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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Dec 3 2025 has been entered.
Status of Claims
Claims 36-38, 41-44 and 47-59 are pending. As detailed previously, applicant’s species election has been acknowledged and noted to be:
First species: CBG, total dose up to 150 mg; CBD, total dose up to 40 mg; and
THC, total dose up to 2mg. Microcrystalline cellulose as the excipient, comprising from 1 % to 60% by weight of the immediate release (IR) formulation; and
Methacrylic acid-ethyl acrylate copolymer as the polymer of the delayed release
(DR) components of the pH sensitive delayed-release (DR)formulation, comprising from 4% to 25% by weight of the DR formulation.
Second species: Inflammatory Gastrointestinal (GI) Disease/disorder: Irritable Bowel Disease. Upon search and examination of the elected species, the inflammatory GI disorder encompasses species such as Crohn’s disease and ulcerative colitis (UC).
Claim Interpretation
With regard to claim 36, the limitation detailed below is broadly and reasonably interpreted to be an intended use limitation of the claimed composition.
the oral pulse-release dosage form provides a release profile such that when the pulse-release dosage form is placed in 3-stage dissolution media for a period of up to 2 hours, comprising an aqueous solution of pH 1-5 at 37°C ± 0.5°C, followed by an aqueous solution of pH 5.5 at 37°C ± 0.5°C, followed by an aqueous solution of pH 6.8 at 37°C ± 0.5°C, the pulse-release dosage form provides release of the second portion of the CBG from the second pulse-release component (C2) beginning at least about 1 hour after release of the first portion of the CBG from the first pulse-release component (C1) begins.
This release profile is a mere intended use of the claimed composition comprising component C1 and component C2, as it merely describes the function of the composition when placed in a particular 3-stage dissolution media. It provides no structural elements to define the claimed composition comprising the administration of the first pulse-release component (C1) and second pulse component (C2). Claim 36, which broadly recite the structural elements of C1 immediate release and C2 delayed release components are reasonably presumed to possess the intended use release profile as recited in claim 36.
Response to Arguments
Applicant's arguments filed Dec 3 2025 have been fully considered but they are not persuasive. See below Response to Attorney Arguments regarding the 103 rejection of claims 36-38, 41-44, and 47-59, WO 164 in view of Irving and Borelli, evidenced by US Pub 108.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 36-38, 41-44 and 47-59 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2011/063164 (WO 164), in view of Irving et al. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis, Inflamm Bowel Dis Volume 24, Number 4, April 2018 and Borrelli et al. Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease, Biochem Pharmacol. 2013; 85 (9):1306-1316, as evidenced by US Pub 2005/0266108 (US Pub 108). US 11654130, WO 164, Irving and Borrelli are cited on the IDS. US Pub 108 is cited on the PTO-892 form. WO 164, Irving and Borrelli are cited on the submitted IDS. US Pub 2005/0266108 is cited on the PTO-892 form.
Claim 36 recites a method treating an inflammatory GI1 disorder in a human subject comprising: oral administration of a therapeutically effective amount of oral pulse release dosage form, said form comprising:
a first pulse-release component (C1) comprising a first portion (P1) of one or more cannabinoid active pharmaceutical ingredients (API) (API-P1);
a second pulse-release component (C2) comprising a second portion (P2) of the one or more cannabinoid API (API-P2)
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Regarding claim 36 and the limitation of said oral dosed composition with a first and second pulsed component, WO 164 teaches a medicament/formulation comprising a cannabinoid partitioned immediate release and delayed release compartment. See claim 36. WO 164 discloses tablet formulations comprising cannabinoid pellets (dronabinol or other THC). See Table 7 (pellet in a capsule), see paragraph 248; and a bilayer/matrix tablet see Table 8, paragraph 255.
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See also Table 9 (paragraph 263) among other examples therein disclosing instant/delayed release formulations of WO 164. With regard to the cannabinoids present in both the first and second pulse release components (C1 and C2), WO 164 teaches that its compositions comprise cannabinoids that are any member of a group of substances that are structurally related to THC. See paragraph 49. The cannabinoid can be a naturally occurring compound, such as those present in Cannabis plants. See paragraph 49. See also paragraph 51 noting natural cannabinoids, purified cannabinoids and synthesized cannabinoids as per US Pub 2005/0266108. WO 164 teaches the present medicaments provide oral dosing of about 0.1 to about 75 mg of a cannabinoid, that overlaps the limitation of up to 150 mg claimed. See paragraph 18 and MPEP 2144.05(I).
WO 164 teaches cannabinoids such as THC and the particular variant Delta 9 THC aka dronabinol. See paragraphs 51 and 54.
WO 164 suggests the claimed subject in need treated for an inflammatory GI disorder where it teaches ulcerative colitis and Crohn’s disease. See paragraph 17.
While WO 164 teaches an oral dosed pulsed formulation, comprising cannabinoid with a first immediate release pulse formulation and a second pulse delayed release formulation in amounts that overlap that those claimed such as THC/dronabinol, it does not necessarily recite limitations regarding identity and amounts of the claimed cannabinoid active ingredients, such as those elected, in particular 150 mg of CBG. Elected species: Cannabigerol (CBG), total dose up to 150 mg; Cannabidiol (CBD), total dose up to 40 mg; and THC, total dose up to 2mg.
However, a person having ordinary skill in the art (PHOSITA) would look towards the use of CBG, CBD and THC for the treatment of an inflammatory GI disorder with a reasonable expectation of success as these are known in the art to treat inflammatory GI disorders.
Initially, with regard to total CBG total dose of up to 150 mg, WO 164 teaches cannabinoid dosages of up 0.1 to 75 mg, which falls within the claimed range. MPEP 2144.05(I).
WO 164 provides a teaching, suggestion and motivation to look towards not only exemplified THC, but other cannabinoids such as CBG, and CBD where it explicitly teaches to a PHOSITA,
The compositions of the present invention provide one or more cannabinoids in a medicament that can deliver to a subject a desired target PK profile, where the PK profile achieves a therapeutic level of a cannabinoid during a therapeutic window. Cannabinoids of the present invention are any member of a group of substances that are structurally related to tetrahydrocannabinol and that bind to a cannabinoid receptor such as CB1 or CB2 or both (THC) . The cannabinoid can be a naturally occurring compound (e.g. present in Cannabis), a compound metabolized by a plant or animal, or a synthetic derivative. See paragraph 49.
The cannabinoids of the present invention are further meant to encompass natural cannabinoids, natural cannabinoids that have been purified or modified, and synthetically derived cannabinoids, for example, United States Patent Application Publication 2005/0266108, hereby incorporated by reference in its entirety, describes a method of purifying cannabinoids obtained from plant material. See paragraph 51.
WO 164 references and incorporates the teachings of US Pub 2005/0266108 (US Pub 108), which is incorporated by reference, where it is noted US Pub 108 teaches by definition, the class of cannabinoid compounds envisioned by WO 164 to be incorporated into its oral dosed pulsed formulation includes THC (delta 9 tetrahydro cannabinol), cannabidiol (CBD) and cannabigerol (CBG). See paragraphs 4-5.
Therefore, WO 164 teaches the compatibility of its oral dosed pulsed formulation with the genus of cannabinoid compounds, including CBD and CBG (claimed), as well as THC, exemplified by WO 164 and claimed by Applicant.
With regard to choice of CBG, CBD and THC as cannabinoids Irving teaches
a CBD (cannabidiol) rich extract contained not only CBD but also smaller amounts of other compounds such as cannabigerol (CBG) and THC. See page 715 column 1. Irving teaches that the CBD rich extract (comprising CBD, CBG and THC) when administered to inflammatory bowel disease patients, suggested its data that CBD rich botanical extract (comprising CBD, CBG and THC) may be beneficial for symptomatic treatment of ulcerative colitis (UC). See abstract. Irving teaches there is evidence that the combination of CBD and THC may offer additive effects in models of inflammatory bowel disease (IBD). See page 715, column 1. Irving teaches that a study by Jamontt 2010 that this combination not only reduced inflammation but also lowered the occurrence of functional disturbances, interpreted to be symptoms of IBD. Id.
Borrelli teaches the beneficial effect of the cannabinoid CBG in an experimental model of IBD, a murine model of colitis induced in mice models. See abstract. “CBG could be considered for clinical experimentation in IBD patients.” See abstract.
A person having ordinary skill in the art (PHOSITA) following the teachings of WO 164 (as evidenced by US Pub 108) would have found it prima facie obvious to formulate the claimed pulse oral composition for use in treating IBS, Crohn’s disease or UC in view of Irving and Borelli, as these are taught by the combination of the cited prior art.
More specifically, the rationale to support a finding of obviousness includes the prior art elements of WO 164 noting oral pulsed dosage forms comprising a first immediate release formulation of a cannabinoid (dronabinol/THC), a second delayed release formulation of (dronabinol/THC) suggested for use in treating IBS, Crohn’s disease or UC, combined with known methods (CBD, CBG and/or THC treating inflammatory bowel diseases) to predictably arrive at the claimed invention.
With regard to the oral pulse-release dosage form release profile in a 3-stage dissolution media for 3 hours, as discussed above, such release profile is an intended use of the claimed composition comprising component C1 and component C2. As such it is treated to have no patentable weight as it is not a structural limitation per se to define the claimed composition comprising components C1 and C2. It does not provide physical, structural limitations to define the claimed composition, but rather describes a release profile the claimed composition possesses.
Regarding claims 37, 41 and 44, and upper gastrointestinal (GI) inflammation, lower GI tract inflammation, or both, official notice is given that UC, Crohn' s disease and IBS involve both upper and lower GI tract. The GI tract consists only of an upper and lower tract and UC, Crohn' s Disease and IBS are known to affect the GI tract. As discussed above, the combination of WO 164, Irving and Borrelli teach IBS, Crohn's disease and UC, where the symptoms of claim 44 (pain, bloating, diarrhea) are noted to be associated with IBS, Crohn' s disease or UC. It would be routine for one of ordinary skill in the art to optimize the treatment of the upper and/or lower GI tract for the symptoms claimed.
Regarding claims 38, dosing the patient 1-4 times a day, and claims 42-43, where treatment disorder and/or symptoms occurs within 6, 12, 24 or greater than 24 hours post-dose, or 1-24 hours, or greater than 24 hours, WO 164 teaches its compositions are suitable for treating conditions by therapeutic levels for more than about 5 hours, i.e. about 6-8 hours or for as long as about 8 to about 12 hours. See paragraph 16.
Regarding claim 47 and the claimed second time peak release rate (PPR2), as WO 164, Irving and Borrelli disclose the claimed method and the claimed subject in need. Therefore, such release rate claimed is necessarily present in the cited prior art.
Regarding claim 48 and the limitation of where the cannabinoid of the first pulse component is 10-50% of total and cannabinoid of second pulse is 50-90% of total dose, WO 164 discloses various tablet formulations comprising cannabinoid pellets (dronabinol or other THC) see Table 7 (pellet in a capsule), see paragraph 248; and a bilayer/matrix tablet see Table 8, paragraph 255. See Tables 7 and 8 where 2.5 mg dronabinol is in first immediate release component (25% w/w of total 10 mg) , 7.5 mg is in second delayed release (75% w/w of total 10 mg), thus teaching the limitations of claim 48.
Regarding claims 49 and 50 and the limitations of the excipients therein, WO 164 discloses Tables 7 and 8 with various excipients including microcrystalline cellulose (Avicel PH 101).
Regarding claim 51, it is noted that WO 164 teaches that with Table 8, microcrystalline cellulose comprises 39.5 mg (out of 100 mg) of the immediate release component, for a percentage of 39.5% w/w, within the claimed range of 1-60% w/w.
Regarding claims 52-55 and the limitations of a delayed cannabinoid API core and pharmaceutically acceptable excipients; with polymers (such as methacrylic acid copolymer, Eudragit) of the delayed release components layer or integrated, pH sensitive or not pH sensitive, WO 164 discloses its formulations are selected from the various formulations with delayed release components, such as bilayer/matrix type, monolithic/matrix-type, monolithic/coated -type, enteric coating-type, 2 pulse type, 3 pulse type, solid adsorbate type, pellet-type, and continuous release-type, see claim 26. These formulations are either coated or non-coated and either pH or non-pH sensitive. Further, with regard to polymer coated/integrated delayed release components, WO 164 discloses Table 9 paragraph 263, with both an instant release and delayed release component, where methacrylic acid co polymer type C (Eudragit) is used to coat the delayed release pellet component.
Regarding claim 56 and the limitation polymer being 4 to 25% weight of the delayed release portion, WO 164 discloses 13.2 mg of Eudragit out of the subtotal of 172.5 mg, which is 7.65%, see above Table 9.
Regarding claims 57-59 and the limitation of pellets and pellets contained in a capsule, WO 164 Table 7 discloses pellets enclosed in a capsule, see above.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response states Irving does not teach using CGB for treatment of inflammatory bowel disease but instead focuses on CBD and THC.
The Attorney response states the Action has not provided any rationale whatsoever to rebut Applicant's argument that, in view of the disclosure of WO' 164 and Irving, persons of ordinary skill in the art would not have been motivated to substitute the THC in the immediate release and delayed release formulation of WO' 164 for CBG in view of Irving, cite to MPEP 707.07(f).
In response, a PHOSITA following the teachings of WO 164 (as evidenced by US Pub 108) would have found it prima facie obvious to formulate the claimed pulse oral composition for use in treating IBS, Crohn’s disease or UC in view of Irving and Borelli, as these are taught by the combination of the cited prior art.
More specifically, the rationale to support a finding of obviousness includes the prior art elements of WO 164 noting oral pulsed dosage forms comprising a first immediate release formulation of a cannabinoid (dronabinol/THC), a second delayed release formulation of (dronabinol/THC) suggested for use in treating IBS, Crohn’s disease or UC, combined with known methods (CBD, CBG and/or THC treating inflammatory bowel diseases) to predictably arrive at the claimed invention. As detailed above, WO 164 is intended to include the class of cannabinoid compounds, including not only THC but also including CBD and CBG, as defined and evidenced by US Pub 108, incorporated by reference per WO 164. See paragraphs 49 and 51 defining cannabinoids as a class, incorporating by reference, the teachings of US Pub 108, where the combination of the two, suggest and motivate the use of the claimed CBD, CBG and THC for the oral pulsed dosed formulations of WO 164.
Therefore, WO 164 teaches the compatibility of its oral dosed pulsed formulation with the genus of cannabinoid compounds, including CBD and CBG (claimed), as well as THC, exemplified by WO 164.
The Attorney response argues that its arguments regarding Borelli have not been addressed for the failure of Borelli to remedy the deficiency of WO 164. The Attorney response references/states preclinical animal data limits the applicability of finding to humans. The Attorney response Borelli is confined to preclinical induced model; lacks human clinical data; does not account for species-species difference, i.e. human appropriate dosing, safety and complexity of human IBD and intraperitoneal administration of a CBG in a mouse model.
In response, that Borelli cannot be relied upon as a reference for use in a human for clinical treatment of IBD, at the outset it is pointed out that Borelli “investigated the effect of cannabigerol (CBG), a non-psychotropic Cannabis-derived cannabinoid, in a murine model of colitis,” i.e. colitis induced in mice by intracolonic administration of DNBS. See abstract. It is clear at the outset that Borelli intends for its preclinical research is intended to be used for furthering the art with regard to clinical use in humans.
While Borelli does not teach a human clinical trial demonstrating CBG for the treatment of human IBD, it is well understood by a PHOSITA that the DNBS-induced colitis [rodent model] allows a PHOSITA to study the pathogenesis of IBD associated environmental triggers such as stress and diet, the effects of potential therapies, and the mechanisms underlying intestinal inflammation and mucosal injury. See Morampudi et al.2 abstract. While the Attorney response argues the teaching away of Borelli precludes the prima facie case because of the study occurring in a mouse model, a PHOSITA would have reasonable expectation of success to rely upon the teachings of Borelli’s preclinical experiments to be applicable to the invention regarding use in a human.
Further, while Borelli is acknowledged to take place in a clinical mouse DNBS induced model administered CBG intraperitoneally, motivation to look towards using CBG to treat IBD in human subject is provided by the combined cited art., such as the oral dosage form of WO 164. WO 164 is intended to include the class of cannabinoid compounds, including not only THC but also including CBD and CBG, as defined and evidenced by US Pub 108, incorporated by reference per WO 164. See paragraphs 49 and 51 defining cannabinoids as a class, incorporating by reference, the teachings of US Pub 108, where the combination of the two, suggest and motivate the use of the claimed CBD, CBG and THC for the oral pulsed dosed formulations of WO 164.
Therefore, WO 164 teaches the compatibility of its oral dosed pulsed formulation with the genus of cannabinoid compounds, including CBD and CBG (claimed), as well as THC, exemplified by WO 164 and claimed by Applicant.
The Attorney response argues that there is no disclosure, teaching, or suggestion in WO' 164, Irving, or Borelli, alone or in combination, of at least the feature of the oral pulse-release dosage form that provides a release profile claimed when placed in a 3-stage dissolution media for a period of up to 2 hours.
In response, it is noted that such release profile is an intended use of the claimed composition comprising component C1 and component C2. As such it is treated to have no patentable weight as it is not a structural limitation per se to define the claimed composition comprising components C1 and C2. It does not provide physical, structural limitations to define the claimed composition, but rather describes an intended use of the claimed composition.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
RESPONSE TO ATTORNEY ARGUMENTS:
Applicant rebuts the double patenting rejection over conflict patent US 11654130 in view of WO 164, Irving and Borelli for the reasons discussed with the 103. In response, these arguments are addressed above and incorporated herein for ODP rejection.
Applicant stated this rejection will be addressed once it becomes the only rejection remaining. This is non-responsive and the double patenting rejection below has been issued.
Claims 36-38, 41-44 and 47-59 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 U.S. Patent No. 11654130 B2 (cited on PTO 892) in view of WO 2011/ 063164 (WO 164), Irving et al. Inflamm Bowel Dis Volume 24, Number 4, April 2018 and Borrelli et al. Biochem Pharmacol. 2013; 85 (9):1306-1316, as evidenced by US Pub 2005/0266108 (US Pub 108). US 11654130, WO 164, Irving and Borrelli are cited on the IDS. US Pub 108 is cited on the PTO-892 form.
The subject matter of claim 36 has been discussed above and its contents are discussed below.
Regarding claim 36, reference patent claims 1 and 9 are directed to an oral pulse dosage form comprising a total daily dose of a first cannabinoid active pharmaceutical ingredient (API1) and a total daily dose of a second cannabinoid API (API2), wherein the oral pulse-release dosage form comprises: a first pulse-release component (C1) comprising a first portion (P1) of the first cannabinoid API (API1P1) and a first portion (P1) of the second cannabinoid API (API 2P1); and at least a second pulse-release component (C2) comprising a second portion (P2) of the first cannabinoid API (API1P2) and a second portion (P2) of the second cannabinoid API (API2P2); wherein the total daily dose of each of the API1 and the API2 is divided between the first portion (P1) in the first pulse-release component (C1) and at least the second portion (P2) in the at least second pulse-release component (C2). While teaching the claimed oral dosage form as detailed above, the reference patent does not necessarily teach a total amount of CBG of up to 150 mg.
Further, although US 11654130 B2 discloses the claimed composition as well as various cannabinoids including cannabigerol, it does not necessarily recite the treatment of GI disorders such as inflammatory bowel disease/disorder as claimed in claim 36.Nor does it specify the elected species of CBD, CBG and THC, or a total CBG dose of up 150 mg.
However, one of skill in the art would look towards the use of cannabinoids (elected species CBG, CBD and THC) for the treatment of an inflammatory GI disorder with a reasonable expectation of success as these are known in the art, as well as a total CBG total dosage of 150 mg.
Regarding claim 36 and limitation of total amount of cannabinoid of up to 150 mg CBG, WO 164 provides a teaching of a controlled release cannabinoid formulation, where the present medicaments provide oral dosing of about 0.1 to about 75 mg of a cannabinoid, that overlaps the limitation claimed. See paragraph 18.
While WO 164 teaches cannabinoid dosages of up 0.1 to 75 mg, which falls within the claimed range, it does not explicitly point to CBG or the other elected cannabinoids species, CBD and THC. With regard to choice of CBD, THC and CBG, the choice is taught as follows.
WO 164 provides a teaching, suggestion and motivation to look towards not only exemplified THC, but other cannabinoids such as CBG, and CBD where it explicitly teaches to a PHOSITA,
The compositions of the present invention provide one or more cannabinoids in a medicament that can deliver to a subject a desired target PK profile, where the PK profile achieves a therapeutic level of a cannabinoid during a therapeutic window. Cannabinoids of the present invention are any member of a group of substances that are structurally related to tetrahydrocannabinol and that bind to a cannabinoid receptor such as CB1 or CB2 or both (THC) . The cannabinoid can be a naturally occurring compound (e.g. present in Cannabis), a compound metabolized by a plant or animal, or a synthetic derivative. See paragraph 49.
The cannabinoids of the present invention are further meant to encompass natural cannabinoids, natural cannabinoids that have been purified or modified, and synthetically derived cannabinoids, for example, United States Patent Application Publication 2005/0266108, hereby incorporated by reference in its entirety, describes a method of purifying cannabinoids obtained from plant material. See paragraph 51.
WO 164 incorporates the teachings of US Pub 2005/0266108 (US Pub 108), where US Pub 108 teaches by definition, the class of cannabinoid compounds envisioned by WO 164 to be incorporated into its oral dosed pulsed formulation includes THC (delta 9 tetrahydro cannabinol), cannabidiol (CBD) and cannabigerol (CBG). See paragraphs 4-5.
Therefore, WO 164 teaches the compatibility of its oral dosed pulsed formulation with the genus of cannabinoid compounds, including CBD and CBG (claimed), as well as THC, exemplified by WO 164 and claimed by Applicant.
Per Irving, a CBD (cannabidiol) rich extract contained not only CBD but also smaller amounts of other compounds such as cannabigerol (CBG) and THC. See page 715 column 1. Irving teaches the CBD rich extract when administered to patients, may be beneficial for symptomatic treatment of ulcerative colitis (UC). See abstract. Irving teaches there is evidence the combination of CBD and THC may offer additive effects in models of inflammatory bowel disease (IBD). See page 715, column 1. Irving teaches that a study by Jamontt 2010 discloses this combination not only reduced inflammation but also lowered the occurrence of functional disturbances, reasonably interpreted to be symptoms of IBD. Id.
Further, Borrelli teaches the beneficial effect of the cannabinoid CBG in an experimental model of IBD, a murine model of colitis induced in mice models. See abstract. “CBG could be considered for clinical experimentation in IBD patients.” See abstract.
A PHOSITA following the teachings of the reference patent would have found it prima facie obvious to formulate the claimed pulse oral composition for use in treating IBS, Crohn’s disease or UC in view of WO 164, Irving and Borelli, as these are taught by the combination of the cited prior art
The rationale to support a finding of obviousness are the prior art elements of the reference patent, noting oral pulsed dosage forms as claimed combined with the teachings of Irving and Borrelli (CBD, CBG and THC useful for treating IBS, UC and/or Crohn’s disease) to predictably arrive at the claimed invention.
With regard to the oral pulse-release dosage form release profile in a 3-stage dissolution media for 3 hours, as discussed above, such release profile is an intended use of the claimed composition comprising component C1 and component C2. As such it is treated to have no patentable weight as it is not a structural limitation per se to define the claimed composition comprising components C1 and C2. It does not provide physical, structural limitations to define the claimed composition, but rather describes a release profile the claimed composition possesses.
Regarding claims 37, 41 and 44, and inflammation of the upper, lower GI tract, or both, official notice is given that UC, Crohn’s disease and IBS involve both upper and lower GI tract. The GI tract consists only of an upper and lower tract and UC, Crohn’s Disease and IBS are known to affect the GI tract. As discussed above, the combination of WO 164, Irving and Borrelli teach IBS, Crohn’s disease and UC, where the symptoms of claim 44 (pain, bloating, diarrhea) are noted to be associated with IBS, Crohn’s disease or UC. It would be routine for one of ordinary skill in the art to optimize the treatment of the upper and/or lower GI tract for the symptoms claimed.
Regarding claim 38 and dosing the patient 1-4 times a day, and claims 42-43, where treatment disorder and/or symptoms occurs within 6, 12, 24 or greater than 24 hours post-dose, or 1-24 hours, or greater than 24 hours, the reference patent discloses the pulse-release dosage form provides release of the API1P2 and the API2P2 beginning from 2 to 6 hours after release of the API1P1 and the API2P1 begins. See claim 1.
As required by claim 47 and the claimed second time peak release rate (PPR2), as the reference patent, Irving and Borrelli discloses disclose the claimed method and the claimed subject in need, such release rate claimed is necessarily present in the cited prior art.
Regarding claim 48 and the limitation of where the cannabinoid of the first pulse component is 10-50% of total and cannabinoid of second pulse is 50-90% of total dose, the reference patent teaches for each API, the first portion (P1) is independently selected from 25% to 75% of the total daily dose, and for each API the second portion (P2) is independently selected from 25% to 75% of the total daily dose. See claim 1.
As required by claims 49 and 50 and the limitations of the excipients therein, the reference patent discloses microcrystalline cellulose as the excipient for the first pulse release component C1. See clam 16.
Regarding claim 51, the reference patent teaches the binders comprise from 1 to 60% (w/w). See claim 7.
As required by claims 52-55 and the limitations of a delayed cannabinoid API core and pharmaceutically acceptable excipients; with polymers (such as methacrylic acid copolymer, Eudragit) of the delayed release components layer or integrated, pH sensitive or not pH sensitive, WO 164 discloses its formulations are selected from the various formulations with delayed release components, such as bilayer/matrix type, monolithic/matrix-type, monolithic/coated -type, enteric coating-type, 2 pulse type, 3 pulse type, solid adsorbate type, pellet-type, and continuous release-type, see claim 26. These formulations are either coated or non-coated and either pH or non-pH sensitive. Further, with regard to polymer coated/integrated delayed release components, WO 164 discloses Table 9 paragraph 263, with both an instant release and delayed release component, where methacrylic acid co polymer type C (Eudragit) is used to coat the delayed release pellet component.
Regarding claim 56 and the limitation polymer being 4 to 25% weight of the delayed release portion, WO 164 discloses 13.2 mg of Eudragit out of the subtotal of 172.5 mg, which is 7.65%, see above Table 9.
As required by claims 57-59 and the limitation of pellets and pellets contained in a capsule, WO 164 Table 7 and Table 9 disclose pellets enclosed in a capsule, see above.
Claims 36-38, 41-44 and 47-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-15, and 17-18 of copending Application No. 18455378 in view of WO 2011/ 063164, Irving et al., Inflamm Bowel Dis Volume 24, Number 4, April 2018 and Borrelli et al. Biochem Pharmacol. 2013; 85 (9):1306-1316, as evidenced by US Pub 2005/0266108 (US Pub 108). US 11654130, WO 164, Irving and Borrelli are cited on the IDS. US Pub 108 is cited on the PTO-892 form.
The subject matter of claim 36 has been discussed above and its contents are discussed below.
Regarding claim 36 reference application claim 1, among others discloses an oral pulse dosage form comprising a total daily dose of a first cannabinoid active pharmaceutical ingredient (API1) and a total daily dose of a second cannabinoid API (API2), wherein the oral pulse-release dosage form comprises: a first pulse-release component (C1) comprising a first portion (P1) of the first cannabinoid API (API1P1) and a first portion (P1) of the second cannabinoid API (API 2P1); and at least a second pulse-release component (C2) comprising a second portion (P2) of the first cannabinoid API (API1P2) and a second portion (P2) of the second cannabinoid API (API2P2); wherein the total daily dose of each of the API1 and the API2 is divided between the first portion (P1) in the first pulse-release component (C1) and at least the second portion (P2) in the at least second pulse-release component (C2),
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While teaching the claimed oral dosage form as detailed above, the reference patent does not necessarily teach a total amount of CBG of up to 150 mg.
Further, although the reference application discloses the claimed composition as well as various cannabinoids including cannabigerol, it does not necessarily recite the treatment of GI disorders such as inflammatory bowel disease/disorder as claimed in claim 36.Nor does it specify the elected species of CBD, CBG and THC, or a total CBG dose of up 150 mg.
However, one of skill in the art would look towards the use of cannabinoids (elected species CBG, CBD and THC) for the treatment of an inflammatory GI disorder with a reasonable expectation of success as these are known in the art, as well as a total CBG total dosage of 150 mg.
While WO 164 teaches cannabinoid dosages of up 0.1 to 75 mg, which falls within the claimed range, it does not explicitly point to CBG or the other elected cannabinoids species, CBD and THC. With regard to choice of CBD, THC and CBG, the choice is taught as follows.
WO 164 provides a teaching, suggestion and motivation to look towards not only exemplified THC, but other cannabinoids such as CBG, and CBD where it explicitly teaches to a PHOSITA,
The compositions of the present invention provide one or more cannabinoids in a medicament that can deliver to a subject a desired target PK profile, where the PK profile achieves a therapeutic level of a cannabinoid during a therapeutic window. Cannabinoids of the present invention are any member of a group of substances that are structurally related to tetrahydrocannabinol and that bind to a cannabinoid receptor such as CB1 or CB2 or both (THC) . The cannabinoid can be a naturally occurring compound (e.g. present in Cannabis), a compound metabolized by a plant or animal, or a synthetic derivative. See paragraph 49.
The cannabinoids of the present invention are further meant to encompass natural cannabinoids, natural cannabinoids that have been purified or modified, and synthetically derived cannabinoids, for example, United States Patent Application Publication 2005/0266108, hereby incorporated by reference in its entirety, describes a method of purifying cannabinoids obtained from plant material. See paragraph 51.
WO 164 incorporates the teachings of US Pub 2005/0266108 (US Pub 108), where US Pub 108 teaches by definition, the class of cannabinoid compounds envisioned by WO 164 to be incorporated into its oral dosed pulsed formulation includes THC (delta 9 tetrahydro cannabinol), cannabidiol (CBD) and cannabigerol (CBG). See paragraphs 4-5.
Therefore, WO 164 teaches the compatibility of its oral dosed pulsed formulation with the genus of cannabinoid compounds, including CBD and CBG (claimed), as well as THC, exemplified by WO 164 and claimed by Applicant.
Per Irving, a CBD (cannabidiol) rich extract contained not only CBD but also smaller amounts of other compounds such as cannabigerol (CBG) and THC. See page 715 column 1. Irving teaches the CBD rich extract when administered to patients, may be beneficial for symptomatic treatment of ulcerative colitis (UC). See abstract. Irving teaches there is evidence the combination of CBD and THC may offer additive effects in models of inflammatory bowel disease (IBD). See page 715, column 1. Irving teaches that a study by Jamontt 2010 discloses this combination not only reduced inflammation but also lowered the occurrence of functional disturbances, reasonably interpreted to be symptoms of IBD. Id.
Further, Borrelli teaches the beneficial effect of the cannabinoid CBG in an experimental model of IBD, a murine model of colitis induced in mice models. See abstract. “CBG could be considered for clinical experimentation in IBD patients.” See abstract.
A PHOSITA following the teachings of the reference application would have found it prima facie obvious to formulate the claimed pulse oral composition for use in treating IBS, Crohn’s disease or UC in view of WO 164, Irving and Borelli, as these are taught by the combination of the cited prior art
The rationale to support a finding of obviousness are the prior art elements of the reference application, noting oral pulsed dosage forms as claimed combined with the teachings of Irving and Borrelli (CBD, CBG and THC useful for treating IBS, UC and/or Crohn’s disease) to predictably arrive at the claimed invention.
With regard to the oral pulse-release dosage form release profile in a 3-stage dissolution media for 3 hours, as discussed above, such release profile is an intended use of the claimed composition comprising component C1 and component C2. As such it is treated to have no patentable weight as it is not a structural limitation per se to define the claimed composition comprising components C1 and C2. It does not provide physical, structural limitations to define the claimed composition, but rather describes a release profile the claimed composition possesses.
Regarding claims 37, 41 and 44, and inflammation of the upper, lower GI tract, or both, official notice is given that UC, Crohn’s disease and IBS involve both upper and lower GI tract. The GI tract consists only of an upper and lower tract and UC, Crohn’s Disease and IBS are known to affect the GI tract. As discussed above, the combination of WO 164, Irving and Borrelli teach IBS, Crohn’s disease and UC, where the symptoms of claim 44 (pain, bloating, diarrhea) are noted to be associated with IBS, Crohn’s disease or UC. It would be routine for one of ordinary skill in the art to optimize the treatment of the upper and/or lower GI tract for the symptoms claimed.
Regarding claim 38 and dosing the patient 1-4 times a day, and claims 42-43, where treatment disorder and/or symptoms occurs within 6, 12, 24 or greater than 24 hours post-dose, or 1-24 hours, or greater than 24 hours, the reference application discloses the pulse-release dosage form provides release of the API1P2 and the API2P2 beginning from 2 to 6 hours after release of the API1P1 and the API2P1 begins. See claim 1.
As required by claim 47 and the claimed second time peak release rate (PPR2), as the reference application, Irving and Borrelli discloses disclose the claimed method and the claimed subject in need, such release rate claimed is necessarily present in the cited prior art.
Regarding claim 48 and the limitation of where the cannabinoid of the first pulse component is 10-50% of total and cannabinoid of second pulse is 50-90% of total dose, the reference application teaches for each API, the first portion (P1) is independently selected from 25% to 75% of the total daily dose, and for each API the second portion (P2) is independently selected from 25% to 75% of the total daily dose. See claim 1.
As required by claims 49 and 50 and the limitations of the excipients therein, the reference application discloses microcrystalline cellulose as the excipient for the first pulse release component C1. See clam 9, among other teachings.
Regarding claim 51, the reference application teaches the binders comprise from 1 to 60% (w/w). See claim 8.
As required by claims 52-55 and the limitations of a delayed cannabinoid API core and pharmaceutically acceptable excipients; with polymers (such as methacrylic acid copolymer, Eudragit) of the delayed release components layer or integrated, pH sensitive or not pH sensitive, WO 164 discloses its formulations are selected from the various formulations with delayed release components, such as bilayer/matrix type, monolithic/matrix-type, monolithic/coated -type, enteric coating-type, 2 pulse type, 3 pulse type, solid adsorbate type, pellet-type, and continuous release-type, see claim 26. These formulations are either coated or non-coated and either pH or non-pH sensitive. Further, with regard to polymer coated/integrated delayed release components, WO 164 discloses Table 9 paragraph 263, with both an instant release and delayed release component, where methacrylic acid co polymer type C (Eudragit) is used to coat the delayed release pellet component.
Regarding claim 56 and the limitation polymer being 4 to 25% weight of the delayed release portion, WO 164 discloses 13.2 mg of Eudragit out of the subtotal of 172.5 mg, which is 7.65%, see above Table 9.
As required by claims 57-59 and the limitation of pellets and pellets contained in a capsule, WO 164 Table 7 and Table 9 disclose pellets enclosed in a capsule, see above.
This is a provisional nonstatutory double patenting rejection.
Conclusion
All claims are currently rejected. No claims are currently allowed.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 Elected species: Inflammatory Gastrointestinal (GI) Disease/disorder: Irritable Bowel Disease.
2 Morampudi et al. DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat, J Vis Exp. 2014 Feb 27:(84):e51297.