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 .
Election/Restrictions
Applicant’s election with traverse of Group II, Claims 8-20 drawn to a method of Isolation and Analysis of CBT-C involving chiral separation and TDDFT validation in the reply filed on May 13 2026 is acknowledged. The traversal is on the ground that Groups I and II are identified in the same classification, A61K31/58, and therefore allegedly would not require a different field of search. Applicant’s argument has been considered but is not persuasive. The mere fact that the groups may share the same or overlapping classification does not establish that restriction is improper. Group I is drawn to a medicament/composition comprising CBT-C and a carrier, whereas Group II is drawn to methods of isolation, chiral separation, stereochemical analysis, ECD/optical rotation determination, and TDDFT validation of CBT-C. These groups require materially different searches and examination. Search and examination of Group I would require art directed to pharmaceutical compositions, carriers, medicaments, formulation components, dosage forms, and therapeutic composition limitations. Search and examination of Group II would require art directed to cannabinoid isolation/purification, chiral stationary phases, chromatographic separation of enantiomers, ECD spectroscopy, optical rotation, stereochemical assignment, Computational spectroscopy — relevant spectral assignment tools and TDDFT/DFT validation methods. Thus, search for one group would not be likely to result in the most pertinent art for the other group, and the groups raise different examination issues. Accordingly, upon reconsideration, the restriction requirement is maintained and made FINAL.
Claims 1-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on May 13 2026.
Status of the Claims
Claims 1-20 are pending. Claims 1-7 are withdrawn.
Claims 8-20 are under examination in accordance with the elected a method of isolation and analysis of CBT-C involving chiral separation and TDDFT validation.
Priority
The instant application 18/516,608 filed on November 21, 2023 claims priority to, and the benefits of U.S. Provisional Application No. 63/426,973 filed on November 21, 2022.
Claim Objections
Claims 16, 17, 19, and 20 are objected to because of the following informalities:
Claims 16 and 17 recite “further determining.” Applicant is required to amend the claims to recite a complete method step, such as by changing the wording to further comprising determining.
Claim 19 recites “the(1S,3S,4R)” without a space, change to the (1S,3S,4R).
Claim 20 recites “validating the configuration to each.” Applicant is required to amend the claim to clarify the grammatical relationship between the configuration and each enantiomer, for example by reciting validating the configuration of each enantiomer.
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 11-20 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.
Claim 11 recites “ellipticity within 5 degrees of 0 against a wavelength from 180–300 nm.” This limitation is indefinite because it is unclear whether the ellipticity must be within 5 degrees of zero at every wavelength within the 180–300 nm range, at any selected wavelength within that range, or as an average or integrated value across the range. The claim also does not recite sufficient measurement conditions for determining the recited ellipticity.
Claim 12 recites that “two separated CBT-C (3) enantiomers have equal peak areas.” This limitation is indefinite because “equal peak areas” lacks an objective boundary. It is unclear whether exact equality is required or whether substantially equal peak areas are intended. The claim also does not recite an acceptable tolerance or chromatographic conditions for determining equality.
Claim 13 depends from claim 10 and recites “a first CBT-C (3) enantiomer and a second CBT-C (3) enantiomer” based on a chromatographic peak assigned to each. However, claim 13 does not depend from claim 12 and therefore does not incorporate the prior limitation requiring separation of “two CBT-C (3) enantiomers” by a chiral-phase column. As a result, it is unclear whether claim 13 requires isolation of exactly two CBT-C enantiomers, isolation of any two enantiomeric fractions, or isolation of two selected peaks from a larger number of chromatographic peaks. Claims 14–20 depend directly or indirectly from claim 13 and are indefinite for at least the same reason.
Claim 20 further recites “validating the configuration to each of the first enantiomer and the second enantiomer based on at least one TDDFT determination at a selected level of theory.” This limitation is indefinite because the phrase “validating the configuration to each” is grammatically unclear and because “validating” does not provide an objective standard for when validation has occurred. The phrase “a selected level of theory” is also unclear because the claim does not specify the functional, basis set, solvent model, conformational protocol, or comparison criterion required for the TDDFT determination.
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 8–10 are rejected under 35 U.S.C. §103 as being unpatentable over Wood et al. (Magnetic Resonance in Chemistry 2021, 60(2), 196) in view of Brumar et al. (WO2021127787A1), further in view of Mazzoccanti et al. (Chem. Commun., 2017, 53, 12262) and further in view of Runco et al. (US20170283391A1).
Wood et al. teaches cannabicitran, also referred to as CBT-C, as a known cannabinoid natural product found in purified commercial cannabidiol extract preparations (See e.g. p. 196 Abstract, introduction). Wood et al. therefore teaches a cannabinoid/CBD extract containing CBT-C. Wood et al. further teaches structural characterization of CBT-C using NMR and density-functional calculations (See e.g. p. 196, Abstract).
Wood et al. does not expressly teach the step of isolating CBT-C from the extract.
Brumar et al. teaches cannabicitran-containing cannabinoid compositions and methods of synthesizing cannabicitran (See e.g. [0002]). Brumar et al. teaches the cannabicitran is found in the cannabis sativa plant and cannabis extracts, but it is challenging to isolate e(See e.g. [0003]). Brumar et al. teaches cannabinoid compositions having enhanced cannabicitran concentration and purifying cannabicitran from cannabis-derived materials, Brumar et al. teaches purification methods including chromatography, flash chromatography, reversed-phase C18 chromatography, simulated moving bed chromatography, and states that chromatography methods may be effective for the isolation of cannabicitran (See e.g. [0004], [0008], [0027]).
Wood et al. and Brumar et al. do not expressly teach that the isolated CBT-C is a racemate.
Mazzoccanti et al. teaches that phytocannabinoids are chiral and that stereochemical composition/enantiomeric purity of cannabinoid samples is an analytical concern (See e.g. p. 12262, col. I-2). Mazzoccanti further teaches chemo- and enantioselective chromatographic separation of phytocannabinoids (See e.g. p. 12262, title), and teaches determining the enantiomeric excess of Δ9-THC in medicinal marijuana using enantioselective UHPSFC(See e.g. p. 12264).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to provide a cannabinoid or CBD extract containing CBT-C, as taught by Wood et al., isolate CBT-C from a cannabinoid or CBD extract using known cannabicitran purification methods, as taught by Brumar et al., and determine whether the isolated CBT-C was racemic or enantiomerically enriched using known phytocannabinoid enantioselective analytic methods, as taught by Mazzoccanti et al. The motivation would have been to obtain and stereochemically characterize a known chiral cannabinoid constituent from a cannabinoid extract. The combination would have been predictable because it applies known cannabinoid isolation and known phytocannabinoid stereochemical analysis methods to a known cannabinoid compound.
Claim 9 further recites that the cannabinoid extract is a CBD extract. Wood et al. teaches CBT-C in purified commercial CBD extract preparations.
Claim 10 further recites that the cannabinoid extract is a sample of CBT-C obtained from the CBD extract. Wood et al. teaches CBT-C in CBD extract preparations, and Brumar et al. teaches purification/isolation of cannabicitran from cannabis-derived materials. Therefore, obtaining a CBT-C sample from a CBD extract would have been obvious.
Claims 11 is rejected under 35 U.S.C. §103 as being unpatentable over Wood et al. in view of Brumar et al., further in view of Chen et al. (Journal of Chromatography A, 2021 Volume 1654,462446) and Nugroho et al. (J Nat Med 2014, 68, 1–10).
Wood et al. and Brumar et al. teach or suggest isolated CBT-C from cannabinoid/CBD extracts as discussed above, do not expressly teach determining that CBT-C has ellipticity within 5 degrees of zero over 180-300 nm. Chen et al. teach that experimental ECD and calculated ECD comparison are known methods for stereochemical analysis and absolute-configuration assignment of chiral compounds and natural products (See Chen et al. e.g. p. 1, Abstract), and Nugroho et al. teaches that TDDFT-calculated ECD spectra are commonly used for absolute-configuration determination of natural products. (See Nugroho et al. e.g. p. 1, introduction and computational methods).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to determine the ECD/ellipticity of isolated CBT-C because chiroptical characterization was a known and routine method for evaluating chiral natural products. To the extent claim 11 requires a near-zero ECD response for a racemate, such near-zero response would have been expected because equal and opposite enantiomeric ECD contributions cancel in a racemic mixture.
Claims 12-13 are rejected under 35 U.S.C. §103 as being unpatentable over Wood et al. in view of Brumar et al., further in view of Mazzoccanti et al. (Chem. Commun., 2017,53, 12262) and further in view of Runco et al. (US20170283391A1).
Wood et al. and Brumar et al. teach or suggest isolated CBT-C from cannabinoid/CBD extracts as discussed above, Mazzoccanti et al. teaches chemo- and enantioselective chromatographic separation of phytocannabinoids (See e.g. p. 12262, title). These references do not expressly teach separating first and second CBT-C enantiomers by a chiral-phase column.
Runco et al. teaches chiral separation of cannabinoid enantiomers using CO₂-based chromatography and chiral columns, including separation of at least two THC isomers/enantiomers in a sample (See e.g. p.1, title) (See e.g. [0006], [0009]). Runco et al. also teaches that chiral separation is important where stereoisomeric quantification of drug substances is required, chiral separation provides chromatograms showing separation of cannabinoid enantiomers using chiral columns (See e.g. [0005]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to apply known chiral chromatographic separation methods to isolated CBT-C to determine whether CBT-C contained separable enantiomers and to isolate the corresponding enantiomeric peaks. Equal or substantially equal peak areas would have been expected when the starting CBT-C material was racemic.
Claims 14-17 and 20 are rejected under 35 U.S.C. §103 as being unpatentable over Wood et al. in view of Brumar et al., further in view of Mazzoccanti et al. and Runco et al. and further in view of Chen et al. and Nugroho et al.
Wood et al. and Brumar et al. teach or suggest isolated CBT-C from cannabinoid/CBD extracts. Mazzoccanti et al. and Runco et al. teach that cannabinoid or phytocannabinoid enantiomers are separable by chiral chromatographic methods. Chen et al. and Nugroho et al. teach that experimental ECD, optical rotation, and TDDFT-calculated ECD comparison are known methods for assigning absolute configuration of chiral compounds and natural products.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to measure ECD signals of separated CBT-C enantiomers and assign their absolute configurations by comparing experimental ECD data with TDDFT-calculated ECD spectra. Equal and opposite ECD signals are expected for separated enantiomers measured under the same conditions. The mirror-image configurations recited in claims 16 and 17 are the predictable stereochemical assignments obtained after routine chiral separation and ECD/TDDFT comparison.
Claim 20 merely recites validating the assigned configuration by TDDFT at a selected level of theory. Chen et al. and Nugroho et al. teach this type of calculated/experimental ECD comparison as a known stereochemical assignment method. The claim does not require a new TDDFT algorithm, new functional, new basis set, or nonconventional validation protocol.
Claims 18-19 are rejected under 35 U.S.C. §103 as being unpatentable over Wood et al. in view of Brumar et al., further in view of Mazzoccanti et al. and Runco et al. and further in view of Chen et al. and Nugroho et al.
The applied references teach or suggest isolation of CBT-C, chiral separation of cannabinoid enantiomers, and assignment of absolute configuration using ECD and TDDFT comparison as discussed above. Claims 18 and 19 further recite determining specific rotation values for the assigned CBT-C enantiomers in methanol at about 589 nm.
Measuring optical rotation is a conventional chiroptical characterization technique for isolated enantiomers. Once the CBT-C enantiomers are separated and their configurations are assigned, it would have been obvious to measure their optical rotations as confirmatory stereochemical characterization. The opposite signs of rotation are expected for enantiomers, and the claimed ranges are properties of the separated enantiomers under the recited measurement conditions.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to combine Wood et al. and Brumar et al. with Mazzoccanti et al. Runco et al., Chen et al. and Nugroho et al., because the references address the same problem of isolating, separating, and stereochemically characterizing chiral cannabinoid or natural-product compounds. Wood et al. and Brumar et al. teach CBT-C/cannabicitran in cannabinoid/CBD extracts and purification of cannabicitran-containing compositions; Mazzoccanti et al. and Runco et al. teach that cannabinoid enantiomers are separable by chiral chromatographic methods; Chen et al. and Nugroho et al. teach that experimental ECD, optical rotation, and TDDFT-calculated ECD comparison are known methods for assigning absolute configuration.
One of ordinary skill in the art would have been motivated to apply these known chiral separation, stereochemical characterization methods to CBT-C to determine whether CBT-C contained separable enantiomers, isolate the enantiomeric peaks, measure their chiroptical properties, and assign their absolute configurations. The combination would have been predictable because it merely applies known analytical methods to a known cannabinoid compound. A racemic mixture would be expected to show near-zero net ECD, separated enantiomers would be expected to show equal and opposite ECD signals and opposite optical rotations, and TDDFT/ECD comparison would predictably assist in configuration assignment.
Accordingly, claims 8–20 do not recite a new chiral column, a new chromatographic principle, a new ECD method, a new TDDFT algorithm, or a nonconventional stereochemical workflow. The claimed near-zero racemate ECD, equal peak areas, equal and opposite ECD signals, mirror-image configurations, and opposite optical rotations are expected results or inherent properties obtained from routine separation and characterization of CBT-C enantiomers.
Therefore, claims 8–20 are unpatentable under 35 U.S.C. §103.
Conclusion
No claims are allowed.
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/G.S./ Examiner, Art Unit 1628 /AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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