DETAILED ACTION
Notice of AIA Status
The present application is subject to the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ). The application contains or contained at any time at least one claim to a claimed invention having an effective filing date on or after 16 March 2013. Accordingly, the application is being examined under the first inventor to file provisions of the AIA (see MPEP § 2159.02 and § 2159.03).
Continued Examination Under 37 CFR § 1.114
A request for continued examination under 37 CFR § 1.114, including the fee set forth in 37 CFR § 1.17(e) and a qualifying submission, was filed after final rejection. Since this application is eligible for continued examination under 37 CFR § 1.114, and the required fee has been timely paid, the finality of the previous Office Correspondence has been withdrawn pursuant to 37 CFR § 1.114. The applicant's submission filed on 14 July 2026 has been entered (see MPEP § 706.07(h) and 35 U.S.C. § 132(b)).
Status of the Claims
Amendments to the Claims and Arguments/Remarks filed 14 July 2026, in response to the Office Correspondence dated 14 April 2026, are acknowledged.
The claim listing filed 14 July 2026 are examined. Claims 6-17 and 21-23 are pending. Claims 6 and 21 are currently amended, and claims 1-5, and 18-20 are canceled.
Response to Amendment
All amendments are supported by the original disclosure. No new matter has been added under 35 U.S.C. § 132(a) or 35 U.S.C. § 112(a). The amendments merely clarify limitations that were already present in the specification as filed. The Request for Continued Examination and accompanying amendment and remarks have been fully considered. The amendments to claims 6 and 21 have been entered.
Claim 9 is objected to for misspellings, claims 8, 9, and 16 are rejected under 35 U.S.C. § 112(b), as outlined below, and claim 16 is rejected under 35 U.S.C. § 112(d) for depending from a cancelled claim, as outlined below. Upon further consideration of the amended claims and the prior art, the previously stated rejections over Tamarkin in view of Besonov and Tamarkin in view of Besonov and Zhang are withdrawn. New rejections under 35 U.S.C. § 103 are set forth below.
The withdrawal of the previous grounds should not be understood as an indication that every proposition advanced in applicant’s remarks concerning those references is necessarily agreed with. Rather, because the presently entered rejections rely upon a materially different evidentiary basis that more directly addresses the limitations emphasized by the applicant’s amendments and arguments, further prosecution is most appropriately based upon the newly stated grounds.
The present rejections do not depend upon converting Tamarkin’s emulsion into the applicant’s claimed solution, inferring the claimed antifungal/local-anesthetic combination from generalized lists of active agents, or that one solvent would solubilize both active agents. The pending claims, nevertheless, remain subject to the new rejections set forth below for the reasons separately articulated therein.
Claim Objections
Claim 9 is objected to because of the following informalities:
Claim 9 contains the apparent misspelling “cholorozylenol.” The intended compound appears to be “chloroxylenol,” particularly because the claim immediately identifies the substance parenthetically as “para-chloro-meta-xylenol.” The same typographical error appears in the published specification and original claim 9, and thus its origin is evident from the record. Also in claim 9, "naftifin" should be "naftifine" (the correct INN name). Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. § 112(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.
Claims 8, 9, and 16 are rejected under AIA 35 U.S.C. § 112(b), 2nd paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor/inventors, regards as the invention.
Claim 8 recites, in pertinent part, “the antifungal agent consists of at least one selected from the group comprising: clioquinol; haloprogin; miconazole nitrate; povidone iodine; undecylenic acid and its salts of calcium, copper, and zinc; and clotrimazole ...”. Claim 9 similarly recites, “the antifungal agent comprises at least one selected from the group comprising: [enumerated antifungal alternatives] ...”, wherein the phrase “selected from the group comprising” renders the recited grouping open-ended and leaves unclear which additional, unrecited alternatives fall within the group from which the claimed selection may be made.
A conventional Markush grouping is a closed grouping of alternatives ordinarily introduced by language such as “selected from the group consisting of”. MPEP §2173.05(h) instructs that where a Markush grouping requires selection from an open list, such as a “group comprising” the recited alternatives, the claim should generally be rejected under §112(b) because it is unclear what additional alternatives are intended to be encompassed (see also Abbott Laboratories v. Baxter Pharmaceutical Products, Inc., 334 F.3d 1274, 1280-81, 67 USPQ2d 1191, 1196-97 (Fed. Cir. 2003)).
The surrounding language does not cure the defect. In claim 8, although the antifungal agent itself is introduced by the closed transitional phrase “consists of”, the universe from which the “at least one” antifungal agent is selected is independently defined as the open “group comprising” the recited alternatives. Thus, the claim does not distinctly identify whether antifungal substances other than the enumerated species are members of that selection group. Similarly, claim 9's use of “comprises” before “at least one selected from” permits additional ingredients in the antifungal-agent component but does not identify the boundaries of the group from which the selected member is drawn.
To overcome this rejection, the applicant may consider, for example, amending each claim to recite “at least one selected from the group consisting of ...”, if that closed group expresses the intended scope. The words “at least one” may remain if combinations of two or more listed species are intended.
Further, claim 16 recites, "The treatment solution of claim 1, wherein the treatment solution further includes at least one of: emollients, surfactants, essential oils, thickening agents, texturizers, preservatives, and exfoliants." Claim 1 has been canceled. Therefore, there is no antecedent basis for the dependency on claim 1. A dependent claim must refer to a previously presented claim that is still pending. Because claim 1 no longer exists, claim 16 lacks a proper antecedent basis and is indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. § 112(d):
REFERENCE IN DEPENDENT FORMS. Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
A dependent claim must incorporate all limitations of the claim from which it depends and specify an additional limitation (see Pfizer, Inc. v. Ranbaxy Laboratories Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006)).
Claim 16 is rejected under AIA 35 U.S.C. § 112(d), 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 16 recites, “The treatment solution of claim 1, wherein the treatment solution further includes at least one of: emollients, surfactants, essential oils, thickening agents, texturizers, preservatives, and exfoliants.” However, claim 1 has been canceled. Accordingly, there is no presently operative base claim from which claim 16 may incorporate the limitations necessary to define the claimed “treatment solution”.
The Federal Circuit has confirmed that failure of a dependent claim to satisfy the statutory requirements for proper dependency renders the claim unpatentable (see Pfizer, Inc. v. Ranbaxy Laboratories Ltd., 457 F.3d 1284, 1291-92, 79 USPQ2d 1583, 1589-90 (Fed. Cir. 2006); see also MPEP §608.01(n)).
The applicant may overcome the rejection by, for example, amending claim 16 to depend from an appropriate pending claim, such as claim 6 if that is the intended subject matter, or by rewriting claim 16 in independent form incorporating all intended limitations of the canceled base claim, provided that the amendment is supported by the original disclosure and introduces no new matter. Based on the surrounding claim structure, claim 6 appears to be the most likely intended dependency. If the applicant intended claim 16 to further limit the antifungal/anesthetic treatment solution of claim 6, an amendment to, for example, “The treatment solution of claim 6, wherein ...”
would cure the dependency defect and appears consistent with the disclosed subject matter.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. § 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. 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. The applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. § 102(b)(2)(C) for any potential 35 U.S.C. § 102(a)(2) prior art against the later invention.
The following is a quotation of 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries underlying obviousness under 35 U.S.C. § 103 are those set forth in Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966), and 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.
The analysis must consider the claim as a whole and provide an articulated reason with a rational underpinning for the proposed modification or combination (see KSR International Co. v. Teleflex Inc., 550 U.S. 398, 418-22 (2007); In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006)).
A person of ordinary skill in the art at the relevant time would have had a bachelor’s or master’s degree in pharmacy, pharmaceutical sciences, chemistry, chemical engineering, or a closely related field, coupled with at least 2-5 years of hands-on experience in topical or dermatological formulation development. This individual would be well-versed in solubility theory, including the use of Hansen solubility parameters, logP/logKow, and cosolvency systems to dissolve poorly water-soluble active pharmaceutical ingredients. They would possess practical knowledge of volatile solvents, heterocyclic acetals (e.g., dioxolane), surfactants, and aqueous carrier systems, and would be familiar with the challenges of formulating stable, essentially alcohol-free solutions that are both cosmetically acceptable (non-greasy, quick-drying) and pharmaceutically effective.
Additionally, a person of ordinary skill in the art would have working knowledge of the FDA’s OTC antifungal monographs, including the approved active ingredients (tolnaftate, clotrimazole, miconazole, undecylenic acid, etc.), their required concentrations, and the regulatory status of topical anesthetics such as lidocaine, benzocaine, and pramoxine. They would understand the interplay between solvent choice, active ingredient solubility, skin permeation, and product stability, and would be capable of designing and evaluating formulations that meet both performance and regulatory criteria, all without relying on the high-alcohol content typical of conventional sprays and creams. This definition is consistent with the level of skill and knowledge displayed by the cited prior art references cited below and is appropriate for evaluating the patentability of the instant claimed invention.
During examination, a pending claim is given its broadest reasonable interpretation consistent with the specification, as the claim language would be understood by a person of ordinary skill in the art (see In re Morris, 127 F.3d 1048, 1054-1055 (Fed. Cir. 1997); In re Suitco Surface, Inc., 603 F.3d 1255, 1260 (Fed. Cir. 2010); MPEP § 2111). Where the prior art recognizes that a variable affects the pertinent property or result, determination of an optimum or workable value generally constitutes routine optimization (In re Aller, 220 F.2d 454, 456 (CCPA 1955); In re Applied Materials, Inc., 692 F.3d 1289, 1295-97 (Fed. Cir. 2012); MPEP § 2144.05). A claimed numerical range that overlaps or lies within a prior art range ordinarily establishes a prima facie case of obviousness (see In re Peterson, 315 F.3d 1325, 1329-30 (Fed. Cir. 2003)). The prior art need only provide a reasonable expectation of success, rather than absolute predictability (see In re O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988); MPEP § 2143.02).
The applicant’s Specification states that “alcohols” for purposes of “essentially free of alcohol” include SD alcohol, denatured alcohol, isopropyl alcohol, ethanol, and mixtures thereof, and explains that “essentially free of” includes formulations in which such alcohols are not intentionally included, such as less than 1 wt%. The applicant separately treats propylene glycol and heterocyclic-acetal solvents as solvents rather than the excluded “alcohols.”
Claims 6, 9, 12, 15-17 and 21-23 are rejected under AIA 35 U.S.C. § 103 as being unpatentable over Okudaira et al. (JP2003055205A, published 26 February 2003), in view of Tamarkin and Besonov (US20090130029A1, published 21 May 2009; hereinafter “Besonov”), further in view of Mallard and Willcox (US20120309753A1, published 06 December 2012; hereinafter “Mallard”), and Campbell and Michaelis (US20120149779A1, published 14 June 2012; hereinafter “Campbell”).
For purposes of the following rejections only, the examiner has conservatively treated 15 March 2018 as the effective filing date. The rejection therefore does not depend upon a determination that the presently amended claims are entitled only to the later continuation-in-part filing date. The cited references qualify as prior art because they are published prior to the instant effective filing date, and therefore predate the instant claimed invention.
Okudaira is directed to external preparations for treating fungal skin diseases containing an antifungal together with a local anesthetic. Okudaira expressly teaches terbinafine or a salt thereof as the antifungal and lidocaine, dibucaine, or procaine, or salts thereof, as the local anesthetic, and expressly contemplates a liquid for external use among the dosage forms (¶[0005]-[0008]). Okudaira further teaches application or spraying onto the affected skin and permits conventional formulation additives including surfactants, thickeners, dissolution aids, preservatives, and flavoring agents (¶[0007]-[0008]).
Most significantly, Okudaira Example 1 prepares an external-use liquid containing 5 g terbinafine hydrochloride; 15 g lidocaine; 50 g urea; 10 g macrogol; 10 g propylene glycol; and q.s. to 1 liter purified water. Okudaira teaches mixing the components with purified water and adding additional purified water to obtain the dissolved external-use preparation (Example 1). Thus, Okudaira provides an aqueous fluid for topical skin application containing an antifungal, a topical anesthetic, propylene glycol/macrogol, and water. However, Okudaira does not expressly characterize the propylene glycol as an antifungal agent solvent that solubilizes both the antifungal and topical anesthetic using the exact functional terminology of instant claim 6.
Mallard supplies direct antifungal specific solvent evidence. Mallard experimentally reports substantial terbinafine-HCl solubility in propylene glycol and further reports approximately 2.2 wt% terbinafine-HCl solubility in a 50:50 water/propylene-glycol system (Solubility Study, ¶[0078] section A-1 and ¶[0087] section A-3). Thus, the same propylene glycol present in Okudaira is established as an aqueous-compatible solvent for the same antifungal.
Campbell supplies the complementary anesthetic teaching. Its aqueous lidocaine HCl formulations expressly contain propylene glycol and identify the function of propylene glycol as solvent/delivery agent, wherein water is also present as a solvent/vehicle (¶[0075], Table 2A; see also Table 2B).
Besonov additionally provides an express reason to maintain the topical formulation substantially free of lower alcohols. Besonov teaches substantially alcohol-free formulations containing less than about 5% lower alcohol, preferably less than about 2%, and more preferably less than about 1%, and identifies ethanol, propanol/isopropanol, butanol/isobutanol/t-butanol, and pentanol as lower alcohols whose presence is less desirable because of skin irritation (¶[0204]).
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, to use the propylene glycol already present in Okudaira according to its known solvent function for the terbinafine and lidocaine while avoiding unnecessary addition of irritating lower alcohols. Okudaira provides the aqueous antifungal/local anesthetic external-use framework, Mallard demonstrates that propylene glycol solubilizes the exact antifungal (including in water), Campbell demonstrates the same solvent/delivery agent function for the local anesthetic, and Besonov teaches minimizing lower alcohols in skin-contacting compositions. This modification involves application of known properties of an ingredient already present in the primary-reference formulation and produces the predictable result of maintaining the two active agents in an aqueous topical solution (see KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 416-418 (2007); MPEP § 2143).
There also would have been a strong reasonable expectation of success in doing so because the proposed composition need not be reconstructed from unrelated ingredients. Okudaira actually prepares the aqueous terbinafine/lidocaine/propylene glycol liquid, while the secondary references empirically establish the relevant solvent functions (see In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)). Accordingly, instant claim 6 is obvious.
Instant claim 9 further requires an antifungal selected from a group expressly including terbinafine hydrochloride. Okudaira Example 1 uses terbinafine hydrochloride. Accordingly, instant claim 9 is unpatentable for the reasons stated for instant claim 6. Instant claim 12 requires that the antifungal agent solvent comprise a solvent miscible with the carrier fluid. Okudaira actually incorporates propylene glycol and purified water into a single external-use liquid. Mallard further studies a homogeneous 50:50 water/propylene glycol solvent system for terbinafine-HCl solubility. Thus, the cited art establishes the aqueous compatibility/miscibility required by instant claim 12. Instant claim 12 is therefore unpatentable for the reasons stated for instant claim 6. Instant claim 15 requires that the topical anesthetic comprise one of lidocaine, benzocaine, tetracaine, pramoxine, or prilocaine. Okudaira Example 1 expressly contains lidocaine. Instant claim 15 is therefore unpatentable for the reasons stated for instant claim 6.
Instant claim 16 presently depends from canceled claim 1. Accordingly, instant claim 16 is rejected as incomplete and must be amended to provide an operative dependency (see MPEP § 608.01(n)), as detailed above. In the interest of compact prosecution, for examination, instant claim 16 is understood as intended to depend from instant claim 6. The additional subject matter of instant claim 16 is nevertheless addressed on the conditional merits. Okudaira teaches that its antifungal/local anesthetic topical compositions may contain conventional additives including surfactants, thickeners, and preservatives (¶[0008]), each of which independently satisfies an alternative recited in instant claim 16. Accordingly, if instant claim 16 is amended to depend from instant claim 6, it would be rejected under § 103 over the references applied to instant claim 6, with Okudaira itself supplying the additional limitation.
Instant claim 17 requires the treatment solution to further include at least one of peppermint and eucalyptus. Okudaira provides the additional limitation. Example 4 employs peppermint oil in a topical antifungal/local anesthetic composition. Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, to include peppermint oil in the tolnaftate-containing formulation because Okudaira establishes its use in the same antifungal/local anesthetic topical formulation context. The modification requires no change in therapeutic mechanism and simply employs a conventional additive in the manner taught by the primary reference. Instant claim 17 is therefore obvious.
The antifungal, topical-anesthetic, solvent, carrier-fluid, and fluid-for-skin-application limitations are taught or suggested for the reasons given above with respect to instant claim 6. Instant claim 21 additionally requires an alcohol content of 15 wt% or below. Okudaira Example 1 does not identify ethanol, isopropanol, SD alcohol, or denatured alcohol as ingredients. Besonov teaches that topical compositions preferably contain less than about 5% lower alcohol, more preferably less than about 2%, and still more preferably less than about 1% (¶[0204]). Every such amount is within instant claim 21’s broad maximum of 15 wt%. One of ordinary skill in the art would have been motivated to employ the low-alcohol formulation because Besonov expressly identifies irritation associated with the short-chain alcohols, while Okudaira, Mallard, and Campbell establish that the active ingredients can instead be accommodated in an aqueous propylene glycol-containing solvent system. Accordingly, instant claim 21 is obvious.
Instant claim 22 recites a series of alternative maximum alcohol concentrations terminating in 2 wt% or below. Besonov teaches a preferred lower-alcohol concentration of less than about 2% and a still more preferred concentration below about 1% (¶[0204]). Thus, at least the 2 wt% or below alternative is directly suggested and is therefore obvious. Instant claim 23 requires one of lidocaine, benzocaine, tetracaine, pramoxine, or prilocaine. Okudaira Example 1 teaches lidocaine, thus instant claim 23 is prima facie obvious.
Claims 6 and 7 are rejected under AIA 35 U.S.C. § 103 as being unpatentable over Okudaira et al. (JP2003055205A, published 26 February 2003), in view of Tamarkin and Besonov (US20090130029A1, published 21 May 2009; hereinafter “Besonov”), further in view of Mallard and Willcox (US20120309753A1, published 06 December 2012; hereinafter “Mallard”), and Campbell and Michaelis (US20120149779A1, published 14 June 2012; hereinafter “Campbell”), as applied to claim 6 above, and in further view of Sawaya (US5519059A, published 21 May 1996) and Iwata et al. (US4621090A, published 04 November 2004; hereinafter “Iwata”).
For purposes of the following rejections only, the examiner has conservatively treated 15 March 2018 as the effective filing date. The rejection therefore does not depend upon a determination that the presently amended claims are entitled only to the later continuation-in-part filing date. The cited references qualify as prior art because they are published prior to the instant effective filing date, and therefore predate the instant claimed invention.
Okudaira, in view of Besonov, Mallard, and Campbell, teaches the limitations of instant claim 6, as described above, from which instant claim 7 depends, however do not explicitly teach the specific limitations of instant claim 7.
Okudaira supplies the underlying topical antifungal/local anesthetic formulation and demonstrates the compatibility of tolnaftate with a local anesthetic. In particular, Okudaira Example 3 contains terbinafine hydrochloride, tolnaftate, and procaine hydrochloride. Sawaya independently teaches topical tolnaftate liquid formulations (Abstract) and states that tolnaftate is soluble in propylene glycol (col. 3, ll. 3-6). Sawaya further discusses conventional topical formulations containing approximately 1% tolnaftate, including a formulation containing water and propylene glycol (col. 2, ll. 43-49). Campbell, as discussed above, identifies propylene glycol as a solvent/delivery agent for lidocaine, and Besonov supplies the reason to avoid unnecessary lower alcohols.
Instant claim 7 requires a naphthyl thiocarbamate. Iwata identifies tolnaftate as O-2-naphthyl N-methyl-N-3-methylphenylthiocarbamate and describes it as a known antifungal for cutaneous fungal infection (col. 1, ll. 14-19). Iwata is therefore relied upon not to create an additional formulation modification, but to establish the chemical identity/classification of the tolnaftate already suggested by Okudaira and Sawaya.
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, to substitute tolnaftate for the antifungal of Okudaira Example 1, or otherwise employ the tolnaftate embodiment taught by Okudaira in the aqueous external-use framework, because Okudaira itself teaches tolnaftate together with a local anesthetic and Sawaya establishes that the propylene glycol solvent used by Okudaira is capable of solubilizing tolnaftate. This is not an unsupported substitution among chemically unrelated drugs, rather, the primary reference itself identifies the replacement antifungal in the same therapeutic formulation context. There would have been a reasonable expectation of success in doing so because the compatibility of tolnaftate and an anesthetic is demonstrated in Okudaira, and tolnaftate’s solubility in the proposed propylene glycol solvent is expressly established by Sawaya.
Claims 6 and 8 are rejected under AIA 35 U.S.C. § 103 as being unpatentable over Okudaira et al. (JP2003055205A, published 26 February 2003), in view of Tamarkin and Besonov (US20090130029A1, published 21 May 2009; hereinafter “Besonov”), further in view of Mallard and Willcox (US20120309753A1, published 06 December 2012; hereinafter “Mallard”), and Campbell and Michaelis (US20120149779A1, published 14 June 2012; hereinafter “Campbell”), as applied to claim 6 above, and in further view of Su and Sequeira (US4775678A, published 04 October 1988; hereinafter “Su”), and Murrell and Gupta-Murrell (US20140154338A1, published 05 June 2014; hereinafter “Murrell”).
For purposes of the following rejections only, the examiner has conservatively treated 15 March 2018 as the effective filing date. The rejection therefore does not depend upon a determination that the presently amended claims are entitled only to the later continuation-in-part filing date. The cited references qualify as prior art because they are published prior to the instant effective filing date, and therefore predate the instant claimed invention.
Okudaira, in view of Besonov, Mallard, and Campbell, teaches the limitations of instant claim 6, as described above, from which instant claim 8 depends, however do not explicitly teach the specific limitations of instant claim 8.
Instant claim 8 includes, among its alternatives, clotrimazole at 1 wt%. Murrell provides particularly direct evidence concerning the drug/anesthetic combination, wherein Example 1 contains approximately 83 wt% water, 2 wt% lidocaine, and 1 wt% clotrimazole in a topical composition (¶[0037]).
Su teaches topical clotrimazole compositions containing propylene glycol (Abstract) and identifies propylene glycol as a solubility enhancer for clotrimazole, with propylene glycol being preferred, in water-containing topical formulations (col. 1, ll. 36-47). Su’s disclosed clotrimazole concentrations encompass approximately 1 wt% (claims 1-3). Campbell independently establishes propylene glycol as a solvent/delivery agent for lidocaine, while Besonov supplies the low-alcohol rationale.
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, to substitute 1 wt% clotrimazole for the antifungal in Okudaira’s aqueous antifungal/anesthetic liquid because clotrimazole was a known topical antifungal for the same general indication; Murrell demonstrates the precise 1% clotrimazole, lidocaine, and water combination; Su establishes propylene glycol as a preferred solubility enhancer for clotrimazole; and Campbell establishes the corresponding solvent function for lidocaine. The combination therefore supplies both a reason to make the substitution and a strong reasonable expectation of formulation success. Accordingly instant claim 8 is obvious.
Claims 6 and 10 are rejected under AIA 35 U.S.C. § 103 as being unpatentable over Okudaira et al. (JP2003055205A, published 26 February 2003), in view of Tamarkin and Besonov (US20090130029A1, published 21 May 2009; hereinafter “Besonov”), further in view of Mallard and Willcox (US20120309753A1, published 06 December 2012; hereinafter “Mallard”), and Campbell and Michaelis (US20120149779A1, published 14 June 2012; hereinafter “Campbell”), as applied to claim 6 above, and in further view of Sawaya (US5519059A, published 21 May 1996).
For purposes of the following rejections only, the examiner has conservatively treated 15 March 2018 as the effective filing date. The rejection therefore does not depend upon a determination that the presently amended claims are entitled only to the later continuation-in-part filing date. The cited references qualify as prior art because they are published prior to the instant effective filing date, and therefore predate the instant claimed invention.
Okudaira, in view of Besonov, Mallard, and Campbell, teaches the limitations of instant claim 6, as described above, from which instant claim 10 depends, however do not explicitly teach the specific limitations of instant claim 10, expressly requiring tolnaftate.
Okudaira supplies the underlying topical antifungal/local anesthetic formulation and demonstrates the compatibility of tolnaftate with a local anesthetic. In particular, Okudaira Example 3 contains terbinafine hydrochloride, tolnaftate, and procaine hydrochloride. Campbell, as discussed above, identifies propylene glycol as a solvent/delivery agent for lidocaine, and Besonov supplies the reason to avoid unnecessary lower alcohols. Sawaya independently teaches topical tolnaftate liquid formulations (Abstract) and states that tolnaftate is soluble in propylene glycol (col. 3, ll. 3-6). Sawaya further discusses conventional topical formulations containing approximately 1% tolnaftate, including a formulation containing water and propylene glycol (col. 2, ll. 43-49).
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, to substitute tolnaftate for the antifungal of Okudaira in the aqueous external-use framework, because Okudaira itself teaches tolnaftate together with a local anesthetic and Sawaya establishes that the propylene glycol solvent used by Okudaira is capable of solubilizing tolnaftate. This is not an unsupported substitution among chemically unrelated drugs, rather the primary reference itself identifies the replacement antifungal in the same therapeutic formulation context. In addition, there would have been a reasonable expectation of success in doing so because the compatibility of tolnaftate and an anesthetic is demonstrated in Okudaira, and tolnaftate’s solubility in the proposed propylene glycol solvent is expressly established by Sawaya. The foregoing teachings directly provide the instant claim 10 species, thus instant claim 10 is obvious.
Claims 6, 11, 13, and 14 are rejected under AIA 35 U.S.C. § 103 as being unpatentable over Okudaira et al. (JP2003055205A, published 26 February 2003), in view of Tamarkin and Besonov (US20090130029A1, published 21 May 2009; hereinafter “Besonov”), further in view of Mallard and Willcox (US20120309753A1, published 06 December 2012; hereinafter “Mallard”), and Campbell and Michaelis (US20120149779A1, published 14 June 2012; hereinafter “Campbell”), as applied to claim 6 above, and in further view of Hitt et al. (US20070287675A1, published 13 December 2007; hereinafter “Hitt”), Sundberg et al. (US20140329906A1, published 06 November 2014; hereinafter “Sundberg”), and Samour et al. (US6224887B1, published 01 May 2001, hereinafter “Samour”).
For purposes of the following rejections only, the examiner has conservatively treated 15 March 2018 as the effective filing date. The rejection therefore does not depend upon a determination that the presently amended claims are entitled only to the later continuation-in-part filing date. The cited references qualify as prior art because they are published prior to the instant effective filing date, and therefore predate the instant claimed invention.
Okudaira, in view of Besonov, Mallard, and Campbell, teaches the limitations of instant claim 6, as described above, from which instant claims 11, 13, and 14 depend, however do not explicitly teach the specific limitations of instant claims 11, 13, and 14.
Okudaira supplies the aqueous external-use formulation containing an antifungal, a local anesthetic, propylene glycol/macrogol, and purified water, while Besonov supplies the reason to maintain the formulation substantially free of lower alcohols. However, Okudaira does not expressly employ a heterocyclic-acetal/dioxolane solvent.
Hitt teaches active agents including antifungal pharmaceutical agents and explicitly identifies, among others, tolnaftate, terbinafine, and clotrimazole that may be brought into solution using one or more organic solvents and expressly identifies 1,3-dioxolane as a suitable organic solvent (¶[0044]). Hitt separately confirms that 1,3-dioxolane is an organic solvent (¶[0051]).
Samour independently places the dioxolane teaching in the topical antifungal formulation art (Abstract). Samour teaches substituted 1,3-dioxolanes, including 2-n-heptyl-, 2-n-nonyl-, and 2-n-undecyl-1,3-dioxolane, in topical antifungal preparations and expressly teaches that such compounds function as solubilizing agents for the antifungal agent and other active principles (col. 5, ll. 10-30).
Sundberg supplies the complementary anesthetic solubilization teaching. Sundberg teaches water-containing local anesthetic compositions and identifies additional solubilizers including propylene glycol, benzyl alcohol, glycerol formal, glycofural, polysorbate 80, and ethyl acetate (¶[0029]-[0030]). Sundberg further teaches dermal administration to healthy, diseased, or injured skin (¶[0038]). The applicant’s Specification itself places glycerol formal within the disclosed dioxolane-solvent class, identifying a glycerol-formal mixture containing 1,3-dioxolane-4-methanol and 5-hydroxy-1,3-dioxane. Thus, Sundberg is pertinent evidence concerning the anesthetic solubilizing function of the claimed solvent class under the broadest reasonable interpretation.
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, to replace at least part of Okudaira’s conventional propylene glycol solvent system with a dioxolane class solvent because the prior art expressly taught use of organic solvents to bring antifungals including terbinafine/tolnaftate into solution, with 1,3-dioxolane expressly identified by Hitt, use of dioxolane family materials as antifungal solubilizers in topical compositions by Samour, and use of glycerol formal as a local-anesthetic solubilizer in aqueous dermal formulations by Sundberg. The references therefore provide an articulated formulation reason extending to both active agent classes rather than merely selecting dioxolane from an undifferentiated solvent list.
Although Hitt’s ultimate dosage form context differs from Okudaira’s external-use topical liquid, Hitt is relied upon for its solvent selection teaching directed to the same technical problem of bringing poorly water-soluble antifungal pharmaceutical agents into solution using pharmaceutically acceptable organic solvents. A reference constitutes analogous art if it is either from the same field of endeavor or is reasonably pertinent to the problem confronting the inventor (see In re Bigio, 381 F.3d 1320, 1325 (Fed. Cir. 2004); see also MPEP § 2141.01(a)). A reference outside the identical end-use field is reasonably pertinent when its subject matter logically would have commended itself to the skilled artisan’s attention in addressing the particular problem. A pharmaceutical formulator faced with solubilizing a poorly water-soluble antifungal reasonably would have consulted solvent/solubility teachings directed to those same antifungal molecules. Samour independently confirms that dioxolane-family antifungal solubilizers were used in the topical field, further reducing any distinction arising from Hitt’s ultimate dosage form.
Instant claim 11 requires a heterocyclic acetal solvent and instant claim 13 expressly requires dioxolane. 1,3-Dioxolane is a cyclic acetal, and Hitt explicitly teaches its use as an antifungal organic solvent (¶[0044], ¶[0051]), wherein Samour corroborates use of substituted 1,3-dioxolanes as topical antifungal solubilizing agents (claim 1), and Sundberg supplies the local-anesthetic/dioxolane class solubilization teaching (¶[0029]-[0030]) and ¶[0038]). Thus, instant claims 11 and 13 are obvious.
Instant claim 14 requires, in addition to the limitations inherited from instant claim 6, a tolnaftate at a concentration of at least 1 wt% and dioxolane at 2-4 wt% as the antifungal-agent solvent. The inherited aqueous antifungal/topical-anesthetic external-use formulation and low-alcohol limitations are taught or suggested by Okudaira and Besonov for the reasons stated above. Okudaira itself establishes that tolnaftate can be employed together with a local anesthetic, wherein Example 3 contains tolnaftate and procaine hydrochloride.
Samour also identifies tolnaftate among the suitable topical antifungal agents (col. 11, ll. 47-60) and teaches active antifungal concentrations generally of about 0.5-20 wt% (claim 23) or preferably 1-10 wt% of the composition (col. 12, ll. 9-14; see also claim 38). Thus, the claimed lower boundary of at least 1 wt% is explicitly encompassed by Samour’s preferred antifungal concentration. Accordingly, selecting tolnaftate at 1 wt% or greater for a topical antifungal composition is suggested by the prior art.
Hitt teaches the solvent/solute relationship that was not established by Okudaira alone. Hitt identifies tolnaftate among the relevant antifungal active agents and teaches that those active agents may be brought into solution using one or more organic solvents, expressly including 1,3-dioxolane among the suitable solvents (¶[0044]). Thus, Hitt is not relied upon merely because dioxolane appears somewhere in a general excipient list. Hitt affirmatively connects the disclosed antifungal class that includes tolnaftate with solution in the disclosed organic-solvent class that expressly includes simple 1,3-dioxolane.
Accordingly, one of ordinary skill in the art selecting tolnaftate for the Okudaira topical antifungal/anesthetic system would have had an express reason to consider 1,3-dioxolane as a solubilizing solvent. Hitt identifies that solvent for the relevant antifungal class and Samour confirms antifungal-solubilizing behavior of dioxolane-family compounds in topical antifungal formulations.
Samour teaches that the amount of its dioxolane-family enhancer/solubilizer is selected according to such formulation considerations as desired delivery, product stability, adverse effects, and carrier composition. Samour discloses a broad concentration of about 0.5-35 wt% (claim 23), wherein preferably from about 2-3% or more (col. 5, ll. 23-30), depending on other composition formulation ingredients. Sundberg independently teaches a local anesthetic solubilizer at 0-10 wt%, more preferably about 1-5 wt% (¶[0018]) and identifies glycerol formal among the suitable additional solubilizers (¶[0029]). Sundberg further teaches water-containing formulations and dermal administration (¶[0030], ¶[0038]).
Thus, the instant claimed 2-4 wt% range therefore falls within Sundberg’s preferred 1-5 wt% solubilizer region and lies within Samour’s disclosed dioxolane family formulation concentration range of 0.5-35 wt%. Where the prior art discloses a range that encompasses or overlaps the claimed range, the claimed range ordinarily supports a prima facie case of obviousness absent evidence of criticality or unexpected results (see In re Peterson, 315 F.3d 1325, 1329-30 (Fed. Cir. 2003); MPEP § 2144.05).
Moreover, Samour teaches that the amount of dioxolane family material is selected based on formulation performance considerations (col. 4, l. 4-col. 5, l. 38). Thus, concentration was recognized in the prior art as a formulation variable affecting the properties of the composition. Once the prior art establishes the general conditions and identifies the parameter as result-affecting, routine determination of an optimum or workable value generally would have been within ordinary skill (see In re Aller, 220 F.2d 454, 456 (CCPA 1955); MPEP § 2144.05). Hitt and Samour first establish the antifungal/dioxolane solubilization relationship, and Sundberg and Samour then establish concentration ranges encompassing or bordering the claimed 2-4 wt% range.
Sundberg additionally addresses instant claim 6’s requirement that the solvent system solubilize the topical anesthetic. Sundberg teaches local anesthetic compositions containing lidocaine and other local anesthetics together with pharmaceutical solubilizers (¶[0031]) and identifies glycerol formal as an additional solubilizer (¶[0029]), includes water (Table 3; ¶[0073]), and teaches dermal administration (¶[0038]). The applicant’s Specification itself categorizes glycerol formal within the disclosed dioxolane-solvent family. Thus, the record provides evidence supporting both sides of the functional limitation, wherein Hitt and Samour supply dioxolane class solvent for the antifungal and Sundberg supplies the dioxolane class/glycerol formal solubilizer for the topical anesthetic.
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, starting with Okudaira, to make the proposed modifications because Okudaira already teaches a topical antifungal/local anesthetic preparation and separately demonstrates tolnaftate with a local anesthetic. In selecting tolnaftate, a poorly water-soluble topical antifungal, a skilled formulator would have sought a solvent capable of maintaining the active in the solution. Hitt recommends organic solvents including 1,3-dioxolane to bring the antifungal class including tolnaftate into solution. Samour independently confirms that dioxolane family compounds function as antifungal solubilizers in topical formulations. Sundberg teaches the corresponding dioxolane class/glycerol formal solubilizer for aqueous dermal local-anesthetic compositions and places the solvent amount in the low-single-digit concentration range.
Thus, the proposed combination reflects the predictable application of established pharmaceutical solvent teachings to solve the solubility requirements expressly imposed by Okudaira’s external-use formulation (see KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 416-418 (2007). There would likewise have been a reasonable expectation of success in doing so because Okudaira actually establishes antifungal/local anesthetic coformulation, Okudaira expressly demonstrates tolnaftate together with a local anesthetic, Hitt teaches 1,3-dioxolane for bringing antifungal actives including tolnaftate into solution, Samour establishes topical use and antifungal solubilizing behavior of dioxolane-family compounds, and Sundberg establishes solubilization of local anesthetics using the corresponding solvent class in water-containing dermal compositions. Accordingly, the proposed modification is not predicated upon mere speculation that an arbitrarily selected solvent might work and instant claim 14 is therefore obvious.
The rejection rests on the complementary teachings identified above, bodily incorporation of every feature of one reference into another or that one reference itself contains the entire claimed arrangement is not required. The issue is whether the claimed invention as a whole would have been obvious in light of the combined teachings and knowledge of one of ordinary skill (see KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 416-421 (2007); MPEP § 2145). Here, the instant claimed invention as a whole would have been obvious in light of the combined teachings and knowledge of one of ordinary skill.
Response to Arguments
Applicant Arguments/Remarks of the reply, filed 14 July 2026, have been fully considered. The applicant argues that the prior rejection failed to establish a treatment solution rather than an emulsion; an antifungal agent and topical anesthetic actually present together; a solvent capable of solubilizing both active agents; the claimed low-alcohol or essentially alcohol-free condition; and a composition formulated for application to skin as a fluid. Those arguments do not overcome the presently stated rejections.
The applicant contends that Tamarkin teaches only emulsions and that the claimed "solution" is not disclosed. This argument is unpersuasive. Tamarkin teaches that the composition may include water as part of the aqueous phase (¶[0027]) and that the "organic carrier" may include polar solvents, including dioxolane, which are water-miscible and routinely used in aqueous or hydroalcoholic systems (13-15; ¶[0039], ¶[0042]). Tamarkin does not exclude water or solution formulationsm, wherein it broadly teaches foamable compositions where the internal phase may include aqueous components, and the system may be formulated across a spectrum from emulsion to solution depending on solvent selection.
In addition, Besonov bridges this gap by teaching that the same class of compositions may be formulated as a "single-phase formulation/solution" or "homogeneous suspension" as interchangeable formats (¶[0360], claim 22). Besonov explicitly teaches that the composition "can be in the form of a single-phase formulation/solution, homogenous suspension, or alternatively as a stable emulsion" (claim 23). Thus, the combination of Tamarkin and Besonov expressly suggests aqueous solution formulations.
Furthermore, the choice between an emulsion and a solution is a routine formulation decision. As the Supreme Court held in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007), "[w]hen there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense." Here, the skilled artisan would recognize from Besonov's teachings that solution formulations are a known, predictable alternative to emulsions for the same purpose. Selecting the solution form for simplicity, stability, and consumer appeal is precisely the type of routine optimization that is prima facie obvious.
Moreover, unlike the previously applied Tamarkin formulation, Okudaira clearly teaches a “liquid for external use”. Okudaira Example 1 combines terbinafine hydrochloride, lidocaine, propylene glycol, macrogol, and purified water and states that the ingredients are dissolved to prepare the external-use liquid. Okudaira therefore explicitly supplies an actual aqueous topical liquid rather than the inference that it is obvious to reformulate the emulsion as a solution. Okudaira also identifies the preparation as a liquid for external use and teaches application or spraying of its preparations onto affected skin. Thus, the presently claimed formulation “to be applied to skin as a fluid” is addressed directly by the primary reference rather than being inferred from a pressurized foam system.
The applicant contends that long lists of active agents in Tamarkin and Besonov, without teaching the specific combination of an antifungal and a topical anesthetic, are insufficient to render the claimed combination obvious. This argument is not persuasive. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose (see In re Kerkhoven, 626 F.2d 846 (CCPA 1980)). Here, both Tamarkin and Besonov teach topical compositions for treating skin conditions, and both list antifungal agents and topical anesthetics among the active agents useful for such compositions. A person of ordinary skill in the art, treating a condition involving both pain/discomfort and a fungal infection (e.g., tinea with secondary excoriation or inflammation), would have found it obvious to combine a known antifungal agent with a known topical anesthetic to treat both symptoms simultaneously.
Furthermore, KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 418 (2007) rejected the rigid application of the teaching-suggestion-motivation test, holding that "a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was independently known in the prior art," but that "it can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does". Here, the reason is clear- the desire to provide simultaneous relief from both fungal infection and associated pain or itching. The combination of an antifungal with a topical anesthetic is a mere aggregation of known compounds for their known purposes, which does not yield an unexpected result.
The fact that the specific combination appears in a long list does not defeat obviousness. As the Federal Circuit has explained, a known composition is prima facie obvious when it is merely a combination of known prior art elements, each performing its known function, and the combination yields no more than predictable results (see KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 416 (2007)). The skilled artisan would be motivated to select from the list those active agents that address the particular condition being treated.
The applicant argues that Besonov ¶[0240], sets out pairs of active agents and solvents but does not teach two active agents, and that assuming a single solvent constitutes improper hindsight. This argument is not persuasive. Besonov claim 15 teaches topical compositions comprising "a local anesthetic and/or fungicides." The term "and/or" plainly encompasses compositions containing both a local anesthetic and a fungicide. Besonov ¶[0240] provides non-limiting examples of solubility data for various active agents, including metronidazole and ketoconazole, in various solvents. This teaching informs the skilled artisan that certain solvents are capable of solubilizing multiple active agents. The use of dioxolane at 2-4% is consistent with the examples in Besonov indicating the use of >1% polar solvent for active agents that are practically insoluble in mineral oil.
The argument that this constitutes improper hindsight is unavailing. Hindsight is not invoked when the prior art provides a reason for the combination. In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006) teaches the 'suggestion' need not be found in the prior art references themselves, wherein it may be supplied by the knowledge of one of ordinary skill in the art. Here, the knowledge that dioxolane is a polar solvent with high solubilizing capacity (Besonov, ¶[0235]) and is miscible with both water and oil (Besonov, ¶[0236]) provides a sufficient reason for one of ordinary skill to use it as a single solvent for both active agents.
Moreover, the applicant’s contention that the art merely provides unrelated lists of antifungal and anesthetic agents does not apply to Okudaira. Example 1 expressly combines the antifungal terbinafine hydrochloride and the local anesthetic lidocaine in the same preparation. Okudaira additionally discloses tolnaftate together with procaine hydrochloride in Example 3. The present rejection therefore does not reconstruct the claimed therapeutic pairing by selecting two unrelated agents from independent lists.
The applicant argues that neither Tamarkin nor Besonov teaches a single solvent that solubilizes both the antifungal agent and the topical anesthetic. This argument is not persuasive. Tamarkin teaches compositions comprising at least two active agents (claim 21) and lists both antifungal agents and topical anesthetics among the active agents (claim 20). Besonov similarly teaches topical compositions comprising a local anesthetic and/or fungicides (claim 15) and lists polar solvents including dioxolane that possess high solubilizing capacity and contribute to the skin penetration of an active agent (¶[0235]). Dioxolane is described as a "penetration enhancer" that is "an organic solvent, typically soluble in both water and oil" (¶[0236]).
A solvent that solubilizes an active agent and enhances its penetration is, by definition, a solubilizer. These properties inherently enable solute dissolution. In formulation science, the same compound frequently performs multiple roles (e.g., solvent, co-solvent, penetration enhancer). The claim recitation of "to solubilize" reflects an intended use, not a structural limitation. An intention or ability to perform a function does not necessarily impart patentability when the prior art discloses a composition that is capable of performing that function (see In re Schreiber, 128 F.3d 1473, 1478 (Fed. Cir. 1997)). Moreover, it would have been obvious to one of ordinary skill to use the same non-alcoholic solvent (e.g., dioxolane) for both the antifungal and the anesthetic, given the teachings that dioxolane is miscible with both water and oil phases and possesses high solubilizing capacity for a wide range of active agents. The selection of a single compatible solvent for multiple actives is a routine formulation optimization, not an inventive step.
The applicant argues that all embodiments of Besonov include alcohol in the form of glycol ethers, thus teaching away from alcohol-free systems. This argument is not persuasive. Glycol ethers are not "alcohols" in the conventional sense of volatile lower aliphatic alcohols (e.g., ethanol, isopropanol) targeted by the applicant's own claims. The prior art Tamarkin (¶[0121]) and Besonov (¶[0204]) define "alcohol-free" in terms of low levels of short-chain aliphatic alcohols, not exclusion of all oxygenated solvents. Besonov teaches that embodiments may be "substantially alcohol-free, defined as <5% final concentration" of aliphatic alcohols (¶[0204]), falling squarely within the applicant's claimed ranges (e.g., ≤15 wt%). The presence of glycol ethers in certain stock solutions does not render every embodiment alcoholic.
Furthermore, the mere existence of alcoholic embodiments does not negate the obviousness of selecting non-alcoholic ones. A reference does not teach away unless it "criticizes, discredits, or otherwise discourages" the solution claimed (see In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004)). Neither Tamarkin nor Besonov criticizes or discourages alcohol-free formulations, rather, to the contrary, both teach them as desirable for reducing skin irritation.
Moreover, Okudaira Example 1 does not identify ethanol, isopropanol, SD alcohol, or denatured alcohol among its ingredients. The claimed low-alcohol limitations therefore do not require any amount of speculative optimization. In addition, the present rejection does not merely assume that the propylene glycol present in Okudaira performs the claimed solvent function for both active agents. Mallard provides experimental solubility data establishing propylene glycol, including aqueous propylene-glycol systems, as a solvent for terbinafine hydrochloride. Campbell independently identifies propylene glycol as a solvent/delivery agent in aqueous lidocaine formulations. Thus, the secondary references provide affirmative evidence that the same solvent component already present in Okudaira is recognized as performing a solvent/solubilizing function for each active ingredient.
The applicant argues that Zhang teaches a solidified compound for a transdermal patch, not a solution, and therefore does not cure the deficiencies. This argument is not persuasive. Zhang teaches compositions for dermal delivery that include more than one pharmaceutically active agent, a solvent vehicle, and solidifying agent carriers (claims 1 and 17), wherein at least one of the drugs is selected from the group including lidocaine (claim 18) and tolnaftate (claim 19), and wherein the non-volatile solvent system includes at least one member selected from the group consisting of alkyl dioxolanes (claim 13). While Zhang's primary focus is on solidifying agents for transdermal patches, the disclosure of tolnaftate and dioxolane-containing solvent systems is relevant to the obviousness analysis.
The substitution of one known antifungal for another is a classic example of obviousness (see MPEP § 2143). Tolnaftate has been FDA-approved since 1965 for use at 1% w/w of the total composition for the effective treatment of cutaneous tinea infections. A person of ordinary skill, seeking to provide another effective antifungal agent within the alcohol-free formulation taught by Tamarkin, would be motivated to substitute the antifungals taught by Tamarkin with tolnaftate as taught by Zhang, with a reasonable expectation of success. The claimed concentrations (e.g., 1 wt% tolnaftate, 2-4 wt% dioxolane) fall within overlapping or predictable ranges disclosed in the prior art. Tolnaftate at 1% is the FDA-approved concentration. Dioxolane at 2-4% is consistent with Besonov's teachings of using >1% polar solvent for active agents (¶ [0240]) and Tamarkin's teachings of dioxolane as a polar solvent (claim 14). Adjusting concentrations within known ranges is routine optimization, not invention (see In re Aller, 220 F.2d 454, 456 (CCPA 1955). Moreover, the additional prior art cited in the rejection above establishes a compelling prima facie obviousness case.
Accordingly, the applicant’s arguments directed to the factual gaps alleged in the previous Tamarkin and Besonov or Tamarkin, Besonov, and Zhang rejections do not establish patentability over the newly applied art. The present rejections are based upon aqueous antifungal/local-anesthetic topical liquid and upon secondary references directed to the particular solvent, active-agent, alcohol-content, and dependent-claim limitations identified in each rejection, as detailed above.
Conclusion
No claims are allowed.
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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
