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 .
Current Status
This action is responsive to the amended claims of 03/25/2026. Claims 1, 3-9, 12, and 15-35 are pending. Claims 2, 10-11, and 13-14 have been canceled. Claims 23 and 29-30 have been withdrawn. Claims 1, 3-9, 12, 15-22, 24-28, and 31-35 have been examined on the merits.
Election/Restrictions
The amendments have overcome the 102-type rejections of the prior action; however, the amendments/arguments have not been found persuasive regarding the 103-type rejections. Since the elected species are still subject to prior art rejections, the Markush search will not be extended to further species in this action, in accordance with Markush search practice.
The elected species cannabidiol, mannitol, focal onset seizure, Dravet Syndrome, and phenobarbital read on claims 1, 3-9, 12, 15-22, 24-28, and 31-35.
Claims 23 and 29-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/14/2025.
Priority
The effective filing date remains 04/27/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/13/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Examiner acknowledges receipt of and has reviewed the amendments and remarks of 03/25/2026; no new matter is found.
The objection to claims 3-4 is withdrawn since Applicant has addressed the typo.
The 112b rejection of claim 26 is withdrawn since Applicant has amended “infantile spasm (West syndrome)” to “infantile spasm, West syndrome”.
The 112b rejection of claim 35 is withdrawn since “such as” and the limitations following have been struck from the claim.
The 102(a)(1) and 102(a)(2) rejections of claims 1, 7-8, 10-11,15-16, 18-19, 25-26, 31, and 34 over BRUNN, evidenced by BUTLER, are both withdrawn since claim 1 has been amended to recite the composition is lyophilized. BRUNN does not teach a lyophilized form.
The 103 rejection of claims 1-12, 15-19, 22, 24-28, 31-32, and 34 over BRUUN in view of: GROTHER, BROOKS, and LATANZI is maintained for claims 1, 3-9, 12, 15-19, 22, 24-28, 31-32, and 34 below. Claims 2 and 10-11 have been cancelled. Applicant's arguments filed 03/25/2026 have been fully considered but they are not persuasive. Applicant argues:
The success of BRUUN’s dosage form is due to the specific features of said form, but the obviousness combination does not include any of the features of BRUNN. Further, BRUUN’s disintegration time is slower than GROTHER’s and GROTHER does not contain a suggestion that the Zydis form would improve speed of absorption. Examiner disagrees; the rejection utilizes the same ingredients of pure and solid CBD, gelatin, and mannitol wherein the gelatin and mannitol overlap with the fast-disintegrating form of GROTHER. Both forms are for “rapid” disintegration. While the GROTHER form is faster than BRUUN, Applicant makes this argument without considering the contribution of BROOKS as explained in the rejection: BROOKS provides a reasonable expectation of success that the CBD will work within GROTHER’s Zydis form since BROOKS teaches development of CBD use in the Zydis form. Thus, the artisan would have motivation to move the CBD of BRUUN to a faster disintegrating form with similar ingredients (gelatin, mannitol).
The solid CBD of 95-99% purity would be recognized by the artisan as insoluble in saliva, thus, the combination suggested by the Examiner would eliminate sublingual absorption and would be unlikely to succeed. Examiner disagrees; the teachings of BROOKS are not considered by Applicant here (see above). Further, BROOK teaches sublingual administration of solid, pure CBD (Pg. 13 Lines 25-30, Pg. 21 line 1-2, Pg. 47 Lines 1-9 – cited previously). Thus, this argument fails to be persuasive.
Applicant now relies on SEAGER (pub. 1998; provided in IDS of 05/12/2023) to teach insoluble drugs formulated in Zydis units are swallowed in the normal way, i.e., they are not absorbed via the buccal/oral mucosa. Examiner cites evidentiary reference CATALENT (Catalent, “Catalent to Partner with Ethicann on New Fast-Dissolve Cannabinoid-Based Treatment for Multiple Sclerosis Spasticity,” 3 Dec. 2019, retrieved from www.catalent.com/catalent-news). CATALENT discloses a property of the Zydis dosage form: for notoriously insoluble and poorly bioavailable drugs, Zydis sublingual dosage forms avoid first pass metabolism (Pg. 2 ¶3). This property of the Zydis form contradicts the teachings of SEAGER. Moreover, it is unclear how the instant composition differs from the Zydis unit. If SEAGER teaches the Zydis unit does not allow buccal administration, how has Applicant achieved such result? The instant specification does not provide any data corresponding to the instantly claimed composition which would prove improved bioavailability is achieved by the composition of instant claim 1. Further, since SEAGER is a much older document (1998) than CATALENT and any of the relevant prior art, the artisan would not look to SEAGER as the state of the art regarding Zydis and buccal administration of insoluble drugs. Moreover, Catalent is the Applicant on the GROTHER reference, so the artisan would look to Catalent as the expert on the Zydis form. Further, since BRUUN teaches CBD can be buccally administered, the artisan would have a reasonable expectation of success (as discussed in the reiterated rejections below).
The Applicant also argues BROOKS does not teach the instant dosage form. BROOKS does not need to teach the details of the instant dosage form, since these details are covered by BRUUN and GROTHER.
Applicant also argues BROOKS does not provide expectation of success since: 1) BROOKS teaches cannabinoid oils not solids and 2) BROOKS is not a scientific paper but a press release from Catalent. While these two points are factually correct, Examiner disagrees with the conclusion lacking an expectation of success. A reasonable expectation of success includes a reasonable amount of experimentation. Based on the teachings of all of the combined references the artisan would have enough guidance to create the lyophilized Zydis form comprising solid CBD, since both BRUUN and GROTHER teach solid forms of compound are used in their respective fast disintegrating forms (see previous rejection). Further, while BROOKS is a press release, the artisan would reasonably expect the development of CBD + Zydis form to be successful since Catalent (the Applicant on GROTHER), with years of experience, is investing in such development. Thus, it would be obvious to start such development based on related teachings – i.e., BRUUN and GROTHER for fast-disintegrating CBD and Zydis, respectively.
Applicant argues LATANZI does not teach the lyophilized form. LATANZI does not need to teach the lyophilized form since BRUUN and GROTHER do. Applicant also argues the dosages of LATANZI; however, these teachings were not relied upon in this rejection. Rather this argument is addressed in the following paragraph regarding instant claims 20-21. Applicant further argues LATANZI does not cure the deficiencies of the other references; however, Examiner disagrees with these “deficiencies” as discussed above. So, LATANZI merely has to teach that CBD has some effect in treatment of CBD (no matter how small), which it does (see all teachings cited previously). Further, since BRUUN teaches the fast-disintegrating CBD form is used for treating epilepsy (Pg. 50 Lines 23-24), the artisan’s expectation of success remains.
Applicant has provided a Declaration; however, this declaration does not apply to this application. The declaration responds to rejections in a different application (no. 17/225,738). None of the instant arguments or references are addressed, thus, the arguments are not mapped onto the instantly debated subject matter and cannot be found persuasive. Further, no unexpected results regarding treatment of epilepsy are provided within.
After review of the remarks of 03/25/2026 and the specification, Examiner has not found any data regarding treatment of epilepsy via administration of the claimed dosage form. At most, the specification at Pg. 50 states an adverse event rate of 6.4% is reported in a cohort of post-surgical pain patients. Effects in epilepsy patients are not disclosed. This adverse event rate is lower than that shown in clinical trials for other CBD dosages forms; however, these comparative dosage forms are not the closest prior art: epidiolex is not a buccal administration form and Sativex contains THC which is an active ingredient not present in the instant dosage form. BRUNN still represents the closest prior art since it is CBD formulated for buccal administration, but is not lyophilized. Applicant argues the instant dosage form provides superior bioavailability, but the instant disclosure does not provide any data on superior bioavailability compared to the closest prior art. While the specification provides an example formulation of the claimed composition (Pg. 47 Table 2), no data regarding dissolution rate or bioavailability/pharmacokinetics of this formulation are provided. Thus, no surprising or unexpected results are found.
For these reasons, the arguments are not found to be persuasive.
The 103 rejection of claims 1, 20-21, and 32-33 over BRUUN in view of: GROTHER, BROOKS, and LATANZI, as applied to claim 1 (above), further in view of ANSEL is maintained. Applicant’s arguments are not found to be persuasive. See the arguments already discussed above. Further:
Applicant argues LATANZI teaches CBD dosages for epilepsy well above the instant dosages, thus, the much smaller instant dosages would not be expected to be successful by the artisan. As cited previously, LATANZI teaches dosages of 5 mg/kg twice a day (Pg. 1795 Table 1) which is considered to overlap/approach the instantly claimed 0.1 to 5 mg/kg/day wherein doses are given 1-3 times per day (claims 20-21). The recitation of “mg/kg” in both the prior art and the instant claims is understood to mean mg of CBD per kg of the patient. Thus, the teaching of LATANZI is very close to and overlaps with the instant claims. As discussed in the rejection, in view of ANSEL’s teachings of the importance of dosage modification, the artisan would have a reasonable expectation of success.
Applicant also argues ANSEL does not teach the instant lyophilized form. Since Examiner utilized BRUUN, GROTHER, and BROOKS to teach the lyophilized form, ANSEL does not need to.
The 103 rejection of claims 1 and 34-35 over BRUUN in view of: GROTHER, BROOKS, and LATANZI, as applied to claim 1 (above), further in view of ZHANG is maintained. Applicant’s arguments are not found to be persuasive. See the arguments already discussed above. Further:
Applicant also argues ZHANG does not teach the instant lyophilized form. Since Examiner utilized BRUUN, GROTHER, and BROOKS to teach the lyophilized form, ZHANG does not need to.
The obviousness-type nonstatutory double patenting rejection of claims 1-12, 15-22, 24-28, and 31-35 over claims 16-25 of U.S. Patent No. 11,672,761 is withdrawn because Applicant has filed an accepted terminal disclaimer.
The obviousness-type nonstatutory double patenting rejection of claims 1-12, 15-22, 24-28, and 31-35 over claims 21-24, 31-32, and 37 of copending Application No. 18/307,228 is withdrawn because Applicant has filed an accepted terminal disclaimer.
Response to Amendment
Claim Objections
Claim 35 is objected to because of the following informalities: please add the word “and” before “valproic acid or its salts”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 9 and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 9 and 20 recites the limitation "the CBD or derivative/analog thereof". There is insufficient antecedent basis for this limitation in the claim. Neither claim recites “a” derivative or analog of CBD. Both claims depend from claim 1; after the most recent amendment, claim 1 no longer recites “a derivative/analog” of CBD. Thus, the derivative/analog of CBD recited in claims 9 and 20 are outside of the scope of claim 1. Therefore, the metes and bounds of the claim are undefined rendering the claim indefinite.
To overcome: please strike “or derivative/analog thereof” from the claims.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 9 and 20 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 9 and 20 recite “the CBD or derivative/analog thereof”. This is outside of the scope of parent claim 1 which encompasses only the CBD itself, not a derivative/analog thereof. Therefore, claims 9 and 20 do not properly further limit parent claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1, 3-9, 12, 15-19, 22, 24-28, 31-32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over BRUUN (WO 2020/211915, pub. 22 Oct. 2020, effectively filed 17 April 2020) in view of:
GROTHER (WO 2022/074127, effectively filed 08 Oct. 2020, priority document cited as “PD” below),
BROOKS (Brooks, K. Contact Pharma, 2019, 1-17), and
LATTANZI (Lattanzi, S. et al., Drugs, 2018, 78, 1791-1804).
All references provided previously by Examiner, on 11/28/2025.
The instant claims are drawn to a method of treating epilepsy via buccal-administration of a lyophilized dosage form comprising pure, solid CBD, a sugar alcohol, and gelatin. Treatment of epilepsy with CBD is known and such dosage form is made obvious by the combined references.
Determining the Scope and Contents of the Prior Art:
BRUUN teaches a fast-disintegrating cannabinoid tablet which disintegrates in contact with oral saliva (Pg. 92 claim 1) comprising cannabidiol (CBD) (Pg. 19 Lines 15-17 & 24), mannitol (Pg. 94 claim 21), and gelatin (Pg. 96 claim 39). The tablet is for oral administration (Pg. 1 Line 6), preferably for treatment of epilepsy (Pg. 50 Lines 23-24). The sugar alcohol is present in at least 20% weight of the tablet (Pg. 92 claim 1) or 30% weight of the tablet (Pg. 94 claim 17). The cannabinoid is in solid form (Pg. 21 line 1-2) and is purified corresponding to 95%, more preferably 96-99% (Pg. 47 Lines 1-9). The tablet comprises at least one excipient selected from sweetener, flavor, or colorant (Pg. 97 claim 44). Sweeteners include sucralose and acesulfame potassium in combination (Pg. 33 Lines 4-7) and flavors include lemon-lime (Pg. 33 Line 14). Sensory properties including flavor and sweetness are important to ensure effective oral delivery wherein taste masking is critical (Pg. 2 Lines 14-31).
BRUUN teaches buccal administration (Pg. 13 Lines 25-30). Further, reducing dissolution time and improving speed of cannabinoid absorption improves patient compliance (Pg. 6 Lines 3-4) especially for buccal administration (Pg. 13 Lines 24-31). The tablet may be used to treat seizures, Dravet syndrome, Lennox Gastaut syndrome, myoclonic seizures, juvenile myoclonic epilepsy, refractory epilepsy, juvenile spasms, West syndrome, infantile spasms, refractory infantile spasms, and tuberous sclerosis complex (Pg. 51 Lines 1-7). The tablet is suitable for co-administration with an anti-convulsive medication (i.e., an antiepileptic drug) (Pg. 50 Lines 29-31).
GROTHER teaches a lyophilized oral dispersible/disintegrating dosage form suitable for sublingual delivery (Pg. 9 ¶ 95; PD ¶ 94) comprising epinephrine, 10-40 wt. % matrix former, and 10-40 wt. % structure former (Pg. 63 claim 1; PD claim 1) wherein the matrix former is bovine gelatin (Pg. 63 claim 7-8; PD claim 7-8) and the structure former is mannitol (Pg. 63 claim 10; PD claim 10). The dosage form includes about 25-65 wt.% active agent (Pg. 19 ¶ 0137; PD ¶ 136); also including coloring agents, flavoring agents, and sweeteners (Pg. 11 ¶ 0102; PD ¶ 101). Suitable coloring agents are yellow iron oxides and FD&C dyes and flavoring agents include lemon (Pg. 11 ¶ 0102; PD ¶ 101). Suitable sweeteners include sucralose and acesulfame K (Pg. 11 ¶ 0103; PD ¶ 102). The active agent is micronized to a diameter of about 10-40 microns (Pg. 15 ¶ 0122; PD ¶ 121), and teaches examples with a D50 of 10-38 microns (Pg. 173 Fig. 76; PD Fig. 76). GROTHER further teaches a method of treating a patient by placing the dosage form in the oral cavity’s buccal region (Pg. 64 claims 19-20; PD claims 19-20).
GROTHER teaches a specific example wherein the dosage form consists of 4% w/w bovine gelatin, 3% w/w mannitol and 4% epinephrine prior to lyophilization (Pg. 21 Table 1; PD ¶ 143), which is about, but slightly less than, 36% gelatin, 27% mannitol, and 36% epinephrine after freeze drying to remove the water. Note, there is also an undisclosed but small amount of citric acid which was used for pH adjustment; the pH modifier is present in an amount of 1-10 wt.% (Pg. 15 ¶ 119; PD ¶ 118). The exemplary dosage forms disperse in less than 2 seconds in 20°C water (Pg. 21 Table 1 & Pg. 22 ¶ 148-149; PD ¶ 143). This dosage form is the Zydis unit (Pg. 89 Fig. 21A; PD Fig. 21A).
BROOKS teaches a composition to deliver pharmaceutical grade CBD based on the Zydis orally disintegrating tablet of Catalent (Pg. 2), i.e., the dosage form taught by GROTHER.
LATTANZI teaches adjunctive CBD treatment in patients with Dravet syndrome uncontrolled by concomitant anti-epileptic drugs is effective to reduce seizure frequency (Pg. 1791-1792 Abstract & Key points). LATTANZI teaches ≥50% reduction in monthly frequency of all types of seizure including focal onset (Pg. 1792 sect. 2.3 & Pg. 1798 Table 3). LATTANZI teaches CBD dosages of 5 mg/kg twice a day were given to children aged 4-10 years with a history of Dravet Syndrome uncontrolled by other antiepileptics; further generalized seizures (i.e., generalized onset) are treated with CBD (Pg. 1795 Table 1).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
BRUUN does not teach the dosage form is lyophilized, the instant disintegration times, the instant wt%, the micronized CBD, the type of epilepsy, convulsion frequency, and the species of secondary anti-epileptic.
GROTHER does not teach treatment of epilepsy with a CBD dosage form.
BROOKS does not teach a method of treating epilepsy.
LATTANZI does not teach the instant composition.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of dosage forms useful for treatment of epilepsy and possesses the technical knowledge necessary to make adjustments to the dosage form to optimize the treatment outcomes. Said artisan has also reviewed the problems in the art regarding cannabinoid dosage forms and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references BRUUN in view of: GROTHER, BROOKS, and LATTANZI.
Regarding claims 1, 3-4, 6, and 8, the artisan would be motivated to treat epilepsy by administering the dosage form of GROTHER comprising cannabidiol (CBD) as the active agent. The artisan would be motivated to substitute the oral dosage form of BRUUN with the lyophilized oral dosage form of GROTHER since reducing dissolution time improves patient compliance, as recognized by BRUUN (Pg. 6 Lines 3-4) and GROTHER’s dosage form dissolves in ~2 seconds (Pg. 21 Table 1 & Pg. 22 ¶ 148-149; PD ¶ 143); i.e., within the instant 1-30 and 1-5 sec. ranges. The artisan would be motivated to have the composition comprise bovine gelatin and mannitol since GROTHER teaches this is the composition that dissolves quickest (Pg. 21 Table 1 & Pg. 22 ¶ 148-149; PD ¶ 143). Further, the artisan would be motivated to choose CBD as the active cannabinoid in order to reduce epileptic seizure frequency as recognized by LATTANZI (Pg. 1791-1792 Abstract & Key points). Moreover, the artisan would have a reasonable expectation of success since the Zydis dosage form of GROTHER may be formulated with CBD, as recognized by BROOKS (Pg. 2).
Further, since BRUUN teaches the cannabinoid is in solid form (Pg. 21 line 1-2) and is more preferably 96-99% pure (Pg. 47 Lines 1-9) the instant limitations are explicitly taught. Further, it would be obvious for the CBD to be in a solid form since the final dosage form of GROTHER is lyophilized, i.e., a freeze dried solid. Since the final dosage form is solid it would follow that the components are solid.
Further regarding claims 3-4, GROTHER teaches 20°C water vs. the instant 37°C water; however, MPEP 2144.05(II)(A) states: “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. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” Thus, the instantly claimed dissolution time at the instant temperature would be well within the practice of the artisan.
Regarding claim 5, the artisan would have been motivated to optimize the wt.% of gelatin. MPEP 2144.05(II)(A) provides guidance about the routine optimization of prior art conditions: "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. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.").” Furthermore, MPEP 2144.05(I) provides guidance about overlapping ranges: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.”
Here, GROTHER teaches bovine gelatin at less than 36 wt.% (Pg. 21 Table 1; PD ¶ 143) and in the range of 10-40 wt. % (Pg. 63 claim 1; PD claim 1) which overlaps with the instant range of 10-35 wt.%. Since the wt.% is the concentration of gelatin, the instant case is equivalent to the difference in concentration cited in the MPEP. Therefore, the determination of the optimum or workable gelatin wt.% is well within the practice of the artisan. Furthermore, absent any evidence demonstrating a patentable difference between the instant and prior art compositions and the criticality of the claimed wt.%, the determination of the optimum or workable wt.% given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Regarding claim 7, BRUUN teaches the sugar alcohol (i.e., mannitol) is at least 20% weight of the tablet (Pg. 92 claim 1) or 30% weight of the tablet (Pg. 94 claim 17) and GROTHER teaches 27% mannitol (Pg. 21 Table 1; PD ¶ 143). These percentages lie within the instant range of 5-35 wt.%. Further, the instant range would be obvious by the same logic applied to claim 5, above. Thus, the claim is obvious.
Regarding claim 9, the 25-65 wt.% active agent, i.e., CBD, taught by GROTHER (Pg. 19 ¶ 0137; PD ¶ 136) lies within the instantly claimed range of 20-70 wt.%. Further, the instant range would be obvious by the same logic applied to claims 5 & 7, above. Thus, the claim is obvious.
Regarding claim 12, the D50 of 10-38 microns taught by GROTHER (Pg. 173 Fig. 76; PD Fig. 76) lies within the instantly claimed range of 1-50 microns. Thus, the claim is obvious.
Regarding claims 15-18, both BRUUN (Pg. 97 claim 44) and GROTHER (Pg. 11 ¶ 0102; PD ¶ 101) teach the dosage form includes sweeteners, flavors, or colorants. The artisan would be motivated to include the sweeteners sucralose and acesulfame K in combination (BRUUN Pg. 33 Lines 4-7; GROTHER Pg. 11 ¶ 0103; PD ¶ 102) and the flavor lemon-lime (BRUUN Pg. 33 Line 14) since taste masking via flavorings and sweeteners is critical to ensure effective oral delivery, as recognized by BRUUN (Pg. 2 Lines 14-31). Further the artisan would be motivated to use lemon-lime since GROTHER also teaches lemon flavor (Pg. 11 ¶ 0102; PD ¶ 101) and the two would be understood as obvious variants since both are citrus flavors. GROTHER teaches suitable coloring agents include yellow iron oxides and FD&C dyes (Pg. 11 ¶ 0102; PD ¶ 101); the instant FD&C Yellow #5 is an obvious variant of the dyes. It would be obvious to use this color since the flavor is lemon-lime and lemons are yellow.
Regarding claim 19, the artisan would be motivated, with an expectation of success, to administer the dosage form via the buccal mucosa since GROTHER teaches this as a preferred route (Pg. 64 claims 19-20; PD claims 19-20). Further, BRUUN targets buccal administration (Pg. 13 Lines 25-30) and recognizes reduced dissolution time is particularly useful for buccal administration (Pg. 13 Lines 24-31). Thus, the quick dissolution time of GROTHER makes the dosage form obvious for buccal administration.
Regarding claims 22, 24, and 32, since LATTANZI teaches CBD treatment results in ≥50% reduction in frequency of all types of seizure including focal onset (Pg. 1792 sect. 2.3 & Pg. 1798 Table 3) and teaches generalized seizures (i.e., generalized onset) are treated with CBD (Pg. 1795 Table 1), the artisan would be motivated to treat focal onset and/or generalized onset seizures with the CBD composition made obvious by BRUUN, GROTHER, and BROOKS. Further, the artisan would expect the CBD composition to reduce seizure frequency by at least 50%, in view of LATTANZI. Note, these instant claims do not recite a certain dosage that achieves such reduction.
Regarding claims 25-28 and 31, LATTANZI teaches patients’ seizure frequency is reduced by CBD administration (Pg. 1791-1792 Abstract & Key points) and the patients were children aged 4-10 years with a history of Dravet Syndrome uncontrolled by other antiepileptics (i.e., drug-resistant) (Pg. 1795 Table 1). Thus, the artisan would be motivated to treat this patient population (i.e., children with drug-resistant Dravet syndrome) with the CBD composition made obvious, above, in order to reduce seizure frequency.
Regarding claim 34, the artisan would be motivated, with an expectation of success, to administer the CBD composition with another antiepileptic drug since BRUUN (Pg. 50 Lines 29-31) teaches the CBD dosage may be administered with an anticonvulsant and LATTANZI teaches CBD concomitant with antiepileptics is an effective treatment (Pg. 1791-1792 Abstract & Key points).
Claims 1, 20-21, and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over BRUUN (WO 2020/211915, pub. 22 Oct. 2020, effectively filed 17 April 2020) in view of:
GROTHER (WO 2022/074127, effectively filed 08 Oct. 2020, priority document cited as “PD” below),
BROOKS (Brooks, K. Contact Pharma, 2019, 1-17), and
LATTANZI (Lattanzi, S. et al., Drugs, 2018, 78, 1791-1804)
as applied to claim 1 above, and further in view of:
ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53).
All references provided previously by Examiner, on 11/28/2025.
The instant claims are drawn to specific dosages of CBD in the lyophilized dosage form and specific % reduction of seizure frequency. Such dosages and resulting % reduction in the disease symptoms can be optimized by routine experimentation.
Determining the Scope and Contents of the Prior Art:
BRUUN, GROTHER, BROOKS, and LATTANZI teach the instant claim 1, see above rejection.
ANSEL teaches the safe and effective dose of a drug depends on a number of
factors including characteristics of the drug, the dosage form, and a variety of patient
factors (Pg. 48 Left Col. para 2) and the effective dose may be different for different
patients (Pg. 48 Left Col. para 4). ANSEL further teaches the schedule of dosage or the
dosage regimen is determined based on a drug’s duration of action, pharmacokinetics, and characteristics of the dosage form (Pg. 40 Right Col. para 2).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
BRUUN, GROTHER, BROOKS, and LATTANZI do not teach the instant dosages and effects thereof.
ANSEL does not teach the instant method.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods useful for treatment of epilepsy and possesses the technical knowledge necessary to make adjustments to the dosage regimen to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding dosing of cannabinoids and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references BRUUN in view of: GROTHER, BROOKS, and LATTANZI, further in view of: ANSEL.
Regarding claims 1 and 20-21, the artisan would be motivated to optimize the dosage and dosing regimen of the CBD. See ¶28, under claim 5 above, for the citations of MPEP 2144.05(I)-(II)(A) regarding routine optimization of prior art conditions.
In the instant case, LATTANZI teaches dosages of 5 mg/kg twice a day (Pg. 1795 Table 1) which is considered to approach the instantly claimed 0.1 to 5 mg/kg/day wherein doses are given 1-3 times per day. Since ANSEL teaches the safe and effective dose of a drug depends on many factors (Pg. 48 Left Col. para 2), the effective dose may be different for different patients (Pg. 48 Left Col. para 4), and the dosage regimen is determined by the drug’s pharmacokinetics and characteristics of the dosage form (Pg. 40 Right Col. para 2), the artisan would recognize the dosage/dosing regimen as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Therefore, absent any evidence demonstrating the contrary, the determination of the optimum or workable dosage/dosing regimen of the CBD and composition thereof would have been well within the practice of the artisan.
Regarding claims 32-33, in view of ANSEL, the artisan would recognize the relationship between a drug’s dosage and the drug’s effect on the target disease. Thus, the artisan would recognize the efficacy of a drug as an outcome of the dosage/dosing regimen and would recognize the dosage/dosing regimen as a results-effective variable, i.e., a variable that achieves a recognized result. In the instant case, since the optimization of the CBD dosage/dosing regimen is obvious, the optimization of the drug’s efficacy at reducing seizure frequency would naturally follow. Furthermore, in view of LATTANZI teaching ≥50% reduction in seizure frequency (Pg. 1792 sect. 2.3 & Pg. 1798 Table 3), the artisan would have a reasonable expectation of success in reducing the total seizure frequency (i.e., convulsive frequency) by at least 50% or at least 70% upon optimization of the dosage/dosing regimen.
Claims 1 and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over BRUUN (WO 2020/211915, pub. 22 Oct. 2020, effectively filed 17 April 2020) in view of:
GROTHER (WO 2022/074127, effectively filed 08 Oct. 2020, priority document cited as “PD” below),
BROOKS (Brooks, K. Contact Pharma, 2019, 1-17), and
LATTANZI (Lattanzi, S. et al., Drugs, 2018, 78, 1791-1804)
as applied to claim 1 above, and further in view of:
ZHANG (Zhang, L.L. et al., Epileptic Disord., 2011, 13(4), 349-365).
All references provided previously by Examiner, on 11/28/2025.
The instant claims are drawn to administration of the lyophilized CBD form and a second anti-epileptic drug, phenobarbital. This combination is obvious.
Determining the Scope and Contents of the Prior Art:
BRUUN, GROTHER, BROOKS, and LATTANZI teach the instant claim 1, see above rejection.
ZHANG teaches phenobarbital, an antiepileptic drug, is widely used because of its low cost (Pg. 349 Abstract).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
BRUUN, GROTHER, BROOKS, and LATTANZI do not teach wherein the antiepileptic drug is phenobarbital.
ZHANG does not teach administration of the instant composition
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of epilepsy and possesses the technical knowledge necessary to make adjustments to the composition/drugs administered to optimize/enhance the treatment. Said artisan has also reviewed the problems in the art regarding antiepileptic drugs and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references BRUUN in view of: GROTHER, BROOKS, and LATTANZI, further in view of: ZHANG.
The artisan would be motivated to administer the instant CBD dosage form by the method made obvious by BRUUN, GROTHER, BROOKS, and LATTANZI to a patient receiving phenobarbital in order to further reduce seizure frequency. The artisan would have an expectation of success in administering the concomitant therapies since 1) phenobarbital is widely used, as recognized by ZHANG (Pg. 349 Abstract) and 2) adjunctive CBD treatment is effective at reducing seizure frequency in treatment with concomitant antiepileptics, as recognized by LATTANZI (Pg. 1791-1792 Abstract & Key points).
Moreover, the artisan would have a reasonable expectation of success that by combining the instant CBD dosage form with phenobarbital, one would have achieved a composition useful for treating epilepsy since both are taught by the prior art as suitable for the treatment of epilepsy. As set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two agents each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art.
Conclusion
Claims 1, 3-9, 12, 15-22, 24-28, and 31-35 are rejected.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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