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 2, 3, 7, 11, 12, 14-18, 21, 23, 26 and 27 are pending.
Claims 1, 4-6, 8-10, 13, 19, 20, 22, 24, 25, and 28-31 are canceled.
Claims 2, 3, and 14 are amended.
Claims 2, 3, 7, 11, 12, and 14-18 are in the prosecution.
Withdrawn Objections/Rejections
The objections to claims 5 and 21 are withdrawn.
New Rejections
Applicants’ amendments have necessitated the following grounds of rejection:
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 2, 3, and 7 are rejected under 35 U.S.C. § 103 as being obvious over Livney (US 2016/0220502 A1) in view of Harel et al. (US 2016/0038428 A1) with evidence from Cambridge (Cambridge Polymer Group, Fatty Acid and Triglyceride Analysis: Linseed Oil, 2017, pages 3 and 4 of 5, archive verified June 2018).
Livney discloses a nanoparticle made of a potato protein (PP) and a hydrophobic bioactive compound bound to the potato protein (abstract, [0011], claim 1). Livney discloses a nanoparticle (or a plurality of nanoparticles) comprising a potato protein; a bioactive compound bound to the potato protein ([0024], claims 1, 12). The nanocapsule or nanoparticle has a structure which comprises a nano-vesicular system that is formed in a core-shell arrangement ([0026]). Here the teachings of Livney are read on the particle consisting of a core encapsulated in an amphiphilic shell (line 1 of instant claim 2) and wherein said amphiphilic plant protein is a potato protein (PP) (i.e., lines 6-7 of instant claim 2).
Regarding the amphiphilic single layer shell, Livney does not mention more than one layer of the shell in the core-shell arrangement.
Regarding the shell comprises a hydrophobic compound and the core comprises a plant oil limitation, Livney teaches an oil-soluble vitamin, a polyunsaturated fatty acid or its ester, an antioxidant, a phytochemical, an omega-3 fatty acid, or its ester as the said hydrophobic bioactive compound (claim 3, 19). Carotenoid is taught as the bioactive in paragraph [0032]. Looking at the instant disclosure curcuminoids include curcumin (see Spec., [0116]). Applicants disclose exemplary oil-soluble hydrophobic compounds to include a carotenoid, a natural phenol (e.g., resveratrol), hydrophobic vitamin A, D, E, K, a cannabinoid, poly-unsaturated fatty acid (e.g., omega-3 fatty acid), a phytosterol, and curcumin (see Spec., [0111]). The Examiner notes that Livney discloses carotenoids in examples, i.e., Vitamin D. This is not to be read on the claimed bioactive curcuminoid (i.e., line 6 of instant claim 2).
However, Harel is provided to teach curcuminoid as the bioactive.
Harel discloses a composition comprising hydrophobic droplets coated by a shell and dispersed in a matrix and a consumable product comprising the composition (abstract). The hydrophobic droplets comprise a hydrophobic compound, the shell comprises an irreversibly denatured protein, and the matrix comprises a protein, a starch, and a polysaccharide (title, abstract, claim 1). The ratio between the protein and the hydrophobic compound is from 0.1:1 to 1:1 by weight ([0009]) and the proteins may be corn zein and vegetable proteins ([0010]). The hydrophobic compound may be a biologically active or bioactive agent to include vitamins, antibiotics, carotenoids, plant extracts, fruit extracts, vegetable extracts, antioxidants, lipids, steroids, phytochemicals and drugs ([0028]). The composition may further comprise resveratrol, quercetin, carotenoids (e.g., α-, β-, and γ-carotene, astaxanthin), curcuminoids, and polyphenols ([0030], claim 11). The hydrophobic droplets may further comprise an edible oil selected from the group consisting of vegetable oils which may be selected from the group consisting of flaxseed oil, and oil comprising an omega-3 fatty acid or a conjugated linoleic acid ([0034]). Harel teaches hydrophobic compounds to include soluble vitamins, (e.g., Vit A, D, E, and K), tocotrienols, carotenoids, xanthophylls (e.g., astaxanthin) ([0035]).
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 combine the teaching of curcuminoids from Harel with the nanoparticle of Livney with expected results. Given that Harel and Livney both share the same objective to encapsulate bioactive(s) in a plant-based shell and as Harel cites Livney (see Harel, [0037]), their teachings of flaxseed oil, carotenoids, and ratios of protein to hydrophobic compound all overlap. One would be motivated to combine Harel and Livney because Livney provides results that show potato protein prevents the hydrophobic compound from degrading ([0113-0116] see degradation studies).
Regarding the hydrophobic compound to plant protein (0.01:1 to 1:1); plant protein to plant oil (0.1:1 to 10:1), Livney teaches lipid to potato protein concentration ratio 20:1 to 1:20 ([0030]), potato protein at a concentration of 0.1-100 g/L ([0014], [0088], claim 28), and bioactive compound from 0.1 microgram/ml to 1 mg/ml ([0046], claim 16).
Livney teaches a plant (i.e., potato) protein to plant oil (i.e., vitamin) ratio ranging from 0.1:0.0001 to 1,000:1 (0.1-1,000 mg/ml of potato protein; 0.0001-1 mg/ml bioactive/oil) which encompasses a 1:1 ratio which falls within the claimed range. MPEP 2144.05 states that a prima facie case of obviousness exists in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art.
Regarding a microparticle having an average particles size between 1- and 20-microns limitation of claim 2, Livney discloses nanoparticles with a diameter of 10-100 nm ([0033], claim 6) and discloses the size of the nanoparticles in the examples are 20-80 nm in diameter to enable the desired clear solutions ([0104]). Harel teaches that more than about 50% of the coated droplets may have a particle size within the range of about 0.1 μm to about 5.0 μm ([0039], claim 4) to be read on the claimed range. Further, one skilled in the art would optimize and apply routine experimentation to achieve the optimal or desired particle size. MPEP 2144.05.
Regarding wherein at least 80% of the weight of said hydrophobic compound is located in the amphiphilic shell, Livney provides results that show most (80-96%) of the bioactive e.g., vitamin D (VD) is retained in the PP-VD complexes ([0118], see Fig. 6).
Regarding the shell devoid of an additional protein limitation of claim 3, Livney discloses that the potato protein of the composition is devoid of an additional emulsifier ([0012]). No additional proteins are mentioned; one skilled in the art would recognize whey protein as a common emulsifier that is also a protein.
Regarding claim 7, Livney teaches flax seed oil as the bioactive compound ([0031]). As evidenced by Cambridge, flax seed oil, also known as linseed oil, is a triglyceride oil (see page 3 of 5 in the document previously provided).
Claims 11, 12, and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Livney (US 2016/0220502 A1) in view of Harel et al. (US 2016/0038428 A1) with evidence from Cambridge (Cambridge Polymer Group, Fatty Acid and Triglyceride Analysis: Linseed Oil, 2017, pages 3 and 4 of 5, archive verified June 2018) as applied to claims 2, 3 and 7 above, further in view of Shi et al. (US 2013/0315831).
The teachings of Livney, Harel, and Cambridge above are incorporated herein.
Livney discloses that the nanocapsule may encapsulate an inner liquid core, a solid core, or a partly liquid and partly solid core ([0026]).
Olive oil is not disclosed in Livney.
Shi discloses a particle comprising an aqueous core; a first amphiphilic layer surrounding the aqueous core; and a polymeric matrix surrounding the first amphiphilic layer (abstract, [0007], claim 1 ). Shi teaches curcumin (i.e., a curcuminoid) in paragraph [0121], and olive oil in paragraph [0201].
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 olive oil of Shi in the core taught by Livney in view of Harel with expected results. One would be motivated to do so because Shi teaches that the aqueous core may contain lipids ([0045]). In addition, Shi teaches olive oil as a pharmaceutically acceptable carrier ([0201]).
As mentioned above, Livney discloses the bioactive compound at 0.1 µm/ml to 1 mg/ml; 0.5 mg/ml to 5 mg/ml ([0046]) and the ratio of lipid to potato protein is 20:1 to 1:20 ([0030]). Livney does not teach a ratio of bioactive compound to an (encapsulated) oil. Substituting the lipid of Livney in view of Harel with the olive oil of Shi would provide ratios that overlap with the claimed range(s). MPEP 2144.05 states that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
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 olive oil of Shi in the core taught by Livney in view of Harel. Both Shi and Livney focus on encapsulation efficiency and controlling, e.g., slowing release (see Shi [0024], [0053] and Livney [0027], [0077]). One would be motivated to do so because Shi teaches that the encapsulation of multiple agents improves particle stability and high loading efficiency ([0006]). Likewise, Livney teaches a combination of compounds comprising the bioactive ([0026], [0029]).
Regarding claims 14-18, looking to the instant disclosure applicants describe a double-layered shell is described as comprising a first inner layer (i.e., surrounding the core) which comprises a surfactant, and a second outer layer comprising a plant protein (see Spec., [093]). As mentioned above, Livney does not mention more than one layer.
Regarding a particle consisting of a hydrophobic core in contact with and surrounded by an amphiphilic shell, Shi discloses a particle with an aqueous core that may contain a nucleic acid surrounded by an inner lipid layer where the hydrophobic portions of the inner lipids interact (i.e., contact) with a polymeric shell ([0045-0047]).
Regarding the second layer, Shi discloses the core of the particle being surrounded by an amphiphilic layer while this amphiphilic layer is surrounded by a polymer matrix (claims 1, 2) and that surrounding the matrix is an optional second amphiphilic layer ([0007], [0010], [0018], claim 2).
Regarding the first layer comprising surfactant, Shi teaches that any or all of the following may include one or more active agents: core, first amphiphilic layer, polymeric matrix, and second amphiphilic layer, ([0007]). Either the first or second amphiphilic layer, or both, can be mono- or multilayered ([0009]). The first amphiphilic compound can be a naturally derived lipid, or surfactant ([0009], [0019]). Figure 1D depicts an exemplary particle formulation where the polymeric shell is surrounded by an outer surfactant (e.g., polyvinyl alcohol) layer ([0047], [0062]). While Livney mentions that the core may be devoid of a surfactant or is substantially free of a surfactant ([0027]), nevertheless, the use of surfactants is not prohibitive.
Regarding the low molecular weight surfactant, Shi teaches sodium lauryl sulfate and magnesium stearate ([0202]).
Regarding the second layer comprising plant protein, Livney teaches a nanoshell consisting of potato protein ([0011], [0024], [0092], Examples 1-2, claims 1, 12, 22). Potato protein isolates (PPI) are touted by Livney as being highly functional, having excellent solubility and good emulsifying and foaming abilities ([0007]). Livney underscores the benefits of utilizing potato protein in this context to include economic advantages, ample availability, nutritional value, and its Generally Recognized as Safe (GRAS) designation ([0007]). In light of these teachings, a skilled artisan would be motivated to use potato protein as the plant protein in the second layer of Shi, absent evidence to the contrary.
Regarding the amphiphilic plant protein to surfactant (1:1 to 500:1), Livney teaches potato protein at a concentration of 0.1 to 100 g/L ([0014], claim 28) and typically at a concentration of 0.7 to 1.5 g/L ([0088]). Livney teaches that in some embodiments, the w/v of a subject compound, more preferably from about 0.1% to about 2.0% ([0079]). Looking at Fig. 1D of Shi, surfactant surrounds the polymer shell while outer lipid (e.g., lecithin, i.e., surfactant) and is taught as an amphiphilic lipid to form an amphiphilic layer ([0046], [0061]). Shi discloses that the particles comprise 5% to 20% lipid (by weight) ([0061]). Here the prior art teaches a range of plant protein to surfactant that falls within the claimed range.
Regarding the hydrophobic compound to surfactant ratio, Livney’s disclosure of the bioactive compound is present at a concentration of 0.1 microgram/mL to 1 mg/mL (claim 16) along with Shi’s teaching of lipid (i.e., surfactant) overlaps the claimed range (i.e., 0.01:1 to 1:10). MPEP 2144.05 states that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Regarding the plant protein and surfactant in the shell, Shi shows that the lecithin forms a phospholipid bilayer having the hydrophilic (polar) heads and hydrophobic tails ([0061]). Thus, a skilled artisan would immediately consider plant protein of Livney and lecithin of Shi because the non-covalent interactions between lecithin and plant protein are well known in the art. Shi teaches lecithin in the second amphiphilic layer ([0009], [0044], [0061], claim 26), indicating it can be used in other delivery devices since lecithin is a natural lipid with FDA approval ([0061]).
Regarding low solubility in plant oil, looking to the instant disclosure applicants define hydrophobic compound as having low solubility in the plant oil; phenolic compounds, tannins, stilbenes, curcuminoids, coumarins, lignans, quinones as examples (see Spec., [015]).
The prior art meets the limitation by teaching curcuminoid (see Shi paragraph [0121], Harel’s claim 11). Livney describes the bioactive compound as a compound having maximal aqueous solubility below 1 g/l ([0011], [0028], claims 2, 18). MPEP § 2112.01 states that if a composition is physically the same, it must have the same properties. Thus, the properties recited in claims are presumed to be present in any composition that meets the structural requirements of the claims, absent evidence to the contrary.
Regarding the particle is anhydrous limitation, looking to the instant specification, a powder composition having less than 1 w/w% water is given (see Spec. [038]). Livney teaches that in one embodiment the nanoparticles can be provided as a powder ([0070]) or in powder form to possibly in kits for constitution with a suitable vehicle ([0086]).
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 combine the teachings of Livney in further view of Shi with expected results. One would be motivated to do so because Shi teaches that within the layers of the particle there can be other layers. Shi teaches that having more than one component within the layers with respect to amphiphilic compounds advantageously improves encapsulation yields and release control ([0024]). Shi provides a particle that has advantages of both polymer- and lipid-based nanoparticles ([0043]). Shi teaches that hydrophobic portions of inner lipids non-covalently interact with the active ([0045]).
Regarding claim 15, Livney teaches that the bioactive compound is a carotenoid ([0032-0033]), phytochemical ([0029], claims 3, 19), and phytosterol ([0031]).
Regarding claim 16, Livney teaches a phytochemical as the bioactive compound ([0029], claims 3, 19) which encompasses polyphenols.
Regarding claim 17, Livney teaches that the bioactive is a carotenoid ([0032]).
Regarding claim 18, Livney teaches potato protein ( [0024], claims 1, 12, 22).
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 Livney is completely silent regarding a shell consisting of potato protein and curcuminoid and at least 80% by weight of curcuminoid being in the shell (Remarks, page 6, paragraph 8).
The Examiner respectfully disagrees because Livney teaches bioactive bound to potato protein (PP) throughout and provides and shows results demonstrating that 80-96% of the bioactive is retained in the PP-VD complexes ([0118]). Harel is provided to read on the curcuminoid limitation.
Applicants argue Harel teaches a matrix that has a distinct composition, and Harel’s droplets do not show a particle core mainly composed of oil whereas the major curcuminoid portion location being in the claimed shell (Remarks page 7, paragraphs 1-4).
In response to applicants’ citing example 6 and suggestion of antioxidants, a skilled artisan would know that ingredients may suggest more than one benefit, but this does not diminish the teaching of curcuminoid by Harel. See MPEP §2123(II). Given that Harel and Livney both share the same objective to encapsulate bioactive(s) in a plant-based shell and as Harel cites Livney (see Harel, [0037]), their teachings of flaxseed oil, carotenoids, and ratios of protein to hydrophobic compound all overlap. One would be motivated to combine Harel and Livney because Livney provides results that show potato protein prevents the hydrophobic compound from degrading ([0113-0116] see degradation studies).
Applicants argue Shi teaches an aqueous core and not the claimed oil-core particles (Remarks, at the end of page 7).
Shi teaches curcumin (i.e., a curcuminoid) in paragraph [0121], and olive oil in paragraph [0201]. Shi teaches that the aqueous core may contain lipids ([0045]). In addition, Shi teaches olive oil as a pharmaceutically acceptable carrier ([0201]).
Applicants argue that the PCL or polysaccharide of Livney is not the low-molecular weigh surfactant (Remarks, page 8, paragraph 2).
Shi teaches sodium lauryl sulfate and magnesium stearate ([0202], see surfactant [0009], [0019]). While Livney mentions that the core may be devoid of a surfactant or is substantially free of a surfactant ([0027]), nevertheless, the use of surfactants is not prohibitive.
Regarding the arguments with respect to the anhydrous limitation, looking to the instant specification, a powder composition having less than 1 w/w% water is given (see Spec. [038]). Livney teaches that in one embodiment the nanoparticles can be provided as a powder ([0070]) or in powder form to possibly in kits for constitution with a suitable vehicle ([0086]).
Regarding the surprising experimental results showing superior curcumin protection (e.g., Fig. 17) (Remarks, page 9, paragraph 1), applicants have the burden of providing and showing results comparatively to the prior art of record. Livney, as mentioned above, Livney provides results that show most (80-96%) of the bioactive e.g., vitamin D (VD) is retained in the PP-VD complexes ([0118]) to suggest advantageously stable potato protein nano encapsulated products (see Fig. 6 protein + VD).
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.
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/Karen A Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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