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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/9/2026 has been entered.
Information Disclosure Statement
The submitted information disclosure statement (IDS) were filed on 06/18/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of Application
Applicants' arguments/remarks filed 05/29/2026 are acknowledged. Claims 1, 8, 13, 22-23, 25 and 28 are currently amended. Claims 1-6, 8, 10, 12-16, 18, 22-23, 25 and 27-29 are examined on the merits within and are currently pending.
Maintained Rejections
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 non-obviousness.
Claim(s) 1-5, 15, 16, 18, 22-23, 25 and 27-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanderson (US 20200405797 A1), Hetherington et al. (US 20200138737Al), Savel et al. (US 20210138069Al) and Bromley, (US 20200000860Al) in view of Deng et al. (US 20110064794A1).
Claims 1, 18, 22-23
Sanderson teaches nanocarrier including lipid-nanoparticles (LNPs) (0009), comprising: a biologically active material: a cannabis extract, or a synthetic agonist, a tetrahydrocannabinol (THC), a hydrophobic therapeutic agent, in concentrations of 0% to 95% w/v, a cannabinoid in concentrations between 0 and 95% w/v, and a terpene in concentrations between 0% and 25% w/v. (0005). Terpenes are what make certain cannabis plants smell or taste different from others. They may work with the plant's cannabinoids and other compounds to produce medicinal effects. In other embodiments, the biologically active substance comprises one or more bioactive(s). (0029). Two types of LNPs are solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). SLNs have a surfactant component composed of a hydrophilic, lipophilic or amphiphilic material with a concentration between about 0.5 to 5.0% by weight. In some other embodiments, the surfactant component is an amphiphilic emulsifier selected from a group consisting of egg lecithin, soya lecithin, phosphatidylcholines. (0024); a sterol, cholesterol, (0009), cholesterol, 2%. (0075); a medium chain triglyceride. (0011); and water, (0013), 87.4% (0046). A lipid encapsulated bioactive nano-emulsion sizes are in the range of 40-800 nm. (0038). NLCs are differentiated from SLNs by the composition of the solid matrix; in particular, the lipid component in NLCs contain both solid phase and liquid phase lipids at body and ambient temperatures. The liquid phase lipids are selected from a group consisting of: medium chain triglycerides, (0025), but at a low concentration 1.8%. (0046).
Sanderson teaches delivery device for delivering a biologically active substance, (0001), which includes one or more of biologically active materials, many of them are hydrophilic substances. (0006). Sanderson does not teach percentages of these hydrophilic active materials.
Hetherington et al. teach compositions comprising cannabinoids for relieving pain in a subject and to methods of using such compositions for relieving pain in a subject. (Abs). The composition 2 includes 5% w/w CBD (hydrophobic therapeutic agent), 15% w/w triethanolarnine salicylate (hydrophilic therapeutic agent). (Table 1, 0104).
Sanderson does not teach medium chain triglycerides in the composition ranging
from 2.5% to 15%.
Savel et al. teach, otic agents and/or other pharmaceutical agents are optionally incorporated within controlled release particles, lipid complexes, liposomes, nanoparticles, microspheres, nanocapsules or other agents to facilitate the localized delivery of the otic agent. In some embodiments, a single formulation or composition is used, in which at least one active pharmaceutical ingredient is present, while in other embodiments, a pharmaceutical formulation or composition that comprises a mixture of two or more distinct formulations. (0933). The amount of active ingredient in the final formulation ranges from 0.1 to 5.0%. (0971). Suitable phospholipids for use in the present compositions are, for example, phosphatidyl choline. The amount of phospholipid used in the present formulation ranges from about 10 to about 30%, preferably from about 15 to about 25%. (0968). The otic pharmaceutical formulation further comprises cholesterol. In some embodiments, the otic pharmaceutical formulation comprises between about 0.01% to about 20% by weight of the cholesterol. In some embodiments, the otic pharmaceutical formulation comprises between about 0.01% to about 10% by weight of the cholesterol. In some embodiments, the otic pharmaceutical formulation comprises between about 0.01% to about 5% by weight of the cholesterol. (0015). In some embodiments, formulations or compositions comprising nanoparticles. (0803). The otic pharmaceutical formulation comprises between about 50% to about 99.99% by weight of the triglycerides. (0011). Triglycerides:medium chain triglycerides ratios can be varied from 0.1:99.9 to 99.9:0.1), while triglycerides percentages in the formulation can be 99.98-70, 80% or 90% of the composition. (Table K, L and M, pg. 109). In some embodiments, liposomes or lipid particles are also employed to encapsulate the otic agent formulations or compositions, in an aqueous medium form multilayer vesicles or single layer vesicles, commonly referred to as liposomes, with sizes of about 10-1000 nm. (0967).
Bromley teaches nanoemulsions with diameters less than 1000 nm or typically, less than 500 nm. (0158). The stable emulsions can contain one or more delivery vehicles selected from among micelles, liposomes and cubosomes and mixtures thereof, that encapsulate the probiotic. (0134). The emulsion compositions provided contain one or more mucoadhesive proteins and an agent to be delivered. (Abs). Concentrations of the total amount of probiotic plus mucoadhesive protein, such as lactoferrin in the emulsions are at or at least about 5% -25% (wt %) of the emulsion. The emulsions microencapsulated the probiotic with the mucoadhesive protein, such as lactoferrin. The emulsion compositions contain about or at 1-10% probiotic and 2-10% Lactoferrin. (0006). (Probiotic is considered as the 1st API and Lactoferrin is the 2nd API). Natural lipids, i.e. cholesterol, and choline (Phosphatidylcholine) are the surface active agents. (0123-0124). The amount of surface-active agent can be from less than 0.1% by weight up to 35% or more. (0135). The amount of oil, such as MCT oil, is about or is 10-20%, by weight, the amount of polar solvent, such as water is about 40%-65%. (0161). MCT (medium chain triglycerides) oil is called a solvent. (0070). In certain embodiments, the oils are short, medium or long chain triglycerides. In certain embodiments, the oils are MCTs. (0119). The amount of the oil is about 1%-95% or more by weight. (0120).
Sanderson, Hetherington et al., Savel et al. and Bromley do not teach upon exposure to sterilization conditions, the average size of the nanoparticles changes less than 2%.
Deng et al. teach nano-drug delivery system comprising nanoparticles (NP), nanospheres (NS), nanocapsules (NC), nanomicelles (NM), nano-liposomes (NL) and nano-emulsions (NE). (0006), which comprise phosphatidylcholine (0009), medium chain triglyceride (MCT) (0022), cholesterol (0025), freeze drying or spray drying (0039) and filter sterilize by passing through a porous membrane (0046). The average particle size of nanoparticles was 90.3 nm, and increased to 90.6 nm after filtering through 0.22 µm micropore film; (0105); after sterilization by filtering, the particle size change about 0.33%. The average particle size of nanoparticles was 91.8 nm, and increased to 92.2 nm after filtering through 0.22 µm micropore film; (0106); after sterilization by filtering, the particle size change about 0.43%. The average particle size of nanoparticles was 93.6 nm, and increased to 93.8 nm after filtering through 0.22 µm micropore film; (0107); after sterilization by filtering, the particle size change about 0.21%.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lipid-based particle composition, comprising:
two or more therapeutic agents; the 1st therapeutic agent, a cannabinoid is hydrophobic, composition ranging from concentrations of 0% to 95% w/v taught by Sanderson, the 2nd therapeutic agent triethanolarnine salicylate is hydrophilic, at 15% w/w in the, taught by Hetherington et al.; a phosphatidylcholine at a weight percent in the composition ranging from 0.5 to 5.0% by weight; a sterol, (0009), which is Cholesterol, 2%; and a medium chain triglyceride, water 87.4% and particle sizes are 50-500 nm taught by Sanderson, Savel et al., and Bromley and 50% to about 99.99% by weight of the triglycerides, with MCT oil, is about or is 10-20%, taught by Bromley, wherein, upon exposure to filtering sterilization conditions, the average size of the nanoparticles changes less than 2%, taught by Deng et al. since they have proven it should be feasible to do so.
With regard to claim 2,
Sanderson teaches bilosome bile salt stabilized liposomes, (0032), and a lipid encapsulated bioactive nanoemulsion. (0013).
Savel et al. teach controlled-release options include but are not limited to liposomes and emulsions. (0850).
Bromley teach the stable emulsions provided herein can contain one or more delivery vehicles selected from among micelles, liposomes and cubosomes and mixtures thereof. (0134).
With regard to claim 3, Bromley teaches the instantly claimed emulsions and spray dried powders produced therefrom are shelf stable at room temperature for up to 3 months, 6 months, or a year or more. (0008).
With regard to claim 4, Bromley teaches the instantly claimed emulsions and spray dried powders produced therefrom are shelf stable at room temperature for up to 3 months, 6 months, or a year or more. (0008).
With regard to claim 5, Savel et al. teach anti-emetic agents are optionally used in combination with any otic formulations and compositions comprising cannabinoids (0760). In some instances, upon administration ( e.g., intratympanic injection) of a conventional otic formulation or composition (e.g., DSP in a buffer), the concentration of a drug in the perilymph of an individual will rise sharply Cmax at about 1-2 hours. (0996).
With regard to claim 15,
Savel et al. teach general Methods of Sterilization (0789), Sterilization by Heat (0794-0976), which is Pasteurization,
Bromley teaches UV sterilization. (0217).
With regard to claim 16,
Sanderson teaches flavonol, (0007).
Savel et al. teach flavonoids, (0007).
Bromley teaches flavor agents, (0156).
With regard to claim 25, Sanderson teaches nanocarrier including lipid-nanoparticles (LNPs) (0009), comprising: a biologically active material: a cannabis extract, such as tetrahydrocannabinol (THC) in concentrations of 0% to 95% or Cannabinoids such as Cannabidiol (CBD) may be present in amounts between 0 and 95% (0005) as the hydrophobic therapeutic agent. In other embodiments, the biologically active substance can comprise one or more hydrophobic therapeutic agent consisting of bisabolol. (0029).
With regard to claim 27,
Savel et al. teach treating otic disorders by providing a constant, variable and/or extended source of a therapeutic agent (otic agent) to the individual or patient suffering from an otic disorder, and reducing or eliminating the variability of treatment. (0312).
Bromley teaches treating a subject by administering a therapeutically effective amount
to a subject. (0081).
With regard to claim 28,
Sanderson teaches method of manufacturing of a transmucosal delivery device comprising a mucosal permeation enhancing agent and a nanocarrier carrying a biologically active substance are embedded within a colloidal polymer thin film, (Abs), which comprises phosphatidylcholine, (0008), medium chain triglycerides, (0011). Method for manufacturing a transmucosal delivery device comprising: selecting a biologically active material; admixing a lipid component, a surfactant component, and the biologically active material to form a lipid nanocarrier mixture; subjecting the lipid nanocarrier mixture to shear forces sufficient to create a lipid encapsulated bioactive nano-emulsion; combining the bioactive nano-emulsion with a polymeric precursor base solution to form a hydrated thin film polymer composition; and dehydrating the thin film polymer composition to form a strip. An excipient component can be admixed with the lipid component, surfactant component, and biologically active material. The shear forces can be provided by a process selected from a group consisting of: high pressure homogenization, solvent emulsification, evaporation or diffusion, supercritical fluid extraction of emulsions, and ultrasonication. (0013).
Hetherington et al. teach To prepare the compositions outlined in Table 1, water soluble ingredients are weighed into a suitable vessel and heated in a water bath while mixing with a propeller stirrer. The water insoluble ingredients are weighed into a suitable vessel and mixed well. The mixture is heated on a hot plate using a propeller stirrer at slow speed. A coarse emulsion is prepared by gradually adding the water insoluble phase into the water-soluble phase. The coarse-emulsion is homogenized. Homogenization is stopped and the mixture is then mixed with a propeller mixer to allow the mixture to congeal and form a homogenous product. (0105). Hydrophobic therapeutic agent is cannabinoids CBD. And triethanolarnine salicylate is hydrophilic therapeutic agent. (Table 1, 0104).
Savel et al. teach the formulations are further subjected to an appropriate process to reduce particle size, such as homogenization with a microfluidizer or high-energy ball
milling. (1049).
With regard to claim 29,
Sanderson teaches the polymeric precursor base solution can be composed of a
stabilizers and emulsifiers, and water. (0013).
Claim(s) 1 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanderson et al., (US 20200405797 A1), Hetherington et al. (US 20200138737Al), Savel et al. (US 20210138069Al) and Bromley, (US 20200000860Al) in view of Deng et al. (US 2011/0064794 A1) and further in view of Thibonnier (US 20210079392 A1).
The teachings of Sanderson et al., Hetherington et al., Savel et al., Bromley, and Deng et al., are described in claim 1 above.
Sanderson et al., Hetherington et al., Savel et al., Bromley, and Deng et al., do not teach the lipid-based particle, wherein, upon storage for a period of one month, the average size of the nanoparticles changes by less than about 20% and/or the polydispersity of the nanoparticles in the composition is less than or equal to 0.25.
Thibonnier teaches the pharmaceutical compositions and formulations are in the form of oil-in-water emulsions. (0168). Some aspects of the present disclosure are directed towards a liposome. (0118). The liposome a peak mean diameter of 140 nm, a polydispersity index (PDI) of <0.01, with no significant changes during storage over 1 month at 4° C. (0273).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lipid-based particle composition, comprising:
two or more therapeutic agents; the 1st therapeutic agent, a cannabinoid is hydrophobic, composition ranging from concentrations of 0% to 95% w/v taught by Sanderson, the 2nd therapeutic agent triethanolarnine salicylate is hydrophilic, at 15% w/w in the, taught by Hetherington et al.; a phosphatidylcholine at a weight percent in the composition ranging from 0.5 to 5.0% by weight; a sterol, (0009), which is Cholesterol, 2%; and a medium chain triglyceride, water 87.4% and particle sizes are 50-500 nm taught by Sanderson, Savel et al., and Bromley and 50% to about 99.99% by weight of the triglycerides, with MCT oil, is about or is 10-20%, taught by Bromley, wherein, upon exposure to filtering sterilization conditions, the average size of the nanoparticles changes less than 2%, taught by Deng et al. and upon storage for a period of one month at 4° C, these liposomes polydispersity index (PDI) of <0.01, with no significant changes during storage over 1 month at 4° C, taught by Thibonnier since they have proven it should be feasible to do so.
Claim(s) 1 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanderson et al., (US 20200405797 A1), Hetherington et al. (US 20200138737Al), Savel et al. (US 20210138069Al) and Bromley, (US 20200000860Al) in view of Deng et al. (US 2011/0064794 A1) and further in view of Stauderman et al. (WO 2018/140796 Al).
The teachings of Sanderson et al., Hetherington et al., Savel et al., Bromley, and Deng et al., are described in claim 1 above.
Sanderson et al., Hetherington et al., Savel et al., Bromley and Deng et al. do not teach the stability of lipid nanoparticles in relation to D90 particle sizes over 90 days at storage conditions of 25°C and 60% of humidity.
Stauderman et al. teach emulsion (Abs), pharmaceutical compositions of nanoparticles, size 50-500nm, (0005, pg. 3, last par. – pg. 4, 1st par.). The particle sizes D90 were measures at t0 48nm, (pg. 69, Table 51) and different conditions, Table 52B: T = l month (25 ± 3 °C/60%RH), D90 46 nm (pg. 70) and Table 53B: T = 3 Mo (25 ± 3 ° C / 60% Relative Humidity), D90 40.6 nm (pg. 71). The change of D90 from t0 to 1 month is 4.1% and to 3 months is 15.4%, which is less than 20%.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lipid-based particle composition, comprising:
two or more therapeutic agents; the 1st therapeutic agent, a cannabinoid is hydrophobic, composition ranging from concentrations of 0% to 95% w/v taught by Sanderson, the 2nd therapeutic agent triethanolarnine salicylate is hydrophilic, at 15% w/w in the, taught by Hetherington et al.; a phosphatidylcholine at a weight percent in the composition ranging from 0.5 to 5.0% by weight; a sterol, (0009), which is Cholesterol, 2%; and a medium chain triglyceride, water 87.4% and particle sizes are 50-500 nm taught by Sanderson, Savel et al., and Bromley and 50% to about 99.99% by weight of the triglycerides, with MCT oil, is about or is 10-20%, taught by Bromley, wherein, upon exposure to filtering sterilization conditions, the average size of the nanoparticles changes less than 2%, taught by Deng et al. and the lipid nanoparticle size D90 stored at 25°C and 60% relative humidity, within 3 months would have D90 change less than 20%, taught by Stauderman et al., since they have proven it should be feasible to do so.
Claim(s) 1 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanderson et al., (US 20200405797 A1), Hetherington et al. (US 20200138737Al), Savel et al. (US 20210138069Al) and Bromley, (US 20200000860Al) in view of Deng et al. (US 2011/0064794 A1) and further in view of Mudumba et al. (AU 2013200089 A1).
The teachings of Sanderson et al., Hetherington et al., Savel et al., Bromley, and Deng et al. are described in claim 1 above.
Sanderson et al., Hetherington et al., Savel et al., Bromley, and Deng et al. do not teach the lipid-based particle composition of claim 1, wherein composition has a shelf life of greater than 18 months at 25°C and 60% relative humidity.
Mudumba et al. teach stable formulations comprising therapeutic agents (Abs), as emulsion, self-emulsifying formulation, nanosuspensions (0052) and define a “stable formulation,” is a formulation containing a therapeutic agent, wherein the formulation retains at least about 60% formula strength agent after a period of storage relative to when it was just prepared; put another way, a stable formulation is a formulation containing a therapeutic agent, wherein at least about 60% of the formulation strength remains relative to the starting level of the therapeutic agent when it was just prepared. In some variations the stable formulations described herein retain at least about 60%, or at least about 99% of the level of the therapeutic agent after a period of storage, relative to the starting level of the therapeutic agent in the formulation. (0053). In some variations, the formulation strength is at least 60% for 18 months, 20 months, 22 months, or 24 months at 25° C and 60% relative humidity. In some variations, the formulation strength is at least 90% for at least 18 months, 20 months, 22 months, or 24 months at 25°C and 60% relative humidity. (0015).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lipid-based particle composition, comprising:
two or more therapeutic agents; the 1st therapeutic agent, a cannabinoid is hydrophobic, composition ranging from concentrations of 0% to 95% w/v taught by Sanderson, the 2nd therapeutic agent triethanolarnine salicylate is hydrophilic, at 15% w/w in the, taught by Hetherington et al.; a phosphatidylcholine at a weight percent in the composition ranging from 0.5 to 5.0% by weight; a sterol, (0009), which is Cholesterol, 2%; and a medium chain triglyceride, water 87.4% and particle sizes are 50-500 nm taught by Sanderson, Savel et al., and Bromley and 50% to about 99.99% by weight of the triglycerides, with MCT oil, is about or is 10-20%, taught by Bromley, wherein, upon exposure to filtering sterilization conditions, the average size of the nanoparticles changes less than 2%, taught by Deng et al. and some variations, formulation strength is at least 60% or 90% for 18 months, 20 months, 22 months, or 24 months at 25° C and 60% relative humidity, taught by Mudumba et al., since they have proven it should be feasible to do so.
Claim(s) 1 and 12-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanderson et al., (US 20200405797 A1), Hetherington et al. (US 20200138737Al), Savel et al. (US 20210138069Al) and Bromley, (US 20200000860Al) in view of Deng et al. (US 2011/0064794 A1) and further in view of Cui et al. (US 20200384007 A1).
Claim 1 and 12,
The teachings of Sanderson et al., Hetherington et al., Savel et al., Bromley and Deng et al. are described in claim 1 above.
Sanderson et al., Hetherington et al., Savel et al., Bromley, and Deng et al. do not teach the lipid-based particle composition, wherein, when exposed to simulated gastric fluid at a pH of 1.6 and/or wherein, when exposed to simulated intestinal fluid at a pH of 6.5, for a period of at least 1 hour, the average size of the nanoparticles changes less than or equal to 10%.
Cui et al. teach lipid nanoparticles containing pharmaceutical and/or nutraceutical agents (Title) and stability of DHA-dFdC-SLNs in stimulated gastrointestinal fluids (SGF or SIF). Particle diameter of DHA-dFdC-SLNs as measured by DLS did not change more than 10% during 6 hours of incubation in SGF or SIF (FIG. 8A). Indeed, particle size decreased slightly (5.4% in SIF and 6.1% in SGF, as compared to in PBS) (FIG. 8A). (0223).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lipid-based particle composition, comprising:
two or more therapeutic agents; the 1st therapeutic agent, a cannabinoid is hydrophobic, composition ranging from concentrations of 0% to 95% w/v taught by Sanderson, the 2nd therapeutic agent triethanolarnine salicylate is hydrophilic, at 15% w/w in the, taught by Hetherington et al.; a phosphatidylcholine at a weight percent in the composition ranging from 0.5 to 5.0% by weight; a sterol, (0009), which is Cholesterol, 2%; and a medium chain triglyceride, water 87.4% and particle sizes are 50-500 nm taught by Sanderson, Savel et al., and Bromley and 50% to about 99.99% by weight of the triglycerides, with MCT oil, is about or is 10-20%, taught by Bromley, wherein, upon exposure to filtering sterilization conditions, the average size of the nanoparticles changes less than 2%, taught by Deng et al. and the lipid-based particle composition, wherein, when exposed to simulated gastric fluid at a pH of 1.6 and/or wherein, when exposed to simulated intestinal fluid or simulated gastric fluid for a period of 6 hours, the average size of the nanoparticles changes 5.4% in SIF and 6.1% in SGF, taught by Cui et al., since they have proven it should be feasible to do so.
Claim(s) 13 and 14
Sanderson teaches nanocarrier including lipid-nanoparticles (LNPs) (0009), comprising: a biologically active material: a cannabis extract, or a synthetic agonist, a tetrahydrocannabinol in concentrations of 0% to 95% w/v, a cannabinoid in concentrations between 0 and 95% w/v, and a terpene in concentrations between 0% and 25% w/v. (0005). A terpene is a 2nd therapeutic agent. Terpenes are what make certain cannabis plants smell or taste different from others. They may work with the plant's cannabinoids and other compounds to produce medicinal effects. In other embodiments, the biologically active substance comprises one or more bioactives. (0029). Two types of LNPs are solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). SLNs have a sterol, cholesterol, (0009), cholesterol, 2%. (0075); a medium chain triglyceride. (0011). A lipid encapsulated bioactive nano-emulsion sizes are in the range of 40-800 nm. (0038). NLCs are differentiated from SLNs by the composition of the solid matrix; in particular, the lipid component in NLCs contain both solid phase and liquid phase lipids at body and ambient temperatures. The liquid phase lipids are selected from a group consisting of: medium chain triglycerides, (0025), but at a low concentration 1.8%. (0046). SLNs have a surfactant component composed of a hydrophilic, lipophilic or amphiphilic material with a concentration between about 0.5 to 5.0% by weight. In some other embodiments, the surfactant component is an amphiphilic emulsifier selected from a group consisting of egg lecithin, soya lecithin, phosphatidylcholines. (0024).
Hetherington et al. teach compositions comprising cannabinoids for relieving pain in a subject and to methods of using such compositions for relieving pain in a subject. (Abs). The composition 2 includes 5% w/w CBD (hydrophobic therapeutic agent), 15% w/w triethanolarnine salicylate (hydrophilic therapeutic agent). (Table 1, 0104).
Sanderson teaches low concentrations of sterol or cholesterol, triglyceride and phosphatidylcholine.
Savel et al. teach, otic agents and/or other pharmaceutical agents are optionally incorporated within controlled release particles, lipid complexes, liposomes, nanoparticles, microspheres, nanocapsules or other agents to facilitate the localized delivery of the otic agent. In some embodiments, a single formulation or composition is used, in which at least one active pharmaceutical ingredient is present, while in other embodiments, a pharmaceutical formulation or composition that comprises a mixture of two or more distinct formulations. (0933). The amount of active ingredient in the final formulation ranges from 0.1 to 5.0%. (0971). Suitable phospholipids for use in the present compositions are, for example, phosphatidyl choline. The amount of phospholipid used in the present formulation ranges from about 10 to about 30%. (0968). The otic pharmaceutical formulation further comprises cholesterol. In some embodiments, the otic pharmaceutical formulation comprises between about 0.01% to about 20% by weight of the cholesterol. In some embodiments, the otic pharmaceutical formulation comprises between about 0.01% to about 10% by weight of the cholesterol. In some embodiments, the otic pharmaceutical formulation comprises between about 0.01% to about 5% by weight of the cholesterol. (0015). In some embodiments, formulations or compositions comprising nanoparticles. (0803). The otic pharmaceutical formulation comprises between about 50% to about 99.99% by weight of the triglycerides. (0011). Triglycerides:medium chain triglycerides ratios can be varied from 0.1:99.9 to 99.9:0.1), while triglycerides percentages in the formulation can be 99.98-70, 80% or 90% of the composition. (Table K, L and M, pg. 109). In some embodiments, liposomes or lipid particles are also employed to encapsulate the otic agent formulations or compositions, in an aqueous medium form multilayer vesicles or single layer vesicles, commonly referred to as liposomes, with sizes of about 10-1000 nm. (0967).
Sanderson and Savel teach low concentrations of phosphatidylcholine.
Bromley teaches nanoemulsions with diameters less than 1000 nm or typically, less than 500 nm. (0158). The stable emulsions can contain one or more delivery vehicles selected from among micelles, liposomes and cubosomes and mixtures thereof, that encapsulate the probiotic. (0134). The emulsion compositions provided contain one or more mucoadhesive proteins and an agent to be delivered. (Abs). Concentrations of the total amount of probiotic plus mucoadhesive protein, such as lactoferrin in the emulsions are at or at least about 5% -25% (wt %) of the emulsion. The emulsions microencapsulated the probiotic with the mucoadhesive protein, such as lactoferrin. The emulsion compositions contain about or at 1-10% probiotic and 2-10% Lactoferrin. (0006). (Probiotic is considered as the 1st API and Lactoferrin is the 2nd API). Natural lipids, i.e. cholesterol, and choline (Phosphatidylcholine) are the surface active agents. (0123-0124). The amount of surface-active agent can be from less than 0.1% by weight up to 35% or more. (0135). The amount of oil, such as MCT oil, is about or is 10-20%, by weight, the amount of polar solvent, such as water is about 40%-65%. (0161). MCT (medium chain triglycerides) oil is called a solvent. (0070). In certain embodiments, the oils are short, medium or long chain triglycerides. In certain embodiments, the oils are MCTs. (0119). The amount of the oil is about 1%-95% or more by weight. (0120).
Bromley teaches stable dry powders and emulsions. (Title). The emulsions are then spray-dried to produce the powders. They can be prepared by any suitable method for making emulsions. (0007). The powders are the water soluble are free-flowing, i.e., not sticky. (0157).
The spray dried particles can be between at or about 0.5 microns or less than 1 micron. (241). The free-flowing powder to yield a clear (or relatively clear) liquid dilution composition upon dilution in an aqueous medium. (0245). The powders can be diluted into a suitable beverage for oral ingestion. (0342).
Sanderson, Savel et al. and Bromley do not teach wherein, upon reconstitution, nanoparticles within the aqueous solution have an average size ranging from about 20 nm to about 500 nm; and wherein, upon exposure to sterilization conditions, the average size of the
nanoparticles changed less than 2%.
Deng et al. teach nano-drug delivery system comprising nanoparticles (NP), nanospheres (NS), nanocapsules (NC), nanomicelles (NM), nano-liposomes (NL) and nano-emulsions (NE). (0006), which comprise phosphatidylcholine (0009), medium chain triglyceride (MCT) (0022), cholesterol (0025), freeze drying or spray drying (0039) and filter sterilize by passing through a porous membrane (0046). The average particle size of the nanoparticles was 156 nm, and was redispersible and the average particle size after redispersion was 166 nm. (0088). The average particle size of nanoparticles was 90.3 nm, and increased to 90.6 nm after filtering through 0.22 µm micropore film; (0105); after sterilization by filtering, the particle size change about 0.33%. The average particle size of nanoparticles was 91.8 nm, and increased to 92.2 nm after filtering through 0.22 µm micropore film; (0106); after sterilization by filtering, the particle size change about 0.43%. The average particle size of nanoparticles was 93.6 nm, and increased to 93.8 nm after filtering through 0.22 µm micropore film; (0107); after sterilization by filtering, the particle size change about 0.21%.
Sanderson et al., Hetherington et al., Savel et al., Bromley, and Deng et al. do not teach the lipid-based particle composition, wherein, when exposed to simulated gastric fluid at a pH of 1.6 and/or wherein, when exposed to simulated intestinal fluid at a pH of 6.5, for a period of at least 1 hour, the average size of the nanoparticles changes less than or equal to 10%.
Cui et al. teach lipid nanoparticles containing pharmaceutical and/or nutraceutical agents (Title) and stability of DHA-dFdC-SLNs in stimulated gastrointestinal fluids (SGF or SIF). Particle diameter of DHA-dFdC-SLNs as measured by DLS did not change more than 10% during 6 hours of incubation in SGF or SIF (FIG. 8A). Indeed, particle size decreased slightly (5.4% in SIF and 6.1% in SGF, as compared to in PBS) (FIG. 8A). (0223).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lipid-based particle composition, comprising: two or more therapeutic agents; the 1st therapeutic agent, a cannabinoid is hydrophobic, composition ranging from concentrations of 0% to 95% w/v taught by Sanderson, the 2nd therapeutic agent triethanolarnine salicylate is hydrophilic, at 15% w/w in the, taught by Hetherington et al.; a phosphatidylcholine at a weight percent in the composition ranging from 0.5 to 5.0% by weight; a sterol, (0009), which is Cholesterol, 2%; and a medium chain triglyceride, water 87.4% and particle sizes are 50-500 nm taught by Sanderson, Savel et al., and Bromley and 50% to about 99.99% by weight of the triglycerides, with MCT oil, is about or is 10-20%, stable dry powder taught by Bromley, wherein, upon exposure to filtering sterilization conditions, the average size of the nanoparticles changes less than 2%, taught by Deng et al., since they have proven it should be feasible to do so.
Double Patenting
The non-statutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim numbers below provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim corresponding claim numbers of copending Application No. 18/001636 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because these claims sometimes combine with other claims of different numbers.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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Response to Arguments
Rejections Under 35 U.S.C. § 103
Applicant argues about the response in the Advisory Action regarding Sanderson nowhere teaches a composition comprising these five components. Rather, Sanderson presents numerous laundry lists of materials: Firstly, the Office has not identified an appropriate lead compound or lead formulation in Sanderson. In order to select a lead, there must be a motivation to select the lead from among the alternatives and use it as the starting point for "modification to seek improved properties." Eisai at 1358. Secondly, the Office is entirely silent regarding the details of such an alleged motivation, or where such a motivation derives from. The cited art does provide a finite number of identified, predictable solutions. Nothing in Hetherington, Savel, and Bromley and Deng alters the foregoing. Hetherington, Savel, and Bromley are relied upon in the rejection for no more than teaching concentrations of certain elements. Deng is relied upon in the rejection for no more than teaching the extent of size change of nanoparticles. Accordingly, the burden for a selection rationale has not been met and a prima facie rationale for obviousness has not been provided.
Applicant's arguments have been fully considered but they are not persuasive since the basis for 103 rejection is that no one reference has to teach all the claim limitations for an obviousness rejection and therefore several references are combined to render the claims obvious. One with ordinary skill in the art can learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results even though some prior arts may teach more and may teach different things. In response to applicant's argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, lipid-based particle compositions are every common in the formulation/drug delivery system areas. Some prior arts list excipients for formulations, some other prior arts include more percentages in the compositions, depending on properties of therapeutic agents and their percentages, one with skill in the art can select one of these excipients and varies combinations of excipients and their percentages, which lead to the rejection by several prior arts especially in claim 1. One with skill in the art, is known for solving the same problem, is represented with design choices, may modify the teachings of the prior arts until they can achieve better outcome results.
Double Patenting
Applicant requests that the provisional rejection be held in abeyance until the claims are
otherwise in condition for allowance. We do not hold rejections in abeyance; it is therefore repeated above until Applicant submit a Terminal Disclaimer.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGOC-ANH THI NGUYEN whose telephone number is (571)270-0867. The examiner can normally be reached Monday - Friday 8:00 am.
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
Prosecution Insights