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 .
Specification
The use of the terms Cremophor EL, Solutol HS 15, Tween 40, Tween 60, and Tween 80, which are trade names or a marks used in commerce, have been noted in this application. Specifically, the trade names or marks appear on page 23 lines 26 – 35, page 24 lines 1 – 5, page 29 lines 13 – 33, and page 30 lines 1 – 36. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 2 – 4, and 8 – 10 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.
Claim 2 recites the limitation "the total daily dose" in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claim 3 recites the limitation "the total clinically administered PTSD scale (CAPS-5) score" in lines 1 – 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites the limitation "the CAPS-5 score" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the Post-traumatic Stress Disorder Checklist (PCL-5) score" in lines 1 – 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the General Anxiety Disorder (GAD-7) score" in lines 1 – 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "the Beck Depression Inventory (BDI) score" in lines 1 – 2. There is insufficient antecedent basis for this limitation in the claim.
Moreover, claims 3 – 4, and 8 – 10 recite different assessment instruments without reciting which versions of each of the assessment instruments and what cut off values are within the scope of the claim. Additionally, one of ordinary skill in the art would not be reasonably appraised to which version of the assessment instruments are required for the method. For instance, the PCL-5 checklist recited in claim 8 has different versions depending on whether the patient is in the military or not. Furthermore, the Beck Depression Inventory assessment tool three different versions. As a consequence, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically one of ordinary skill in the art would not be reasonably apprised of whether the claims direct to generic measures of post-traumatic stress disorders (PTSD) or to the specific assessment instruments as recited in claims 3 – 4, and 8 – 10.Therefore, given the uncertainty around the versions of the assessment instruments claims 3 – 4, and 8 – 10 are rejected under 35 U.S.C. 112(b).
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.
Claims 2, 8, 15, 19, 21 – 22, 26, 33, 37 – 38, 43, 48, 50, 52, and 70 are rejected under 35 U.S.C. 103 as being unpatentable over Elms et. al. ((2019), Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series, 25, 392 – 397) in view of International Publication Number WO 2020/234650 A1 to Betty (Betty’650) as evidenced by Kolliphor EL. ((2026, May 29th). In Wikipedia. Wayback Machine. https://web.archive.org/web/20131005084822/https://en.wikipedia.org/wiki/Kolliphor_EL), and Polysorbate 80. ((2026, May 29th). In Wikipedia. Wayback Machine. https://web.archive.org/web/20180308023201/https://en.wikipedia.org/wiki/Polysorbate_80).
Regarding claims 2, 8, 15, 19, 21 – 22, 26, 33, 37 – 38, 43, 48, 50, 52, and 70, Elms et. al. teach that post-traumatic stress disorder (PTSD) is a relatively common psychiatric condition with a lifetime prevalence of 6.1% in the United States. See page 392 column 1 paragraph 1. See claim 2 limitation for a method of treating PTSD. Moreover, Elms et. al. teach that PSTD often presents in clusters of symptoms, including the re-experiencing of traumatic events through intrusive memories and nightmares, avoidance of certain distressing factors, and alterations in mood, level of arousal, and cognition. See page 392 column 1 paragraph 1 and column 2 paragraph 2. Furthermore, Elms et. al. teach that the development of additional treatment agents is important because current medications, including selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, antiadrenergic agents, and second generation antipsychotics, have questionable efficacy and often carry significant undesirable side-effect profiles. See page 393 column 1 paragraph 1. Thus, Elms et. al. suggest that need for additional therapeutic agents for the treatment of PTSD.
Additionally, Elms et. al. teach that cannabidiol (CBD) was shown to be helpful for decreasing anxiety through a simulated public speaking test at doses of 300–600 mg in single dose studies. See page 393 column 1 paragraph 3. See claim 15 limitation for a total daily dose of about 100 mg/day to 2000 mg/day. Likewise, Elms et. al. teach one case where the administration of 12–37 mg of oral CBD daily was associated with a reduction in anxiety symptoms and sleep disturbances in a 10-year-old patient with PTSD due to sexual trauma. See page 393 column 1 paragraph 5. Specifically, Elms et. al. teach a retrospective chart review of adult psychiatric patients with a diagnosis of PTSD who consented to treatment with CBD as augmentation to routine psychiatric treatment at an outpatient psychiatric clinic. See page 393 column 2 paragraph 3. Moreover, in this study, Elms et. al. teach that after the initial baseline assessment, PCL-5 assessments were completed by patients every 4 weeks to monitor changes in the severity of PTSD symptoms. See page 393 column 2 paragraph 4. See claim 8 limitation for the total clinically administered PTSD scale (CAPS-5) score. Additionally, Elms et. al. teach that four of the 11 patients received CBD as an oral capsule only, one patient only received CBD in the form of an oral liquid spray, and six patients received both forms of CBD either concurrently or sequentially over the course of the study. See page 393 column 2 paragraph 5. See claim 2 limitation for oral administration. See claim 26 limitation where the at least one cannabinoid is a non-psychoactive cannabinoid, selected from the group consisting of cannabidiol (CBD). See claim 70 limitation for wherein the pharmaceutical composition is administered as a tablet, a capsule.
Moreover, Elms et. al. teach that the mean total starting dose of CBD (liquid or capsular or both) was 33.18 mg (standard deviation [SD] = 23.34). See page 394 column 1 paragraph 2. Likewise, Elms et. al. teach that the mean total dose of CBD prescribed at the 8-week follow-up appointment at the conclusion of the study period was 48.64 mg (range: 2–100). See page 394 column 1 paragraph 2. See claim 2 limitation for a method where the total daily dose of cannabinoid administered to the subject is at least 50 mg/day. See claim 15 limitation for a total daily dose of about 100 mg/day to 2000 mg/day. See claim 19 limitation for a total daily dose of about 50 mg/day to 100 mg/day. See claim 21 limitation for total daily dose of cannabinoids is administered to the subject in a single daily dose.
Furthermore, Elms et. al. teach that the dose of CBD was adjusted at each 4-week appointment based on the patient’s presentation and experience with most patients having received an increase in the dose of CBD because treatment was provided to maximize PTSD symptom reduction, which seemed to be directly correlated with dose. See page 394 column 1 paragraph 2. Likewise, Elms et. al. teach that after 4 weeks of treatment, 91% (n = 10) of patients from this group reported a decrease in symptoms of PTSD with PCL-5 scores declining from 51.82 to 40.73 (SD = 12.92), which is a decrease of 21%. See page 395 column 1 paragraph 2. See claim 8 limitation where the Post-traumatic Stress Disorder Checklist (PCL-5) score in the subject is reduced by the administration of the pharmaceutical composition to the subject, as compared to the subject's pre-treatment score.
Regarding claim 2 limitation for a method where the total daily dose of cannabinoid administered to the subject is at least 50 mg/day; Elms et. al. teach that the mean total dose of CBD prescribed at the conclusion of the study period was 48.64 mg (range: 2–100). Additionally, as taught above, the patients were given a single dosage a day. Thus teaching of 48.64 mg is close to the limitation of 50 mg/ day. Therefore, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). See MPEP 2144.05 (I).
Regarding claim 15 limitation for a total daily dose of about 100 mg/day to 2000 mg/day; Elms et. al. teach that the mean total dose of CBD prescribed at the conclusion of the study period was 48.64 mg (range: 2–100). Additionally, as taught above, the patients were given a single dosage a day. Moreover, Elms et. al. taught that the dose of CBD was adjusted based on the patient’s presentation and experience to maximize PTSD symptom reduction, which seemed to be directly correlated with dose. Thus the teaching of the range of 2 – 100 mg of CBD over laps with the lower range of claim 15. Hence in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05 (I).
Regarding claim 19 limitation for a total daily dose of about 50 mg/day to 100 mg/day; Elms et. al. teach that the mean total dose of CBD prescribed at the conclusion of the study period was 48.64 mg (range: 2–100). Additionally, as taught above, the patients were given a single dosage a day. Moreover, Elms et. al. taught that the dose of CBD was adjusted based on the patient’s presentation and experience to maximize PTSD symptom reduction, which seemed to be directly correlated with dose. Thus the teaching of the range of 2 – 100 mg of CBD over laps with the range of claim 19. Hence in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05 (I).
However, Elms et. al. fail to teach a method where the pharmaceutical composition, which would be the capsule in above study, comprises at least one cannabinoid, at least one oil; at least one hydrophilic surfactant; at least one co-surfactant; and less than 1 wt% water. See claim 2.
Nevertheless, Betty’650 teaches compositions comprising cannabidiol (CBD) and one or more terpene molecules within a carrier. See page 1 paragraph 0002. Moreover, Betty’650 teaches that the bioavailability of oral cannabinoids is typically reduced to about 6 % which means that high amounts of compounds must be given in order to reach a therapeutic efficacy. See page 15 paragraph 0056. Furthermore, Betty’650 teaches that even with higher doses, cannabinoids are partially broken down within the stomach before absorption can occur in first-pass metabolism. See page 15 paragraph 0056. Thus, Betty’650 teaches that cannabinoids have proven to be difficult to use because the options typically require smoking, which introduces the THC compound, or nonuse in oral forms, which many find undesirable because of the low bioavailability. See page 15 paragraph 0056. Additionally Betty’650 teach that increasing bioavailability is a key issue as it allows a reduction in the total lipophilic agents, while either maintaining the total concentration of the agents within the body or blood stream, or allows for a total increase in the blood plasma concentration levels within the body. See page 22 paragraph 0078. Furthermore, Betty’650 teach that preventing first-pass metabolism, increasing the rate of uptake, or both will increase the bioavailability of the cannabinoids and terpene molecules of the present formulations. See page 22 paragraph 0078.
Betty’650 teaches a preferred embodiment for a composition comprising at least 5% cannabidiol, at least 2% β-caryophyllene, at least 2% linalool, at least one emulsifying agent comprising between 50% and 80% by weight of the composition, at least one oil comprising between 1% and 10% by weight of the composition, at least one cosurfactant comprising between 1% and 10% by weight of the composition, and at least one antioxidant comprising between 1% and 10% of the composition, wherein the composition is suitable for oral dosage to a mammal. See page 3 paragraph 0009. See claim 2 limitation for the pharmaceutical composition comprising at least one cannabinoid, at least one oil; at least one hydrophilic surfactant; at least one co-surfactant; and less than 1 wt% water. See claim 33 limitation where the composition comprises between about 0.1 and 20 wt% of at least one cannabinoid. See claim 37 limitation where the composition comprises between about 5 and 10 wt% of at least one cannabinoid. See claim 38 limitation where the composition comprises between 0.5 and 20 wt% of oils. See claim 52 limitation where the composition comprises between 1 and 50 wt% of co-surfactants.
Furthermore, Betty’650 teaches another embodiment, where the emulsifying agent is a combination of Kolliphor EL, Tween 80 and Phosal 50 PG, wherein the cosurfactant is propylene glycol and wherein the oil is an MCT oil, and wherein the antioxidant is vitamin E. See page 5 paragraph 0017. Moreover, Betty’650 teaches in a further embodiment that the composition comprises between 30% and 40% Kolliphor EL, between 25% and 35% Tween 80, and between 5% and 10% Phosal 50 PG, between 5% and 10% of the co-surfactant as propylene glycol, and between 1% and 5% of the oil as an MCT oil, and wherein the antioxidant is between 1% and 5% and is vitamin E. See page 6 paragraph 0021. See claim 43 limitation where the composition comprises between 30 and 85 wt% of hydrophilic surfactants. See claim 48 limitation where the composition comprises a first hydrophilic surfactant having a range of about 30 and 50 wt % and a second hydrophilic surfactant having a range of about 10 and 30 wt %. See claim 50 limitation where the composition comprises a first hydrophilic surfactant having a range of about 45 and 50 wt %, a second hydrophilic surfactant having a range of about 10 and 12 wt %, and a third hydrophilic surfactant having a range of about 10 and 12 wt %. Moreover, Betty’650 teaches that for treatments of 200, 300, or 400 mg, multiple oral dosage forms can be consumed, i.e. 2, 3, or 4 pills or gel caps, to reach the necessary dosage. See page 33 paragraph 0118. See claim 22 limitation where the total daily dose of cannabinoids is administered to the subject as a split daily dose.
Regarding claim 2 limitation for a method where the pharmaceutical composition comprising less than 1 wt% water. Betty’650 teaches a preferred composition comprising at least 5% cannabidiol, at least 2% β-caryophyllene, at least 2% linalool, at least one emulsifying agent comprising between 50% and 80% by weight of the composition, at least one oil comprising between 1% and 10% by weight of the composition, at least one cosurfactant comprising between 1% and 10% by weight of the composition, and at least one antioxidant comprising between 1% and 10% of the composition, which is silent on the inclusion of water in the composition. Thus Betty’650 suggest a composition comprising 0 wt % of water which is less than 1 wt%.
Regarding claims 33 and 37 limitation where the composition comprises between about 0.1 and 20 wt% of at least one cannabinoid; and where the composition comprises between about 5 and 10 wt% of at least one cannabinoid; Betty’650 taught a composition comprising at least 5% cannabidiol. Thus the teaching of at least 5% cannabidiol over laps with the lower range of claims 33 and 37. Hence in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05 (I).
Regarding claim 38 limitation where the composition comprises between 0.5 and 20 wt% of oils; Betty’650 taught a composition comprising between 1% and 5% of the oil. Thus the teaching of at least between 1% and 5% of the oil over laps with the range of claim 38. Hence in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05 (I).
Regarding claims 43, 48, 50, and 52 limitation where the composition comprises between 30 and 85 wt% of hydrophilic surfactants; where the composition comprises a first hydrophilic surfactant having a range of about 30 and 50 wt % and a second hydrophilic surfactant having a range of about 10 and 30 wt %; where the composition comprises a first hydrophilic surfactant having a range of about 45 and 50 wt %, a second hydrophilic surfactant having a range of about 10 and 12 wt %, and a third hydrophilic surfactant having a range of about 10 and 12 wt %; and where the composition comprises between 1 and 50 wt% of co-surfactants; Betty’650 taught a preferred composition comprising between 30% and 40% Kolliphor EL, between 25% and 35% Tween 80, and between 5% and 10% of the co-surfactant as propylene glycol.
Given that Kolliphor EL, Tween 80, are non-ionic surfactants, as evidenced by their respective Wikipedia pages, and propylene glycol is a surfactants; Betty’650 teaches a composition comprising three surfactants at ranges from 5 – 40 % which over laps with ranges of claims 43, 48, 50, and 52. Hence in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05 (I). Hence in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05 (I).
Therefore, it would have been obvious before the effective filing date of the instant application to modify the method of Elms et. al., for a method of treating PTSD comprising administering cannabinoid as an oral capsule in view of Betty’650, that is for an oral capsule comprising at least one cannabinoid, at least one oil; at least one hydrophilic surfactant; at least one co-surfactant; and less than 1 wt% water. One of ordinary skill in the art would have been motivated to make this modification to improve efficacy and reduce undesirable side-effect profiles. One of ordinary skill in the art would have had a reasonable expectation of success because techniques for modifying pharmaceutical formulations for improved oral bioavailability are well known in the art.
Claims 71, 74 – 76 are rejected under 35 U.S.C. 103 as being unpatentable over Elms et. al. ((2019), Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series, 25, 392 – 397) in view of International Publication Number WO 2020/234650 A1 to Betty (Betty’650).
The teachings of Elms et. al. and Betty’650 as they relate to claim 2, from which claims 71, 74 – 76 depend, are given previously in this office action and are fully incorporated here.
However, Elms et. al. and Betty’650 is silent about a method where the pharmaceutical composition is in the form of a soft gel capsule for administration orally as a split daily dose and provides a total daily dose of CBD of about 600 mg/day to about 2000 mg/day. See claim 71. Additionally, Elms et. al. and Betty’650 is silent about a method where the total daily dose of CBD increases from 200 mg/day CBD to 400 mg/day CBD after 1 week of treatment. See claim 74. Moreover, Elms et. al. and Betty’650 is silent about a method where the total daily dose of CBD increases from 200 mg/day CBD to 400 mg/day CBD after 2 weeks of treatment. See claim 75. Furthermore, Elms et. al. and Betty’650 is silent about a method where the total daily dose of CBD increases from 400 mg/day CBD to 600 mg/day CBD after 2 weeks of treatment. See claim 76.
Nevertheless, as taught above, Elms et. al. teach that PSTD often presents in clusters of symptoms, including the re-experiencing of traumatic events through intrusive memories and nightmares, avoidance of certain distressing factors, and alterations in mood, level of arousal, and cognition. See page 392 column 1 paragraph 1 and column 2 paragraph 2. Furthermore, Elms et. al. teach that the development of additional treatment agents is important because current medications, including selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, antiadrenergic agents, and second generation antipsychotics, have questionable efficacy and often carry significant undesirable side-effect profiles. Moreover, Elms et. al. teach that cannabidiol (CBD) was shown to be helpful for decreasing anxiety through a simulated public speaking test at doses of 300–600 mg in single dose studies. See page 393 column 1 paragraph 3. And, Elms et. al. teach that the mean total starting dose of CBD (liquid or capsular or both) was 33.18 mg (standard deviation [SD] = 23.34). See page 394 column 1 paragraph 2.
Likewise, Elms et. al. teach that the mean total dose of CBD prescribed at the 8-week follow-up appointment at the conclusion of the study period was 48.64 mg (range: 2–100). Elms et. al. teach that the dose of CBD was adjusted at each 4-week appointment based on the patient’s presentation and experience with most patients having received an increase in the dose of CBD because treatment was provided to maximize PTSD symptom reduction, which seemed to be directly correlated with dose. See page 394 column 1 paragraph 2. Moreover, Betty’650 teaches that for treatments of 200, 300, or 400 mg, multiple oral dosage forms can be consumed, i.e. 2, 3, or 4 pills or gel caps, to reach the necessary dosage. See page 33 paragraph 0118.
Therefore it would have been obvious to one of ordinary skill, in an attempt to treat PTSD, to use the prior art teachings of both Elms et. al. and Betty’650 the art to try and treat patients suffering with PTSD by using the dosing amounts and regiments in claims. One of ordinary skill in the art would have been modification because the prior art of Elms et. al. taught the CBD was useful in ranges from 2 – 600 mg amounts for overlapping psychiatric disorders. Moreover, the prior art taught of Elms et. al. taught a frequency regimen of at least 1 dose a day with monitoring every 4 weeks. Likewise, the prior art of Betty’650 taught the ability to formulate oral CBD compositions into multiple oral dosages that can be consumed a 2, 3, or 4 pills or gel caps, to reach the necessary dosage total daily dose for a particular patient. Thus given that the skill level of one of ordinary skill in the pharmaceutical arts is relatively high it would have been within the purview of such artisan to modifying the doses and dosing frequency in an attempt to maximize PTSD symptom reduction, since the prior art of Elms et. al. taught that there seemed to be a direct correlation between a reduction in PTSD symptoms and dose. Moreover, it would have been within the purview of such artisan to recognize when and how to adjust a patients dosage and dosing regimen.
Claims 3 – 4, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Elms et. al. ((2019), Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series, 25, 392 – 397) and International Publication Number WO 2020/234650 A1 to Betty (Betty’650) as applied to claims 2, 8, 15, 19, 21 – 22, 26, 33, 37 – 38, 43, 48, 50, 52, 70 – 71, and 74 – 76 above, and further in view of Mughal et. al. ((2020), A systematic review of validated screening tools for anxiety disorders and PTSD in low to middle income countries, BMC Psychiatry, 20, 1 – 18) and Franklin et. al. ((2016), Examining potential overlap of DSM-5 PTSD criteria D and E, Psychiatry Research, 246, 250 – 254).
The teachings of Elms et. al. and Betty’650 as they relate to claim 2, from which claims 3 – 4, and 9 depend, are given previously in this office action and are fully incorporated here.
Now while the prior art of Elms et. al. taught a method for treating PTSD where Post-traumatic Stress Disorder Checklist (PCL-5) score is used, neither the prior art of Elms et. al. or Betty’650 teach a method where the total clinically administered PTSD scale (CAPS-5) score in the subject is reduced by the administration of the pharmaceutical composition to the subject, as compared to the subject's pre-treatment score. See claim 3. Moreover, the prior art of Elms et. al. and Betty’650 fails to teach a method where the CAPS-5 score for PTSD symptom cluster B, cluster C, cluster D, and/or cluster E in the subject is reduced by the administration of the pharmaceutical composition to the subject, as compared to the subject's pre-treatment score. See claim 4. Furthermore, neither the prior art of Elms et. al. or Betty’650 teach a method where the General Anxiety Disorder (GAD-7) score is reduced by the administration of the pharmaceutical composition to the subject, as compared to the subject's pre-treatment score. See claim 9.
Nevertheless, Mughal et. al. teach that mental health disorders, including anxiety and posttraumatic stress disorder (PTSD) are among the leading contributors to global disability adjusted life years, comprising five of the top twenty contributing disorders. See page 2 column 1 paragraph 1. Mughal et. al. teach that Anxiety and PTSD in low to middle income countries (LMICs) are highly prevalent and require further study given that access to care is hindered by availability and stigma. See page 2 column 1 paragraph 2. Thus Mughal et. al. teach the Use of brief screening tools have been proposed as a way to improve identification and management of mental health problems, and may be useful in LMICs, especially among populations with elevated risk (e.g., pregnant women, refugees/displaced persons, and youth) within LMIC communities. See page 2 column 1 paragraph 2. Moreover, Mughal et. al. teach that despite multiple screening instruments for CMDs, there are significantly fewer screening instruments for anxiety and PTSD that have been validated in LMIC populations. See page 2 column 2 paragraph 3. Thus, Mughal et. al. teach a study to systematically review screening tools for anxiety and PTSD within LMIC populations. See page 2 column 2 paragraph 2.
Subsequently, Mughal et. al. teach that after systematically searched four databases (MEDLINE, EMBASE, Global Health and PsychINFO) from inception to April 22, 2020 reference standards included unstructured clinical diagnostic interviews as well as structured clinical interviews including the Mini International Neuropsychiatric Interview (MINI and MINI-KID), Structured Clinical Interview for DSM (SCID, SCID-1 and NetSCID), Composite International Diagnostic Interview (CIDI and CIDI-PHCV), Clinical Interview Schedule-Revised (CIS-R), Psychiatric Assessment Schedule (PAS), Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS and K-SADS-PL) and Clinician-Administered PTSD Scale (CAPS and CAPS-5). See page 3 column 1 paragraph 1. See claim 3 limitation CAPS-5. Furthermore, Mughal et. al. teach the most commonly used tools to screen for generalized anxiety disorder were the Kessler-10 (K-10) and the Generalized Anxiety Disorder-7 item scale (GAD-7), totaling seven and six validations respectively. See page 9 column 2 paragraph 1. Additionally, Mughal et. al. teach that GAD-7 reported some of the highest sensitivities for detection of generalized anxiety disorder. See page 7 column 2 paragraph 3.
Additionally, Mughal et. al. teach PTSD had far fewer validations with a wide range of tools receiving between one and three validations, similar to the screening tools validated for both anxiety and depression. See claim 9 limitation GAD-7. Now while, Mughal et. al. does not teach the validated use of GAD-7 for detecting PTSD; Mughal et. al. does teach the validation of GAD-7 as a general measure for anxiety. Moreover, the prior art of Mughal et. al. does teach the limitation of screening PTSD, since PTSD had far fewer validations with a wide range of tools. Thus given that the skill level of one of ordinary skill in the pharmaceutical arts is relatively high it would have been within the purview of such artisan to have known all of the different anxiety measuring tools available within the art and the include the either the GAD-7 or the well-established CAPS-5 in a method for treating PTSD.
However, the prior art of Mughal et. al. is silent about a method where the CAPS-5 score for PTSD symptom cluster B, cluster C, cluster D, and/or cluster E in the subject is reduced by the administration of the pharmaceutical composition to the subject, as compared to the subject's pre-treatment score. See claim 4.
Nevertheless, Franklin et. al. teach that the release of the Diagnostic and Statistical Manual, Fifth Edition (DSM-5; American Psychiatric Association, 2013) has garnered much attention, as it includes significant changes across various psychiatric disorders at both the nosology and symptom levels. See page 250 column 1 paragraph 1. Specifically, Franklin et. al. teach that a new chapter was created and titled “Trauma-and Stress-Related Disorders” to capture diagnoses that emerge following exposure to traumatic sequela. See page 250 column 1 paragraph 2. Moreover, Franklin et. al. teach that Changes also were made to the PTSD symptom structure based on converging factor analytic research which supported a four, rather than three-factor structure. See page 250 column 1 paragraph 3. Additionally, Franklin et. al. teach that negative alterations in cognition and mood were added as a new criterion D cluster and several new symptoms characteristic of general distress and dysphoria. See page 250 column 2 paragraph 1. Furthermore, Franklin et. al. teach that these new DSM-5 criterion D symptoms, specifically D2, D3, and D4, were added because they are characteristic of the cognitive errors, negative thinking, and negative emotions often seen in individuals with a PTSD diagnosis. See page 250 column 2 paragraph 1. See claim 4 limitation where the CAPS-5 score for PTSD symptom cluster D in the subject is reduced by the administration of the pharmaceutical composition to the subject.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the method of Elms et. al. in view of Betty’650, for a method of treating PTSD comprising administering cannabinoid as an oral capsule comprising at least one cannabinoid, at least one oil; at least one hydrophilic surfactant; at least one co-surfactant; and less than 1 wt% water, further in view of Mughal et. al. to use either CAPS-5 or GAD-7 as assessment tools to assess the efficacy of the treatment in view of Franklin et. al. where the CAPS-5 score for PTSD symptom cluster D in the subject is reduced. One of ordinary skill in the art would have been motivated to make this modification to validate screening instruments for PTSD in LMIC populations. Moreover, one of ordinary skill in the art would have been motivated to include the CAPS-5 score for PTSD symptom cluster D because cognitive errors, negative thinking, and negative emotions often seen in individuals with a PTSD diagnosis. One of ordinary skill in the art would have had a reasonable expectation for success because both CAPS-5 and GAD-7 are structured clinical interviews useful for assessing anxiety and PTSD.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Elms et. al. ((2019), Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series, 25, 392 – 397) and International Publication Number WO 2020/234650 A1 to Betty (Betty’650) as applied to claims 2, 8, 15, 19, 21 – 22, 26, 33, 37 – 38, 43, 48, 50, 52, 70 – 71, and 74 – 76 above, and further in view of Palmer et. al. ((2014), Psychometric Properties of the Beck Depression Inventory-II for OEF/OIF Veterans in a Polytrauma Sample, Military Medicine, 179, 879 – 884).
The teachings of Elms et. al. and Betty’650 as they relate to claim 2, from which claim 10 depends, are given previously in this office action and are fully incorporated here.
Now while the prior art of Elms et. al. taught a method for treating PTSD where the Post-traumatic Stress Disorder Checklist (PCL-5) score is used, neither the prior art of Elms et. al. or Betty’650 teach a method where the Beck Depression Inventory (BDI) score is reduced by the administration of the pharmaceutical composition to the subject, as compared to the subject's pre-treatment score. See claim 10.
Nevertheless, Palmer et. al. teach that the term “polytrauma” has been used by the Department of Veterans Affairs to describe injuries to multiple body parts and organs occurring as a result of blast-related wounds seen in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). See page 879 column 1 paragraph 1. Moreover, Palmer et. al. teach that traumatic brain injury (TBI) frequently occurs in combination with other disabling conditions including post-traumatic stress disorder (PTSD), depression, and other mental health/medical conditions. See page 879 column 1 paragraph 1. And, Palmer teach that depression is a commonly reported problem for both outpatient and inpatient populations following a TBI. See page 879 column 1 paragraph 2. Moreover, Palmer et. al. teach that the Beck Depression Inventory (BDI) and its latest revision, the Beck Depression Inventory-II (BDI-II), have been widely studied with a variety of different populations. See page 879 column 2 paragraph 1.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the method of Elms et. al. in view of Betty’650, for a method of treating PTSD comprising administering cannabinoid as an oral capsule comprising at least one cannabinoid, at least one oil; at least one hydrophilic surfactant; at least one co-surfactant; and less than 1 wt% water, further in view of Palmer et. al. to use BDI as the assessment tools to assess the efficacy of the treatment. One of ordinary skill in the art would have been motivated to make this modification because TBI frequently occurs in combination PTSD and depression especially in the context of active military personnel. One of ordinary skill in the art would have had a reasonable expectation for success because (BDI) have been widely studied with a variety of different populations.
Conclusion
Claims 2 – 4, 8 – 10, 15, 19, 21 – 22, 26, 33, 37 – 38, 43, 48, 50, 52, 70 – 71, and 74 – 76 are rejected.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
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