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 .
Status of the Claims
The amendments submitted on February 27, 2026 have been entered.
New claims 72-76 have been added. Claims 73-76 are new and withdrawn.
Claims 54, 59, and 64-76 are pending.
Claims 59, 64, 66-71, and 73-76 are withdrawn from consideration.
Claims 54, 65, and 72 are examined in this Office action.
Status of Objections and Rejections
All previous objections and rejections not set forth below have been withdrawn in view of Applicants’ amendments and/or upon further consideration.
The text of those sections of Title 35 U.S. Code, not included in this action, can be found in a prior Office action.
Claim Interpretation
The term “terpenes” refers to hydrocarbon compounds constructed from one or more five-carbon isoprene units which are combined to produce a diversity of skeletons; see Specification, page 17, last paragraph.
The term “terpenoids”, also commonly referred to as isoprenoids, refer to terpene derivatives or analogs; see Specification, page 18, first paragraph.
The Specification states at page 1, penultimate paragraph, that “[c]annabis plants produce cannabinoids, terpenes, and other compounds. Cannabinoids, the most studied group of secondary metabolites in cannabis, are a large family of approximately 150 active compounds that activate cannabinoid receptors in cells and alter neurotransmitter release in the brain.”
Claim Objections
New claim 72 recites the genus name “Cannabis” (plant), which should be italicized in scientific nomenclature: ---Cannabis---.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
Scope of Enablement
Claims 54 and 65 remain rejected, and claim 72 is newly rejected, under 35 U.S.C. § 112(a), because the specification, while being enabling for a method of modulating transport of cannabinoid terpenes in Cannabis sativa plants and in yeast and tobacco cells, does not reasonably provide enablement for modulating the transport of all possible terpenes in all possible plants (or even in Cannabis and tobacco). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. All dependent claims are included in these rejections unless they contain a limitation that overcomes the deficiencies of the parent claim from which they depend.
The claims are broadly drawn to a method of modulating transport of (i) cannabinoids and (ii) terpenes in plants and yeast, which comprises introducing into at least one cell of the plants or yeast organism a nucleic acid construct comprising a polynucleotide encoding a polypeptide having an ATP-binding cassette transporter activity, which modulates transport of a cannabinoid across a cell membrane or a cell wall, said polypeptide being at least 98% identical to SEQ ID NO: 47, and a cis-acting regulatory element heterologous to said polynucleotide for directing expression of said polynucleotide in a cell, thereby modulating the transport of the metabolites in the organism; and further wherein the plant is Cannabis or tobacco.
Applicants describe the selection of ABC and PTR Transporter genes in Cannabis sativa.
Applicants describe that the instant SEQ ID NO: 47 is annotated as an ABC-G transporter in Cannabis sativa (Pg. 64, lines 16-29; Table 8), and that expression of a nucleic acid encoding the protein of SEQ ID NO:47 in yeast cells modified the uptake of several terpenoids (Pg. 11, lines 13-18; Pg. 12, lines 1-3; Figure 3; Figure 7).
With the exception of uptake of CBD into transformed yeast and tobacco BY-2 cells, Applicants have not provided working examples of the modulation of transport of any other terpenes in any other plant, in a method claim to modulating transport of all possible terpenes in all possible plants ((or even in Cannabis and tobacco).
Initially, it is noted that Applicants concede that even cannabinoids, the most studied group of secondary metabolites in cannabis, are a large family of approximately 150 active compounds; see claim Interpretation, supra.
Recent scientific reviews and research articles further demonstrate the unpredictability of the state of the art with respect to the instant claims. Selected number of these are highlighted below.
For example, it is known in the art that the ATP-binding cassette (ABC) protein superfamily is the largest protein family known (Sánchez-Fernández et al., 2001, The Arabidopsis thaliana ABC Protein Superfamily, a Complete Inventory, J. Biol. Chem. 276: 30231-30244; at 30231, Introduction). Arabidopsis was found to contain a total of 129 open reading frames (more than 0.5% of the total ORFs) capable of encoding ABC proteins (Id., Abstract).
Furthermore, ABC transporters are members of a very large superfamily of genes, one of the largest and most ancient family of genes found in all kingdoms, from prokaryotes to protists, fungi, plants and animals. Plants have a large number of ABC transporter genes, for example Arabidopsis thaliana has 130 ABC transporter genes, and rice has 125 ABC transporter genes. Although ABC transporter genes are characterized and grouped based on their gene structure, very little is known about most ABC transporters functionally, and no ABC transporter protein has been crystallized so far. Also the substrates of most ABC transporters are not known and difficult to identify. These factors do not appear to have been adequately addressed in the instant application.
It is also known in the art that terpenoids are the most diverse class of specialized metabolites in plants, despite being derived from two simple precursors, isopentenyl diphosphate and dimethylallyl diphosphate (X. Wang and G. Wang, Plant Terpenoid Diversity: From Pathway Elucidation to Ecological Functions, 2025, Engineering, https://doi.org/10.1016/ j.eng.2025.11.021). The vast diversity of scaffold-modifying reactions in terpenes has long posed a central challenge in plant terpenoid research. This difficulty arises because downstream tailoring enzymes, such as oxidases (e.g., cytochrome P450s), glycosyltransferases, and acyl transferases, typically belong to large, functionally diversified gene families, often comprising scores to hundreds of members, which complicates the assignment of precise enzymatic functions (Fig. 1(b)) (paragraph bridging pages 3-4). See also Fig. 2. These factors do not appear to have been adequately addressed in the instant application.
Similarly, it is known in the art that terpenoids are a group of compounds with enormous structural and functional diversity, which are found in all branches of life and represent one of the largest classes of metabolites in nature. In the plant kingdom they occur with exceptional diversity serving a broad range of physiological functions in key processes such as photosynthesis, respiration, growth, and development. These primary metabolic activities require terpenoids including chlorophylls, carotenoids, quinones, dolichols, sterols, and the hormones gibberellins, strigolactones, brassinosteroids, and abscisic acid. To date, despite the extensive knowledge on individual enzymatic steps, we are still far from a complete and comprehensive understanding of the plant terpenoid biosynthetic network. In particular little is known about the multiple regulatory mechanisms acting at the genomic, transcriptional, metabolite, and enzymatic levels. In addition, a detailed understanding of compartmentalization, transport processes, and formation of protein complexes remains elusive (Bergman et al., 2024, Plant terpenoid biosynthetic network and its multiple layers of regulation, 2024, Progress in Lipid Research 95:101287, pp 1-23; at Introduction). These factors do not appear to have been adequately addressed in the instant application.
Even with respect to cannabinoids only, the diversity and unpredictability are remarkable. In the plant, phytocannabinoid synthesis is a multistep process, including different precursor molecules which are further metabolised by four phytocannabinoid synthases: cannabigerolic acid synthase (CBGA synthase), tetrahydrocannabinolic acid synthase (THCA synthase), cannabidiolic acid synthase (CBDA synthase) and cannabicromenic acid synthase (CBCA synthase). CBGA synthase is a prenyltransferase, whereas THCA, CBDA and CBCA synthases are all closely related oxidocyclases (Figure 1a) (Melzer et al., 2022, Evolution, genetics and biochemistry of plant cannabinoid synthesis: a challenge for biotechnology in the years ahead, Current Opinion in Biotechnology 75: 102684, pp 1-8; at page 1). The presence and absence of THCA synthase and CBDA synthase differs even between Cannabis cultivars, providing the most important distinction between plants in terms of phytocannabinoid profile: high or low THC content in the female inflorescences (Id.). CBDA and THCA synthase appear to be encoded by a complex genetic locus interspersed with transposable elements and limited similarities between the hemp and marijuana genomes, making recombination between the haplotypes infrequent (Figure 1c). The complex genomic arrangement of the phytocannabinoid synthases is further complicated by the presence of numerous pseudogenes and additional full-length, putatively functional phytocannabinoid synthases which differ between some Cannabis genomes (Figure 1a). The biochemical activity of those synthases is currently uncharacterized, but they may account for the observation that hemp lines which do not possess an active THCA synthase still produce small amounts of THCA (page 2). These factors do not appear to have been adequately addressed in the instant application.
Regarding production of cannabinoids and terpenes in tobacco BY-2 cells, terpenes are derived from the mevalonate (cytosolic) and methylerythritol phosphate (plastidic) pathways, producing the 5‑carbon precursors IPP and DMAPP. In BY‑2, diverting these intermediates toward terpene biosynthesis—especially triterpenes like squalene—requires metabolic engineering. Studies show that diverting IPP/DMAPP from the cytosolic mevalonate pathway is difficult, as regulatory mechanisms and competing pathways limit flux.
Therefore, one of ordinary skill in the art would not know how to use the instantly recited methods requiring only the expression of instant SEQ ID NO:47 for modulating transport of all possible cannabinoids and terpenes in all possible plants (or even in Cannabis or tobacco) and yeast.
Given the absence of guidance in the specification, and given the relatively high level of unpredictability in the art, one of skill in the art cannot predict the effect of introducing the claimed polynucleotide encoding a polypeptide at least 98% identical to SEQ ID NO: 47 and having an ATP-binding cassette transporter activity, which modulates transport of a cannabinoid across a cell membrane or a cell wall, on modulating transport of all possible cannabinoids and terpenes in all possible plants (or even in Cannabis or tobacco) and yeast. Accordingly, given the lack of guidance in the instant Specification, undue trial and error experimentation would have been required for one skilled in the art to use the claimed invention.
Response to Applicant’s arguments:
The Applicant’s arguments in the response submitted on February 27, 2026 have been carefully considered but they were not found to be persuasive. The Applicant contends that the claim amendments are sufficient to overcome the previously states rejections (Remarks, section bridging pages 6-7). Applicant argues that the application shows altered uptake of cannabidiol (CBD in transformed yeast cells and in tobacco BY-2 cells, and the modulation of α-pinene, limonene, and caryophyllene in yeast cells (Id.).
The Examiner disagrees.
Initially, it is noted that this is a new rejection necessitated by the claim amendments.
Applicant argues that the instantly recited methods requiring only instant SEQ ID NO:47 for modulating transport of all possible cannabinoids and terpenes in all possible plants and yeast are adequately enabled. However, as described above, in the unpredictable arts of chemistry and biology, and in particular with respect to cannabinoids and terpenes, given the lack of guidance in the instant Specification, undue trial and error experimentation would have been required for one skilled in the art to use the claimed invention.
It is also known in the art that tobacco BY-2 cells may not be ideal for every metabolite (namely cannabinoids and terpenes) assay because some metabolites are produced at very low levels, some are not naturally abundant in tobacco cells, some assays require tissue types with different physiology, and cell suspension cultures can differ from whole plants. As well, the limits of cannabinoids and terpenes production in tobacco BY-2 cells are primarily metabolic (lack of native biosynthetic machinery) and process-related (nutrient/oxygen limitations, viscosity, by-product accumulation). Plant cell cultures like BY-2 are not naturally adapted for cannabinoid and terpene production and output. Regulatory feedback loops, compartmentalization, and resource allocation toward growth rather than specialized metabolism constrain cannabinoid and terpene flux.
Therefore, for at least the reasons of record, and those reasons indicated above, the rejection is maintained.
Subject Matter Free of the Art
Claims 54, 65, and 72 are deemed free of the prior art.
Summary
No claim is allowed.
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Examiner’s Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRATISLAV STANKOVIC whose telephone number is (571)270-0305. The examiner can normally be reached Monday-Friday, 08:00-17:00 h EST.
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BRATISLAV STANKOVIC, JD, PhD
Supervisory Patent Examiner
Art Units 1661 & 1662
/BRATISLAV STANKOVIC/SPE, Art Units 1661 & 1662
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