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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on March 11, 2026. Pursuant to amendment filed March 11, 2026, claims 14, 20, 23-24, 39, 44, and 47-48 are amended. Claims 14, 23, 39, and 47 are independent claims. Claims 1-7, 10-13, and 28-38 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Election was made without traverse in the reply filed on August 22, 2025.
Therefore, claims 14-20, 23-24, 27, 39-44, 47-48 and 51 are currently under examination.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2020/051543 filed on September 18, 2020. Applicants' claim for the benefit of a prior-filed application parent provisional application 62/990,633, filed March 17, 2020, and 62/926,875, filed October 28, 2019, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c).
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 112 as follows: The later-filed application must be an application for a patent for an invention that is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later -filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Specifically, claims 15-17, 29-30, and 40-41 are drawn to SEQ ID NOs: 8, 9 and 10 which is not supported by the earlier specifications filed October 28, 2019 and March 17, 2020. Should the applicant disagree, the applicant is encouraged to point out with particularity by page and line number where such support might exist in each intervening document. In order to properly claim priority, the support for each of the claim limitations must exist in each of the intervening documents.
Thus, the earliest possible priority for the instant application is September 18, 2020
Response to Applicants’ arguments as they apply to the Priority
Applicants’ arguments filed March 11, 2026, have been fully considered but they are not persuasive. At pages 10-11 of the remarks filed on March 11, 2026, Applicants essentially argue the following:
Applicant argues the provisional likely provided sufficient enablement and at the very least there was inherent support for the sequences recited in the claims as the sequences were known prior and the provisional application cited the earlier work. Applicant states a person having ordinary skill in the art would have understood that Applicant was in possession of the claimed subject matter. Applicant argues since the first provisional cites to the work of (Fricke, J., Blei, F., & Hoffmeister, D. (2017). Enzymatic synthesis of psilocybin. Angewandte Chemie International Edition, 56(40), 12352-12355), which originally published the underlying sequences, the provisional likely provided sufficient enablement such that undue experimentation was not necessary.
This argument is not persuasive because the evidence relied upon by Applicant is insufficient to establish entitlement to the claimed benefit. The sequence were not found in the referenced documents. Applicant’s reliance on external publications and general knowledge in the art does not demonstrate that the earlier-filed applications convey possession of the presently claimed subject matter. Applicant’s arguments rely on incorporation by reference and on what a person of ordinary skill in the art could find in an external paper, rather than pointing to the actual written description support in each earlier application for the claimed sequences. The evidence of record is therefore insufficient to establish entitlement to the claimed benefit.
The Appendix to the provisional specifications filed October 28, 2019 and March 17, 2020 reference the original publication document Fricke et al. (Fricke, J., Blei, F., & Hoffmeister, D. (2017). Enzymatic synthesis of psilocybin. Angewandte Chemie International
Edition, 56(40), 12352-12355, see IDS filed 04/27/2022, Cite No. 6). In the Appendix to the specification, pg. 2, first full paragraph, the reference states:
“These new advancements fueled our interest in developing a more cost-effective and easily manipulated host for the biosynthetic production of psilocybin. Utilizing the gene sequences recently identified by the Hoffmeister group from P. cubensis encoding an L- tryptophan decarboxylase (PsiD), a kinase (PsiK), and an S-adensoyl-L-methionine (SAM)-dependent N-methyltransferase (PsiM) (Fricke et al., 2017), together with the promiscuity of the native Escherichia coli tryptophan synthase (TrpAB) (Buller et al., 2015; Romney et al., 2017; van den Berg et al., 2010; Wilcox, 1974), the biosynthesis pathway capable of psilocybin production from 4-hydroxyindole, was expressed in the prokaryotic, model organism E. coli BL21 star™ (DE3) (Fig. 1d).”
There are no sequences disclosed. The prior specifications reference the Hoffmeister group in 2 instances, first stating:
“These promising results have motivated researchers to investigate biosynthetic routes for the production of psilocybin. The Hoffmeister group recently identified the enzymatic pathway from Psilocybe cubensis (a native fungal psilocybin producer) and demonstrated in vitro synthesis of psilocybin from 4-hydroxytryptophan. In a subsequent work, they utilized the promiscuity of the tryptophan synthase from P. cubensis to make psilocybin from 4-hydroxyindole and serine. Additionally, the Hoffmeister group produced psilocybin in vivo using an eukaryotic fungal host, Aspergillus nidulans, at titers reported near 100 mg/L.” ([0006])
Then stating:
“The exogenous pathway genes encoding the enzymes PsiD, PsiK, and PsiM contained on plasmids pJF24, pJF23, and pFB13, respectively, were a generous gift from the Hoffmeister group.” ([00051])
A review of Fricke did not identify the claimed sequences. Applicant is invited to submit a declaration under 37 C.F.R. 37 CFR §1.132 presenting evidence sufficient to overcome this rejection.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/03/2026 and 03/12/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Withdrawn Claim Rejection- 35 USC§ 102
In view of Applicants’ amendments to the instant claims, requiring the expression vector wherein the promoter is selected from the consisting of G6 mutant T7, H9 mutant T7, H10 mutant T7, C4 mutant T7, trc, GAP, and xylA promoter, the rejection of claims 14-20, 23-24, 27, 39-44, 47-48 and 51 under 35 U.S.C. 102(a)(1) as being anticipated by Protzko (US 11,661,617 B2, citations are to prior published September 12, 2019, WO 2019/173797 A1) has been withdrawn. Applicants’ arguments are moot in view of the withdrawn rejection. A response to Applicant’s arguments pertinent to a new or remaining rejection can be found below.
New 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 14-20, 23-24, 27, 39-44, 47-48 and 51 are newly rejected under 35 U.S.C. 103 as being unpatentable over Protzko (US 11,661,617 B2, citations are to prior published September 12, 2019, WO 2019/173797 A1), in view of Jones et al. (Sci Rep. 2015 Jun 11:5:11301., see IDS filed 04/27/2022, Cite No. 5), and further in view of Qu et al. (US 2020/0165632 A1, published May 28, 2020). This is a new rejection necessitated by Applicants’ amendments to the claims in the response filed on 03/11/2026.
Regarding claims 14, 19-20, 23-24, 39, 43-44, and 47-48, Protzko teaches recombinant microbial prokaryote cells and vectors comprising genes including psiD, psiK and psiM, encoding amino acid sequences corresponding to 100% sequence identity of the psilocybin production genes psiD, psiK and psiM (claims 1, 45, 78; [0017]; pg. 26, Table 1). Protzko teaches operably linked promoters to include the species such as T7, tac, Lac, LacUV5 ([00112]; [00123]; [00128-00129]; [00133]), in monocistronic configuration ([00129]; claims 11-12). Additionally, Protzko teaches a plasmid expression vector comprising a psiD gene, a psiK gene and a psiM gene ([0028]).
Specifically, regarding the inclusion or exclusion of the claimed genes, including the selection of either psiD, psiK, psiM, and combinations thereof, Protzko teaches recombinant prokaryotic host cells and expression vectors comprising psilocybin biosynthetic genes different subsets of pathway genes, including the psiD tryptophan decarboxylase, psiK kinase, and psiM transferase, along with their individual stepwise introduction [00128-00131]. Protzko teaches these genes may be expressed to produce intermediates and modulate pathway flux using various promoter configurations, comprising one or more of the claimed genes ([0004-0006]; [0010]; [00112]). Protzko teaches the use of arrangements equivalent to monocistronic, operon, and pseudooperon configurations to control gene expression with one or more enzymes of the biosynthetic pathway ([0010]; [00128-00129]; [00133]; claims 1, 17-22, and 28).
While Protzko teaches the consensus sequence for T7 and other suitable promoters, Protzko does not specifically teach presently claimed promoter such as H10 mutant T7 nor C4 mutant T7.
However, Jones teaches engineered libraries of mutant T7 promoters, including the C4 mutant T7 promoter, for utility in combinatorial optimization of multi-gene biosynthetic pathways in prokaryotic systems. Jones further teaches that varying promoter strength across pathway genes allows for balancing metabolic flux, reducing bottlenecks, and improving yield of desired products. Jones specifically taches the use of the C4 mutant T7 promoter in genetic construct architectures for pathway optimization and demonstrates that systematic variation of promoter strength provides improved production in engineered metabolic pathways (Abstract; pg. 3, para. 2-4; pg. 5-6, bridging para.).
Before the effective filing date, the person of ordinary skill in the art would have found it obvious to simply substitute the known C4 mutant T7 promoter, as taught by Jones, as a suitable promoter for expression in bacteria in place of the consensus T7 promoter, as taught by Protzko, to obtain the predictable result of generating the recombinant prokaryotic cell with expression vector with a gene or combinations selected from psiD, psiK and psiM, driven by the C4 mutant T7 promoter for the expression of the psilocybin biosynthetic genes. The ordinary artisan would have been motivated to do so because Protzko recognized the importance of promoter selection and gene expression balancing to improve production yields and Jones teaches the utility of well-characterized T7 promoter variants specifically designed to fine-tune gene expression in multi-gene pathways. The teachings of Protzko and Jones are both directed to recombinant prokaryotic expression systems and metabolic pathway engineering, and the ordinary artisan would have found a reasonable expectation of success utilizing the C4 mutant T7 in the expression system taught by Jones.
Furthermore, the ordinary artisan would have recognized the prior art taught pathway engineering and intermediate production along with omission of downstream enzymes, such as psiM as a conventional strategy to accumulate upstream intermediates or adjust pathway performance ([00102]; [00121]; [00128-00129]). Moreover, Jones teaches mutant T7 promoter libraries, including G6, H9, H10, and C4, for fine-tuning gene expression in multi-gene pathways to balance metabolic flux and improve production outcomes (pg. 1 through pg. 2, para. 3; pg. 3, para. 1-2). Thus, the ordinary artisan would have found it obvious to employ psiD and psiK without psiM in the system of Protzko and to control their expression using the promoter variants of Jones to optimize pathway performance, with a reasonable expectation of success.
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Regarding claims 15 and 40, the combined teachings of Protzko and Jones render claims 14 and 39 obvious. Additionally, Protzko teaches SEQ ID NO: 14. SEQ ID NO: 14 is disclosed as corresponding to psiD with 100% identity to instant SEQ ID NO: 8 ([0028]; [00129]; pg. 34, last row).
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Regarding claims 16 and 41, the combined teachings of Protzko and Jones render claims 14 and 39 obvious. Additionally, Protzko teaches SEQ ID NO: 41. SEQ ID NO: 41 is taught as corresponding to psiK with 100% identity to instant SEQ ID NO: 9 ([0028]; [00129]; [00133]; [00137]; pg. 41, row 2).
Regarding claim 17, the combined teachings of Protzko and Jones render claim 14 obvious. Protzko teaches SEQ ID NO: 21. SEQ ID NO: 21 is taught as corresponding to psiM with 100% identity to instant SEQ ID NO: 10 ([0028]; [0031]; [00129]; [00133]; pg. 36, row 3).
Regarding claims 18 and 42, the combined teachings of Protzko and Jones render claims 14 and 39 obvious. Additionally, Protzko teaches the prokaryotic cell is selected from species, such as Escherichia coli or Corynebacterium glutamicum (claim 47).
Regarding claims 27 and 51, the combined teachings of Protzko and Jones render claims 23 and 47 obvious. Protzko teaches routine laboratory supplies ([00130-00131]; [00135]; [00140]). However, the combined teachings of Protzko and Jones do not explicitly teach a transfection kit.
Qu teaches vector transfection kits and kit packaging and design ([0220-0223]; [0245]).
Before the effective filing date of the instant application, the ordinary artisan would have found it obvious to apply the known technique of providing the expression vector, as taught by Protzko and Jones, in the form of a packaged transfection kit, as taught by Qu, with a reasonable expectation of success at packaging components in an efficient kit form. The ordinary artisan would have been motivated to provide the expression vector system in packaged kit form for improved streamlined and standardized delivery in laboratory settings.
Additionally, there is no patentable structural distinction between the kit and expression vector of claims 23 and 47. The instant specification only defines the kit to contain conventional and established laboratory materials, such as vials, test tubes reagents for compartmentalization and components already addressed, such as cells, vectors, etc. (see instant specification [0074] and [0097]).
Response to Applicants’ arguments as they apply to the rejection of Claims 14-20, 23-24, 27, 39-44, 47-48 and 51 under 35 USC § 102
Applicants’ arguments filed March 11, 2026, have been fully considered but they are not persuasive. At pages 10-11 of the remarks filed on March 11, 2026, Applicants essentially argue the following:
Applicants argue Protzko fails to disclose the amended promoters.
Applicant’s arguments with respect to claims 14-20, 23-24, 27, 39-44, 47-48 and 51 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Jones teaches the C4 mutant T7 promoter for the same purposes of recombinant protein production while simultaneously reducing metabolic burden for metabolic engineering applications.
Applicant claims Protzko does not anticipate or teach the claimed inventions of claim 39 and 47, because the claims do not require psiM.
This argument is not persuasive because, firstly, even if the claims were amended to expressly exclude psiM, the subject matter would have been obvious over Protzko, in view of Jones. Protzko teaches recombinant prokaryotic host cells and expression vectors comprising one or more psilocybin biosynthetic genes including psiD, psiK, psiM; and further teaches that different subsets of pathway genes may be expressed to produce intermediates and modulate pathway flux using various promoter configurations and taught elements of the biosynthesis pathway, comprising one or more of the claimed genes ([0004-0006]; [0010]; [00112]). Applicant only references a single embodiment, bNAB003, but Protzko also teaches bNAB001, bNAB002, bNAB003, and bNAB004, as well as specifically teaching the expression vector may comprise discrete elements along the biosynthesis pathway ([00128-00129]; [00133]).
The ordinary artisan would have recognized the prior art taught pathway engineering and intermediate production along with omission of downstream enzymes, such as psiM as a conventional strategy to accumulate upstream intermediates or adjust pathway performance ([00121]; [0060]; [00129]). Moreover, Jones teaches mutant T7 promoter libraries, including G6, H9, H10, and C4, for fine-tuning gene expression in multi-gene pathways to balance metabolic flux and improve production outcomes (pg. 1 through pg. 2, para. 3; pg. 3, para. 1-2). Thus, the ordinary artisan would have found it obvious to employ psiD and psiK without psiM in the system of Protzko and to control their expression using the promoter variants of Jones to optimize pathway performance, with a reasonable expectation of success.
The Examiner respectfully submits that patents are relevant as prior art for all they contain. "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983). With that, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, even nonpreferred embodiments. See MPEP § 2123: Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989); Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005).
Secondly, this argument is not persuasive because, the claims are not interpreted as being limited by an exclusion of psiM, as presently recited. The claims recite an expression vector “comprising a psilocybin production gene selected from the group consisting of psiD, psiK and combinations thereof.”
Claim 39 presently recites “A recombinant prokaryotic cell comprising one or more expression vectors and a promoter, wherein each expression vector comprises a psilocybin production gene selected from the group consisting of psiD, psiK and combinations thereof; wherein…”
Claim 47 presently recites “An expression vector comprising a psilocybin production gene selected from the group consisting of psiD, psiK and combinations thereof, wherein…”
The translational term “comprising” is open-ended and permits the inclusion or presence of additional unrecited elements. The use of the indefinite article “a” does not limit the claim to a single gene, but rather means “one or more”. While the Markush phrase “selected from the group consisting of” limits the identity of an included recited psilocybin production gene to psiD, psiK, or combinations thereof, it does not exclude the presence of additional genes in the vector, including where the vector comprises other psilocybin biosynthetic transferase genes. Thus, the claims encompass vectors that include psiD and/or psiK, even where additional genes such as psiM are also present. There is no explicit negative limitation or requirement of the absence of psiM.
Conclusion
Claims 14-20, 23-24, 27, 39-44, 47-48 and 51 are rejected. No claims are 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOEL D LEVIN whose telephone number is (571)270-0616. The examiner be reached 8:00 am to 5:00 pm, Monday through Friday.
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/J.D.L./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699