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 .
Status of the Claims
Claims 1-4, 27-31, 44 and 46 are pending.
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 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Blanchard (WO 2019/014380 A1).
Regarding instant claims 1 and 4, 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.
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.
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 21 August 2025 have been fully considered but they are not persuasive. Applicant argues that Blanchard provides a long list of more than 100 possible APIs for its compositions and mentions a myriad of possible excipients across broad categories such as penetration enhancers, gelling agents, preservatives, chelating agents, neutralizing agents, fragrances, and coloring agents. However, Blanchard's examples only exemplify use of a single API, ketoprofen, which is less lipophilic than and structurally distinct from ibuprofen. Nothing in Blanchard's broad disclosure 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 recited components and formulate them together in the recited amounts at the particular concentration ranges recited in the claims, 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 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.
In response to applicant's argument that it is only the Applicant's own disclosure which teaches ibuprofen-containing formulations that exhibit a 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).
Conclusion
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 (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nathan W Schlientz whose telephone number is (571)272-9924. The examiner can normally be reached 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
/Mina Haghighatian/Primary Examiner, Art Unit 1616