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 .
Status of the Claims
Claims 1 – 5, 7 – 17, 20 – 25, 33 – 34, 36, 39 – 42, 70, 98 and 127 are pending.
Claims 1 – 5, 8 – 17, 20 – 21, 33 – 34, 36, 39 – 41 and 127 are rejected.
Claims 7, 22 – 25, 42, 70 and 98 are withdrawn.
Election/Restriction
Applicant’s election without traverse of Group I (claims 1 – 5, 7 – 17, 20 – 25, 33 – 34, 36, 39 – 41 and 127) in the reply filed on July 28, 2026 is acknowledged. Further, Applicant has specifically elected cannabinol as a compound of Formula (II), and Alzheimer’s Disease as a neurodegenerative disease or disorder. The structure of cannabinol is presented below:
PNG
media_image1.png
292
402
media_image1.png
Greyscale
.
The compound reads on the compound of Formula (II)
PNG
media_image2.png
346
420
media_image2.png
Greyscale
, wherein:
R1 and R6 are each hydrogen,
R2 is C5 alkyl, and
R3, R4 and R5 are each C1 alkyl.
Examination: Claims 1 – 5, 8 – 17, 20 – 21, 33 – 34, 36, 39 – 41 and 127 read on the elected species. The elected species are not allowable over the prior art. Pursuant to Federal Register, Vol. 76, No. 27, dated February 9, 2011, page 7166 (middle column):
“Under principles of compact prosecution, the examiner should also require the applicant to elect a species or group of indistinct species for search and examination (i.e., an election of species). If the examiner does not find the species or group of indistinct species in the prior art, then the examiner should extend the search to those additional species that fall within the scope of a permissible Markush claim. In other words, the examiner should extend the search to the species that share a single structural similarity and a common use. The improper Markush claim should be examined for patentability over the prior art with respect to the elected species or group of indistinct species…within the scope of a proper Markush claim.”
In the interest of compact prosecution, the search has been further extended to include the scope, wherein the cannabinoid is cannabichromene (CBC), cannabidivarin (CBDV, also known as cannabidivarol), and cannabidivarin acid (CBDVA). Subject matter not embraced by the elected embodiment or the scope searched is therefore withdrawn from further consideration. Claims 7, 22 – 25, 42, 70 and 98 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/ species, there being no allowable generic or linking claim.
Priority
PNG
media_image3.png
44
320
media_image3.png
Greyscale
Information Disclosure Statement
The information disclosure statements (IDS) submitted on June 12, 2024, October 25, 2024, March 19, 2025, April 29, 2025 and January 7, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 17 is objected to because of the following informalities:
Lines 1 – 2 and 19 – 20 of the claim: The limitation “… the cannabinoid is selected from the group consisting of cannabichromene (CBC)… dihydrocannabielsoin (H2CBE), tetrahydrocannabigerol (H4CBG), and combinations thereof” is grammatically incorrect because it does not recite proper singular form and Markush group language. In order to overcome the objection, Applicant may amend the limitation as follows: “… the cannabinoid is selected from the group consisting of cannabichromene (CBC)… dihydrocannabielsoin (H2CBE), and tetrahydrocannabigerol (H4CBG), or a combination thereof”.
Appropriate correction is required.
Improper Markush Group Rejection
Claims 4 – 5 and 8 – 17 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the compound of Formula (I), the compound of Formula (II), the compound of Formula (III), the compound of Formula (IV), the compound of Formula (V), the compound of Formula (VI), the compound of Formula (VII), or the compound of Formula (VIII) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Claim 1 is directed to a method of treating a neurodegenerative disease or condition in a subject, comprising administering a therapeutically effective amount of a cannabinoid to the subject. Dependent claim 4 is directed to the method of claim 1, wherein the cannabinoid is a compound of Formula (I), a compound of Formula (II), a compound of Formula (III), a compound of Formula (IV), a compound of Formula (V), a compound of Formula (VI), a compound of Formula (VII), or a compound of Formula (VIII):
PNG
media_image4.png
560
710
media_image4.png
Greyscale
.
Further, dependent claim 17 is directed to the method of claim 1, and recite several compounds that read on the compounds of Formulae (I) – (VIII) as presented below:
PNG
media_image5.png
535
960
media_image5.png
Greyscale
PNG
media_image6.png
290
960
media_image6.png
Greyscale
The structures associated with each of the Formulae (I) – (VIII) above do not share a substantial feature to each other. The compounds of each of the Formulae (I) – (VIII) as claimed in claim 4 do not belong to the same art-recognized class or chemical class of compounds because there is no common core structure shared among all of the compounds that would enable them to be categorized the same. For example, the compound of Formula (I) can be classified in CPC class C07C17, the compound of Formula (IV) can be classified in CPC class C07D307/91, the compound of Formula (II) can be classified in C07D311/80, and the compound of Formula (VI) can be classified in C07D493/08. There is no shared structure amongst all of the alternatives of the compounds of the Formulae (I) – (VIII) as claimed. The compounds do not belong to the same recognized physical or chemical class or to the same art-recognized class and each compound would possess different physical and chemical properties in view of the functional and cyclic groups such that they would not be expected to have the necessary common use. Thus, the compounds of the Markush grouping cannot be considered to share a “single structural similarity” that is essential from which a common use flows.
In order to overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1 – 5, 8 – 17, 20 – 21, 33 – 34, 36, 39 – 41 and 127 is rejected under 35 U.S.C. 103 as being unpatentable over Iuvone et al. WO2013/005017 A1, cited in IDS dated June 12, 2024, in view of Schubert et al., Molecular Neurobiology (2019), 56: pp. 7719-7730, cited in IDS dated January 7, 2026, evidenced by Cayman Chemical, Product Information, Cannabinol, Item No. 25495, CAS Registry No. 521-35-7, https://www.caymanchem.com/product/25495/ cannabinol, Accessed on August 20, 2026.
Determining the scope and contents of the prior art
Iuvone et al. teach “[n]eurodegenerative diseases or disorders often occur as a result of oxidative stress…[o]xidative stress occurs to the cells in an organism when the effects of pro-oxidants (such as free radicals, reactive oxygen and reactive nitrogen species) exceed the ability of anti-oxidants to neutralise them…[w]hen levels of free radicals or other pro-oxidants increase to such an extent, they can cause damage to cell membranes which in turn may result in cell death (oxytosis) or damage to genetic material”. See, e.g., paragraph [0003]. Iuvone teaches a method of treating neurodegenerative diseases or disorders comprising administering to a subject in need thereof a therapeutically effective amount of one or more of phytocannabinoids (a type of cannabinoid), specifically cannabichromene (CBC), cannabidivarin (CBDV) and/ or cannabidivarin acid (CBDVA). See, e.g., Abstract, paragraph [0035], and claim 6. The neurodegenerative disease or disorder is preferably Alzheimer’s Disease. See, e.g., paragraphs [0025], [0037] and [0080], and claim 8. Iuvone teaches that the effective daily (per day) dose of cannabinoid is between 5 mg and 1000 mg, preferably between 10 mg and 50 mg. See, e.g., paragraph [0040], and claim 12.
Ascertaining the differences between the prior art and the claims at issue
Compared to instant claims, the difference is that Iuvone does not explicitly teach that the cannabinoid is cannabinol (CBN), as elected by the Applicant.
Rationale for a prima facie case of obviousness
According to MPEP §2141(III), two of the rationales in the KSR decision states “(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success”… (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Schubert et al. teach a “number of non-psychoactive cannabinoids are neuroprotective in a novel pre-clinical AD (Alzheimer’s Disease) and neurodegeneration drug-screening platform… [t]his drug discovery paradigm has yielded several compounds in or approaching clinical trial for AD”. See, e.g., Abstract. Schubert also teaches the biological activity of 11 cannabinoids for five different assays, including oxytosis. See, e.g., Table 1. The structure and the biological activity of CBN (cannabinol) (See, e.g., pp. 7722, Figure 1 and Table 1) are presented below:
PNG
media_image7.png
269
476
media_image7.png
Greyscale
.
PNG
media_image8.png
94
1041
media_image8.png
Greyscale
Schubert demonstrates that CBN is a potent inhibitor of oxytosis and Amyloid β (Aβ) toxicity. See, Table 1. Schubert concludes “some non-psychoactive cannabinoids (including CBN) are effective at nanomolar levels in a drug screening platform that has been used to identify bona fide AD drug candidates”. See, e.g., pp. 7728, Conclusion, 1st paragraph. Thus, Schubert et al. specifically identify CBN (cannabinol) can be used for the treatment of Alzheimer’s Disease.
A person who has ordinary skill in the art would have been motivated to perform routine experimentation, such as administering cannabinol, in the method as taught by Iuvone et al. The purpose of the routine experimentation would have been to determine which cannabinoid would be optimal for the treatment of Alzheimer’s Disease. Based on the teachings of Schubert, the PHOSITA would have an expectation of success in administering a therapeutically effective amount of cannabinol (CBN) in the method of treating Alzheimer’s Disease in a subject in need thereof.
Therefore, the teachings of Schubert et al. and Iuvone et al. render the instant claims prima facie obvious as presented below:
Claims 1, 3 – 5, 8 – 17, 21, 33 – 34, 36 and 127, directed to a method of treating Alzheimer’s Disease in a subject, comprising administering a therapeutically effective amount of cannabinol (CBN). The structure of CBN reads on the compound of Formula (II):
PNG
media_image2.png
346
420
media_image2.png
Greyscale
, wherein:
R1 and R6 are each hydrogen,
R2 is C5 alkyl, and
R3, R4 and R5 are each C1 alkyl.
With respect to claims 2 and 39 – 40, Schubert teaches “[o]xytosis is a programmed cell death pathway in which glutamate inhibits the uptake of cystine into neurons, thereby reducing the synthesis of glutathione, stimulating mitochondrial ROS production, oxidative stress, the influx of calcium, and ultimately cell death”. Schubert states that oxytosis is identical to ferroptosis pathway and multiple cannabinoids, including cannabinol (CBN), prevented oxytosis. See, e.g., pp. 7721, 1st paragraph, Table 1.
With respect to claim 20, Schubert teaches that all cannabinoids were purchased from Cayman Chemicals. See, e.g., pp. 7720, Reagents, 1st paragraph. According to Cayman Chemicals, Cannabinol (CAS Registry No. 521-35-7) has a purity of greater than or equal to 98% ( > 98%). See attached Product Information, pp. 1 line 6.
With respect to claim 41, Iuvone teaches that the effective daily dose of cannabinoid is between 5 mg and 1000 mg, preferably between 10 mg and 50 mg. See, e.g., paragraph [0040], and claim 12. In the instant case, the range disclosed by Iuvone et al. lies within the claimed daily dose of about 1 mg/kg/day to about 50 mg/kg/day.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sagar Patel whose telephone number is (571)272-1317. The examiner can normally be reached Monday - Friday: 9am to 5pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Sagar Patel/Examiner, Art Unit 1626
/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626
Prosecution Insights