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 .
DETAILED ACTION
Status of claims
The amendment filed on Jan. 29, 2026 is entered. Claims 2-4, 6-9, and 15-42 have been canceled and claims 7-9 has been withdrawn. Claims 1, 5, and 10-14 are under examination in the instant office action.
Applicants' arguments, filed on Jan. 29, 2026, have been fully considered but they are not deemed to be persuasive or moot in view of new grounds of rejection, which are necessitated by the amendments (newly added concentration ranges and ratio of cannabinoid and NAD+ precursors). Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 in view of amendments. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112 (a)
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention
New matter Rejection
Claims 1, 5, and 10-14 are rejected 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 as amended recites “said composition comprising: one or more cannabinoids in a cannabinoid concentration level in the composition, wherein the cannabinoid concentration level is at least 2 μM; and one or more NAD+ precursors in a NAD+ precursor concentration level in the composition, wherein the NAD+ precursors concentration level is at least 300 μM.
However, the original disclosure does not support newly recited concentration ranges of the cannabinoid and NAD+ precursor in the composition. While the specification discloses the concentrations of CBD (0.67 μM, 2 μM, and 6 μM) and niacin (100 μM, 300μM, and 900 μM), those concentrations are their final concentrations in cell culture wells, not their concentration in the composition itself as claimed (see p5, [0054] and Table 1). Also, the concentration is limited to CBD and Niacin only, not for the other cannabinoid and NAD+ precursors encompassed by the claim. In addition, the claimed concentrations of “at least 2 μM” and “at least 300 μM” have no upper limit and thus, encompass any concentrations, which are equal to or greater than 2 μM” and “at least 300 μM, respectively. There is no support for such generic range as claimed. As such, it is considered as new matter.
New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 (a) to § 608.04(c).
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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, and 10-14 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0343776 (hereafter, KAPLAN; cited in IDS filed on 8/16/2022) as evidenced by US 20170267709 (hereafter, MIGAUD) in view of Burstein (Bioorganic & Medicinal Chemistry, 23:1377-1385. 2015) and Li et al. (The Journal of Nutritional Biochemistry, 26 (11): 1338-1347, November 2015).
KAPLAN teaches a nutraceutical composition comprising a therapeutically effective amount of Vitamin C, Vitamin B1, Vitamin B2, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B9, Vitamin B12, and zinc, wherein said therapeutically effective amount mitigates veisalgia by providing molecular support for basic metabolism, building blocks to replenish spent enzymes and coenzymes, support to liver detoxification processes, support to cellular energy production, anti-inflammatory and antioxidant activity, which further comprises a therapeutically effective amount of cannabidiol (CBD) (claims 1 and 11-12 and [0043]). KAPLAN further teaches the therapeutically effective amount of CBD further provides molecular support for metabolism, anti-inflammation and to scavenge and process toxins ([0043]).
KAPLAN specifically disclose that the composition comprises 0.9 mg to 30 mg of Vitamin B3 and 0.01 mg to 100 mg of CBD (claim 12, [0043]), and [0046]). KAPLAN further teaches that Vitamin B3 is no less than 10.8 mg ([0046]). Dietary vitamin B3 encompasses nicotinamide (“Nam” or “NM”), nicotinic acid (“NA”), and nicotinamide riboside (“NR”), which is a precursor to the coenzyme nicotinamide adenine dinucleotide (“NAD+”) as evidenced by MIGAUD ([0004]). Thus, the vitamin B3 comprises nicotinic acid.
Also, KAPLAN teaches that the nutraceutical composition may be administered by a cream, lotion, solution, ointment, patch, gel, strip, film, powder, chewable, tablet, fast absorbing tablet, quick dissolving tablet, capsule, caplet, gel cap, liquid, spray, droplet, auto-injector, atomizer, bong, cigarette, vape, vaporizer, volcano, suppository, or enema, depending on the desired delivery route ([0044]). These compositions are suitable for oral administration, topical administration, mucosal administration, pulmonary administration, subcutaneous administration, intravenous administration, intraperitoneal administration, suppository administration, or intramuscular administration.
KAPLAN does not specifically disclose the claimed minimum concentrations of cannabinoid and NAD+ precursor and their molar ratio recited in amended claim 1.
Burstein teaches effects of CBD on inflammation (title and abstract). Burstein discloses LPS-induced TNF-α production by RAW 264.7 mouse macrophage cells was completely inhibited by treatment with 8 μM CBD (p1381, 4.2. Cytokine). Burstein discloses CBD, studied at 1, 5 and 10 μM, decreased the production and release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and interferon-β, from LPS-activated BV-2 microglial cells (p1381, col 2, para 2).
Li et al. teach that nicotinic acid (NA) has shown to inhibit inflammatory response in cardiovascular disease and NA possesses anti-inflammatory and antioxidant properties independent of their lipid-lowering action (abstract and col 1, para 1). Li et al. discloses NA treatment (1 mM=1000 μM) significantly reduced the secretion of IL-1β in the cell culture supernatants, suggesting that the inhibitory effect of NA on the IL-1β production may be related with CD40 and NA protects against vascular inflammatory responses through SIRT1/CD40-dependent signaling pathway (p143, col 1, para 2-3, Fig. 5C, and abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the concentration of CBD and vitamin B3 (nicotinamide/nicotinic acid) and their molar ratio for obtaining best effects. Also, Burstein and Li et al. teach the molar concentrations of CBD (e.g., 8 μM) and NA (1000 μM) effective for inhibiting the production and release of proinflammatory cytokines such as IL-1β, which fall within the claimed ranges. Based on the effective concentrations disclosed in the prior art in combination, the skilled artisan would be able to determine suitable effective molar concentrations of both compounds and their molar ratio (e.g., 8:1000=1:125) depending on types and total weight of the composition for obtaining desired anti-inflammatory effects through routine or manipulative experimentation.
Absent some demonstration of unexpected results from the claimed concentration and molar ratio, the optimization of such parameters would have been obvious before the effective filing date of the claimed invention. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05 IIA.
Claims 1, 5 and 10-14 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016103254 (hereafter, SINAI; cited in IDS filed on 8/16/2022) in view of US 2004/0102358 (hereafter, SCIVOLETTO) and in further view of Burstein (Bioorganic & Medicinal Chemistry, 23:1377-1385. 2015) and Li et al. (The Journal of Nutritional Biochemistry, 26 (11): 1338-1347, November 2015).
SINAI teaches a pharmaceutical composition comprising a therapeutically effective amount of at least one cannabinoid selected from the group consisting of: cannabidiol (CBD) or a derivative thereof, tetrahydrocannabinol (THC) or a derivative thereof, and a combination thereof, useful for treatment or prevention of psoriasis (inflammatory condition) (abstract and claims 1-2). SINAI further teaches said composition additionally comprises at least one ingredient selected from the group consisting of cannabis oil, vitamin B3, keratolytic agent, anti- irritation agent, anti-oxidant, a terpene, a cannabis terpene, anti-skin redness agent and any combination thereof (claim 14).
SINAI specifically disclose a cream formulation containing cannabis oil and niacinamide (vitamin B3), wherein the cannabis oil comprises about 30% THC and about 30% CBD and thus the cream contains final concentration of about 3% THC and about 3% CBD. ([52] and [211], Table 1).
Also, SINAI teaches that said composition is administered in a route selected from the group consisting of: intranasal, transdermal, intravenous, oral, topical and any combination thereof (claim 7).
In addition, SINAI teaches that said composition is formulated in a form selected from the group consisting of cream, ointment, lotion, foam, film, transdermal patch and any combination thereof (claim 8).
SINAI does not specifically disclose nicotinic acid as recited in claim 11. Also, SINAI does not specifically disclose the claimed minimum concentrations of cannabinoid and NAD+ precursor and their molar ratio recited in amended claim 1.
However, it was known in the art that nicotinamide (niacinamide), nicotinic acid, and nicotinic esters are interchangeably used for treating inflammatory skin conditions such as psoriasis as evidenced by SCIVOLETTO (abstract, claim 1, and [0025]). Also, SCIVOLETTO teaches that nicotinamide, nicotinic acid, and nicotinic esters are present in a concentration of 0.01 to 90% or 0.01 to 20% by weight in a composition (claims 10 and 22).
Burstein teaches effects of CBD on inflammation (title and abstract). Burstein discloses LPS-induced TNF-α production by RAW 264.7 mouse macrophage cells was completely inhibited by treatment with 8 μM CBD (p1381, 4.2. Cytokine). Burstein discloses CBD, studied at 1, 5 and 10 μM, decreased the production and release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and interferon-β, from LPS-activated BV-2 microglial cells (p1381, col 2, para 2).
Li et al. teach that nicotinic acid (NA) has shown to inhibit inflammatory response in cardiovascular disease and NA possesses anti-inflammatory and antioxidant properties independent of their lipid-lowering action (abstract and col 1, para 1). Li et al. discloses NA treatment (1 mM=1000 μM) significantly reduced the secretion of IL-1β in the cell culture supernatants, suggesting that the inhibitory effect of NA on the IL-1β production may be related with CD40 and NA protects against vascular inflammatory responses through SIRT1/CD40-dependent signaling pathway (p143, col 1, para 2-3, Fig. 5C, and abstract).
As to claim 11, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use nicotinic acid in place of niacinamide in the treatment of inflammatory condition such as psoriasis as taught by SINAI because they both are vitamin B3, which can be interchangeably used for the same purpose as evidenced by SCIVOLETTO and Li et al. teach that NA possesses anti-inflammatory and antioxidant properties. The skilled artisan would have expected a success in substituting niacinamide with nicotinic acid because SCIVOLETTO teaches that both compounds were known to be suitable for treating the same disorder. The person of ordinary skill in the art would have found it obvious to make the substitution because the ordinarily skilled artisans would have predicted that nicotinic acid would provide similar effects with those of niacinamide based on their shared activity.
As to the claimed minimum concentrations of cannabinoid and NAD+ precursor and their molar ratio, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the concentration of CBD and vitamin B3 such as nicotinamide and nicotinic acid and their ratio for obtaining best effects. Also, Burstein and Li et al. teach the molar concentrations of CBD (e.g., 8 μM) and NA (1000 μM) effective for inhibiting the production and release of proinflammatory cytokines such as IL-1β, which fall within the claimed ranges. Based on the effective concentrations disclosed in the prior art in combination, the skilled artisan would be able to determine suitable effective molar concentrations of both compounds and their molar ratio (e.g., 8:1000=1:125) depending on types and total weight of the composition for obtaining desired anti-inflammatory effects through routine or manipulative experimentation.
Absent some demonstration of unexpected results from the claimed concentration and molar ratio, the optimization of such parameters would have been obvious before the effective filing date of the claimed invention. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05 IIA.
Response to Applicant’s arguments
Responses are limited to Applicants' arguments relevant to either reiterated or newly applied rejections.
As to alleged unexpected synergistic effects of the claimed combination, it is noted that it is applicant's burden to demonstrate unexpected results over the prior art. See MPEP 716.02, also 716.02 (a) - (g). Furthermore, the unexpected results should be demonstrated with evidence that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). Moreover, evidence as to any unexpected benefits must be "clear and convincing" In re Lohr, 137 USPQ 548 (CCPA 1963), and be of a scope reasonably commensurate with the scope of the subject matter claimed, In re Linder, 173 USPQ 356 (CCPA 1972).
First, the alleged unexpected result is not commensurate with the scope of the claimed invention. Applicant presented test data of alleged synergistic effect for only two concentrations (2 μM and 6 μM CBD and 300μM and 900 μM niacin) and one ratio (1:150) in cell culture mediums, not for the entire ranges as claimed. As stated above, the claimed concentrations of “at least 2 μM” and “at least 300 μM” have no upper limit and thus, encompass any concentrations which are equal to or greater than 2 μM” and “at least 300 μM, respectively. Also, those concentrations are their final concentrations in cell culture wells, not their concentration in the composition itself as claimed (see p5, [0054] and Table 1). Also, the test results are limited to the combination of CBD and niacin only, not for other combinations comprising other cannabinoids and NAD+ precursors encompassed by the claim. There is no adequate basis for concluding that similar results would be obtained over the entire range as claimed and for other combinations comprising other cannabinoids and NAD+ precursors. Thus, the evidence is insufficient to rebut the prima facie case of obviousness since a skilled artisan could not ascertain a trend in the exemplified data that would allow him to reasonably extend the probative value thereof to the entire scope of the subject matter claimed. In addition, it is noted that the test results disclosed in the specification are inconsistent and unclear to show the criticality of the claimed parameters. For example, the combination of CBD and niacin in high concentrations (6 μM CBD and 900 μM) actually showed lower inhibitory effects on IL-4 (pro-inflammatory cytokine) than 6 μM CBD alone (see Fig. 3). Clarification is required.
For the foregoing reasons, Applicant’s arguments have not been found to be persuasive.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BONG-SOOK BAEK whose telephone number is 571-270-5863. The examiner can normally be reached 9:00AM-6:00PM Monday-Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611