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 . 1
Status of Claims
Claims 26, 31-32, 35, 39, 43 and 78-84 are under examination. Applicant’s elected the species of generalized tonic clonic seizures, liquid Formulation #LFlO comprising 31.09% pure CBD, 0.2 % Vit. E antioxidant, 68.785 % caprylic/capric triglyceride, flavoring and sweetener. 2
Response to Arguments
Applicant’s arguments, filed 07/07/2026, with respect to claims(s) 26,31-32,35,39,43 and 78-84 under 35 U.S.C. 103 as obvious over US Pub 6603 in view of Pediatric Pharmacotherapy 19964 and Whalley US Pub 3985 have been considered but are not persuasive. See below rejection and response to Attorney response.
Claim Interpretation
Claim 26 recites the phrase “consisting essentially of” that limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention.” See MPEP 2111.03. The recitation “consisting essentially of” in claim 26 is interpreted under the broadest reasonable interpretation of MPEP 2111, consistent with Applicants specification, to include unrecited excipients sweeteners, etc. [0031].
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 26,31-32,35,39,43 and 78-84 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 2013/0296398 A1 (Whalley US Pub 398) in view of US 20110306660A1 (US Pub 660) and Buck PharmD, Contributing Editor: A Guide to Pharmaceutical Excipients, Pediatric Pharmacotherapy, Newsletter Children’s Medical Center at the University of Virginia Volume 2 Number 9 September 1996 (Pediatric Pharmacotherapy 1996). Whalley US Pub 398 and Pediatric Pharmacotherapy 1996 were previously cited by the Examiner. US Pub 660 is cited as US Pub Ref. 17 on the IDS dated 4/11/2022.
Claim 26 is a method of reducing seizure frequency in a pediatric subject with refractory epilepsy, comprising orally administering to the subject an alcohol-free composition consisting essentially6 of
20% to 35% w/w cannabidiol having a purity of greater than 98% w/w;
5% to 30% w/w polyethylene glycol [PEG];
5% to 35% w/w propylene glycol [PPG]; and
4% to 8% w/w water;
wherein the composition contains less than 0.3% w/w delta-9-tetrahydrocannabinol.
Regarding claim 26 and treatment of a pediatric patient with refractory epilepsy, Whalley US Pub 398 teaches the need to treat epileptic seizures during childhood. See paragraph 24. Whalley US Pub 398 teaches treatment of the subject who is refractory to existing medication. See claim 6 and paragraph 48.
Whalley US Pub 398 teaches a “method for treating epilepsy comprising administering to a subject in need thereof cannabidiol (CBD), at a dose of greater than 300 mg/day, in combination with a standard anti-epileptic drug (SAED) which acts via sodium or calcium channels, for use in the treatment of epilepsy.” See claim 1.
While not disclosing the claimed percentage amounts of CBD for the treatment of pediatric epilepsy, a PHOSITA would routinely optimize concentrations of CBD in a formulation, based on the known dosage of 300 mg/day of CBD administered to the pediatric patient.
With regard to the purity limitation of claim 26 of greater than 98%, while not explicitly recited in Whalley US Pub 398, it nonetheless teaches the administration of isolated CBD, which, given the plain meaning of isolated, is taken to mean a purified version of CBD meeting the claimed purity. See paragraphs 56, 69, 76 and 89.
While disclosing the treatment of a pediatric patient with refractory epilepsy with a composition comprising CBD, Whalley does not teach the claimed orally dosed composition comprising cannabinoid such as CBD, PEG, propylene glycol (PPG) and water. However, the treatment of these patients with a CBD formulation consisting essentially of PEG, PPG and water is known in the art as detailed below.
Regarding claim 26 and the limitations of the orally dosed formulation, US Pub '660 teaches formulations comprising a cannabinoid (such as dronabinol) and the following ingredients: (i) from about 0 to about 40% water, (ii) from about 15 to about 65% alcohol, preferably ethanol, and (iii) a cosolvent that is (a) propylene glycol from about 0% to about 50%, (b) polyethylene glycol from about 0 to about 50%, and/or (c) a combination of (a) and (b), the solution having a combined total of 100%, wherein the formulations are suitable for oral administration, see paragraph 7.
Of note, while the formulation of paragraph 7, with its concentration percentage ranges of water, PPG and PEG overlap those as claimed by claim 26, it also further recites an amount of alcohol.
However, it would have been prima facie obvious to substitute art known equivalents one for another, MPEP 2144.06, to replace the amounts of co-solvents, such as ethanol taught by US Pub ‘660 with, functional equivalents, PPG and PEG. Paragraph 59 teaches PEG, PPG and ethanol as equivalent Co-Solvents. See below.
Co-Solvents
[0059]. In certain embodiments, the co-solvents are organic. Solvents such as dehydrated alcohol, ethanol, propanol, isopropanol, propylene glycol, polyethylene glycol, and combinations thereof that are pharmaceutically acceptable based on the desired formulation.
Note paragraph 62 with an emphasis on the two claimed co-solvents, PPG and PEG in ranges overlapping the claimed concentrations.
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It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) to replace known co-solvents, one for another so as to arrive at a formulation consisting essentially of a cannabinoid, water, PPG and PEG, in overlapping ranges as those claimed. Also noted is the recognition by a PHOSITA to avoid ethanol formulations with certain patient populations, such as the claimed subject in need, pediatric patients.
Pediatric Pharmacotherapy teaches that since 1993, a committee representing the FDA and Nonprescription Drug Manufacturers Association concluded that OTC products designed for children under 6 should be alcohol free; product for children ages 6-12 should contain no more than 5% alcohol; product for children over 12 years should be limited to 10% alcohol. See page 3, column 1 bridging to column 2.
Regarding the limitations of treatment of epilepsy and similar to Whalley, US Pub ‘660 teach the treatment of epilepsy. See paragraph 91.
Regarding claim 26 and the limitation of cannabidiol (CBD) as choice of cannabinoid for the formulation, US Pub ‘660 states that although its teachings provide a focus on the cannabinoid, dronabinol, a PHOSITA will appreciate the present invention [US Pub ‘660] is applicable to the class of pharmaceutically acceptable cannabinoids, inclusive of cannabidiol (CBD). See paragraph 50.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the primary reference (Whalley US Pub 398) to reduce seizure frequency in a pediatric patient with refractory epilepsy by administering CBD, where per US Pub ‘660, such composition would comprise PEG, propylene glycol and water, (which teaches the art equivalent co-solvents, ethanol, PPG and PEG, prima facie obvious to substitute one for another per MPEP 2144.06), which are known to be orally dosed, and per Pediatric Pharmacotherapy, where such formulation would be alcohol-free for pediatric patients.
The PHOSITA would have had a reasonable expectation of success because it is known in the prior art to treat the claimed pediatric subjects with the cannabinoid, CBD, where formulation of cannabinoid formulations comprising known equivalent substitutes, (per MPEP 2144.06, ethanol a co-solvent substitute equivalent to PPG and PEG, where a formulation consisting essentially of PEG, PG and water are known to be orally administered to pediatric subjects, who require ethanol free formulations.
With regard to claim 31 and the claimed subject suffering from tonic-clonic (aka grand mal) seizures this taught by Whalley. See Whalley US Pub 398 paragraph 22 for the definition of the condition. See paragraph 48 for the reduction in incidence of tonic-clonic seizures.
As required by claim 32 directed to generalized tonic-clonic (grand mal) seizures, treatment of such is noted by Whalley US Pub 398 paragraph 22 and the definition of tonic-clonic. See also paragraphs 47-48.
Regarding claim 35 and the limitation where the refractory epilepsy comprises infantile spasms, it is pointed out that US Pub 660 teaches treatment of muscle spasms, but not necessarily infantile spasms. See paragraph 91. However, it would be obvious to do so as Whalley US Pub 398 teaches the need to treat epileptic seizures during childhood. See paragraph 24. It would be routine for a PHOSITA to optimize treatment of spasms in pediatric refractory epilepsy subjects, including in infants.
Regarding claim 39 reciting synthetically prepared cannabidiol (CBD), it is noted that the isolated CBD would be the same as the synthetically prepared CBD of claims 39 and 56. The fact that one is sourced naturally and later isolated as per Whalley versus synthetically prepared does not change the fact no matter how sourced, CBD is being claimed and taught by the prior art. 7
Regarding claim 43 and the limitations of wherein the composition comprises about 0.01 to about 1 % w/w of alpha-tocopherol, Murty US Pub 583 teaches alpha-tocopherol. See paragraph 55. Murty US Pub 583 teaches the antioxidant is in the range of 0.01-15 wt %; 0.01-12.5 wt %. See paragraphs 58 and 61 respectively.
Regarding claims 78-79 and the limitations of concentrations of PEG and propylene glycol claimed therein, US Pub ‘660 teaches ranges of PEG and propylene glycol that encompass those claimed, (a) propylene glycol from about 0% to about 50%, (b) polyethylene glycol from about 0 to about 50%, see paragraph 7.
Regarding claim 80 and the limitation where the composition comprises 30% to
35% w/w cannabidiol, while not disclosing the claimed percentage amounts of CBD for the treatment of pediatric epilepsy, a PHOSITA would routinely optimize concentrations of CBD in a formulation, based on the known dosage of 300 mg/day of CBD administered to the pediatric patient. See claim 1.
Regarding claim 81, wherein said cannabidiol is prepared synthetically and has a purity greater than 99% w/w, it is noted that the isolated CBD would be the same as the synthetically prepared CBD of claims 39 and 56. The fact that one is sourced naturally and later isolated as per Whalley versus synthetically prepared does not change the fact no matter how sourced, CBD is being claimed and taught by the prior art. With regard to the purity limitation of claim 81 of greater than 99%, while not explicitly recited in Whalley, Whalley US Pub 398 teaches the administration of isolated CBD, which, given the plain meaning of isolated, is taken to mean a purified version of CBD. See paragraphs 56, 69, 76 and 89.
Regarding claim 82 wherein said cannabidiol has a purity greater than 99.5% w/w, while not explicitly recited in Whalley, Whalley US Pub 398 teaches the administration of isolated CBD, which, given the plain meaning of isolated, is taken to mean a purified version of CBD. See paragraphs 56, 69, 76 and 89.
Regarding claim 83 and the limitation of further comprising excipients such as flavoring agent/sweetener, antioxidant/preservative or combinations thereof, US Pub ‘660 teaches use of the stabilizers, i.e. antioxidants/preservatives BHA and BHT. See paragraph 20. See also paragraph 25 listing various antioxidants. Paragraph 64 of US Pub ‘660 teaches flavoring agents, sweeteners or taste masking agents, among other excipients.
Regarding claim 84, similar to claim 26, the combined teachings of US Pub ’660, Whalley US Pub 398 and Pediatric Pharmacotherapy 1996 teach the claimed method of treating the claimed subject in need, with a CBD, PEG, propylene glycol and water composition with taught and overlapping concentrations or CBD concentration range that can be routinely optimized from the art teachings of dosing 300 mg/day of CBD.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response states US Pub 660 fails to address the lack of a composition teaching in Whalley US Pub 398. The Attorney response argues that US Pub 660 does not teach that ethanol is equivalent to/or interchangeable with PPG and/or PEG in the lipid compositions of US Pub 660.
First, the Attorney response states that ethanol is a required solvent in the liquid compositions of US Pub 660, referencing paragraph 2; Examples of Tables 1, 4 and 10; and paragraphs 7 and 152. The Attorney response states PPG, PEG and water are not essential to the compositions of US Pub 660; the Attorney response describes PPG and PEG as co-solvents for use together with the “essential” solvent ethanol and are not described with or as replacements for ethanol.
Contrary to the characterization of ethanol as “essential” to the formulations of US Pub 660, the term is not used to describe ethanol or any other alcohol as essential to the formulations of US Pub 660. Various embodiments of US Pub 660 disclose ethanol containing formulations, but there is no description in the reference to describe it as essential.
In response to the Attorney response that equivalency of the solvents must be taught by US Pub 660, quoting MPEP 2144.06 II. “the equivalency must be recognized in the prior art and cannot be based on applicant’s disclosure or the mere fact that components are functional or mechanical equivalents, the Examiner does not rely upon Applicant’s disclosure but rather a teaching of equivalency from the cited prior art. Paragraph 59 teaches PEG, PPG and ethanol as equivalent Co-Solvents. See below.
Co-Solvents
[0059]. In certain embodiments, the co-solvents are organic. Solvents such as dehydrated alcohol, ethanol, propanol, isopropanol, propylene glycol, polyethylene glycol, and combinations thereof that are pharmaceutically acceptable based on the desired formulation.
Note paragraph 62 with an emphasis on the two claimed co-solvents, PPG and PEG in ranges overlapping the claimed concentrations.
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Second, the Attorney response states the limitation of an ethanol -free liquid composition in claim 26 is contrary to “the teaching of US Pub 660 that ethanol is essential and present in at least about 15% by weight, as recognized by the Examiner.”
The Attorney response states a PHOSITA would find US Pub 660, as a whole for obviousness purposes, teaches away from “alcohol-free liquid compositions” as recited in Applicant’s claim 26. The response references an embodiment of a THC formulation containing 50% ethanol from US Pub 660, where the PHOSITA would have to ignore the “essential” teaching from the reference that include an alcohol (ethanol). The response states the Examiner’s statements are out of context, i.e. US Pub 660 does not teach PEG and/or PPG may replace ethanol.
Contrary to the characterization of ethanol as “essential” to the formulations of US Pub 660, the term essential is not used to describe ethanol/alcohol as essential to the formulations of US Pub 660. US Pub 660 teaches embodiments that comprise ethanol, but also teaches the equivalency of PEG, PPG and ethanol as solvents, see paragraph 59. Various embodiments of US Pub 660 disclose ethanol containing formulations. However, it is noted that Pediatric Pharmacotherapy, teaches, suggests and/or motivates a PHOSITA to consider ethanol/alcohol free formulations for the claimed pediatric patient subject.
Third, the Attorney response states the Examiner has not established the prior art would motivate a PHOSITA to modify US Pub 660’s compositions to arrive at ethanol/alcohol free compositions, with further reference to Pediatric Pharmacotherapy 1996 to remove the ethanol from every composition of US 660. The Attorney response disagrees that a PHOSITA would routinely formulate the Schedule I cannabidiol (CBD) for use in pediatric patients at the time of invention. The Attorney response states the Pediatric Pharmacotherapy reference reflects general knowledge regarding alcohol avoidance in pediatric/children patients and does not translate to Schedule I cannabinoids such as THC, known to be formulated in alcohol.
In response, it is pointed out that in 2013, Porter and Jacobson8 report the use of CBD-enriched cannabis use in pediatric treatment-resistant epilepsy. See title. Porter and Jacobson report, a survey of 19 responses of parents whose children suffered from treatment-resistant epilepsy.
Sixteen (84%) of the 19 parents reported a reduction in their child's seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25–60% seizure reduction. Other beneficial effects included increased alertness, better mood, and improved sleep. See abstract.
Thus prior to the time of invention, a PHOSITA knew of treatment of pediatric seizures with then Schedule I CBD and would predictably treat them with CBD formulations that would be ethanol free as per Pediatric Pharmacotherapy 1996.
Applicant argues claims 31-32, 35, 39, 43, and 78-84 are similarly nonobvious as being dependent upon independent claim 26. As detailed above, claim 26 remains prima facie obvious. Therefore, prior to the time of invention and filing of the priority application, a PHOSITA would have found it obvious to treat pediatric seizures/epilepsy with CBD as claimed.
Conclusion and Correspondence
In summary, no claims are allowed. THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a DIV of USSN 14724351, filed 05/28/2015 and issued as US PAT 11224660. USSN: 14724351 claims earlier domestic priority to PRO 62154660 filed 04/29/2015 and PRO 62004495 filed 05/29/2014.
2 See the #LF formulations of Tables 25 and 26 of the specification
3 US 20110306660A1
4 Buck PharmD, Contributing Editor: A Guide to Pharmaceutical Excipients, Pediatric Pharmacotherapy, Newsletter Children’s Medical Center at the University of Virginia Volume 2 Number 9 September 1996
5 U.S. 2013/0296398 A1
6 Interpreting claim 26 MPEP 2111.03 III., notes the transition phrase “consisting essentially of” limits the scope of the claim to specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention.
7 See MPEP 2112.01 II. "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
8 Porter and Jacobson Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy, Epilepsy & Behavior, Volume 29, Issue 3, 2013, Pages 574-577,
ISSN 1525-5050, https://doi.org/10.1016/j.yebeh.2013.08.037.
(https://www.sciencedirect.com/science/article/pii/S1525505013004629)
