ranges would be a matter of routine formulation optimization for a particular indication.
The use of pH adjusting agents, wherein the specific use of sodium citrate, citric acid buffer, or combinations thereof would be an obvious choice, in taught (specification ‘428 page 3, column 5, lines 26-29 and specification ‘816, page 3, column 5, lines 20-23) and wherein the pH of the composition is about 4 to about 5 (claim 1). Solvent evaporation forming a barrier film in preferably less than three minutes after application to the skin surface is taught (specification ‘428, page 2, column 4, lines 59-63 and specification ‘816, page 2, column 4, lines 53-57). The composition having a viscosity of less than 30 cPs at room temperature is also taught (specification ‘428, page 5, column 9, lines 53-57 and specification ‘816, page 5, column 9, lines 45-51). The composition has a water vapor transmission rate, as a fraction compared to a non-occluded control, not less than 0.50 over a 48-hour period when applied and dried on a porous substrate (specification ‘428, page 11, column 21, lines 43-49 and drawing figure 4 and specification ‘816, page 10, column 20, lines 34-37 and drawing figure 4).
The presence of 1-10% water in the claims, versus the ‘428 and ‘816 for 30 parts or less of water to dissolve one part of the film forming excipient (claim 1), is a routine formulation adjustment. The reference platforms are not limited to anhydrous systems, it teaches controlling water content for quick drying. A skilled formulator would adjust water content as needed for solubility or stability of spironolactone without inventive effort. The specific concentration ranges of spironolactone (1-20% w/v) versus testosterone (10-25% w/w) in ‘428 and ‘816 are overlapping and may reflect different potencies and standard dosing of these two active pharmaceutical ingredients, which would be determined through routine pharmacological and clinical experimentation.
Thus, the instant claims are directed to the same inventive concept as the reference ‘428 and ‘816 claims, a sprayable, film-forming vehicle for a steroidal active pharmaceutical ingredient that prevents crystallization. The only material difference is the specific steroidal compound (spironolactone/canrenone vs. testosterone). Given the structural and therapeutic relationship between these steroids, the matching excipients, and the identical critical function of the formulation, this variation is obvious and does not produce a patentably distinct invention.
Claims 1, 5, 8, 9,11, 12, 14, 16, 18, 20, 23, 24, 26, 28-30, 41, and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, and 5 of US Patent No. 12,186,326 B2 (US Application No. 17/255,022; granted 07 January 2025, hereinafter referred to as reference “’022”). Although the claims at issue are not identical, they are not patentably distinct from each other because for the reasons outlined below.
The instant claims are directed to an obvious variant of the same inventive concept disclosed in the commonly owned patent ’022, and merely substitutes one known steroidal active pharmaceutical ingredient with another while maintaining the same inventive vehicle platform and critical functional properties.
The ’022 reference discloses a sprayable liquid film-forming composition for topical application of steroidal drugs (i.e., testosterone and estradiol; claims 1 and 5) comprising a solvent system of one or more solvents, specifically acetone, ethanol, or isopropyl alcohol (claim 1); one or more water soluble film-forming excipients to prevent crystallization of the active ingredient during solvent evaporation, selected from the group consisting of for example, methacrylic acid and methyl methacrylate copolymers (1:1 and 1:2) and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1 (claims 1 and 4); one or more penetration enhancers (claims 1, 11 and 12), selected from the group consisting of 1-dodecylazacycloheptan-2-one [azone], glycerol monooleate, isopropyl myristate, octisalate, oleic acid, and diethylene glycol monoethyl ether [including Transcutol® P] (claim 1); and one or more washability enhancers/plasticizers (claim 1, wherein polyethylene glycol 400 would be an obvious selection from those listed in the specification; see specification page 4, column 7, lines 28-31), wherein the wherein said composition when dried on a porous substrate, has a water vapor transmission rate, as a fraction compared to a non-occluded control, not less than 0.50 over a 48 hour period.
The specification details that the composition absorbed preferably in less than 3 minutes and is contained in a container comprising a spray pump with a metering valve and dose indicator (specification page 3, column 5, lines 38-56), wherein the spray container claimed in instant claims 33 and 56 are obvious variants of the ’022 composition spray container or a method of use. Claiming a container with the use of a propellant or dual-chamber device containing the obvious composition variant does not render the claims patentably distinct. A pH range of 4-5 is taught (specification page 3, column 6, lines 20-22) and the addition of a pH adjusting agents (specification page 4, column 7, lines 39-44), in which the choice of a citrate buffer would be obvious. The viscosity is taught to be <30 cPs at room temperature (specification page 5, column 9, lines 50-56). Claiming a more specific combination of aliphatic solvent of about 15-60% w/v ethyl acetate, 10-65% w/v di-isopropyl adipate, and 5-60% w/v ethanol as in instant claim 8, is a matter of routine formulation experimentation to optimize the formulation. Adding additional synergistic active ingredients such as minoxidil, finasteride, dutasteride, niacinamide or combinations thereof to the composition within known effective topical concentration dose ranges would be a matter of routine formulation optimization for a particular indication.
Instant claim 41 is an obvious method claim variant of the method of administering the composition to provide testosterone replacement therapy in males for conditions such as hypogonadism (specification page 5, column 10, lines 28-33) composition taught by ’022. It would have been obvious to use an obvious variant of that composition containing the anti-androgen spironolactone to treat dermatological conditions mediated by androgens, such as acne, hirsutism, or pattern hair loss, which are well-established therapeutic uses for topical spironolactone.
The presence of 1-10% water in the instant claims, versus the ‘022 preference for 30 parts or less of water to dissolve one part of said film forming excipient, is a routine formulation adjustment. The ‘022 reference teaches controlling water content for quick drying. A skilled formulator would adjust water content as needed for solubility or stability of spironolactone without inventive effort. The specific concentration range of spironolactone (1-20% w/v) is encompassed within the testosterone concentration range (0.1-25% w/w) taught by ‘022, and standard dosing of these two active pharmaceutical ingredients would be determined through routine pharmacological and clinical experimentation.
Thus, the pending instant claims are directed to the same inventive concept as the reference claims, a sprayable, film-forming vehicle for a steroidal active pharmaceutical ingredient that prevents crystallization. The only material difference is the specific steroidal compound (spironolactone/canrenone vs. testosterone/estradiol). Given the structural and therapeutic relationship between these steroids, the matching excipients, and the identical critical function of the formulation, this variation is obvious and does not produce a patentably distinct invention.
It would have been obvious to a person of ordinary skill in the art to substitute one well-known topical steroid, spironolactone, for another, testosterone/estradiol, in ‘022’s proven, enabling formulation platform. Both classes of drugs suffer from similar formulation challenges (i.e., poor solubility, crystallization), and both are used to treat related endocrine-mediated dermatological conditions (e.g., androgen excess). No unexpected results or critical new properties arise from this substitution. Applying the same platform with an obvious alternative steroid spironolactone to treat conditions known to be responsive to that steroid (e.g., acne, hirsutism, female pattern hair loss) is an obvious method. The use of a propellent in the spray container and the specific compositions in the chambers are obvious variations of the ingredients taught in the ‘022. Using a dual-chamber device for stability is a known technique. This claim is an obvious combination of the formulation with a known device.
Claims 1, 5, 8, 9,11, 12, 14, 16, 18, 20, 23, 24, 26, 28-30, 41, and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 11, 15-18, 20, 25, 29-31, 33, 38, 42, 49-51, and 53 of co-pending US Application No. 17/761,507 (published 03 November 2022, hereinafter referred to as reference “’507”). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons outlined below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are directed to an obvious variant of the same inventive concept disclosed in the commonly owned patent application ’507, and merely substitutes one known active pharmaceutical ingredient with another while maintaining the same inventive vehicle platform and critical functional properties.
The reference ‘507 claims disclose a sprayable liquid film-forming composition for topical application of an active pharmaceutical drug lidocaine (at least 40% w/w or about 2-50% w/w; claims 1, 15, 29, 42, and 49), which is prone to crystallization from an amorphous or supersaturated state during solvent evaporation when applied to the skin, which can negatively affect drug delivery and efficacy. The composition further comprises an aliphatic solvent (claims 1, 42 and 49), specifically acetone, ethanol, or isopropyl alcohol or a mixture thereof (claims 15 and 29); one or more water soluble film-forming excipients/ viscosity increasing agent to prevent crystallization of the active ingredient during solvent evaporation (claims 1, 29, 42, and 49), selected from the group consisting of for example, methacrylic acid and methyl methacrylate copolymers (1:1 and 1:2) and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1 (claims 15 and 29); one or more penetration enhancers (claims 2, 42 and 49), selected from the group consisting of azone, glycerol monooleate, isopropyl myristate, octisalate, oleic acid, and diethylene glycol monoethyl ether [including Transcutol® P] (claims 16, 30 and 50); one or more washability enhancers/plasticizers (claims 1, 42 and 49), selected from polyethylene glycol 400 (claims 3, 15, 17, 29 and 51); and less than 10% w/w water (claims 1, 15, 29, 42, and 49). The water vapor transmission rate composition when dried on a porous substrate, as a fraction compared to a non-occluded control is not disclosed by ‘507, however ‘507 teaches adjusting water concentration in the formulation therefore arriving at a not less than 0.50 over a 48-hour period water vapor transmission rate is a matter of routine formulation optimization.
The specification details that the composition absorbed preferably in less than 3 minutes and is contained in a container comprising a spray pump with a metering valve and dose indicator (¶[0021]), wherein the spray container claimed in instant claims 33 and 56 are obvious variants of the ’507 composition spray container with a pump (claims 6, 20, 33, and 53). Claiming a container with the use of a propellant or dual-chamber device containing the obvious composition variant does not render the claims patentably distinct.
A pH range of 4-5 is taught (claim 1) and the addition of a pH adjusting agents (¶[0085]), in which the choice of a citrate buffer would be obvious. The viscosity is taught to be <30 cPs at room temperature (¶[0093]). Claiming a more specific combination of aliphatic solvent of about 15-60% w/v ethyl acetate, 10-65% w/v di-isopropyl adipate, and 5-60% w/v ethanol as in instant claim 8, is a matter of routine formulation experimentation to optimize the formulation. Adding additional synergistic active ingredients such as minoxidil, finasteride, dutasteride, niacinamide or combinations thereof to the composition within known effective topical concentration dose ranges would be a matter of routine formulation optimization for a particular indication.
Instant claim 41 is an obvious method claim variant of the method of administering the composition the specific pharmaceutical active ingredient for a known indication. Lidocaine is known to be used as a topical analgesic. It would have been obvious to use an obvious variant of that composition to change the active ingredient and to administer a composition containing that active ingredient for its known indication, such as the anti-androgen spironolactone to treat dermatological conditions mediated by androgens, such as acne, hirsutism, or pattern hair loss, which are well-established therapeutic uses for topical spironolactone. The specific concentration range of spironolactone (1-20% w/v) would vary from the concentration range of the active ingredient lidocaine taught by ‘507, as standard dosing of these two active pharmaceutical ingredients would vary and be determined through routine pharmacological and clinical experimentation.
Thus, the pending instant claims are directed to the same inventive concept as the reference claims, a sprayable, film-forming vehicle for an active pharmaceutical ingredient that prevents crystallization. The only material difference is the specific compound (spironolactone/canrenone vs. lidocaine). Given that both dermatological active ingredients prone to crystallization when applied to the topically, the matching excipients, and the identical critical function of the formulation, this variation is obvious and does not produce a patentably distinct invention.
It would have been obvious to a person of ordinary skill in the art to substitute one well-known topical steroid, spironolactone, prone to crystallization for another topical active ingredient prone to crystallization, lidocaine, in ‘507’s proven, enabling formulation platform. Both classes of topical dermatological drugs suffer from similar formulation challenges (i.e., poor solubility, crystallization). No unexpected results or critical new properties arise from this substitution. Applying the same platform with an obvious alternative active ingredient spironolactone to treat conditions known to be responsive to that steroid (e.g., acne, hirsutism, female pattern hair loss) is an obvious method. The use of a propellent in the spray container and the specific compositions in the chambers are obvious variations of the ingredients taught in the ‘507. Using a dual-chamber device for stability is a known technique. This claim is an obvious combination of the formulation with a known device. One of ordinary skill, seeking to formulate a spray for spironolactone, would have been motivated to employ the successfully disclosed vehicle from ‘507 that is specifically designed to prevent crystallization of a drug during solvent evaporation, as spironolactone crystallization is a known formulation challenge. The results-effective variables, the active pharmaceutical ingredient choice and specific concentration ranges, would have been optimized through routine experimentation.
Claims 1, 5, 8, 9,11, 12, 14, 16, 18, 20, 23, 24, 26, 28-30, 41, and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 36, 44, 52, 53 and 69 of co-pending US Application No. 18/502,863 (published 06 November 2023, hereinafter referred to as reference “’863”). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons outlined below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The ’863 reference discloses a sprayable liquid film-forming composition for topical application of the antimuscarinic drug oxybutynin (about 1-20%, 8%, 0.5-15% w/v; claims 1, 2, 36, 44 and 69), wherein topical products are prone to oxybutynin crystallization (¶[0032]), which is not as readily absorbed. The composition comprises an aliphatic solvent (claims 1 and 2), specifically acetone, ethanol, or isopropyl alcohol (claim 4); one or more water soluble film-forming excipients (claims 1, 2, 5-8) to prevent crystallization of the active ingredient during solvent evaporation, selected from the group consisting of for example, methacrylic acid and methyl methacrylate copolymers (1:1 and 1:2) and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1 (claims 6, 8 and 44); one or more penetration enhancers (claims 1 and 2), selected from the group consisting of 1-dodecylazacycloheptan-2-one [azone], glycerol monooleate, isopropyl myristate, octisalate, oleic acid, and diethylene glycol monoethyl ether (Transcutol® P) (claims 3, 8 and 44); and one or more washability enhancers (claim 9), as polyethylene glycol 400 (claim 10); wherein the said composition when dried on a porous substrate, has a water vapor transmission rate, as a fraction compared to a non-occluded control, not less than 0.50 over a 48 hour period (¶[0013]). The presence of 1-10% water in the instant claims is a routine formulation adjustment from ’863 wherein the at least 65% w/v aliphatic solvent may or may not include water, as the film-forming excipient is also preferably soluble in water (¶[0055]). The reference does not preclude the presence of water. A skilled formulator would adjust water content as needed for solubility or stability of spironolactone without inventive effort.
The specification details that the composition absorbed in less than 5 minutes (encompassing the instant claimed range of less than 3 minutes; ¶[0032]) and is contained in a container comprising a spray pump with a metering valve and dose indicator (claims 52 and 53), wherein the spray container claimed in instant claims 33 and 56 are obvious variants of the ’863 composition spray container or a method of use. Claiming a container with the use of a propellant or dual-chamber device containing the obvious composition variant does not render the claims patentably distinct.
A pH range of 4-5 is taught (claims 1 and 2) and the addition of a pH adjusting agents (¶[0065]), in which the choice of a citrate buffer would be obvious. The viscosity is taught to be <30 cPs at room temperature (¶[0076]). Claiming a more specific combination of aliphatic solvent of about 15-60% w/v ethyl acetate, 10-65% w/v di-isopropyl adipate, and 5-60% w/v ethanol as in instant claim 8, is a matter of routine formulation experimentation to optimize the formulation. Adding additional synergistic active ingredients such as minoxidil, finasteride, dutasteride, niacinamide or combinations thereof to the composition within known effective topical concentration dose ranges would be a matter of routine formulation optimization for a particular indication.
Instant claim 41 is an obvious method claim variant of the method of administering the composition the specific pharmaceutical active ingredient for a known indication. Oxybutynin is known to be used as a topical pharmaceutical active ingredient for treating hot flashes, hyperhidrosis, osmiodrosis, incontinence, and bladder spasms. It would have been obvious to use an obvious variant of that composition to change the active ingredient and to administer a composition containing that active ingredient for its known indication, such as the anti-androgen spironolactone to treat dermatological conditions mediated by androgens, such as acne, hirsutism, or pattern hair loss, which are well-established therapeutic uses for topical spironolactone. The specific concentration range of spironolactone (1-20% w/v) is the same as that taught for the antimuscarinic drug oxybutynin (about 1-20%; claims 1) in ’863, as standard dosing of these two active pharmaceutical ingredients would be determined through routine pharmacological and clinical experimentation.
Thus, the pending instant claims are directed to the same inventive concept as the reference claims, a sprayable, film-forming vehicle for a steroidal active pharmaceutical ingredient that prevents crystallization. The only material difference is the specific steroidal compound (spironolactone/canrenone vs. oxybutynin). Given both topical active pharmaceutical ingredients are prone to crystallization, the matching excipients, and the identical critical function of the formulation, this variation is obvious and does not produce a patentably distinct invention.
It would have been obvious to a person of ordinary skill in the art to substitute one well-known topical active pharmaceutical ingredient prone to crystallization, spironolactone, for another, oxybutynin, in ’863’s proven, enabling formulation platform. Both classes of drugs suffer from similar topical formulation challenges (i.e., poor solubility, crystallization). No unexpected results or critical new properties arise from this substitution. Applying the same platform with an obvious alternative active pharmaceutical ingredient, spironolactone, to treat conditions known to be responsive to that active pharmaceutical ingredient (e.g., acne, hirsutism, female pattern hair loss) is an obvious method. The use of a propellent in the spray container and the specific compositions in the chambers are obvious variations of the ingredients taught in the ’863. Using a dual-chamber device for stability is a known technique. This claim is an obvious combination of the formulation with a known device. One of ordinary skill, seeking to formulate a topical spray for a new dermatological indication with an active ingredient prone to recrystallization, would have been motivated to employ the successfully disclosed vehicle from the reference.
New Rejections
The following new rejections are made from the previous Office Correspondence dated 16 December 2025, as the Applicant's amendment necessitated the new grounds of rejection presented below based on the amended/newly cited limitations.
Claim Objections
Claims 8 and 12 are objected to because of the following informalities:
Claim 8 recites "comprises a. about 15% w/v..." and "b. about 10% w/v...", which is missing a colon and should be corrected to "comprises: a".
Claim 12 is objected to because it recites "The composition of clam 1" which is a typographical error. The correct antecedent should read "claim 1." Correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. § 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which Applicant regards as his invention.
Claims 56, 59 and 60 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, regards as the invention.
Claim 56 is indefinite because the film-forming excipient appears only in the second chamber in claim 56(b) as, "about 5% w/w to about 7% w/w film forming excipient". Because the percentage is expressed relative to the total weight of both compositions, and the weight ratio of the first composition to the second composition is not specified (i.e., the film-forming excipient appears only in the second chamber and its percentage relative to the total combined weight of both chambers is ambiguous because the total weight of the two chambers is not fixed), one of ordinary skill cannot determine the absolute amount of film-forming excipient in the second chamber or the concentration of film-forming excipient within the second chamber itself (e.g., whether 5-7% w/w refers to the weight of the second chamber alone, the combined weight of both chambers, or some other basis).
The claim purports to define a device with two chambers, but the percentage basis renders the scope ambiguous because the total weight of the two chambers is not fixed and the relative amounts of the two compositions are not disclosed (see Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 910 (2014)). Accordingly, claim 56 is rejected under 35 U.S.C. § 112(b) and dependent claims 59 and 60 are likewise indefinite, as they do not cure the defect in claim 56 noted above. To overcome this rejection, the applicant is advised to either specify the ratio of the first composition to the second composition in the dual chamber device, or amend claim 56 to recite percentages for the second composition components relative to the weight of the second composition alone.
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-AlA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AlA) 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 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.
Claim 56, 59 and 60 are rejected under 35 U.S.C. § 103 as being unpatentable over Dandiker (US20210236514A1; published 05 August 2021) in view of Zhang et al. (US20070189980A1; published 16 August 2007, hereinafter referred to as “Zhang”), in further view of Kim et al. (EP0410348A1; published 30 January 1991, hereinafter referred to as “Kim”) and Ruiz de Gopegui and Wang (US7789278B2; published 07 September 2010, hereinafter referred to as “Ruiz de Gopegui”).
Dandiker in view of Zhang, Kim, and Ruiz de Gopegui teach the limitations of instant claim 56, as described above, from which the instant claims 59 and 60 depend.
The specific composition in the second chamber (ethanol 50-60% w/w, octisalate 4-7% w/w, PEG 400 1.5% w/w, film-forming excipient 5-7% w/w) is an obvious combination of ingredients taught by Dandiker (high ethanol, octisalate, PEG 400, Eudragit® film-forming polymers), Zhang (topical spironolactone, ethanol, octisalate, PEG 400, film-forming polymers), and Kim (di-isopropyl adipate solvent optimization for spironolactone). Separating ethyl acetate (first chamber) from ethanol (second chamber) in a dual-chamber device is an obvious solution to the known hydrolytic instability of ethyl acetate in ethanol. Ruiz de Gopegui provides the device. No unexpected results are alleged.
Claims 59 and 60 are new dependent claims reciting specific film-forming excipients methacrylic acid and methyl methacrylate copolymer 1:2 (claim 59), and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1 (claim 60). Dandiker explicitly teaches both polymers as suitable film-forming excipients (¶[0052], naming Eudragit® L100 (methacrylic acid and methyl methacrylate copolymer 1:1), Eudragit® S100 (methacrylic acid and methyl methacrylate copolymer 1:2), and Eudragit® E100 (poly(butylmethacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate 1:2:1 terpolymer)). Thus, Dandiker alone teaches both instant claimed film-forming excipients in the context of a sprayable, high-ethanol, film-forming composition. Zhang also teaches these polymers (claims 26 and 28). Selecting these specific, well-known polymers from the disclosed classes is obvious as a matter of routine optimization.
Claim Rejections – Nonstatutory 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).
Claims 56, 59 and 60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-8, 10-16 of US Patent No. 11,523,994 B2 (US Application No. 16/960,428; granted 13 December 2022, hereinafter referred to as reference “’428”) and US Patent No. 12,208,169 B2 (US Application No. 18/054,816; granted 28 January 2025, hereinafter referred to as reference “’816”). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The rejection of claim 56 is described above, in which claims 59 and 60 depend from. These newly added claims are directed to obvious variants of the same inventive concept disclosed in the commonly owned references ’428 and ‘816, and merely substitutes one known steroidal active pharmaceutical ingredient with another while maintaining the same inventive vehicle platform and critical functional properties.
The commonly owned references ’428 and ‘816 explicitly teach the exact film-forming excipients recited in claims 59 and 60 (see claim 5 of ’428 and ‘816), wherein the film-forming excipient is used in a sprayable liquid composition that prevents crystallization of the active ingredient. While ’428 and ‘816 do not explicitly recite a "dual chamber device," they teach a spray container comprising the composition and a metering valve (claims 4 and 10). One of ordinary skill in the art would recognize that packaging the composition in a dual chamber device is an obvious variant of a single-chamber spray container, particularly where components are incompatible (e.g., ethyl acetate hydrolytically unstable in ethanol).
One of ordinary skill in the art would have found it obvious to select the specific polymers recited in claims 59 and 60 from the list of polymers taught by ’428 and ‘816. The selection of a particular polymer from a finite list of known alternatives is a matter of routine optimization and does not render the claims patentably distinct (see In re Hoeschele, 406 F.2d 1403, 1406 (CCPA 1969), wherein selecting a specific compound from a known class of compounds is prima facie obvious).
Claims 1, 5, 8, 9,11, 12, 14, 16, 18, 20, 23, 24, 26, 28-30, 41, and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, and 5 of US Patent No. 12,186,326 B2 (US Application No. 17/255,022; granted 07 January 2025, hereinafter referred to as reference “’022”). Although the claims at issue are not identical, they are not patentably distinct from each other because for the reasons outlined below.
The rejection of claim 56 is described above, in which claims 59 and 60 depend from. The new claims are directed to an obvious variant of the same inventive concept disclosed in the commonly owned patent ’022, and merely substitutes one known steroidal active pharmaceutical ingredient with another while maintaining the same inventive vehicle platform and critical functional properties.
The commonly owned reference ’022 explicitly teaches the exact film-forming excipients recited in claims 59 and 60, wherein the film-forming excipient is used in a sprayable liquid composition that prevents crystallization of the active ingredient. One of ordinary skill in the art would have found it obvious to select the specific polymers recited in claims 59 and 60 from the list of polymers taught by ’022. The selection of a particular polymer from a finite list of known alternatives is a matter of routine optimization and does not render the claims patentably distinct (see In re Hoeschele, 406 F.2d 1403, 1406 (CCPA 1969), wherein selecting a specific compound from a known class of compounds is prima facie obvious).
Claims 1, 5, 8, 9,11, 12, 14, 16, 18, 20, 23, 24, 26, 28-30, 41, and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 11, 15-18, 20, 25, 29-31, 33, 38, 42, 49-51, and 53 of co-pending US Application No. 17/761,507 (published 03 November 2022, hereinafter referred to as reference “’507”). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons outlined below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejection of claim 56 is described above, in which claims 59 and 60 depend from. The new claims are directed to an obvious variant of the same inventive concept disclosed in the commonly owned patent application ’507, and merely substitutes one known active pharmaceutical ingredient with another while maintaining the same inventive vehicle platform and critical functional properties. The '507 application discloses the same film-forming polymers.
The '507 application discloses "methacrylic acid and methyl methacrylate copolymer (1:1) and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1" as film-forming excipients (claims 15 and 29). Thus, claims 59 and 60 are not patentably distinct from the '507 application because they merely select specific polymers from lists explicitly disclosed in the reference.
Claims 1, 5, 8, 9,11, 12, 14, 16, 18, 20, 23, 24, 26, 28-30, 41, and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 36, 44, 52, 53 and 69 of co-pending US Application No. 18/502,863 (published 06 November 2023, hereinafter referred to as reference “’863”). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons outlined below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejection of claim 56 is described above, in which claims 59 and 60 depend from. The new claims are directed to an obvious variant of the same inventive concept disclosed in the commonly owned patent application ’863. The '863 application discloses the same film-forming polymers.
The '863 Application discloses "methacrylic acid and methyl methacrylate copolymer (1:1 and 1:2) and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1" as film-forming excipients (claims 6, 8, and 44). Thus, claims 59 and 60 are not patentably distinct from the '863 application because they merely select specific polymers from lists explicitly disclosed in the reference.
The applicant is advised that the obviousness-type double patenting rejections may be overcome by filing a terminal disclaimer under 37 CFR § 1.321(c) disclaiming the terminal portion of any patent granted on this application that would extend beyond the expiration date of the granted patent applications and filing a terminal disclaimer upon allowance over the co-pending applications, or demonstrating that the claims are patentably distinct. The applicant is further advised that the USPTO will not accept a terminal disclaimer that is conditional or that attempts to hold the rejection in abeyance (see MPEP § 1490).
Response to Arguments
The applicant’s amendments to the claims and Arguments/Remarks of the reply, filed 16 March 2026, have been fully considered but are not persuasive. The applicant’s remarks traverse the outstanding rejections and present amended claims directed to a sprayable liquid composition containing spironolactone or canrenone, and a dual-chamber device. The applicant argues that the claimed compositions are non-obvious due to purported crystallization challenges unique to spironolactone and that the cited prior art fails to teach or suggest the claimed inventions. For the reasons set forth below, the applicant’s arguments are unpersuasive, and the amendments fail to overcome the prior art rejections.
The applicant argues that spironolactone’s physicochemical properties (e.g., higher melting point, polar surface area, lower ethanol solubility) distinguish it from testosterone and estradiol such that one of ordinary skill would not have expected success in formulating it in a high-ethanol sprayable composition without crystallization. This argument has been considered but is not persuasive.
Dandiker explicitly teaches that its formulation platform prevents crystallization of steroid-based active ingredients during solvent evaporation (¶[0042], claim 74). The platform is not limited to testosterone and estradiol, but is a general solution for steroids prone to crystallization. Spironolactone is a steroid. One of ordinary skill would reasonably expect that a platform designed to prevent crystallization of steroids would work for another steroid, especially given the structural and functional similarities (both are hydrophobic, androgen receptor modulators with limited aqueous solubility).
In addition, Zhang explicitly teaches spironolactone in sprayable topical film-forming systems (claim 7 and ¶[0044]). Zhang discloses volatile solvent systems comprising ethanol, ethyl acetate, and isopropyl alcohol (claims 14-16 and ¶[0049]), and film-forming polymers similar to those claimed, demonstrating that spironolactone can be formulated in such systems. The applicant’s argument that spironolactone crystallization is an insurmountable problem is directly contradicted by Zhang, which teaches effective delivery from a solidified matrix without crystallization (¶[0043]). Thus, both references address film-forming delivery systems, volatile solvent evaporation, and dermal delivery of lipophilic actives. The substitution is therefore a predictable use of prior art elements, within the level of ordinary skill.
The applicant’s reliance on melting point and polar surface area differences is also unpersuasive. Spironolactone’s melting point (198-207°C) is higher than testosterone’s (155°C) and estradiol’s (173-179°C), but Dandiker’s formulation is specifically designed to maintain drugs in an amorphous or supersaturated state upon solvent evaporation, which is a principle that applies regardless of melting point. Higher melting point drugs require more robust stabilization, but Dandiker’s combination of film-forming polymers (e.g., Eudragit® L100, S100, E100) and controlled solvent evaporation is well-suited to this task. The Brandao reference attached by the applicant merely confirms that spironolactone is slightly soluble in ethanol, but it does not teach that spironolactone cannot be formulated in high-ethanol sprayable compositions, nor does it negate the teachings of Dandiker and Zhang. The differences in solubility or crystallization merely require routine optimization of solvent ratios and excipients, which is explicitly taught in both Dandiker and Zhang. Thus, the rejection of claims 1, 5, 9, 11, 12, 14, 16, 20, 23, 24, 26, 28-30, and 41 under 35 U.S.C. § 103 as being unpatentable over Dandiker in view of Zhang is maintained.
The applicant relies on solubility challenges and argues that Kim teaches away from using ethanol because Kim states that “[m]any alcohols, particularly alcohols having a low number of carbon atoms, degrade spironolactone” (page 4, lines 43-50). This argument is not persuasive.
A reference teaches away only when it criticizes, discredits, or otherwise discourages the claimed solution (see DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1326 (Fed. Cir. 2009)). Kim teaches diisopropyl adipate as a stabilizing solvent and buffered systems for spironolactone stability, wherein Kim’s statement is a general caution about degradation, not an absolute prohibition. Moreover, Kim’s compositions are creams containing nonvolatile solvents. Kim does not address sprayable, quick-drying films where ethanol rapidly evaporates, minimizing degradation. One of ordinary skill would recognize that rapid evaporation of ethanol in a thin film (i.e., less than 3 minutes) reduces degradation risk compared to prolonged contact in a cream and a person of ordinary skill in the art would balance volatile and non-volatile solvents and mitigate degradation via formulation design. Thus, Kim does not teach away and at most, merely identifies a consideration that a skilled formulator would address through routine optimization (e.g., controlling pH, using stabilizers).
Neither Dandiker nor Zhang discourages use of spironolactone in volatile systems. Zhang teaches solidified film matrices, implying control over crystallization and routine formulation adjustments (e.g., solvent blends, polymers, enhancers) are expected. Thus, the rejection of claims 1, 8, and 18 under 35 U.S.C. § 103 as being unpatentable over Dandiker in view of Zhang and Kim is maintained.
The applicant argues that Ruiz de Gopegui fails to teach a high-ethanol spironolactone composition in a spray system. This argument is not persuasive. The rejection combines Ruiz de Gopegui’s dual-chamber spray mechanism system that keeps incompatible components separate until dispensing and mixing at point of delivery (Abstract) with the composition taught by Dandiker, Zhang, and Kim. Ethyl acetate in the composition is hydrolytically unstable in ethanol, providing clear motivation to separate them in a dual-chamber devices known in the art for such is an obvious solution to this known instability concern. The claimed arrangement represents predictable separation of phases by a straightforward combination of applying a known device solution to a known formulation incompatibility problem. Thus, the rejection of claim 56 under 35 U.S.C. § 103 as being unpatentable over Dandiker in view of Zhang, Kim and Ruiz de Gopegui is maintained.
Regarding the amendment to claims 1 and 8 specifying a combination of a 70-90% w/v total aliphatic solvent with ethanol and a second aliphatic solvent in a 20:80 to 80:20 ratio, where the second solvent comprises 15-20% w/v ethyl acetate and 10% w/v di-isopropyl adipate, the components of the claimed composition are addressed by Dandiker, Zhang, and Kim.
Zhang discloses a volatile solvent system (high aliphatic solvent system) of water and at least one solvent selected from ethanol, isopropyl alcohol, ethyl acetate, or combinations thereof, explicitly names "spironolactone" as a drug that can be used in the formulation, discloses the use of a mixture of volatile solvents, including ethanol and ethyl acetate, and solidifying agents that are film-forming polymers (e.g., polyvinylpyrrolidone, hypromellose, ethyl cellulose).
Dandiker explicitly teaches washable film-forming compositions with barrier properties that prevent crystallization during solvent evaporation and maintain active ingredients in an amorphous state during and after solvent evaporation. Dandiker teaches ethanol as a solvent in a concentration as high as 30% w/w to 95% w/w, which encompasses the 70-90% w/v instant claimed range for the first solvent and about 10-40% w/w isopropyl alcohol. Kim teaches the second solvent by teaching the use of di-isopropyl adipate as a suitable solvent for topical spironolactone compositions. Combining high-ethanol sprayable systems that prevent active ingredient crystallization taught by Dandiker with spironolactone as an active ingredient taught by Zhang and solvent optimization as taught by Kim renders the instant invention obvious. The selection of a specific ratio of 20:80 to 80:20 ethanol:second solvent within the broad range taught by the prior art is obvious and a routine optimization parameter to prevent spironolactone crystallization.
Regarding the amendments to claim 29, the newly claimed parameters are routine optimization. Selecting a specific application rate (12.5 µl/cm²), testing duration (48 hours), and substrate type (acrylate surgical tape) would be matters of routine experimentation for one of ordinary skill. The specific substrate parameters (acrylate, porosity <15s/100cc/in², MVTR ~6200 g/m²/day, thickness ~0.17mm) are merely the inherent properties of a commercially available product (3M Transpore™ tape) that was publicly available before the filing date. Measuring WVTR of films was standard practice using established methods like ASTM E96E or desiccant methods, the use of microporous films and porous substrates for WVTR testing was well-known in the art, and comparing WVTR of a coated substrate to an uncoated control is a conventional way to express film breathability. The applicant has not demonstrated that the claimed values are critical (i.e., achieving a WVTR fraction of at least 0.50 or maintaining at least 50% of the substrate's baseline breathability) is critical and that the claimed composition unexpectedly achieves this while also preventing spironolactone crystallization.
Regarding the amendments to claim 56, Ruiz de Gopegui establishes that dual chamber devices for storing incompatible components (ingredients that would be unstable or degrade if stored together) separately and mixing them at the time of spraying were well-known in the art prior. Dandiker, Zhang, and Kim provide the specific composition by teaching the individual components (i.e., spironolactone, ethyl acetate, di-isopropyl adipate, ethanol, octisalate, film-forming polymers, PEG 400). Kim explicitly teaches that low-carbon alcohols degrade spironolactone, which suggests that storing spironolactone separately from ethanol is ideal.
One of ordinary skill, seeking to formulate a sprayable spironolactone composition where components are incompatible (e.g., ethyl acetate hydrolytically unstable in ethanol), would look to known dual chamber spray devices to keep components separate until use. The specific compositions in each chamber are merely the known components from Dandiker, Zhang, and Kim, separated based on compatibility. The applicant has not provided data showing that the dual chamber configuration provides unexpectedly superior stability, crystallization prevention, or spray characteristics, to support non-obviousness.
Regarding the nonstatutory obviousness-type double patenting rejections, nonstatutory obviousness-type double patenting rejections are proper where the claims at issue are not patentably distinct from the claims of a reference patent or application, (i.e., where the differences between the claims are such that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time of the later effective filing date; see In re Berg, 140 F.3d 1428, 1431-32 (Fed. Cir. 1998) and In re Goodman, 11 F.3d 1046, 1052 (Fed. Cir. 1993). The test is whether the later claim defines an invention that is an obvious variation of the invention claimed in the reference (see In re Longi, 759 F.2d 887, 893 (Fed. Cir. 1985)).
The applicant argues one of ordinary skill would not find it obvious to swap the testosterone of the reference patents with spironolactone because spironolactone has different physicochemical properties (e.g., higher melting point, higher polar surface area, lower ethanol solubility) and a greater tendency to crystallize. As noted above, the prior art (Zhang) already teaches spironolactone in sprayable film-forming compositions. The reference patents disclose the identical vehicle platform (i.e., same polymers, enhancers, solvents) for a different steroid. One of ordinary skill seeking to formulate spironolactone would look to these successful platforms for guidance. The claimed concentration ranges (1-20% w/v spironolactone) overlap with the testosterone ranges (0.1-25% w/w) taught in the reference patents. No unexpected results are alleged. The obviousness-type double patenting rejection is therefore proper.
Moreover, the reference patents are not limited to testosterone. They disclose a platform technology specifically designed to prevent crystallization of steroidal active ingredients during solvent evaporation. The patents explicitly teach that the composition prevents crystallization of the active ingredient (claims 1). Also, the reference patents teach that the composition can contain "other active agents" beyond testosterone. One of ordinary skill would recognize spironolactone as an obvious candidate for such substitution given its structural similarity to testosterone (both are steroid hormones) and its established topical use for androgen-mediated dermatological conditions. Furthermore, one of ordinary skill, seeking to formulate a sprayable, film-forming composition for spironolactone, a known steroidal drug with recognized crystallization challenges, would be directly motivated to employ this proven platform.
In addition, the applicant's reliance on melting point and polar surface area differences is not persuasive. The reference patents teach the use of specific film-forming polymers (e.g., Eudragit® L100, S100, E100) that are designed to maintain drugs in an amorphous or supersaturated state upon solvent evaporation. This mechanism is not dependent on the melting point of the active ingredient, but is a function of polymer-drug interactions and controlled evaporation kinetics. Higher melting point drugs require more robust stabilization, but the reference patents provide precisely that by teaching a combination of polymers, controlled solvent ratios, and penetration enhancers that together inhibit crystallization.
The applicant argues that the provisional nonstatutory obviousness-type double patenting rejections over the '507 and '863 applications are improper because those applications are directed to lidocaine and oxybutynin, respectively, rather than steroids. This argument is not persuasive. The '507 and '863 applications disclose the same vehicle platform as the reference patents- a sprayable, film-forming composition containing aliphatic solvents (ethanol, acetone, isopropyl alcohol), film-forming polymers (Eudragit® L100, S100, E100), penetration enhancers (azone, isopropyl myristate, octisalate, oleic acid, diethylene glycol monoethyl ether), and washability enhancers (polyethylene glycol 400). The active ingredient in each reference is different (testosterone, lidocaine, oxybutynin), but the vehicle is substantially the same. The inventive concept is the vehicle itself, a sprayable liquid that forms a quick-drying, washable or peelable film that prevents crystallization of the active ingredient.
One of ordinary skill, having before them a vehicle platform that successfully prevents crystallization of multiple different active ingredients (testosterone, lidocaine, oxybutynin), would reasonably expect that same platform to work for another active ingredient prone to crystallization, such as spironolactone. The fact that the platform works across structurally diverse active ingredients (e.g., steroid, amide local anesthetic, antimuscarinic) demonstrates its robustness and increases the expectation of success, not decreases it.
The applicant does not allege any unexpected results arising from the substitution of spironolactone for testosterone, lidocaine, or oxybutynin. No comparative data are provided showing that spironolactone behaves differently in the claimed formulation than the active ingredients in the reference patents and applications. In the absence of such evidence, applicant's attorney argument cannot overcome a prima facie case of obviousness (see In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984).
The claims are directed to the same inventive concept, a sprayable liquid film-forming composition for an active ingredient that prevents crystallization. The instant claims claim a sprayable liquid film-forming composition for a different steroidal active ingredient (spironolactone or canrenone) that prevents crystallization. The excipients, solvents (ethanol, ethyl acetate, acetone), film-forming polymers (methacrylic acid copolymers, polyacrylate polymers), penetration enhancers (azone, isopropyl myristate, octisalate, oleic acid, diethylene glycol monoethyl ether), and washability enhancers (PEG 400) are substantially identical.
The functional properties of a washable/peelable film formation, barrier film formation in less than three minutes, viscosity less than 30 cPs, water vapor transmission rate not less than 0.50 are also substantially identical. One of ordinary skill would recognize that substituting one steroid for another in a proven formulation platform is an obvious variation (see In re Dillon, 919 F.2d 688, 692-93 (Fed. Cir. 1990) (en banc), wherein substitution of one known compound for another in a known composition is prima facie obvious where the compounds are structurally similar and perform the same function).
The concentration ranges overlap (assuming a composition density of about 0.9 g/mL standard for hydroalcoholic sprays) or are routine optimizations, wherein selecting an appropriate concentration for a different drug is routine optimization (see In re Aller, 220 F.2d 454, 456 (CCPA 1955), wherein the determination of the optimum concentration of a material in a composition is a matter of routine experimentation). The method claims are obvious variants of treating conditions appropriate for the claimed active ingredients in the claimed composition. For example, one of ordinary skill would recognize that a composition containing an anti-androgen (spironolactone) would be useful for treating androgen-mediated conditions (acne, hirsutism, pattern hair loss), just as a composition containing an androgen (testosterone) is useful for treating androgen deficiency. The method claims are obvious variants of the reference method claims.
The dual-chamber device containing spironolactone in one chamber and ethanol/polymer/enhancer in the other of instant claim 56 is an obvious variant of the reference patents and patent applications as well. The dual-chamber device is not explicitly taught, but they teach the composition itself. Using a dual-chamber device to separate incompatible components (e.g., ethyl acetate from ethanol) is a well-known formulation technique. One of ordinary skill would find it obvious to package the known composition in a dual-chamber device to improve stability. This is not a patentably distinct invention.
The applicant requests that the provisional rejections over the '507 and '863 applications be held in abeyance until allowable subject matter can be determined. The proper response to an obviousness-type double patenting rejection is to file a terminal disclaimer disclaiming the terminal portion of the patent term that would extend beyond the expiration date of the reference patent or, in the case of a provisional rejection, to file a terminal disclaimer upon allowance over the reference application or by demonstrating patentable distinctness (see 37 CFR § 1.321(c); MPEP § 1490 and § 804(I)(B)). The applicant is advised that the nonstatutory double patenting rejections may be overcome by filing terminal disclaimers over the US Patent No. 11,523,994 B2, US Patent No. 12,208,169 B2, US Patent No. 12,186,326 B2, and the co-pending US Application No. 17/761,507, and US Application No. 18/502,863. The applicant is also advised that the USPTO will not accept a terminal disclaimer that is conditional or that attempts to hold the rejection in abeyance.
Conclusion
No claims are allowed.
The applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 (87 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 REBECCA L. SCOTLAND whose telephone number is (571) 272-2979. The examiner can normally be reached M-F 9:00 am to 5:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’ s supervisor, Robert A. Wax can be reached at (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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