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
The instant application is a continuation of US application 18/244,391 filed 11 September 2023 which is a continuation of US application 16/837,213 filed 1 April 2020. Acknowledgement is made of the Applicant’s claim of domestic priority to provisional US application 62/919,873 filed 2 April 2019.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4 December 2025 has been entered.
Examiner’s Note
Applicant's amendments and arguments filed 4 December 2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 4 December 2025, it is noted that no claims have been amended. No new matter or claims have been added.
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.
Claims 1-3, 5-14, and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Stinchcomb et al. (US 2010/0273895) in view of Yeomans et al. (US 9,629,894) in view of PreveCeutical (2018) in view of Selvaraj et al. (WO 2020/186246) in view of Bradley et al. (US 2006/0241125).
The Applicant claims, in claim 1, a method of treating a CNS condition comprising administering intranasally directly to a brain to an upper third of a nasal passage through direct nose-to-brain delivery using a pressurized container, pump, spray, atomizer, or nebulizer the composition comprising cannabidiol (CBD). Claim 1 requires the method to provide greater bioavailability of the CBD (>6-13%) compared to oral administration and reduce potential drug-drug interactions associated with systemic delivery, which is considered an inherent property of administering CBD using the claimed method steps. Claim 1 requires the composition be a fine mist comprising CBD with a particle size of less than about 5 microns. Claim 1 recites the bioavailability increase achieved which is considered an inherent property of administering CBD using the claimed method steps. Claims 2-3 require administration be an electrohydrodynamic atomizer with actuation between 1-100 mL. In claim 5, the CBD is a dry powder and claim 6 is a solution of suspension. In claim 7, the composition comprises any of a solvent, propellant, flavor, or sweetener. In claims 8-14 the CNS condition is narrowed to various neurodegenerative conditions. Claims 16-19 mirror earlier claims but require the administration to be by aerosol.
Stinchcomb teaches a pharmaceutical composition comprising a cannabinoid, such as cannabidiol (CBD), and a penetration enhancer (abstract). The penetration enhancer is useful for improving the absorption of the CBD across the skin [0013]. Regarding mode of administration, intranasal administration is disclosed [0015] whereas the composition may be in the form of a suspension, solution, spray, or mist [0156]. The composition of Stinchcomb can also comprise alcohol and water solvents (claims 1, 12). Stinchcomb teaches that, in response to neurodegeneration conditions of the brain, CBD is known to have neuroprotective effects [0005]. CBD also can be used to treat epilepsy, anxiety, and glaucoma [0003]. The composition can be in the form of a gel [0069].
Stinchcomb does not teach a method of treating a CNS condition by intranasal administration of CBD to the upper third of the nasal cavity. Stinchcomb does not teach treating neurodegenerative diseases such as Parkinson’s, depression, and bipolar. Stinchcomb does not teach administration via a pressurized container, pump, spray, atomizer, or nebulizer. Stinchcomb does not teach the particle size of CBD.
PreveCeutical teaches that CBD is used to treat pain, multiple sclerosis, and fibromyalgia, has potential to prevent symptoms of Alzheimer’s, and can suppress the growth of cancer cells (pg 1). PreveCeutical teaches that there are inherent metabolic issues in the consistent and effective delivery of cannabinoids and that new techniques of administration are necessary (pg 1). Conventional inhalation requires the cannabinoids first pass through the bloodstream and liver at which point they are metabolized (pg 2). The blood brain barrier also presents a major challenge in delivering targeted therapeutic relieve (pg 2). PreveCeutical teaches the solution is to deliver CBD sol-gel using a nose-to-brain delivery platform via nasal spray, which bypasses the blood brain barrier (pgs 2-3).
Yeomans teaches that “intranasal administration” refers to delivery to the nose, nasal passageways, or nasal cavity by spray, powder, or inhalant (col 6, lns 30-33). Both dry and liquid formulations can be administered by aerosol means (col 22, ln 64-col 23, ln 4). Yeomans further breaks down “nasal cavity” as including both the inferior (i.e. lower two thirds) and superior (i.e. upper third) regions (col 6, lns 34-40) and teaches that intranasal delivery can include delivery to either region or the entire nasal passage (col 26, lns 26-32).
Selvaraj teaches pharmaceutical compositions comprising cannabinoids (abstract). It is taught that cannabinoids are useful for treating pain, epilepsy, depression, schizophrenia, Alzheimer’s anxiety, neurodegeneration, diabetes, Parkinson’s, traumatic brain injury and others (pg 1, lns 13-20).
Bradley teaches a compound for therapy (title) wherein the compound can be administered intranasally or by inhalation, in the form of a dry powder from an aerosol spray or atomizer such as an electrohydrodynamic spray to form a fine mist [0266]. The dry powder can be stored as a solution or suspension [0267]. The actuation volume of the electrohydrodynamic atomizer is preferred to be in the range of from 1-100 mL for inhaled/intranasal administration [0270]. Bradley discloses that a suitable particle size for inhalation of a drug is typically less than 5 microns [0268].
It would have been prima facie obvious to prepare the composition of Stinchcomb which consists only of CBD, solvent, and a penetration enhancer such as DMSO. It would have been obvious to apply this composition intranasally for the treatment of neurodegeneration and pain due to the teachings that CBD is a neuroprotective agent and that intranasal administration is suitable for the invention of Stinchcomb. Treatment of epilepsy, schizophrenia, Alzheimer’s, Parkinson’s, and traumatic brain injury would have also been obvious. Yeomans defines “intranasally” as comprising all regions, including the upper third, of the nasal cavity. PreveCeutical teaches that due to metabolic issues and a desire to avoid the bloodstream, it is beneficial and desired to administered CBD intranasally in a direct nose-to-brain technique. Stinchcomb is silent as to which portion of the nasal cavity to which the composition is being administered thus, in lieu of evidence to the contrary and based on the definitions in the prior art and the desire to avoid metabolism by direct nose-to-brain delivery of CBS, it would have been obvious to target the upper third of the nasal cavity during intranasal administration of the CBD composition.
The instant claims require the CBD to be powdered, however it is noted that in the presence of a solvent that solubilizes CBD, the physical form of the CBD is no longer relevant. Stinchcomb teaches that the CBD is dissolved, in one embodiment, using ethanol as the solvent [0157]. Therefore, upon selecting at least ethanol as the solvent of choice, the CBD will always be dissolved and the physical form upon administration is in solution and not powdered. Since the Applicant is silent as to the selection of solvent, it would have been obvious to select any solvent including those that solubilize CBD. That being said, even if the CBD was not solubilized in the selected solvent, it would still be in a suspended state and not a powder form. Moreover, the particle size of CBD would have been obvious to formulate as less than 5 microns to include in an inhalation delivery system.
Regarding the mode of administration, Stinchcomb teaches a spray but does not provide further details, thus it would have been obvious to look to PreveCeutical which teaches direct nose-to-brain delivery of CBD via nasal spray. It would have been further obvious to look to Bradley, which teaches how to administer a therapeutic agent via intranasal administration by way of an electrohydrodynamic atomizer. Thus, it would have been obvious to use an electrohydrodynamic atomizer with an actuation volume between 1-100 mL as the spray or aerosol delivery method of Stinchcomb.
Since Lowe teaches that CBD can treat both neuropathic pain and other neurological disorders such as bipolar disorders, Parkinson’s disease, and Alzheimer’s disease, it would have been obvious to apply the composition of Stinchcomb to treat these other neurodegenerative diseases. In summary, it would have been obvious to treat neurological disorders such as depression, epilepsy, anxiety, traumatic brain injury, bipolar disorders, Parkinson’s disease, and Alzheimer’s disease by administering intranasally (preferably to the upper third of the nasal passage) a composition comprising CBD (a fine mist of particles less than 5 microns) that is solubilized or suspended in ethanol along with DMSO as a penetration enhancer. The resulting formulation necessarily has the bioavailability to the brain as required in instant claim 1. It is noted that “products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP 2112.01 (II)). Claims 1-3, 5-14, and 16-19 are accordingly rejected in view of the prior art above.
Claims 1-3 and 5-19 are rejected under 35 U.S.C. 103 as being unpatentable over Stinchcomb et al. (US 2010/0273895) in view of Yeomans et al. (US 9,629,894) in view of PreveCeutical (2018) in view of Selvaraj et al. (WO 2020/186246) in view of Bradley et al. (US 2006/0241125) in view of Mecha et al. (Cell Death and Disease (2012) 3, e331).
In claim 15, the CNS condition is narrowed to various stress conditions.
Stinchcomb, Yeomans, PreveCeutical, Selvaraj, and Bradley as applied supra, are herein applied in their entirety for the teachings of a method of treating a disease by administering CBD intranasally directly to the brain.
Stinchcomb does not teach wherein the CNS condition is associated with oxidative stress, endoplasmic stress, or excitotoxic stress.
Mecha teaches that CBD offers protection to oligodendrocyte
progenitor cells (OPC) against inflammation-induced damage, as well as protecting the cells from oxidative stress by reducing reactive oxygen species production (pg 2, ¶2). In other words, CBD was shown to prevent OPC death induced by inflammatory, oxidative, or endoplasmic reticulum stress (pg 4, ¶5).
Response to Arguments
Applicant's arguments filed 4 December 2025 have been fully considered but they are not persuasive. The Applicant argues, on pages 5-6 of their remarks, that the cited references fail to teach the claimed invention. Specifically, the Applicant argues that Bradley fails to teach CBD and targeting the upper third of a nasal passage.
In response to Applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Bradley is applied for its teachings of how to administer a therapeutic agent via intranasal administration by way of an electrohydrodynamic atomizer. Primary reference Stinchcomb teaches application of CBD and the secondary references provide motivation and reasons why Stinchcomb would have been modified to change the mode of administration to intranasal delivery to the upper third of the nasal passage for direct nose-to-brain delivery.
The Applicant argues, on pages 6-7 of their remarks, that references Lajoie and Tai exemplify the unpredictability and challenges associated with the use of CBD. Specifically, the Applicant argues that Tai teaches CBD as having limited excipients that can solubilize it and that further in vivo testing is required to investigate the impact of inhalable formulation on the PK profile of CBD. Regarding Lajoie, the Applicant argues that the reference teaches the poor bioavailability of THC and CBD as well as the poor solubility.
In response, these references are not sufficient in overcoming the pending rejection. The Lajoie reference is directed to oral dosages of cannabinoids and emulsifying agents that improve stability thereof. Lajoie does not discuss intranasal dosage forms. The above rejection provides motivation to modify the transdermal application of CBD to an intranasal administration, not oral. Regarding Tai, the reference teaches the poor water solubility of CBD, which was already known, and provides excipients to improve the solubility of inhalable powders. Stinchcomb, as applied in the above rejection, previously recognized the issue of CBD water solubility and included solubility agents such as propylene glycol in their formulations [0011, 0169, 0181].
The Applicant argues, on page 7 of their remarks, that PreveCeutical fails to affirmatively disclose that nose-to-brain delivery is possible or enabled.
In response, the PreveCeutical article positively identifies metabolic problems with CBD administration and then provides a clear solution. The solution is “the world's first nose-to-brain drug delivery platform” using sol-gel technology that bypasses the blood brain barrier, gels upon contact with mucosal tissue, and effectuates targeted drug delivery directly to the brain. Applicant is reminded that “a reference is presumed operable until applicant provides facts rebutting the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Therefore, applicant must provide evidence showing that a process for making was not known at the relevant time.” (see MPEP 2121.02 (I)). The Applicant has failed to provide evidence that the delivery platform of PreveCeutical could not have been made at the time of publication of the prior art reference. In addition, "Even if a reference discloses an inoperative device, it is prior art for all that it teaches." Beckman Instruments v. LKB Produkter AB, 892 F.2d 1547, 1551, 13 USPQ2d 1301, 1304 (Fed. Cir. 1989). Therefore, "a non-enabling reference may qualify as prior art for the purpose of determining obviousness under 35 U.S.C. 103." (see MPEP 2121.01 (II)).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW S ROSENTHAL whose telephone number is (571)272-6276. The examiner can normally be reached M-F 8-5pm EST.
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/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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