FINAL DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Receipt is acknowledged of amendment and remarks filed on 18 February 2026.
Claims 1-76 and 80-84 are cancelled.
Claims 77 has been amended.
Claims 85-91 remains withdrawn from consideration.
Claims 92-108 have been added.
Claims 93 and 100-107 are withdrawn from consideration for being directed towards non-elected species of oil and surfactant, respectively.
Claims 77-79, 92, 94-99 and 108 are presented for examination herein to the extent that the oil phase is medium chain triglycerides, the surfactant is non-ionic emulsifying wax and the antioxidant is butylated hydroxytoluene, e.g., applicant's elected species.
Information Disclosure Statement
The information disclosure statement (IDS) filed 12/16/2025, 04/01/2026 and 05/15/2026 have been considered by the Examiner. A signed and initialed copy of the IDS is included with the instant Office Action.
Objections and/or Rejections Withdrawn
The objection of claim 1 for reciting “Formula 1 and 12”, which is not complete, is withdrawn in view of the claim amendments filed on 18 February 2026.
Rejections Modified as Necessitated by the Claim Amendments, Maintained and Newly Made Towards New Added Claims
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.h
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 77-79, 92, 94-99 and 108 are rejected under 35 U.S.C. 103 as being unpatentable over EDELSON (US 2012/0328701 A1, publication date of 27 December 2012) in view of ZHANG (“The preparation of 3,5-dihydroxy-4-isopropylstilbene nanoemulsion and in vitro release”, International Journal of Nanomedicine, 2011:6, pages 649-657; cited in IDS filed 09/01/2023) and BAKER (US 2012/0064136 A1, published date of 15 March 2012).
Edelson is primarily directed towards nanoparticle compositions, and systems and methods utilizing them for treating disorders and/or conditions (abstract).
Regarding claims 77-79, 92, 94-95 and 97-99, Edelson discloses nanoparticle compositions useful as therapeutic agents (paragraph [0005]). Edelson discloses a nanoparticle compositions comprising an oil, an aqueous dispersion medium, a surfactant and an active agent (paragraph [0007]). Edelson discloses that the composition can comprise emulsifying wax (e.g., surfactant) (paragraph [0016]). Edelson discloses the composition demonstrates effective and efficient delivery of a therapeutic agent to the dermis without clinically significant side effects including unwanted systemic side effects (e.g., administration results in reduction of side effects in the patient) (paragraph [0029]). Edelson discloses that the composition is stable including size range and distribution of particles are maintained over a period of time including about 6 months (paragraph [0066]). Edelson discloses that the nanoparticle composition is uniform (e.g., homogeneous emulsion) and has nanoparticles where the majority including 90% (e.g., D90) have diameters below a specified size (paragraph [0076]). Edelson discloses that the oil includes medium chain triglyceride containing 6-12 carbons atoms (paragraphs [0087] and [0089]). Edelson discloses that the emulsifying wax is emulsifying wax NF (e.g., non-ionic emulsifying wax) (paragraph [0137]). Edelson discloses a composition where only the emulsifying wax is included as the emulsifying agent (e.g., surfactant) and amount of petrolatum of 2% w/w (e.g., <3% of petrolatum, ≤2% of petrolatum) (Table 2). Edelson discloses that the majority (e.g., including 90%/D90) have diameter between 10 nm and 150 nm (paragraph [0157]). The range of between 10 nm and 150 nm (e.g., between .01 and .150 µm) overlaps the range of “from about 0.1 microns to about 0.75 microns”, recited in claims 77 and 92. Thus, the range is rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. Edelson discloses that the percent of oil ranges between 0% and 50% (paragraph [0216]). The range of between 0% and 50% overlaps the range of “about 5% to about 25%” recited in claims 77 and 92. Thus, the range is rendered prima facie obvious. MPEP 2144.05 (quoted supra). Edelson discloses that the percent of the surfactant ranges between 0%-30% (paragraph [0221]). The range of between 0%-30% overlaps the range of “greater than 5% to about 15%” recited in claims 77. Thus, the range is rendered prima facie obvious. MPEP 2144.05 (quoted supra). Edelson discloses that the amount of the therapeutic agent is present at a concentration of including about 0.5%, about 0.75%, 1% and about 2% (paragraph [0233]). The concentration of about 0.5%, about 0.75%, 1% and about 2% lies inside the range of “about 0.5% to about 2%” recited in claims 77 and 92 and overlaps the range of “about 0.1% to about 1%” recited in claim 95. Thus, the range is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Edelson discloses that the aqueous dispersion medium including water can range from 0% to 99% (paragraph [0219]). Edelson discloses that the composition is for treatment of including atopic dermatitis and psoriasis (paragraph [0343]). Edelson discloses that the composition includes appropriate excipients including buffering agents, thickening agents, coloring agents, perfuming agents and preservatives (e.g., chemically stabile) can be included in the composition (paragraph [0514]). Edelson discloses that the composition are formulated as including a cream, foam or lotion (paragraph [0516]).
Regarding claim 108, Edelson discloses that excipients including buffering agents can be included in the composition (paragraph [0514]). Edelson discloses that the excipients are included in an amount of including between about 0.1% and about 1% (paragraph [0122]).
Edelson does not specifically teach that the active agent is 3,5-Dihydroxy-4-isopropyl-trans-stilbene and that the composition includes butylated hydroxytoluene (e.g., antioxidant). The deficiencies are made up for by the teachings of Zhang and Baker.
Zhang is primarily directed towards 3,5-dihydroxy-4-isopropylstilbene nanoemulsion (abstract).
Regarding claims 77 and 92, Zhang teaches that 3,5-dihydroxy-4-isopropylstilbene is a drug for atopic dermatitis and psoriasis (page 649). Zhang teaches that 3,5-dihydroxy-4-isopropylstilbene incorporated into nanoemulsion concentrate so that the solubility and skin permeability of 3,5-dihydroxy-4-isopropylstilbene, and its therapeutic efficacy could be enhanced (page 650, first column, first paragraph).
Baker is primarily directed towards methods for treating aging skin comprising administering to the subject in need thereof a nanoemulsion composition (abstract).
Regarding claims 77, 92 and 96, Baker teaches nanoemulsion administered to the skin of subject (paragraph [0027]). Baker teaches that the composition contained additional ingredients including preservatives (paragraph [0138]). Baker teaches that preservatives include butylated hydroxytoluene (paragraph [0139]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to provide a composition in the form of a nanoemulsion with nanoparticles that comprises 3,5-dihydroxy-4-isopropylstilbene as an active in an amount of including about 0.5%, about 0.75%, 1% and about 2%, an oil including medium chain triglyceride containing 6-12 carbon atoms in an amount of including between 0% and 50%, an aqueous dispersion medium including water in an amount of including from 0% to 99%, a surfactant including emulsifying wax NF (e.g., non-ionic emulsifying wax) in an amount of including between 0%-30%, and additional ingredients including a preservative further including butylated hydroxytoluene; wherein the amount of the preservative includes between about 0.1% and about 1%; wherein the composition demonstrates effective and efficient delivery of an active agent to the dermis without clinically significant side effects including unwanted systemic side effects (e.g., the administration reduces side effects in the patient); wherein if petrolatum is included the petrolatum is included in an amount of 2% w/w; wherein the majority of the nanoparticles including 90% have a diameter between 10 nm and 150 nm; wherein the composition is administered to patient. The person of ordinary skill in the art would have been motivated to make those modifications because 3,5-dihydroxy-4-isopropylstilbene is an active for treating atopic dermatitis or psoriasis (e.g., same as Edelson actives) that can benefit from the composition of Edelson that is suitable for formulation as a nanoemulsion; and suitable preservatives for topical nanoemulsions include butylated hydroxytoluene, as taught by Baker, which one of ordinary skill in the art would expect to be suitable as a preservative to include into the nanoemulsion of Edelson. The person of ordinary skill in the art would have reasonably expected success because Edelson discloses a nanoparticle compositions comprising an oil, an aqueous dispersion medium, a surfactant and an active agent (paragraph [0007]). Edelson discloses that the composition can comprise emulsifying wax (e.g., surfactant) (paragraph [0016]). Edelson discloses the composition demonstrates effective and efficient delivery of a therapeutic agent to the dermis without clinically significant side effects including unwanted systemic side effects (e.g., administration results in reduction of side effects in the patient) (paragraph [0029]). Edelson discloses that the composition is stable including size range and distribution of particles are maintained over a period of time including about 6 months (paragraph [0066]). Edelson discloses that the nanoparticle composition is uniform (e.g., homogeneous emulsion) and has nanoparticles where the majority including 90% (e.g., D90) have diameters below a specified size (paragraph [0076]). Edelson discloses that the oil includes medium chain triglyceride containing 6-12 carbons atoms (paragraphs [0087] and [0089]). Edelson discloses that the emulsifying wax is emulsifying wax NF (e.g., non-ionic emulsifying wax) (paragraph [0137]). Edelson discloses a composition where only the emulsifying wax is included as the emulsifying agent (e.g., surfactant) and amount of petrolatum of 2% w/w (e.g., <3% of petrolatum, ≤2% of petrolatum) (Table 2). Edelson discloses that the majority (e.g., including 90%/D90) have diameter between 10 nm and 150 nm (paragraph [0157]). The range of between 10 nm and 150 nm (e.g., between .01 and .150 µm) overlaps the range of “from about 0.1 microns to about 0.75 microns”, recited in claims 77 and 92. Thus, the range is rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. Edelson discloses that the percent of oil ranges between 0% and 50% (paragraph [0216]). The range of between 0% and 50% overlaps the range of “about 5% to about 25%” recited in claims 77 and 92. Thus, the range is rendered prima facie obvious. MPEP 2144.05 (quoted supra). Edelson discloses that the percent of the surfactant ranges between 0%-30% (paragraph [0221]). The range of between 0%-30% overlaps the range of “greater than 5% to about 15%” recited in claims 77. Thus, the range is rendered prima facie obvious. MPEP 2144.05 (quoted supra). Edelson discloses that the amount of the therapeutic agent is present at a concentration of including about 0.5%, about 0.75%, 1% and about 2% (paragraph [0233]). The concentration of about 0.5%, about 0.75%, 1% and about 2% lies inside the range of “about 0.5% to about 2%” recited in claims 77 and 92 and overlaps the range of “about 0.1% to about 1%” recited in claim 95. Thus, the range is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Edelson discloses that the aqueous dispersion medium including water can range from 0% to 99% (paragraph [0219]). Edelson discloses that the composition is for treatment of including atopic dermatitis and psoriasis (paragraph [0343]). Edelson discloses that the composition includes appropriate excipients including buffering agents, thickening agents, coloring agents, perfuming agents and preservatives (e.g., chemically stabile) can be included in the composition (paragraph [0514]). Edelson discloses that the composition are formulated as including a cream, foam or lotion (paragraph [0516]). Zhang teaches that 3,5-dihydroxy-4-isopropylstilbene is a drug for atopic dermatitis and psoriasis (page 649). Zhang teaches that 3,5-dihydroxy-4-isopropylstilbene incorporated into nanoemulsion concentrate so that the solubility and skin permeability of 3,5-dihydroxy-4-isopropylstilbene, and its therapeutic efficacy could be enhanced (page 650, first column, first paragraph). Baker teaches that preservatives include butylated hydroxytoluene (paragraph [0139]).
Regarding the recitation “composition is chemically and physically stable when stored at standard ICH conditions for up to 6 months” (e.g., claim 92), although the combination of Edelson, Zhang and Baker, do not specifically teach that the composition is chemically and physically stable when stored at standard ICH conditions for up to 6 months, the claimed method of administering to a patient a chemically and physically stable topical pharmaceutical oil-in-water emulsion composition comprising: an active ingredient that is 3,5-dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof in an amount of about 0.5% to about 2% by weight, based on the total weight of the composition, an oil phase in an amount of about 5% to about 25% by weight, based on the total weight of the composition, wherein the oil phase is selected from the group consisting of a fatty acid, an ester, an ester of glycerin a fatty alcohol, a wax, a sterol, a siloxane, a silane, a hydrocarbon, an essential oil, a vegetable oil, a mineral oil, an animal oil, an edible oil and mixtures thereof, a water phase in an amount of about 30% to about 80% by weight, based on the total weight of the composition, a total surfactant content in an amount of greater than 5% to about 15% by weight, based on the total weight of the composition, wherein the total surfactant content consists of one or more non-ionic surfactants, and a dermatologically acceptable excipient selected from the group consisting of an antioxidant, a pH adjusting agent, a preservative, a co-solvent, a chelating agent, a penetration enhancer, a humectant, a viscosity building agent, a fragrance, a colorant, and combinations thereof; wherein the oil phase contains <3% of petrolatum; wherein a D90 of an average droplet size of the oil phase is from about 0.1 to about 0.75 microns (paragraphs [0029], [0066], [0087-0089], [0122], [0137], [0157], [0216], [0219], [0221], [0233], [0343], and [0514], and Table 2 of Edelson; page 649 of Zhang; and paragraphs [0138-0139] of Baker) appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Thus, the claimed invention as a whole is clearly prima facie obvious over the teachings of the prior art.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 95 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 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 95 which depends on claim 92, recites “from about 0.1% to about 1% by weight” of the active ingredient which is outside the range of “about 0.5% to about 2% by weight” recited in claim 92. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Applicant’s arguments will be addressed as they pertain to the new grounds of rejection above.
Applicant argues on pages 10-11 that a person of ordinary skill in the art would not have found it obvious to combine 3,5-dihydroxy-4-isopropylstilbene with Edelson’s formulation to reduce side effects as instantly claimed with a reasonable expectation of success based on the unpredictability of formulating homogenous emulsion composition using 3,5-dihydroxy-4-isopropylstilbene as the active. Applicant argues that POSITA would recognize that the physicochemical properties of an active ingredient and excipients must be considered when formulating topical compositions. Applicant argues that active ingredient and each excipient, along with their interactions, may impact quality attributes such as viscosity, oil droplet size, pH, physical stability, chemical stability, and skin penetration. Applicant argues that although 3,5-dihydroxy-4-isopropylstilbene may treat similar indications as taught by Edelson, a POSITA would not have any reasonable expectation of success form formulating a stable, suitable formulation with a different active than any of the actives taught by Edelson based on structure and function. Applicant argues that evidence in the instant application shows that 3,5-dihydroxy-4-isopropylstilbene creates problems for formulating a stable emulsion composition that demonstrates that the prior art modification, as proposed by the Office, would not have a reasonable expectation of success. Applicant argues on page 11 that Edelson focuses on nanoparticle compositions, with particular emphasis on botulinum toxin, a large biologic agent structurally and functionally distinct from 3,5-dihydroxy-4-isopropylstilbene. Applicant argues that Edelson does not teach 3,5-dihydroxy-4-isopropylstilbene, not does Edelson address the formulation challenges posed by amphiphilic small-molecule active ingredients. Applicant argues that as discussed in the instant application, 3,5-dihydroxy-4-isopropylstilbene may destabilize emulsions by interactions at the surfactant interface. Applicant notes that the paragraph [0048] of the instant specification which states "the active ingredient was believed to cause the emulsion destabilization by perhaps interacting at the surfactant interface (liquid crystals)" and that "the non-uniform emulsions illustrated in Figure 1 were determined to be dependent on the concentration of the active ingredient." Applicant argues that due to 3,5-dihydroxy-4-isopropylstilbene’s amphiphilic nature, it increases the packing parameters of the emulsion and thus destabilizes the emulsion. Applicant argues that Formulation 10 which does not include 3,5-dihydroxy-4-isopropylstilbene was stable and homogenous, while formulations 11-14 that contains 0.1%-2% 3,5-dihydroxy-4-isopropylstilbene were all unstable and non-homogenous. Applicant argues that Edelson fails to appreciate or predict solving the challenges of formulations that include 3,5-dihydroxy-4-isopropylstilbene. Applicant points to the declaration of Dr. Marc Brown, on page 12, which describes that POSITA attempting to formulate 3,5-dihydroxy-4-isopropylstilbene in a stable and non-irritating composition for the claimed method would not look to formulations of active ingredients that are completely dissimilar in both structure and physicochemical properties. Applicant argues on page 13 that Baker does not cure the deficiencies of Edelson. Applicant argues on page 16 to 17 that POSITA would not simply substitute or combine one active ingredient for another when the two have distinct physicochemical properties, such as the botulinum toxin of Edelson and the 3,5-dihydroxy-4-isopropylstilbene of Zhang because the formulations are complex and unpredictable. Applicant argues that looking to Edelson in view of Baker and Zhang, a POSITA would have no indication of which elements to choose to arrive at the claimed compositions and there would be no reasonable expectation of success.
Applicant's arguments filed on 18 February 2026 have been fully considered but they are not persuasive. In response, Edelson discloses that the nanoemulsion contain any known therapeutic agent and/or independently active biologically active agent (paragraph [0005]). Edelson discloses methods and compositions for including psoriasis and atopic dermatitis (paragraph [0343]). Edelson discloses a nanoparticle compositions comprising an oil, an aqueous dispersion medium, a surfactant and an active agent (paragraph [0007]). Edelson discloses that the composition can comprise emulsifying wax (e.g., surfactant) (paragraph [0016]). Edelson discloses the composition demonstrates effective and efficient delivery of a therapeutic agent to the dermis without clinically significant side effects including unwanted systemic side effects (e.g., administration results in reduction of side effects in the patient) (paragraph [0029]). Edelson discloses that the composition is stable including size range and distribution of particles are maintained over a period of time including about 6 months (paragraph [0066]). Edelson discloses that the nanoparticle composition is uniform (e.g., homogeneous emulsion) and has nanoparticles where the majority including 90% (e.g., D90) have diameters below a specified size (paragraph [0076]). Edelson discloses that the oil includes medium chain triglyceride containing 6-12 carbons atoms (paragraphs [0087] and [0089]). Edelson discloses that the emulsifying wax is emulsifying wax NF (e.g., non-ionic emulsifying wax) (paragraph [0137]). Edelson discloses a composition where only the emulsifying wax is included as the emulsifying agent (e.g., surfactant) and amount of petrolatum of 2% w/w (e.g., <3% of petrolatum, ≤2% of petrolatum) (Table 2). Edelson discloses that the majority (e.g., including 90%/D90) have diameter between 10 nm and 150 nm (paragraph [0157]). The range of between 10 nm and 150 nm (e.g., between .01 and .150 µm) overlaps the range of “from about 0.1 microns to about 0.75 microns”, recited in claims 77 and 92. Thus, the range is rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. Edelson discloses that the percent of oil ranges between 0% and 50% (paragraph [0216]). The range of between 0% and 50% overlaps the range of “about 5% to about 25%” recited in claims 77 and 92. Thus, the range is rendered prima facie obvious. MPEP 2144.05 (quoted supra). Edelson discloses that the percent of the surfactant ranges between 0%-30% (paragraph [0221]). The range of between 0%-30% overlaps the range of “greater than 5% to about 15%” recited in claims 77. Thus, the range is rendered prima facie obvious. MPEP 2144.05 (quoted supra). Edelson discloses that the amount of the therapeutic agent is present at a concentration of including about 0.5%, about 0.75%, 1% and about 2% (paragraph [0233]). The concentration of about 0.5%, about 0.75%, 1% and about 2% lies inside the range of “about 0.5% to about 2%” recited in claims 77 and 92 and overlaps the range of “about 0.1% to about 1%” recited in claim 95. Thus, the range is rendered prima facie obvious. See MPEP 2144.05 (quoted supra). Edelson discloses that the aqueous dispersion medium including water can range from 0% to 99% (paragraph [0219]). Edelson discloses that the composition is for treatment of including atopic dermatitis and psoriasis (paragraph [0343]). Edelson discloses that the composition includes appropriate excipients including buffering agents, thickening agents, coloring agents, perfuming agents and preservatives (e.g., chemically stabile) can be included in the composition (paragraph [0514]). Zhang teaches that 3,5-dihydroxy-4-isopropylstilbene is for including atopic dermatitis and psoriasis (page 649). Zhang teaches that 3,5-dihydroxy-4-isopropylstilbene incorporated into nanoemulsion concentrate so that the solubility and skin permeability of 3,5-dihydroxy-4-isopropylstilbene, and its therapeutic efficacy could be enhanced (page 650, first column, first paragraph). Baker teaches nanoemulsion administered to the skin of subject (paragraph [0027]). Baker teaches that he composition contained additional ingredients including preservatives (paragraph [0138]). Baker teaches that preservatives include butylated hydroxytoluene (paragraph [0139]). Thus, from the disclosure of Edelson and the teachings of Zhang and Baker, it would have been prima facie obvious for one of ordinary skill in the art to substitute in 3,5-dihydroxy-4-isopropylstilbene as the active in the composition of Edelson which is a stable nanoemulsion with ingredients including preservatives to maintain the composition’s stability and can deliver the active without clinically significant side effects of unwanted systemic side effects, in order to provide 3,5-dihydroxy-4-isopropylstilbene for treating including atopic dermatitis and psoriasis without clinically significant side effects of unwanted systemic side effects. The person of ordinary skill in the art would have expected success because Edelson discloses that the nanoemulsion composition of Edelson can include any know active and even a combination of different actives and Zhang teaches that 3,5-dihydroxy-4-isopropylstilbene can be in a composition in the form of a nanoemulsion. Applicant is reminded that obviousness does not require absolute predictability, however, at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976). See MPEP 2143.02(II).
Applicant argues at the end of page 12 to beginning of page 13 that the prior art combination would have no reason to modify Edelson to develop a formulation for use in the instant claims and would have little guidance as to which ingredients to choose. Applicant argues that they would have no indication of which amounts of which ingredients would arrive at a stable, homogenous topical formulation of 3,5-dihydroxy-4-isopropylstilbene for use in the instantly claimed method. Applicant argues that none of the cited prior art discuss the negative effects of petrolatum in formulations of the instant claims. Applicant argues that data in the instant specification at paragraph [0311] show that including more than 3% petrolatum caused formulations to be unstable.
In response, Edelson discloses that the oil includes medium chain triglyceride containing 6-12 carbons atoms (paragraphs [0087] and [0089]). Zhang teaches that DHPS is almost insoluble in liquid paraffin (e.g., mineral oil) and did not choose liquid paraffin as the oil phase (page 652, second column, first paragraph). POSITA would have been motivated to select other oil phases other than liquid paraffin as the oil phase and selected including medium chain triglyceride as the oil phase. Edelson does not require petrolatum as the oil phase but for the compositions that did have petrolatum (e.g., Table 2 and 7 of Edelson), Edelson included 2% w/w of petrolatum which would not have the problem of stability since it is less than 3%. Thus, if POSITA includes petrolatum in the composition the amount of petrolatum included would have been 2% w/w in light of the disclosure of Edelson.
Applicant argues on page 13 to 14 that Zhang teaches away from larger droplet sizes such as a d90 of about 0.1 to about 0.75 microns and instantly claimed. Applicant argues that Zhang states that droplet size has a direct influence on the behavior of the nanoemulsion, especially the bioavailability of the delivered drug and that the smaller the droplet size in the nanoemulsion, the more favorable the expected result for in vivo application. Applicant argues that the droplet size of the instant claims are much larger than the droplet size of Zhang. Applicant argues that Zhang states that smaller droplet sizes are necessary for stability and bioavailability. Applicant argues that Zhang wants systemic exposure while the instantly claimed method reduces side effects.
In response, Edelson discloses that the composition can comprise emulsifying wax (e.g., surfactant) (paragraph [0016]). Edelson discloses the composition demonstrates effective and efficient delivery of a therapeutic agent to the dermis without clinically significant side effects including unwanted systemic side effects (e.g., administration results in reduction of side effects in the patient) (paragraph [0029]). Edelson discloses that the composition is stable including size range and distribution of particles are maintained over a period of time including about 6 months (paragraph [0066]). Edelson discloses that the nanoparticle composition is uniform (e.g., homogeneous emulsion) and has nanoparticles where the majority including 90% (e.g., D90) have diameters below a specified size (paragraph [0076]). Edelson discloses that the majority (e.g., including 90%/D90) have diameter between 10 nm and 150 nm (paragraph [0157]). The range of between 10 nm and 150 nm (e.g., between .01 and .150 µm) overlaps the range of “from about 0.1 microns to about 0.75 microns”. Thus, one of ordinary skill in the art would use the nanoparticle sizes of Edelson in order to obtain a nanoemulsion of 3,5-dihydroxy-4-isopropylstilbene that is stable, uniform and provides effective and efficient delivery of a therapeutic agent to the dermis without clinically significant side effects including unwanted systemic side effects as taught by Edelson.
Thus, for the reasons of record and for the reasons presented above claims 77-79, 92, 94-99 and 108 are rejected under 35 U.S.C. 103(a).
Conclusion and Correspondence
No claims are allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN P NGUYEN whose telephone number is (571)270-5877. The examiner can normally be reached Monday-Friday 10am-6pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on (571) 272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOHN P NGUYEN/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/
Primary Examiner, Art Unit 1600
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