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 .
Election/Restrictions
Applicant's election with traverse of claims 1-12 in the reply filed on 06/17/2026 is acknowledged. The traversal is on the ground(s) that the composition recited in the claims 13-15 is especially suitable for the method recited in the claims 1-12. This is not found persuasive because pharmaceutical compositions comprising pure cannabidiol are generally understood in the art to be useful for applications outside of mental and psychotic disorders like schizophrenia (examples: epilepsy) (see [19] of Davis et al. in US 20190201347 A1, as cited in IDS submitted on 10/11/2023). This is not found persuasive because the instant application is a national stage entry filed under 35 U.S.C. 371 and is therefore subject to lack of unity practice, see MPEP 1893.03(d). The test is whether or not special technical features can be established. It is noted that inventions listed as Groups I and II do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, the common feature between the groups does not provide a contribution over the prior art, and, thus cannot be a special technical feature as set forth in paragraph 4 of the previous Office Action.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statement filed 06/30/2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because the copy of reference 2, Stabilnih et al (“Homogenization and Characterization of Cannabidiol (CBD) Isolates”, Mat Tech, 2018, 1 page), that was submitted is illegible. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a) and MPEP 609.04(a)(II).
Claim Objections
Claim 1 objected to because of the following informalities: in lines 1 and 3, “in vitro” should read “in vitro” for convention. Appropriate correction is required.
Claim 3 objected to because of the following informality: in line 1, there should be a comma after “claim 1”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-12 are rejected under 35 USC 101 because the claimed invention is directed to an abstract idea without significantly more. The claims will be analyzed below according to MPEP 2106.
Inquiry 1: Is the claim directed to a statutory category of invention (process, machine, manufacture, or composition of matter)?
Claims 1-12 are drawn to a process of determining the efficacy of a treatment of a subject having a mental disorder by administration of cannabidiol.
Inquiry 2A Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Claim 1 recites “determining in vitro a level of cannabidiol in a sample from said subject having said mental disorder, wherein said treatment is considered efficient if”. Both “determining” and ‘considering’ are mental processes that can be performed in the human mind and/or with pen and paper, which is considered an abstract idea. Claims 2-12 are dependent on claim 1 and therefore also are drawn to this abstract idea. See MPEP 2106.04(a)(2)(III).
Inquiry 2A Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
Claims 1-12 do not integrate the judicial exceptions into a practical application.
Regarding claim 1, because there is nothing that prefaces or follows the determination and ‘considered’ step, there is no practical application of the judicial exceptions.
Regarding claims 2-12: claims 2-9 and 12 pertain to the type of mental disorder that is being treated, the parameters of the determination step, or the target level of cannabidiol in the patient, but none of these additional recitations apply the judicial exceptions to a practical application because nothing occurs after the determination/’considered’ step; at best, this amounts to mere instructions to apply the judicial exception. See MPEP 2106.05(f). Claims 10-11 pertain to an additional adjustment step, where the treatment being monitored is adjusted to increase or decrease the dose of cannabidiol based on the level of cannabidiol in the subject as compared to a ‘target’ value of 25 µL/L; as worded, the steps in claims 10-11 read as optional, which is insufficient for amounting to a practical application. Regarding claim 10, if a subject was determined to have a level of cannabidiol that is greater than 25 g/mL, then nothing would occur and the judicial exception is not integrated into a practical application; similarly, regarding claim 11, if a subject had a level of cannabidiol that is lower than 25 g/mL, then nothing would occur and the judicial exception is again not integrated into a practical application. MPEP 2106.04(d)(I).
Inquiry 2B: Does the claim recite additional limitations that amount to significantly more than the judicial exception?
No, claims 1-12 do not amount to significantly more than the judicial exception.
Regarding claim 1, because there is nothing that prefaces or follows the determination and ‘considered’ step, the claim does not amount to significantly more than the judicial exceptions. Furthermore, the limitations of claim 1 are well-understood, routine, and conventional in the arts: Makiol et al. (Non-Patent Literature, Australian & New Zealand Journal of Psychiatry, Vol. 53, No. 3, pgs 262-265, 2018, as cited in the IDS submitted on 10/11/2023) teaches a method of monitoring a treatment of schizophrenia by measuring the concentration of cannabidiol in a subject and making adjustments of the treatment to lead to improved clinical outcomes (see pg. 1 middle column).
Regarding claims 2-9 and 12, these claims are being interpreted to amount to mere instructions to apply the judicial exceptions, as discussed above in Step 2A Prong Two. See MPEP 2106.05(f). Regarding claims 10-11, because these limitations read as optional, they are insufficient for amounting to significantly more that the judicial exception; as worded, they amount to, at best, mere instructions to apply the judicial exception. See MPEP 2106.05(f). Furthermore, the concepts recited in claims 2-12 are well-understood, routine, and conventional in the arts: Makiol et al. (Non-Patent Literature, Australian & New Zealand Journal of Psychiatry, Vol. 53, No. 3, pgs 262-265, 2018, as cited in the IDS submitted on 10/11/2023) teaches a method of monitoring a treatment of schizophrenia by measuring the concentration of cannabidiol in a subject (which is at least 25 or 30 µg/mL) 12 hours after treatment and making adjustments of the dosage of cannabidiol (increasing from 500 mg to 750 mg, orally, 2x daily) treatment to lead to improved clinical outcomes (see pg. 1 middle column); Pigliasco et al. (Non-Patent Literature, Molecules, Vol. 25, 2020, pgs. 3608-3619) teaches a method of determining levels of cannabidiol in subjects using liquid chromatography tandem mass spectrometry; Hiemke et al. (Non-Patent Literature, Pharmacopsychiatry, Vol. 44, 2011, pgs. 195-235) teaches a method of drug treatment monitoring that involves monitoring drug levels in a subject and increasing/decreasing the dosage of drugs based on a target therapeutic concentration, and a method of waiting 7 days before determining the level of cannabidiol for the first time. See MPEP 2106.05(d).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5, 9, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Makiol et al. (Non-Patent Literature, Australian & New Zealand Journal of Psychiatry, Vol. 53, No. 3, pgs 262-265, 2018, as cited in IDS submitted on 10/11/2023). For clarity, citations to Makiol made in this office action utilize a more legible copy that is provided.
Regarding claim 1, Makiol teaches an in vitro method for determining efficacy of a treatment of a subject having a mental disorder by administration of cannabidiol (first page left column first paragraph) (we report a patient with treatment-resistant schizophrenia remitting following adjunctive CBD), the method comprising determining in vitro a level of cannabidiol in a sample from said subject having said mental disorder (First page, middle column second paragraph) (added oral CBD… (blood level 12 hours after intake: 90–107 ng/mL) or increasing CBD… (121-144ng/mL)), wherein said treatment is considered efficient if the level of cannabidiol is at least 25 µg/l (First page, middle column second paragraph) (added oral CBD… (blood level 12 hours after intake: 90–107 ng/mL or increasing CBD… (121-144ng/mL), voices gradually ceased… negative symptoms further improved). Note that “ng/mL” is synonymous with “µg/l”.
Regarding claim 2, Makiol teaches the method of claim 1 as rejected above, wherein said cannabidiol level is at least about 30 µg/l (First page, middle column) (blood level 12 hours after intake: 90–107 ng/mL or increasing CBD… (121-144ng/mL), voices gradually ceased… negative symptoms further improved). Note that “ng/mL” is synonymous with “µg/l”.
Regarding claim 3, Makiol teaches the method of claim 1 as rejected above, wherein said method is useful for optimizing and/or monitoring the efficacy of said treatment (First page, middle column) (We therefore added oral CBD 500 mg… resulting in markedly softened, but still continuous acoustic hallucinations and reduced negative symptoms).
Regarding claim 4, Makiol teaches the method of claim 1 as rejected above, wherein said mental disorder is a psychotic disorder (first page, left column, second paragraph) (woman with a 21-year history of schizophrenia was admitted).
Regarding claim 5, Makiol teaches the method of claim 4 as rejected above, wherein said psychotic disorder is selected from the group consisting of schizophrenia, delusional disorder, and schizoaffective disorder (first page, left column, second paragraph) (woman with a 21-year history of schizophrenia was admitted).
Regarding claim 9, Makiol teaches the method of claim 1 as rejected above, wherein said cannabidiol is administered to the subject at one of: a dose of 5 mg to 1200 mg per day, or a dose of 8 to 12 mg per kg body weight per day (First page, middle column) (oral CBD 500 mg twice daily).
Regarding claim 12, Makiol teaches the method of claim 1 as rejected above, wherein a dose of cannabidiol, which is to be administered, is to be administered intravenously, orally, sublingually, nasally, rectally, topically or by inhalation, or wherein a dose of cannabidiol, which is to be administered, is to be administered as a capsule (First page, middle column) (oral CBD 500 mg twice daily).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Makiol et al. (Non-Patent Literature, Australian & New Zealand Journal of Psychiatry, Vol. 53, No. 3, pgs 262-265, 2018, as cited in IDS submitted on 10/11/2023) in view of Pigliasco et al (Non-Patent Literature, Molecules, Vol. 25, 2020, pgs. 3608-3619).
Regarding claim 6, Makiol teaches the method of claim 1 as rejected above.
Makiol is completely silent to the method in which cannabidiol (CBD) levels are determined.
In the analogous art of developing strategies to monitor CBD levels in patients being treated with CBD, Pigliasco teaches a method of determining CBD concentrations in patient samples using a liquid chromatography tandem mass spectrometry method (abstract) (ultra-high-performance liquid chromatography-tandem mass spectrometry… for the quantification of cannabidiol (CBD)). Pigliasco teaches that methods of liquid chromatography tandem mass-spectrometry are known in the art for the analysis of cannabidiol (sixth page first paragraph) (another paper describing LC-MS/MS method for quantification of… CBD… has been published). Accordingly, Pigliasco teaches all of the claimed elements.
The combination of the known elements is achieved by a known method of first separating the elements of a sample containing cannabidiol using liquid chromatography and then determining the amount of cannabidiol in that sample with mass spectrometry. Furthermore, all the claimed elements would continue to operate in the same manner. Specifically, it would have led to the determination of the level of cannabidiol in a sample. It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to measure the cannabidiol as taught by Makiol with the liquid chromatography tandem mass spectrometry method taught by Pigliasco because they are no more “than the predictable use of prior-art elements according to their established functions.”. See MPEP 2143(I)(A).
Claim(s) 7 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Makiol et al. (Non-Patent Literature, Australian & New Zealand Journal of Psychiatry, Vol. 53, No. 3, pgs 262-265, 2018, as cited in IDS submitted on 10/11/2023).
Regarding claim 7, Makiol teaches the method of claim 1 as rejected above, wherein said level of cannabidiol is determined 12 hours after the onset of treatment (First page, middle column) (blood level 12 hours after intake: 90–107 ng/mL).
Makiol does not clearly teach wherein said level of cannabidiol is determined every 12-48 hours or determined every about 24 hours beyond the initial 12-48 or 24 hour determination.
However, because the implementation of additional determination steps would functionally be the same as the first determination step taught by Makiol, the presence of additional determination steps amounts to mere duplication of parts, which does not hold patentable significance. It would have been obvious to a person having ordinary skill in the art before the effective filing date of the instant application to duplicate the step of determining cannabidiol levels 12 hours after onset of treatment as taught by Makiol to occur every 12 hours because it would lead to the expected result of determining the level of cannabidiol in a subject to determine the efficacy of a treatment. See MPEP 2144.04.
Regarding claim 10, Makiol teaches the method of claim 1 as rejected above. Makiol teaches of a dose of cannabidiol, which is to be administered within a predetermined time period (first page middle column second paragraph) (oral CBD 500 mg twice daily), being increased after measuring the subject’s cannabidiol concentration to more effectively manage the symptoms of the subject (first page middle column second paragraph) (blood level after 12 hours after intake: 90-107ng/mL… still continuous acoustic hallucinations and reduced negative symptoms…after increasing CBD to 750mg… voices gradually ceased). Makiol teaches that a target therapeutic cannabidiol concentration is a result-effective variable, because a subject’s cannabidiol concentration of 121-144 ng/mL was effective in the treatment of schizophrenia in a subject (first page middle column second paragraph) (After increasing CBD to 750 mg twice daily (121–144 ng/mL), voices gradually ceased).
Makiol is silent to a target cannabidiol concentration of 25 µg/mL.
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to try a dose of cannabidiol that leads to a concentration of 25 µg/L instead of 121-144 ng/mL because the concentration is a result-effective variable that can be lowered through routine optimization to lead to the predictable outcome of managing the subject’s symptoms with a reasonable chance of success (see first page middle column second paragraph of Makiol). See MPEP 2144.05(II).
Claim(s) 8 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Makiol et al. (Non-Patent Literature, Australian & New Zealand Journal of Psychiatry, Vol. 53, No. 3, pgs 262-265, 2018, as cited in IDS submitted on 10/11/2023) in view of Hiemke et al. (Non-Patent Literature, Pharmacopsychiatry, Vol. 44, 2011, pgs. 195-235).
Regarding claim 8, Makiol teaches the method of claim 1 as rejected above. Makiol teaches of initially measuring cannabidiol concentrations in subjects after 12 hours of treatment initiation (first page middle column second paragraph) (added oral CBD 500 mg twice daily for 7 weeks (blood level 12 hours after intake: 90–107 ng/mL)).
Makiol is silent to wherein said level of cannabidiol is determined for the first time at least 5 days, 6, 7, 8, 9, 10, 11, 12, 13, 14 days after commencement of the treatment with the cannabidiol.
In the analogous art of defining therapeutic drug monitoring (TDM) guidelines for psychiatric treatments, Hiemke teaches of waiting 7 days before the initial measurement of drug concentrations in a subject (pg. 215 right column first paragraph) (In clinical practice, the appropriate sampling time for most psychoactive drugs is one week after stable daily dosing). Hiemke teaches that this time is advantageous because the drug concentration readings stabilize after at least 4 drug elimination half-lives, which requires at least 2-6 days (pg. 215, starting at left column bottom paragraph) (Blood should therefore be collected after at least 4 drug elimination half-lives after the start of or a change in dosage and during the terminal ß-elimination phase. For most psychotropic drugs, elimination half-lives vary between 12 and 36 h).
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify the initial measurement of Makiol (12 hours after onset of treatment) to instead initially measure cannabidiol after 7 days as suggested by Heimke because it would lead to stabilized drug concentrations due to the passage of at least four drug elimination half-lives with a reasonable chance of success (see first page middle column second paragraph of Makiol and pg. 215, starting at left column bottom paragraph of Heimke). See MPEP 2143(I)(G).
Regarding claim 11, Makiol teaches the method of claim 1 as rejected above. Makiol teaches of adjusting the dose of cannabidiol to reach an effective concentration of cannabidiol in the subject (first page middle column second paragraph) (blood level… 90-107ng/mL… still continuous acoustic hallucinations… After increasing CBD to 750 mg twice daily (121–144 ng/mL) voices gradually ceased). Makiol teaches that a target therapeutic cannabidiol concentration is a result-effective variable, because a subject’s cannabidiol concentration of 121-144 ng/mL was effective in the treatment of schizophrenia in a subject (first page middle column second paragraph) (After increasing CBD to 750 mg twice daily (121–144 ng/mL), voices gradually ceased).
Makiol is silent to a target cannabidiol concentration of 25 µg/mL.
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to try a dose of cannabidiol that leads to a concentration of 25 µg/L instead of 121-144 ng/mL because the concentration is a result-effective variable that can be lowered through routine optimization to lead to the predictable outcome of managing the subject’s symptoms with a reasonable chance of success (see first page middle column second paragraph of Makiol). See MPEP 2144.05(II).
Makiol is silent to decreasing the dose of cannabidiol if the determined level of cannabidiol is above 25 µg/mL.
In the analogous art of defining therapeutic drug monitoring (TDM) guidelines for psychiatric treatments, Hiemke teaches of lowering the dose of a drug if the concentration of drug in the subject is determined to be above a therapeutic target (pg. 217, right column, sixth paragraph) (the medication should be changed if the patient exhibited sufficiently high drug concentrations). Heimke teaches that this approach is beneficial for correcting the drug’s dose to account for subjects with too much drug in their blood for extended periods of time, which can reduce adverse effects or non-response (pg. 217, right column, fifth and sixth paragraph) (adaptation of the dose is… recommended when clinical reasons, such as adverse effects or non-response clearly justify such a decision and medication should be changed if the patient exhibited sufficiently high drug concentrations for a sufficiently long treatment period). See also modified figure 3 (highlighted to show relevant portions):
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It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify the adjustment of the cannabidiol dose to reach a desired concentration of 25 µg/mL as taught by modified Makiol by lowering the dose of cannabidiol if the amount of cannabidiol in the subject is determined to be above 25 µg/mL as suggested by Heimke because it would lead to the predictable outcome of accounting for patients with too high of drug concentrations for extended periods of time, which may also reduce adverse effect or non-response, with a reasonable chance of success (see first page middle column second paragraph of Makiol and (pg. 217, right column, fifth and sixth paragraphs of Heimke). See MPEP 2143(I)(G).
Conclusion
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/H.D.C./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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