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 Application
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/23/2026 has been entered.
Receipt of Applicants’ Arguments, Remarks and amended claims filed on 03/23/2026 is acknowledged.
Claims 1-4, 7-16,18-26 and 28-47 are pending.
Claims 2, 5, 6, 17, 27, and 48-83 have been have been cancelled.
Claim 1 is amended.
Claims 1, 3-4, 7-16, 18-26 and 28-47 are pending and under examination in this application.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-4, 7-16, 18-26, and 28-47 are rejected under 35 U.S.C. 103 as being unpatentable over Self-microemulsifying drug-delivery system for improved oral bioavailability of probucol: preparation and evaluation (hereinafter the article is referred as Sha) in view of Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies (hereinafter the article is referred as Pouton), Optimized formulation of solid self-microemulsifying sirolimus delivery systems and further (hereinafter the article is referred as Cho), (WO 2018/185780 A1) (hereinafter the reference is referred as Olene) and further in view of Enclosing materials in natural transport system (hereinafter the reference is referred as Edwards).
Sha teaches lipid-based formulation, comprising oils, surfactant dispersions, self-emulsifying formulations, emulsions, liposomes and Self-microemulsifying drug-delivery systems are mixtures of drugs, lipids, surfactants, and cosurfactants, which form a fine oil-in-water (O/W) microemulsion with a droplet size of less than 100 nm when exposed to aqueous media under conditions of gentle agitation or digestive motility that would be encountered in the gastrointestinal (GI) tract (page 705, last ¶). Moreover, Sha discloses that self-microemulsifying drug-delivery system (SMEDDS) has recently emerged as one of the most interesting approaches to improve oral absorption for poorly water-soluble drugs (page 705, last ¶). Furthermore, Sha discloses the advantages of SMEDDS include ease of production, enhanced solvent capacity, increased stability, and the potential to administer the final product as an oral soft gelatin capsule (page 705, last line to page 706, left column, lines 1-3). Furthermore, Sha discloses the commercially available formulation cyclosporine is a microemulsion preconcentrate with improved oral bioavailability and reduced inter and intra subject variability compared to the original crude emulsion product, SandimmuneTM, and similar lipid-based formulations for human immunodeficiency virus (HIV) protease inhibitors, saquinavir, ritonavir, and amprenavir (706, left column, 1st ¶), wherein all of these drugs are poorly water soluble.
Sha fails to specifically teach phosphatidylcholine in oil-based emulsion.
Pouton teaches Lipid-based delivery systems range from simple oil solutions
to complex mixtures of oils, surfactants, co-surfactants and cosolvents wherein the mixtures are typically self-dispersing systems often referred to as self-emulsifying drug delivery systems (SEDDS) or self-microemulsifying drug delivery systems (SMEDDS) and are often thermodynamically stable (page 1, left column, Intro ¶).
Pouton fails to specifically teach terpene oil chosen from turmeric oil.
Cho teaches optimization of solid self-microemulsifying drug delivery system (SMEDDS) formulation for sirolimus to enhance its solubility, stability, and bioavailability (page 1, ¶ Background).
Cho fails to specifically teach turmeric oil, terpene oil, citrus oil in the emulsion oil system.
Olene teaches options for increasing the water-solubility of hydrophobic molecule (curcumin) comprising use of an emulsifier in manufacture of self-emulsifying drug delivery systems (SEDDS) (page 2, ¶ 4).
Olene fails to specifically teach propolis, zinc acetate, hesperetin, luteolin, spearmint oil, milk thistle extract, Andrographis, artemisinin, and hemp oil in SMEDDS. However, it would have been obvious to a person having ordinary skill in the art (PHOSITA) to select and add any of the water-soluble, alcohol-soluble or oil-soluble species with the desired properties in an ingestible and edible SMEDDS composition and adjust their customary proportions to optimize the desired result effective variables.
Edwards teaches edible composition comprising emulsions and edible materials in transport system and in some embodiments, the edible substance are encapsulated (¶ 0003-0004 and ¶ 0012). Furthermore, Edwards discloses in some embodiments, edible particles are selected from the group consisting of particles of a food, particles of an energy supplement, particles of a dietary supplement, particles of confection, particles of nutraceuticals, particles of pharmaceutical, particles of metabolic intermediate of a pharmaceutical, particles of metabolic by-product of a pharmaceutical, and combinations thereof (¶ 0016). Notably, Edwards discloses the transport systems contain and protect ingestible/edible substances, for example, as food, within edible or biodegradable membranes (matrix or matrices) and/or shells and the edible membranes/shells of the transport systems can be formed from various substances allowing different compositions to be transported and consumed (¶ 0043). For example, in some embodiments, it is contemplated herein that micelles are formed within membranes and between membrane layers and/or between the inner membrane and the edible or potable substance. Micelles can alter the taste experience or mouth feel for the final encased product. Additionally, micelles engineered into the final membrane coated product may contain other ingestible including sweeteners, flavors (fruits, herbs and spices, etc.), herbal extracts, energy supplements, dietary supplements, pharmaceuticals, over the counter drugs, sleep aids, appetite suppressants, weight gain agents, antioxidants, nutraceuticals, confections, etc., and combinations thereof
(¶ 0067).
Regarding Claim 1, Sha teaches a SMEDDS composition comprising an oil-based formulation including oils, surfactants, and cosurfactants, where the system is a mixture of drugs, lipids, surfactants, and cosurfactants forming a fine OIW microemulsion with a droplet size of less than 100 nm upon exposure to aqueous media (Sha, page 705, last ¶). Sha discloses SMEDDS as an approach to improve oral absorption for poorly water-soluble drugs, with the formulation administered via gelatin capsule (Sha, page 705–706). Sha teaches an optimal formulation comprising olive oil (13% w/w), Lauroglycol FCC (27% w/w), Cremophor EL (20% w/w), Tween-80 (20% w/w), and PEG-400 (20% w/w), with droplet sizes measured at approximately 80 nm (Sha, page 711, Conclusion ¶). Sha thus teaches the general architecture of an exterior capsule enclosing an oil-based solution comprising an emulsion system with an emulsion oil component and surfactant components that forms a thermodynamically stable OIW microemulsion with average droplet diameter falling within the claimed 10–100 nm range upon exposure to aqueous GI fluid. However, Sha fails to specifically teach: (a) a phospholipid as a component of the surfactant system; (b) a resin system comprising turmeric oleoresin, propolis, or related resins; (c) a polyethylene glycol derivative as defined in the claims; or (d) the specific 1:5 to 1:30 phospholipid:PEG derivative ratio.
Pouton teaches that lipid-based delivery systems range from simple oil solutions to complex mixtures of oils, surfactants, cosurfactants, and cosolvents forming self-emulsifying systems thermodynamically stable upon dilution (Pouton, page 626, left column, introductory ¶). Pouton further teaches that self-emulsifying systems are formed when the surfactant concentration exceeds 25% w/w, with an optimum concentration range of 30–40% surfactant (Pouton, page 633, section 5.5). Pouton thus establishes that the surfactant system preferably constitutes 27–35% by weight of the oil-based solution, overlapping with the claimed range. Pouton teaches medium chain triglycerides (MCT) derived from coconut oil comprising C8 (50–80%) and C10 (20–45%) fatty acid glycerol esters (Pouton, page 628, section 3.2), teaching the emulsion oil system comprising associating oil from medium chain triglyceride sources. However,
Pouton fails to specifically teach turmeric oil as a terpene component of the emulsion oil system, phospholipid as a component of the surfactant system with a defined ratio to a PEG derivative, or a resin system.
Cho teaches optimization of solid SMEDDS formulations for sirolimus comprising phosphatidylcholine (phospholipid), D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, a PEG derivative), and polysorbate 80, where the weight ratio of each liquid component varied by 10% among different formulations (Cho, page 1674, left column, lines 1–2; page 1674, right column, first ¶; page 1675, left column, preparation ¶). Cho thus specifically teaches a phospholipid (phosphatidylcholine) and a PEG glycol derivative (TPGS, polysorbate 80) as components of a surfactant system in a SMEDDS formulation. Cho teaches that droplet size affects drug release and that smaller droplets provide better drug release through a larger interfacial area (Cho, page 1678, left column, second ¶ through right column, first ¶), teaching optimization of droplet size including values below 200 nm, with the “good” formulations exhibiting mean droplet sizes as low as 93.9 nm.
A PHOSITA would have been motivated to incorporate the phospholipid and PEG derivative surfactant pair taught by Cho into the liquid SMEDDS formulation of Sha, because: (i) Cho teaches that phosphatidylcholine and TPGS are known surfactants in SMEDDS; (ii) both components are widely known to function in liquid oil systems, and their utility is not limited to solid dosage forms; (iii) a PHOSITA would have recognized that these surfactant components impart advantageous emulsification properties regardless of dosage form; and (iv) combining known surfactant components from the same class of drug delivery systems (SMEDDS) would have been routine formulation optimization. The reasonable expectation of success is high because phospholipid/PEG derivative combinations are well-established surfactant systems for OIW microemulsion formation, as confirmed by Olene. Furthermore, the ratio of phospholipid to PEG derivative (1:5 to 1:30) represents optimization of a result-effective variable and a PHOSITA optimizing surfactant system composition would systematically vary this ratio and arrive at the claimed range. In re Boesch, 617 F.2d 272 (CCPA 1980).
Olene (WO 2018/185780 A1) teaches increasing water-solubility of hydrophobic molecules including curcumin by manufacture of self-emulsifying delivery systems (SEDDS) using emulsifiers comprising lecithin/phospholipids, polyethylene glycols and derivatives, D-α-tocopheryl polyethylene glycol 1000 succinate, polysorbate 80 (Olene, page 5, ¶ 2). Olene further teaches that the herbal composition contains 1–98% of one or more natural or synthetic emulsifiers (Olene, page 4, ¶ 3). Olene discloses compositions including both lecithin (phospholipid) and polysorbate 80 together (Olene, Composition I, page 9–10; Composition X, page 12), establishing that a phospholipid and PEG derivative can be used together in self-emulsifying compositions. Olene further teaches turmeric oleoresin (0.1–99.8%, abstract), turmeric essential oil (1–98%, abstract), medium chain triglycerides (Olene, page 5, last ¶), orange essential oil, lemon oil, Boswellia serrata oil (Olene, page 4, last ¶), and terpene oils (Olene, page 6, ¶ 2 and claim 7). Olene thus teaches both the association oil and terpene oil components of the emulsion oil system, the phospholipid and PEG derivative components of the surfactant system, and resin components (turmeric oleoresin).
A PHOSITA would have found it obvious to combine the phospholipid:PEG derivative surfactant pair of Cho and Olene with the SMEDDS framework of Sha (as taught by Pouton) because all references address the same problem, which is improving bioavailability of poorly water-soluble compounds through self-emulsifying systems and the surfactant components are known to be functionally interchangeable within this class. The motivation to use a phospholipid/PEG derivative combination is provided by Olene’s explicit teaching of their combined use. The motivation to establish a defined ratio between them is provided by Cho’s ternary optimization approach, which a PHOSITA would apply to a liquid system.
Edwards teaches an edible and ingestible composition comprising emulsions and edible materials in transport systems where micelles can be formed from polyethylene glycol, polysorbates, turmeric extract, propolis extract, and citrus oils (Edwards, ¶ 0043, 0067, 0069, 0092). Edwards specifically discloses propolis extract at 3% (Edwards, page 16, line 9 from bottom) and turmeric oleoresin/turmeric extract 4:1 (Edwards, page 17, line 5), either alone or in combination (Edwards, ¶ 0074). Edwards thus teaches a resin system comprising turmeric oleoresin and propolis, satisfying the resin system limitation of claim 1. A PHOSITA formulating a SMEDDS composition incorporating botanical deliverables would have been motivated to consult Edwards because Edwards teaches the same type of botanical ingredients (turmeric, propolis, Boswellia serrata) in a self-emulsifying context targeting similar biological objectives (pain relief, inflammation). The motivation to incorporate a resin system is provided by the art’s recognition that resins such as turmeric oleoresin serve both as functional emulsion components and as bioactive ingredient carriers. The reasonable expectation of success is high because Edwards demonstrates that propolis and turmeric oleoresin are compatible with polysorbate-based micelle-forming systems, indicating no technical barrier to their inclusion in the Sha-based SMEDDS framework.
It would therefore have been prima facie obvious to a PHOSITA to formulate the SMEDDS as taught by Sha in view of Pouton, incorporate the phospholipid and PEG derivative surfactant pair as taught by Cho and Olene, include the resin system components as taught by Olene and Edwards, and optimize the phospholipid:PEG derivative ratio to achieve the desired thermodynamically stable microemulsion with 10–100 nm droplet diameter. The combined teachings of these references address every limitation of claim 1. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
Regarding Claim 3, Sha in view of Cho teaches thermodynamic stability. Sha’s SMEDDS microemulsion is thermodynamically stable by definition (droplet formation without shear); Cho confirms SMEDDS are generally thermodynamically stable (Cho, page 1674, left column, second ¶). The thermodynamic stability limitation is therefore met.
Regarding Claim 4, the composition of claim 1 further configured to form liposomes in the aqueous GI tract comprising water-core liposomes with a water-soluble deliverable. Sha teaches that lipid-based formulations including liposomes represent one approach to drug delivery (Sha, page 705, ¶ 4). A PHOSITA would have known that phosphatidylcholine, the phospholipid introduced from Cho is the primary lipid used to form liposomes in aqueous environments (specification ¶s 003–006), and that when present in the SMEDDS alongside the PEG derivative, water-core liposome formation in the aqueous GI tract would be an expected outcome. No additional teaching is required because liposome formation from phospholipids in aqueous systems is general knowledge.
Regarding Claims 7 and 8 (droplet diameter 10–80 nm and 10–60 nm), Sha discloses droplet sizes around 80 nm (Sha, page 711, Conclusion). Cho reports mean droplet sizes ranging from 93.9 nm down to well below 100 nm across good formulations, with several below 200 nm and some approaching 100 nm (Cho, page 1678). A PHOSITA seeking better drug release would have been motivated to formulate smaller droplets in the 10–80 nm or 10–60 nm range, as Cho explicitly teaches that smaller droplets produce better drug release (Cho, page 1678, left column, second ¶). The reasonable expectation of success in achieving these droplet sizes is confirmed by Sha’s actual measured droplet size of approximately 80 nm.
Regarding Claim 9 (surfactant system comprises phospholipid and PEG derivative). This limitation is taught by Cho and Olene as discussed regarding Claim 1.
Regarding Claim 10 (phospholipid is glycerophospholipid isolated from lecithin),
Olene teaches lecithin/phospholipids as emulsifier components (Olene, page 5, ¶ 2). Cho teaches phosphatidylcholine, which is a glycerophospholipid commercially isolated from lecithin, as a component of the SMEDDS surfactant system (Cho, page 1674, left column). The limitation is met.
Regarding Claim 11 (phospholipid chosen from PC, PE, PI, Cer-PE, SPH, and combinations), Cho teaches phosphatidylcholine specifically (Cho, page 1674). Olene teaches soya phospholipids and related glycerophospholipids from lecithin isolates (Olene, page 5). The limitation of phospholipid chosen from the named class is met.
Regarding Claim 12 (phospholipid chosen from PC, PE, and combinations thereof). This limitation is taught by Cho’s explicit use of phosphatidylcholine (Cho, page 1674) and Olene’s soya phospholipid teachings. Optimization to phosphatidylcholine or phosphatidylethanolamine would have been routine.
Regarding Claim 13 (phospholipid is at least 80% phosphatidylcholine by weight). Cho teaches phosphatidylcholine as the phospholipid component. The specification defines the preferred phospholipid as a lecithin isolate that includes 80% (w/w) of the specified phospholipid (specification, ¶ 0058). Cho’s use of phosphatidylcholine as the sole phospholipid component encompasses the ≥80% limitation. The recitation of ≥80% phosphatidylcholine is met by Cho’s teaching of phosphatidylcholine as the phospholipid in the SMEDDS surfactant system.
Regarding Claim 14 (PEG derivative chosen from TPGS, polysorbate 40, 60, 80, and combinations). Cho teaches Vitamin E TPGS and polysorbate 80 as PEG derivative components (Cho, page 1674). Olene teaches D-α-tocopheryl polyethylene glycol 1000 succinate and polysorbate 80 (Olene, page 5). The limitation is met.
Regarding Claim 15 (PEG derivative chosen from TPGS, polysorbate 40, and combinations thereof). Cho teaches Vitamin E TPGS (Cho, page 1674). Olene teaches TPGS and polysorbate 80 (Olene, page 5). Polysorbate 40 is recognized in the specification as interchangeable with polysorbate 80 in SMEDDS contexts. A PHOSITA would have found it obvious to substitute polysorbate 40 for polysorbate 80 as a routine formulation modification within the same polysorbate class, with a reasonable expectation that the similar HLB values of these surfactants would produce comparable emulsification results.
Regarding Claim 16 (surfactant system comprises 27–35% by weight of the oil-based solution). Pouton teaches that the optimum surfactant concentration for self-emulsifying systems is 30–40% w/w, overlapping with the claimed 27–35% range (Pouton, page 633, section 5.5). A PHOSITA would have optimized the surfactant concentration to achieve the claimed range based on Pouton’s teachings.
Regarding Claims 18-20 (emulsion oil system comprising medium chain triglyceride (MCT) associating oil, specific MCT sources). Pouton teaches MCT oils derived from coconut and palm kernel oils including C8 and C10 fatty acids (Pouton, page 628, section 3.2). Olene teaches medium chain triglycerides (Olene, page 5, last ¶). The named MCT sources (caproic, caprylic, capric, lauric acid) in claims 18–20 correspond to the C6–C12 fatty acids of MCT oils as taught by both Pouton and Olene. The limitation is met.
Regarding Claim 21 (citrus oil chosen from orange oil, lemon oil, and combinations thereof). Olene teaches orange essential oil and lemon oil as components of the emulsion oil system (Olene, page 4, last ¶). The limitation is met.
Regarding Claims 22–24 (emulsion oil system further comprises terpene oil; terpene oil from turmeric oil, cinnamon oil, peppermint oil, spearmint oil, or blends; terpene oil is turmeric oil). Olene teaches terpene oil (Olene, page 6, ¶ 2 and claim 7), turmeric essential oil (Olene, page 5, line 1), and cinnamon oil and peppermint oil (Olene, page 4, ¶ 5). The limitation of terpene oil chosen from the listed sources is met by Olene.
Regarding Claim 25 (emulsion oil system comprises 38–55% by weight). Olene teaches SMEDDS compositions wherein medium chain triglycerides and essential oils collectively constitute the oil phase, with Composition IX specifying 10 g turmeric oleoresin, 10 g MCT oil, and 10 g essential oil components in a 100 g batch (Olene, page 13), yielding an oil-phase contribution approaching 30% by weight in that base formulation. Pouton teaches that the oil phase in SMEDDS is routinely optimized between 20–60% w/w depending on drug solubility and desired droplet size (Pouton, page 628, section 3.2; page 633, section 5.5). The emulsion oil system at 38–55% by weight represents a sub-range within this established optimization space. A PHOSITA seeking to maximize deliverable solubilization capacity while maintaining thermodynamic stability with both properties taught as desirable by Sha, Pouton, and Olene, would have been motivated to increase oil phase loading toward the upper portion of Pouton’s taught range, with a reasonable expectation of arriving at the 38-55% window through routine formulation screening. The claimed range is therefore a result-effective variable subject to routine optimization. In re Boesch, 617 F.2d 272, 276 (CCPA 1980).
Regarding Claim 26 (ratio of associating oil to terpene oil from 1:1.7 to 1:5.5). Olene teaches medium chain triglycerides as associating oil and essential oils including turmeric oil as terpene oil (Olene, page 5). A PHOSITA would have been motivated to optimize the ratio of associating oil to terpene oil to achieve a stable oil system compatible with the surfactant monolayer, with the ratio representing a result-effective variable that would have been optimized through routine experimentation.
Regarding Claim 28 (resin system consists essentially of turmeric oleoresin).
Olene teaches turmeric oleoresin 0.1–99.8% by weight (Olene, abstract). The limitation of a resin system consisting essentially of turmeric oleoresin is met by Olene’s disclosure of turmeric oleoresin as a primary resin component.
Regarding Claim 29 (resin system consists essentially of propolis). Edwards teaches propolis extract 3% (Edwards, page 16, line 9 from bottom). Olene also teaches propolis-free formulations with turmeric oleoresin as the sole resin. Edwards and Olene together teach that propolis can serve as the sole resin component. A PHOSITA formulating a resin system for a SMEDDS would have found it obvious to use propolis as the resin system component based on Edwards’ teaching of propolis in micelle-forming compositions.
Regarding Claim 30 (resin system consists essentially of turmeric oleoresin and propolis). Edwards teaches turmeric extract and propolis together (Edwards, ¶s 0030, 0074). Olene teaches turmeric oleoresin (Olene, abstract). The limitation of a resin system consisting essentially of turmeric oleoresin and propolis in combination is taught by Edwards.
Regarding Claim 31 (resin system comprises 3-18% by weight). Olene teaches turmeric liquid oleoresin at 10 g in Composition IX (Olene, page 13), overlapping with the claimed 3-18% range. Edwards teaches propolis at 3% (Edwards, page 16), within the claimed range. The resin system weight percentage limitation is met.
Regarding Claim 32 (ratio of propolis to turmeric oleoresin from 1:1.7 to 1:5). Edwards teaches propolis 3% and turmeric 4:1 extract together (Edwards, page 16–17). Olene teaches turmeric oleoresin in varying amounts across compositions I–XV (Olene, pages 9–18). A PHOSITA would have been motivated to optimize the propolis:turmeric oleoresin ratio as a result-effective variable governing resin system performance, with the claimed range representing routine optimization of known resin compositions. The ratio disclosed across Edwards’ and Olene’s compositions overlaps with or approaches the claimed 1:1.7 to 1:5 range.
Regarding Claim 33 (ratio of resin system to surfactant system to emulsion oil system of 1:2–4:3.5–6 ±20%). Olene teaches compositions I–XV specifying the proportions of resin (oleoresin), surfactant (lecithin/polysorbate), and oil (MCT, essential oils) components (Olene, pages 9–18). The ratio of these three system components across Olene’s compositions encompasses the claimed 1:2–4:3.5–6 range within ±20% deviation. The limitation is met.
Regarding Claims 34–36 (deliverable chosen from specific alcohol-soluble, oil-soluble species). As discussed in the prior Office Action, Olene teaches curcumin 25-55% (Olene, page 2, ¶s 4-5), Boswellia serrata oil (Olene, page 4, ¶ 5 and claim 5), berberine, quercetin, and resveratrol (Olene, page 6, ¶ 2) as alcohol-soluble deliverables; and cannabis extract and cinnamon oil as oil-soluble species (Olene, page 6, ¶ 1). Edwards teaches milk thistle extract, quercetin, resveratrol, and Boswellia serrata extract (Edwards, page 16, bottom; ¶ 0091). The deliverable limitations are met.
Regarding Claims 37-39 (deliverable further comprises water-soluble deliverable; mineral salt; zinc, magnesium, or calcium salt). Cho teaches zinc sulfate 400 μL 6.25% w/v as a water-soluble deliverable (Cho, page 1674, right column, line 3; page 1676, left column, last ¶). The water-soluble mineral salt limitation is met.
Regarding Claim 40 (oil-based solution configured to solubilize 50-200 mg deliverable per gram). Sha teaches that 60 mg of probucol was dissolved in 1 g of mixture (Sha, page 707, right column, ¶ 3), corresponding to 60 mg/g. This overlaps with the claimed 50-200 mg/g range.
Regarding Claim 41 (oil-based solution comprises 10-20% deliverable by weight). Sha teaches dissolution of 60 mg probucol per 1 g formulation mixture, corresponding to approximately 6% w/w deliverable loading (Sha, page 707, right column, ¶ 3). Cho teaches sirolimus solubility in various SMEDDS oil and cosolvent systems reaching 50 mg/g in the oil phase alone (Cho, page 1679, left column, third ¶), and further teaches that increasing drug loading within the SMEDDS oil phase is a recognized formulation objective to minimize capsule fill volume and improve dose efficiency (Cho, page 1676, right column). Olene teaches SMEDDS compositions with curcumin at 25–55% by weight of the total composition (Olene, page 2, ¶s 4–5), demonstrating that high-loading botanical deliverables in self-emulsifying systems are well within PHOSITA knowledge. A PHOSITA optimizing deliverable loading in the Sha-based SMEDDS framework, motivated by the dose efficiency objectives taught by Cho and the high-loading precedent of Olene, would have been led through routine formulation development to increase the deliverable weight fraction into the 10–20% range. The claimed range represents optimization of a result-effective variable with a reasonable expectation of success. In re Boesch, 617 F.2d 272, 276 (CCPA 1980); KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
Regarding Claim 42 (ratio of deliverable to emulsion system from 1:4-8 ±20%).
Sha teaches the deliverable to formulation ratio with 60 mg probucol per 1 g of mixture (Sha, page 707, right column, ¶ 3). A PHOSITA would have been motivated to optimize the deliverable:emulsion ratio to achieve maximum solubilization efficiency within the SMEDDS, with the claimed 1:4–8 range representing optimization of a result-effective variable.
Regarding Claim 43 (composition configured to deliver measurable plasma concentration within 20 minutes of fasted oral consumption). Sha’s pharmacokinetic study demonstrates measurable plasma concentrations of probucol from SMEDDS following oral administration to fasted rats, confirming gastrointestinal absorption of drug from the SMEDDS formulation (Sha, page 707, left column, bioavailability study ¶). The 20-minute limitation recites a functional outcome of rapid absorption rather than a structural feature, and is a property inherently associated with SMEDDS compositions having small droplet diameters. Cho teaches that droplet size directly governs drug release rate through interfacial area effects, and that formulations with smaller droplets produce faster and more complete drug release (Cho, page 1678, left column, second ¶). The claimed SMEDDS compositions have droplet diameters of 10-100 nm (claim 1) or as low as 10-60 nm (claim 8), which are among the smallest achievable in lipid-based delivery systems. Pouton teaches that SMEDDS compositions undergo rapid and spontaneous emulsification upon contact with GI fluid (Pouton, page 626, introductory ¶), resulting in immediate formation of a high-surface-area oil-in-water microemulsion available for absorption. The art therefore establishes that (i) SMEDDS compositions are rapidly absorbed following fasted oral administration, (ii) smaller droplets accelerate drug release kinetics, and (iii) the sub-100 nm droplet sizes achievable by the claimed compositions would be expected to produce measurable plasma concentrations within a 20-minute window. This outcome represents an inherent or immediately foreseeable property of the optimized SMEDDS taught by the combined references, not a separate inventive contribution. See MPEP (2112. IV) Par Pharm., Inc. v. TWi Pharms., Inc., 773 F.3d 1186, 1194–95 (Fed. Cir. 2014) (inherency in obviousness context does not require explicit prior art recognition of the property).
Regarding Claims 44-47 (specific ingestible and edible compositions for pain relief, microbial load, controlling inflammation, and zinc supplementation). As discussed in the prior Office Action, Olene and Edwards together teach all of the specific ingredients recited in claims 44–47, including turmeric oleoresin, propolis, turmeric oil, cinnamon oil, peppermint oil, hemp oil, piperine, curcumin, Boswellia serrata, berberine HCl, milk thistle extract, artemisinin, andrographis, quercetin, resveratrol, hesperetin, spearmint oil, zinc acetate, and luteolin. The specific weight ranges recited in these claims represent result-effective variables that a PHOSITA would optimize based on the teachings of Olene and Edwards. The motivation to formulate these specific combinations is provided by the recognized biological activities of each ingredient in the context of the stated therapeutic objectives (pain relief, antimicrobial, anti-inflammatory, zinc supplementation).
Response to Arguments
Applicant's arguments filed 03/23/2026 have been fully considered but they are not persuasive.
Regarding Sha: The Office concurs with Applicant that Sha does not specifically teach a phospholipid as a component of the surfactant system nor a resin system. Sha is relied upon solely for its foundational teaching of SMEDDS compositions comprising oils, surfactants, cosurfactants, and poorly water-soluble deliverables forming an OIW microemulsion upon contact with aqueous GI fluid, establishing the general framework of the claimed oil-based solution. The Office does not rely on Sha for the phospholipid, PEG derivative ratio, or resin system limitations.
Regarding Cho: Applicant argues that Cho’s solid SMEDDS formulations cannot be combined with the liquid-phase teachings of Sha and Pouton because combining a solid with a liquid system would result in inoperability. The Office disagrees. Cho teaches the use of phosphatidylcholine (a phospholipid) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, a PEG derivative) as surfactant components in SMEDDS compositions (Cho, page 1674, left column, lines 1–2; page 1674, right column, first ¶). The relevance of Cho is not to adopt the solid dosage form as a whole, but to establish that a phospholipid (phosphatidylcholine) and a PEG glycol derivative (TPGS) are known surfactant pair components in SMEDDS formulations. A PHOSITA would have understood that these surfactant components function equivalently in liquid-phase SMEDDS regardless of whether the overall final form is solid or liquid, and would have been motivated to incorporate these known surfactant components into a liquid SMEDDS formulation taught by Sha. The legal principle against combining references where the combination produces inoperability does not apply here because the phospholipid and PEG derivative components themselves are not rendered inoperable when transferred from a solid to a liquid matrix — only the solid excipients (e.g., Aerosil, Avicel) used to adsorb the liquid would be irrelevant to a liquid formulation, and no such excipients are claimed.
Regarding the 1:5 to 1:30 phospholipid to PEG derivative ratio: Applicant argues that no reference teaches or suggests this specific ratio, and that the Office has not identified where in Pouton this ratio appears. The Office acknowledges that Pouton does not specifically exemplify this ratio as a discrete teaching directed to phospholipid:PEG derivative optimization. However, Cho teaches SMEDDS formulations comprising phosphatidylcholine and vitamin E TPGS as components of the surfactant system, with each component varying independently across a ternary space of oil:cosolvent:surfactant (Cho, page 1675, right column, first ¶, Table 1). The varied concentrations of phosphatidylcholine and TPGS across Cho’s ternary formulations encompass ratios that fall within the 1:5 to 1:30 range claimed. Furthermore, Olene/Nirvanashetty teaches lecithin/phospholipids and PEG derivatives as components of the emulsifier system used alone or in combination (Olene, page 5, ¶ 2), with compositions I and X demonstrating different proportions of lecithin to polysorbate 80. A PHOSITA would have recognized the phospholipid:PEG ratio as a result-effective variable in controlling emulsification efficiency and particle size, and would have been motivated through routine optimization to arrive at the claimed 1:5 to 1:30 range. See In re Boesch, 617 F.2d 272, 276 (CCPA 1980) (optimization of result-effective variables is prima facie obvious); KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
Regarding Olene/Nirvanashetty: Applicant argues that Nirvanashetty treats lecithin and polysorbate as interchangeable and never uses both together in a defined ratio. The Office notes that Nirvanashetty’s Composition I discloses a formulation using Lecithin/Lecithin Powder/Polysorbate 80 totaling 10.0 (Olene, page 9–10), and Composition X discloses this same component at 80.0 (Olene, page 12), demonstrating that the compositions do include lecithin (phospholipid) and polysorbate 80 (PEG derivative) together. The fact that Nirvanashetty does not separately report the within-component ratio does not negate the disclosure that both components are present together and functional. A PHOSITA reading Nirvanashetty in view of Cho would have had motivation and reasonable expectation of success in optimizing the phospholipid:PEG ratio to achieve desired emulsification properties.
Regarding Edwards: Edwards is maintained as a secondary reference for the independent disclosure of resinous, propolis-containing compositions including turmeric extract, propolis, and various botanical ingredients encapsulated in micelle-forming systems containing polyethylene glycol and polysorbates (Edwards, ¶s 0066–0067, 0069, 0074). Edwards is not relied upon for the liquid SMEDDS architecture or the phospholipid:PEG ratio, but for the independent teaching of resin system components (propolis, turmeric oleoresin) used in conjunction with polysorbate-based surfactant systems. The teaching field of Edwards - edible, ingestible encapsulated formulations containing botanical resins - is not so far removed from SMEDDS nutraceutical formulations as to preclude a PHOSITA from consulting it. In re Clay, 966 F.2d 656, 659 (Fed. Cir. 1992) (analogous art test).
Conclusion
No claims are allowed.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615