DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7 May 2026 has been entered.
Status of the Claims
Claims 1-4, 27-31, 44, 46 and 52-53 are pending.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 7 May 2026 and 23 June 2026 were filed after the mailing date of the final Office action on 8 December 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Declaration under 37 C.F.R. 1.132
The declaration under 37 CFR 1.132 filed 7 May 2026 is insufficient to overcome the rejection of claims 1-4, 27-31, 44, 46 and 52-53 based upon Blanchard (WO 2019/014380 A1) as set forth in the last Office action because: the declaration does not compare against the closest prior art. Blanchard discloses formulations comprising ketoprofen, which is an NSAID and is structurally similar ibuprofen. The declaration provides a comparison of formulations comprising ibuprofen against formulations comprising histamine dihydrochloride, which is not an NSAID and does not share structural similarity with ibuprofen. Therefore, the declaration is not a sufficient comparison with the closest prior art. Also, Blanchard teaches topical formulations comprising an NSAID as the active agent, and the NSAID preferably includes ibuprofen (Table IV; Claim 1). Therefore, it would have been prima facie obvious to prepare the compositions according to Blanchard, wherein the NSAID is ibuprofen.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-4, 27-31, 44, 46 and 52-53 are rejected under 35 U.S.C. 103 as being unpatentable over Blanchard (WO 2019/014380 A1).
Regarding instant claims 1, 4 and 52-53, Blanchard teaches topical delivery systems for active pharmaceutical ingredients (pg. 4, ln. 4). Blanchard teaches that the topical delivery systems comprise at least one active pharmaceutical ingredient (API), a penetration enhancer, a gelling agent (i.e. thickener), and an aqueous carrier. The topical formulations may further comprise a neutralizing agent to adjust pH (i.e., buffer), a chelating agent (i.e., sequestering agent), a preservative, a fragrance, and optionally, a coloring agent (pg. 4, ln. 11-15; pg. 12, ln. 29 to pg. 13, ln. 7; Claim 1). Blanchard further teaches that the active pharmaceutical ingredients include NSAIDs, including ibuprofen (pg. 4, ln. 16-17; pg. 6, ln. 8-19; pg. 12, ln. 7-10; Table IV; Claim 1).
Blanchard teaches that the API is a NSAID present in a weight percent of between 0.1 and 25.0, the penetration enhancer is diethylene glycol monoethyl ether (DEGEE) present in a weight percent of between 3.0 and 30, and the gelling agent is a carbomer polymer (i.e., polymer of acrylic acid lightly crosslinked with allyl ethers of polyalcohols) present in a weight percent of between 0.3 and 3.5, and further optionally comprises a neutralizing agent, a chelating agent, a preservative, and a fragrance, wherein the neutralizing agent preferably is present in a weight percent of between 0.2 and 2.5, the chelating agent is present in a weight percent of between 0.04 and 0.20, the preservative is present in a weight percent of between 0.01 and 2.5, and the fragrance is present in a weight percent of between 0.1 and 0.8, and the neutralizing agent preferably comprises triethanolamine and the chelating agent comprises disodium EDTA dihydrate (pg. 6, ln. 3-6, 8-19; pg. 26, ln. 29 to pg. 30, ln. 26; pg. 30, ln. 28 to pg. 31, ln. 11).
Blanchard teaches that the preservative preferably includes 2-phenoxyethanol (pg. 5, ln. 23 to pg. 6, ln. 1; pg. 22, ln. 1-2, 10; Claim 8). Blanchard further teaches that since, in some embodiments, water constitutes a major component of the formulation, deionized water should be used to minimize the impact of any ions on the stability of the formulation (pg. 32, ln. 23-25). See also Table V.
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to prepare topical delivery systems according to Blanchard, wherein the system comprises 0.1-25 wt.% ibuprofen, 3-30 wt.% diethylene glycol monoethyl ether, 0.3-3.5 wt.% cross-linked polyacrylic acid polymer, 0.2-2.5 wt.% triethanolamine, 0.01-2.5 wt.% phenoxyethanol, 0.04-0.2 wt.% disodium EDTA dihydrate, and water. Also, it would have been obvious for a person of ordinary skill in the art to adjust the concentrations within a reasonable amount outside the ranges taught by Blanchard in order to determine through routine optimization the workable ranges of components. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. See MPEP 2144.05.
Regarding instant claims 2-3, Blanchard further teaches that the term "topical" refers to a semisolid preparation (e.g., ointment, cream, or gel) to be applied onto a mammalian body surface to provide a desired therapeutic effect (e.g., pain relief) locally, at or beneath the application site (pg. 10, ln. 23-25).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to prepare topical delivery systems for active pharmaceutical ingredients according to Blanchard, wherein the API is ibuprofen, the formulation comprises DEGEE as a penetration enhancer, a carbomer polymer as a thickening agent, triethanolamine as a buffer/neutralizing agent, disodium EDTA dihydrate as a sequestering agent, 2-phenoxyethanol as a preservative and water, in amounts that are within the scope of the instant claims, and in the form of an ointment, cream or gel.
A person of ordinary skill in the art would have a reasonable expectation of success because Blanchard teaches transdermal formulations comprising an API, a penetration enhancer, a thickening agent, a buffering agent, a sequestering agent, a preservative, and deionized water, wherein the components are present in amounts that are within or overlap the instantly claimed ranges, and the claimed compounds are taught as suitable for use in the formulations of Blanchard.
Regarding the lag effect of claim 1, Blanchard teaches that topical formulations can achieve LETD in a variety of ways, such as by the use of occlusion, the addition of penetration-enhancing agents, and the use of different molecular entities than those used in equivalent oral formulations. One mechanism whereby LETD can occur is via the formation of intracutaneous depots in the upper layers of the epidermis. Conceivably, these depots may allow a drug to largely avoid the blood capillaries present at the epidermal-dermal junction in the skin, thereby minimizing any uptake into the systemic circulation. While not wishing to be bound by theory, it is believed that some penetration enhancers, such as diethylene glycol monoethyl ether (DEGEE), promote the formation of intracutaneous depots of API and thereby can achieve LETD. Penetration enhancers that can promote depot formation are ideally suited for topical therapies since they increase the concentration of the drug locally, i.e., at the site of application, but inhibit the drug from being absorbed into the systemic circulation. One example compound which exhibits this property is the cosolvent DEGEE (distributed under the trademark Transcutol® P) (pg. 18, ln. 7-21). A depot for drug-solvent complexes enables slow and localized diffusion of the API over time (pg. 25, ln. 10-17).
Blanchard does not explicitly teach the lag effect instantly claimed. However, Blanchard teaches topical formulations comprising components that are within the scope of the instant claims. In the absence of evidence to the contrary the formulations of Blanchard would have the instantly claimed lag effect.
The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Regarding instant claims 27-31, Blanchard teaches that the penetration enhancer preferably comprises diethylene glycol monoethyl ether (DEGEE or Transcutol) (pg. 18, ln. 15-21; pg. 21, ln. 2-9; pg. 23, ln. 30 to pg. 26, ln. 27; Table V; Claim 4), the thickening agent comprises carbomers (pg. 26, ln. 28 to pg. 30, ln. 26; Table V; Claim 5), the pH modifier comprises triethanolamine (pg. 22, ln. 20-29; pg. 30, ln. 27 to pg. 32, ln. 17; Table V; Claim 8), the sequestering agent comprises disodium EDTA dihydrate (pg. 22, ln. 12-19; pg. 32, ln. 18-27; Table V; Claim 8), and the preservative comprises 2-phenoxyethanol (pg. 22, ln. 1-11; pg. 32, ln. 28 to pg. 33, ln. 6; Table V; Claim 8).
Thus, it would have been prima facie obvious for a person of ordinary skill in the art to prepare transdermal formulations according to Blanchard comprising ibuprofen, diethylene glycol monoethyl ether penetration enhancer, carbomer thickening agent, triethanolamine pH modifier/buffer, phenoxyethanol preservative, disodium EDTA dihydrate sequestering agent, and water, within the concentrations taught by Blanchard. Also, it would have been obvious to prepare said compositions in the form of an ointment, cream or gel.
Regarding instant claims 44 and 46, Blanchard teaches formulations that can be used to treat a variety of musculoskeletal conditions by providing excellent relief of pain (pg. 4, ln. 27-29; pg. 12, ln. 20; pg. 33, ln. 16; pg. 35, ln. 7-9).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to treat pain with the compositions according to Blanchard in view of the teaching that formulations can be used to treat a variety of musculoskeletal conditions by providing excellent relief of pain.
Response to Arguments
Applicant's arguments filed 7 May 2026 have been fully considered but they are not persuasive. Applicant argues that Blanchard discloses more than 100 possible APIs for its compositions, along with myriad possible excipients across broad categories such as penetration enhancers, gelling agents, preservatives, chelating agents, neutralizing agents, fragrances, and coloring agents. Despite this broad disclosure, Blanchard's examples only exemplify formulation of a single API, ketoprofen. Notably, these examples include only 5.0% to 6.7% w/w of Transcutol® P as the penetration enhancer. Nothing in Blanchard's broad disclosure or their specific examples would have led a person of ordinary skill to make the many necessary selections from the many options presented in Blanchard to select each of the components recited in the pending claims and formulate them together in the recited amounts at the particular concentration ranges recited in the claims (e.g., about 18% w/w to about 25% w/w penetration enhancer), as required to arrive at the presently claimed ibuprofen formulations.
The examiner respectfully argues that Blanchard specifically states, “In another preferred embodiment the API is a nonsteroidal anti-inflammatory drug (NSAID) present in a weight percent between 0.1 and 25.0, the penetration enhancer is DEGEE, present in a weight percent between 3.0 and 30, and the gelling agent is a carbomer polymer present in a weight percent between 0.3 and 3.5, and further optionally comprises a neutralizing agent, a chelating agent, a preservative, and a fragrance, wherein the neutralizing agent preferably is present in a weight percent of between 0.2 and 2.5, the chelating agent is present in a weight percent of between 0.04 and 0.20, the preservative is present in a weight percent of between 0.01 and 2.5, and the fragrance is present in a weight percent of between 0.1 and 0.8, and the neutralizing agent preferably comprises triethanolamine and the chelating agent comprises disodium EDTA dihydrate. In such preferred embodiment, the composition has a pH between 4.0 and 9.0, preferably a pН between 4.4 and 5.0” (pg. 6, ln. 8-19). Blanchard further teaches that the preservative preferably includes 2-phenoxyethanol (pg. 5, ln. 23 to pg. 6, ln. 1; pg. 22, ln. 1-2, 10; Claim 8). Blanchard further teaches that since, in some embodiments, water constitutes a major component of the formulation, deionized water should be used to minimize the impact of any ions on the stability of the formulation (pg. 32, ln. 23-25). The NSAID preferably includes ibuprofen (Table IV; Claim 1).
Blanchard further teaches examples of four compositions comprising ketoprofen (an NSAID), DEGEE (transcutol), a carbomer (Ultrez), triethanolamine, disodium EDTA dihydrate, a preservative (Paragon III), and deionized water (Table V).
Therefore, Blanchard provides motivation for preparing a topical delivery system comprising between 0.1 and 25.0 wt.% of an NSAID, between 3.0 and 30 wt.% of DEGEE, between 0.3 and 3.5 wt.% of a carbomer polymer, between 0.2 and 2.5 wt.% of triethanolamine, between 0.04 and 0.20 wt.% of disodium EDTA dihydrate, between 0.04 and 0.20 wt.% of 2-phenoxyethanol, and water.
Applicant further argues that the Scarlata Declaration provides evidence of the criticality of the recited penetration enhancer concentration range, and also presents other experimental data supporting non-obviousness, as explained by Mr. Scarlata, during the development of the ibuprofen formulation described in Example 43, "18% w/w of the penetration enhancer was the working concentration that was selected due to the solubility of ibuprofen in the formulation."
The examiner respectfully argues that the declaration is not sufficient to overcome the instant rejection for the reasons discussed above. Notably, the declaration does not compare against formulations comprising ketoprofen, as disclosed by Blanchard.
Applicant further argues that he claimed lag effect and Blanchard's depot effect are different phenomena and are not inherently related to each other. Applicant further argues that even if Blanchard's formulations are assumed to exhibit some depot effect (which the record does not support), the demonstration of a depot effect would not render obvious a formulation as claimed, that exhibits a lag effect as recited in claim 1.
The examiner respectfully argues that the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). As discussed above, Blanchard provides motivation for a person of ordinary skill in the art to prepare topical formulations comprising ibuprofen in the place of ketoprofen as the NSAID active agent.
Applicant respectfully disagrees with this rationale as applied to the pending claims, which appears to invoke the doctrine of inherency despite Blanchard's failure to render obvious a formulation having the specification components and amounts thereof recited in the claims.
The examiner respectfully argues that Blanchard specifically states, “In another preferred embodiment the API is a nonsteroidal anti-inflammatory drug (NSAID) present in a weight percent between 0.1 and 25.0, the penetration enhancer is DEGEE, present in a weight percent between 3.0 and 30, and the gelling agent is a carbomer polymer present in a weight percent between 0.3 and 3.5, and further optionally comprises a neutralizing agent, a chelating agent, a preservative, and a fragrance, wherein the neutralizing agent preferably is present in a weight percent of between 0.2 and 2.5, the chelating agent is present in a weight percent of between 0.04 and 0.20, the preservative is present in a weight percent of between 0.01 and 2.5, and the fragrance is present in a weight percent of between 0.1 and 0.8, and the neutralizing agent preferably comprises triethanolamine and the chelating agent comprises disodium EDTA dihydrate. In such preferred embodiment, the composition has a pH between 4.0 and 9.0, preferably a pН between 4.4 and 5.0” (pg. 6, ln. 8-19). Blanchard further teaches that the preservative preferably includes 2-phenoxyethanol (pg. 5, ln. 23 to pg. 6, ln. 1; pg. 22, ln. 1-2, 10; Claim 8). Blanchard further teaches that since, in some embodiments, water constitutes a major component of the formulation, deionized water should be used to minimize the impact of any ions on the stability of the formulation (pg. 32, ln. 23-25). The NSAID preferably includes ibuprofen (Table IV; Claim 1).
Therefore, Blanchard provides sufficient motivation to prepare a composition comprising the instantly claimed components within the instantly claimed concentration ranges. Following the suggestions of Blanchard, a person of ordinary skill in the art would have been motivated to prepare compositions within the scope of the instant claims.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nathan W Schlientz whose telephone number is (571)272-9924. The examiner can normally be reached 10:00 AM to 6:00 PM, Monday through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached on (571) 272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.W.S/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
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