DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
The listing of claims filed 02 December 2024, have been examined. Claims 109-131 are pending. Claims 1-108 are canceled.
Claim Objections
Claim 122 is objected to because of the following informalities:
Claim 122 recites, "...one or more hydrophilic solvents in an amount of at least 5% by weight of the by weight of the one or more SEDDS." The phrase "by weight of the by weight of" contains a typographical error and renders the claim grammatically improper and should be corrected to "...in an amount of at least 5% by weight of the one or more SEDDS."
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 Applicant regards as his invention.
Claims 109-131 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, regards as the invention.
The claim 109 term "self-emulsifying drug delivery systems (SEDDS)" is a functional definition describing a mixture that forms an emulsion when contacted with an aqueous phase. The claims do not specify the physical state, components, or ratios required to achieve this function, nor do they specify the test conditions (e.g., type of aqueous medium, temperature, dilution ratio, method of agitation) under which self-emulsification is determined. This introduces ambiguity as to whether a particular formulation falls within the scope of "a SEDDS." The specification provides only a general definition of "will form an emulsion when presented with an alternate phase with a minimum energy requirement", which is insufficient to establish clear boundaries for the claim. The metes and bounds of the claimed invention are therefore unclear (see Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898 (2014)). Dependent claims 110-131 are included in this rejection because they do not cure the defect noted above.
In addition, in claim 110 the phrase "in addition to any water-soluble agents present in the one or more SEDDS comprises less than 20% by weight of water-soluble agents by weight of the formulation" is confusing and internally inconsistent. The claim is directed to the entire "formulation," which includes the SEDDS. By stating "in addition to any water-soluble agents present in the one or more SEDDS," the claim attempts to mathematically excise a sub-component of the SEDDS before calculating the total water-soluble agent content of the whole formulation. The method of this calculation (whether to subtract, exclude, or measure independently) is not defined, rendering the claim's scope unclear. Similarly, claim 122 “wherein the one or more SEDDS further comprises one or more hydrophilic solvents in an amount of at least 5% by weight of the by weight of the one or more SEDDS”; claim 124 “the one or more surfactants having a chemical structure that does not include a PEG moiety being present in an amount of 0.1 to 20% by weight of the one or more SEDDS”; and claim 129 “one or more permeation enhancers in an amount of 5-15% by weight of the one or more SEDDS”, suffer from the same lack of clarity.
Claim 131 is rejected as being indefinite for failing to particularly point out and distinctly claim the subject matter regarded as the invention. The claim recites a capsule with a specific property "wherein the absolute bioavailability of the one or more cannabinoids is at least 4.0%." This is a functional result that depends entirely on the method of administration to a subject, the fed/fasted state of the subject, and other physiological variables, not solely on the structural composition of the capsule. The limitation does not define any structural feature of the capsule itself but rather a desirable pharmacokinetic outcome. The limitation "the absolute bioavailability of the one or more cannabinoids is at least 4.0%" fails to specify the conditions under which bioavailability is determined and therefore does not provide objective boundaries for determining infringement.
The metes and bounds of the claim are unclear because the claim fails to specify under what dosing conditions bioavailability is measured; species tested; fed or fasted state; dosage amount; comparator intravenous dose; measurement protocol. Although the specification generally states "bioavailability is measured as the dose corrected blood plasma level relative to intravenous administration", the claim does not incorporate this limitation. A person of ordinary skill would not be able to determine with reasonable certainty whether a given capsule falls within or outside the claim scope.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. § 102 and 103 (or as subject to pre-AIA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. § 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. § 102(b)(2)(C) for any potential 35 U.S.C. § 102(a)(2) prior art against the later invention.
Claims 109-128, 130, and 131 are rejected under 35 U.S.C. § 103 as being unpatentable over Benita and Nassar (US20220202712A1; published 30 June 2022, hereinafter “Benita”) in view of Murty and Murty (US20070104741A1; published 10 May 2007, hereinafter “Murty”).
Benita teaches a self-emulsifying drug delivery system (SEDDS) for peroral cannabinoid delivery in hard or soft capsules including liquid formulation (¶[0039]-[0040], ¶[0042], ¶[0069], and ¶[0098]), cannabinoid loading ≥10 wt% (¶[0072] at 0.05-40 wt%, wherein 10 wt% is routine optimization within this range), oil content 10-60 wt% (¶[0059]; Table 1 exemplifies ~20 wt% tripropionin oil as 200 mg tripropionin in a ~1000 mg formulation which overlaps and renders a range of 1-50% an obvious), PEG-containing surfactant (Cremophor RH40, TPGS, polysorbate 80; ¶[0061]),m ≥5 wt% structurants/co-solvents (Table 1: 350 mg PEG 400 and 350 mg PG in ~1000 mg formulation = 35% each; ¶[0065]), oils (tripropionin, tributyrin C4 triglyceride, MCT C6-C12 triglycerides) and lipids (glyceryl monooleate) (¶[0055]-[0058]; wherein the range C4-C14 is a routine selection of known triglycerides) in an essentially water-free formulation (¶[0042], claim 9).
Benita’s exemplary formulation (Table 1) is >95% SEDDS components plus cannabinoid. Having less than 20% water soluble agents is an property of Benita’s formulations, wherein a person of ordinary skill would understand that water soluble agents are minimized to maintain self-emulsifying properties. Benita also discloses glyceryl caprylate/caprate, propylene glycol dicaprylocaprate, alpha tocopherol (¶[0055]-[0058], ¶[0061], ¶[0065]).
Benita’s formulations do not contain sugar alcohols or sugars (Table 1). As sugars or sugar alcohols are not required for self-emulsification, omitting nonessential ingredients to simplify a formulation is ordinarily obvious (see MPEP § 2144.04 Subsection I.A. and In re Larson, 340 F.2d 965 (CCPA 1965)). One of ordinary skill in the art might be motivated to exclude sugars and sugar alcohols from a SEDDS capsule formulation for a lipophilic drug due to physical instability, chemical incompatibility, and compromised drug-loading performance.
Murthy teaches the same core platform of both liquid and semi‑solid SEDDS for lipophilic drugs (¶[0029], Table 3), confirming the broad applicability, interchangeability of components, and the conventional nature of the capsule format for such liquid lipid systems (¶[0056]-[0058]). Murty similarly discloses oils such as oleic acid, soybean oil, sesame oil (¶[0097], Table 1) and the use of C8-C10 MCT (¶[0063]-[0064]), lipophilic compounds (glyceryl monooleate, propylene glycol dicaprylate/dicaprate, benzyl alcohol, isopropyl myristate; ¶[0060]-[0062] and ¶[0068]), and hydrophilic co-solvents (PEG 400, PG, ethanol; ¶[0074]). The list is a standard set of SEDDS excipients, and selecting any of them is obvious.
Further, Benita teaches that formulation components should be compatible with capsule shells to prevent embrittlement or leakage (¶[0085]-[0086]). Murty teaches that excipient selection and proportion are routine optimization to achieve desired self-emulsification, drug loading, and stability (¶¶[0041]-[0050]). Therefore, a person of ordinary skill in the art would be motivated to limit water-soluble agents to <20% to maintain capsule integrity, exclude sugars/sugar alcohols to avoid osmotic incompatibility, and ensure SEDDS plus cannabinoid constitute ≥50% for formulation efficiency. These are routine experimental optimizations, not inventive concepts.
Benita explicitly teaches PEG-containing surfactants/ PEGylated emulsifiers (Cremophor RH40, TPGS, polysorbate 80; ¶[0061]) exemplified in Table 1, wherein the surfactant content can be at least 20% by weight of the SEDDS as ~ 35 wt% wherein 350 mg Cremophor RH40 in a ~1000 mg formulation is used. A person of ordinary skill would be motivated to select a surfactant concentration of at least 20 wt% to achieve optimal self-emulsification and drug solubilization, as taught by Benita’s own examples. No modification beyond routine optimization is required.
Murty provides an exhaustive list that directly overlaps with and extends Benita's teachings to sugar-lipid PEGs, such as PEG-20 sorbitan monolaurate, monopalmitate, monostearate, monooleate (Tween series; ¶[0071]); PEG-containing polymers, such as poloxamers 124, 188, 338, 407 (¶[0070]); PEGylated emulsifiers such as PEG-30 castor oil (Cremophor EL), PEG-35 castor oil, PEG-40 hydrogenated castor oil, PEG-6 lauroyl glycerides (Labrafil), PEG-8 caprylic/capric glycerides (Labrasol), polyoxyl 20 cetostearyl ether (¶[0066]-[0072]). A person of ordinary skill would find these specific esters obvious alternatives (¶[0068]). Sucrose palmitate and stearate are well known alternatives in SEDDS formulations and would be obvious to try (see MPEP § 2143(e) and (b) and KSR International Co. v. Teleflex Inc., 550 U.S. at 421 (2007)).
A person of ordinary skill would substitute a known poloxamer for a PEG containing surfactant to adjust HLB or temperature responsiveness. Murty teaches poloxamers are well known PEG based block copolymers with self-emulsifying properties (¶[0070]). Combining Benita’s SEDDS with Murty’s teaching of poloxamers is a simple substitution of one known PEG surfactant for another, with a reasonable expectation of success (see MPEP § 2143(b) and KSR International Co. v. Teleflex Inc., 550 U.S. at 398 (2007)).
Benita's system is not limited to PEG-only surfactants (claim 29 encompasses mixtures; ¶[0061] mentions sorbitan monooleate). Murty extensively teaches non-PEG surfactants including monoglycerides, such as glyceryl monooleate (¶[0068]); sugar-lipid surfactants, such as sorbitan monolaurate, monopalmitate, monooleate, monostearate, tristearate (¶[0071]); polyglycerol esters such as polyglyceryl oleate, polyglyceryl-2 dioleate, polyglyceryl-10 trioleate, polyglyceryl-10 laurate and specifically decaglycerol mono/dioleate, polyglycerol esters of oleic acid (¶[0068]); and propylene glycol esters, such as propylene glycol monocaprylate, propylene glycol monolaurate (¶[0068]). Thus, the addition of a non-PEG surfactant is therefore, obvious. Murty teaches glyceryl monooleate (monoglyceride; ¶[0068]) and teaches sorbitan esters (sugar lipid-based surfactants; ¶[0071]). These are standard.
Benita does not explicitly teach use of a non-PEG surfactant 0.1-20% by weight of SEDDS, however, the claimed non-PEG surfactant range of 0.1-20% is a routine optimization within Murty's 5-90 wt% total surfactant range (¶[0044]; see In re Peterson, 315 F.3d 1325, 1329-30 (Fed. Cir. 2003)). Substituting one known surfactant is a simple combination of known elements with predictable results.
Benita also teaches structurants or co solvents, including hydrophilic co-solvents, such as PEG, propylene glycol, and glycerin (¶[0065]), and Table 1 shows 350 mg PEG 400 and 350 mg propylene glycol in a ~1000 mg formulation (35% each). Thus, ≥5% hydrophilic co-solvent by weight of SEDDS is taught in Benita’s examples. Murty likewise teaches co solvents such as PEG 400, propylene glycol, ethanol (¶[0074]).
Benita's preferred embodiment is liquid SEDDS in capsules. Benita does not explicitly teach the solid carriers, however the conversion of a liquid SEDDS to a solid or semi-solid form by adsorption onto a solid carrier and filling into a capsule is a notoriously well-known technique for stabilizing and handling lipid-based formulations. Murthy teaches that liquid SEDDS can be converted to a solid dosage form by mixing with viscosity modifying agents that can serve as solid carriers, including unmodified starches, pregelatinized starches, hydroxymethylpropyl cellulose, hydroxyethylcellulose, hydroxypropylmethylcelluose, carboxymethylcellose sodium, ethylcellulose, and cellulose acetate, and cellulose acetate phthalate (¶[0076]). Murty’s SEDDS can be filled into capsules, and the addition of such solid carriers is for controlled release or solidification.
Further, the instant claimed solid carriers (e.g., silica- a common pharmaceutical adsorbent (e.g., Aerosil), MCC, cellulose, silicified MCC, clay, talc, starch, pregelatinized starch, calcium carbonate, dicalcium phosphate, magnesium carbonate, etc.) are a routine set of pharmaceutical excipients known to be used in solid dosage forms and as adsorbents for liquid SEDDS to convert them to solid SEDDS. The inclusion of such would be obvious to one of skill as a standard glidant/adsorbent. Thus, it would have been obvious to a person of ordinary skill in the art to adsorb the liquid SEDDS in the formulation of Benita onto a solid carrier such as silica or microcrystalline cellulose, as taught by Murthy, for the known benefit of simplifying capsule filling of a low-melting or liquid fill, with a reasonable expectation of success. The motivation to combine the capsule format of Benita with the specific excipient guidance of Murthy is to improve to improve handling and stability and create an easy-to-manufacture, and convenient unit dose.
Both Benita and Murty are directed towards improving oral bioavailability, teaching substantially similar cannabinoid SEDDS formulations comprising cannabinoids, PEG-containing surfactants, and lipid excipients intended to increase oral absorption. Benita cites that some studies in humans showed values as low as 6% for oral administration of oil solutions (¶[0164]) and exemplary formulations resulting from the invention of Benita show 5.73 to 11.1-fold increases in AUC (oral bioavailability) of THC compared to standard MCT oil carriers (Table 11-1) and 4-fold improvement in CBD (Table 11-2). Thus, the formulations of Benita then innately produce an oral bioavailability of a cannabinoid from an oral SEDDS formulation of ≥4.0%. Accordingly, a person of ordinary skill in the art would have reasonably expected the prior-art cannabinoid SEDDS formulations to achieve ≥4% bioavailability, the limitation merely reflects the natural consequence of employing known cannabinoid SEDDS systems.
Evidentiary reference Vangara et al. (US20200360286A1; published 19 November 2020), also supports the teachings of Benita and Murty, by teaching that SEDDS for peroral cannabinoid (1-40% w/w cannabidiol and Examples show 10-30.5% w/w CBD which is ≥10% by weight of the formulation) delivery in hard or soft capsules (¶[0048], claim 9) were known in the art at the time of the instant invention using PEG-containing surfactants (claim 1); 1-50% w/w oils including but not limited to glyceryl monolinoleate, glyceryl monooleate, propylene glycol dicaprylocaprate, glycerol monostearate, a medium chain triglyceride (preferably C8/C10) or a combination thereof (¶[0034] and ¶[0035]); lipophilic compounds including polyglyceryl-3 dioleate (¶[0027], claim 1), and alpha-tocopherol (¶[0041] and ¶[0043]); PEGylated emulsifiers including PEG 40 hydrogenated castor oil, polysorbate which is PEG-modified, caprylocaproyl polyoxyl-8 glycerides (Labrasol), and linoleoyl polyoxyl-6 glycerides (Labrafil M 2125 CS) (¶[0020] and ¶[0027]; 1-10% w/w polysorbate 80 ¶[0033]); hydrophilic co-solvents ≥5% by weight of the one or more SEDDS (¶[0037] teaches cosolvents propylene glycol, polyethylene glycol, ethanol or a combination thereof and ¶[0039]-[0040] teach ethanol 5-15% w/w ethanol and 5-10% w/w propylene glycol); non-PEG surfactants including 1-15% w/w of a polyglycerol ester of fatty acid as polyglyceryl-3 dioleate (¶[0027] and ¶[0030]), sorbitan monooleate, propylene glycol monocaprylate, and propylene glycol monolaurate (claim 1); and improved bioavailability of cannabinoids in dogs as assessed by plasma Cmax and AUC values (Example 3, Table 6).
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to combine the teachings of Benita and Murty because Benita and Murty are both directed towards SEDDS for lipophilic drugs and address the same problem of poor oral bioavailability of lipophilic drugs, including cannabinoids, due to low aqueous solubility and extensive first-pass metabolism (Benita ¶[0033]-[0036]; Murty ¶[0007], and ¶[0013]-[0014]). Both teach SEDDS formulations comprising oils, PEG-containing surfactants, and optional co-solvents that spontaneously emulsify upon aqueous dilution to enhance absorption (Benita ¶[0036]; Murty ¶[0022]).
A person of ordinary skill in the art would be motivated to combine Benita's cannabinoid-specific SEDDS with Murty's expanded excipients because the components are interchangeable. SEDDS is an excipient-based platform where components are selected based on physicochemical properties (HLB, solubilization capacity), not drug identity. Murty explicitly frames its teachings as applicable to "a wide variety of active agents" including poorly water-soluble drugs, making its excipient guidance directly transferable to Benita's cannabinoid formulations (Murty Abstract; ¶[0007]-[0010]).
In addition, substituting one functionally equivalent pharmaceutical excipient (e.g., surfactant, oil, co-solvent) for another to achieve a known, expected result is prima facie obvious (KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007)). Murty provides an exhaustive list of SEDDS components that are structurally and functionally analogous to those in Benita, and a person of ordinary skill in the art would be motivated to consult this reference to optimize stability, drug loading, emulsification, and bioavailability. Also, optimization of excipient selection is routine for SEDDS formulation with predictable results. The combination of Benita's cannabinoid SEDDS with Murty's excipient guidance would yield a stable, optimized capsule formulation with a reasonable expectation of success.
The claimed invention is a predictable combination of Benita's specific cannabinoid SEDDS problem with Murty's general SEDDS optimization tools. A person of ordinary skill in the art would have been motivated to combine their teachings to create a stable, optimized cannabinoid capsule formulation with reasonable expectation of success through routine experimentation.
Claim 109 and 129 are rejected under 35 U.S.C. § 103 as being unpatentable over Benita and Nassar (US20220202712A1; published 30 June 2022, hereinafter “Benita”) in view of Murty and Murty (US20070104741A1; published 10 May 2007, hereinafter “Murty”), and in further view of Rajadhyaksha and Sehgal (WO1996033706A1; published 31 October 1996, hereinafter "Rajadhyaksha").
Benita and Murty teach the limitations of instant claim 109, as described above, from which instant claim 129 depends, however does not explicitly teach the specific limitations of instant claim 129, wherein the capsule comprises one or more permeation enhancers at 5-15% by weight of one or more SEDDS.
Rajadhyaksha teaches formulations comprising active agents, lipophilic permeation enhancer, and a self-emulsifying agent (Abstract), wherein, "The lipophilic permeation enhancers will typically be present in the compositions of the invention in an amount of from about 0.1 % to about 20%..." (page 7, lines 20-21).
Rajadhyaksha teaches formulations allowing the active agents to produce both a rapid onset and longer duration comprising active agents, lipophilic permeation enhancer, and a self-emulsifying agent (Abstract), wherein, "The lipophilic permeation enhancers will typically be present in the compositions of the invention in an amount of from about 0.1 % to about 20%..." (page 7, lines 20-21).
Both Benita and Murthy explicitly address the challenge of delivering lipophilic active agents, including cannabinoids (CBD/THC). They both note that these compounds suffer from poor water solubility and extensive first-pass metabolism in the liver, which significantly reduces their bioavailability (Benita, ¶[0033]; Murthy, ¶[0007]).
The Benita and Murthy references both propose SEDDS as a solution to this problem. SEDDS are designed to spontaneously form fine oil-in-water emulsions in the gastrointestinal tract, which increases the drug's surface area for absorption and can promote lymphatic transport, thereby bypassing first-pass metabolism (Benita, ¶[0036]; Murthy, ¶[0022]).
This shared problem and solution framework creates a clear motivation to look for further improvements to the SEDDS approach. One way to improve absorption is by enhancing the permeation of the drug through the intestinal epithelium, which is exactly what Rajadhyaksha teaches, increased epithelium penetration (Abstract). Rajadhyaksha teaches the use of lipophilic permeation enhancers to improve the passage of drugs across biological membranes (Summary of the Invention), wherein the principle of using lipophilic enhancers to facilitate drug transport through lipid-rich barriers is well-known. Hence, one of ordinary skill in the art would be motivated to add a lipophilic permeation enhancer as a complementary enhancement to that of Benita and Murthy for improving the oral bioavailability of poorly soluble lipophilic drugs like cannabinoids.
A person of ordinary skill in the art would have had a reasonable expectation of success in combining these elements because the use of fatty acids, fatty alcohols, and their esters as permeation or absorption enhancers was well-established in the pharmaceutical field before 2006 (as evidence by Rajadhyaksha). These compounds are known to interact with biological membranes to increase fluidity and enhance drug permeation.
In addition, the lipophilic permeation enhancers taught by Rajadhyaksha (e.g., oleic acid, glyceryl monooleate, medium-chain triglycerides) are similar to, and in some cases the same as, the oils and surfactants already used in the SEDDS formulations of Benita and Murthy. This chemical compatibility means the enhancers could be incorporated into the SEDDS preconcentrate without disrupting its self-emulsifying properties.
One would have a reasonable expectation of success in adding a permeation enhancer to a SEDDS formulation because it is straightforward. The SEDDS creates the fine emulsion to solubilize and deliver the drug, while the lipophilic permeation enhancer, incorporated into the oil droplets, acts in concert to increase the drug's penetration through the intestinal wall. This is a logical and predictable step to further improve the oral bioavailability that the SEDDS itself is designed to achieve.
Claim Rejections – Nonstatutory Double Patenting
The nonstatutory 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).
Claims 109-131 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-141 of co-pending US Application No. 18/891,058 (hereinafter “‘058”), in view of Benita and Nassar (US20220202712A1; published 30 June 2022, hereinafter “Benita”) and/or Murty and Murty (US20070104741A1; published 10 May 2007, hereinafter “Murty”). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons outline below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 109 of the instant application is directed to a capsule for peroral delivery of cannabinoids comprising a cannabinoid formulation contained in a hard shell or soft shell of the capsule, the formulation comprising one or more self-emulsifying drug delivery systems (SEDDS) comprising one or more surfactants having a chemical structure that includes a polyethylene glycol (PEG) moiety in an amount of at least 20% by weight of the one or more SEDDS; and one or more cannabinoids comprising one or more isolated or synthetic cannabinoids in an amount of at least 10% by weight of the formulation.
Claim 116 of the co-pending ‘058 is directed to a liquid dosage form for delivery of cannabinoids comprising a formulation, the formulation comprising one or more self-emulsifying drug delivery systems (SEDDS) comprising one or more surfactants having a chemical structure that includes a polyethylene glycol (PEG) moiety in an amount of at least 30% by weight of the one or more SEDDS; and one or more cannabinoids comprising one or more isolated or synthetic cannabinoids in an amount of at least 20% by weight of the formulation.
Claim 141 of the co-pending ‘058 is directed to a solid dosage form for delivery of cannabinoids comprising a formulation, the formulation comprising one or more self-emulsifying drug delivery systems (SEDDS) comprising one or more surfactants having a chemical structure that includes a polyethylene glycol (PEG) moiety in an amount of at least 30% by weight of the one or more SEDDS; and one or more cannabinoids comprising one or more isolated or synthetic cannabinoids in an amount of at least 10% by weight of the formulation.
The co-pending ‘058 specification expressly teaches that the disclosed embodiments apply to both liquid and solid dosage forms; solid dosage forms may include tablets and formulations containing solid carriers; all disclosed SEDDS compositions, lipids, oils, PEG surfactants, non-PEG surfactants, permeation enhancers, hydrophilic solvents, bioavailability limitations, and sugar-free embodiments are applicable to the solid dosage forms.
The co-pending ‘058 claims a dosage form for delivery of cannabinoids that incorporates the core elements of the instant application, a formulation comprising a SEDDS having PEG-containing surfactants and one or more cannabinoids. The reference's specification extensively discloses that the SEDDS can be formulated as a solid or liquid dosage form and may be contained in capsules (see, e.g., co-pending ‘058 at ¶[0006]-[0008] defining liquid and solid dosage forms, ¶[0032] capsule embodiments, Examples 4A-4C preparation of SEDDS filled into capsules). The ‘058’s broad disclosure of dosage forms encompasses capsules as a delivery vehicle. The instant application's claimed capsule is a species of the generic dosage form taught by the co-pending ‘058. Claiming a capsule dosage form for the same SEDDS-cannabinoid formulation would not patentably distinguish the instant claims from the co-pending reference.
The only material difference between independent claim 109 and the co-pending ‘058 claims is the recited dosage form (capsule vs. liquid/solid dosage form) and the lower minimum percentages for PEG-containing surfactant (20% vs. 30%) and cannabinoid content (10% vs. 20%). These are minor variations in parameters that do not alter the fundamental nature of the invention. A person of ordinary skill in the art would have a background in pharmaceutical formulation, drug delivery systems, or a related field, with knowledge of self-emulsifying drug delivery systems and cannabinoid formulations.
The differences between the claims are insufficient to patentably distinguish the instant claims from the co-pending ‘058. Adapting the SEDDS-cannabinoid formulation of the co-pending ‘058 to a capsule dosage form would have been obvious to a person of ordinary skill in the art, particularly given the reference's own disclosure that the formulation may be used in capsules. (see co-pending ‘058 at ¶[0032], ¶[0247], and Examples 4A-4C capsule embodiments). The selection of specific parameter values (e.g., 20% vs. 30% PEG surfactant, 10% vs. 20% cannabinoid) would have been a matter of routine optimization, not an inventive step, as the reference itself teaches a range of values for these parameters (see, e.g., co-pending ‘058 at ¶[0083]-[0097] for range of PEG surfactant content, ¶[0042]-[0059] for range of cannabinoid content). Furthermore, the use of a hard-shell or soft-shell capsule is a conventional and well-known dosage form in the pharmaceutical arts, as recognized by the co-pending ‘058's disclosure of capsules for peroral administration.
Instant claims 110-131, which depend from claim 109, further define details of the formulation, including specific components, amounts, and properties. These limitations are either disclosed in the co-pending ‘058 (e.g., SEDDS components, surfactants, lipids, cannabinoids, carriers, bioavailability) or would have been obvious to one of ordinary skill in the art as conventional excipients or routine optimization for the capsule dosage form See co-pending ‘058 specification ¶[0068]-[0071] for instant claim 110 (<20% water-soluble agents); claim 123 and specification ¶[0072] for instant claim 111 (no sugar alcohols or sugars); claim 124 and specification ¶[0074]-[0080] for instant claim 112 (SEDDS+cannabinoids ≥50%); claim 127 and specification ¶[0104] for instant claim 113 (liquid SEDDS); claims 128-129 for instant claim 114 (lipids/oils); instant claim 115 (C4-C14 triglycerides); claim 132 for instant claim 118 (lipophilic compounds list); specification ¶[0122] for instant claim 118 (1-50 wt.% lipids); claim 133 for instant claim 118; claim 134 for instant claim 119; claim 135 for instant claim 120; claim 136 for instant claim 121; claim 137 for instant claim 122; claim 138 for instant claim 123; specification ¶[0154]-[0156] for instant claim 124; claim 139 for instant claim 125; claim 140 for instant claim 126; specification ¶[0159] for instant claim 127; specification ¶[0160] for instant claim 128; specification ¶[0166]-[0170] for instant claim 129; and specification ¶[0198]-[0206] for instant claim 130).
Each of these limitations is either identically claimed in the co-pending application; or expressly taught as a preferred embodiment for the same cannabinoid/SEDDS formulation. Selecting one disclosed embodiment from a disclosed genus does not confer patentable distinctness. Accordingly, claims 110-130 are not patentably distinct from co-pending claims 116-141.
Instant claim 131 requires absolute bioavailability of the cannabinoids of at least 4.0%. Co-pending ‘058 claim 121 recites absolute bioavailability of the cannabinoids is at least 4.0%. The limitation is identical. The co-pending ‘058 specification additionally teaches that the disclosed embodiments are applicable to both liquid and solid dosage forms. Therefore claim 131 lacks patentable distinction over at least co-pending ‘058 claim 121 when applied to the solid dosage form/capsule embodiment.
The claimed capsule merely represents an obvious species or presentation form of the co-pending ‘058 application's claimed solid dosage form and incorporates substantially the same cannabinoid/SEDDS formulation. The remaining limitations are either identical to, expressly taught by, or obvious selections from the co-pending ‘058 claims and specification. The differences would have been obvious to a person of ordinary skill in the pharmaceutical formulation arts at the time of invention and do not render the instant claims patentably distinct.
To further support the obviousness of the claimed capsule, Benita is directed to self-emulsifying drug delivery systems for lipophilic compounds such as cannabinoids and explicitly contemplates oral administration, including in capsule form (see, e.g., ¶[0001]-[0003], ¶[0032], ¶[0053], ¶[0098]-[0100]). Benita further provides guidance on formulating SEDDS for cannabinoids and the use of surfactants, oils, and other components that overlap with the instant claims (see ¶[0031], ¶[0065]-[0077]). Benita's disclosure would have motivated a person of ordinary skill in the art to adapt the SEDDS-cannabinoid formulations of the co-pending reference into a capsule dosage form, as this is a well-known and conventional oral delivery vehicle for such formulations.
Alternatively, Murty further supports the obviousness of the claimed capsule. Murty is directed to self-emulsifying drug delivery systems for lipophilic drugs such as cannabinoids (e.g., THC) for oral administration to enhance bioavailability (see, e.g., ¶[0001]-[0005], ¶[0014]-[0017]. Murty explicitly teaches that the delivery system can be administered as a liquid or semi-solid matrix within a capsule shell (¶[0005]). This disclosure would have directly motivated a person of ordinary skill in the art to combine the SEDDS formulation of the co-pending ‘058 with a capsule dosage form, as taught by Murty.
For the reasons set forth above, the claims of the instant application are not patentably distinct from the claims of the co-pending ‘058. The claimed capsule is an obvious variation of the SEDDS-cannabinoid formulations disclosed in the co-pending ‘058 in view of the knowledge of one of ordinary skill in the art, Benita, and/or Murty. Accordingly, a prima facie case of nonstatutory obviousness-type double patenting has been established. To overcome this rejection, the applicant may file a terminal disclaimer in compliance with 37 CFR 1.321(c), or amend the claims to include patentably distinct subject matter not taught, suggested, or rendered obvious by the co-pending claims and specification.
Claims 109-131 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 164-172 of US Patent No. 12,533,367 B2 (hereinafter “‘367”), in view of Benita and Nassar (US20220202712A1; published 30 June 2022, hereinafter “Benita”) and/or Murty and Murty (US20070104741A1; published 10 May 2007, hereinafter “Murty”). Although the claims at issue are not identical, they are not patentably distinct from each for the reasons outline below.
Instant claim 109 is directed to a capsule for peroral delivery of cannabinoids comprising a cannabinoid formulation contained in a hard shell or soft shell of the capsule, the formulation comprising one or more self-emulsifying drug delivery systems (SEDDS) comprising one or more surfactants having a chemical structure that includes a polyethylene glycol (PEG) moiety in an amount of at least 20% by weight of the one or more SEDDS; and one or more cannabinoids comprising one or more isolated or synthetic cannabinoids in an amount of at least 10% by weight of the formulation.
Claim 164 of ‘367 is directed to an orally dissolvable or chewable tableted powder formulation, comprising one or more carrier systems present in an amount of 30 to 1500 mg, the one or more carrier systems comprising one or more liquid or solid self-emulsifying systems loaded with cannabinoids in an amount of at least 10% by weight of the tableted powder formulation; wherein the self-emulsifying systems include: i) at least one or more surfactants, one or more lipids and one or more isolated or synthetic cannabinoids when the self-emulsifying system is a liquid self-emulsifying system, and ii) at least one or more surfactants, one or more waxes and one or more isolated or synthetic cannabinoids when the self-emulsifying system is a solid self-emulsifying system; one or more water-soluble agents comprising one or more sugar alcohol particles in an amount of 20-80% by weight; and one or more flavors, wherein said one or more self-emulsifying systems is stable at a pH of about 1-4 and operable to gastrointestinal tract delivery of the one or more cannabinoids upon release of the one or more carrier systems in the oral cavity. Claim of 172 ‘367 further specifies that the one or more self-emulsifying systems comprises the one or more isolated or synthetic cannabinoids and one or more lipids in a weight ratio of cannabinoid to lipid of 10:1 to 1:10.
Critically, the issued patent ‘367 expressly contemplates and enables capsule formulations. The specification explicitly states, "[I]n another aspect of the invention, there is provided a capsule formulation comprising: one or more carrier systems comprising one or more liquid or solid self-emulsifying systems loaded with cannabinoids in an amount of at least 10% by weight of the formulation..." (¶[0300]). Patent ‘367 further clarifies, "In some embodiments of the invention, the capsule comprises an orally dissolvable or chewable powder formulation." (¶[0314]).
Thus, ‘367 claims and discloses a dosage form for delivery of cannabinoids that incorporates the core elements of the instant application, a formulation comprising a SEDDS having surfactants (including PEG-containing surfactants) and one or more cannabinoids. The reference's specification extensively discloses that the SEDDS can be formulated as a liquid or solid self-emulsifying system and may be contained in capsules (see, e.g., ‘367 at ¶[0300]-[0314] for capsule formulation aspects, ¶[0067]-[0068] for liquid self-emulsifying systems, ¶[0091]-[0093] for solid self-emulsifying systems, and Examples 7-8 premix with mesoporous carriers and SEDDS).
Patent ‘367 further discloses PEG-containing surfactants in its SEDDS formulations (¶[0026]-[0041] for PEG moiety surfactants in amounts of at least 20%, 25%, 30%, 35%, 40%, 50%, 60% by weight, and ¶[0099]-[0108] for specific PEG-containing surfactants including polyoxyethylene sorbitan derivatives, poloxamers, PEGylated emulsifiers). Patent ‘367 also discloses high cannabinoid loads (¶[0042]-[0058] for cannabinoids in amounts of at least 10%, 15%, 20%, 25%, 30%, 35%, 40% by weight of the self-emulsifying system, and at least 5%, 10%, 15%, 20%, 25% by weight of the tableted powder formulation).
The only material differences between independent claim 109 and ‘367 claims are the dosage form, surfactant content, and cannabinoid content. However, the active formulation itself remains substantially the same having cannabinoid-loaded SEDDS; PEG-containing surfactant; ≥10 wt% cannabinoid; and gastrointestinal delivery. The instant application claims a "capsule" with "hard shell or soft shell," whereas ‘367 claims an "orally dissolvable or chewable tableted powder formulation" but expressly contemplates capsule embodiments. Changing the known cannabinoid SEDDS composition from a chewable tablet matrix into a conventional capsule constitutes merely the use of a known alternative oral dosage form. Capsules and tablets are recognized pharmaceutical equivalents for delivery of liquid or semi-liquid SEDDS formulations. The issued patent repeatedly emphasizes that the invention resides in the cannabinoid-loaded SEDDS composition rather than in any unique tablet structure. A person of ordinary skill would have recognized that the disclosed liquid SEDDS formulations are routinely filled into soft gelatin or hard-shell capsules.
The instant application recites PEG-containing surfactant in an amount of "at least 20%" of the SEDDS, while ‘367 recites an amount of "at least 10%" of the tableted powder formulation, which corresponds to a higher percentage of the SEDDS given the loading and also explicitly discloses PEG-containing surfactants in amounts of at least 20%, 25%, 30%, and higher by weight of the SEDDS (¶[0032]-[0041]). The instant application recites "at least 10% by weight of the formulation," whereas ‘367 recites "at least 10% by weight of the tableted powder formulation" and "at least 10% by weight of the self-emulsifying systems." (¶[0043]-[0058]). These are minor variations in parameters that do not alter the fundamental nature of the invention.
A person of ordinary skill in the art would have a background in pharmaceutical formulation, drug delivery systems, or a related field, with knowledge of self-emulsifying drug delivery systems and cannabinoid formulations. The differences between the claims are insufficient to patentably distinguish the instant claims from ‘367. Adapting the SEDDS-cannabinoid formulation of ‘367 to a capsule dosage form would have been obvious to a person of ordinary skill in the art, particularly given the ‘367's own express disclosure that the formulation may be used in capsules (¶[0300]-[0314] "capsule formulation comprising" the claimed carrier systems and self-emulsifying systems). The selection of specific parameter values (e.g., "at least 20%" vs. "at least 10%" for cannabinoid content, "at least 20%" vs. "at least 30%" for PEG surfactant content) would have been a matter of routine optimization, not an inventive step, as ‘367 teaches a range of values for these parameters (e.g., ¶[0032]-[0041] for range of PEG surfactant content: at least 20%, 25%, 30%, 35%, 40%, 50%, 60%; and ¶[0042]-[0058] for range of cannabinoid content: at least 10%, 15%, 20%, 25%, 30%, 35%, 40%). Furthermore, the use of a hard-shell or soft-shell capsule is a conventional and well-known dosage form in the pharmaceutical arts, as recognized by the ‘367's own disclosure of capsules for peroral administration. The capsule form is simply an obvious alternative dosage form for the same SEDDS-cannabinoid formulation.
Instant claims 110-131, which depend from claim 109, further define details of the formulation, including specific components, amounts, and properties. These limitations are either disclosed in ‘367 or would have been obvious to one of ordinary skill in the art as conventional excipients or routine optimization for the capsule dosage form (‘367 specification ¶[0068] formulation in addition to any water-soluble agents comprises less than 20% teaches <20% water-soluble agents of instant claim 110; ¶[0148] does not comprise sugar alcohol or sugars teaches the limitations of instant claim 111; ¶[0055] at least 10% by weight of tableted powder teaches the limitation of instant claim 112 having SEDDS + cannabinoids ≥50% of formulation; ¶[0067]-[0068] and ¶[0093] teaches SEDDS is liquid limitation of instant claim 113; ¶[0068]-[0082] teaches SEDDS comprises lipids and/or oils of instant claim 114; ¶[0073]-[0081] teaches triglycerides, lipophilic compounds of instant claims 115 and 116; ¶[0083]-[0087] teaches 1-50% by weight lipids of instant claim 117; ¶[0099]-[0108] teaches PEG-containing surfactants of instant claims 118-121; ¶[0113]-[0120] teaches hydrophilic solvents ≥5% of instant claim 122; ¶[0126]-[0148] teaches non-PEG surfactants of instant claims 123-128; ¶[0123] teaches 5-15% permeation enhancers of instant claim 129; ¶[0173]-[0180] teaches solid carriers of instant claim 130). Thus, the dependent claims are rejected for the same reasons as independent claim 109.
Instant claim 131 recited the limitation of absolute bioavailability of at least 4.0%. Patent ‘367 repeatedly teaches unexpectedly enhanced cannabinoid uptake resulting from PEG-containing surfactant SEDDS systems (¶[0027]-[0031], ¶[0128]-[0131]). A bioavailability threshold merely characterizes an inherent result of administering the claimed composition. Where a claimed property naturally flows from an otherwise obvious composition, the property does not render the claim patentably distinct (see In re Best, 562 F.2d 1252 (CCPA 1977). Accordingly claim 131 does not confer patentable distinctness.
To further support the obviousness of the claimed capsule, Benita is directed to self-emulsifying drug delivery systems for lipophilic compounds such as cannabinoids and explicitly contemplates oral administration, including in capsule form (¶[0001]-[0003], ¶[0032], ¶[0053], ¶[0098]-[0100]). Benita further provides guidance on formulating SEDDS for cannabinoids and the use of surfactants, oils, and other components that overlap with the instant claims (¶[0031], ¶[0065]-[0077]). Benita's disclosure would have motivated a person of ordinary skill in the art to adapt the SEDDS-cannabinoid formulations of ‘367 into a capsule dosage form, as this is a well-known and conventional oral delivery vehicle for such formulations.
Alternatively, Murty further supports the obviousness of the claimed capsule. Murty is directed to self-emulsifying drug delivery systems for lipophilic drugs, such as cannabinoids (e.g., THC) for oral administration to enhance bioavailability (¶[0001]-[0005], ¶[0014]-[0017]). Murty explicitly teaches that the delivery system can be administered as a liquid or semi-solid matrix within a capsule shell (¶[0005]). This disclosure would have directly motivated a person of ordinary skill in the art to combine the SEDDS formulation of ‘367 with a capsule dosage form, as taught by Murty.
Thus, ‘367claims and expressly describes the same cannabinoid-loaded SEDDS compositions. The instant claims merely place those known SEDDS compositions into a conventional capsule dosage form. The capsule format represents a predictable and well-known alternative oral dosage form. The remaining dependent claim limitations are expressly disclosed in the issued patent specification or constitute obvious formulation optimizations and inherent properties. Benita and Murty further demonstrate that cannabinoid SEDDS systems were conventionally formulated in capsules, confirming the obviousness of the dosage-form substitution.
For the reasons set forth above, the claims of the instant application are not patentably distinct from the claims of ‘367. The claimed capsule is an obvious variation of the SEDDS-cannabinoid formulations disclosed in ‘367 in view of the knowledge of one of ordinary skill in the art, Benita, and/or Murty. Accordingly, a prima facie case of nonstatutory obviousness-type double patenting has been established. This rejection may be overcome by filing a timely terminal disclaimer in compliance with 37 CFR § 1.321(c), disclaiming any term of extension that would extend beyond the expiration date of the issued patent or by showing patentable distinctness.
Conclusion
No claims are allowed.
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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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