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 .
DETAILED ACTION
Status of the Claims
Claims 1-16 are pending. Claims 1-5 and 12-16 have been withdrawn. Claims 6-11 have been amended. Claims included in the prosecution are claims 6-11.
Withdrawn Objections/Rejections
The objections to the specification and the claims are withdrawn.
In light of the new amendments regarding trademarks/trade names the rejection of claims 7 and 11 under 35 U.S.C. § 112 (b) as being indefinite is withdrawn.
In light of the new amendments, e.g., removal of the term “stock,” and/or upon further consideration the rejection of claim 6 under 35 U.S.C. § 112 (b) as being indefinite is withdrawn.
New Rejections
Applicants’ amendments have necessitated the following grounds of rejection:
Claim Rejections - 35 USC § 112
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.
Claim 6 and all dependent claims 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 claim(s) contains 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.
Applicants describe mixing analgesic lipid phase and surfactant solution and then obtain a solid lipid nanoparticulate stock formulation (see Spec., pg. 17, Step 5) but no mention of encapsulating the active. A thorough search of the instant specification appears to show no support of encapsulation of natural analgesic as claimed.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. § 103 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Rahmani (WO 2022040773 A1) in view of Mishra et al. (Solid Lipid Nanoparticles: Emerging Colloidal Nano Drug Delivery Systems. Pharmaceutics, 2018, 10, 191, pg. 1-21).
Rahmani discloses a composition comprising an oil-in-water nano-emulsion dispersed in an external oil phase, the oil-in-water nano-emulsion comprising an internal oil phase dispersed in an aqueous phase and stabilized by a film-forming thermoreversible emulsifier, wherein the internal oil phase comprises a liquid oil in combination with a charged lipid; the external oil phase comprises a combination of solid lipids, the aqueous phase comprises a humectant ([0075], claim 1). Rahmani teaches that the embodiments for the active ingredients, natural and/or herbal active agents with anti-inflammatory, analgesic, terpenoids; essential oils or combinations thereof can be varied ([00137]). The Nano-Emulsion SR Cream taught by Rahmani comprises THC distillate, CBD oil to obtain a smooth and homogeneous product, and CBD isolate ([00100], [00174] see CBD isolate in Example 9) to read on cannabinoid isolate species of instant claim 9 and as such reads on claim 6. Here the prior art meets the requirement of the two phases of the claimed invention, each comprising a lipid matrix forming agent.
Rahmani teaches the internal oil phase comprises a liquid oil in combination with a charged lipid; the external oil phase comprises a combination of solid lipids ([0011-0012]). Glyceryl palmitostearate is taught as being in the combination of solid lipids ([00118]) to read on the first OR second lipid matrix forming agent selected from glyceryl palmitostearate species of instant claim 7 thereby meeting the requirement of claim 6.
Regarding a permeability enhancer, Rahmani teaches that in some embodiments, the penetration enhancer comprises a natural penetration enhancer. In another embodiment, the natural penetration enhancer is one or more terpenoids. In another embodiment, the terpenoid is cineol, eucalyptol limonene, linalool, menthol or combinations thereof. In another embodiment, the penetration enhancer comprises menthol ([0071]) to read on the menthol species of instant claim 8 thereby meeting the requirement of claim 6.
Regarding a solubilizer in claim 6, Rahmani teaches that liquid emollients and penetration enhancers can be polar or non-polar and suitably have the ability to dissolve soluble and poorly water-soluble active ingredients, respectively ([00120-00121]). Ethoxy diglycol (i.e., diethylene glycol monoethyl ether) as a safer compared to the commonly used solubilizer DMSO ([0071]).
With respect to surfactant solutions in claim 6, Rahmani discloses purified water and poloxamer (i.e., surfactant) serve as the film-forming thermoreversible emulsifier amphoteric tri-block copolymer that is a polyethylene glycol-b-polypropylene glycol-b-polyethylene glycol (poloxamer) (claim 9).
Regarding the last lines of instant claim 6 (i.e., particle size limitation, solid lipid core matrix), as mentioned above, Rahmani teaches a nano-emulsion core stabilized in the above-mentioned Nano-Emulsion SR Cream ([0010]). Rahmani teaches compositions that can entrap (i.e., encapsulate) lipophilic active ingredients in both the internal and external oil phase ([0096]).
Rahmani differs from the instant claims insofar as not disclosing wherein the formulation comprises solid lipid nanoparticles (SLN) having a particle size ranging from 10 nm to 1000 nm.
However, Mishra teaches that SLNs are made up of solid lipids (high melting fat matrix) and that SLNs are nanoscopic size from 50 nm to 1000 nm (page 1, Introduction). Here the teachings of Mishra meet the solid lipid core matrix requirement and teaches a particle size that falls within the claimed range of 10-1000 nm.
It would have been prima facie obvious apply the teachings of Mishra to those of Rahmani to create nanoparticles of the instantly claimed size. One skilled in the art would have been motivated to do so because Rahmani recognizes appropriate particle sizes influence the stability ([00110]). Mishra teaches that SLNs are enabled to bypass spleen and liver filtration because of their nano size range (page 2, section 1.1). As such, SLNs can provide high stability to incorporated drugs and improve bioavailability of poorly water-soluble molecules (page 2, section 1.1). This is important to Rahmani with respect to drug delivery of formulations containing CBD isolate (see Rahmani [0025], claim 28). Moreover, immobilizing drug molecules within solid lipids provides protection from photochemical, oxidative, and degradation of drug (see Mishra page 2, section 1.1). Mishra supports Rahmani’s objectives to reduce oxidative reactions and provide sustained pain relief in the transdermal delivery of natural active agents ([0010], [0072], [00160]).
Claim 6, with the limitations of steps, e.g., independent selection, homogenizing, is a product by process claim. MPEP 2113 states that “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Rahmani (WO 2022040773 A1) in view of Mishra et al. (Solid Lipid Nanoparticles: Emerging Colloidal Nano Drug Delivery Systems. Pharmaceutics, 2018, 10, 191, pg. 1-21) as applied to claims 6-9 above and further in view of Woo et al. (US 6428821 B2).
The teachings of Rahmani and Mishra above are incorporated herein.
As mentioned above, Rahmani teaches ethoxy diglycol (i.e., penetration enhancer) and polyethylene glycol- b-polypropylene glycol-b-polyethylene glycol (e.g. Poloxamer 407) (i.e., film forming thermoreversible emulsifier) ([0076-0078]).
Regarding claims 10 and 11, in Rahmani polyethylene glycol and polypropylene glycol are of poloxamer ([0076]), while polysorbate 80 is in isohexadecane and polysorbate 80 (e.g., SIMULGEL 600) ([0069]).
Woo teaches polyethylene glycol and polysorbate 80 as solubilizer and surfactant.
Woo discloses a micro-emulsion composition of Carduus marianus containing a major amount of silybin as the active ingredient in a stable emulsion (col. 1, line 15). The composition comprises a surfactant which promotes the wetting of the active ingredient (col. 2, line 35). Polyoxyethylene-sorbitan-fatty acid esters (Tween®, e.g., polysorbate 80), polyoxyethylene-polyoxypropylene block copolymer (Poloxamer®), and phospholipids (col. 2, lines 42, 49, 52) are taught as surfactants.
Woo explains that the co-surfactant assists the formulation of a uniform emulsion of the active ingredient and keeps the emulsion stable during a storage. The co-surfactant which may be used includes propylene glycol (1,2-dihydroxypropane), polyethylene glycol, e.g., having a molecular weight of 200 to 600, transcutol (diethylene glycol monoethyl ether), or a mixture thereof (col. 2 lines 18-25; claim 3, see Ex. 4). Here Woo discloses an essential component that is effectively used to solubilize (the active). Components that are disclosed in Rahmani are also taught by Woo (i.e., poloxamer, diethylene glycol monoethyl ether).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to incorporate the polyethylene glycol of Woo and/or substitute the ethoxy diglycol of Rahmani with the polyethylene glycol of Woo for a similar purpose of solubilizing the active. Simple substitution of one solubilizer for another is within the purview of the skilled artisan and would yield predictable results.
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to incorporate the surfactants taught by Woo in the composition taught by Rahmani in view of Mishra with expected results. One would be motivated to do so with an expectation of success because Woo et al. demonstrates improved bioavailability of the active (col. 1, line 13). And the oral composition taught by Woo meets the safety expectations of topical compositions and therefore supports Rahmani’s objective in providing formulations using natural components (see Rahmani, natural oils and active agents, claims 4, 29, 38 and 58).
Response to Arguments
Applicants’ arguments are based on newly amended limitations which have been addressed by the new grounds of rejection above.
Applicants’ arguments have been fully considered but they are not persuasive.
Applicants argue that Rahmani’s composition is a multiple emulsion system in which an oil-in-water nano-emulsion is dispersed within an external solid lipid phase (Remarks, page 9, last paragraph).
Rahmani teaches the lipid phases and combination of solid lipids to deliver a natural analgesic. Rahmani suggests adding the third mixture comprising the combination of solid lipids to the oil-in-water nano-emulsion as an advantage during manufacturing due to the respective volumes of these components ([00135]). The order of providing mixtures in claims and the current record does not support a finding that mixing the second mixture (B) and the third mixture (C) together to form a fourth mixture (D) is critical. The selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. MPEP §2144.04.
In response to applicants’ argument that the independently selected matrix forming agents contribute to the forming of the solid lipid core matrix and is a functional requirement, the Examiner submits that the rejected claims are product claims not method claims. There must be a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art of record. Where an applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim, but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103.
Applicants argue that Rahmani does not teach the species of rejected claim 9.
Rahmani teaches that the compositions of the present disclosure can entrap lipophilic active ingredients ([0095]). Rahmani teaches combining solid lipids wherein at least two lipids are selected ([0034]). Rahmani discloses CBD isolate ([00100-0101], see Example 9 [00174] CBD isolate 99%)
Applicants argue Rahmani teaches menthol as an active ingredient.
The Examiner asserts Rahmani clearly teaches menthol as a permeability enhancer in paragraph [0071].
Applicants argue that Woo’s teaching of sorbitan monostearate makes it entirely different from the claimed solid lipid nanoparticulate stock formulation. Applicants argue that substituting the ethoxy diglycol of Rahmani with polyethylene glycol of Woo on the basis that both are well-known, functionally equivalent co-surfactants that can be interchanged with predictable results have not been established.
Rahmani teaches a lipid matrix forming agent. In response to Applicants’ argument that Rahmani’s disclosure of poloxamer does not teach a surfactant, Woo et al. is brought in to teach surfactant and solubilizer. In response to the substitution of ethoxy diglycol with polyethylene glycol, one skilled in the art would recognize the cost benefit of readily available and versatile PEG and the potential for irritation of ethoxydiglycol as Rahmani alludes to the toxicity in paragraph [0071]. As such, Woo et al. improves upon Rahmani.
For these reasons, Applicants’ arguments are found unpersuasive.
Conclusion
All claims under consideration remain rejected; no claims are allowed. Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no case, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Karen Ketcham whose telephone number is (571)270-5896. The examiner can normally be reached 0830-1630.
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/Karen A Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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