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 .
Priority
This application is a continuation of U.S. Application No. 16/221,244 filed on December 14, 2018, which is a continuation of PCT/US2017/037797 filed on June 15, 2017 which claims priority from U.S. Provisional Application No. 62/350,702, filed on June 15, 2016.
Response to Amendment
Applicant’s amendment filed on August 8, 2025 amending claims 44, 56 and 57 has been entered. Claims 1-43 are canceled. Claims 46, 47 and 49 are withdrawn from further consideration.
Claims 44, 45, 48 and 50-63 are currently presented for examination.
Response to Arguments
Due to Applicant’s amendments to the claims, the previous rejections under 35 USC 103 are hereby withdrawn. Specifically the claims have been amended by removing terpene from the solution and requiring quillaja extract and the rejections of record do not address a solution comprising quillaja extract. However, upon further search and consideration, new rejections are detailed below which render obvious the currently amended claims requiring the inclusion of quillaja extract. Since it was previously indicated that Applicant’s elected species of quillaja extract was not found in the prior art, this action is NON-final.
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 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.
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 44, 45, 50-53, 55-58 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Kleidon et al. WO 2016/094810 A2 (Provided on IDS) in view of Park et al. U.S. Publication No. 2004/0028758 A1 (Provided on IDS).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The cited claims of the instant application claim a method for reducing oxidative stress in a subject, comprising administering to said subject in need thereof an amount of a composition comprising a solution comprising quillaja extract and a plurality of microcapsules comprising a cannabinoid compound such as cannabidiol (CBD) and at least one enzymatic antioxidant such as superoxide dismutase, glutathione peroxidase, glutathione reductase, catalases, or ascorbate oxidase, wherein a microcapsule of said plurality of microcapsules has a diameter of at most 2 micrometers (m) and encapsulates said cannabinoid compound, thereby reducing oxidative stress in said subject.
Kleidon et al. teaches a composition comprising a plurality of microcapsules, wherein an individual microcapsule of the plurality comprises (a) at least one cannabinoid compound and (b) at least one terpene compound present in an amount of at least about one microgram [0006]. Kleidon et al. teaches that the at least one cannabinoid compound comprises cannabidiol (CBD) [0010]. Kleidon et al. teaches that in some embodiments, the individual microcapsule of the plurality of microcapsules comprises less than 0.3% tetrahydrocannabinol (THC) [0010]. In some cases, a composition of the present disclosure does not contain a psychoactive amount of THC [0053]. Kleidon et al. teaches in some embodiments, the composition further comprises alginate [0010]. Kleidon et al. teaches in some examples, a composition of the present disclosure comprises ingredients including vitamin C and other antioxidants ([0014], [0068], [0071], [0074]-[0076], [0080]-[0081], [0083], [0085], [0088]-[0091]).
Kleidon et al. teaches a method of preparing a cannabinoid containing composition comprising providing a solution comprising cannabinoids and micro-encapsulating said solution to form a plurality of microcapsules of a composition of the present disclosure [0019]. Kleidon et al. teaches a composition suitable for oral consumption, food preparation, or topical application, comprising at least 0.04% by weight of a cannabinoid compound and a coconut product [0020]. In some embodiments of aspects provided herein, said cannabinoid compound is a cannabidiol (CBD) compound [0022]. In some embodiments said cannabinoid compound is encapsulated within microcapsules [0022]. In some embodiments said composition is solid, semi-solid, gel, or liquid [0022]. Kleidon et al. teaches that the encapsulated cannabinoids can be present in a quantity of at least about 0.1% by weight of a microcapsule [0045].
Kleidon et al. specifically teaches microencapsulation can be performed via an emulsification process, for example, compositions can be emulsified in a mixer, such as an agitator, impeller, centrifugal mixer, or high-shear mixer [00102]. Microencapsulation processes can be conducted with the aid of one or more emulsifiers or surfactants, wherein the emulsifiers and surfactants can include but are not limited to saponins (e.g., quillaja tree extract such as Q-NATURALE®, yucca extract), lecithin, soy lecithin, mustard seed hull extract, sodium stearoyl lactylate, polysorbate 20, and combinations thereof [00103]. Microcapsules can comprise one or more stabilizers or gelling agents, which can be used to stabilize a microcapsule or emulsion, wherein the stabilizers or gelling agents can include but are not limited to alginate (also algin or alginic acid) and agar [00104]. Alginate can be used in a variety of forms, including but not limited to inorganic salts such as sodium alginate, potassium alginate, calcium alginate, and combinations thereof, and can be derived from sources such as seaweed (e.g., Macrocystis pyrifera, Ascophyllum nodosum, Laminaria spp.) or bacteria (e.g., Pseudomonas spp., Azotobacter spp.) [00104].
Microcapsules can be characterized by a size (e.g., a diameter), wherein the microcapsule size can be about 0.154 micrometers [00105]. The microcapsule size can be less than or equal to about 0.154 micrometers [00105].
Kleidon et al. further teaches that terpenes and/or essential oils can be included in the composition including alpha-pinene can be used as an anti-inflammatory, an antiangiogenic, an anti-ulcer agent, and a bronchodilator ([0062]-[0063], [0092]).
Kleidon et al. further teaches the use of antioxidants and ingredients for the composition selected to reduce oxidative stress ([0071], [0075], [0079]).
Kleidon et al. further teaches compositions of the present disclosure can be used to treat various diseases or conditions in subjects (e.g., humans, mammals, vertebrates), including but not limited to ALS, Alzheimer's, antibacterial resistant infections, anxiety, atherosclerosis, arthritis, asthma, cancer, colitis, Crohn's, diabetes, depression, endocrine disorders, epilepsy, seizures, fibromyalgia, glaucoma, heart disease, Huntington's, inflammation, irritable bowel syndrome (IBS), kidney disease, liver disease, motion sickness, nausea, neurodegeneration, neuropathic pain, neuropathy, obesity, obsessive compulsive disorder (OCD), osteoporosis, Parkinson's, prion diseases, Mad Cow disease, post-traumatic stress disorder (PTSD), rheumatism, schizophrenia, sickle cell anemia, skin conditions (e.g., psoriasis, dermatitis, allergic inflammation, chronic pruritus), sleep disorders (e.g., sleep-wake disorders, apnea), spinal cord injury, stress, stroke, and traumatic brain injury (TBI) [0097].
Kleidon et al. teaches a hemp oil composition is produced, comprising cannabinoids including cannabidiol, additional essential oils, alginate (e.g., sodium alginate) and quillaja tree extract [00128]. The composition is microencapsulated via a microfluidic nozzle device and the microcapsules are packaged in a suspension [00128]. Kleidon et al. teaches formulations comprising quillaja extract (e.g., Q Natural), hemp oil, water, and optionally sodium alginate were prepared using a microfluidic fluid processor (e.g., Microfluidizer from Microfluidics/IDEX Corporation) [00135].
Thus Kleidon et al. teaches a similar formulation as claimed for reducing oxidative stress and treating one or more heath conditions wherein the formulation comprises a solution comprising quillaja extract and a plurality of microcapsules comprising a cannabinoid compound such as cannabidiol (CBD), wherein a microcapsule of said plurality of microcapsules has a diameter of less than 2 micrometers (m).
Kleidon et al. does not teach including at least one enzymatic antioxidant selected from superoxide dismutase, glutathione peroxidase, glutathione reductase, catalases, or ascorbate oxidase.
Although Kleidon et al. does not teach including at least one enzymatic antioxidant in the formulation, as detailed above, Kleidon et al. teaches that other ingredients may further be included in the composition including antioxidants. As such, it would have been obvious and within the skill of an ordinary artisan practicing the invention of Kleidon et al. to select a suitable antioxidant well-known in the art.
Kleidon et al. teaches the use of non-enzymatic antioxidants such as vitamin C [0014]. However, prior to the effective filing date of the instant application, enzymatic and non-enzymatic antioxidants served the same function of reducing the production of reactive oxygen species in the body and at the same time, preventing oxidation that causes irrecoverable damages to the cells (see Park et al. U.S. Publication No. 2004/0028758 A1 paragraph [0002]).
Park et al. teaches that natural antioxidants include antioxidant enzymes such as superoxide dismutase, catalase, peroxidase, and glutathione peroxidase as well as non-enzymatic antioxidants such as vitamin E, vitamin C and glutathione [0003]. Park et al. further teaches that the actions of reactive oxygen species can be reduced by antioxidant enzymes such as superoxide dismutase, catalase and peroxidase, and antioxidant substances such as vitamin C, vitamin E and glutathione [0002].
Accordingly, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art practicing the invention of Kleidon et al., to utilize any suitable antioxidant known in the art including an enzymatic antioxidant with a reasonable expectation of predictable results. Thus, in the absence of secondary considerations such as a demonstration of criticality or unexpected results, including an enzymatic antioxidant in the formulation of Kleidon et al. having the same function of reducing oxidative stress as the components in the composition of Kleidon et al. would have been seen as selecting an obvious alternative and within the skill of an artisan practicing the invention. Furthermore, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980). Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Kleidon et al. WO 2016/094810 A2 (Provided on IDS) in view of Park et al. U.S. Publication No. 2004/0028758 A1 (Provided on IDS) as applied to claims 44, 45, 50-53, 55-58 and 63 above and further in view of Hampson et al. U.S. Patent No. 6,630,507 B1 (Provided on IDS) and Stein (Nutrition, Volume 18, Number 10, 2002, pages 867-871).
Claim 48 of the instant application claims the subject is traveling in outer space.
Kleidon et al. does not teach treating a subject traveling in outer space.
Although Kleidon et al. does not teach treating a subject traveling in outer space, as detailed above Kleidon et al. teaches that the formulations contain components that reduce oxidative stress. In addition, as detailed above, Kleidon et al. teaches that the pharmaceutical composition is for treating diseases, disorders, dysfunctions or syndromes including neurodegenerative related syndromes.
In addition, prior to the effective filing of the instant application, cannabinoids were known in the art to have antioxidant properties and to be useful as neuroprotectants for the treatment of neurodegenerative diseases (abstract Hampson et al.). Hampson et al. specifically demonstrates that cannabidiol has antioxidant properties and is useful for the treatment of neurodegenerative diseases (see examples 4-9 columns 14-20).
Stein teaches that there is a balance within the body between oxidant production and antioxidant defenses, with the balance shifted slightly in favor of oxidants (page 867). Oxidative damage from free radicals to DNA and lipids has been implicated in the etiology of a wide variety of chronic diseases and acute pathologic states. The chronic diseases range from cancer to cardiovascular disease and neurodegenerative disease including Alzheimer and Parkinson diseases. Other factors that can result in increased oxidative damage include environmental pollutants, cigarette smoke, radiation, severe nutritional depletion undernutrition, and space flight (page 867). Thus Stein teaches that space flight is associated with an increase in oxidative stress.
Accordingly, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Kleidon et al. which teaches formulations containing a cannabinoid such as CBD combined with other antioxidants which can provide neuroprotection against oxidative stress with the teachings of Hampson et al. which specifically teach that cannabinoid containing formulations including cannabidiol (CBD) have antioxidant properties and are useful as neuroprotectants for the treatment of neurodegenerative diseases, and with the teachings of Stein which teaches that subjects traveling in outer space face increased oxidative stress. Thus, an ordinary skilled artisan would have been motivated to use the antioxidant formulations of Kleidon et al. in a subject traveling in outer space with a reasonable expectation of reducing oxidative stress to lessen the severity of oxidative stress associated with space flight.
Thus claim 48 is rendered obvious in view of the cited prior art teachings.
Claims 59-61 are rejected under 35 U.S.C. 103 as being unpatentable over Kleidon et al. WO 2016/094810 A2 (Provided on IDS) in view of Park et al. U.S. Publication No. 2004/0028758 A1 (Provided on IDS) as applied to claims 44, 45, 50-53, 55-58 and 63 above and further in view of Li et al. (2013, Int. J. Mol. Sci., 14, pages 24438-24475 Provided on IDS).
Claims 59-61 of the instant application claim further (i) detecting said oxidative stress in said subject, which detecting comprises determining one or more levels of oxidative stress in said subject, and (ii) administering said composition to said subject based on said oxidative stress detected in (i).
Kleidon et al. in view of Park et al. is as set forth above.
Kleidon et al. in view of Park et al. does not teach detecting oxidative stress in a subject by determining one or more levels of oxidative stress in the subject.
However, it would have been within the skill of an ordinary artisan to evaluate and monitor a patient prior to and during treatment to determine an appropriate treatment regimen based on procedures well-known in the art.
Prior to the effective filing date of the instant application, methods to detect oxidative stress were known in the art. Li et al. teaches that oxidative stress not only occurs through the overproduction of reactive oxygen/nitrogen species but also under a case of a depleted or weakened antioxidant system, for example the depletion of glutathione in the cell (page 24454). Li et al. teaches measuring redox status of cells by a method to measure intracellular or intramitochondrial ROS/RNS accumulation and/or in some cases the strength of antioxidant systems (page 24454). Thus Li et al. teaches methods to determine ROS and RNS generation as well as methods to measure the strength of antioxidant systems (pages 24454-24459).
Accordingly, prior to the effective filing date of the claimed invention it would have been obvious to a person of ordinary skill in the art to first determine if a patient is in need of treatment with a formulation that reduces oxidative stress by using methods well-known in the art to determine if the patient is in need of treatment to reduce oxidative stress. Moreover, it would have been obvious to a person of ordinary skill in the art to monitor a patient’s progress to determine any adjustments necessary in treatment. Thus, in the absence of secondary considerations, claims 59-61 of the instant application are rendered obvious.
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over Kleidon et al. WO 2016/094810 A2 (Provided on IDS) in view of Park et al. U.S. Publication No. 2004/0028758 A1 (Provided on IDS) as applied to claims 44, 45, 50-58 and 63 above and further in view of Rossi et al. U.S. Publication No. 2012/0263785 A1 (Provided on IDS).
Claim 62 of the instant application claims the composition is stored in a container sealed in a substantially oxygen free atmosphere or under vacuum.
The cited references are as detailed above.
The cited references do not teach the composition is stored in a container sealed in a substantially oxygen free atmosphere or under vacuum.
Rossi teaches that storage and handling of cannabinoid compositions to aid in the stability of the composition can be improved by placing the composition in bottles and filling the bottles until the bottles are about full with the composition under an inert atmosphere (e.g., argon or nitrogen) [0074]. This reduces the chance for oxidation by air. The composition of the bottles may be any material or materials which are known in the art to be air impermeable, preferably, the bottles are made of glass, more preferably borosilicate. Ideally, the caps used to cover the bottles establish an absolute oxygen barrier to the composition [0074]. Rossi further teaches storing the cannabinoid pharmaceutical compositions and products by placing the compositions in at least one of a capsule or a capped bottle and then into an impermeable and sealable bag with or without an oxygen absorbent material. Preferably, the capsule, bottle and bag are all sealed to prevent oxygen and other gases from contacting the composition. Preferably, the bags are capable of being vacuum sealed and are first vacuum sealed before receiving the bottle or capsule [0075].
According, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art to seal the cannabinoid formulation of Kleidon et al. in a container free of oxygen or under vacuum since Rossi teaches that oxygen can degrade cannabinoids and sealing cannabinoid formulations in a sealed container free of oxygen or vacuum sealed can improve storage and handling of cannabinoid compositions to aid in the stability of the composition. Thus claim 62 is rendered obvious in view of the cited prior art teachings.
Claims 44, 45, 50-58 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Morgan WO 2014/100231 A1 (Provided on IDS) in view of Denniston U.S. Publication No. 2017/0266127 A1 and Park et al. U.S. Publication No. 2004/0028758 A1 (Provided on IDS).
Claims 44, 45, 50-58 and 63 of the instant application claim a method for reducing oxidative stress in a subject, comprising administering to said subject in need thereof an amount of a composition comprising a solution comprising quillaja extract, and a plurality of microcapsules comprising a cannabinoid compound such as cannabidiol (CBD) and at least one enzymatic antioxidant such as superoxide dismutase, glutathione peroxidase, glutathione reductase, catalases, or ascorbate oxidase, wherein a microcapsule of said plurality of microcapsules has a diameter of at most 2 micrometers (m) and encapsulates said cannabinoid compound, thereby reducing oxidative stress in said subject.
Morgan teaches a pharmaceutical composition comprising an isolated cannabinoid receptor modulator and optionally a blend of terpenes in a pharmaceutically acceptable carrier (page 11 lines 1-3). Suitable terpenes for the composition include a blend of two or more terpenes selected from limonene, pinene, myrcene, linalool, terpineol, terpinolene, and beta-caryophyllene (page 11 lines 4-10). Morgan teaches in some embodiments the terpene mixture comprises alpha-pinene (page 14 line 19).
Morgan further teaches a suitable cannabinoid receptor modulator is cannabidiol (CBD) (Page 11 lines 17-24 and page 13 lines 1-13 and page 17 lines 13-21). Morgan teaches the pharmaceutical compositions are in the form for oral administration, vaporization-ready, nebulization-ready, nanoparticle formulations, liposomal formulation, and other parenteral forms (page 12 lines 1-4).
Morgan teaches that the pharmaceutical composition is for treating diseases, disorders, dysfunctions or syndromes including seizures, cognition and memory disorders, inflammation, neurodegenerative related syndromes, cognitive impairment, etc. (page 12 lines 16-24).
Morgan further teaches methods of ameliorating or treating a cannabinoid receptor mediated disease, disorder or syndrome in a human subject by such steps as administering to the subject an effective amount of a composition containing cannabinoid receptor modifiers and/or terpenes such as d-limonene, pinene, myrcene, linalool, beta caryophyllene or a combination thereof (page 29 lines 1-5).
Morgan further teaches treating diseases, disorders, dysfunctions or syndromes secondary to organophosphate exposure including seizures, cognition and memory disorders, inflammation, neurodegenerative related syndromes, cognitive impairment, etc. (page 20 lines 13-22).
Morgan specifically teaches that the combination of CB agonists and supplemental terpenes provide neuroprotection against oxidative stress (page 22 lines 14-17).
Morgan teaches the CB receptor agonist is administered via inhalation to mucosal membranes and alveoli of the respiratory tract via the mouth or nose via vaporization, or a nebulization via a mask nebulizer, below the temperature of combustion so as to be less irritating to mucosal and alveoli of the respiratory tract via the mouth or nose (page 25 lines 7-19). Morgan also teaches in yet another embodiment, the cannabinoid formulation is administered by inhalation, via, nose and/or via mouth in the form of a nanomolar formulation or a liposomal formulation that includes added terpenes and/or atropine dry powder via suitable metered dose inhaler, or an electronic nebulizer, designed to deliver therapeutically effective amount of the agonist to the lung (page 25 lines 7-19).
Morgan further teaches formulations suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges, powders, granules, or as a solution or suspension (page 31 lines 16-21). Morgan teaches that the solid dosage forms for oral administration, i.e. capsules, tablets, pills, and the like are prepared by mixing the active ingredients with one or more pharmaceutically acceptable carrier, including binders such as alginates (page 32 lines 3-9). Morgan further teaches that the tablets and other solid dosage forms such as dragees, capsules, pills and granules may be prepared with coating and shells such as enteric coating and other coatings well known in the pharmaceutical formulating art (page 32 lines 29-32). Morgan further teaches that they may be formulated to provide slow or controlled release of the active ingredients such as preparing liposomes and/or microspheres or nanoparticles utilizing polymeric substances and waxes (page 33 lines 1-8). Morgan further teaches that the active ingredients can also be in microencapsulated form (page 33 line 9). Morgan et al. further teaches that injectable depot forms may be prepared by forming microencapsule matrices of the active ingredients in biodegradable polymers (page 35 lines 29-30). Morgan teaches that depot injectable formulations are prepared by entrapping the active ingredients in liposomes or microemulsions or nanoparticles which are compatible with the body tissue (page 36 lines 2-4). Water-soluble nanoparticles are rendered obvious since Morgan teaches the use of polymeric materials to form the nanoparticles which are water-soluble materials.
Morgan further teaches that other ingredients may further be included in the composition including antioxidants (page 13 lines 14-17; page 21 lines 11-15).
Morgan teaches in one aspect of the invention, the cannabinoid therapy includes a terpene blend containing limonene, alpha pinene, myrcene, linalool and beta caryophyllene and further contains CBD (without THC) (page 36 lines 19-23). Morgan specifically teaches administration of CBD (without THC) and the terpene blend containing alpha pinene, myrcene and beta caryophyllene (page 38 lines 3-4 and page 39 lines 29-30).
Morgan teaches that the cannabinoid formulation may be in particle form including liposomes, microspheres or nanoparticles (page 12 lines 1-5, page 27 line 29-page 28 line 1, page 33 lines 3-9, page 34 lines 29-32). Liposomes contain active components encapsulated within. Morgan specifically teaches that the cannabinoids are in liposomes having particle size diameters ranging from 10 nm to 3000 nm and preferably ranging from 50 nm to 2000 nm (2 m) (page 25 lines 20-22). Thus, Morgan teaches particle sizes preferably up to 2 m as claimed in the instant claims.
Morgan further teaches liquid dosage forms for oral administration of the active ingredient(s) include pharmaceutically-acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs (page 33 lines 10-12). Morgan further teaches that in addition to the active ingredients, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl acetate, butyl alcohol, benzyl benzoate, propylene glycol, glycol, oils (in particular, cottonseed, groundnut, com, germ, olive, castor, hempseed, coconut, and sesame oils), terpenes or terpenoids, glycerol or glycerol, amyl alcohol, tetrahydrofuryl polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof (page 33 lines 10-18).
Morgan does not teach including quillaja extract. Morgan does not teach including at least one enzymatic antioxidant selected from superoxide dismutase, glutathione peroxidase, glutathione reductase, catalases, or ascorbate oxidase.
Although Morgan does not teach including quillaja extract, Morgan does teach that liquid dosage forms in addition to the active ingredients, may contain inert diluents commonly used in the art, such as, emulsifiers, such as terpenes or terpenoids (page 33 lines 10-18).
Denniston teaches that cannabinoids are not soluble in water and require an array of emulsifiers or surfactants for liquid preparations for ease of use and maintaining the integrity of the emulsion [0003]. Denniston teaches a suitable emulsifier for the cannabinoids may include a natural emulsifier such as, but not limited to, natural Quillaja tree extract [0030]. Denniston teaches the nutraceutical composition having an amount of Quillaja selected to impart a stabilizing and emulsifying effect when the preparation is mixed with a targeted amount of water [0037].
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Morgan which teaches liquid dosage forms comprising in addition to the active ingredients, inert diluents commonly used in the art, such as, emulsifiers, such as terpenes, with the teachings of Denniston which teaches that cannabinoids are not soluble in water and require an array of emulsifiers or surfactants for liquid preparations such as the natural emulsifier Quillaja tree extract. Thus an ordinary skilled artisan would have been motivated to add quillaja extract to the liquid preparation of Morgan comprising cannabinoids with a reasonable expectation of improving stabilization of the composition.
Although Morgan does not teach including at least one enzymatic antioxidant in the formulation, Morgan teaches that other ingredients may further be included in the composition including antioxidants (page 13 lines 14-17; page 21 lines 11-15). As such, it would have been obvious and within the skill of an ordinary artisan practicing the invention of Morgan to select a suitable antioxidant well-known in the art.
Morgan teaches the use of non-enzymatic antioxidants such as vitamin E and vitamin C (see pages 21 lines 14-15). However, prior to the effective filing date of the instant application, enzymatic and non-enzymatic antioxidants served the same function of reducing the production of reactive oxygen species in the body and at the same time, preventing oxidation that causes irrecoverable damages to the cells (see Park et al. U.S. Publication No. 2004/0028758 A1 paragraph [0002]).
Park et al. teaches that natural antioxidants include antioxidant enzymes such as superoxide dismutase, catalase, peroxidase, and glutathione peroxidase as well as non-enzymatic antioxidants such as vitamin E, vitamin C and glutathione [0003]. Park et al. further teaches that the actions of reactive oxygen species can be reduced by antioxidant enzymes such as superoxide dismutase, catalase and peroxidase, and antioxidant substances such as vitamin C, vitamin E and glutathione [0002].
Accordingly, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art practicing the invention of Morgan, to utilize any suitable antioxidant known in the art including an enzymatic antioxidant with a reasonable expectation of predictable results. Thus, in the absence of secondary considerations such as a demonstration of criticality or unexpected results, including an enzymatic antioxidant in the formulation of Morgan would have been seen as selecting an obvious alternative and within the skill of an artisan practicing the invention.
With respect to claim 63 of the instant application which claims the plurality of microcapsules comprise at most about 0.1% of said cannabinoid by weight, which is equivalent to at most 1000 mg/kg, Morgan teaches that the dosages of phytocannabinoids will range between about 0.0001-100 mg per kg of body weight per day (page 28). Thus a formulation containing at most 0.1% as claimed is rendered obvious in view of the teachings of Morgan et al.
Thus, the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Morgan WO 2014/100231 A1 (Provided on IDS) in view of Denniston U.S. Publication No. 2017/0266127 A1 and Park et al. U.S. Publication No. 2004/0028758 A1 (Provided on IDS) as applied to claims 44, 45, 50-58 and 63 above and further in view of Hampson et al. U.S. Patent No. 6,630,507 B1 (Provided on IDS) and Stein (Nutrition, Volume 18, Number 10, 2002, pages 867-871).
Claim 48 of the instant application claims the subject is traveling in outer space.
Morgan does not teach treating a subject traveling in outer space.
Although Morgan does not teach treating a subject traveling in outer space, Morgan teaches that the formulations containing a cannabinoid such as CBD combined with terpenes including alpha-pinene, myrcene and -caryophyllene provide neuroprotection against oxidative stress (page 22 lines 14-17). In addition, Morgan teaches that the pharmaceutical composition is for treating diseases, disorders, dysfunctions or syndromes including neurodegenerative related syndromes (page 12 lines 16-24).
In addition, prior to the effective filing of the instant application, cannabinoids were known in the art to have antioxidant properties and to be useful as neuroprotectants for the treatment of neurodegenerative diseases (abstract Hampson et al.). Hampson et al. specifically demonstrates that cannabidiol has antioxidant properties and is useful for the treatment of neurodegenerative diseases (see examples 4-9 columns 14-20).
Stein teaches that there is a balance within the body between oxidant production and antioxidant defenses, with the balance shifted slightly in favor of oxidants (page 867). Oxidative damage from free radicals to DNA and lipids has been implicated in the etiology of a wide variety of chronic diseases and acute pathologic states. The chronic diseases range from cancer to cardiovascular disease and neurodegenerative disease including Alzheimer and Parkinson diseases. Other factors that can result in increased oxidative damage include environmental pollutants, cigarette smoke, radiation, severe nutritional depletion undernutrition, and space flight (page 867). Thus Stein teaches that space flight is associated with an increase in oxidative stress.
Accordingly, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Morgan which teaches formulations containing a cannabinoid such as CBD combined with terpenes including myrcene and -caryophyllene which can provide neuroprotection against oxidative stress with the teachings of Hampson et al. which specifically teach that cannabinoid containing formulations including cannabidiol (CBD) have antioxidant properties and are useful as neuroprotectants for the treatment of neurodegenerative diseases, and with the teachings of Stein which teaches that subjects traveling in outer space face increased oxidative stress. Thus, an ordinary skilled artisan would have been motivated to use the antioxidant formulations of Morgan in a subject traveling in outer space with a reasonable expectation of reducing oxidative stress to lessen the severity of oxidative stress associated with space flight.
Thus claim 48 is rendered obvious in view of the cited prior art teachings.
Claims 59-61 are rejected under 35 U.S.C. 103 as being unpatentable over Morgan WO 2014/100231 A1 (Provided on IDS) in view of Denniston U.S. Publication No. 2017/0266127 A1 and Park et al. U.S. Publication No. 2004/0028758 A1 (Provided on IDS) as applied to claims 44, 45, 50-58 and 63 above and further in view of Li et al. (2013, Int. J. Mol. Sci., 14, pages 24438-24475 Provided on IDS).
Claims 59-61 of the instant application claim further (i) detecting said oxidative stress in said subject, which detecting comprises determining one or more levels of oxidative stress in said subject, and (ii) administering said composition to said subject based on said oxidative stress detected in (i).
Morgan in view of Park et al. is as set forth above.
Morgan in view of Park et al. does not teach detecting oxidative stress in a subject by determining one or more levels of oxidative stress in the subject.
However, it would have been within the skill of an ordinary artisan to evaluate and monitor a patient prior to and during treatment to determine an appropriate treatment regimen based on procedures well-known in the art.
Prior to the effective filing date of the instant application, methods to detect oxidative stress were known in the art. Li et al. teaches that oxidative stress not only occurs through the overproduction of reactive oxygen/nitrogen species but also under a case of a depleted or weakened antioxidant system, for example the depletion of glutathione in the cell (page 24454). Li et al. teaches measuring redox status of cells by a method to measure intracellular or intramitochondrial ROS/RNS accumulation and/or in some cases the strength of antioxidant systems (page 24454). Thus Li et al. teaches methods to determine ROS and RNS generation as well as methods to measure the strength of antioxidant systems (pages 24454-24459).
Accordingly, prior to the effective filing date of the instant application it would have been obvious to a person of ordinary skill in the art to first determine if a patient is in need of treatment with a formulation that reduces oxidative stress by using methods well-known in the art to determine if the patient is in need of treatment to reduce oxidative stress. Moreover, it would have been obvious to a person of ordinary skill in the art to monitor a patient’s progress to determine any adjustments necessary in treatment. Thus, in the absence of secondary considerations, claims 59-61 of the instant application are rendered obvious.
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over Morgan WO 2014/100231 A1 (Provided on IDS) in view of Denniston U.S. Publication No. 2017/0266127 A1 and Park et al. U.S. Publication No. 2004/0028758 A1 (Provided on IDS) as applied to claims 44, 45, 50-58 and 63 above and further in view of Rossi et al. U.S. Publication No. 2012/0263785 A1 (Provided on IDS).
Claim 62 of the instant application claims the composition is stored in a container sealed in a substantially oxygen free atmosphere or under vacuum.
The cited references are as detailed above.
The cited references do not teach the composition is stored in a container sealed in a substantially oxygen free atmosphere or under vacuum.
Rossi teaches that storage and handling of cannabinoid compositions to aid in the stability of the composition can be improved by placing the composition in bottles and filling the bottles until the bottles are about full with the composition under an inert atmosphere (e.g., argon or nitrogen) [0074]. This reduces the chance for oxidation by air. The composition of the bottles may be any material or materials which are known in the art to be air impermeable, preferably, the bottles are made of glass, more preferably borosilicate. Ideally, the caps used to cover the bottles establish an absolute oxygen barrier to the composition [0074]. Rossi further teaches storing the cannabinoid pharmaceutical compositions and products by placing the compositions in at least one of a capsule or a capped bottle and then into an impermeable and sealable bag with or without an oxygen absorbent material. Preferably, the capsule, bottle and bag are all sealed to prevent oxygen and other gases from contacting the composition. Preferably, the bags are capable of being vacuum sealed and are first vacuum sealed before receiving the bottle or capsule [0075].
According, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art to seal the cannabinoid formulation of Morgan in a container free of oxygen or under vacuum since Rossi teaches that oxygen can degrade cannabinoids and sealing cannabinoid formulations in a sealed container free of oxygen or vacuum sealed can improve storage and handling of cannabinoid compositions to aid in the stability of the composition. Thus claim 62 is rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 44, 45, 48 and 50-63 are rejected. Claims 1-43 are canceled. Claims 46, 47 and 49 are withdrawn. No claims are allowed.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM