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 .
Information Disclosure Statement
The information disclosure statements filed on August 13, 2024; November 21, 2024; June 9, 2025; February 19, 2026; April 7, 2026; May 5, 2026; and June 08, 2026 are acknowledged. The forms filed November 21, 2024; June 9, 2025; February 19, 2026; April 7, 2026; May 5, 2026; and June 08, 2026 have been considered by the examiner.
The information disclosure statement filed August 13, 2024 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. In this instance:
The non-patent literature document “Lipiodol® Ultra-Fluid, registered April 21, 2021” is provided entirely in a language that is not English and does not provide an English explanation of relevance.
The foreign patent document JPS61500849A lacks an English explanation of relevance. The document provided appears to be lacking an abstract.
It has been placed in the application file, but the information referred to therein has not been considered.
The information disclosure statement filed August 13, 2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. In this instance:
JP 7210542 B2 is listed as a foreign patent document on the IDS, but this reference has not been provided.
WO 2019/030024 A1 is listed as a foreign patent document on the IDS, but this reference has not been provided. While the abstract from WO 2019/030024 A1 is provided, this abstract is appended to JP 2020/529441 A. Thus, the WO 2019/030024 A1 reference is considered to not be provided.
JPS61500849A is listed as a foreign patent document on the IDS, but this reference has not been provided. There appears to be a bibliographical sheet related to this document provided, but the content of the patent document in its entirety is missing.
These references are thus crossed out on the signed IDS form. It has been placed in the application file, but the information referred to therein has not been considered.
Specification
The use of tradenames or marks used in commerce have been noted in this application.
On pg. 4, line 1, Sandimmune Neoral is recited. NEORAL is a tradename or mark used in commerce.
On pages 27-30, many tradenames and marks used in commerce are provided in the example polyoxyethylene castor oils, polyoxyethylene sorbitan fatty acid esters, macrogol 15 hydroxystearate, polyoxyethylene alkyl ethers, caprylocaproyl polyoxylglycerides, and poloxamers.
On pages 53-58, there are numerous recitations of tradename surfactant compounds (e.g., Tween, Etocas, and Kolliphor surfactants).
These terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 4-15 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claims should refer to other claims in the alternative only and/or cannot depend from any other multiple dependent claim. See MPEP § 608.01(n).
Claim 9 is objected to for the following informalities: the claim appears to contain lists of options within lists and parenthetical phrases but only uses commas to separate each concept, making the claim language difficult to read for grammatical reasons. When providing a list of lists, colons and semicolons improve the clarity. The examiner suggests amending the language (if keeping all words from the current version) to “…wherein the surfactant is selected from compounds containing at least one hydrophilic group independently selected from polyoxyethylene groups having from 3-60, preferably 4-40, ethyleneoxy units, monosaccharides, disaccharides, and sugar alcohols; as well as at least one hydrophobic group independently selected from a saturated or unsaturated hydrocarbon group, preferably alkyl group, said hydrocarbon group having 8-20, preferably 12-18 carbon atoms.” Appropriate correction is required.
Claim 11 is objected to for the following informalities: the limitation “is more than 2% and 30% or less” appears to have grammatical issues and the formatting of the two limitations in combination appears to be missing a word. The examiner suggests inserting “and” or “or” between “preferably between 10 and 40 %” and “the weight of the surfactant” as these are two separate limitations of the composition. Furthermore, regarding the first aspect of the latter limitation, the examiner suggests this portion of the claim should instead read as “is between 2% and 30%” or “is more than 2% and less than 30%.” Appropriate correction is required.
Claim Interpretation
Claim 1 is interpreted to be a product by process claim. Embodiment (Ae) recites “wherein the emulsion is obtained by an emulsification employing a low energy or ultra-low energy emulsification method.” In such a claim, the emulsion is only limited by the structure implied by the steps, not the performance of the recited steps (MPEP § 2113). Determination of patentability is based on the product itself. Therefore, if art reads on the structure as defined in the claim, even if the specific method of making recited was not performed, it will read on the claim.
Claims 2 and 3 are interpreted to contain functional language. Both claims contain multiple recitations of the phrase “for emulsification.” The examiner interprets this phrase to describe the intended use of these product claims. Please note that a recitation of intended use does not distinguish a product over the prior art if the prior art possesses the required structural features of the product and is capable of performing the intended use as recited (MPEP § 2111.02(II)).
Claims 2 and 3 are interpreted to refer to nonfunctional printed matter. Both claims contain a limitation requiring instructions. The examiner interprets the instructions to be nonfunctional printed matter. Therefore, the content of the printed matter does not distinguish the claimed product from the prior art (MPEP § 2112.01(III)).
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 defines the broad scope of the surfactant and ester components of the emulsion, product for emulsification, and premix product and most of the dependent claims. The scope of ester components as described in claim 1 is very broad, encompassing a vast array of chemical structures. The R1 group of Formula I is a hydrocarbon containing up to 30 carbon atoms which may be substituted with halogens. The R2 group of Formula I may be linear or branched alkyl, alkenyl, alkynyl, aryl, heteroaryl, or non-aromatic heterocycles of varying lengths and substitution states. However, the disclosure does not provide examples or detailed descriptions of emulsions, products for emulsification, or premix products made using a range of molecules representative of the full scope of ester component structures as described in claim 1. The only detailed descriptions use ethyl oleate, ethyl esters of poppy seed oil, ethyl di-iodo stearate, isopropyl myristate, butyl stearate, and methyl linoleate as the ester components. These ester components only possess R2 groups that can be described as linear-chain C1-4 alkyl and branched-chain C3 alkyl. These molecules also only possess R1 groups that can be described as linear C13 or C17 alkyl or alkenyl groups that are either unsubstituted or substituted with two iodine atoms. This range of examples is not an adequate representation of the breadth of possible chemical structures within the scope of claim 1. No examples are provided for R1 groups with short (C12 and shorter) or very long (C18 and longer) hydrocarbon chains or any chain form that is not linear. No R1 examples are provided for substitution with any halogen other than iodine and no example is provided with 3-6 halogen substitutions. No examples are provided for R2 groups that are alkenyl, alkynyl, aryl, heteroaryl, or non-aromatic heterocycles. No examples are provided for R2 groups that are longer than C4 linear or branched groups. It is not clear whether all ester components within the scope of claim 1 would be capable of forming emulsions or share similar properties to those disclosed through examples. Therefore, there is insufficient written disclosure for the full scope of the ester component structures as described in claim 1. This also applies to claims to the premix product, product for emulsification, and method of preparing an emulsion, as there are no examples of these products or methods being performed with alternative ester components. Furthermore, this rejection applies to all dependent claims as well. While some dependent claims narrow the scope of ester components in one way, none result in limiting the scope to a range of ester components adequately represented by the breadth of species provided in the disclosure.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrase “low energy or ultra-low energy” in claims 1-4 and 14 is a relative phrase which renders the claim indefinite. The phrase “low energy or ultra-low energy” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While examples of low energy and ultra-low energy methods are provided in the specification, this does not limit the claim. It is not clear what boundaries apply to this phrase. Out of all possible emulsification methods, it is not clear what methods do or do not belong to this categorization. Furthermore, claims 2-15 are also rejected due to their dependence on these claims.
Regarding claims 1-3, and 10, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claims 1-3 contain multiple such clauses. For the purpose of examination, the examiner will interpret that each of these “such as” clauses do not limit the scope of these claims. Furthermore, claims 2-15 are also rejected due to their dependence on these claims.
Regarding claims 5-12 and 15, the current language claims both a process (method of making an emulsion) and several products (the emulsion itself, a premix, and a product for emulsification). Per MPEP § 2173.05(p)(II), a single claim which claims both a product and the method steps of using the product is indefinite. The method of making the emulsion is interpreted to be a method of using a premix or a product for emulsification. Furthermore, the claims that depend from each of these claims, including claims 13 and 14 are rejected for said dependence.
Regarding claims 5-15, these claims are multiple dependent claims that depend on multiple dependent claims. Therefore, it is not clear what the scope of the claimed embodiment is for each of these claims. This ambiguity renders these claims indefinite. Furthermore, the claims that depend from each of these claims are rejected for said dependence.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance:
Claim 1, embodiment Ce1, recites the broad limitation “…linear or branched C1-C6 alkyl groups or linear or branched C1-C6 alkenyl groups,” and the claim also recites “preferably linear or branched C1-C4 alkyl groups or linear or branched C1-C4 alkenyl groups,” which is the narrower statement of the range/limitation.
Claim 1, embodiments Ce3 and Ce4, recites the broad limitation “polyoxyethylene castor oils wherein the total number of oxyethylene units is … even up to 200,” and the claim also recites “… the total number of oxyethylene units is preferably 4 or 5 or any high number up to 20,” which are narrower statements of the range/limitation.
Claim 1, embodiments Ce3 and Ce4, recites the broad limitation “polyoxyethylene sorbitan fatty acid esters wherein the total number of oxyethylene units is …any higher number up to 20,” and the claim also recites “the total number of oxyethylene units is preferably 4, 5,” which is the narrower statement of the range/limitation.
Claim 3, embodiments App, Bpp and Cpp, recites the broad limitation “weight ratio of the ester component to surfactant is in the range from 50:1 to 2:3,” and the claim also recites “or wherein the weight ratio of the ester component to the surfactant is in the range from 10:1 to 2:3,” which is the narrower statement of the range, limitation.
Claim 3, embodiments App, Bpp and Cpp, recites the broad limitation “weight of the ester component relative to the total weight of ester component and surfactant is from 2 to 60%,” and the claim also recites “or wherein … the weight of the ester component relative to the total weight of ester component and surfactant is in the range from 10 to 60%,” which is the narrower statement of the range/limitation.
Claim 7 recites the broad limitation “R2 is an unsubstituted group selected from a linear C1-4 alkyl group, a branched C3-4 alkyl group, a linear 2-4 alkenyl group, a branched C3-4 alkenyl group, a linear C2-4 alkynyl group, and a branched C4 alkynyl group,” and the claim also recites “preferably a C1-4 alkyl group,” which is the narrower statement of the range/limitation.
Claim 9 recites the broad limitation “polyoxyethylene groups having from 3-60 … ethyleneoxy units,” and the claim also recites “preferably 4-40 ethyleneoxy units,” which is the narrower statement of the range/limitation.
Claim 9 recites the broad limitation “saturated or unsaturated hydrocarbon group,” and the claim also recites “preferably alkyl group,” which is the narrower statement of the range/limitation.
Claim 9 recites the broad limitation “said hydrocarbon group having 8-20 … carbon atoms,” and the claim also recites “preferably 12-18 carbon atoms,” which is the narrower statement of the range/limitation.
Claim 10 recites the broad limitation “soft drinks,” and the claim also recites “preferably cola, lemonade, or ginger ale,” which is the narrower statement of the range/limitation.
Claim 10 recites the broad limitation “pharmaceutically acceptable buffers,” and the claim also recites “preferably citrate, borate, phosphate, carbonate, acetate, saline, glucose, sucrose, mannitol, and sorbitol solution,” which is the narrower statement of the range/limitation.
Claim 11 recites the broad limitation “between 5 and 50 %,” and the claim also recites “preferably between 10 and 40 %,” which is the narrower statement of the range/limitation.
Claim 11 recites the broad limitation “more than 2% and 30% or less,” and the claim also recites “preferably between 4 and 26 %,” which is the narrower statement of the range/limitation.
Claim 12 recites the broad limitation “the ester component-to-surfactant ratio is between 40:1 and 40:60,” and the claim also recites “particularly between 90:10 and 40:60,” “preferably … between 20:1 and 45:55,” “particularly between 85:15 and 45:55,” “more preferably … between 10:1 and 70:30,” and “particularly between 50:50 and 70:30,” which are narrower statements of the range/limitation.
Claim 12 recites the broad limitation “the water-to-surfactant radio is between 1000:1 and 55:45,” and the claim also recites “preferably … between 400:1 and 65:35,” and “more preferably … between 100:1 and 80:20,” which are narrower statements of the range/limitation.
Claim 12 recites the broad limitation “the water-to-ester component ratio is between 1000:1 and 4:6,” and the claim also recites “preferably … between 400:1 and 45:55,” and “more preferably … between 100:1 and 1:1,” which are narrower statements of the range/limitation.
Claim 13 recites the broad limitation that “the surfactant is present in a weight of 2 to 60 %,” and the claim also recites “preferably 4 to 55 %,” “more preferably 9 to 50 %,” “or … the surfactant is present in a weight of 10 to 60 %,” “preferably 15 to 55 %,” and “more preferably 30 to 50 %,” which are narrower statements of the range/limitation.
Claim 14 recites the broad limitation that “using an ultra-low energy method” and also recites “preferably by shaking by hand,” which is a narrower statement of the limitation.
Claim 14 recites the broad limitation “1.5 s to 120 s,” and the claim also recites “preferably 1.5 to 60 s,” and “more preferably 2 s to 30 s,” which are narrower statements of the range/limitation.
The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For the purpose of examination, the examination will consider the scope of the claim to be that of the broadest limitation in each instance. Furthermore, claims 2-15 are rejected due to their dependence on these claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4-9, and 14-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Agrawal (Agrawal, A. G.; et al., Arch. Pharm. Res., 2014).
Agrawal teaches a self-emulsifying drug delivery system for the delivery of coenzyme Q10 (pg. 1, Abstract). Agrawal teaches the preparation of nanoemulsions of various formulations of ethyl oleate with non-ionic surfactants (pg. 4, Table 1; and pg. 4, Preparation of SNEDDS formulations). Agrawal selects formulation C7 as the optimized formulation (pg. 11, left column, third paragraph), which is made from 160 mg ethyl oleate, 220 mg CREMOPHOR® RH 40, and 40 mg TRANSCUTOL® P and loaded with 30 mg Coenzyme Q10 (pg. 4, Table 1). Agrawal teaches dilution of the C7 formulation 10-fold, 100-fold, and 1,000-fold with purified water, 0.1 N HCl, and phosphate buffer pH 6.8 and demonstrates that the nanoemulsion is robust and not separated in each of these conditions (pg. 4, Robustness to dilution; pg. 8, Robustness to dilution; and pg. 9, Table 4). Agrawal teaches multiple methods of preparing emulsions from the mixture of ester and surfactants by adding water and stirring at 50 rpm at 37°C for 93-162 seconds (pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) or stirring for 2 minutes (pg. 4, Droplet size analysis). Agrawal describes this method as using mild agitation (pg. 9, Determination of self-emulsification time).
Regarding claim 1, the nanoemulsion of C7 diluted 1000-fold in purified water and stirred at 50 rpm at 37°C for 97 seconds (pg. 4, Table 1; pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) anticipates embodiments (Ae), (Be), (Ce1), (Ce3), and (Ce4) of this claim. The ethyl oleate ester reads on the ester component of Formula I, as R1 is a linear alkenyl hydrocarbon group that contains 17 carbon atoms and is not substituted (as is optional in the claim scope) and R2 is a linear-chain C2 alkyl group. The nanoemulsion also comprises one non-ionic surfactant compound in CREMOPHOR® RH 40, a further cosurfactant compound in TRANSCUTOL® P, and is describes as being diluted in purified water. The CREMOPHOR® RH 40 surfactant is a polyoxyethylene castor oil with 40 oxyethylene units. Furthermore, in this embodiment wherein 500 mg of C7 is diluted into 500 mL of purified water (pg. 4, Determination of self-emulsification time), there is ~186 mg ethyl oleate present (equivalent to ~0.037% w/w ester to the sum of ester, surfactant, and water; which is more than 0 wt. %), ~232 mg surfactant component (equivalent to ~0.046% w/w surfactant to the sum of ester, surfactant and water; which is more than 0 wt. %) (these values are greater than the values of 160 mg and 200 mg provided in Table 1 because the sum of the components in C7 of Table 1 add to 430 mg, but the method required 400 mg of a composition of this makeup, so all values were multiplied by ~1.16 to calculate the equivalent amounts of each component in a 500 mg preparation of C7). Furthermore, as the nanoemulsion was prepared using stirring at 50 rpm and Agrawal describes the method as mild agitation (pg. 4, Determination of self-emulsification time), the examiner interprets this to read on “a low energy or ultra-low energy emulsification method.” As claim 1 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 4, the nanoemulsion of C7 diluted 1000-fold in purified water and stirred at 50 rpm at 37°C for 97 seconds (pg. 4, Table 1; pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) anticipates embodiments (Am), (Bm), and (Cm) of this claim. As described above, the emulsion made by the aforementioned method anticipates embodiments (Ae), (Be), (Ce1), (Ce3), and (Ce4). Additionally, as the nanoemulsion was prepared using stirring at 50 rpm and Agrawal describes the method as mild agitation (pg. 4, Determination of self-emulsification time), the examiner interprets this to read on “emulsifying the composition using a low energy or ultra-low energy emulsification method.” As claim 4 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claims 5 and 6, the nanoemulsion of C7 diluted 1000-fold in purified water and stirred at 50 rpm at 37°C for 97 seconds (pg. 4, Table 1; pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) anticipates at least the embodiment of each of claims 5 and 6 drawn to the emulsion of any embodiment of claim 1 wherein R1 is further defined. As described above, Agrawal anticipates embodiments (Ae), (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes ethyl oleate as the ester, which has an R1 group having 17 carbon atoms that are unsubstituted. As claims 5 and 6 provide the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claims on the whole.
Regarding claim 7, the nanoemulsion of C7 diluted 1000-fold in purified water and stirred at 50 rpm at 37°C for 97 seconds (pg. 4, Table 1; pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) anticipates at least the embodiment of claim 7 drawn to the emulsion of any embodiment of claim 1 wherein R2 is further defined. As described above, Agrawal anticipates embodiments (Ae), (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes ethyl oleate as the ester, which has an ethyl R2 group that can be described as an unsubstituted linear C2 alkyl group. As claim 7 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 8, the nanoemulsion of C7 diluted 1000-fold in purified water and stirred at 50 rpm at 37°C for 97 seconds (pg. 4, Table 1; pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) anticipates at least the embodiment of claim 8 drawn to the emulsion of any embodiment of claim 1 wherein the surfactant is further defined. As described above, Agrawal anticipates embodiments (Ae), (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes CREMOPHOR® RH 40 as the only non-ionic surfactant compound. Therefore, the surfactant is a single surfactant. Agrawal describes TRANSCUTOL® P as a cosurfactant (pg. 7, Screening of cosurfactants), which is understood by the examiner to refer to a compound that further stabilizes an emulsion but is not a surfactant itself and therefore is considered a further component and not another surfactant compound (pg. 3, Screening of cosurfactants). As claim 8 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 9, the nanoemulsion of C7 diluted 1000-fold in purified water and stirred at 50 rpm at 37°C for 97 seconds (pg. 4, Table 1; pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) anticipates at least the embodiment of claim 9 drawn to the emulsion of any embodiment of claim 1 wherein the surfactant is further defined. As described above, Agrawal anticipates embodiments (Ae), (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes CREMOPHOR® RH 40 as the only non-ionic surfactant compound. This surfactant can be described as having polyoxyethylene groups having 40 ethyleneoxy units and three hydrophobic alkyl groups containing 17 carbon atoms each (pg. 2, Fig. 1). As claim 9 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 14, the method of making the nanoemulsion of C7 diluted 1000-fold in purified water and stirred at 50 rpm at 37°C for 97 seconds (pg. 4, Table 1; pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) anticipates at least the embodiment of claim 14 dependent on claim 4 wherein the method is further defined. As described above, Agrawal anticipates embodiments (Am), (Bm), and (Cm) of claim 4. As the nanoemulsion was prepared using stirring at 50 rpm and Agrawal describes the method as mild agitation (pg. 4, Determination of self-emulsification time), the examiner interprets this to read on “using an ultra-low energy method.” Furthermore, Agrawal describes the emulsion as completely prepared in 97 seconds of stirring (pg. 9, Table 5), which is between 1.5 and 120 seconds. As claim 14 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 15, the nanoemulsion of C7 diluted 1000-fold in purified water and stirred at 50 rpm at 37°C for 97 seconds (pg. 4, Table 1; pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) anticipates at least the embodiment of claim 15 drawn to the emulsion of any embodiment of claim 1 wherein the composition of the emulsion is further defined. As described above, Agrawal anticipates embodiments (Ae), (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes TRANSCUTOL® P as a cosurfactant compound (pg. 7, Screening of cosurfactants). As this compound is not the ester component, surfactant, or water component, this reads as an optional further component. TRANSCUTOL® P is a liquid and Agrawal describes homogenizing this compound with ethyl oleate (pg. 3, Screening of cosurfactants), demonstrating that TRANSCUTOL® P is miscible with the ester component. As claim 15 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Claims 1, 5-10, 12, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Agrawal (Agrawal, A. G.; et al., Arch. Pharm. Res., 2014).
As described above, Agrawal teaches a self-emulsifying drug delivery system for the delivery of coenzyme Q10 (pg. 1, Abstract). Agrawal teaches the preparation of nanoemulsions of various formulations of ethyl oleate with non-ionic surfactants (pg. 4, Table 1; and pg. 4, Preparation of SNEDDS formulations). Agrawal selects formulation C7 as the optimized formulation (pg. 11, left column, third paragraph), which is made from 160 mg ethyl oleate, 220 mg CREMOPHOR® RH 40, and 40 mg TRANSCUTOL® P and loaded with 30 mg Coenzyme Q10 (pg. 4, Table 1). Agrawal teaches dilution of the C7 formulation 10-fold, 100-fold, and 1,000-fold with purified water, 0.1 N HCl, and phosphate buffer pH 6.8 and demonstrates that the nanoemulsion is robust and not separated in each of these conditions (pg. 4, Robustness to dilution; pg. 8, Robustness to dilution; and pg. 9, Table 4). Agrawal teaches multiple methods of preparing emulsions from the mixture of ester and surfactants by adding water and stirring at 50 rpm at 37°C for 93-162 seconds (pg. 4, Determination of self-emulsification time; and pg. 9, Table 5) or stirring for 2 minutes (pg. 4, Droplet size analysis). Agrawal describes this method as using mild agitation (pg. 9, Determination of self-emulsification time).
Regarding claim 1, the nanoemulsion of C7 diluted 10-fold in phosphate buffer pH 6.8 (pg. 4, Table 1; pg. 4, Robustness to dilution; and pg. 9, Table 4) at least anticipates embodiments (Be), (Ce1), (Ce3), and (Ce4) of this claim. As described above, the ethyl oleate ester reads on the ester component of Formula I. The nanoemulsion also comprises one non-ionic surfactant compound in CREMOPHOR® RH 40, a further cosurfactant compound in TRANSCUTOL® P, and is describes as being diluted in phosphate buffer pH 6.8. The CREMOPHOR® RH 40 surfactant is a polyoxyethylene castor oil with 40 oxyethylene units. Furthermore, in this embodiment, if 430 mg of C7 (the sum of the values in Table 1) were diluted 10-fold in phosphate buffer pH 6.8, there would be 160 mg ethyl oleate, 200 mg CREMOPHOR® RH 40, and 4.3 g water. In this instance, amount of ester component is equivalent to ~3.4% w/w (ester to the sum of ester, surfactant, and water; which is more than 0 wt. %) and the amount of surfactant is equivalent to ~4.3% w/w (surfactant to the sum of ester, surfactant and water; which is more than 0 wt. %). As claim 1 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claims 5 and 6, the nanoemulsion of C7 diluted 10-fold in phosphate buffer pH 6.8 (pg. 4, Table 1; pg. 4, Robustness to dilution; and pg. 9, Table 4) anticipates at least the embodiment of each of claims 5 and 6 drawn to the emulsion of any embodiment of claim 1 wherein R1 is further defined. As described above, this embodiment of Agrawal anticipates embodiments (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes ethyl oleate as the ester, which has an R1 group having 17 carbon atoms that are unsubstituted. As claims 5 and 6 provide the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claims on the whole.
Regarding claim 7, the nanoemulsion of C7 diluted 10-fold in phosphate buffer pH 6.8 (pg. 4, Table 1; pg. 4, Robustness to dilution; and pg. 9, Table 4) anticipates at least the embodiment of claim 7 drawn to the emulsion of any embodiment of claim 1 wherein R2 is further defined. As described above, this embodiment of Agrawal anticipates embodiments (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes ethyl oleate as the ester, which has an ethyl R2 group that can be described as an unsubstituted linear C2 alkyl group. As claim 7 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 8, the nanoemulsion of C7 diluted 10-fold in phosphate buffer pH 6.8 (pg. 4, Table 1; pg. 4, Robustness to dilution; and pg. 9, Table 4) anticipates at least the embodiment of claim 8 drawn to the emulsion of any embodiment of claim 1 wherein the surfactant is further defined. As described above, this embodiment of Agrawal anticipates embodiments (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes CREMOPHOR® RH 40 as the only non-ionic surfactant compound. Therefore, the surfactant is a single surfactant. Agrawal describes TRANSCUTOL® P as a cosurfactant (pg. 7, Screening of cosurfactants), which is understood by the examiner to refer to a compound that further stabilizes an emulsion but is not a surfactant itself and therefore is considered a further component and not another surfactant compound (pg. 3, Screening of cosurfactants). As claim 8 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 9, the nanoemulsion of C7 diluted 10-fold in phosphate buffer pH 6.8 (pg. 4, Table 1; pg. 4, Robustness to dilution; and pg. 9, Table 4) anticipates at least the embodiment of claim 9 drawn to the emulsion of any embodiment of claim 1 wherein the surfactant is further defined. As described above, this embodiment of Agrawal anticipates embodiments (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes CREMOPHOR® RH 40 as the only non-ionic surfactant compound. This surfactant can be described as having polyoxyethylene groups having 40 ethyleneoxy units and three hydrophobic alkyl groups containing 17 carbon atoms each (pg. 2, Fig. 1). As claim 9 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 10, the nanoemulsion of C7 diluted 10-fold in phosphate buffer pH 6.8 (pg. 4, Table 1; pg. 4, Robustness to dilution; and pg. 9, Table 4) anticipates at least the embodiment of claim 10 drawn to the emulsion of any embodiment of claim 1 wherein the water component is further defined. As described above, this embodiment of Agrawal anticipates embodiments (Be), (Ce1), (Ce3), and (Ce4) of claim 1. In this embodiment, the water component is a phosphate buffer (pg. 4, Robustness to dilution), which is among the claimed list of pharmaceutically acceptable buffers. As claim 10 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 12, the nanoemulsion of C7 diluted 10-fold in phosphate buffer pH 6.8 (pg. 4, Table 1; pg. 4, Robustness to dilution; and pg. 9, Table 4) anticipates at least the embodiment of claim 12 drawn to the emulsion of any embodiment of claim 1 wherein the composition of the emulsion is further defined. As described above, this embodiment of Agrawal anticipates embodiments (Be), (Ce1), (Ce3), and (Ce4) of claim 1. As described above, this embodiment can be described as containing 4.3 mL (4,300 mg) phosphate buffer pH 6.8, 160 mg ethyl oleate, and 200 mg CREMOPHOR® RH 40. In this emulsion, the ester component to surfactant ratio is 40:50 (w/w) (which is between 40:1 and 40:60). The emulsion also possesses a ratio of water-to-surfactant ratio of 21.5:1 (w/w) (which is between 1000:1 and 55:45). Furthermore, the ratio of water-to-ester component is ~27:1 (w/w) (which is between 1000:1 and 4:6). As claim 12 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 15, the nanoemulsion of C7 diluted 10-fold in phosphate buffer pH 6.8 (pg. 4, Table 1; pg. 4, Robustness to dilution; and pg. 9, Table 4) anticipates at least the embodiment of claim 15 drawn to the emulsion of any embodiment of claim 1 wherein the composition of the emulsion is further defined. As described above, this embodiment of Agrawal anticipates embodiments (Be), (Ce1), (Ce3), and (Ce4) of claim 1. The formulation of C7 of Agrawal includes TRANSCUTOL® P as a cosurfactant compound (pg. 7, Screening of cosurfactants). As this compound is not the ester component, surfactant, or water component, this reads as an optional further component. TRANSCUTOL® P is a liquid and Agrawal describes homogenizing this compound with ethyl oleate (pg. 3, Screening of cosurfactants), demonstrating that TRANSCUTOL® P is miscible with the ester component. As claim 15 provides the listed embodiments in the alternative, Agrawal anticipating at least one of these embodiments anticipates the claim on the whole.
Claims 1, 6-7, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Babic (WO 2020/165349 A1 – provided in IDS filed August 13, 2024).
Babic teaches a method of diagnosis of cachexia or precachexia by computed tomography using a CT contrast agent (pg. 1, lines 4-5). The CT contrast agent may be a nanoemulsion (pg. 4, lines 16-20). Babic defines that the nanoemulsion is a colloidal system of lipophilic ingredient in water (pg. 14, lines 11-16). These nanoemulsions contain an iodinated fatty acid component of Formula I of Babic (pg. 19, line 14 through pg. 20, line 4). Babic teaches the synthesis of ethyl monoiodostearic acid (pg. 28, line 21 through pg. 30, line 3), ethyl 16-iodohexadecanoate (pg. 43-44, Examples 3-5), ethyl 12-iododecanoate (pg. 44-45, Examples 6-8), and ethyl triiodooctadecanoate (pg. 46-47, Example 10), which are all molecules that fit the scope of the aforementioned iodinated fatty acid component, serving as specific examples of this component. Babic also teaches that the amount of the iodinated fatty acid component in the nanoemulsion composition is 10-40% by weight (pg. 35, lines 11-14). The nanoemulsions further contain biocompatible emulsifiers, of which lecithins, polysorbates, and sorbitan esters are preferred surfactants (pg. 24, line 28 through pg. 25, line 4). Babic discloses that polysorbates (TWEEN®) 20, 40, 60, and 80 and sorbitan esters (SPAN®) 20, 40, 60, 80, and 85 are among the specific examples of the short-list of biocompatible emulsifiers / surfactants for use in this nanoemulsion (pg. 33, lines 7-9). Babic teaches that the amount of the surfactant in the nanoemulsion is 5-30% w/w of the total nanoemulsion (pg. 25, lines 5-6).
Regarding claim 1, the nanoemulsion of Babic contains an iodinated fatty acid component of Formula I of Babic (pg. 19, line 14 through pg. 20, line 4). Babic specifically teaches the synthesis of ethyl monoiodostearic acid (pg. 28, line 21 through pg. 30, line 3), ethyl 16-iodohexadecanoate (pg. 43-44, Examples 3-5), ethyl 12-iododecanoate (pg. 44-45, Examples 6-8), and ethyl triiodooctadecanoate (pg. 46-47, Example 10), as molecules that fit the scope of this iodinated fatty acid component. Each of these molecules are ethyl esters that at least read on the requirements in the embodiment of (Ce1). Furthermore, the nanoemulsion of Babic further contains biocompatible emulsifiers, of which lecithins, polysorbates, and sorbitan esters are preferred surfactants (pg. 24, line 28 through pg. 25, line 4). Babic discloses that polysorbates (TWEEN®) 20, 40, 60, and 80 and sorbitan esters (SPAN®) 20, 40, 60, 80, and 85 are among the specific examples of the short-list of biocompatible emulsifiers / surfactants for use in this nanoemulsion (pg. 33, lines 7-9). These are non-ionic surfactant molecules. Babic defines that the nanoemulsion is a colloidal system of lipophilic ingredient in water (pg. 14, lines 11-16), which is interpreted to mean that the nanoemulsion contains a water component. Additionally, Babic teaches that the amount of the iodinated fatty acid component in the nanoemulsion composition is 10-40% by weight (pg. 35, lines 11-14) and that the amount of the surfactant in the nanoemulsion is 5-30% w/w of the total nanoemulsion (pg. 25, lines 5-6). Thus, the nanoemulsion of Babic at least anticipates embodiment (Ce1). As claim 1 provides the listed embodiments in the alternative, Babic anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claims 6 and 7, the nanoemulsion of Babic contains an iodinated fatty acid component of Formula I of Babic (pg. 19, line 14 through pg. 20, line 4). Babic specifically teaches the synthesis of ethyl monoiodostearic acid (pg. 28, line 21 through pg. 30, line 3), ethyl 16-iodohexadecanoate (pg. 43-44, Examples 3-5), ethyl 12-iododecanoate (pg. 44-45, Examples 6-8), and ethyl triiodooctadecanoate (pg. 46-47, Example 10), as molecules that fit the scope of this iodinated fatty acid component. Of these molecules, ethyl monoiodostearic acid, ethyl 16-iodohexadecanoate, and ethyl triiodooctadecanoate each can be described as ester components containing R2 and R1 structures that read on the limitations of claims 6 and 7. Therefore, the nanoemulsion of Babic at least anticipates the embodiments of claims 6 and 7 drawn to dependence on the emulsion of claim 1, embodiment (Ce1). As claims 6 and 7 provide the listed embodiments in the alternative, Babic anticipating at least one of these embodiments anticipates the claims on the whole.
Regarding claim 11, Babic teaches that the amount of the iodinated fatty acid component in the nanoemulsion composition is 10-40% by weight (pg. 35, lines 11-14) and that the amount of the surfactant in the nanoemulsion is 5-30% w/w of the total nanoemulsion (pg. 25, lines 5-6). Therefore, the nanoemulsion of Babic at least anticipates the embodiments of claim 11 drawn to dependence on the emulsion of claim 1, embodiment (Ce1). As claim 11 provides the listed embodiments in the alternative, Babic anticipating at least one of these embodiments anticipates the claims on the whole.
Claims 1, 5-6, 9, 11-12, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hameyer (US 2007/0178144 A1 – provided in IDS filed August 13, 2024).
Hameyer teaches prolonged-stability, low-viscosity, fine oil-in-water emulsions and their preparation (pg. 1, [0001]). Such emulsions include at least one non-ionic primary emulsifier, one or more oils, and a water phase (pg. 2, [0039]-[0048]). One specific embodiment of the emulsion of Hameyer is that of Example emulsion 8 (pg. 7, [0126]), which contains 7.5% ethylhexyl palmitate, 2.5% Emulsifier 7 (which is 77% polyglyceryl-4 laurate, 19% sorbitan laurate, and 4% dilauryl citrate (pg. 6, [0115])), 0.8% EUXYL® K 300, 0.2% perfume, and 89% water. Hameyer teaches that Example emulsion 8 has a hydrodynamic radius of 75 nm, which is equivalent to a diameter of 150 nm (pg. 8, [0130]).
Regarding claim 1, the Example emulsion 8 of Hameyer contains ethylhexyl palmitate (pg. 7, [0126]). This is an ester component that reads on at least the requirements of Formula I in embodiment (Be) of claim 1. Furthermore, the emulsion contains polyglyceryl-4 laurate and sorbitan laurate, which are non-ionic surfactant molecules. This emulsion also contains perfume, EUXYL® K 300, and dilauryl citrate, which are interpreted to be one or more optional further components. The emulsion also contains water. As Emulsifier 7 is 77% polyglyceryl-4 laurate, 19% sorbitan laurate, and 4% dilauryl citrate (pg. 6, [0115]), this means the emulsion contains 1.925% polyglyceryl-4 laurate and 0.475% sorbitan laurate, for a sum of 2.4% of the total composition being non-ionic surfactant. In Example emulsion 8, the amount of ester component relative to the ester, non-ionic surfactant, and water is ~7.6% and the amount of non-ionic surfactant to the same total is ~2.4%. Thus, the Example 8 emulsion of Hameyer at least anticipates embodiment (Be). As claim 1 provides the listed embodiments in the alternative, Hameyer anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claims 5 and 6, the Example 8 emulsion of Hameyer contains ethylhexyl palmitate (pg. 7, [0126]), which is an ester component that can be described as possessing a branched chain C8 alkyl R2 group and an unsubstituted linear alkyl R1 group containing 15 carbon atoms. Therefore, this emulsion of Hameyer at least anticipates the embodiments of claims 5 and 6 drawn to dependence on the emulsion of claim 1, embodiment (Be). As claims 5 and 6 provide the listed embodiments in the alternative, Hameyer anticipating at least one of these embodiments anticipates the claims on the whole.
Regarding claim 9, the Example emulsion 8 of Hameyer contains polyglyceryl-4 laurate and sorbitan laurate, as non-ionic surfactant molecules (pg. 7, [0126]). Both of these surfactants are composed of a sugar alcohol linked to a hydrocarbon group having 12 carbon atoms. Thus, this emulsion of Hameyer at least anticipates the embodiment of claim 9 dependent on the emulsion of claim 1, embodiment (Be). As claim 9 provides the listed embodiments in the alternative, Hameyer anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 11, the Example emulsion 8 of Hameyer contains 7.5% ethylhexyl palmitate ester component, 2.5% Emulsifier 7, and 89% water (pg. 7, [0126]). As Emulsifier 7 is 77% polyglyceryl-4 laurate, 19% sorbitan laurate, and 4% dilauryl citrate (pg. 6, [0115]), this means the emulsion contains 1.925% polyglyceryl-4 laurate and 0.475% sorbitan laurate, for a sum of 2.4% of the total composition being non-ionic surfactant. In Example emulsion 8, the amount of ester component relative to the ester, non-ionic surfactant, and water is ~7.6% and the amount of non-ionic surfactant to the same total is ~2.4%. Thus, the Example 8 emulsion of Hameyer at least anticipates the embodiment of claim 11 dependent on the emulsion of claim 1, embodiment (Be). As claim 11 provides the listed embodiments in the alternative, Hameyer anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 12, as described above, the Example emulsion 8 of Hameyer contains 7.5% ethylhexyl palmitate ester component, 2.4% total non-ionic surfactant component, and 89% water (pg. 7, [0126]; and pg. 6, [0115]). Therefore, the ester component-to-surfactant ratio is 40:12.8, the water-to-surfactant ratio is ~1000:27, and the water-to-ester component ratio is ~1000:84. Thus, the Example emulsion 8 of Hameyer at least anticipates the embodiment of claim 12 dependent on the emulsion of claim 1, embodiment (Be). As claim 12 provides the listed embodiments in the alternative, Hameyer anticipating at least one of these embodiments anticipates the claim on the whole.
Regarding claim 15, the Example emulsion 8 of Hameyer also contains EUXYL® K 300 (pg. 7, [0126]), which is described as a cosurfactant (pg. 4, [0067]). As described in the above Agrawal rejection, a cosurfactant is a compound that further stabilizes an emulsion but is not a surfactant itself, reading on the further component limitation. Furthermore, Hameyer teaches a related example clear oil phase 8 that is equivalent to a concentrate of the ester component, emulsifier, and cosurfactant of example emulsion 8 with negligible water present (pg. 6, [0117]). This is evidence that the EUXYL® K 300 is miscible in the ester component. Thus, the Example emulsion 8 of Hameyer at least anticipates the embodiment of claim 15 dependent on the emulsion of claim 1, embodiment (Be). As claim 15 provides the listed embodiments in the alternative, Hameyer anticipating at least one of these embodiments anticipates the claim on the whole.
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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Hameyer (US 2007/0178144 A1 – provided in IDS filed August 13, 2024) further in view of Provence (French Apple Cider Vinaigrette, A Touch of Provence, Webpage, captured October 17, 2019, provided with examiner-appended last 2 pages with higher resolution images), Stuart (The simplest of salad dressings – Vinaigrette, We are not foodies, Webpage, captured January 25, 2015), and Mazon-Chambers (The best simple vinaigrette recipe, Cooking with cocktail rings, Webpage, published October 5, 2021).
As described above, Hameyer teaches prolonged-stability, low-viscosity, fine oil-in-water emulsions and their preparation (pg. 1, [0001]). Such emulsions include at least one non-ionic primary emulsifier, one or more oils, and a water phase (pg. 2, [0039]-[0048]). One specific embodiment of the emulsion of Hameyer is that of Example emulsion 8 (pg. 7, [0126]), which contains 7.5% ethylhexyl palmitate, 2.5% Emulsifier 7 (which is 77% polyglyceryl-4 laurate, 19% sorbitan laurate, and 4% dilauryl citrate (pg. 6, [0115])), 0.8% EUXYL® K 300, 0.2% perfume, and 89% water. Hameyer teaches that the emulsion is typically prepared using a simple stirrer apparatus at room temperature and that no additional homogenization step is required (pg. 4, [0079]-[0080]).
Hameyer does not explicitly teach a product comprising a container containing a composition and instructions wherein the composition consists of an ester component, a surfactant, a water component, and one or more optional further components and is not in the form of an emulsion
Provence provides a French apple cider vinaigrette bottle for sale on a webpage (pg. 6). On the back label of this bottle are instructions to “shake well before using” (pg. 7, annotated at higher resolution on pages 11-12).
Stuart teaches that vinaigrettes are an emulsion of an oil and an aqueous phase (acid) (pg. 2, paragraph 1). Stuart also teaches that such an emulsion can be made just by shaking the ingredients (paragraph split between pg. 3-4). Stuart also describes that the vinaigrette ingredients will settle out over time and separate, but can be re-emulsified (paragraph split between pg. 3-4).
Mazon-Chamber also teaches that vinaigrettes are mixtures of oils and aqueous (acid) phases that are prepared by an emulsification process (pg. 2, paragraph 1; and pg. 22, Instruction step 2). Mazon-Chambers also teaches that vinaigrettes may contain emulsifying agents in them to improve the stability of the emulsion by keeping the oil and acid components together (pg. 5, Dijon). Mazon-Chambers also teaches that vinaigrettes may be emulsified by shaking the mixture of ingredients in a container (pg. 7, Method 2).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the means of making the emulsion product of Hameyer by packaging the composition in a container with instructions to shake as taught by Provence, as such shaking could be used to emulsify the product itself or any fraction of the composition that had separated, as taught by Stuart and Mazon-Chambers (MPEP § 2143(I)(G)). This would result in the predictable result of a product with instructions containing water, ester, surfactant, and one or more optional further components not yet emulsified before shaking.
A person of ordinary skill in the art would have a reasonable expectation of success in making such a product because Hameyer describes preparing the emulsion with “a simple stirrer apparatus,” (pg. 4, [0079]) to impart agitation on the mixture to form the emulsion. This is a low energy means. Stuart and Mazon-Chambers teach that emulsions may be prepared by shaking the ingredients. If a simple stirrer is capable of preparing an emulsion, shaking in a container containing the non-emulsified composition would predictably also be able to prepare the emulsion.
The skilled artisan would have been motivated to make this modification because putting the composition in a container such as the one disclosed by Provence provides a means for distributing the product to consumers in a ready to prepare form. As Stuart describes that emulsions can separate over time, including instructions to shake before use on a container would encourage the end-user to re-emulsify any portion of the composition not in the form of an emulsion at that time, likely improving the utility of the product and benefit to the user.
Regarding claim 2, as described in the above 102 rejection, the Example emulsion 8 of Hameyer anticipates at least embodiment (Be) of claim 1 (pg. 7, [0126]). Furthermore, Provence teaches providing a vinaigrette in a container with instructions to shake well before use (pg. 6-7 and pg. 11-12). Stuart (paragraph split between pg. 3-4) and Mazon-Chambers (pg. 7, method 2) teach that a vinaigrette is an emulsion product that can be made by shaking, so the container of Provence is interpreted to contain instructions to emulsify by manual shaking of the container. The aforementioned modification is to modify the method of Hameyer to prepare the emulsion by shaking in a bottle instead of using a simple stirrer apparatus. Thus, when the ingredients are combined in the bottle, for the time period before shaking occurs, the composition is not in the form of an emulsion. Furthermore, Stuart teaches that emulsions can separate over time (paragraph split between pg. 3-4). Thus, even after emulsification in the container, over time, some portion of the composition will no longer be emulsified; therefore, the container will contain some amount of composition not in the form of an emulsion.
Therefore, the combined teachings of Hameyer, Provence, Stuart, and Mazon-Chambers render claim 2 obvious. As claim 2 provides the listed embodiments in the alternative, the combination of the above references rendering at least one of these embodiments obvious rejects the claim on the whole.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Hameyer (US 2007/0178144 A1 – provided in IDS filed August 13, 2024) further in view of Novartis (Novartis, Sandimmun Neoral®, July, 2020).
As described above, Hameyer teaches prolonged-stability, low-viscosity, fine oil-in-water emulsions and their preparation (pg. 1, [0001]). Such emulsions include at least one non-ionic primary emulsifier, one or more oils, and a water phase (pg. 2, [0039]-[0048]). Hameyer teaches preparing the emulsions by mixing a clear oil phase (which itself may lack water, pg. 6, [0117]) with water at room temperature using a simple stirrer apparatus (pg. 7, [0122]). Hameyer states that such clear oil phase compositions are advantageous for the preparation of fine oil in water emulsions (pg. 4, [0081]). One specific embodiment of the clear oil phase of Hameyer is that of Example clear oil phase 7 (pg. 6, [0117]), which contains 70.7% ethylhexyl palmitate, 23.6% Emulsifier 7 (which is 77% polyglyceryl-4 laurate, 19% sorbitan laurate, and 4% dilauryl citrate (pg. 6, [0115])), and 5.7% EUXYL® PE 9010.
Hameyer does not teach a product consisting of an ester component, a surfactant, and one or more optional further components that does not contain water wherein the product is further provided with instructions.
The Novartis reference is a document describing the product Sandimmun Neoral®. This document describes the composition of the oral solution product as containing ciclosporin, triglycerides, macrogolglycerol hydroxystearate, and polyoxyl 40 hydrogenated castor oil (pg. 1, Active Substance; and pg. 1-2, Oral solution). Novartis describes the product as a microemulsion preconcentrate and states that the microemulsion is formed by combining the product with water (pg. 1, Active Substance, paragraph 3). Provided in the document are instructions for using the oral solution microemulsion concentrate (pg. 23-25). The instructions direct the user to combine the composition with water and stir it to mix it (pg. 24, Step 8).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the clear oil phase 7 of Hameyer by including instructions to mix with water as taught by Novartis because combining instructions with a pre-emulsion product is an element known in the art and one of ordinary skill in the art could have combined these features by known methods with no change in their respective functions, and their combination would have yielded the predictable outcome of a premix composition provided with instructions.
A person of ordinary skill in the art would have a reasonable expectation of success in combining these features because providing instructions for use of a pre-emulsion product is a feature demonstrated by Novartis to be known in the art. The addition of instructions to the clear oil phase pre-emulsion composition of Hameyer does not change the function of either feature. As both Hameyer and Novartis relate to compositions that can be described as emulsion preconcentrates that are prepared for final use by mixing with water and agitating, there would be an expected success in combining the instructions of Novartis with the product of Hameyer.
The skilled artisan would have been motivated to make this modification because providing instructions for how to prepare and use a product to an end-user would improve the experience of said user and increase the proper use, and therefore utility, of the product by the user.
Regarding claim 3, Example clear oil phase 7 of Hameyer contains 23.6% emulsifier 7, 70.7% ethylhexyl palmitate, and 5.7% Euxyl® PE 9010 (pg. 6, [0117]). Ethylhexyl palmitate is an ester component that reads on the ester component limitations of claim 1 wherein R1 is a hydrocarbon group containing 15 carbons that is not substituted and R2 is an unsubstituted C8 branched chain alkyl group. As Emulsifier 7 is 77% polyglyceryl-4 laurate, 19% sorbitan laurate, and 4% dilauryl citrate (pg. 6, [0115]), this means the clear oil phase contains ~18% polyglyceryl-4-laurate and ~4.5% sorbitan laurate, for a sum of ~22.5% of the total composition being non-ionic surfactant. The EUXYL® PE 9010 is described by Hameyer to be a cosurfactant preservative (pg. 4, [0068]), which reads on being a further additional component, which is permitted in the scope of each embodiment of claim 3. The composition of Example clear oil phase 7 of Hameyer does not contain water. The weight ratio of ester component to non-ionic surfactant is ~3:1 and the weight of non-ionic surfactant relative to the total weight of ester component and surfactant is ~24%. As described in the 102 rejection using the Hameyer reference above, ethylhexyl palmitate and Emulsifier 7 read on the requirements of at least the ester and surfactant components of embodiment (Be) of claim 1. Therefore, the Example clear oil phase 7 of Hameyer reads on at least the premix composition of (Bpp) of claim 3. Additionally, Novartis provides instructions (pg. 23-25) to be provided with a microemulsion preconcentrate (pg. 1, Active substance), which is a formulation of oils and emulsifiers lacking water (similar to the clear oil phase of Hameyer) that is to be mixed with water to prepare an emulsion (similar to Hameyer). For the above stated reasons, it would have been obvious to combine the instructions of Novartis with the composition of Hameyer to produce a product with instructions. Novartis teaches that mixing the Neoral® product with water will produce a microemulsion (pg. 1, Active substance) and the instructions direct the user to add the product to water and mix with water by stirring (pg. 24, Step 8), which the examiner interprets to be a low energy or ultra-low energy method. Therefore, the combined teachings of Hameyer and Novartis render claim 3 obvious. As claim 3 provides the listed embodiments in the alternative, the combination of the above references rendering at least one of these embodiments obvious rejects the claim on the whole.
Regarding claim 13, Example clear oil phase 7 of Hameyer contains 23.6% emulsifier 7, 70.7% ethylhexyl palmitate ester component, and 5.7% Euxyl® PE 9010 (pg. 6, [0117]). As Emulsifier 7 is 77% polyglyceryl-4 laurate, 19% sorbitan laurate, and 4% dilauryl citrate (pg. 6, [0115]), this means the clear oil phase contains ~18% polyglyceryl-4-laurate and ~4.5% sorbitan laurate, for a sum of ~22.5% of the total composition being non-ionic surfactant. Therefore, in this premix composition, the surfactant is present in a weight of ~24% relative to the total weight of ester component and surfactant. This value is within the range of 2-60%, which is the scope of the claim (see associated 112(b) rejection) and therefore renders the range obvious (MPEP § 2144.05). Furthermore, as described above, the Example clear oil phase 7 of Hameyer reads on the composition of at least the premix of embodiment (Bpp). Therefore, the combined teachings of Hameyer and Novartis render claim 13 obvious. As claim 13 provides the listed embodiments in the alternative, the combination of the above references rendering at least one of these embodiments obvious rejects the claim on the whole.
Conclusion
No claim is allowed.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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