DETAILED ACTION
Status of the Application
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1, 2, 4, and 5 are pending.
3. Claims 1, 2, 4, and 5 are examined.
4. The rejection of claims 1, 2, 4, and 5 under 35 U.S.C. 112(a) for lack of written description is withdrawn in view of Applicant’s amendments to the claims.
Continued Examination Under 37 CFR 1.114
5. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 8, 2025 has been entered.
Election/Restrictions
6. Applicant’s election without traverse of Group I, claims 1-5, and SEQ ID NO: 1 as a species, in the reply filed on August 1, 2024 is acknowledged. Claims 6-20, which were previously withdrawn from consideration have been canceled by Applicant.
Claim Objections
7. In claim 1, line 4, the term “according to” should be amended to recite, for example, “comprising,” for clarity. In line 7, the comma before “and” should be deleted. Appropriate correction is required.
Specification
8. The specificaiton is objected because the numbering of tables appears to start at “Table 4,” on page 83, which is then followed by “Supplemental Table 1” and “Supplemental Table 2” on pages 101 and 103; “Table 1” appears on page 114 (see the Specification filed on April 29, 2025). This is improper. The tables should be renumbered with consecutive numbers beginning with “Table 1.” Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Indefiniteness
9. 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.
10. Claims 1, 2, 4, ad 5 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.
In claim 1, the limitation “glycosylating said cannabinoid forming a cannabinoid glycoside” renders the claim indefinite. The limitation is recited as a method step yet the glycosylation of a cannabinoid is accomplished as a natural function of the enzyme, which is also recited in the claim and is required to possess glycosyltransferase activity. It is thus unclear how one would practice said step in the context of the method of claim 1. The recitation “introducing said cannabinoid to said yeast cell” introduces further ambiguity into the claim language, because it is unclear what “to said yeast cell” means. For example, it is unclear whether the cell is contacted with the cannabinoid or it is merely introduced into the suspension in which the cell is growing. Given that claims 2, 4, and 5 depend from claim 1 and fail to recite additional limitations overcoming its indefiniteness, their metes and bounds are unclear as well.
It is suggested that the claim be amended to expressly recite the steps of establishing a suspension culture and introducing said cannabinoids into said culture.
Claim Rejections - 35 USC § 112(a)
11. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Enablement
12. Claims 1, 2, 4, and 5 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
This rejection was modified in view of Applicant’s amendments to the claims. Applicant’s argument submitted on December 8, 2025 was fully considered but it is not persuasive.
Applicant claims a method for producing water-soluble compounds comprising the step of providing a yeast cell expressing a heterologous nucleic acid sequence encoding a UDP-glucosyltransferase (UGT) having glycosylation activity towards at least one of the cannabinoids recited in claim 1, wherein the UGT is “according to” SEQ ID NO: 1.
The method is not enabled.
The specification, in Examples 20 and 21, merely teaches that SEQ ID NO’s 1-9181 were identified from public databases as UGTs, groups them into “structural groupings,” and appears to predict some affinity towards cannabinoids for those groups, but supplies no explanation or guidance for how to interpret the information in “Supplemental Table 1.”
The specification has not reduced to practice any methods of producing a water-soluble cannabinoid compound using the full-length SEQ ID NO: 1, nor any other sequences listed in said Supplemental Table 1. Neither has the specification provided any guidance for how to practice said method using SEQ ID NO: 1. It would thus be highly unpredictable to attempt to practice the method of the claims.
The state of the prior art is consistent with the lack of teachings in the specification. The art related to the use of exogenous glycosyltransferases (including glucosyltransferases) to glycosylate cannabinoid compounds in yeast cells or cultures is very limited. For example, there is nothing in the teachings of Hardman et al, Tanaka et al or Poulos et al that would indicate that SEQ ID NO: 1 could be used in a method of glycosylating a cannabinoid when overexpressed in any organism (of record; Hardman et al, BioRxiv Preprint Server for Biology (Cold Spring Harbor) pg. 1-25; Tanaka et al, J. Nat. Products (1993) 56:2068-2072; Poulos et al, US Patent Publication 2016/0010126).
For these reasons, it would be highly unpredictable to one of ordinary skill in the art to attempt to practice the method of the instant claims without substantial further trial and error experimentation.
Response to Arguments
Applicant argues that the claims have been amended. Applicant argues that “SEQ ID NO. 1 is a known and identified glycosyltransferase, which only has a single enzymatic action, namely the transfer of a sugar to a target compound. Moreover, the organism from which it is derived is also known as noted by the Office. Additionally, the structural motifs which allow for docking of SEQ ID NO. 1 are known (See Example 21). Third, the actual binding affinity of enzymes from the highly homologous group of enzymes, to which SEQ ID NO. 1 belongs, namely 5tzk which are all derived from Gram+ bacteria is stablished in Supplemental Table 1. , enzyme from 5tzk have a common structure which exhibits a high binding affinity for CBD (-9.18445 kcal/mol), and THC (-10.76935 kcal/mol), respectively. As one of ordinary skill would know, a binding affinity of between -9 and -10 kcal/mol would be considered strong in most biochemical contexts. Finally, as one of ordinary skill would understand, a binding affinity for an enzyme such as a glycosyltransferase -10 kcal/mol or lower (more negative) usually indicates high-affinity binding, often desirable in drug design (pages 3-4 of the Remarks).
Applicant’s argument is not found to be persuasive. Applicant has not reduced to practice any methods of using SEQ ID NO: 1, a protein from Fusobacterium necrophorum, to produce glycosylated cannabinoids either in a yeast culture or in any other system. All teachings regarding any activity of SEQ ID NO: 1 in the specificaiton are entirely prophetic. Table 1, for example, lists “predicted binding affinity” towards what appears to be also predicted structural features within UGTs. Similarly, the specificaiton provides no evidence that any of the domains or motifs identified via database searches and predictive computer analysis are necessary and/or sufficient for the claimed cannabinoid glycosylation function.
The state of the art supports the Examiner’s position. As discussed in the rejections above, the prior art indicates that one of ordinary skill in the art cannot reliably infer a cannabinoid glycosylation function from the mere presence of a motif in a UGT. This conclusion is also consistent with the instant specification, which teaches substantial variability in cannabinoid glycosylation activity among the few assayed tobacco NtGT’s (see Examples 12-16). The rejection is maintained.
The Examiner notes that factual evidence showing the activity of SEQ ID NO: 1 in the context of the claimed method, i.e., glycosylation activity towards CBD or THC, could potentially help overcome the above rejections.
Conclusion
13. No claims are allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MYKOLA V KOVALENKO whose telephone number is (571)272-6921. The examiner can normally be reached Mon.-Fri. 9:00-5:30 PST.
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/MYKOLA V. KOVALENKO/Primary Examiner, Art Unit 1662