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 .
Priority
This application is a National-Stage entry of PCT/US2022/079321, filed 11/4/2022, which claims benefit to U.S. Provisional Patent Application Nos. 63/263,623, filed 11/5/2021 and 63/263,616, filed 11/5/2021. 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.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 2/4/2025 and 5/27/2026 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.
Election/Restrictions
Applicant’s election without traverse of Group1-4, 6, 8-9, 12-13, and 16-19), in the reply filed on 5/27/2026 is acknowledged. Claims 26-27, 29-31, and 42-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-4, 6, 8-9, 12-13, and 16-19 are pending and examined on the merits herein.
Claim Interpretation
Claim 2 recites the term “non-naturally occurring derivative”, which is described in the specification as encompassing 6-bromopsilocybin, 7-bromopsilocybin, 6-chloropsilocybin, 7-chloropsilocybin, 5-fluoropsilocybin, 6-fluoropsilocybin, 7-fluoropsilocybin, 6-iodopsilocybin, 7-iodopsilocybin, 6-methoxypsilocybin, 7-methoxypsilocybin, 6-methylpsilocybin, or 7-methylpsilocybin ([0139]). Under the B.R.I. of the term, in view of the specification, the term is understood to encompass any possible non-naturally occurring derivative, however these will be used as exemplary embodiments for searching and comparing to the prior art.
In claims 8 and 12, the terms “operon configuration”, “pseudooperon configuration”, and “monocistronic configuration” are being interpreted under the broadest reasonable interpretation (B.R.I.) in view of the specification and the general knowledge in the art regarding these terms.
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There are no explicit or special definitions for these terms in the specification. In Fig. 3, the expression vectors of JF01, JF02, and JF03 are described. These are configured as “operon configuration”, “pseudooperon configuration”, and “monocistronic configuration” respectively (see [0164] and Table 1 of the specification). A portion of Fig. 3 is reproduced below:
An “operon configuration” is understood to have each gene under the control of a single promoter and terminator, a “pseudooperon configuration” has separate promoters with one terminator, and a “monocistronic configuration” has independent promoters and terminators for each gene.
Claim Rejections - 35 USC § 112(b)
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 1-4, 6, 8-9, 12-13, and 16-19 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 1 is drawn to a method “for the production of a tryptophan, a tryptamine, or an intermediate or a side product thereof, or a derivative thereof,”. The recitation of “or an intermediate or a side product thereof, or a derivative thereof” renders the claimed method indefinite. There is no manner in which one having ordinary skill in the art can determine the metes and bounds that define the products which are encompassed by the claim. The meaning of “an intermediate or a side product thereof, or a derivative thereof” cannot be determined. What does “an intermediate or a side product thereof” encompass? Any possible intermediate or side product of a tryptophan and a tryptamine appears to be encompassed. What is intended to be defined by “a side product”? This could be any possible metabolite of tryptophan and tryptamine, under the plain meaning of the term. Further, the reactions and pathways described in the specification involve decarboxylases and hydroxylases, and according to FIG. 1, CO2 and H2O are side products of the reaction with PsiD. It is unclear if such reaction side products are meant to fall within the meaning of the claim terms.
Also, the element of “a derivative thereof” renders the claim indefinite because one cannot determine what “a derivative thereof” is referring to. As presented, it could mean any derivative of tryptophan or tryptamine, or it could mean any derivative of any of intermediates and/or side products, because it immediately follows these. There does not appear to be any special definition for a derivative. Thus, this term also appears to be unlimited because a derivative could be essentially any modification or metabolite of the tryptophan, tryptamine, or intermediates.
Because claim 1 fails to specify what structures are encompassed by the terms “intermediates”, “side products”, and “derivates”, the claim encompasses an indefinite amount of compounds which could fall under the accepted meaning of these terms.
As merely a suggestion, claim 16 limits the intermediate or side products to “norbaeocystin, baeocystin, 4-hydroxytryptophan, 4-hydroxytryptamine, aeruginascin, psilocin, norpsilocin, or 4-hydroxy-N,N,N-trimethyltryptamine (4-OH-TMT).” Replacement of “or an intermediate or a side product thereof, or a derivative thereof,” with the specific structures of claim 16 would address the issues discussed above.
Claim 2 recites the term “non-naturally occurring derivative”. This term is essentially infinite as there is no method to determine what constitutes a derivative or not, as discussed above. The specification, at ([0139]) states: “It is also envisaged that any non-naturally occurring tryptophan, tryptamine, intermediate or side product may be produced by any of the methods described herein. In some embodiments, the non-naturally occurring tryptamine is 6-bromopsilocybin, 7-bromopsilocybin, 6-chloropsilocybin, 7-chloropsilocybin, 5-fluoropsilocybin, 6-fluoropsilocybin, 7-fluoropsilocybin, 6-iodopsilocybin, 7-iodopsilocybin, 6-methoxypsilocybin, 7-methoxypsilocybin, 6-methylpsilocybin, or 7-methylpsilocybin.”
Thus, although some examples are provided in the specification, it is evident that the meaning of “non-naturally occurring derivative” is not limited and is meant to encompass any possible derivative of the indicated molecules. Because there is no manner for one the of the claimed “non-naturally occurring derivative”, there is no manner to determine the full metes and bounds of the claimed subject matter.
Claim 4 recites:
“the psiH gene encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 10 or a sequence having at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto; and
the CPR gene encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 4, 6, 8, or a sequence having at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity thereto.”
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by the narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. The claim is rendered indefinite because one cannot determine the actual claimed sequence identity due to the recitation of multiple narrower limitations in the same claim. The broadest claim limitation is that of “at least 60% identity” and thus, this will be considered for comparing the claimed sequences to the prior art. Further, for the phrase “the amino acid sequence of SEQ ID NO: 2, 4, 6, 8, or a sequence” there should be an additional “or” between 6 and 8, and because the claim is lacking “or” or “and”, it is technically impossible to determine what “sequence identity thereto” is in reference to. It appears that it means that the gene comprises at least one of these sequences. However, because “and” could be incorporated, it could also mean that all of the sequences must be present. Correction is required.
Claim 17 recites: “the group consisting of serine, tryptamine, tryptamine derivatives, tryptophan, tryptophan derivatives, indole, indole derivatives, and combinations thereof, and derivatives thereof.” The claim is indefinite due to the inclusion of “tryptamine derivatives”, “tryptophan derivatives”, “indole derivatives”, and “and derivatives thereof”. As discussed above, the claim encompasses various “derivatives” which refers to multiple elements that are not actually disclosed, thereby rendering the scope of the claim unascertainable. Further, one cannot determine to what the last element “and derivatives thereof” in the Markush style list of alternatives is referencing. A Markush list cannot be open-ended and must be a clearly defined list of alternatives. Because there is no manner in which to determine all of the possible structures and compounds included in the list of alternatives, the claim is rendered indefinite.
All other claims depend directly or indirectly from the rejected claims and are, therefore, also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the reasons set forth above.
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.
Claims 1-4, 6, 8-9, 12-13, and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Protzko (US PGPub No. 20210108238, later issued as US Pat. No. 11,661,617) in view of Roell et al. (“Engineering microbial consortia by division of labor.” Microbial cell factories vol. 18,1 35. 8 Feb. 2019, on IDS filed 5/27/2026).
Protzko pertains to recombinant cells genetically altered to biosynthesize tryptamine and tryptamine derivatives (Title, Abstract). Protzko teaches a recombinant host cell comprising: a heterologous nucleic acid sequence encoding PsiD; a heterologous nucleic acid sequence encoding PsiH; a heterologous nucleic acid sequence encoding PsiK; and a heterologous nucleic acid sequence encoding PsiM, wherein the recombinant host cell may also overexpress a P450 reductase (claims 113 and 114). The instantly recited “CPR” is a cytochrome P450 reductase.
Regarding the selection of a PsiH, Protzko teaches that a microbial cell may be engineered to express or overexpress a tryptamine 4-hydroxylase (claims 94, 113, 114), which are (cytochrome) P450 enzymes that require a P450 reductase pair to provide reducing power via transfer of electrons from NADPH (see [0086]). Protzko teaches that the tryptamine 4-hydroxylase may have an amino acid sequence according to any one of SEQ ID NOs: 32-35 (Table 2 therein), which include tryptamine 4-hydroxylases (e.g. PsiH) from P. cubensis and P. cyanescens. It is noted that the exemplary embodiments of the instant disclosure use a PsiH from Psilocybe cubensis (see e.g. [0162] and [0194] of the instant specification).
Protzko teaches an amino acid sequence for the tryptamine 4-hydroxylase (PsiH) of SEQ ID NO: 32 (claim 113, [0086]), which is 100% identical to that of the instantly recited SEQ ID NO: 10 (e.g. the PsiH from Psilocybe cubensis, see Appendix A below).
Protzko also teaches expression of a partner P450 reductase which may have an amino acid sequence according to any one of SEQ ID NOs: 36-40 ([0087]; Table 2 therein). The amino acid sequence of SEQ ID NO: 38 of Protzko has been determined to be at least 95% to SEQ ID NO: 2 and SEQ ID NO: 4 of the instant disclosure (see Appendices B and C below).
In regards to expression of PsiD, PsiK, and PsiM, Protzko teaches an expression vector comprising coding sequences for tryptophan decarboxylase from P. cubensis (psiD, SEQ ID NO: 14) for converting substituted tryptophans to tryptamines; 4-hydroxytryptamine kinase from P. cubensis (psiK, SEQ ID NO: 41); and tryptamine N-methyltransferase from P. cubensis (psiM, SEQ ID NO: 21) ([0128] and Fig. 2). In addition, Protzko teaches that the cells may comprise genes encoding a tryptophan biosynthetic pathway, trpDCBA (SEQ ID NO: 1) ([0128]).
Regarding claim 2, Protzko teaches that “The methods of the disclosure provide for production of tryptamine derivatives not naturally found in nature or tryptamine derivatives that are not accessible by synthetic chemistry” ([0054]).
Regarding claims 3 and 16, Protzko teaches that the product can include various intermediates and psilocybin derivatives including 4-hydroxy-N,N-diisopropyl-tryptamine, 4-hydroxy-N-methyl-N-isopropyltryptamine, 4-hydroxy-N,N-dimethyltryptamine (psilocin), 4-hydroxy-N,N-tetramethylenetryptamine, 4-hydroxy-N,N-dipropyltryptamine, 4-phosphoryl oxytryptamine (e.g. norbaeocystin), and 4-hydroxytryptamine, among others ([0095]; [0050]). In examples, Protzko teaches the production of psilocin, 4-hydroxy-N,N-dimethyltryptamine, as well as various other intermediates and psilocybin derivatives including 4-hydroxytryptamine (see e.g. [0134]-[0137]).
Regarding claim 6, Protzko teaches that suitable prokaryotic cells include any of Escherichia coli, Corynebacterium glutamicum, Lactobacillus sp., Salmonella sp., Shigella sp., Citrobacter, Enterobacter, Clostridium, Klebsiella, Aerobacter, Bacillus subtilis, Pseudomonas pudita, Pseudomonas aeruginosa, Pseudomonas mevalonii, Rhodobacter sphaeroides, Rhodobacter capsulatus, Rhodospirillum rubrum, Rhodococcus sp. ([0110]).
Regarding claim 8, Protzko describes a cell that has both CPR and a psiH expressed (claim 114). Protzko teaches that the CPR is necessary for the p450 activity of the psiH because the CPR P450 reductase provides reducing power via transfer of electrons from NADPH ([0086]). Protzko also teaches various expression vectors having operon configurations with a single promotor (see e.g. Figures 1-3).
Regarding claim 9, Protzko teaches that “suitable promoters for expression in bacteria may include, but are not limited to, pT7, ptac, pLac, pLacUV5, pTet, pBAD,” ([0115]).
Regarding claims 12 and 13, Protzko teaches applying an expression vector comprising a psiD, psiK, and psiM, wherein each is under the control of a promoter in an operon configuration ([0128]: “Coding sequences were oriented in a multicistronic operon downstream of a T7 promoter sequence.”; FIG. 2). Protzko also teaches that “suitable promoters for expression in bacteria may include, but are not limited to, pT7, ptac, pLac, pLacUV5, pTet, pBAD,” ([0115]).
Regarding claims 17-18, Protzko teaches that the culture may be supplemented with compounds including serine ([0103]), indole and indole derivatives ([0015]; [0064]-[0067]), or tryptophan or tryptophan derivatives ([0016]; [0057]). Protzko teaches that supplements may be added via constant dilution in culture (i.e. feeding continuously) ([0103]-[0104]).
Regarding claim 19, Protzko teaches that the cultures of microbial cells are growing (see e.g. [0127]-[0130]).
Thus, Protzko is considered to teach a method for producing tryptophan, tryptamine, or an intermediate or derivative of either, wherein the method comprises contacting prokaryotic host cells with expression vectors having genes encoding PsiH and/or CPR, as well as cells with expression vectors having genes encoding PsiD, PsiK, and PsiM.
However, Protzko does not explicitly teach in a single embodiment using a first prokaryotic host cell and a second prokaryotic host cell which are independently contacted with expression vectors, and co-cultured together.
Roell et al. is a review article that teaches during biosynthetic processes, metabolic burdens can lead to a significant drop in cell performance and that one solution to address metabolic burden is Division of Labor (DoL) via natural and synthetic microbial consortia (Abstract; Fig. 1). Roell et al. teaches that synthetic consortia can be formed from several strains of the same species, such as engineered E. coli strains, and are used to produce high-value chemicals (pg. 2, left col). Particularly, Roell discusses that “introduction of long-step biosynthetic pathways in a single bacterial strain can cause severe metabolic burden due to the overwhelming consumption of cellular build blocks and ATP for enzyme synthesis. In contrast, dividing the pathway into multiple strains in a synthetic consortium can split the overall metabolic burden among the constituent strains, with each strain bearing significantly lower stresses” (Fig. 4; pg. 5, right col under “Division of long-step biosynthesis pathways among different species”). Roell teaches that another advantage of using a microbial consortium is that the use of multiple species in one pathway can ensure that all genes are properly expressed (pg. 5, right col, last paragraph). Roell teaches that when it is difficult to maximize every synthesis module simultaneously in a single strain, division of labor can facilitate the functional expression of the complete pathway (pg. 6, left col). Also, Roell teaches that the optimization of microbial consortia is somewhat easier than fine adjustments to a single strain because it can be achieved simply by changing the ratio of the constituent strains (pg. 6, left col, top paragraph).
Therefore, prior to the effective filing date of the instant invention, it would have been prima facie obvious to one of ordinary skill to combine the teachings of Protzko and Roell to arrive at a method for producing tryptophan, tryptamine, or an intermediate or derivative of either, wherein the method comprises contacting prokaryotic host cells with expression vectors having genes encoding PsiH and/or CPR, as well as cells comprising expression vectors having genes encoding PsiD, PsiK, and PsiM, as taught in Protzko, wherein the genes expressing PsiH and its partner reductase CPR are expressed in a separate independent prokaryotic cell, according to the teachings of Roell, for the expected benefits of improved metabolism and optimized enzyme expression.
Protzko teaches the production of cells comprising vectors having an operon comprising PsiD, PsiK, and PsiM, as well as the inclusion of PsiH and a CPR partner because PsiH activity produces the intermediate of 4-hydroxytryptamine, known to be relevant for psilocybin synthesis. One of ordinary skill and knowledge in the art would have been aware of the issues taught in Roell concerning expressing multiple genes involved in complex biosynthesis pathways. Thus, as suggested in Roell, one would have been led to a solution involving the separation of parts of the pathways into multiple strains of cells, particularly E. coli as this is a commonly used and well-characterized bacteria with many known genetic tools.
MPEP § 2143.I.(C) discusses that one rationale supporting a finding of obviousness is the use of a known technique to improve similar devices, methods, or products in the same way (KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007); “One of ordinary skill in the art would have been capable of applying this known method of enhancement to a "base" device (method, or product) in the prior art and the results would have been predictable to one of ordinary skill in the art. "It's enough … to show that there was a known problem … in the art, that [another reference] … helped address that issue, and that combining the teachings of [the two references] wasn't beyond the skill of an ordinary artisan. Nothing more is required to show a motivation to combine under KSR." See Intel Corp. v. PACT XPP Schweiz AG, 61 F.4th 1373, 1380-81, 2023 USPQ2d 297 (Fed. Cir. 2023)”. In the instant case, Roell teaches that expression of multiple genes for complex biosynthesis pathways such as that taught in Protzko leads to known problems of deficient metabolism and weak protein expression and this reference teaches a common and accepted solution for this problem involves the division of labor strategy, employing two separate cell strains to achieve the desired protein expression and obtain the desired product.
Regarding claims 2-3 and 16-18, these limitations would all have been obvious selections to one of ordinary skill in the art in view of the teachings of Protzko discussed above.
Regarding claim 4 it would have been obvious in view of Protzko to include at least a PsiH having an amino acid sequence identical to the instant SEQ ID NO: 10 and/or one of the CPR genes having similarity to SEQ ID NOs: 2 and 4 herein. The selection and use of known amino acid sequences for these enzymes, known for production of useful tryptamine intermediates would have been a matter of judicial selection to one of ordinary skill.
Regarding claims 8 and 12, the arrangement of known genes in expression vectors would have been a matter of routine optimization and judicious selection to one having ordinary skill in the art. Protzko teaches expressing all of these genes in one or multiple vectors. Protzko teaches the use of a single promoter in an operon configuration to express psiD, psiK, and psiM. There is no teaching regarding the criticality or unexpected results of having psiH and CPR together in one of these claimed promoter arrangements. Selection and optimization of expression vectors and promoters in E. coli is well known and commonly practiced in the art.
Regarding claims 9 and 13, multiple of these promoters including T7 (i.e. consensus T7), Lac, Lac UV5, and Tac are explicitly taught in Protzko.
Regarding claim 19, although v does not explicitly disclose that the co-culture is “actively” growing, it is obvious that a culture should be used for expression in an exponential growth phase because the metabolism of the bacteria would be optimal in such growth phases. To one having ordinary skill in bacterial biosynthetic production and protein expression, the optimization of culture growth conditions is prima facie obvious, and one would seek to have optimal growth for the highest product yield.
From the teachings of the cited references, it is apparent that there would have been a reasonable expectation of success in combining the teachings therein to arrive at the claimed invention because Protzko teaches the successful use of combinations of the claimed genes, including psiD/psiM/psiK with psiH in cultures to produce various tryptophan and tryptamine-derived products and intermediates, including 4OH-tryptamine and psilocybin and because Roell discusses that dividing gene expression vectors between different strains of bacterial such as E. coli is a proven method for optimizing complex biosynthetic pathways in the art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, as evidenced by the cited references, especially in the absence of evidence to the contrary.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Peiffer et al. (WO-2021248087-A2) discloses non-naturally occurring nucleic acids comprising a sequence encoding an enzyme or regulatory protein in tryptamine metabolism and methods for the production of substituted indoles and related tryptamines in recombinant microorganisms (Abstract, claim 110). Peiffer teaches the co-expression of both PsiH and a CPR and teaches generating a chimeric p450 and CPR gene that results in a fusion protein having both activity for heterologous expression (see Fig. 19).
Vogan et al. (US PGPub No. 20210147888, on IDS filed 2/4/2025) pertains to the expression of genes comprising combinations PsiD, PsiH, PsiK, and PsiM in recombinant yeast cells for the synthesis of psilocybin (Title; Abstract; [0019]).
Borodina et al. (WO-2021052989-A1, on IDS filed 5/27/2026) discloses methods for production of 4-hydroxytryptamine and related psilocybin derivatives in a yeast cell (Title, Abstract). Borodina et al. teaches that the co-expression of at least PsiM, PsiK, and PsiH with PcCPR leads to improved production of psilocin and psilocybin (see e.g. Fig. 4).
The following reference is not valid prior art but is authored by inventors of the instant application and discloses the invention in full.
Flower et al. “Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli” Biotechnology and bioengineering vol. 120,8 (2023): 2214-2229. doi:10.1002/bit.28480.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anand Desai can be reached at 571-272-0947. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
Appendix A: Alignment of SEQ ID NO: 10 to SEQ ID NO: 32 of Protzko
RESULT 1
US-17-012-737-32
(NOTE: this sequence has 20 duplicates in the database searched)
Sequence 32, US/17012737
Publication No. US20210108238A1
LENGTH: 508
TYPE: PRT
ORGANISM: Psilocybe cubensis
Query Match 100.0%; Score 2713; Length 508;
Best Local Similarity 100.0%;
Matches 508; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MIAVLFSFVIAGCIYYIVSRRVRRSRLPPGPPGIPIPFIGNMFDMPEESPWLTFLQWGRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MIAVLFSFVIAGCIYYIVSRRVRRSRLPPGPPGIPIPFIGNMFDMPEESPWLTFLQWGRD 60
Qy 61 YNTDILYVDAGGTEMVILNTLETITDLLEKRGSIYSGRLESTMVNELMGWEFDLGFITYG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YNTDILYVDAGGTEMVILNTLETITDLLEKRGSIYSGRLESTMVNELMGWEFDLGFITYG 120
Qy 121 DRWREERRMFAKEFSEKGIKQFRHAQVKAAHQLVQQLTKTPDRWAQHIRHQIAAMSLDIG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DRWREERRMFAKEFSEKGIKQFRHAQVKAAHQLVQQLTKTPDRWAQHIRHQIAAMSLDIG 180
Qy 181 YGIDLAEDDPWLEATHLANEGLAIA SVPGKFWVDSFPSLKYLPAWFPGAVFKRKAKVWRE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YGIDLAEDDPWLEATHLANEGLAIA SVPGKFWVDSFPSLKYLPAWFPGAVFKRKAKVWRE 240
Qy 241 AADHMVDMPYETMRKLAPQGLTRPSYASARLQAMDLNGDLEHQEHVIKNTAAEVNVGGGD 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AADHMVDMPYETMRKLAPQGLTRPSYASARLQAMDLNGDLEHQEHVIKNTAAEVNVGGGD 300
Qy 301 TTVSAMSAFILAMVKYPEVQRKVQAELDALTNNGQIPDYDEEDDSLPYLTACIKELFRWN 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TTVSAMSAFILAMVKYPEVQRKVQAELDALTNNGQIPDYDEEDDSLPYLTACIKELFRWN 360
Qy 361 QIAPLAIPHKLMKDDVYRGYLIPKNTLVFANTWAVLNDPEVYPDPSVFRPERYLGPDGKP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 QIAPLAIPHKLMKDDVYRGYLIPKNTLVFANTWAVLNDPEVYPDPSVFRPERYLGPDGKP 420
Qy 421 DNTVRDPRKAAFGYGRRNCPGIHLAQSTVWIAGATLLSAFNIERPVDQNGKPIDIPADFT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DNTVRDPRKAAFGYGRRNCPGIHLAQSTVWIAGATLLSAFNIERPVDQNGKPIDIPADFT 480
Qy 481 TGFFRHPVPFQCRFVPRTEQVSQSVSGP 508
||||||||||||||||||||||||||||
Db 481 TGFFRHPVPFQCRFVPRTEQVSQSVSGP 508
Appendix B: Alignment of SEQ ID NO: 2 to SEQ ID NO: 38 of Protzko
RESULT 4
US-17-012-737-38
(NOTE: this sequence has 2 duplicates in the database searched)
Sequence 38, US/17012737
Publication No. US20210108238A1
ORGANISM: Psilocybe cyanescens
Query Match 94.6%; Score 3643; Length 1351;
Best Local Similarity 95.3%;
Matches 690; Conservative 21; Mismatches 13; Indels 0; Gaps 0;
Qy 14 ASSSSDVFVLGLGVVLAALYIFRDQLFAASKPKVAPVSTTKPANGSANPRDFIAKMKQGK 73
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 22 ASSSSDVFVLGLGVVLAALYIFRDQLFAASKPKVAPVSTTKPANGSANPRDFIAKMKQGK 81
Qy 74 KRIVIFYGSQTGTAEEYAIRLAKEAKQKFGLASLVCDPEEYDFEKLDQLPEDSIAFFVVA 133
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 82 KRIVIFYGSQTGTAEEYAIRLAKEAKQKFGLASLVCDPEEYDFEKLDQLPEDSIAFFVVA 141
Qy 134 TYGEGEPTDNAVQLLQNLQDESFEFSSGERKLSGLKYVVFGLGNKTYEHYNLIGRTVDAQ 193
||||||||||||||||||||:|||||:|||||||||||||||||||||||||||||||||
Db 142 TYGEGEPTDNAVQLLQNLQDDSFEFSNGERKLSGLKYVVFGLGNKTYEHYNLIGRTVDAQ 201
Qy 194 LAKMGAIRIGERGEGDDDKSMEEDYLEWKDGMWEAFATAMGVEEGQGGDSADFVVSELES 253
||||||:|:||||||||||||||||||||||||:||| ||||||||||||||||||||||
Db 202 LAKMGAVRVGERGEGDDDKSMEEDYLEWKDGMWDAFAAAMGVEEGQGGDSADFVVSELES 261
Qy 254 HPPEKVYQGEFSARALTKTKGIHDAKNPFAAPIAVARELFQSVVDRNCVHVEFNIEGSGI 313
||||||| ||:||||||||||||||||| |||| ||||||||||||||||||||||||||
Db 262 HPPEKVYLGEYSARALTKTKGIHDAKNPLAAPITVARELFQSVVDRNCVHVEFNIEGSGI 321
Qy 314 TYQHGDHVGLWPLNPDVEVERLLCVLGLAEKRDAVISIESLDPALAKVPFPVPTTYGAVL 373
|||||||||||||||||||||||||||| ||||||||||||||||||||||||||| |||
Db 322 TYQHGDHVGLWPLNPDVEVERLLCVLGLTEKRDAVISIESLDPALAKVPFPVPTTYAAVL 381
Qy 374 RHYIDISAVAGRQILGTLSKFAPTPEAEAFLRNLNTNKEEYHNVVANGCLKLGEILQIAT 433
|||||:|||||||||||||||||||||||||:|||||||||||||||||||||||||:||
Db 382 RHYIDVSAVAGRQILGTLSKFAPTPEAEAFLKNLNTNKEEYHNVVANGCLKLGEILQVAT 441
Qy 434 GNDITVPPTTANTTKWPIPFDIIVSAIPRLQPRYYSISSSPKIHPNTIHATVVVLKYENV 493
|||||| || |||||||||||||||||||||||||||||||:|||||||||||||||||
Db 442 GNDITVAPTPGNTTKWPIPFDIIVSAIPRLQPRYYSISSSPKVHPNTIHATVVVLKYENV 501
Qy 494 PTEPIPRKWVYGVGSNFLLNLKYAVNKEPVPYITQNGEQRVGVPEYLIAGPRGSYKTESF 553
||:|||||||||||||||||||:|:||||||:|||||||||||||||||||||||||||
Db 502 PTDPIPRKWVYGVGSNFLLNLKHAINKEPVPFITQNGEQRVGVPEYLIAGPRGSYKTESH 561
Qy 554 YKAPIHVRRSTFRLPTNPKSPVIMIGPGTGVAPFRGFVQERVALARRSIEKNGPDSLADW 613
:|||||||||||||||||||||||||||||||||||||||||||||||:|||||:|| ||
Db 562 FKAPIHVRRSTFRLPTNPKSPVIMIGPGTGVAPFRGFVQERVALARRSVEKNGPESLNDW 621
Qy 614 GRISLFYGCRRSDEDFLYKDEWPQYEAELKGKFKLHCAFSRQNYKPDGSKIYVQDLIWED 673
|||||||||||||||||||||||||: ||||||||||||||:||||||||||||||||||
Db 622 GRISLFYGCRRSDEDFLYKDEWPQYQEELKGKFKLHCAFSRENYKPDGSKIYVQDLIWED 681
Qy 674 REHIADAILNGKGYVYICGEAKSMSKQVEEVLAKILGEAKGGSGPVEGVAEVKLLKERSR 733
|||||||||||||||||||||||||||||||||:|||||||||| ||||||:||||||||
Db 682 REHIADAILNGKGYVYICGEAKSMSKQVEEVLARILGEAKGGSGAVEGVAEIKLLKERSR 741
Qy 734 LMLD 737
||||
Db 742 LMLD 745
Appendix C: Alignment of SEQ ID NO: 4 to SEQ ID NO: 38 of Protzko
RESULT 4
US-17-012-737-38
(NOTE: this sequence has 2 duplicates in the database searched)
Sequence 38, US/17012737
Publication No. US20210108238A1
ORGANISM: Psilocybe cyanescens
Query Match 96.1%; Score 3648; Length 1351;
Best Local Similarity 95.3%;
Matches 691; Conservative 21; Mismatches 13; Indels 0; Gaps 0;
Qy 1 MASSSSDVFVLGLGVVLAALYIFRDQLFAASKPKVAPVSTTKPANGSANPRDFIAKMKQG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 MASSSSDVFVLGLGVVLAALYIFRDQLFAASKPKVAPVSTTKPANGSANPRDFIAKMKQG 80
Qy 61 KKRIVIFYGSQTGTAEEYAIRLAKEAKQKFGLASLVCDPEEYDFEKLDQLPEDSIAFFVV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 KKRIVIFYGSQTGTAEEYAIRLAKEAKQKFGLASLVCDPEEYDFEKLDQLPEDSIAFFVV 140
Qy 121 ATYGEGEPTDNAVQLLQNLQDESFEFSSGERKLSGLKYVVFGLGNKTYEHYNLIGRTVDA 180
|||||||||||||||||||||:|||||:||||||||||||||||||||||||||||||||
Db 141 ATYGEGEPTDNAVQLLQNLQDDSFEFSNGERKLSGLKYVVFGLGNKTYEHYNLIGRTVDA 200
Qy 181 QLAKMGAIRIGERGEGDDDKSMEEDYLEWKDGMWEAFATAMGVEEGQGGDSADFVVSELE 240
|||||||:|:||||||||||||||||||||||||:||| |||||||||||||||||||||
Db 201 QLAKMGAVRVGERGEGDDDKSMEEDYLEWKDGMWDAFAAAMGVEEGQGGDSADFVVSELE 260
Qy 241 SHPPEKVYQGEFSARALTKTKGIHDAKNPFAAPIAVARELFQSVVDRNCVHVEFNIEGSG 300
|||||||| ||:||||||||||||||||| |||| |||||||||||||||||||||||||
Db 261 SHPPEKVYLGEYSARALTKTKGIHDAKNPLAAPITVARELFQSVVDRNCVHVEFNIEGSG 320
Qy 301 ITYQHGDHVGLWPLNPDVEVERLLCVLGLAEKRDAVISIESLDPALAKVPFPVPTTYGAV 360
||||||||||||||||||||||||||||| ||||||||||||||||||||||||||| ||
Db 321 ITYQHGDHVGLWPLNPDVEVERLLCVLGLTEKRDAVISIESLDPALAKVPFPVPTTYAAV 380
Qy 361 LRHYIDISAVAGRQILGTLSKFAPTPEAEAFLRNLNTNKEEYHNVVANGCLKLGEILQIA 420
||||||:|||||||||||||||||||||||||:|||||||||||||||||||||||||:|
Db 381 LRHYIDVSAVAGRQILGTLSKFAPTPEAEAFLKNLNTNKEEYHNVVANGCLKLGEILQVA 440
Qy 421 TGNDITVPPTTANTTKWPIPFDIIVSAIPRLQPRYYSISSSPKIHPNTIHATVVVLKYEN 480
||||||| || |||||||||||||||||||||||||||||||:||||||||||||||||
Db 441 TGNDITVAPTPGNTTKWPIPFDIIVSAIPRLQPRYYSISSSPKVHPNTIHATVVVLKYEN 500
Qy 481 VPTEPIPRKWVYGVGSNFLLNLKYAVNKEPVPYITQNGEQRVGVPEYLIAGPRGSYKTES 540
|||:|||||||||||||||||||:|:||||||:|||||||||||||||||||||||||||
Db 501 VPTDPIPRKWVYGVGSNFLLNLKHAINKEPVPFITQNGEQRVGVPEYLIAGPRGSYKTES 560
Qy 541 FYKAPIHVRRSTFRLPTNPKSPVIMIGPGTGVAPFRGFVQERVALARRSIEKNGPDSLAD 600
:|||||||||||||||||||||||||||||||||||||||||||||||:|||||:|| |
Db 561 HFKAPIHVRRSTFRLPTNPKSPVIMIGPGTGVAPFRGFVQERVALARRSVEKNGPESLND 620
Qy 601 WGRISLFYGCRRSDEDFLYKDEWPQYEAELKGKFKLHCAFSRQNYKPDGSKIYVQDLIWE 660
||||||||||||||||||||||||||: ||||||||||||||:|||||||||||||||||
Db 621 WGRISLFYGCRRSDEDFLYKDEWPQYQEELKGKFKLHCAFSRENYKPDGSKIYVQDLIWE 680
Qy 661 DREHIADAILNGKGYVYICGEAKSMSKQVEEVLAKILGEAKGGSGPVEGVAEVKLLKERS 720
||||||||||||||||||||||||||||||||||:|||||||||| ||||||:|||||||
Db 681 DREHIADAILNGKGYVYICGEAKSMSKQVEEVLARILGEAKGGSGAVEGVAEIKLLKERS 740
Qy 721 RLMLD 725
|||||
Db 741 RLMLD 745
Prosecution Insights