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 .
Claim Status
Claims 1, 3-6 and 20-26 are currently pending.
Applicant's election with traverse of Group I, claims 1, 3-6 and 20-21 in the reply filed on May 18, 2026 is acknowledged. The traversal is on the ground(s) that there is no search burden because a search for treating steroid dependent IBD/urticaria with CBD would yield tapering art because steroid dependence implicates prior steroid use. A search for art on Group I did identify art relevant to Group II. Therefore, the restriction requirement is withdrawn.
Claims 1, 3-6 and 20-26 are currently active and subject to examination.
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.
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.
Claim(s) 1, 3-6 and 20-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naftali et al. (CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2013;11:1276–1280) in view of Yeshurun & Sagiv (WO 2017/191630 A1).
The effective filing date of the claimed invention is May 16, 2022. The earlier filed applications do not disclose the treatment of steroid-dependent IBD or urticaria.
Claim 1 is directed towards a method of completely tapering off use of a steroid in a subject afflicted with steroid-dependent inflammatory bowel disease (IBD), or steroid dependent urticaria, comprising administering to said subject a steroid and a composition comprising cannabidiol (CBD), cannabidiol (CBD), (-)-7-hydroxy-CBD, (-)-CBD-7-oic acid, dimethylheptyl homologue of (-)-7-hydroxy-CBD, dimethylheptyl homologue of (-)-CBD-7-oic acid or any combination thereof, and reducing said dose of said steroid over time while continuing to administer said composition until said steroid is not administered, thereby completely tapering off use of a steroid in a subject afflicted with steroid-dependent inflammatory bowel disease (IBD), or steroid-dependent urticaria.
Naftali teaches a method completely tapering off use of a steroid in a subject afflicted with steroid-dependent inflammatory bowel disease (IBD) comprising administering to said subject a steroid and a composition comprising a cannabinoid and reducing said dose of said steroid over time while continuing to administer said composition until said steroid is not administered, thereby completely tapering off use of a steroid in a subject afflicted with steroid-dependent inflammatory bowel disease (IBD).
Naftali teaches a prospective placebo-controlled trial of cannabinoid administration for the treatment of patients with active Crohn’s disease, a form of inflammatory bowel disease (IBD):
In a retrospective observational study, we recently reported That cannabis had beneficial effects in Crohn’s disease.11 However, to date, no placebo-controlled trials have been published on the use of cannabis in inflammatory bowel disease (IBD). We conducted a double-blind, placebo-controlled study to investigate the effects of cannabis on patients with active Crohn’s disease…
By using the block method12 in a 1:1 ratio, patients were assigned randomly to receive either medical cannabis or placebo in the form of cigarettes. Both patients and investigators were blinded to the treatment group assignment. Each cigarette contained 0.5 g of dried cannabis flowers (flowers have a higher THC content than leaves), corresponding to 115mg THC. The active cannabis was made from dried flowers of genetically identical plants of Cannabis sativa Variety Indica Erez (courtesy of Tikun Olam, Ltd, Tel Aviv, Israel), known to contain 23% THC and less than 0.5% CBD.
Naftali, p. 1277, col. 1.
Naftali expressly identifies a subpopulation of steroid-dependent subjects, each of whom had relapsed upon attempting to discontinue steroids (id., p. 1278, col. 2), corresponding to the claimed patient population with steroid-dependent inflammatory bowel disease (IBD). Naftali further discloses that concomitant medications remained constant throughout the study except for steroids, which were tapered when possible (id., p. 1277, col. 2), thereby reducing said dose of steroid over time. Naftali further discloses that the three steroid-dependent subjects in the cannabis treatment group discontinued steroids during the study, such that at the conclusion of the study, no subject in the cannabis group required steroids (id.). Naftali characterizes the observed benefit as steroid-free:
Results
Complete remission (CDAI score, <150) was achieved by 5 of 11 subjects in the cannabis group (45%) and 1 of 10 in the placebo group (10%; P = .43). A clinical response (decrease in CDAI score of >100) was observed in 10 of 11 subjects in the cannabis group (90%; from 330 ± 105 to 152 ± 109) and 4 of 10 in the placebo group (40%; from 373 ± 94 to 306 ± 143; P = .028). Three patients in the cannabis group were weaned from steroid dependency. Subjects receiving cannabis reported improved appetite and sleep, with no significant side effects.
Conclusions
Although the primary end point of the study (induction of remission) was not achieved, a short course (8 weeks) of THC-rich cannabis produced significant clinical, steroid-free benefits to 10 of 11 patients with active Crohn's disease, compared with placebo, without side effects.
Id., abstract (emphasis added).
Naftali states that the strain employed was “specifically rich in THC, but other cannabinoids may be beneficial as well” (id., p. 1280, col. 1). Naftali further cites Borreli et al. for the protective effects of CBD in cannabidiol in a murine model of colitis and Jamontt et al. for the effects of THC and CBD on damage and inflammation in rat colitis (id., p. 1277, col. 1; references 9-10), directing the skilled artisan to cannabidiol (CBD) specifically as a candidate for treating intestinal inflammation associated with IBD. Naftali stated concerns regarding the psychotropic effects of THC-rich cannabis, which complicated blinding (id., p. 1280, col. 1).
While Naftali administered a cannabinoid preparation rich in Δ9-tetrahydrocannabinol (THC) rather than CBD, one of ordinary skill in the art would have a reasonable expectation of success to administer a composition comprising cannabidiol because CBD is well known in the art to have similar anti-inflammatory properties and steroid sparing effects without psychoactive properties.
For example, Yeshurun teaches administering a composition comprising CBD or a functional derivative thereof, together with a steroid for the purpose of reducing the dose of the steroid in a subject afflicted with an inflammatory or immune disease:
[017] The invention further provides, in some embodiments, a method for reducing the dose of a steroid in a subject afflicted with an autoimmune disease or liver inflammation, comprising administering to the subject: (1) a steroid and (2) a cannabidiol (CBD) or a functional derivative thereof, thereby reducing the dose of a steroid in a subject afflicted with an autoimmune disease or liver inflammation.
[031] In one embodiment, provided herein a method for reducing the amount of a steroid in the treatment of a subject afflicted with an autoimmune disease or an inflammation, comprising administering to the subject a therapeutically effective amount of a composition comprising a cannabidiol (CBD) or a functional derivative thereof and a therapeutically effective amount of a composition comprising a steroid.
[032] In one embodiment, provided herein a method for reducing the amount of a steroid in the treatment of a subject afflicted with an autoimmune disease or an inflammation, comprising administering to the subject a therapeutically effective amount of a composition comprising a cannabidiol (CBD) or a functional derivative thereof and a reduced amount of a composition comprising a steroid.
[037] In one embodiment, provided herein a method for reducing the weekly or daily dose of a steroid in a subject treated with a steroid, comprising administering to the subject a steroid and a cannabidiol (CBD) or a functional derivative thereof, thereby reducing the weekly or daily dose of a steroid in a subject treated with a steroid.
Yeshurun, Spec., ¶ [017], [031], [032] , [037].
Yeshurun identifies inflammatory bowel disease among the treatable autoimmune conditions (id., ¶ [040]) and further specifies Crohn’s disease and ulcerative colitis (UC) (id., ¶ [050]), two subtypes of IBD. Yeshurun teaches that “[i]n one embodiment, reduction is at least 70% reduction in the daily or weekly steroid dose” (id., [035]). Yeshurun demonstrates a stepwise reduction of prednisolone by 40%, 50%, and 65% over successive weeks of CBD co-administration (Examples 1, 4 and 5). Yeshurun teaches that CBD is a major non-psychoactive cannabinoid, with a remarkable lack of any cognitive or psychoactive actions (id., ¶ [067]).
Yeshurun teaches that functional derivatives of CBD including “but not limited to: (-)-7-hydroxy-CBD and (-)-CBD-7-oic acid and their dimethylheptyl (DMH) homologs, as well as of the corresponding compounds in the enantiomeric (+)-CBD series.” (id., ¶ [068]), corresponding to the species recited in claim 1.
Therefore, claim 1 was prima facie obvious at the time of filing.
Claim 3 is directed towards the method of claim 1, wherein said reducing said dose is reducing said dose every 3-7 days. Regarding claim 3, Naftali tapers corticosteroids over an eight-week treatment period, with evaluations at weeks 0, 2, 8 and 10 (Naftali, p. 1277, col. 2). While Naftali does not explicitly teach reducing the steroid dose every 3-7 days, one of ordinary skill in the art would have a reasonable expectation of success to reduce the steroid dose every 3-7 days because, Yeshurun teaches gradual reduction of the steroid dose at intervals encompassing the claimed 3-7 days, disclosing the reduction of at least 10% per week (id., ¶ [074]), and stepwise weekly reductions in Example 1. Yeshurun further teaches a reduction over a period of three days to six months (id., ¶ [0100]). “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)” (MPEP § 2144.05).
Therefore, claim 3 was prima facie obvious at the time of filing.
Claim 4 is directed towards the method of claim 1, wherein said steroid, said composition, or any combination thereof is administered systemically. Claim 5 is directed towards the method of claim 1, wherein said steroid, said combination, or any combination thereof is administered orally or topically. Naftali teaches that the composition is administered systemically via smoking/ inhalation, but suggests using oral cannabis because of the harmful effects of smoking on the lungs (Naftali, p. 1280, col. 1). One of ordinary skill in the art would have a reasonable expectation of success to administer CBD orally (systemically) because Yeshurun specifically teaches oral administration of CBD compositions (Yeshurun, Spec., ¶¶ [0109], [0114]) and demonstrates oral CBD administration in examples 1-6. Therefore, claims 4-5 were prima facie obvious at the time of filing.
Claim 6 is directed towards the method of claim 1, wherein the CBD is administered daily in doses of between 5 mg to 600 mg. Naftali teaches that patients were administered 0.5 g of cannabis flowers twice daily containing less than 0.5% of CBD (Naftali, p. 1277, col. 1), touching the upper bound of 0.5 mg per day. While Naftali does not explicitly teach to administer 5 mg to 600 mg per day of CBD, one of ordinary skill in the art would have a reasonable expectation of success to administer 5 mg to 600 mg per day because such doses are commonly known in the art. For example, Yeshurun teaches” a therapeutically effective amount of a composition comprising a CBD or a functional derivative thereof comprises 5 mg to 600 mg of a CBD or a functional derivative thereof” (Yeshurun, Spec., ¶ [083]). Therefore, claim 6 was prima facie obvious at the time of filing.
Claim 20 is directed towards the method of claim 1, wherein said steroid dependent IBD or steroid dependent urticaria is IBD or urticaria that is controlled, inhibited, treated or ameliorated by said steroid. Naftali teaches subjects whose IBD was controlled by steroid administration, disclosing steroid dependent subjects who relapsed upon attempting to discontinue steroids (Naftali, p. 1278, col. 2). Yeshurun likewise teaches subjects whose disease requires steroid treatment to maintain control (Yeshurun, Spec., ¶¶ [053-054]]. Therefore, claim 21 was prima facie obvious at the time of filing.
Claim 21 is directed towards the method of claim 6, wherein said CBD dose is 300 mg. While Naftali does not teach 300 mg of CBD, one of ordinary skill in the art would have a reasonable expectation of success to administer 300 mg of CBD because such doses are commonly known in the art. For example, Yeshurun teaches daily administration of about 300 mg CBD (Examples 3, 5 and 6, disclosing 300 mg oral CBD daily or 150 mg BID). Therefore, claim 21 was prima facie obvious at the time of filing.
Claim 22 is directed towards a method for treating steroid-dependent inflammatory bowel disease (IBD), or steroid-dependent Urticaria in a subject in need thereof, comprising administering to said subjectcannabidiol (CBD), (-)-7-hydroxy-CBD, (-)-CBD-7-oic acid, dimethylheptyl homologue of (-)-7-hydroxy-CBD, dimethylheptyl homologue of (-)-CBD-7-oic acid or any combination thereof without administering a steroid, thereby treating steroid-dependent IBD or steroid-dependent urticaria.
Naftali teaches a method of treating steroid-dependent inflammatory bowel disease in a subject in need thereof, comprising administering a cannabinoid to said subject without administering a steroid.
Naftali teaches a prospective placebo-controlled trial of cannabinoid administration for the treatment of patients with active Crohn’s disease, a form of inflammatory bowel disease (IBD) (Naftali, p. 1277, col. 1). Naftali expressly identifies a subpopulation of steroid-dependent subjects, each of whom had relapsed upon attempting to discontinue steroids (id., p. 1278, col. 2), corresponding to the claimed patient population with steroid-dependent inflammatory bowel disease (IBD). Naftali further discloses that concomitant medications remained constant throughout the study except for steroids, which were tapered when possible (id., p. 1277, col. 2). Naftali further discloses that the three steroid-dependent subjects in the cannabis treatment group discontinued steroids during the study, such that at the conclusion of the study, no subject in the cannabis group required steroids (id.). Naftali characterizes the observed benefit as steroid-free (Id., abstract).
Naftali states that the strain employed was “specifically rich in THC, but other cannabinoids may be beneficial as well” (id., p. 1280, col. 1). Naftali further cites Borreli et al. for the protective effects of CBD in cannabidiol in a murine model of colitis and Jamontt et al. for the effects of THC and CBD on damage and inflammation in rat colitis (id., p. 1277, col. 1; references 9-10), directing the skilled artisan to cannabidiol (CBD) specifically as a candidate for treating intestinal inflammation associated with IBD. Naftali stated concerns regarding the psychotropic effects of THC-rich cannabis, which complicated blinding (id., p. 1280, col. 1).
While Naftali administered a cannabinoid preparation rich in Δ9-tetrahydrocannabinol (THC) rather than CBD, one of ordinary skill in the art would have a reasonable expectation of success to administer a composition comprising CBD because CBD is well known in the art to have similar anti-inflammatory properties and steroid sparing effects without psychoactive properties.
For example, Yeshurun teaches a method of treating an immunological disease or disorder or inflammation comprising administering a composition comprising CBD to a subject in need thereof:
In one embodiment, provided herein a method for treating a subject afflicted with an immunological disease or disorder (such as an autoimmune disease) or inflammation, comprising administering to the subject a therapeutically effective amount of a composition comprising a cannabidiol (CBD) or a functional derivative thereof, thereby treating a subject afflicted with an autoimmune disease or liver inflammation.
Yeshurun, Spec., ¶ [019].
Yeshurun identifies inflammatory bowel disease among the treatable autoimmune conditions (id., ¶ [040]) and further identifies Crohn’s disease and ulcerative colitis (UC) (id., ¶ [050]), two subtypes of IBD. Yeshurun teaches that CBD is a major non-psychoactive cannabinoid, with a remarkable lack of any cognitive or psychoactive actions (id., ¶ [067]).
Yeshurun teaches that functional derivatives of CBD including “but not limited to: (-)-7-hydroxy-CBD and (-)-CBD-7-oic acid and their dimethylheptyl (DMH) homologs, as well as of the corresponding compounds in the enantiomeric (+)-CBD series.” (id., ¶ [068]), corresponding to the species recited in claim 22.
Therefore, claim 22 was prima facie obvious at the time of filing.
Regarding claim 23, Yeshurun teaches daily administration of about 300 mg CBD (Examples 3, 5 and 6, each disclosing 300 mg oral CBD daily or 150 mg BID). See the rejection of claims 6 and 20, incorporated herein by reference. Therefore, claim 23 was prima facie obvious at the time of filing.
Regarding claim 24, Yeshurun teaches that a therapeutically effective daily dose of CBD comprises 5 mg to 600 mg (Yeshurun, Spec., ¶ [083]). See the rejection of claims 6 and 20, incorporated herein by reference. Therefore, claim 24 was prima facie obvious at the time of filing.
Regarding claim 25, Naftali teaches administration of the cannabinoid as the sole agent for the disease in the steroid-dependent subjects who discontinued steroids, and Yeshurun teaches the CBD and derivative species, as discussed above in the rejections of claim 1 and claim 22. Therefore, claim 25 was prima facie obvious at the time of filing.
Regarding claim 26, see the discussions of claims 23 and 25 above, incorporated herein by reference. Therefore, claim 26 was prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Conclusion
No claim is found to be allowable.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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